CA1328081C

CA1328081C - Antibacterial antiplaque, anticalculus oral composition

Info

Publication number: CA1328081C
Application number: CA000616610A
Authority: CA
Inventors: Abdul Gaffar; Nuran Nabi; Brian S. Jannone
Original assignee: Individual
Current assignee: Colgate Palmolive Co
Priority date: 1987-01-30
Filing date: 1993-04-01
Publication date: 1994-03-29
Anticipated expiration: 2008-01-29
Also published as: CA1339301C; CA1328623C

Abstract

ANTIBACTERIAL ANTIPLAQUE, ANTICALCULUS ORAL COMPOSITION

ABSTRACT

An oral composition such as a dentifrice, mouthwash, lozenge or chewing gum containing a polyphosphate anticalculus agent, such as tetraalkali metal pyrophosphate and antibacterial antiplaque agent compatible therewith. The antiplaque agent is a substantially water-insoluble noncationic antibacterial agent such as 2,4,4' -trichloro-21-hydroxydiphenyl ether (Triclosan)*.

*Trade-mark

Description

-- I328081 :

This invention relates to an antibacterial antiplaque anticalculus oral composltion. More particularly, it relates to an oral composition containing a polyphosphate anticalculus (that is, antitartar) agent and a compatible antibacterial -agent effective to inhibit plaque.
In U.S. Patents 4,627,977 to Gaffar et al; 4,515,772 to Parran et al; and 4,323,551 to Parran, oral compositions are . .
described whlch include various polyphosphate compounds. In the patent to Gaffar et al, a linear molecular dehydrated , .: - .
polyphosphate salt is employed in con~unctlon with a fluoride ' ' ~ ! , ion-provlding source and a synthetic linear polymeric polycarboxylate to inhibit calculu~ formation.
In the patents to Parran et al and to Parran water ;
. .
soluble dialkall metal pyrophosphate alone or mixed with tetraalkali metal pyrophosphate 18 employed.
Oral compositions whlch inhibit calculus formation on dental surfaces are hlghly desirable since calculus ls one of the causitlve factors in periodontal conditions. Thu~, its reduction promotes oral hygiene. :
Dental plaque is a precursor of calculus. Unlike : , calculus, however, plaque may form on any part of the tooth surface, particularly including at the gingival margin. Hence, besides being unsightly, it is implicated in the occurrence of glngivitis.
Accordingly, it would be highly desirable to include ;
antimicrobial agents which have been known to reduce plague in oral composltions contalning anticalculus agents. Indeed, this has been described in U~S. Patent 4,022,880 to Vinson et al, wherein a compound providing zinc ions as an anticalculus agent is admixed with an antibacterial agent effective to retard the growth of plaque bacteria. A wide variety of antibacterial agents are described with the zinc ~ ;
2 ~

' ~' `

co~pounds lnclud ~ eat~onic mAterlals such s gu2nldes And quaternary amm~nlu~ compounds a~ well as non-catlonic compound~ ~uch a~ halogenated 6allcylanil~de~ and hal~genated hydroxydlphenyl ethers.
~I Hltherto, the catlonlc antlbacterial materlsls such as ,Ichlorhe~ldine, benzthonlu~ chlorlde and cetyl pyrldlnlum chlorlde have ¦been the subJect of greateRt lnvestlgatlon as antlbacterlal antlplnque agents. H~wever, ln spite of thelr belng used ln conJuctlon ~ith zlnc lanticalculus agent, they are not effectlve when u8ed wlth nionic ,l~uterlals ~uch as polyphosphate antlcalculu~ agent. Thls ,¦ineffectiveness is con~itered to be qulte surprising as polyphosphates are chelaeing agents ant the chelating effect has prevlously been known to lncrease the efflcacy of catlonlc antlbacterlal agents.(~ee e.g.
Dlslnfectlon, Sterlllzation and Pre~ervation, 2nd Ed., Black, 1977, page 1915 and Inhibltlon and Destructlon of the W croblal Cell, ~ugo, 1971, 1 1 ,ipage 215). Indeed, quaternary ammonium co~pound 18 pre-ent ln the pl-que control mouthwa~h cont-lning pyropho-phate of U.S. P tent 4,323,551 and bi~-biguanite antiplaque ~gent i~ ~uggested ln the antlcalculus pyropho6phate oral co~po~ition of U.S. Patent 4,515,772.
Il In view of the curpricing lncompatlblllty of cationic ! ¦antibacterial agent~ wlth polyphosphates precent as antlcalculu~ agents, ¦lt was quite unexpected that other antib~cterial Jgent would be effective.
¦~ It 18 n advantage of this inventlon that certain antlbacterlal agent~ are effective in anticalculus oral compo~ition~ to inhibit plaque formation. i ; It 18 a further advantage of thl~ lnventlon that a composltlon ¦18 provlded which is effectlve to reduce plaque and calculus for~ation.
It 18 a further advantage of thl~ invention that an antiplaque, antlcalculus oral composltion i8 provided which is effeceive to reduce ¦
the occurence of glngivltis.

~1 l i I ., ;, , Additional advantages of this invention will be apparent from considerakion of the following specification. - ;
In accordance with certain of its aspects this ; ~
invention relates to an oral composition comprising in an ~ -orally acceptable vehicle, an effective anticalculus amount of material comprising at least one linear molecularly dehydrated polyphosphate salt as essential anticalculus agent and an effective antiplaque amount of a substantially water-insoluble - . .
noncationic antlbacterial agent selected from the group consisting of halogenated diphenyl ethers, phenolic compounds, benzoate esters, and halogenated carbanilides.
~he present invention provides an oral composition ~
comprising in an orally acceptable vehicle, an anticalculus ;
effective amount of material comprislng at least one linear -molecularly dehydrated polyphosphate salt as e~sential antlcalculus agent and an antlplaque effectlve amount of a ~ubstantially water insoluble noncationlc antlbacterial agent selected from the group consistlng of halogenated dlphenyl ethers, phenollc compounds selected from the group consisting .;
of phenol, alkyl phenols, halophenols, alkylhalophenols, aromatic halophenols, resorcinols and bisphenolic compounds and halogenated carbanllides ln whlch oral composltion there ls present a synthetic anionic polymerlc polycarboxylate having a molecular welght of about 1,000 to about 1,000,000 in amount of about 0.05-3% by weight.
The present invention also provides an oral composltion comprlsing in an orally acceptable vehicle, an effective anticalculus amount of anticalculus material -. : :..
comprising at least one linear molecularly dehydrated polyphosphate salt and an effective antiplaque amount of a substantially water insoluble noncatlonic antibacterial agent 13 ,. ::
~ . -1328081 :~ ~

selected from the group consisting of halogenated diphenyl ::
ethers, phenolic compounds selected from the group consisting .
of phenol, alkylphenols, halophenols, alkylhalophenols, aromatic halophenols, resorcinols and bisphenolic compounds and :.
halogenated carbanilides, and sufficient fluoride ion source to release up to 5000 ppm of fluoride ion provided that if the : -fluoride ion source is sodium fluoride it is not present in an amount of 0.22% by weight and lf the fluoride ion source is ::
sodium monofluorophosphate lt ls not present in an amount of 0.80% by weight in which oral compositlon there is present a .
synthetic anionic polymeric polycarboxylate having a molecular weight of about 1,000 to about 1,000,000 in amount of about 0.05-3% by weight.
The present lnvention further provldes an oral compo~ition in the form of a mouthwash comprising in an orally acceptable vehicle, an effective anticalculus amount of :
anticalculus material comprislng at least one linear molecularly dehydrated polyphosphate salt and an effectlve antlplaque amount of a substantlally water-insoluble noncationic antlbacterial agent selected from the group consistlng of halogenated d~phenyl ethers, phenolic compounds selected from the group conslstlng of phenol, -.
alkylphenols~ halophenols, alkylhalophenols, aromatlc .
halophenols, resorclnols and blsphenollc compounds and halogenated carbanllides, and a fluorlde ion source in which . :
oral compositlon there is present a synthetic anionic polymeric polycarboxylate having a molecular welght of about 1,000 to -about 1,000,000 in amount of about 0.05-3% by weight.
These oral compositions are useful to combat calculus . ;
and plaque in a mammal. ~ ~ .
., ,., ," ., . . .
4a .. ~
'''' Typical examples of antibacterial agents which are . ;~
particularly desirable from considerations of antiplaque effectiveness, safety and formulation are~
Haloaenated Di~henvl ~thers ~:.
2',4,4'-trichloro-2-hydroxy-diphenyl ether (Triclosan*) -2,2'-dihydroxy-5,5'-dibromo-diphenyl ether.
Phenolic Com~ounds (including phenol and its homologs, mono- and poly-alkyl and aroma~lc halophenols, resorclnol and its derivatlves and blsphenolic compounds) Phenol and its Homoloas ~ .
Phenol 2 Methyl - Phenol ~ :
3 Methyl - Phenol ', 4 Methyl - Phenol 4 Ethyl - Phenol 2,4-Dlmethyl - Phenol ; ;
2,5-Dimethyl - Phenol 3,4-Dimethyl - Phenol .
, ' ~ . , ....
:' . :., ,,'.,,':.:
.: ,. , ; -. j, .. : .. . -: .,' ~::
,~" . . .
ë~mark 4b . ,. ', ~' ll 1 328081 1 -2,6-Dimethyl - Phenol 4-n-Pr~pyl - Phen~
,4-n-Butyl - Phenol 11 4-n-A~yl - Phenol ¦ ;
4-tert-Amyl - Phenol 14-n-Hexyl - Phenol ;14-n-Heptyl - Phenol .
Mono- ant Poly-Alkyl and ~rooatlc Hslophenol~ j Methyl - p-Chlorophenol Ethyl - p-Chlorophenol jln-Propyl - p-Chlorophenol lln-Butyl - p-Chlorophenol jIn-Amyl - p-Chlorophenol ¦ `;
~ec-Amyl - p-Chlor~phenol n-Hexyl - p-Chlorophenol ICyclohexyl - p-Chlorophenol In-Heptyl - p-Chlorophenol n-Octyl - p-Chlorophenol jO-Chlorophenol jMethyl - o-Chlorophenol ¦
Ethyl - o-Chiorophenol "n-Propyl - o-Chlorophenol n-Butyl - o-Chlorophenol ¦n-A~yl - o-Chlorophenol ~,.. .
tert-Amyl - o-Chlorophenol ! ~ ;
r~-Baxyl - o-Chlorophenol n-Heptyl - o-Chlorophenol , ~ --Chlorophenol ! ~.
o-Benzyl - p-Chlorophenol ! :~

..: :;..:.

-::~ ..::

jl -5- 1 -.j j ., :: , .

i1 ~ 32808 ~

o-Benzyl-m-methyl - p-Chlorophenol o-Benzyl-m, m-dlmethyl - p-Chlorophenol o-Phenylethyl - p-Chlorophenol lo-Phenylethyl-~-~ethgl - p-Chlorophenol ! 3-Methyl - p-Chlorophenol l3,5-M~ethyl - p-Chlorophenol 6-Ethyl-3-~ethyl - p-Chlorophenol jl6-n-Propyl-3-Dethyl - p-Chlorophcnol ¦6-lco-Propyl-3-~ethyl ~ - p-Chlorophenol 2-Ethyl-3,5-tl~ethyl - p-Chlorophenol 6-~ec Butyl-3-methyl - p-Chlorophenol ll2-iso-Propyl-3,5-dlmethyl - p-Chlorophenol i¦6-Dlethyl~ethyl-3-methyl - p-Chlorophenol i6-i~o-Propyl-2-cthyl-3-~ethyl - p-Chlorophenol i!
,12-cec Amyl-3,5-dl~ethyl - p-Chlorophenol l2-D1ethylmethyl-3.5-dl~ethyl - p-Chlorophenol l6-8ec Octyl-3-methyl - p-Chlorophenol 'Ip-Bromophenol ! : ~ ~
¦IMethyl - p-Bro~ophenol ,,Ethyl - p-Bromoph~nol I - :
¦¦n-Propyl - p-Bro~ophenol 'In-Butyl - p-Bro~ophenol n-~myl - p-Bromophenol ' :' ¦~ec-kmyl - p Bromophenol .In-Hexyl - p-8ro~ophenol cyclohexyl - p-Bromophenol jlo-Bromophen ~!tert-Amyl - o-Bro~ophenol ! I n-Hexyl - o-Bro~ophenol ., I . .
, i, .
., .
.
,l -6- 1 ~

.

~ 328081 n-Propyl-m,m-Dimethyl-o-Bromophenol 2-Phenyl Phenol 4-chloro-2-methyl phenol 4-chloro-3-methyl phenol 4-chloro-3,5-dimethyl phenol 2,4-dichloro-3,5-dimethylphenol 3,4,5,6-tetrabromo-2-methylphenol 5-methyl-2-pentylphenol 4-isopropyl-3-methylphenol 10 5-chloro-2-hydroxydiphenylmethane Resorcinol and its Derivatives . :
Resorclnol Methyl - Resorcinol :.
Ethyl - Resorcinol n-Propyl - Resorclnol n-Butyl - Resorcinol n-Amyl - Resorcinol :
n-Hexyl - Resorcinol -~.
n-Heptyl - Resorcinol n-Octyl - Resorcinol n-Nonyl ~ - Resorcinol ~ ;
Phenyl - Resorcinol Benzyl - Resorclnol ;:
Phenylethyl - Resorcinol Phenylpropyl - Resorcinol :: ::
p-Chlorobenzyl - Resorcinol ::~
5-Chloro -2,4-Dihydroxydiphenyl Methane 4'-Chloro -2,4-Dihydroxydiphenyl Methane 5-Bromo -2,4-Dihydroxydiphenyl Methane :
~''',' ' '.' ' ,...

r~ _ 1328081 ~

4 ' -Bromo -2,4-Dihydroxydlphenyl Methane Blsphenollc ComPound~
2,2 -methylene bis (4-chlorophenol) 2,2'-methylene bls (3,4,6-trlchlorophenol) 2,2'-methylene bls ~4-chloro-6-bromophenol) bls ~2-hydroxy-3,5-dichlorophenyl) sulflde bls ~2-hydroxy-5-chlorobenzyl) ~ulflde.
Benzoic Ester3 p-Hydroxybenzoic Acld Methyl - p-Hydroxybenzolc Acid :
~thyl - p-Hydroxybenzolc Acld .~
Propyl - p-Hydroxybenzolc Acid ;
Butyl - p-Hydroxybenzolc Acld Haloqenated Carbanilide~
3,4,4'-trlchlorocarbanllide ; :
3-trifluoromethyl-4,4'-dlchlorocarbanlllde 3,3',4-trlahlorocarbanlllde -.
The antlbacterlal agent 1~ present in the oral -compo~ltlon ln an effeatlve antlplaque amount, typlcally about 0.01-5~ by welght, preferably about 0.03-1~. The antlbacterlal :~ agent i~ substantlally water-lnsoluble, meanlng that lti~
olubllity i~ less than about 1~ by welght ln water at Z5C and ..
may be even leg~ than about 0.1%. If anionizable group i~ ::
;~ pre~ent ~olublllty ls determined at a pH a~ whlch lonlzatlon ~: doe~ not occur.

~ ~ .; .::
i " ~ . . , . ~ .
. : .

: : ., .-. -,~

1 328081 ~
62301-146lD
The preferred halogenated diphenyl ether is Triclo~an*. The preferred phenolic compounds are hexyl resor~inol and 2,2'-methylene bis~4-chloro-6-bromophenol). The --most preferred antibacterial antiplaque compound is Triclosan.
Triclosan is dlsclosed in aforementioned United States Patent .::
4,022,880 as an antibacterial agent in combination with an anticalculus agent which provides zinc ions. It ls also disclosed as an antiplaque agent in a dentifrice formulated to ;
contain a lamellar liquid cry~tal surfactant phase having a ;
lamellar spacing of legs than 6.0 mm and whlch may optionally contaln a zlnc salt ln publlshed European Patent appllcation 0161898 of Lane et al and in a dentifrice containing zinc -~
,, : :. : . : .:
citrate trihydrate in published ~uropean Patent Application '"~ -0161899 to Saxton.

The linear molecularly dehydrated polyphosphate salts operative hereln as antlcalculus agent are well known, belng . ~.. . .
generally employed in the form of their wholly or partially ~
.. : :
neutralized water soluble alkali metal (e.g. potassium and ;~ ; ~
. .. .-. .
preferably sodium) or ammonium salts, and any mixtures thereof.

In a preferred embodiment the polyphosphate salt is selected :: . .
from the group conslsting of water-soluble alkali metal or ammonium tripolypho~phates and hexametaphosphates.
Representatlve examples include sodium hexametaphosphate, : -.: . ...

sodium tripolypho~phate, disodlum diacid, tri~odium monoacid :::: . :
and tetrasodium pyrophosphates and the like. Linear polyphosphates correspond to (NaP03)n where n is about 2 to ~'~'.'A' ''' about 125. They are generally employed in the instant oral compositions in approximate weight amounts of 0.1 to 7% ~ .
. .
preferably 0.1 to 7%, more preferably 2 to 7~. When n is at least 3 in (NaP03)n, said polypho~phates are gla~sy in .. .:-character.

~Trade-mark 9 : '.' ''' 62301-146lD
Particularly desirable anticalculus ayents are tetraalkali metal pyrophosphates, including mixtures thereof, such as tetrasodlum pyrophosphate, tetrapotassium pyrophosphate and mixtures thereof. Preferably the amount of tetrapotassium pyrophosphate is greater than the amount of tetrasodium ,~
pyrophosphate. An anticalculus agent comprising about 4.3% to about 7% by weight of the oral compositions wherein the weight ratlo of tetrapotassium pyrophosphate to tetrasodlum pyrophosphate ls from about 4.3l2.7 to about 6~1 is especially preferred.
In order to optimize the anticalculus effectiveness of the oral composition, inhibitors against enzymatlc hydrolysls of the polyphosphate are desirably present. Such a~ents are an amount of a fluoride lon source sufflclent to supply 25 ppm. to 5,000 ppm. of fluorlde lons, and 0% to 3% of a synthetic anionlc polymerlc polycarboxylate havlng a molecular welght of about 1,000 to about 1,000,000, preferably :
about 30,000 to about 500,000.
The sources of fluorlde lons, or fluorlne-provldlng component, as acld phosphatase and pyrophosphatase enzyme lnhlbltor component, are well known ln the art as antl-caries agents. These compounds may be sllghtly soluble in water or may be fully water-soluble. They are characterized by their abllity to release fluorlde ions in water and by freedom from undeslred reactlon with other compounds of the oral preparation. Among these materlals are lnorganlc fluorlde salts, such as soluble alkali metal, alkaline earth metal salts, for example, sodium fluoride, potassium fluoride, ammonlum fluoride, calcium fluoride, a copper fluoride such as cuprous fluoride, zinc fluoride, barium fluoride, sodium fluorosilicate, ammonium fluorosilicate, sodium ~-J. ~

fluorozirconate, sodium fluorozirconate, sodium -monofluorophosphate, aluminum mono- and di-fluorophosphate, and fluorinated ~odlum calcium pyrophosphate. Alkali metal and tin fluorides, such as sodium and stannous fluorldes, sodium monofluorophosphate (MFP) and mixtures thereof, are preferred. :

, ;''' ' , ' .

''' ,' '~ " "~'.

- lOa ~
~ ' ' ',' '', 1 3280~

The amount of fluorlne-provldlng compound i~
dependent to some extent upon the type of compound, its solublllty, and the type or oral preparation, but it must be a non-toxic amount, genera~ly abut 0.005 to about 3.0~ ln the preparatlon. In a dentlrice preparatlon, e.g. dental 921, toothpaste (lncludlng cream), toothpowder, or dental tablet, an amount of such compound whlch releases up to about 5,000 ppm of F lon by welght of the preparation i~ consldered ~atisfactory.
Any suitable mlnlmum amount of such compound may be used, but it 1~ preferable to employ ~ufflclent co~pound to releaso about 300 or, preferably 1085, to 2,000 ppo. more preferable about ~ -800 to about 1,500 ppm of fluorlde lon.
Typlcally, ln the ca~e~ o~ alkall metal 1uorldes, thl~ component 1~ present ln an amount up to about 2% by welght, based on the welght of the preparatlon, and preferably ln the rango of about O.OS% to 1~, partlcularly ln oxce~ of 0.22%. In the ca~o of sodlum ~ono1uorophosphate, the co~pound may be present ln an amount of about 0.1-3%, more typlcally about 0.76%, proferably ln exoess of 0.80t.
In dentlfrlce preparatlon~ such a~ lozenge~ and chewlng gu~, the fluorlne-providlng compound 1~ typlcally present ln an amount ~uf~icient to release up to about 500 ppm, preerably about 25 to 300 pp~ by welght of fluorlde lon.
Generally about 0.005 to about 1.0 wt.% of ~uch compound i~
pr~sent.
The synthetic anionlc polymerlc polycarboxylate ls an lnhibltor o~ alkaline pho~phata~e enzyme. Synthetic anionic polymeric polycarboxylate~ and their complexes wlth various cationlc germicide~, zinc and magneslum have been prevlously dlsclo~ed ~8 antlcalculus agent~ per ~e ln, for example U.S.
Patent No. 3,429,963 to Shedlov~ky; U.S. Patent No. 4,152,420 ~
.,': :'. ,.
: . .
.
, 1 328081 6230l-lq6l to Gaffar; U.S. Patent No. 3,956,480 So Dlchter et al; U.S.
~:......
Patent q,l38,477 to Gaffar; and U.5. Patent No. 4,183,914 to Gaffar et al. However, only ln aforementloned U.S. Patent q,627,977 to Gaffar et al 1~ there dlsclosed use of su~h -~
polycarboxylates alone for lnhiblting sallvary hydrolysl~ of pyrophosphate antlcalculu agent~, ~uch les~ in combination with a compound providing a ~ource of fluoride ion. It ls to be under~tood that the synthetic anlonic polymeric polycarboxylate3 so disclo3ed in the~e several patents are operative ln the compositions and method~ of thi~ invention. - -The synthetic anlonic polymeric polycarboxylates optionally but preferably employed herein are, a~ lndicated above, well known, being often e~ployed ln the ~or~ of thelr free acid~ or preferably partially or more preferably fully neutrallzed water ~oluble alkall metal (e.g. potas~ium and preferably oodlum) or ammonlum salts. Preferred are 1l4 to 4 copolymer~ of malelc anhydrlde or acld wlth anoth~r polymerlzable ethylenlcally uneaturated monomer, preferably methyl vlnyl ether ~malelc anhydrlde) havlng a molecular weight ~M.W.) of about 30,000 to about 1,000,000. These copolymers are avallable for example a~ Gantrez~ ~AN 139 ~H.W. 500,000), A.N. 119 ~H.W. i50,000)~ and proferably S-97 Pharmaceutlcal Grade ~H.W. 70,000), of GAF Corporatlon. The tero ~syntheticn 18 lntended to exclude known thlckenlng or gelllng agents comprl~lng carboxym~thylcellulo~e and other derlvatlves of cellulose and natural gu~s.
Other operatlve polymeric polycarboxylate~ include those disclo~ed ln U.S. Patent No. 3,956,480 referred to above, . . .
such a~ the 1l1 copolymer~ of malelc anhydrlde wlth ethyl . . -acrylate, hydroxyethyl methacrylate, N-vlnyl-2-pyrollldone, or ethylene, the latter belng avallable for exa~ple a~ Monsanto~

~rade-mark - 12 : .

,: .

1 328081 ~-62301-1461 :
EMA No. 1103~, N.W. 10,000 and EMA Grade 61~, and 1l1 copolymers of acryllc acld wlth methyl or hydroxyethyl :-methacrylate, methyl or ethyl acrylate, 1-~obutyl vlnyl ether or N-vinyl-2-pyrrolldine.
, '- :,," ' ' ''"'-',', '.
.... . . . .
. .. .
: ,',~ ;
,,,','",'.~",.
-.
."' " :,' '-'''..
~Trade~mark - 12a -Additional operative polymeric polycarboxylates disclosed in above referred to U.S. Patent No. 4,138,477 and 4,183,914, include copolymers of maleic anhydride with styrene, isobutylene or ethyl vinyl ether, polyacrylic, polyitaconic and polymaleic acids, and sulfoacrylic oligomers of M.W. as low as 1,000, available as Uniroyal ND-2. ;
Suitable generally are polymerized olefinically or ethylenically unsaturated carboxylic acids containing an :~ ,.., ,.: :.
activated carbon-to-carbon olefinlc double bond and at least ~-one carboxyl group, that is, an acld containing an olefinic ... ...... ...
double bond whlch readily functlons ln polymerizatlon because of lts presence ln the monomer molecule either in the alpha~
beta posltion with respect to a carboxyl group or as part of a termlnal methylene grouplng. Illustrative of such aclds are acryllc, methacryllc, ethacryllc, alpha-chloroacrylic, crotonic, beta-acryloxy propionlc, sorblc, alpha-chlorsorbic, clnnamlc, beta-styrllacryllc, muconlc, ltaconlc, cltraconla, mesaconlc, glutaconlc, aconltlc, alpha-phenylacryllc, 2-benzyl acryllc, 2--cyclohexylacryllc, angelic, umbellic, fumaric, malelc aclds and anhydrldes. Other different olefinlc monomers copolymerizable wlth such carboxyllc monomers lnclude vlnylacetate, vinyl chloride, dimethyl maleate and the like.
Copolymers contaln sufficient carboxyllc salt groupis for water-.. .. .
:: ..: . , .
solubillty. :
, ;, Also uieful hereln are so-called carboxyvlnyl polymers dlsclosed as toothpaste components in U.S. 3,980,767 to Chown et al; U.S. 3,935,306 to Roberts et al; U.S. 3,919,409 to Perla et al; U.S. 3,911,904 to Harrison, and U.S. 3,711,604 ,,:, , to Colodney et al. They are commercially available for example under the trademarks Carbopol 934, 940 and 941 of B. F. -Goodrlch, these products consisting essentially of a '.~";'' '' '' " ' t ~ ' 13 '' colloidally water-soluble polymer of polyacrylic acid crosslinked with from about 0.75% to about 2.0% of polyallyl sucrose or polyallyl pentaerythritol as cross linking agent.

r ~ 13a :
B~
.~. .

ln~ synthetic anlonlc polymerlc polycarbo~ylate component is mainly a hydrocarbon with optional halogen and O-contalnlng substltuents and l~nkages as present in for example ester, ether and OH group6, and when present 16 generally employed ln the lnstsnt composltlons ln iiapproximate welght amounts of 0.05 to 3Z, preferably 0.05 to 2%, more preferably 0.l to 2X. Amount6 ln the upper portions of these ranges are typlcally employed in dentifrice compo~itions typically containing a dental abrasive and used ln conJunction wlth brushlng of the teeth, e.g.
tooth pastes (lncludlng creams), gelc, powders and tablets. Amounts ln excess of these ranges may be employed for thlckening or gelling purposes.
As lndicated above, these polymerlc polycarboxyla~es have been fount to be effectlve lnhibltors of alkallne phoephata~e enzyme. Slnce ¦
thls enzyme has llttle actlvlty (for hydrolgzlng pyrophosphate) at about pH 7.0 or below, the polymerlc polycarbo~cylate co~ponent may, lf deelret, be omltted from oral preparatlon~ formulated to operate at ~uch ' pH of 7.0 or below. Such omlsslon however could reduce the ver3atlllty ! : ;
and antlcalculus effectlveness of the present oral compo~ltlons over the I ;
. . . ..
Il broad pH range of about 4.5 to about lO.

il In oral preparatlons such as mouthwashes, lozenges and chewing ,, . ~ , .
¦gum, the fluorlne-provltlng compound may be typlcally pre~ent ln an !iamount sufflclent to release up to about 500 ppm, preferably about 25 to ~ ~ -~! about 300 ppm by welght of fluoride lon. Generally about 0.005 to about , 1.0 wt.Z of such compount 18 present.
Tn certaln hlghly preferred forms of the lnventlon the oral composltion may !~e substantlally liquld ln character, such as a mouthwash or rlnse. In ~uch a preparatlon the vehlcle ls typlcally a waeer-alcohol mixture desirably lncludlng a humectant as descrlbed belo7.~. Generally, the welght ratlo of water to alcohol 1~ ln the range ~ i . . , ' ' -14~
. , ~ , .

,. , ;
of from about l:l to aDout 20:1, preferably about 3:1 to 10:1 and ~ore preferably about 4:1 to about 6:1. The total amount of ~ater-alcohol mixture ln thls type of preparat~on ls typlcally ln the range of from 'about 70 to about 99.9X by welght of the preparation. The alcohol is Ityplcally ethanol or isopropanol. Ethanol 16 preferred.
The pH of such liquid and other preparatlons of the lnvention is generally in the range of from about 4.5 to about 9 and typically from about 5.5 to 8. The pH 18 preferably ln the range of from about 6 lto about 8Ø It 18 noteworthy that the compo~ltlons of the lnventlon jmay be applled orally at a pH below 5 wlthout substantlally decalclfylng or otherwlse damaglng dental enamel. The pH can be controlled wlth scld 1 -ll~e-g- cltrlc acld or benzolc acld) or base (e.g. ~odlum hydroxlde) or jlbuffered (as wlth sotlum cltrate, bcnzoate, carbonate, or bic~rbonate, ¦
¦dlsodlum hydrogen phosphate, ~odium dlhydrogen phosphate, etc.).
In certaln other deslrable forms of thls lnventlon, the oral composltlon may be substantlally solld or pasty ln chJr-cter, ~uch as toothpowder, a dental tablet or a dentlfrlce, that 18 a toothpa~te (dental cream) or gel dentlfrlce. The vehlcle of ~uch ~olld or pasty joral preparatlon~ generally contalns dentally ~cceptable pollshlng materlal. Examplea of pollshlng materlals are water-lnaoluble aotlum ¦
I metaphosphate, potas~lum metaphosphate, trlcalclum pho~phate, dlhydrated lcalclum phoophate, anhydrou~ dlcalclum pho~phate, calclum pyropho~phate, ¦
,Imagenslum orthopho~phate, trlmagneslum pho~phate, calclum carbonate, ¦lalumlnum ~lllcate, zlrconlum slllcate, ~lllca, bentonlte, and mlxtures thereof. Other sultable pollshlng materlal lnclude the par~lculate thermosettlng reslns descrlbed ln U.S. Pat. No. 3,070,510 of Dec. 15, ! 1962 such as melamlne-, phenolic, ~nd urea-formaldehyde~, and ~! cross-llnked polyepoxlde~ and polyesters. Preferret poll~hlng naterlals :... : .....
i! lnclude crystalllne slllca havlng partlcle ~ized of up to about 5 1 ~

-l5- ~ ;

,i I :-:

i 1 32808~i '~

mlcrvns, a mean partlcle 6lze or up t~, about 1. I mlcrons, and a surface area of up to about 50, 000 cm. /gn., slllca gel or colloldal slllca, i 2nd co~iplex amorphous alkall metal alumlnoslllcate.
~ien vl6ually clear gels are employed, a pollshlng agent of o colloidal slllca, such as tho6e sold under the trademark SYLOID aB
¦Sylold 72 and Syloid 74 or under the trademark SANTOCEI, as Santocel 100 alKali metal almuino-6illcate complexes are particularly u6eful, slnce ~ they have refractlve lndlce6 clo6e to the refractlve lndlces of gelllng ;!agent-llquld ~lncludlng water nnd/or humectant)syEitems commonly used ln ¦ ;
dentlf lces .
Many of the ~o-called 'water-lnsoluble" poll6hlng ~iaterlal6 are , .: .
i anlonlc ln character and al60 lnclude 6mall amounts of soluble materlal . i ;
IlThus, lnsoluble sodluDm metaphosphate may be formed ln any ~ultable manner as lllustrated by Thorpe '8 Dlctionary of ~pplied Chemistry, VOlume 9, 4th Edltlon, pp. 510-511. The forms of lnsoluble ~iodlum , metaphosphate known as Madrell '8 ~ialt and Kurrol ~Ei ~ialt re further examples of oultable materialEi. These metaphosphate Eialts e~chiblt only l!a mlnute siolutillity ln water, and therefore are commooly referred to as !!lnsoluble metaphosphates (IMP). There is present therein a mlnor amount ¦of soluble phosphate materlal as impur1tles, usually a fcw percent ~iuch l;as up to 4% by welght. The amount of ~oluble pho~phate materlal, ~hich !j 19 believed to ~nclude a soluble 60tlum triraetaphosphate in the case of ¦ insoluble metaphosphate, may be reduced or eliminated by washing wlth I i water lf deslred. The lnsoluble alkall metal metaphosphate i8 typlcally , employed ln powder form of a partlcle size ~uch that no more than 1~ of the materlal 19 larger than 37 mlcrons.
The pollshlng maSerlal ls generally present ln the solld or pssty composltions in weight concentrations of about 10% to about 99~.
Preferably, lt i6 present ln amounts ranglng from about 10% to about 75%

, jin toothpaste, ~nd from about 70~ to about 99~ in toothpowder.
j In a toothpaste, the llquld vehlcle may comprise water and ¦humectant eyplcally ln an amvunt ran8ing from about 10% eo about R0% by weight of the preparatlon. Glycerine, propylene glycol, sorbitol, polypropylene glycol and~or polyethylene glycol (e.g. 400-600) e~empllfy ¦sultable hu~ectents/cArrlers. A190 advantageous are llquid ~lxtures of water, glycerine and sorbitol. In clear gels where the refractlve lndex ,ls an important conslderation, about 3-30 wt. X of water, 0 to about 70 wt.Z of glycerlne ~nd about 20-80 wt. Z of sorbltol are preferably employed.
Toothpa~tes, creams and gels typlcally contain a natural or ~loynthetlc thlckener or gelllng agent in proportlon~ of bout 0.1 to ¦
" ~ .
¦!about 10, preferably about 0.5 to about 5wt.~ ultable thickener i~
synthetlc hectorlte, a synthctlc colloldal magnesLu~ alkall metal jslllcate comple~ clay Jvallable for èxample ao Laponlt ~(e.g. CP, SP
2002,D) ~arketed by Laporte Intu~trles Llmlted. Laponlte D analysl~
show~, appro~lmately by welght, 58.00Z S102, 25.40% MgO, 3.05Z Na2O, 0.98~ Li20, and ~ome water and trace metals. Its true ~peclflc gravlty ls 2,53 and lt has an appJrent bulk denslty (g./~l. at 8% mol~ture) of II 1Ø
Other ~ultable thlckeners lnclude Irlsh ~oss, gum tragac~nth, starch, polgvlnylpyrrolldone, hydro~yethypropylcellulose, hydrosybutyl methyl cellulose, hydroxypropyl ~ethyl celluloce, hydro~yethyl cellulo6e ~ ~ -(e.g. avallable as Natroso ~, ~odium carbo~y~ethyl cellulose, and colloldal slllca such as flnely ground Sylold~(e.g. 244).
It wlll be understood that, as i~ conventional, the oral ~preparatlons are to be sold or otherwise dl~trlbuted ln sultable 'labe]led packages. Thu9 a ~ar of mouthrlnse wlll have a label describlng lt, ln ~ub6tance, as a mouthrlnse or ~outhwash ant having -17- ~;

1 3~8081 1 d~rectlon6 for lts use; and a toothpaste, crea~ or gel wlll usually be in a collapslble tube, typlcally slumlnum, llned lead or plastlc, or ~ther squeeze, pump or pressurlzed dlspenser for metering out the contents, hsving a label descrlbing lt, ln substance, as a toothpa~te, I
gel or dental cream. l ¦
Organlc surface-actlve agents are used ln the composltlons of ! :: :
th~ present lnvention to achleve lncreased prophylactlc actlon, asslst !1 ln achlevlng thorough and complete disper~lon of the antlcalculus agent i! throughout the oral cavlty, and render the lnstant composltlon6 more co~metlcally acceptable, The organic Hurface-actlve msterlal 19 preferably anlonlc, nonlonlc or ampholytlc ln nature, and lt 18 ¦¦preferred to employ as the 8urface-actlve agent a deterslve materlal !¦ which lmparts to the composltlon deter~lve and foa~lng psopertleg.
Suitable e~amples of snlonlc curfactant8 are wster-801uble aalt~ of hlgher fatty acld monoglycer1de mono~ulfates, such as the ~odlum ~alt of ~ithe monosulfated monoglycerlde of hydrogenated coconut oll fatty aclds, ;Ihlgher alkyl sulfate~ ~uch a~ sodlum lauryl sulfate, alkyl aryl Igulfonste~ 8uch aa ~odlum dodecyl benzene sulfonate, higher alkyl 'l~ulfoacetste~, hlgher fatty acld esters of 1,2-dlhydro~y propane ¦sulfonate, and the ~ubctantlally saturated hlgher aliphatlc ~cgl mldes j¦of lower sllphatlc amino carbo~yllc acld compounds, euch as tho~e havlng !!12 to 16 carbon~ ln the fatty acld, alkyl or acyl radlcals, and the i~llke. Example~ of the last mentloned amldes are N-lauroyl sarco~lne, ,land the sodlum, potas~lum, nnt ethanolamlne ~alts of N-lauroyl, ,IN-myrlstoyl~ or N-palml~oyl sarcoslne whlch ~hould be substantlally free I -. frOm soap or 61mllar higher fatty acld materlal. The u6e of these ~sarco~lnate compounds ln the oral compo~itions of the present lnvent~on i8 particularly advan~ageous since these materlals e~hiblt 8 prolonged and ~arked effect 1~ the lnhlbltion of acld formgtlon ln the oral cavlty j ...

Ij -18- ~I

due to carbohydrate breakdown in addition to exerting some reduction in the solubility of tooth enamel in acid solutions. Examples of water-soluble nonionic surfactants are condensation products of ethylene oxide with various reactive hydrogen-containing compounds reactive therewith having long hydro-phobic chains (e.g. aliphatic chains of about 12 to 20 carbon atoms), which condensation products ("ethoxamers") contain hydrophilic polyoxyethylene moieties, such as condensation products of poly(ethylene oxide) with fatty ~`
acids, fatty alcohols, fatty amides, polyhydric alcohols (e.g. sobitan mono-sterate) and polypropyleneoxide (e.g. Pluroni ~materials). It is preferred to use from about 0.05 to 5% by weight and preferably about 0.5 to 5% of the foregoing surface active materials in the instant compositions.
Various other materials may be incorporated in the oral prepar-stions of thi~ invention such as whitening agents, preservatives, silicones, chlorophyll compounds and/or ammoniated material such as urea, diammonium phosphate, snd mixtures thereof. These adjuvants, where present, are , .
incorporated in the preparations in amounts which do not substantially adversely afiect the properties and characteristics desired. Significant amounts of zinc, magnesium and other metal salt~ and materials, generally soluble, which would complex with active components of the instant invention are to be avoided.
.. ... .
Any suitable flavoring or sweetening material may also be employed.
Examples of suitable flavoring constituents are flavoring oils, e.g. oil of spearmint, peperment, wintergreen, sassafras, clove, sage, eucalyptus, marjoram, cinnamon, lemon, and orange, and methyl salicylate. Suitable sweetening agents include sucrose, lactose, maltose, sorbitil, xylitol, sodium cyclamate, perillartine, AMP (aspartyl phenyl alanine, methyl ester), ~;
saccharine and the like. Suitably, flavor and sweetening agents may together comprise from about 0.1% to 5% more of the preparation.
In the preferred practice of this invention an oral composition -:: .~ - ; .:: ': ~
',': ''- :':
'"' .,' ~,~
;... :.: :: ::' ,~,...... .... .

1,~,`,. ' '. -:
1 ~ 2 8 0 ~
.1 1 . '.'.'.. :
accord~ng to this ln~entlon such as a mouthwash or dentlfrlce contalnlng the compositlon of the present lnventlon 16 preferably applled regularly to dental enamel, ~uch as every day or every second or thlrd day or lpreferably from l to 3 times dally, at a pH of about 4~5 to about 9, generally about 5.5 to about 8, preferably about 6 to 8, for at least 2 weeks up to 8 weeks or oore up to llfetl~e.
The compo61tluns of thifi lnventlon can be lncorporated ln lozenges, or ln chewlng gum or other products, e.g. by stlrrlng lnto a " warD gu~ bsse or coJtlng the outer surface of a gum base, lllu-tratlve of whlch may be mentloned Jelutone, rubber latex, vlnylite re~ln~, etc., de~lrablg wlth conventlonal plastlclzerQ or softeners, ~ugar or other jsweeteners or carbohydrate~ ~uch a~ glucose, sorbltol and the llke.
.. . .. .
I~ The followlng example~ are further Illu~tratl~e of the nature l'of the pre~ent lnventlon, but lt 1~ underatood that the lnventlon ~8 not lted thereto. ~11 a~ount~ and proportlona referred to hereln and ln the appended clalo~ are by welgbt.

. , .

i !
....

Il. 1, . ..... ... .

: . ..

I ;.~"'':' :.~ ': '. , "

!. -20- 1 :::

Il 1 328081 il :~
E~ample 1 ~

~ .

I Slurrles and ~olutions de~cribed below are prepared to determlne effectiveness ln terms of minlmum lnhlbitory concentratlon (MIC) of ¦varlouc antlbacterlal agents agalnst a variety of orsl bacterlal urganisms impllcated ln formatlon of plaque and leadlng to glnglvltls on dental surfaces. Soft plaque contalns about 1.7 ~ 1011 organlsm/gm.
(net welght). The antlbacterlal agent6 are admlxed wlth anlonlc ! :: :
materlals, partlcularly anlonlc ~urface actlve agent often commonly ~employed ln oral co~posltlons and polyphoophate antlcalculus agent.
j; Minlmum lnhlbltory concentratlon (MIC) of antlbacterlal agent Ijl~ wed to evaluate the efflcacy of the ~gent ln vltro. HIC 1R deflned a~ the mlnlmum concentratlon ln mlcrograms/ml of antlbacterlal agent at ¦whlch the growth of bacterla i~ completely lnhiblted by the agent. The aller the MIC value the greater 18 the cfflcacy of the antlbacterlal ! agent to inhlblt the growth of the bacterla. The ln vitro MIC data 18 ~!related to the efflcacy of the dentlfrlce ln vivo ~lnc~ retentlon ant release of antlbacterlal agent lnto the oral cavlty after toothbrushlng ln the r~nge of mCBtm~
il In the Tabloo, follo~lng tl~closure nd following ~ample~, the !¦ agent Trlclo~an, 2,4,4'-trlchloro-2'-hydro~ydlphenyl thcr 1~ lntlcated a~ "TCHE"; the quaternary ar~onium antibacterial agent~ benzthonlum I ;~
,chlorlde 18 lndicatot as "BTC"; The blguanlte chlorhe~ltlne dlgluconate ~is lndlcated a8 "CH-, ~otlum lauryl 3ulfate 18 lndlcsted as "SLSn; the c~polymer of mslelc anhytrlde and methyl vlnyl ether available from GAF
icorporation as "Gantrez S-97" 18 ldentlflet as "Gantrezn; tetra~odlum pyrophosphate 18 ldentlfiet aY "pyrophosphate~; and godlum fluorlde ls ltentifled a~ "NaF". ¦ ~
'..-. ' ":' '' :

-21~

`~

~ TABLE 1 l -~
; .. . I .:. . ~: .
I' Mlnlmu~ Inhlbltlon Concentratlun ¦Test tMIC) ¦
olutlon _ in mcg/ml Bscterlodes Bacteriodes Actlnobacll~u6 Streptococcus glnglvalls lntermedluc actlno~ycete~- mutang comltan~
l. 0.5% TCHE and 2.5 2.5 5.0 25.0 l~ SLS ln ¦ wster i2. 0.5Z TCHE, 2.5 2.5 5.0 25.0 i l~ SLS, I 1% Gantrez, ! 2% Pyrophusphate I and 0.2Z NaF ln I wster l3. lZ SLS ln NE NE NE NE
li water ! 4. lX SLS, NE NE NE NE ¦
; 1~ Gantre~ snd j ~, I 2% Pyropho-ph9te 'I ln water ¦¦note: NE - not effectlve The result~ lntlcste that TCHE in the pre~ence of anlonlc ;~
surfactant inhlblted four dental plaque organlsms, Bacterlode~
~lngiv~ , Bacteroldeo lntermedlus, Actlnobacllluo actlnomycetemcoQltan- and Strep. mutans at 2.5 mcg/ml and 2.5 mcg/ml, 5-0 mcg/ml ~nd 25,.0 mcg/ml respectlvely(l). Sl~ilar antlbacterlal effect is ~een ln the presence of Gantrez/pyrophosphate/fluorlde(2). ~';
, SLS per se ~nd a co~bination of SLS/Gantrez/pYropho~phate/fluoride was ~' ! lneffectlve(3 and 4). 1 ¦ -. le 18 notewortby thst ln human cllnlcsl te~ts wlth cstlonlc ¦ ;
antlbacterlal agents, 0.075X BTC dissolved in water i8 effectlve ln ¦reduclng plaque formatlon whlle 0.075% BTC and 1% pyrosphosph~te 1 ~ ' "dlssolved ln water 1~ not. Slmilarly, 0.01~ CH dl~sol~ed in ~eer i6 ¦effectlve ln reduclng plaque forQstlon whlle 0.01% C~ ~nd lX ~odlum N-lauroyl ssrcoslnnte dl~olved in water i~ not.
l .
I I ", '`''; ', '' Il -22- ~ ~
I ..
I

~ I ::
I1 1 32808~ : ~ ~
E~ample 2 The sdsorptlon to and release from tooth mlnerals for ! antIpl~que/ ~ntltartar efflcacy of agents 18 ss8es8ed by adsorption of antlbacterial agent to saliva coated tooth nlneral hydroxyapatlte ln the ¦presence and the absence of pyropho~phate (soluble tetr-sodlum ¦ ^
llpyrophosphste)/Gantrez/NaF.
'I 200 mg. of hydroxyspatlte (HA) 18 trested wlth humsn salivs for ¦
~,2 hours. The e~cess sallva 18 wsshed off with a buffer and saliva coated HA
18 used for adsorptlon studles. Varlous concentratlons of TCHE ln SLS
ot ln SLS/pyrophosphate/Gantrez/NaF are ml~ed wlth the coated NA and lncubated ~t 37 for 3 hours under contlnuou~ sgltstlon. At the end of ,lncubatlon perlod, the ~lxtures are centrlfuged, HA ~eparated nd the ¦
amounts of TCHE ad~orbed determined by eotlmatlng TCHE ln the 'supernatant at 283nM ln a Gllford spectrophotometer. The aQounts ,ladsorbed are calculated by the dlfference between the amount added and ¦ ;
~he amount left ln the oupernatant after the lncubatlon wlth coated HA. ¦
The tsble below summarlzes the data.

!l I ,1 :, 1 1 ~,.. .
.

,.' ~'. '. .:
~ ~ ;

-. ~
.1 .. :.. ..

~ 23~

I1 1 3280~
1! 1 : ~

C~m~onents and Concentratlons ~ of TCHE Adsorbed to Coated HA
. . , . j û.005X TCHE ln 1% SLS 80Z
.01~ TCHE ln lX SLS 85~ 1~
¦0.015% TCHE in 1% SLS 85% 1 . .
0.02Z TCHE in 1% SLS 88X
~0.005% TCHE ln 1% SLS; 0.5Z 80X
Gantrez; 2% pyrophosphate/
0.24% NaF
0.01% TCHE 85%
. 0.015X TCHE " 86%
0.02% TCHE " 87Z , The tata lndicatea that the atdltlon of pyropho~phste/
'Gantrez/NaF does not ln?alr adsorption of TCHE to sallva coated tooth ~lnerals. .:, .
,1 . I '''' .

~',~' :' '.', ' I j ' ' ' .

!~ l ! ¦ I .'' .. : . ' i !
l i :
i l , . . .
I! ! : --: .
.. . .

, i ', ` ' .. - ~: . .
!1 -24~

l i I

:
-"!1 `-` 1 328081 `-I :

~ Exa~iple 3 1 '.
iDentlfrlce Composltlon~ A B C ¦~
" Parts Parts P~rts Glycerine 15.00 10.20 15.00 ¦¦Polyethylene Glycol 600 5.00 3.00 5.00 ¦
j~Ota Carrageenan 0.60 ~ 0.60 mSodium Carbo~ymethyl Cellulose - 1.00 - j :
" .. :,:
,¦Sodium Saccharln 0.40 - 0.40 : 1:
Sodium Cyclamate - 3.00 ~i ' , :: :' Sodlum Fluorlde 0.243 0.243 0.243 ~j~eionized water 15.08 29.907 23.657 'ITitanium Dlo~lde - - 0.50 'ISodlum Henzoate - 0.50 - ¦ :
~D~C Blue No. l(lX 9O1utlon) 0.400 ~Sorbltol t70X) 19.807 22.50 22.50 ~~ .
IGsntrez S-97 8.330(*) 1.00(**) 1.00(**) i' ' I! Tetra~odlum Pyrophosphate 1.50 1.50 1.50 ITetrspotasslum Pyrophosphate 4.50 4.50 4.50 '¦Preclphated Amorph. Nydrated Sllica 16.00 19.50 - ¦ -'iPreclphated A~iorp. Silica - - 16.00 ¦
¦ii containing com~lned alu~lna ¦ ~-il S~l~ca ~llckener 7.00 - 5-50 Flavor 1.10 0.95 1.10 ;Sodlum Lauryl Sulfate 1.20 1.20 1.20 :.
TCHE 0.50 0 50 0 50 ¦:
':, ' -,.,,, -.
-.- :- .
~* liquid j ~ : :
ii** powder ~
,::
! . :::-i j ! .- . - :.:
il j .....

il -25- ` `

il I . .:.- ,:
il I .... ,.'' ` ~ ~

Example 4 The dentlfrlce de~crlbed ln Example 3A 1~ coGpared ~lth the ~a~e compu61tlun except wlthout ny TCHE and wlth dded 0 50 part6 of water Aqueous extracts of each dentlfrlce are prepared a~ follows S0 ~1 of dlctllled ~ter 1~ added to 1.0 g~ of each dentlfrlce, l~ed ~ell t~r a couple of hours wlth 6tlrrlng bar and centrlfuged, after vhlch the s~pernatant 18 coll~cted a- aqueous extr~ct. ~ntlb-cterlal ctlvlty of the dentlfrlce extr~cts are evaluatcd on Bacterlode~ glnglvall~ ;
Result4 re 4u~marized below T~BLE 3 '~

Inhlbltlon of Gro~th of 8hcteriode~ Clngl~Jl14 Treatm-nt Extr~ct from dentlfr~ce contalnlng 100.0 TCHE (1 500) extract from d-ntifrlcc ~lthout 0.0 ; ' TCHE (l S00) TCHE (S.0 ~cg/~l) by ~t~olf 100 0 The~- re~ult~ ~ndlc-te that TCNE ntlbact-rl~l antlpl~que Jgent 14 co~p-tlble ~n dentlfrlce compo~ltlon cont-lnlng anlonlc ~urfactant plu~ pyropho~ph-te ntlcalculu~ Sngredlent~ ~lth en~yme lnhlbltor6 GAntrer n~ N F. Sl~ r coopar-bl- ffect~ pre~ hen e-ch of hexyl re~orclnol, 2,2'-~ethylene bl~4-chloro-6-bromophenol)/
repl-ce TCHE.

, --26- ~

,~.l ll :
Il 1 32808 1 I
~xa~ple 5 M uthrlnse P~rt~
. .
TetrssodLum Pyropho~phate 2.00 iGsntrez S-97 0.25 j il~
I Glycerlne 10.00 !¦ Sodlum Fluorlde 0.05 ¦
Pluronlc* F108 2.00 ~Polyoxyethylene/Polyoxypropylene Block Copolymer) I TCHE 0.10 j .
.IFlavor 0.40 : I
Water Q.S. to 100.00 1 ~qj l j ,. ", E~amplc 6 . ~ ', '' '' ' ! 75-80X Sug~r ¦
jjl-20% Corn Syrùp ;:;
0.1-1.0 Fla~or 2Z Tetrssodlu0 Pyroph~phate .: -~ :
.: :. , ,:
,jo.25z Cantr-z 8-97 '0.01 to 0.05~ NaF
i I ' ';', ' . '""
0.01 to O.lZ TCHE
¦I to 5~ i~agne~lu~ S`tearate Lubricant I :-. :~
-1 to 0.2~ Water , .-~

! *Trade ~iark ,~ , .. ..

,j . ,,`

., ,, . -, il -27~
il ! . ,. -I1 l 3280~ 1 ~xample 7 Chewing Gum Part6 d Gum base 25.00 ilSorbltol (70X) 17.00 ¦
TCHE 0.50 to 0.10 !l I : . .
Tetra~odium Pyropho~ophate2.00 Gantrez S.97 0.25 NaF O 05 Glycerine 0.50 1l :
! Cry~talllne Sorbltol 53.00 ~lavor and Water Q.S. to 100.00 ~ Thl~ lnventlon ha~ beeo te~crlbet wlth re~pect to certaln lpreferr-t e~bodi~ents and lt wlll be unter~toot that ~otlflcatlons and ,Ivarlatlons thereof obvlou~ to those ~kllled ln th- art re to be jlnclutet wlthln the purvlew of thls appllcatlon and the scope of the ,lappented clalms.

I !
-:
! j ..
-!

. i . . . ..

I i I .- . .

, . . .
I l -28~
I,, ,''' ~ .-~'

Claims

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

1. An oral composition comprising in an orally accep-table vehicle, an anticalculus effective amount of material comprising at least one linear molecularly dehydrated polyphos-phate salt as essential anticalculus agent and an antiplaque effective amount of a substantially water insoluble noncationic antibacterial agent selected from the group consisting of halogenated diphenyl ethers, phenolic compounds selected from the group consisting of phenol, alkyl phenols, halophenols, alkylhalophenols, aromatic halophenols, resorcinols and bisphenolic compounds and halogenated carbanilides in which oral composition there is present a synthetic anionic polymeric polycarboxylate having a molecular weight of about 1,000 to about 1,000,000 in amount of about 0.05-3% by weight.

2. The oral composition claimed in Claim 1 wherein said at least one linear molecularly dehydrated polyphosphate salt is present in amount of about 0.1-7% by weight and said sub-stantially water insoluble noncationic antibacterial agent is present in amount of about 0.01-5% by weight.

3. The oral composition claimed in Claim 2 wherein said antibacterial agent is a halogenated diphenyl ether.

4. The oral composition claimed in Claim 3 wherein said halogenated diphenyl ether is 2,4,4'-trichloro-2-hydroxy-diphenyl ether.

29a 5. The oral composition claimed in Claim 2 wherein said antibacterial agent is about 0.03-1% by weight of 2,4,4'-trichloro-2'hydroxydiphenyl ether and said polyphosphate salt is about 4.3-7% by weight of a mixture of tetrapotassium pyro-phosphate and tetrasodium pyrophosphate in a weight ratio of from about 4.3:2.7 to about 6:1.

6. The oral composition as claimed in any one of Claims 1 to 5 additionally containing sufficient fluoride ion source to release 1085 to 2000 ppm of fluoride ion.

7. The oral composition as claimed in any one of Claims 1 to 5 in the form of a mouthwash and additionally containing a fluoride ion source.

8. The oral composition as claimed in any one of Claims 1 and 3 to 5 in which the said at least one linear molecularly dehydrated polyphosphate salt is present in an amount of 0.1-7%
by weight.

9. The oral composition as claimed in Claim 1 or 2 in which the anticalculus material comprises a mixture of tetrasodium pyrophosphate and tetrapotassium pyrophosphate in which the amount of tetrapotassium pyrophosphate is greater than the amount of tetrasodium pyrophosphate.

10. The oral composition as claimed in Claim 9 in which the polyphosphate salt is a mixture of tetrapotassium pyro-phosphate and tetrasodium pyrophosphate in a weight ratio of from 4.3:2.7 to 6:1.

11. The oral composition as claimed in any one of Claims 1 to 4 in which the antibacterial agent is about 0.03-1% by weight of 2,4,4'-trichloro-2'hydroxydiphenol ether.

12. The oral composition as claimed in any one of Claims 1 to 5 in which the oral composition contains a dentally acceptable water insoluble polishing agent and the said oral composition is a toothpowder, dental tablet, toothpaste or dentifrice.

13. The oral composition as claimed in Claim 12 in which the oral composition contains about 10-80% by weight of a liquid phase comprising water and humectant, about 0.1-10% by weight of a gelling agent and about 10-75% by weight of the polishing agent and the oral composition is a toothpaste or gel dentifrice.

14. The oral composition as claimed in Claim 13 in which the polishing material is a silica polishing material.

15. The oral composition as claimed in any one of Claim 1 to 5 in which the oral composition contains about 70-99.9% by weight of a mixture of water and alcohol in a weight ratio of from about 1:1 to about 20:1 and the oral composition is a mouthrinse.

16. The oral composition as claimed in Claim 15 in which the alcohol is ethanol.

17. An oral composition comprising in an orally acceptable vehicle, an effective anticalculus amount of anti-calculus material comprising at least one linear molecularly dehydrated polyphosphate salt and an effective antiplaque amount of a substantially water insoluble noncationic anti-bacterial agent selected from the group consisting of halo-genated diphenyl ethers, phenolic compounds selected from the group consisting of phenol, alkylphenols, halophenols, alkylhalophenols, aromatic halophenols, resorcinol and bisphenolic compounds and halogenated carbanilides, and sufficient fluoride ion source to release up to 5000 ppm of fluoride ion provided that if the fluoride ion source is sodium fluoride it is not present in an amount of 0.22% by weight and if the fluoride ion source is sodium monofluorophosphate it is not present in an amount of 0.80% by weight in which oral composition there is present a synthetic anionic polymeric polycarboxylate having a molecular weight of about 1,000 to about 1,000,000 in amount of about 0.05-3% by weight.

18. The oral composition as claimed in Claim 17 wherein when the fluoride ion source is sodium fluoride it is present in an amount in excess of 0.22% by weight.

19. The oral composition as claimed in claim 17 wherein the fluoride ion source is sodium monofluorophosphate present in an amount in excess of 0.80% by weight.

20. The oral composition as claimed in Claim 17, 18 or 19 wherein the fluoride ion source is sufficient to release 300 to 2000 ppm of fluoride ion.

21. The oral composition as claimed in Claim 17 or 18 in which the fluoride ion source is sodium fluoride present in an amount of at least 0.24% by weight.

22. The oral composition as claimed in Claim 17, 18 or 19 in the form of a dental gel, toothpaste, dental cream, toothpowder or dental tablet.

23. The oral composition as claimed in Claim 17, 18 or 19 in which the said polyphosphate salt is present in an amount of 0.1-7% by weight.

24. The oral composition as claimed in Claim 23 in which said polyphosphate salt is present in an amount of 2 to 7% by weight.

25. The oral composition as claimed in Claim 17, 18 or 19 in which the said antibacterial agent is present in an amount of 0.01-5% by weight.

26. The oral composition as claimed in Claim 17 in which the said antibacterial agent is a halogenated diphenyl ether.

27. The oral composition as claimed in Claim 26 in which the halogenated diphenyl ether is a 2,4,4'-trichloro-2'-hydroxydiphenyl ether.

28. The oral composition as claimed in any one of Claims 17, 18, 19 and 24 in which the said polyphosphate salt is selected from the group consisting of water-soluble alkali metal or ammonium tripolyphosphates and hexametaphosphates.

29. The oral composition as claimed in Claim 28 wherein the said polyphosphate is sodium tripolyphosphate.

30. The oral composition as claimed in Claim 28 wherein the said hexametaphosphate is sodium hexametaphosphate.

31. The oral composition as claimed in Claim 27 in which the 2,4,4'-trichloro-2'-hydroxydiphenyl ether is present in an amount of about 0.03-1% by weight.

32. The oral composition as claimed in any one of Claims 17, 18, 19 and 24 in which the said polyphosphate salt is a mixture of tetrapotassium pyrophosphate and tetrasodium pyrophosphate in an amount of 4.3 to 7% by weight in which the amount of tetrapotassium pyrophosphate is greater than the amount of tetrasodium pyrophosphate.

33. The oral composition as claimed in Claim 32 in which the said polyphosphate salt is a mixture of tetrapotassium pyrophosphate and tetrasodium pyrophosphate in a weight ratio of from 4.3:2.7 to 6:1.

34. The oral composition as claimed in any one of Claims 17 to 19, 24, 26 and 27 in which said oral composition contains a dentally acceptable water-insoluble polishing agent and the said oral composition is a toothpowder, dental tablet, toothpaste or dentifrice.

35. The oral composition as claimed in Claim 34 in which the said oral composition contains about 10-80% by weight of a liquid phase comprising water and humectant, about 0.1-10% by weight of a gelling agent and about 10-75% by weight of the said polishing agent and the said oral composition is a toothpaste or gel dentifrice.

36. The oral composition as claimed in Claim 34 in which the said polishing agent is a silica polishing material.

37. An oral composition in the form of a mouthwash comprising in an orally acceptable vehicle, an effective anticalculus amount of anticalculus material comprising at least one linear molecularly dehydrated polyphosphate salt and an effective antiplaque amount of a substantially water-insoluble noncationic antibacterial agent selected from the group consisting of halogenated diphenyl ethers, phenolic compounds selected from the group consisting of phenol, alkyl-phenols, halophenols, alkylhalophenols, aromatic halophenols, resorcinols and bisphenolic compounds and halogenated carbanilides, and a fluoride ion source in which oral composition there is present a synthetic anionic polymeric polycarboxylate having a molecular weight of about 1,000 to about 1,000,000 in amount of about 0.05-3% by weight.

38. The oral composition as claimed in Claim 37 in which the said polyphosphate salt is present in an amount of 0.1-7%
by weight.

39. The oral composition as claimed in Claim 37 in which the said antibacterial agent is present in an amount of 0.01-5%
by weight.

40. The oral composition as claimed in Claim 37 or 38 in which the said polyphosphate salt is selected from the group consisting of water-soluble alkali metal or ammonium tripolyphosphates and hexametaphosphates.

41. An oral composition as claimed in Claim 40 wherein the said tripolyphosphate is sodium tripolyphosphate.

42. An oral composition as claimed in Claim 40 wherein the said hexametaphosphate is sodium hexametaphosphate.

35a 43. An oral composition as claimed in Claim 37 or 38 in which the said polyphosphate salt is a mixture of tetra-potassium pyrophosphate and tetrasodium pyrophosphate in an amount of 4.3 to 7% by weight in which the amount of tetra-potassium pyrophosphate is greater than the amount of tetrasodium pyrophosphate.

44. An oral composition as claimed in Claim 37 or 38 which contains about 10-80% by weight of a liquid phase comprising water and humectant.

45. The oral composition as claimed in Claim 43 in which the said polyphosphate salt is a mixture of tetrapotassium pyrophosphate and tetrasodium pyrophosphate in a weight ratio of from 4.3:2.7 to 6:1.

46. The oral composition as claimed in Claim 37 or 38 in which the said oral composition contains about 70-99.9% by weight of a mixture of water and alcohol in a weight ratio of from substantially 1:1 to about 20:1.

47. The oral composition as claimed in Claim 46 in which the said alcohol is ethanol.