CA1339301C - Antibacterial antiplaque, anticalculus oral composition - Google Patents
Antibacterial antiplaque, anticalculus oral compositionInfo
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- CA1339301C CA1339301C CA000616760A CA616760A CA1339301C CA 1339301 C CA1339301 C CA 1339301C CA 000616760 A CA000616760 A CA 000616760A CA 616760 A CA616760 A CA 616760A CA 1339301 C CA1339301 C CA 1339301C
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Abstract
An oral composition such an 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-2 1-hydroxydiphenyl ether (Triclosan).
Description
- -~ 1339301 Thls lnventlon relates to an antlbacterlal antlplaque antlcalculus oral composltlon. More partlcularly, lt relates to ah oral composltlon contalnlng a polyphosphate antlcalculus (that ls, antltartar) agent and a compatlble antlbacterlal agent efféctlve to lnhlblt plaque.
In U.~. Patents 4,627,977 to Gaffar et al; 4,515,772 to Parran et al~ and 4,32~,551 to Parran, oral composltlons are descrlbed whlch lnclude varlous polyphosphate compounds. In the patent ~~o Gaffar et al, a llnear molecular dehydrated poly-phosphate salt ls employed ln con~unctlon wlth a fluorlde lon-provldlng source and a synt~letlc llnear polymerlc polycarboxy-late to lnhlblt calculus formatlon.
In the patents to Parran et al and to Parran water soluble dlalkall metal pyrophosphate alone or mlxed wlth tetra-alkall metal pyrophosphate ls employed.
Oral coMpositlons whlch lnhlblt calculus formatlon on dental surfaces are hlghly deslrable slnce calculus ls one of the causltlve factors ln perlodontal condltlons. Thus, lts reductlon promotes oral hyglene.
Dental playue ls a precursor of calculus. Unllke calculus, however, plaque may form on any part of the tooth surface, partlcularly lncludlng at the glnglval margln. Hence, besldes belng unslghtly, lt ls lmpllcated ln the occurence of glnglvltls.
Accordlngly, lt would be hlghly deslrable to lnclude antlmlcroblal agents whlch have been known to reduce plaque ln oral composltlons contalnlng antlcalculus agents. Indeed, thls has been descrlbed ln U.S. Patent 4,022,880 to Vlnson et al, whereln a compound provldlng zlnc lons as an antlcalculus agent ls admlxed wlth an antlbacterlal agent effectlve to retard the growth of plaque bacterla . A wlde varlety of antlbacterlal tgent~ ere dezcrlbed wlth the zlnc ~r 13~9~01 co ounds lnclud g catlonlc materlals such as guanldes and quaternary ammonlum compounds as well as non-catlonlc compounds such n8 halogensted 6allcylanilldes and halogenated hydroxydlphenyl ethers.
Hltherto, the cAtlonlc sntlbacterlAl mAterlflls such AS
chlorhexldlne, benzthonlum chlorlde and cetyl pyrldlnlum chlorlde have been the sub~ect of greatest lnvestlgatlon as antlbactetlal antlplaque Agents. However, ln splte of thelr belng used ln con~uctlon wlth zlnc antlcalculus agent, they are not effectlve when used wlth anlonlc materl~ls ruch AS polyphosphate anticalculus agent. ThlA
lneffectlveness ls consldered to be qulte surprlsing a6 polyphosphates are chelatlng agents and the chelatlng effect has prevlously been known to lncrease the efflcacy of catlynlc antlbacterlal agents.(see e.g.
Dislnfectlon, Sterllizntlon and Preservatlon, 2nd Ed., Black, 1977, page 915 and Inhlbltlon and Destructlon of the Microblal Cell, Hugo, 1971, page 215). Indeed, quaternary ammonlum compound ls present ln the plaque control mouthwash contalnlng pyrophosphate of U.S. Patent 4,323,551 and bls-blguanlde antlplaque agent ls suggested ln the Antlcalculus pyrophosphate oral composltlon of U.S. Patent 4,515,772.
In vlew of the surprlslng lncompatlblllty of cAtlonlc antlbacterlsl Agents wlth polyphosphates present as sntlcalculus agents, lt was qulte unexpected tilAt other antlbacterlal agent would be effectlve.
It ls an Advantage of thls lnventlon thAt certaln Antlbacterlal Agents Are effectlve ln antlcalculus oral composltlons to lnhlblt plaque formAtlon .
It is a further advantAge of thls lnventlon that a composltlon i6 provlded whlch ls effectlve to reduce plaque and calculus formatlon.
It Is a further advAntAge of thls lnventlon thAt an Antlplaque, antlcalculus orAl composltlon 18 provlded whlch 1B effectlve to reduce the occurence of glnglvltls.
' 1339301 Additional advantages of this invention will be apparent from consideration of the following specification.
In accordance with certain of its aspects tllis lnvention 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 antibacterial agent selected from the group consisting of halogenated diphenyl ethers, phenolic compounds, benzoate esters, and halogenated carbanilides.
The present invention provides 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 polyphosphate salt selected from the group consisting of water-soluble alkali metal or ammonium tripolyphosphates and hexametaphosphates and an effective antiplaque amount of a substantially water-lnsoluble noncationic antibacterial agent 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 a fluoride ion source.
The invention also provides an oral composition comprising in an orally acceptable vehicle, an effective anticalculus amount of anticalculus material selected from the group consisting of water-soluble alkali metal or ammonium tripolyphosphates and hexametaphosphates 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, 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.
The invention further provides an oral composition comprising in an orally acceptable vehicle, an effective anticalculus amount of at least one polyphosphate salt selected from the group consisting of water-soluble alkali metal, tripolyphosphates and hexametaphosphates, as essential anticalculus agent and an effective antiplaque amount of a substantially water-insoluble noncationic antibacterial compound as essential antiplaque agent.
The invention additionally provides an oral composition comprising in an orally acceptable vehicle an effective anticalculus amount of sodium tripolyphosphate as essential anticalculus agent, and an effective antiplaque amount of a substantially water-insoluble noncationic antibacterial compound as essential antiplaque agent.
The invention also provldes an oral composition comprising, in an orally acceptable vehicle, an effective 4a 1~39301 anticalculus amount of at least one water-soluble linear molecularly dehydrated polyphosphate salt as essential anticalculu~ agent and an effective antiplaque amount of a substantially water-insoluble non-cationic antibacterial compound as essential antiplaque agent.
The invention further provides an oral compositlon comprising, in an orally acceptable vehicle, an effective anticalculus amount of pyrophosphate as essential anticalculus agent, an effective antiplaque amount of à substantially water-insoluble non-cationic antibacterial compound as essential antiplaque agent and as essential inhibitor of salivary enzymatic hydrolysis of the polyphosphate salt a fluoride ion-providing source in an amount sufflcient to supply about 25 ppm to about 2,000 ppm of fluoride ions.
The invention additionally provides an oral composition comprising, in an orally acceptable vehicle, an effective anticalculus amount of at least one water-soluble linear molecularly dehydrated polyphosphate salt as essential anticalculus agent, an effective antiplaque amoùnt of a substantially water-insoluble non-cationic antibacterial compound as essential antiplaque agent and as essential inhibitor of salivary enzymatic hydrolysis of the polyphosphate salt a fluoride ion-providing source in an amount sufficient to ~upply about 25 ppm to about 2,000 ppm of fluoride ions.
The invention also provides an oral composition comprising, in an orally acceptable vehicle, a dentally 4b ,f~.
acceptable sillca pollshlng agent, an effectlve antlcalculus amount of at least one water-soluble llnear molecularly dehydrated polyphosphate salt as essential anticalculus agent, an effective antiplaque amount of a substantially water-insoluble non-cationic antibacterial compound as essential antiplaque agent and a mixture of (A) an amount of a fluoride ion-providing source sufficient to supply about 25 ppm to about 2,000 ppm fluoride ions; and (B) about 0.05~ to about 3% of a water-soluble synthetlc anionic polymeric polycarboxylate.
In preferred embodiments of the above aspects of the invention the substantially water-lnsoluble non-cationic antibacterial compound is other than a parahydroxybenzoic acid ester.
Typical examples of antibacterial agents which are particularly desirable from considerations of antiplaque effectiveness, safety and formulation are:
Haloqenated DiphenYl Ethers 2',4,4'-trichloro-2-hydroxy-diphenyl ether ~Triclosan*) 2,2'-dihydroxy-5,5'-dibromo-diphenyl ether.
Phenolic Compounds (including phenol and its homologs, mono- and poly-alkyl and aromatic halophenols, resorcinol and its derlvatives and blsphenollc compounds).
~Trade-mark 4c ,~
1333~1 Phenol and its Homologs Phenol 2 Hethyl - Phenol 3 Methyl - Phenol 4 Hethyl - Phenol 4 Ethyl - Phenol 2,4-Dimethyl - Phenol 2,5-Dimethyl - Phenol 3,4-Dimethyl - Phenol 4d l33~30r 2,6-Dimethyl - Phenol 4-n-Propyl - Phenol - 4-n-Butyl - Phenol 4-n-Amyl - Phenol 4-tert-Amyl - Phenol 4-n-Hexyl - Phenol 4-n-Hertyl - Phenol t Mono- snd Poly-Alkyl and Aromatic H~lophenols Methyl - p-Chlorophenol Ethyl - p-Chlorophenol n-Prupyl - p-Chlorophenol n-8utyl - p-Chlorophenol n-Amyl - p-Chlorophenol ,~- sec-Amyl - p-Chlorophenol n-Hexyl - p-Chlorophenol Cvclohexyl - p-Chlorophenol n-Heptyl - p-Chlorophenol n-~ctyl - p-Chlorophenol O-Chlorophenol Methyl - o-Chlotophenol Ethyl - o-Chlorophenol n-Propyl - o-Chlorophenol n-Butyl - o-Chlorophenol n-Amyl - o-Chlorophenol tert-Amyl - o-Chlorophenol n-l;exyl - o-Chlorophenol n-Heptyl - o-Chlorophenol r~Chl.otuphenol o-Benzyl - p-Chlorophenol -- 13393~1~
o-Benzyl-m-methyl - p-Chlorophenol o-Benzyl-m, m-dlmethyl - p-Chlorophenol o-Phenylethyl - p-Chlorophenol o-Phenylethyl-m-methyl - p-Chlorophenol 3-l~etllyl - p-Chlorophenol 3,5-Dlmethyl - p-Chlorophenol 6-Ethyl-3-methyl - p-Chlorophenol 6-n-Propyl-3-methyl - p-Chlorophenol 6-lso-Propyl-3-methyl - p-Chlotophenol 2-Ethyl-3,5-dimethyl - p-Chlorophenol 6-sec Butyl-3-methyl - p-Chlorophenol 2-16u-Propyl-3,5-dlmethyl - p-Chlorophenol 6-C~lethylmethyl-3-methyl - p-Chlorophenol 6-lfio-Propyl-2-ethyl-3-methyl - p-Chlorophenol 2-sec Amyl-3,5-dimethyl - p-Chlorophenol 2-nt ethylmethyl-3.5-dintethyl - p-Chlorophenol 6-~ec Octyl-3-methyl - p-Chlorophenol p-Bromophenol Methyl- p-Bromophenol Ethyl- p-Bromophenol n-Propyl- p-Bromophenol n-Butyl- p-Bromophenol n-Amvl- p-Bromophenol sec-Amyl- p-Bromophenol n-Hexyl- p-Bromophenol cyclohexyl- p-Bromophenol o-Bromophenol tcrt-Am)l- o-Bromophenol n-He~yl- o-Bromophenol ~ ~ -_ -.-. - ~ 6 13~9301 n-Propyl-m,m-Dimethyl - o-Bromophenol ~-Phenvl Phenol 4-chloro-2-methyl phenol 4-chloro-3-methyl phenol 4-chloro-3,5-dlmethyl phenol 2,4-dlcl-loro-3,5-dimethylphenol 3,4,'i,6-terabromo-2-methylphenol 5-methyl-2-pentylphenol 4-lsopropyl-3-methylphenol 5-chloro-2-hydroxydipheny~ethane Resorclnol and lts Derivatives Resorcinol Methyl - Resorcinol Ethvl - Resotclnol n-Propyl - Resorclnol n-Bu~yl - Resorclnol n-Amyl - Resorclnol n-l~cx l - Resorcinol n-lleptyl - Resorclnol n-Octyl - Resorcinol n-Nonyl - Resorclnol Phenyl - Resorclnol Benzyl - Resorclnol Phenylethyl - Resorclnol Rhenylpropyl - Resorcinol p-Chl_robenzyl - Resorclnol 5-Chloro -2,4-Dlhydroxydiphenyl Methane 4'-Chloro -2,4-Dihydroxydiphenyl Hethsne 5-Bromo -2,4-Dihydroxydlphenyl Methane 4'-~romo -2,4-Dlhydroxydlphenyl Methane Blsphenollc ComPounds 2,2'-methylene bls (4-chloropllenol) 2,2'-methylene bls 13,4,6-trlchlorophenol) 2,2'-methylene bls 14-chloro-6-bromophenol) bls (2-hydroxy-3,5-dlchlorophenyl) sulflde bls 12-hydroxy-5-chlorobenzyl) sulfide.
Benzolc Esters p-Hydroxybenzolc Acld l~ethyl - p-Hydroxybenzolc Acld ~thyl - p-Hydroxybenzolc Acld Propyl - p-Hydroxybenzolc Acld Butyl - p-l~ydroxybenzolc Acld Haloqenated Carbanilldes 3,4,4'-trlchlorocarbanllide 3-trlfluoromethyl-4,4'-dlchlorocarbanlllde 3,3',4-trlchlorocarbanlllde The antlbacterlal agent ls present ln the oral composltlon ln an effective antlplaque amount, typlcally about 0.01-5~ by welght, preferably about 0.03-1~. The antlbacterlal agent ls substantlally water-lnsoluble, meaning that lts solublllty ls le3s than about 1% by welght ln water at 25~C and may be even le6s than about 0.1~. If anlonizable group ls present solubllitY is determlned at a pH at whlch lonizatlon does not occur.
~7:
- 133~3131 , , . .. . .. ..
Tlle preferred halogenated diphenyl ether is Triclosan~. The preferred phenolic compounds are hexyl resor-cinol and 2,2'-methylelle bis(4-chloro-6-bromophenol). The most pref,erred antibacterial antiplaque compound is Triclosan.
Trlclosan is disclosed in aforementioned ~nited States Patent 4,022,880 as an antibacterial agent in combination with an anticalculus agent wllicll provides zinc ions. It is àlso dis-closed as an antiplaque agent in a dentifrice formulated to contaln a lamellar liquid crystal surfactant phase having a , .. -~--- 10 lamellar spacing of less than 6.0 mm and which may optionally contain a zinc salt in published European Patent application 0161898 of Lane et al and in a dentifrice containing zinc citrate - trihydrate in published European Patent Application 0161899 to Saxton.
The linear molecularly dehydrated polyphosphate salts operative herein as anticalculus agent are well known, being generally employed in the form of their wholly or partially neutralized water soluble alkali metal Ce.g. potassium and preferable sodium) or ammonium salts, and any mixtures thereof.
Representative examples include sodium hexametaphosphate, sodium tripolyphospilate, disodium diacid, trisodium monoacid and tetrasodium pyrophosphates and the like. Linear polyphos-phates correspond to (NaPO3)n where n is about 2 to about 125.
They are generally etnployed in the instant oral compositions in approximate weight amounts of 0.1 to 7% preferably 0.1 to 7%, more preferably 2 to 1~. When n is at least 3 in (NaPO3)n, said polyphosphates are glassy in character.
*Trade Mark - 133~301 Partlcularly des;-e~"e allt.tcalculus AgentR are tetraslksll metal pyropho6phate6, lncluding mlxture6 thereof, such as tettssodlum ryrorhosrhAte, tetrsrota~slum pyropho6phate and mlxtures thereof. An nntlcalculus agent comprlslng about 4.3Y0 to about 7X by welght of the orsl composltlons whereln the welght ratlo of tetrApotasslum pyropho6phate to tetrasodlum pyropho6phate ls from sbout 4.3:2.i to about 6:1 is e6peclally preferred.
In order to optimize the antlcalculu6 effectiveness of the oral composltlon, inhlbltors ngain6t enzymatlc hydroly61s of the polyphosphate are desirably present. Such agents are sn amount of a fluorlde ion source 6ufflcient to supply 25 ppm. to 5,000 ppm. of fluorlde lons, snd OX to 3~ of a synthetlc anlonic polymeric polycsrbo~ylAte havlng a molecular welght of about 1,000 to about l,000,000, preferably About 30,000 to sbout 500,000.~
The 60urces of fluoride lons, or fluorlne-providin~ component, as acld phosphatase and pyrophosphatase enzyme inhlbltor component, are well knot~n ln the art as antl-caries agents. These compounds may be htly soluble ln water or m~y be fully wnter-soluble. They are characterized by thelr ablllty to relea6e fluorlde lons ln wnter And by freedom from undeslred reactlon with other compound8 of the oral preparatlon. Among the6e materlsl6 are lnorganlc fluorlde 6alts, such as soluble a~kali metsl, slkaline earth metal salt6, for example, sodium fluorlde, potasslum fluoride, ammonium fluorlde, cslclum fluorlde, a copper fluoride 6uch a8 cuprous fluotlde~ zlnc fluoride, barlum fluorlde, fiodlum flouroslllcste, smmonlum florosilicate, sodium ~
tluotozlrconste, sodlum fluorozirconate, sodlum monofluorophosphate, slumlnum mono- snd dl-fluorophosphate, and fluorinated sodlum cslclum yrophosphste. Alkall metal snd tln fluorldes, such as sodlum and stsnnous fluorldes, sodlum monofluorophosphste (MFP) snd mlxtures thereof, are preferred.
13393~
The amount of fluorlne-provldlng compound ls dependent to some extent upon the type of compound, lts solubillty, and the type or oral preparatlon, hut lt must be a non-toxlc,amount, generally abut 0.005 to about 3.0% ln the preparatlon. In a dentlfrlce preparatlon, e.g. dental gel, toothpaste tincludlng creaml, toothpowder, or dental tablet, an amount of such compound whlch releases up to about 5,~000 ppm of lon by welght of the preparatlon ls consldered satlsfactory.
Any suitable mlnlmum amount of such compound may be used, but lt ls preferable to employ sufflclent compound to release about 300 or, preferably 1085, to 2,000 ppm. more preferable about 800 to about 1,500 ppm of fluorlde lon.
Typlcally, ln the cases of alkall metal fluorldect, thls component ls present ln an amount up to about 2~ by welght, based on the welght of the preparatlon, and preferably ln the rar.~e of about 0.05% to 1~, partlcularly ln excess of 0.22~. In the case of sodium monofluorophosphate, the compound may be present ln an amount of about 0.1-3%, more typlcally about 0.76~, preferably ln excess of O.B0~.
In dentlfrlce preparatlons such a~ lozenges and chewlng gum, the fluorlne-providlng compound ls typlcally present ln an amount sufflclent to relea~te up to about 500 ppm, preferably about 25 to 300 ppm by welght of fluoride lon.
Generally about 0.005 to about 1.0 wt.~ of such compound ls present .
The ~yntl-etlc anionlc polymeric polycarboxylate ls an lnhlbltor of alkallne phosphatase enzyme. Synthetlc anlonlc polymerlc polycarboxylate~ and thelr complexes wlth varlous catlonlc germlcldes, zlnc and magneslum have been prevlously dlsclosed as antlcalculus agents per ~te in, for example U.S.
Patent No. 3,429,963 to Shedlovsky U.S. Patent No. 4,152,'420 133~3~
to Gaffar U.S. Patent No. 3,956,480 to Dlchter et al; U.S.
; Patent 4,138,417 to Gaffar: and U.S. Patent No. 9,183,914 to Gaf~ar et al. Nowever, only in aforementloned U.S. Patent 4,627,977 to Gaffar et al 1B there dlsclosed use of such polycarboxylate3 alone for lnhlblting sallvary hydrolysls of pyrophosphate anticalculus agents, much le6s in comblnation wlth a compound providing a source of fluoride ion. It is to be understood that the synt11etic anionlc polymerlc polycarboxylates so disclo~ed in these several patents are operatlve ln the composltlons and methods of thls lnventlon.
The synthetlc anlonlc polymerlc polycarboxylates optlonally but preferably employed herein are, as lndicated ahove, well known, belng often employed in the form of thelr free acids or preferably partially or more preferably fully neutrallzed water soluble alkall metal ~e.g. pota~sium and preferably sodlum) or ammonium salts. Preferred are 1.4 to 4-1 copolymers of maleic anhydrlde or acld wlth another polymerl7able ethylenlcally unsaturated monomer, preferably methyl vlnyl ether ~malelc anhydrlde) havlng a molecular welght ~M.W.~ of about 30,000 to about 1,000,000. The6e copolymers are available for example as Gantrez~ ~AN 139 ~H.W. 500,000), A.N. ll9-~11.W. 250,000)~ and preferably S-97 Pharmaceutlcal Grade ~I~.W. 70,000), of GAF Corporation. The term "synthetlc"
~ i8 lntended to exclude known thlckenlng or gelllng agents comprlslng carboxymethylcellulose and otller derlvatlves of cellulose and natural gums.
Other operatlve polymerlc polycarboxylates include those disclosed ln U.S. Patent No. 3,956,480 referred to above, such as the 1l1 copolymers of malelc anllydrlde wlth ethyl acrylate, hydroxyethyl methacrylate, N-vlnyl-2-pyrollldone, or ethylene, the latter being avallable for example as Monsanto~
~Trade-mark - 12 -~33930~
EIIA No. 110~, N.W. lO,OOO and EMA Grade 61~, and 1-1 copolymers of acryllc acld wlth methyl or hydroxyethyl methacrylate, methyl or ethyl acrylate, lsobutyl vinyl etller or N-vlnyl-2-pyrrolldlne.
~Trade-mark - 12a -...
13393~1 Additlonal operative polymerlc polycsrboxylates dl6closed ln above referred to U.S. Pstent No. 4,138,477 and 4,183,914, lnclude copolymers of maleic anhydrlde wlth styrene, isobutylene or ethyl vlnyl ether, polyacrylic, polyltaconic and polymalelc aclds, and sulfoacryllc ol1gomers of M.W. as low as 1,000, avallable 88 Unlroyal ND-2.
~--- Sultable generally are polymerlzed oleflnlcslly or e~h~lenlcally unsaturated carboxylic acids contalnlng an actlvated carbon-to-carbon olefinic double bond and at least one carboxyl group, tllat is, an acid contalnlng an olefinlc double hond which readily functions in polymerization because of lts presence ln the monomer molecule either in the alplls-beta po6ition witll respect to n carboxyl group ur as part of a terminal methylene grouping. Illustrative of such aclds are acryllc, methacrylic, ethacryllc, alpha-chloroacrylic, crotonlc, beta-acryloxy propionic, sorblc, slpha-chlorsorblc, clnnamlc, beta-styrllacrylic, muconic, itaconic, cltraconic, mesaconic, g1utaconic, scon1tic, alpha-phenylacryllc, 2-benzyl acrylic, 2-cyclohexylacrylic, angelic, umbellic, fumaric, mslelc aclds and anhvdrldes. Other different oleflnlc monomers copolymerlzsble wlth such carboxyllc monumers lnclude vlnylacetste, vlnyl chlorlde, dlmethyl maleate snd the like. Copolymers contsln Rufflclent csrboxyllc sslt groups for water-solubility.
Also useful hereln sre so-cslled carboxyvlnyl polymers dl~closed as toothpaste components ln 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,gll,904 to llarrlson, and U.S. 3,711,604 to Colodney et al. They are commrrc~Ally available for example under the trRdemQrks CRrbopol 934, 940 and 94l of B. F. Goodrich, these products conslsting essentially of !a colloldally water-soluble polymer of polyacryllc scld crosfilinked wlth from about 0.75% to about 2.0X of polyallyl sucrose or polyallyl ~cntaerythrltol as cross llnklng sgent.
~ 1339301 ne synthetlc anlonlc poly~erlc polycarbo~ylate component 18 mainly a hydrocarbon wlth optlonal halogen and O-contalnlng substltuents and llnkages ss present ln for example ester, ether snd OH group~, and when present~ls generally employed ln the lnYtsnt composltlons ln ~pproxlmate welght amounts of 0.05 to 3~, prefersbly 0.05 to 2Z, more preEerably O.l to 27.. ~mounts ln the upper portlons of these rsnges are typlcally employed in dentlfrlce compo61tlons typlcslly contslnlng a dental sbraslve snd u6ed ln con~unctlon wlth brushlng of the teeth, e.g.
tooth pastes (lncludlng creams~, gels, powderfi snd tablets. Amount6 ln r~ excess of these ranges may be employed for thlckenlng or gelllng purpose~.
As lndlcated above, these polymerlc polycarboxylates have been found to be effective lnhlbltors of alkAllne phosphstase enzyme. Slnce thls enzyme has llttle actlvlty (for hydrolyzlng pyrophosphste) at sbout pH 7.0 or below, the polymerlc polycsrbo~ylate component msy, lf deslred, be omltted from oral prepnratlons formulated to operste st 6uch pH of 7.0 or below. Such omlsslon however could teduce the versatlllty and antlcAlculus effectlveners of the present oral composltlons over the broad pH rsnge of sbout 4.5 to sbout 10.
In oral prepsratlons such as mouthwashes, lozenge8 snd chewlng Rum, the fluorlne-provldlng compound may be typlcally present ln sn amount sufflclent to relesse up to about 500 ppm, preferably about 25 to about 300 ppm by welght of fluorlde lon. Generally sbout 0.005 to sbout 1.0 wt.~ of such compo~nd is present.
In certaln hlghly preferred forms of the Inventlon the oral c~mposltlon may be substantlslly llquld In character, such as a ~outhwash or rlnse. In such 8 prepsrstlon the vehlcle la typlcslly 8 water-slcohol mlxture deslrably lncludlng a humectant as descrlbed below. Generslly, the welght ratlo of water to alcohol is ln the range 1~393~1 of from sbout l:l to aDout 2~:1, prefetAbly about 3:l to lO:l and more preferably about 4:1 to about 6:1. The totai amount of water-alcohol mlIture ln thls type of preparatlon ls typlcally ln the ranBe of from about 70 to sbout 99.9~ by welght of the preparatlon. The AlCOhOl 18 tYP1CA11Y ethanol or lsopropanol. Ethanol lfi preferred.
The pH of such liquid and other prepArAtlons of the lnventlon ls generally ln the range of from about 4.5 to about 9 and typically from about 5.5 to 8. The pU i8 preferably ln the range of from about 6 to about ô.O. It 16 noteworthy that the composltlons of the lnvention may be applied orally at a pH below 5 wlthout substAntlally decalcifying or otherwl6e damaglng dental enamel. The pH can be controlled wlth acld (e.g. cltrlc acld or benzulc scld) or base (e.g. sodlum hydroxlde) or buffered (as wlth sodlum cltrate, benzoate, cArbonate, or blcarbonate, disodium hydrogen phosphate, sodium dlhydrogen phosphAte, etc.).
In cert~in other deslrable forms of thls lnvention, the oral compofiition may be substantiAlly solid or paFty ln character, such afi toothpowder, a dental tablet or a dentlfrlcej that 18 a toothpaste (dental cream) or gel dentlfrlce. The vehlcle of such solld or pasty oral preparAtions generally contains dentally acceptable pollfihlng materlal. ExAmples o~ pollshing mAterials are water-lnsoluble sodlum metaphosphate, potAsslum metapho6phate, tricalclum phosphste, dihydrated calclum phosphate, anhydrous dlcalclum phosphste, calclum pytophosphnte, magenslum orthophosphate, trimAgneslum phosphAte, calclum carbonate, aluminum fillicate, zirconium slllcAte, filllca, bentonlte, and mlxtures thereof. Other sultAble pollshlng material include the particulàte thermosettlng reslns descrlbed ln U.S. Pat. No. 3,070,5lO of Dec. l5 1962 such as melamlne-, phenollc, and urea-formaldehydes, and cross-llnked polyepoxldes and polyesters. Preferred poll8h~ng materlal lnclude crystalllne 8111CA havlng particle sized of up to About 5 - - ~
mlcrun6, a meAn partlcle size or up tu about 1.1 mlcrons, and a surface area of up to About 50, 000 cm. /gm., slllca gel or colloldal slllca, nnd complex amorphou6 alkall metal alumlnoslllcste.
Whe~ vl6ually clear gels are employed, a poll6hlng sgent of collotdal slllca, such a6 thofie 601d under the trademark SYLOID a8 Sylold 72 snd Syloid 74 or under the trademsrk SANTOCEL as Santocel 100 alhall metal almuino-6111cate complexe6 Are partlcularly useful,~slnce they have refractlve indlce6 close to the refractive indices of gelling sgent-liquid (lncludlng water and/or humectsnt)system6 commonly used ln dentlflces.
Many of the so-cslled "water-insoluble" pollshlng materials sre anlonlc ln character snd slso lnclude small smount6 of soluble materlal.
Thus, lnsoluble sodlum metaphosphate msy be formed ln sny sultAble manner as lllustrated by Thorpe's Dlctlonary of Applled Chemlstry, Volume 9, 4th Edltlon, pp. 510-511. The forms of lnsoluble sodlum metaphosphate known as Madrell's salt and Kurrol's salt are further examples of sultable materlals. These metaphosphste salts exhlblt only a mlnute solublllty ln water, and therefore are commonly referred to ss lnsoluble metsphosphates (IMP). There ls present thereln a mlnor amount of ~oluble phosphate materlal a8 Impuritles, usually a few percent such as up to 4% by welght. The amount of soluble phosphate materlal, whlch ls belleved to lnclude a soluble sodlum trlmetaphosphate ln the case oE
lnsoluble metaphosphate, msy be reduced or ellmlnated by washlng wlth water if deslred. The lnsoluble alkall metal metaphosphate ls typlcally employed ln powder form of a partlcle slze such that no more than 1~ of the materlal ls larger than 37 mlcrons.
The pollshlng materlal ls generslly present ln the solld or pasty composltlons in welght concentrstlons of sbout 10% to about 99~.
Preferably, lt 18 present ln amounts ranglng from about 10% to about 7S~
~ ===
.., ln toothpast~, snd from about 70~ to about 99% ln toothpowder.
In 8 toothpsste, the llquld vehicle msy comprlse wster and humectsnt typicslly in an ~mount rsnglng from about 10% to sbout 80% by welght of the preparstlon. Glycerlne, propylene glycol, sorbltol, polypropylene glycol and/or pulyethylene glycol (e.g. 400-600) exempllfy sultAble llumectants/csrrlers. Also sdvantageous sre llquld mlxtures of water, glycerlne and sorbltol. In clear gels where the refractive lndex 1~ An l~portant con61derstlon, sbout 3-30 wt. % of water, O to about 70 wt.X of glycerlne and sbout 20-80 wt. % of sorbltol are preferably employed.
Toothpa~tes, cresms and gels typlcslly contsln a natural or synthetlc thlckener or gelllng agent ln proportlons of about 0.1 to about 10, prefernbly sbout 0.5 to about 5wt.~. A sultable thlckener 18 synthetlc hectorlte, a synthetlc colloldal magneslum alkall metal slllcate complex clay svallable for example as Laponlt ~(e.g. CP, SP
2002,D) marketed by Lsporte Industrle6 Llmlted. Lsponlte D analysls shows, approxlmately by welght, 58.00% S102, 25.40~ MgO, 3.05X Na20, n~a8~0 Li20, and some water snd trsce metals. Its true speclflc grsvity 18 2.53 and lt has an apparent bulk denslty (g./~l. at 8% moisture) of I I . O .
¦ Other sultsble thlckeners lnclude Irlsh mofis, gum tragacanth, ~tarch, polyvlnylpyrrolldone, hydtoxyethypropylcellulose, hydroxybutyl methyl cellulose, hydroxypropyl methyl cellulose, hydroxyethyl cellulose (e.g. avsllsble as Natroso ~ , sodlum carboxymethyl cellulose, and colluldal Glllcs such 88 flnely ground Sylold~(e.g. 244).
It wlll be understood th~t, as 18 conventlonal, the oral prepArstlons are to be sold or otherwlse dlstrlbuted ln sultable l~helled pAcksges. Thus a ~sr o~ mouthrlnse wlll hsve A lAbel descrlblng lt, In substance, a8 a mouthrlnse or mouthwash and havlng .
~~ -1~39301 directlon6 for lts use; and a toothpaste, cream or gel wlll u6ually be in A collapfilble tube, typlcally alumlnum, llned lead or plastlc, or other squeeze, pump or pressurlzed dispenser fvr meterlng vut the contents, havlng a label descrlbing lt, ln substance, 88 a toothpaste, "r~ e' or dental cream.
~~ Organlc surface-actlve agents are used ln the composltl!ons of the present lnventlon to achleve lncreased prophylactlc actlon, asslst ln schlevlng thorough and complete dlsperslon of the Antlcalculus agent throughout the orAl cavlty, and render the lnstant composltlon6 more cvsmet~cally acceptable. n-e organlc surface-actlve msterlsl ls preferably flnlonlc, nonlonlc or ampholytlc ln nature, snd lt 18 preferred to employ a8 the 6urface-actlve agent a detet~lve materlal whlch lmparts to the compofiltlon deterslve and foamlng propertlefi.
Sultsble examples of anlonlc 6urfactantfi are water-soluble fialts of h~gher fatty acld monoglycerlde monofiulfates, fiuch as tlle sodlum sslt Or ~-he mnno~ulfated monoglycerlde of hydrogenated coconut oll fatty aclds, hlgher alkyl sulfates fiuch as sodlum lauryl fiulfate, alkyl aryl sulfonates such as sodlum dodecyl benzene sulfonate, hlgher alkyl - 6ulEoacetates, hlgher fatty acld efiters of 1,2-dlhydroxy propane ~ulfonate, and the substantlally satursted hlgher allphatlc acyl smldefi of lower allphatlc amlno carboxyllc acld compoundfi, such afi those havlng 12 to 16 carbons ln the fatty acld, alkyl or acyl radlcals, and the llke. Examplefi of the last mentloned amldes are N-lauroyl sarcoslne, and the sodlum, potasslum, and ethAnolsmlne ~alts of N-1AUrOY1~
N-myrlstoyl, or N-pslmltoyl fiarcofilne whlch should be substsntlally free f~vm 60ap or slmllar hlgher fatty acid materlal. The use of thefie fiarcoslnate compound~ ln the ùral compofiltlonfi of the present lnventlon tQ partIcularly advantageoufi slnce thefie materlalfi exhlblt a prolonged ! and marked effect ln the Inhlbltton of acld formatlon ln the oral cavlty !' 3393~
-19- 623n~ ,61 due to carbollydrate breakdown in addition to exerting some reduction in tl~e solul)ility of tooth ennmel in acid solutions. ~xamples oE water-solul-le nonionic surEactants are condensation products o( etllylene oxide with various renctive hydrogell-colltainillg compounds reactive therewitll having long hydro-phobic chtlills (e.g. aliphatic cllains oE about 12 to 20 carbon atoms), whicl con(lensat:ioll products t"etlloxalmers") contain hyclrophilic polyoxyethylelle moieLies, sucll as condell~nlioll pro(ltlcts of poly(ethylene oxicle) with tntLy ncids, fatty nlcollols~ Entty nmides~ polyhydric alcohols (e.g. sobi~an mono-sterate) and polypropylelleoxi(le (e.g. rluronic~materials). ~t is pl-eferre(l 1() to use trom nbollt 0.05 to 5Y by weigh~ and preEerably about 0.5 to 5Y oE the foregoing surEace active ~-~nterials in the instant compositions.
Various other materials may be incorporated in the oral prepar-ations of this invention sucll as wllitening agents, preservatives, silicones, cl-lorophyll compollnds and/or ammoniated material such as urea, diammonium phosl-llate, nnd mixtures thereoE. Illese ad juvants~ where present, are incorportlLed in the prcpnrntions in nmounts whicll do not subst-llltinlly adversely aitect the properties and charscteristics desired. Signiricant amoullts of zinc~ magllet;illm and other metnl salts and materials, generally soluble, whicll would complex with active components oE the instant invention are to be avoided.
Any suitable Elavoring or sweetening material may also be employed.
Examptes oE suitnble Elavoring constit~lents are flavoring oils, e.g. oil oE
spenrmil~t, pepcrment, winLergreen, sassaCras, clove, sQge, eucalypLus, Illtll' jllrlllll, ('illlllllll(lll~ 1(!lllOll, 1111(1 tll'llllgt!, nll(l tlletllyl 19111 it'ylllt('~ Slli I 111)11!
sweetenillg agellts inclu(le sucrose, lactose~ maltose, sorbitil, xylitol, sodillm cyclamtlte~ perillartine, AM~ (aspartyl phenyl alanine, methyl ester), snccharine and the like. Suitt3bly, flavor and sweetening agents may together comprise Erom about O.IX to 5~ more of the preparation.
In the preEerred practice oE this invention an oral composition i3~93~1 ~
accordlng to thia lnventlon ~uch a8 a mouthwash or dentlfrlce contslnlng the compusltlon of the present lnventlon ls preferably applled regularly to dentsl enamel, such as every day or evety second or thlrd dsy or prefersbly from I to 3 tlmes dally, at A ptl of nbuut 4.5 to about 9, generally about 5.5 tu about 8, preferably about 6 to 8, for at least 2 weeks up to 8 weeks or more up tu llfetlme.
The compusltlons of thls lnvention cfln be lncorporated In lozenges, or ln cl-ewlng gum or other products, e.g. by stlrrlng lnto a warm gum base or coating the outer surface of a gum base, lllustrative of which may be mentloned ~elutone, rubber latex, vlnylite reslns, etc., deslrably with conventlonal plastici7ers or softeners, sugar or other sweeteners or carbohydrates sucl~ as glucose, sorbltol and the llke.
The followlng examples are further Illustratlve of the nature uf the present lnvention, but it is understood that the invention is not limlted thereto. ~11 amounts and proportions referred to hereln and in the appended clalms are by welght.
.. D
133~301 E~ample l Slurtle~ and solutlons described below are prepared to determlne ef~ectlveness ln terms of mlnlmum lnhlbltory concentratlon (MIC) of varlous antlbscterlal ngents sgalnst 8 varlety of oral bActerlnl urganlsms lmpllcated in formation of plaque and leadlng to glnglvltis on dental surfaces. Soft plsque contalns about,1.7 x lOIl organlsm/gm.
(net welght). The antlbacterlal agent6 are admlxed wlth anlonlc materlals, particularly anionlc surfsce active agent often commonly employed ln oral composltions and polyphosphate antlcalculus sgent.
Minlmum inhlbltory concentrfltlon (MIC) of antibacterlal agent' 18 used to evaluate the efflcacy of the agent ln vltro. MIC 18 deflned 25 the mlnlmum concentratlon ln mlcrogramstml of antlbacterlal agent at whlch the growth of bacterla 18 completely lnhiblted by the agent. The smaller the MIC value the greate~ 18 the efflcacy of the antlbacterlal agent to lnhlblt the growth of the bacterla. The ln vltro MIC data ls rel~ted to the efflcacy of the dentlfrlce ln vlvù since retention nnd release of antlbacterlal agent lnto the oral cavlty after toothbrushlng 18 ln the rsnge of mcg/ml.
In the Tsbles, followlng dlsclosure and followlng E~amples, the sgent Trlclossn, 2,4,4'-trlchloro-2'-hydro~ydlphenyl ether 18 lndlcated as "TCIIE"; the quaternary smmonlum antlbacterlal agents ben~thonlum chlorlde 18 lndlcated as "BTC"; The blguanlde chlothexldlne dlgluconate is lndicated AS "CU-', sodium lauryl sulfate is lndlcated 8S "SLS"; the copolymer of mslelc anhydrlde and methyl vlnyl ether avallable from GAF
corporstlon 88 "Gnntrez S-97" i8 ldentlfled 86 "Gsntrez"; tetrasodlum pyrophosphste 18 Identlfled as "pyrophosphate"; and sodlum fluorlde 18 ldentlfled as "NaF".
TABLE I 1~39301 . ,, '' .. .
Hlnimum Inhlbltlon Concentratlon Test (MIC) Solutlon in mcg/ml Bacterlodes Bacteriodes Actlnobaclllus Streptococcus glnglvalls lntermedlus actlnomycetem- mutans comltans I. O.S% TCIIE nncI 2.5 2.S 5.0 2~.0 1~ SLS ln wster 2. 0.5X ICIIE, 2.5 2.5 S.0 25.0 lX SLS, 1~ Gnntrez, 2Z PytophospIIate and 0.2X NaF ln WAter 3. 12 SLS ln NE NE NE NE
water 4. 1% SLS, NE NE NE NE
1~ Ga--trez nIld 22 PyroplIosphate ~- ~ ~ ~ -c ln wster note: NE - not effectlve The results lndlcate that TCIIE ln the presence of anlonlc surfactant inhlblted four dentsl plaque orgsnl6ms, Bacterlodes glnglvalls, Bacteroldes lntermedlus, Actlnobaclllus actln~mycetemcomltans and Strep. mutAns ~t 2.5 mcg/ml and 2.5 mcg/ml, 5.0 mcg/ml ~nd 25.0 mcg/ml respectlvely(l). Slmllsr antlbacterlAl effect ls seen ln the presence of Gantrez/pyropho~pItAte/flùorlde(2).
SIS per se and a combln~tlon of SLS/Gsntrez/pyropI-osphAte/Eluorlde was lneffectlvet3 snd 4).
It 1R noteworthy that ln human cllnlcRl tests wlth catlonlc ~~ sntlbacterlal flgentS, 0.075% BTC dlssolved ln water ls e~fectlve ln reduclng plaque formatlon whlle 0.075% BTC snd I% pyrosphosphAte dlssolved ln water 18 not. Slmllarly, O.OI~ CH dlssolved ln water 18 effectlve ln reduclng plaque formatlon whlle 0.01~ nd 1% sodlum N-lRuroyl s~rcoslnnte dls601ved ln water 18 not.
1~9301 Example Z
The sdsorptlon to and relesse from tOOt11 mlnetal~ for ~nt~,nlaque/ sntltQrtar efflcacy of agents is ssseRsed by adsotptlon of anLIbA(Lerlal ~gent to sallva coAted tootl~ mlneral hydroxyspatlte In the pre6ence and the absence oE pyropho~phate (~oluble tetrflsodlum pyrorllosphQte)/GAntre2/NaF.
200 mg. of hydruxyapatlte (IIA) ls treAted wlth human sQllva for 2 hours. The excess sallva ls washed o[f with n burrcr at1<1 8al;.V~ coatc<1 11 18 used Eor adsorptlon studles. Varlous concentratlona of TCIIE In SLS
or ln SLS/pyrop11osp11ate/GQt1trez/NAF are mlxed wlth the coated llA and lucubated At 37~ for 3 hours under contlnuous agltatlon. At the end of lncubatlun perlod, the mlxtures are centrlfuged, 1~ separated and the amounts oE TCIIE adsorbed determlned by e~tlmatlng TCIIE ln the supetnatant at 283nM ln a Gllford ~pectrophotometer. The amounts sdsorbed are ca]culated by tlle dlfference between the amount Added and tl1e amount left ln tl1e supernat~nt aEter tl1e lncubatlon wltl1 coated llA.
Tl1e table below summarlzes the data.
,., 13333~1 ~
r~t~mln~!lents and Concentratlons Z of TCIIE Adsorbed to Coated H~
0.005~ TCHE ln IX SLS 80~
O.OIY TCHE ln 1% SLS 85X
0.015% TCHE ln IX SLS 85Z
0.02% TCHE ln 1~ SLS 88Z
0.005X TCI1~ ln 1~ SLS; 0.5X 80X
Gantrez; 2% pyrophosphate/
0.24% NaF
' 0.01% TCIIE " 85Z
~ 0.015% TCHE " 86X
0.02X TCHE " 81X
The data lndltates that the addltlon of pyrophofiphatet Gantrez/NsF doefi not lmpalr adfiorptlon of TCHE to fiallva coated tooth n,lnetals.
.
1~39301 Example 3 Dentlfrlce ComPosltlons A ~ C
Parts Parts Parts Glycerlne 15.00 10.20 15.00 Polyethylene Glycol 6005.00 3.00 5.00 Iota Carrageenan 0.60 - 0.60 Sodlum CarboYymethyl Cellulose - l.00 Sodlum Saccharln 0.40 - 0.40 Sodlum Cyclamate - 3.00 Sodlum Fluorlde 0.243 0.243 0.243 : Delonlzed water 15.08 29.90723.657 Tltanlum Dloxlde - - 0.50 Sodlum ~enzoate - 0.50 FD&C ~lue No. 1(1% Solutlon) 0.400 - -Sorbltol t70%) 19.807 22.50 22.50 Gantrez S-97 8.330( ) 1.00l )1.00~ ) Tetrasodlum Pyrophosphate 1.50 1.50 1.50 Tetrapotasslum Pyrophosphate 4.50 4.50 4.50 Preclpltated Amorph. Hydrated Slllca 16.00 19.50 Preclpltated Amorp. S111CA
contalnlng comblned alumlna - - 16.00 Slllc~ Thlckener 7.00 - 5.50 Flavor 1.10 0.95 1.10 Sodlum Lauryl Sulfate 1.20 1.20 1.20 TCHE 0.50 o 50 0 50 1 iqu ld powder - 1339~01 ExA~ple 4 The dentlfrice descrlbed ln Example 3A 18 compared wlth the same compusltlun except wlthout sny TCIIE snd wlth sdded 0.50 pstt6 of wlter. Aqueous extrActs uf esch dentlfrlce are prepsred A8 follow6: 50 ml of dlstllled wster 16 added to 1.0 ~m of esch dentlfrlce, ~lxed well ror a cuuple oE hour~ wlth 6tlrrlng bar ~nd centrlfuged, sfter uhlch the ~upernntsnt 16 collected ns Aqueuu6 extrsct. Antlbncterlal Actlvlty of the dentlfrlce extrncts sre evnluated on Bacterludes ginglv8118.
Result6 Are 6ummarlzed belo~.
IAB~E 3 Inhlbltlon of Growth of Bacterlode6 Glnglvall6 Trestment %
Extract from dentlfrlce contalnlng 100.0 TCHE ~1:500) Extract from dentlfrlce wltlIout o.O
TCHE (I:500) TCHE (5.0 mcg/ml) by ltself100.0 These re6ults lndlcate thst TCHE sntlbacterial antlplaque a8ent 16 compatlble ln a dentlfrlce composltlon contAInlng anlonlc surfactsnt plus pyrophoAphAte sntlcAlculus lngred1ents wlth en2yme lnhlbltor6 C~ntrer and NaF. Slmllsr compsrsble effects prevall when esch of hexyl resurclnol, 2,2'-methylene bls~4-chloru-6-bromophenol)/
replsce TCHE.
133930~
Example 5 Mouthrlnse Parts Tetrasodlum Pyrophosphate 2.00 Gantrez S-97 0.25 Glycerlne 10.00 Sodlum Fluoride 0.05 Fluronlc F108 2.00 ~Polyoxyethylelle/Polyoxypropylene Block Copolymer) TCHE 0.10 Flavor 0.90 Water Q.S. to 100.00 Example 6 Lozenye 75-80% Sugar 1-20% Corn Syrup 0.1-1.0 Flavor 2~. Tetrasodlum Pyrophosphate 0.25% Gantrez S-97 0.01 to 0.05% MaF
0.01 to 0.1% TCHE
1 to 5~i Magneslum Stearate Lubrlcant 0.01 to 0.2~ Wate~
Trade-mark 27 X
1~39301 Example 7 Chewlng G~m .Parts Gum base 25.00 S~tbltol (70~) 17.00 TCIIE 0.50 to 0.10 Tetrasodlum Pyrophosophate 2.00 Gantrez S.97 0.25 Na~ 0.05 Glycerlne O.S0 Ct-y~talllne Sutbitul 53.00 ~1avor And WAter Q.S. to 100.00 Thls lnventlun has been described wlth respect to certain preferred embodlments and lt wlll be understood that modiflcatlon6 and varlAtluns thereof obvlous to those skllled in the Art sre to be lncluded wlthln the purvlew of thls appllcat~on snd the scope of the appended claims.
In U.~. Patents 4,627,977 to Gaffar et al; 4,515,772 to Parran et al~ and 4,32~,551 to Parran, oral composltlons are descrlbed whlch lnclude varlous polyphosphate compounds. In the patent ~~o Gaffar et al, a llnear molecular dehydrated poly-phosphate salt ls employed ln con~unctlon wlth a fluorlde lon-provldlng source and a synt~letlc llnear polymerlc polycarboxy-late to lnhlblt calculus formatlon.
In the patents to Parran et al and to Parran water soluble dlalkall metal pyrophosphate alone or mlxed wlth tetra-alkall metal pyrophosphate ls employed.
Oral coMpositlons whlch lnhlblt calculus formatlon on dental surfaces are hlghly deslrable slnce calculus ls one of the causltlve factors ln perlodontal condltlons. Thus, lts reductlon promotes oral hyglene.
Dental playue ls a precursor of calculus. Unllke calculus, however, plaque may form on any part of the tooth surface, partlcularly lncludlng at the glnglval margln. Hence, besldes belng unslghtly, lt ls lmpllcated ln the occurence of glnglvltls.
Accordlngly, lt would be hlghly deslrable to lnclude antlmlcroblal agents whlch have been known to reduce plaque ln oral composltlons contalnlng antlcalculus agents. Indeed, thls has been descrlbed ln U.S. Patent 4,022,880 to Vlnson et al, whereln a compound provldlng zlnc lons as an antlcalculus agent ls admlxed wlth an antlbacterlal agent effectlve to retard the growth of plaque bacterla . A wlde varlety of antlbacterlal tgent~ ere dezcrlbed wlth the zlnc ~r 13~9~01 co ounds lnclud g catlonlc materlals such as guanldes and quaternary ammonlum compounds as well as non-catlonlc compounds such n8 halogensted 6allcylanilldes and halogenated hydroxydlphenyl ethers.
Hltherto, the cAtlonlc sntlbacterlAl mAterlflls such AS
chlorhexldlne, benzthonlum chlorlde and cetyl pyrldlnlum chlorlde have been the sub~ect of greatest lnvestlgatlon as antlbactetlal antlplaque Agents. However, ln splte of thelr belng used ln con~uctlon wlth zlnc antlcalculus agent, they are not effectlve when used wlth anlonlc materl~ls ruch AS polyphosphate anticalculus agent. ThlA
lneffectlveness ls consldered to be qulte surprlsing a6 polyphosphates are chelatlng agents and the chelatlng effect has prevlously been known to lncrease the efflcacy of catlynlc antlbacterlal agents.(see e.g.
Dislnfectlon, Sterllizntlon and Preservatlon, 2nd Ed., Black, 1977, page 915 and Inhlbltlon and Destructlon of the Microblal Cell, Hugo, 1971, page 215). Indeed, quaternary ammonlum compound ls present ln the plaque control mouthwash contalnlng pyrophosphate of U.S. Patent 4,323,551 and bls-blguanlde antlplaque agent ls suggested ln the Antlcalculus pyrophosphate oral composltlon of U.S. Patent 4,515,772.
In vlew of the surprlslng lncompatlblllty of cAtlonlc antlbacterlsl Agents wlth polyphosphates present as sntlcalculus agents, lt was qulte unexpected tilAt other antlbacterlal agent would be effectlve.
It ls an Advantage of thls lnventlon thAt certaln Antlbacterlal Agents Are effectlve ln antlcalculus oral composltlons to lnhlblt plaque formAtlon .
It is a further advantAge of thls lnventlon that a composltlon i6 provlded whlch ls effectlve to reduce plaque and calculus formatlon.
It Is a further advAntAge of thls lnventlon thAt an Antlplaque, antlcalculus orAl composltlon 18 provlded whlch 1B effectlve to reduce the occurence of glnglvltls.
' 1339301 Additional advantages of this invention will be apparent from consideration of the following specification.
In accordance with certain of its aspects tllis lnvention 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 antibacterial agent selected from the group consisting of halogenated diphenyl ethers, phenolic compounds, benzoate esters, and halogenated carbanilides.
The present invention provides 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 polyphosphate salt selected from the group consisting of water-soluble alkali metal or ammonium tripolyphosphates and hexametaphosphates and an effective antiplaque amount of a substantially water-lnsoluble noncationic antibacterial agent 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 a fluoride ion source.
The invention also provides an oral composition comprising in an orally acceptable vehicle, an effective anticalculus amount of anticalculus material selected from the group consisting of water-soluble alkali metal or ammonium tripolyphosphates and hexametaphosphates 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, 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.
The invention further provides an oral composition comprising in an orally acceptable vehicle, an effective anticalculus amount of at least one polyphosphate salt selected from the group consisting of water-soluble alkali metal, tripolyphosphates and hexametaphosphates, as essential anticalculus agent and an effective antiplaque amount of a substantially water-insoluble noncationic antibacterial compound as essential antiplaque agent.
The invention additionally provides an oral composition comprising in an orally acceptable vehicle an effective anticalculus amount of sodium tripolyphosphate as essential anticalculus agent, and an effective antiplaque amount of a substantially water-insoluble noncationic antibacterial compound as essential antiplaque agent.
The invention also provldes an oral composition comprising, in an orally acceptable vehicle, an effective 4a 1~39301 anticalculus amount of at least one water-soluble linear molecularly dehydrated polyphosphate salt as essential anticalculu~ agent and an effective antiplaque amount of a substantially water-insoluble non-cationic antibacterial compound as essential antiplaque agent.
The invention further provides an oral compositlon comprising, in an orally acceptable vehicle, an effective anticalculus amount of pyrophosphate as essential anticalculus agent, an effective antiplaque amount of à substantially water-insoluble non-cationic antibacterial compound as essential antiplaque agent and as essential inhibitor of salivary enzymatic hydrolysis of the polyphosphate salt a fluoride ion-providing source in an amount sufflcient to supply about 25 ppm to about 2,000 ppm of fluoride ions.
The invention additionally provides an oral composition comprising, in an orally acceptable vehicle, an effective anticalculus amount of at least one water-soluble linear molecularly dehydrated polyphosphate salt as essential anticalculus agent, an effective antiplaque amoùnt of a substantially water-insoluble non-cationic antibacterial compound as essential antiplaque agent and as essential inhibitor of salivary enzymatic hydrolysis of the polyphosphate salt a fluoride ion-providing source in an amount sufficient to ~upply about 25 ppm to about 2,000 ppm of fluoride ions.
The invention also provides an oral composition comprising, in an orally acceptable vehicle, a dentally 4b ,f~.
acceptable sillca pollshlng agent, an effectlve antlcalculus amount of at least one water-soluble llnear molecularly dehydrated polyphosphate salt as essential anticalculus agent, an effective antiplaque amount of a substantially water-insoluble non-cationic antibacterial compound as essential antiplaque agent and a mixture of (A) an amount of a fluoride ion-providing source sufficient to supply about 25 ppm to about 2,000 ppm fluoride ions; and (B) about 0.05~ to about 3% of a water-soluble synthetlc anionic polymeric polycarboxylate.
In preferred embodiments of the above aspects of the invention the substantially water-lnsoluble non-cationic antibacterial compound is other than a parahydroxybenzoic acid ester.
Typical examples of antibacterial agents which are particularly desirable from considerations of antiplaque effectiveness, safety and formulation are:
Haloqenated DiphenYl Ethers 2',4,4'-trichloro-2-hydroxy-diphenyl ether ~Triclosan*) 2,2'-dihydroxy-5,5'-dibromo-diphenyl ether.
Phenolic Compounds (including phenol and its homologs, mono- and poly-alkyl and aromatic halophenols, resorcinol and its derlvatives and blsphenollc compounds).
~Trade-mark 4c ,~
1333~1 Phenol and its Homologs Phenol 2 Hethyl - Phenol 3 Methyl - Phenol 4 Hethyl - Phenol 4 Ethyl - Phenol 2,4-Dimethyl - Phenol 2,5-Dimethyl - Phenol 3,4-Dimethyl - Phenol 4d l33~30r 2,6-Dimethyl - Phenol 4-n-Propyl - Phenol - 4-n-Butyl - Phenol 4-n-Amyl - Phenol 4-tert-Amyl - Phenol 4-n-Hexyl - Phenol 4-n-Hertyl - Phenol t Mono- snd Poly-Alkyl and Aromatic H~lophenols Methyl - p-Chlorophenol Ethyl - p-Chlorophenol n-Prupyl - p-Chlorophenol n-8utyl - p-Chlorophenol n-Amyl - p-Chlorophenol ,~- sec-Amyl - p-Chlorophenol n-Hexyl - p-Chlorophenol Cvclohexyl - p-Chlorophenol n-Heptyl - p-Chlorophenol n-~ctyl - p-Chlorophenol O-Chlorophenol Methyl - o-Chlotophenol Ethyl - o-Chlorophenol n-Propyl - o-Chlorophenol n-Butyl - o-Chlorophenol n-Amyl - o-Chlorophenol tert-Amyl - o-Chlorophenol n-l;exyl - o-Chlorophenol n-Heptyl - o-Chlorophenol r~Chl.otuphenol o-Benzyl - p-Chlorophenol -- 13393~1~
o-Benzyl-m-methyl - p-Chlorophenol o-Benzyl-m, m-dlmethyl - p-Chlorophenol o-Phenylethyl - p-Chlorophenol o-Phenylethyl-m-methyl - p-Chlorophenol 3-l~etllyl - p-Chlorophenol 3,5-Dlmethyl - p-Chlorophenol 6-Ethyl-3-methyl - p-Chlorophenol 6-n-Propyl-3-methyl - p-Chlorophenol 6-lso-Propyl-3-methyl - p-Chlotophenol 2-Ethyl-3,5-dimethyl - p-Chlorophenol 6-sec Butyl-3-methyl - p-Chlorophenol 2-16u-Propyl-3,5-dlmethyl - p-Chlorophenol 6-C~lethylmethyl-3-methyl - p-Chlorophenol 6-lfio-Propyl-2-ethyl-3-methyl - p-Chlorophenol 2-sec Amyl-3,5-dimethyl - p-Chlorophenol 2-nt ethylmethyl-3.5-dintethyl - p-Chlorophenol 6-~ec Octyl-3-methyl - p-Chlorophenol p-Bromophenol Methyl- p-Bromophenol Ethyl- p-Bromophenol n-Propyl- p-Bromophenol n-Butyl- p-Bromophenol n-Amvl- p-Bromophenol sec-Amyl- p-Bromophenol n-Hexyl- p-Bromophenol cyclohexyl- p-Bromophenol o-Bromophenol tcrt-Am)l- o-Bromophenol n-He~yl- o-Bromophenol ~ ~ -_ -.-. - ~ 6 13~9301 n-Propyl-m,m-Dimethyl - o-Bromophenol ~-Phenvl Phenol 4-chloro-2-methyl phenol 4-chloro-3-methyl phenol 4-chloro-3,5-dlmethyl phenol 2,4-dlcl-loro-3,5-dimethylphenol 3,4,'i,6-terabromo-2-methylphenol 5-methyl-2-pentylphenol 4-lsopropyl-3-methylphenol 5-chloro-2-hydroxydipheny~ethane Resorclnol and lts Derivatives Resorcinol Methyl - Resorcinol Ethvl - Resotclnol n-Propyl - Resorclnol n-Bu~yl - Resorclnol n-Amyl - Resorclnol n-l~cx l - Resorcinol n-lleptyl - Resorclnol n-Octyl - Resorcinol n-Nonyl - Resorclnol Phenyl - Resorclnol Benzyl - Resorclnol Phenylethyl - Resorclnol Rhenylpropyl - Resorcinol p-Chl_robenzyl - Resorclnol 5-Chloro -2,4-Dlhydroxydiphenyl Methane 4'-Chloro -2,4-Dihydroxydiphenyl Hethsne 5-Bromo -2,4-Dihydroxydlphenyl Methane 4'-~romo -2,4-Dlhydroxydlphenyl Methane Blsphenollc ComPounds 2,2'-methylene bls (4-chloropllenol) 2,2'-methylene bls 13,4,6-trlchlorophenol) 2,2'-methylene bls 14-chloro-6-bromophenol) bls (2-hydroxy-3,5-dlchlorophenyl) sulflde bls 12-hydroxy-5-chlorobenzyl) sulfide.
Benzolc Esters p-Hydroxybenzolc Acld l~ethyl - p-Hydroxybenzolc Acld ~thyl - p-Hydroxybenzolc Acld Propyl - p-Hydroxybenzolc Acld Butyl - p-l~ydroxybenzolc Acld Haloqenated Carbanilldes 3,4,4'-trlchlorocarbanllide 3-trlfluoromethyl-4,4'-dlchlorocarbanlllde 3,3',4-trlchlorocarbanlllde The antlbacterlal agent ls present ln the oral composltlon ln an effective antlplaque amount, typlcally about 0.01-5~ by welght, preferably about 0.03-1~. The antlbacterlal agent ls substantlally water-lnsoluble, meaning that lts solublllty ls le3s than about 1% by welght ln water at 25~C and may be even le6s than about 0.1~. If anlonizable group ls present solubllitY is determlned at a pH at whlch lonizatlon does not occur.
~7:
- 133~3131 , , . .. . .. ..
Tlle preferred halogenated diphenyl ether is Triclosan~. The preferred phenolic compounds are hexyl resor-cinol and 2,2'-methylelle bis(4-chloro-6-bromophenol). The most pref,erred antibacterial antiplaque compound is Triclosan.
Trlclosan is disclosed in aforementioned ~nited States Patent 4,022,880 as an antibacterial agent in combination with an anticalculus agent wllicll provides zinc ions. It is àlso dis-closed as an antiplaque agent in a dentifrice formulated to contaln a lamellar liquid crystal surfactant phase having a , .. -~--- 10 lamellar spacing of less than 6.0 mm and which may optionally contain a zinc salt in published European Patent application 0161898 of Lane et al and in a dentifrice containing zinc citrate - trihydrate in published European Patent Application 0161899 to Saxton.
The linear molecularly dehydrated polyphosphate salts operative herein as anticalculus agent are well known, being generally employed in the form of their wholly or partially neutralized water soluble alkali metal Ce.g. potassium and preferable sodium) or ammonium salts, and any mixtures thereof.
Representative examples include sodium hexametaphosphate, sodium tripolyphospilate, disodium diacid, trisodium monoacid and tetrasodium pyrophosphates and the like. Linear polyphos-phates correspond to (NaPO3)n where n is about 2 to about 125.
They are generally etnployed in the instant oral compositions in approximate weight amounts of 0.1 to 7% preferably 0.1 to 7%, more preferably 2 to 1~. When n is at least 3 in (NaPO3)n, said polyphosphates are glassy in character.
*Trade Mark - 133~301 Partlcularly des;-e~"e allt.tcalculus AgentR are tetraslksll metal pyropho6phate6, lncluding mlxture6 thereof, such as tettssodlum ryrorhosrhAte, tetrsrota~slum pyropho6phate and mlxtures thereof. An nntlcalculus agent comprlslng about 4.3Y0 to about 7X by welght of the orsl composltlons whereln the welght ratlo of tetrApotasslum pyropho6phate to tetrasodlum pyropho6phate ls from sbout 4.3:2.i to about 6:1 is e6peclally preferred.
In order to optimize the antlcalculu6 effectiveness of the oral composltlon, inhlbltors ngain6t enzymatlc hydroly61s of the polyphosphate are desirably present. Such agents are sn amount of a fluorlde ion source 6ufflcient to supply 25 ppm. to 5,000 ppm. of fluorlde lons, snd OX to 3~ of a synthetlc anlonic polymeric polycsrbo~ylAte havlng a molecular welght of about 1,000 to about l,000,000, preferably About 30,000 to sbout 500,000.~
The 60urces of fluoride lons, or fluorlne-providin~ component, as acld phosphatase and pyrophosphatase enzyme inhlbltor component, are well knot~n ln the art as antl-caries agents. These compounds may be htly soluble ln water or m~y be fully wnter-soluble. They are characterized by thelr ablllty to relea6e fluorlde lons ln wnter And by freedom from undeslred reactlon with other compound8 of the oral preparatlon. Among the6e materlsl6 are lnorganlc fluorlde 6alts, such as soluble a~kali metsl, slkaline earth metal salt6, for example, sodium fluorlde, potasslum fluoride, ammonium fluorlde, cslclum fluorlde, a copper fluoride 6uch a8 cuprous fluotlde~ zlnc fluoride, barlum fluorlde, fiodlum flouroslllcste, smmonlum florosilicate, sodium ~
tluotozlrconste, sodlum fluorozirconate, sodlum monofluorophosphate, slumlnum mono- snd dl-fluorophosphate, and fluorinated sodlum cslclum yrophosphste. Alkall metal snd tln fluorldes, such as sodlum and stsnnous fluorldes, sodlum monofluorophosphste (MFP) snd mlxtures thereof, are preferred.
13393~
The amount of fluorlne-provldlng compound ls dependent to some extent upon the type of compound, lts solubillty, and the type or oral preparatlon, hut lt must be a non-toxlc,amount, generally abut 0.005 to about 3.0% ln the preparatlon. In a dentlfrlce preparatlon, e.g. dental gel, toothpaste tincludlng creaml, toothpowder, or dental tablet, an amount of such compound whlch releases up to about 5,~000 ppm of lon by welght of the preparatlon ls consldered satlsfactory.
Any suitable mlnlmum amount of such compound may be used, but lt ls preferable to employ sufflclent compound to release about 300 or, preferably 1085, to 2,000 ppm. more preferable about 800 to about 1,500 ppm of fluorlde lon.
Typlcally, ln the cases of alkall metal fluorldect, thls component ls present ln an amount up to about 2~ by welght, based on the welght of the preparatlon, and preferably ln the rar.~e of about 0.05% to 1~, partlcularly ln excess of 0.22~. In the case of sodium monofluorophosphate, the compound may be present ln an amount of about 0.1-3%, more typlcally about 0.76~, preferably ln excess of O.B0~.
In dentlfrlce preparatlons such a~ lozenges and chewlng gum, the fluorlne-providlng compound ls typlcally present ln an amount sufflclent to relea~te up to about 500 ppm, preferably about 25 to 300 ppm by welght of fluoride lon.
Generally about 0.005 to about 1.0 wt.~ of such compound ls present .
The ~yntl-etlc anionlc polymeric polycarboxylate ls an lnhlbltor of alkallne phosphatase enzyme. Synthetlc anlonlc polymerlc polycarboxylate~ and thelr complexes wlth varlous catlonlc germlcldes, zlnc and magneslum have been prevlously dlsclosed as antlcalculus agents per ~te in, for example U.S.
Patent No. 3,429,963 to Shedlovsky U.S. Patent No. 4,152,'420 133~3~
to Gaffar U.S. Patent No. 3,956,480 to Dlchter et al; U.S.
; Patent 4,138,417 to Gaffar: and U.S. Patent No. 9,183,914 to Gaf~ar et al. Nowever, only in aforementloned U.S. Patent 4,627,977 to Gaffar et al 1B there dlsclosed use of such polycarboxylate3 alone for lnhlblting sallvary hydrolysls of pyrophosphate anticalculus agents, much le6s in comblnation wlth a compound providing a source of fluoride ion. It is to be understood that the synt11etic anionlc polymerlc polycarboxylates so disclo~ed in these several patents are operatlve ln the composltlons and methods of thls lnventlon.
The synthetlc anlonlc polymerlc polycarboxylates optlonally but preferably employed herein are, as lndicated ahove, well known, belng often employed in the form of thelr free acids or preferably partially or more preferably fully neutrallzed water soluble alkall metal ~e.g. pota~sium and preferably sodlum) or ammonium salts. Preferred are 1.4 to 4-1 copolymers of maleic anhydrlde or acld wlth another polymerl7able ethylenlcally unsaturated monomer, preferably methyl vlnyl ether ~malelc anhydrlde) havlng a molecular welght ~M.W.~ of about 30,000 to about 1,000,000. The6e copolymers are available for example as Gantrez~ ~AN 139 ~H.W. 500,000), A.N. ll9-~11.W. 250,000)~ and preferably S-97 Pharmaceutlcal Grade ~I~.W. 70,000), of GAF Corporation. The term "synthetlc"
~ i8 lntended to exclude known thlckenlng or gelllng agents comprlslng carboxymethylcellulose and otller derlvatlves of cellulose and natural gums.
Other operatlve polymerlc polycarboxylates include those disclosed ln U.S. Patent No. 3,956,480 referred to above, such as the 1l1 copolymers of malelc anllydrlde wlth ethyl acrylate, hydroxyethyl methacrylate, N-vlnyl-2-pyrollldone, or ethylene, the latter being avallable for example as Monsanto~
~Trade-mark - 12 -~33930~
EIIA No. 110~, N.W. lO,OOO and EMA Grade 61~, and 1-1 copolymers of acryllc acld wlth methyl or hydroxyethyl methacrylate, methyl or ethyl acrylate, lsobutyl vinyl etller or N-vlnyl-2-pyrrolldlne.
~Trade-mark - 12a -...
13393~1 Additlonal operative polymerlc polycsrboxylates dl6closed ln above referred to U.S. Pstent No. 4,138,477 and 4,183,914, lnclude copolymers of maleic anhydrlde wlth styrene, isobutylene or ethyl vlnyl ether, polyacrylic, polyltaconic and polymalelc aclds, and sulfoacryllc ol1gomers of M.W. as low as 1,000, avallable 88 Unlroyal ND-2.
~--- Sultable generally are polymerlzed oleflnlcslly or e~h~lenlcally unsaturated carboxylic acids contalnlng an actlvated carbon-to-carbon olefinic double bond and at least one carboxyl group, tllat is, an acid contalnlng an olefinlc double hond which readily functions in polymerization because of lts presence ln the monomer molecule either in the alplls-beta po6ition witll respect to n carboxyl group ur as part of a terminal methylene grouping. Illustrative of such aclds are acryllc, methacrylic, ethacryllc, alpha-chloroacrylic, crotonlc, beta-acryloxy propionic, sorblc, slpha-chlorsorblc, clnnamlc, beta-styrllacrylic, muconic, itaconic, cltraconic, mesaconic, g1utaconic, scon1tic, alpha-phenylacryllc, 2-benzyl acrylic, 2-cyclohexylacrylic, angelic, umbellic, fumaric, mslelc aclds and anhvdrldes. Other different oleflnlc monomers copolymerlzsble wlth such carboxyllc monumers lnclude vlnylacetste, vlnyl chlorlde, dlmethyl maleate snd the like. Copolymers contsln Rufflclent csrboxyllc sslt groups for water-solubility.
Also useful hereln sre so-cslled carboxyvlnyl polymers dl~closed as toothpaste components ln 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,gll,904 to llarrlson, and U.S. 3,711,604 to Colodney et al. They are commrrc~Ally available for example under the trRdemQrks CRrbopol 934, 940 and 94l of B. F. Goodrich, these products conslsting essentially of !a colloldally water-soluble polymer of polyacryllc scld crosfilinked wlth from about 0.75% to about 2.0X of polyallyl sucrose or polyallyl ~cntaerythrltol as cross llnklng sgent.
~ 1339301 ne synthetlc anlonlc poly~erlc polycarbo~ylate component 18 mainly a hydrocarbon wlth optlonal halogen and O-contalnlng substltuents and llnkages ss present ln for example ester, ether snd OH group~, and when present~ls generally employed ln the lnYtsnt composltlons ln ~pproxlmate welght amounts of 0.05 to 3~, prefersbly 0.05 to 2Z, more preEerably O.l to 27.. ~mounts ln the upper portlons of these rsnges are typlcally employed in dentlfrlce compo61tlons typlcslly contslnlng a dental sbraslve snd u6ed ln con~unctlon wlth brushlng of the teeth, e.g.
tooth pastes (lncludlng creams~, gels, powderfi snd tablets. Amount6 ln r~ excess of these ranges may be employed for thlckenlng or gelllng purpose~.
As lndlcated above, these polymerlc polycarboxylates have been found to be effective lnhlbltors of alkAllne phosphstase enzyme. Slnce thls enzyme has llttle actlvlty (for hydrolyzlng pyrophosphste) at sbout pH 7.0 or below, the polymerlc polycsrbo~ylate component msy, lf deslred, be omltted from oral prepnratlons formulated to operste st 6uch pH of 7.0 or below. Such omlsslon however could teduce the versatlllty and antlcAlculus effectlveners of the present oral composltlons over the broad pH rsnge of sbout 4.5 to sbout 10.
In oral prepsratlons such as mouthwashes, lozenge8 snd chewlng Rum, the fluorlne-provldlng compound may be typlcally present ln sn amount sufflclent to relesse up to about 500 ppm, preferably about 25 to about 300 ppm by welght of fluorlde lon. Generally sbout 0.005 to sbout 1.0 wt.~ of such compo~nd is present.
In certaln hlghly preferred forms of the Inventlon the oral c~mposltlon may be substantlslly llquld In character, such as a ~outhwash or rlnse. In such 8 prepsrstlon the vehlcle la typlcslly 8 water-slcohol mlxture deslrably lncludlng a humectant as descrlbed below. Generslly, the welght ratlo of water to alcohol is ln the range 1~393~1 of from sbout l:l to aDout 2~:1, prefetAbly about 3:l to lO:l and more preferably about 4:1 to about 6:1. The totai amount of water-alcohol mlIture ln thls type of preparatlon ls typlcally ln the ranBe of from about 70 to sbout 99.9~ by welght of the preparatlon. The AlCOhOl 18 tYP1CA11Y ethanol or lsopropanol. Ethanol lfi preferred.
The pH of such liquid and other prepArAtlons of the lnventlon ls generally ln the range of from about 4.5 to about 9 and typically from about 5.5 to 8. The pU i8 preferably ln the range of from about 6 to about ô.O. It 16 noteworthy that the composltlons of the lnvention may be applied orally at a pH below 5 wlthout substAntlally decalcifying or otherwl6e damaglng dental enamel. The pH can be controlled wlth acld (e.g. cltrlc acld or benzulc scld) or base (e.g. sodlum hydroxlde) or buffered (as wlth sodlum cltrate, benzoate, cArbonate, or blcarbonate, disodium hydrogen phosphate, sodium dlhydrogen phosphAte, etc.).
In cert~in other deslrable forms of thls lnvention, the oral compofiition may be substantiAlly solid or paFty ln character, such afi toothpowder, a dental tablet or a dentlfrlcej that 18 a toothpaste (dental cream) or gel dentlfrlce. The vehlcle of such solld or pasty oral preparAtions generally contains dentally acceptable pollfihlng materlal. ExAmples o~ pollshing mAterials are water-lnsoluble sodlum metaphosphate, potAsslum metapho6phate, tricalclum phosphste, dihydrated calclum phosphate, anhydrous dlcalclum phosphste, calclum pytophosphnte, magenslum orthophosphate, trimAgneslum phosphAte, calclum carbonate, aluminum fillicate, zirconium slllcAte, filllca, bentonlte, and mlxtures thereof. Other sultAble pollshlng material include the particulàte thermosettlng reslns descrlbed ln U.S. Pat. No. 3,070,5lO of Dec. l5 1962 such as melamlne-, phenollc, and urea-formaldehydes, and cross-llnked polyepoxldes and polyesters. Preferred poll8h~ng materlal lnclude crystalllne 8111CA havlng particle sized of up to About 5 - - ~
mlcrun6, a meAn partlcle size or up tu about 1.1 mlcrons, and a surface area of up to About 50, 000 cm. /gm., slllca gel or colloldal slllca, nnd complex amorphou6 alkall metal alumlnoslllcste.
Whe~ vl6ually clear gels are employed, a poll6hlng sgent of collotdal slllca, such a6 thofie 601d under the trademark SYLOID a8 Sylold 72 snd Syloid 74 or under the trademsrk SANTOCEL as Santocel 100 alhall metal almuino-6111cate complexe6 Are partlcularly useful,~slnce they have refractlve indlce6 close to the refractive indices of gelling sgent-liquid (lncludlng water and/or humectsnt)system6 commonly used ln dentlflces.
Many of the so-cslled "water-insoluble" pollshlng materials sre anlonlc ln character snd slso lnclude small smount6 of soluble materlal.
Thus, lnsoluble sodlum metaphosphate msy be formed ln sny sultAble manner as lllustrated by Thorpe's Dlctlonary of Applled Chemlstry, Volume 9, 4th Edltlon, pp. 510-511. The forms of lnsoluble sodlum metaphosphate known as Madrell's salt and Kurrol's salt are further examples of sultable materlals. These metaphosphste salts exhlblt only a mlnute solublllty ln water, and therefore are commonly referred to ss lnsoluble metsphosphates (IMP). There ls present thereln a mlnor amount of ~oluble phosphate materlal a8 Impuritles, usually a few percent such as up to 4% by welght. The amount of soluble phosphate materlal, whlch ls belleved to lnclude a soluble sodlum trlmetaphosphate ln the case oE
lnsoluble metaphosphate, msy be reduced or ellmlnated by washlng wlth water if deslred. The lnsoluble alkall metal metaphosphate ls typlcally employed ln powder form of a partlcle slze such that no more than 1~ of the materlal ls larger than 37 mlcrons.
The pollshlng materlal ls generslly present ln the solld or pasty composltlons in welght concentrstlons of sbout 10% to about 99~.
Preferably, lt 18 present ln amounts ranglng from about 10% to about 7S~
~ ===
.., ln toothpast~, snd from about 70~ to about 99% ln toothpowder.
In 8 toothpsste, the llquld vehicle msy comprlse wster and humectsnt typicslly in an ~mount rsnglng from about 10% to sbout 80% by welght of the preparstlon. Glycerlne, propylene glycol, sorbltol, polypropylene glycol and/or pulyethylene glycol (e.g. 400-600) exempllfy sultAble llumectants/csrrlers. Also sdvantageous sre llquld mlxtures of water, glycerlne and sorbltol. In clear gels where the refractive lndex 1~ An l~portant con61derstlon, sbout 3-30 wt. % of water, O to about 70 wt.X of glycerlne and sbout 20-80 wt. % of sorbltol are preferably employed.
Toothpa~tes, cresms and gels typlcslly contsln a natural or synthetlc thlckener or gelllng agent ln proportlons of about 0.1 to about 10, prefernbly sbout 0.5 to about 5wt.~. A sultable thlckener 18 synthetlc hectorlte, a synthetlc colloldal magneslum alkall metal slllcate complex clay svallable for example as Laponlt ~(e.g. CP, SP
2002,D) marketed by Lsporte Industrle6 Llmlted. Lsponlte D analysls shows, approxlmately by welght, 58.00% S102, 25.40~ MgO, 3.05X Na20, n~a8~0 Li20, and some water snd trsce metals. Its true speclflc grsvity 18 2.53 and lt has an apparent bulk denslty (g./~l. at 8% moisture) of I I . O .
¦ Other sultsble thlckeners lnclude Irlsh mofis, gum tragacanth, ~tarch, polyvlnylpyrrolldone, hydtoxyethypropylcellulose, hydroxybutyl methyl cellulose, hydroxypropyl methyl cellulose, hydroxyethyl cellulose (e.g. avsllsble as Natroso ~ , sodlum carboxymethyl cellulose, and colluldal Glllcs such 88 flnely ground Sylold~(e.g. 244).
It wlll be understood th~t, as 18 conventlonal, the oral prepArstlons are to be sold or otherwlse dlstrlbuted ln sultable l~helled pAcksges. Thus a ~sr o~ mouthrlnse wlll hsve A lAbel descrlblng lt, In substance, a8 a mouthrlnse or mouthwash and havlng .
~~ -1~39301 directlon6 for lts use; and a toothpaste, cream or gel wlll u6ually be in A collapfilble tube, typlcally alumlnum, llned lead or plastlc, or other squeeze, pump or pressurlzed dispenser fvr meterlng vut the contents, havlng a label descrlbing lt, ln substance, 88 a toothpaste, "r~ e' or dental cream.
~~ Organlc surface-actlve agents are used ln the composltl!ons of the present lnventlon to achleve lncreased prophylactlc actlon, asslst ln schlevlng thorough and complete dlsperslon of the Antlcalculus agent throughout the orAl cavlty, and render the lnstant composltlon6 more cvsmet~cally acceptable. n-e organlc surface-actlve msterlsl ls preferably flnlonlc, nonlonlc or ampholytlc ln nature, snd lt 18 preferred to employ a8 the 6urface-actlve agent a detet~lve materlal whlch lmparts to the compofiltlon deterslve and foamlng propertlefi.
Sultsble examples of anlonlc 6urfactantfi are water-soluble fialts of h~gher fatty acld monoglycerlde monofiulfates, fiuch as tlle sodlum sslt Or ~-he mnno~ulfated monoglycerlde of hydrogenated coconut oll fatty aclds, hlgher alkyl sulfates fiuch as sodlum lauryl fiulfate, alkyl aryl sulfonates such as sodlum dodecyl benzene sulfonate, hlgher alkyl - 6ulEoacetates, hlgher fatty acld efiters of 1,2-dlhydroxy propane ~ulfonate, and the substantlally satursted hlgher allphatlc acyl smldefi of lower allphatlc amlno carboxyllc acld compoundfi, such afi those havlng 12 to 16 carbons ln the fatty acld, alkyl or acyl radlcals, and the llke. Examplefi of the last mentloned amldes are N-lauroyl sarcoslne, and the sodlum, potasslum, and ethAnolsmlne ~alts of N-1AUrOY1~
N-myrlstoyl, or N-pslmltoyl fiarcofilne whlch should be substsntlally free f~vm 60ap or slmllar hlgher fatty acid materlal. The use of thefie fiarcoslnate compound~ ln the ùral compofiltlonfi of the present lnventlon tQ partIcularly advantageoufi slnce thefie materlalfi exhlblt a prolonged ! and marked effect ln the Inhlbltton of acld formatlon ln the oral cavlty !' 3393~
-19- 623n~ ,61 due to carbollydrate breakdown in addition to exerting some reduction in tl~e solul)ility of tooth ennmel in acid solutions. ~xamples oE water-solul-le nonionic surEactants are condensation products o( etllylene oxide with various renctive hydrogell-colltainillg compounds reactive therewitll having long hydro-phobic chtlills (e.g. aliphatic cllains oE about 12 to 20 carbon atoms), whicl con(lensat:ioll products t"etlloxalmers") contain hyclrophilic polyoxyethylelle moieLies, sucll as condell~nlioll pro(ltlcts of poly(ethylene oxicle) with tntLy ncids, fatty nlcollols~ Entty nmides~ polyhydric alcohols (e.g. sobi~an mono-sterate) and polypropylelleoxi(le (e.g. rluronic~materials). ~t is pl-eferre(l 1() to use trom nbollt 0.05 to 5Y by weigh~ and preEerably about 0.5 to 5Y oE the foregoing surEace active ~-~nterials in the instant compositions.
Various other materials may be incorporated in the oral prepar-ations of this invention sucll as wllitening agents, preservatives, silicones, cl-lorophyll compollnds and/or ammoniated material such as urea, diammonium phosl-llate, nnd mixtures thereoE. Illese ad juvants~ where present, are incorportlLed in the prcpnrntions in nmounts whicll do not subst-llltinlly adversely aitect the properties and charscteristics desired. Signiricant amoullts of zinc~ magllet;illm and other metnl salts and materials, generally soluble, whicll would complex with active components oE the instant invention are to be avoided.
Any suitable Elavoring or sweetening material may also be employed.
Examptes oE suitnble Elavoring constit~lents are flavoring oils, e.g. oil oE
spenrmil~t, pepcrment, winLergreen, sassaCras, clove, sQge, eucalypLus, Illtll' jllrlllll, ('illlllllll(lll~ 1(!lllOll, 1111(1 tll'llllgt!, nll(l tlletllyl 19111 it'ylllt('~ Slli I 111)11!
sweetenillg agellts inclu(le sucrose, lactose~ maltose, sorbitil, xylitol, sodillm cyclamtlte~ perillartine, AM~ (aspartyl phenyl alanine, methyl ester), snccharine and the like. Suitt3bly, flavor and sweetening agents may together comprise Erom about O.IX to 5~ more of the preparation.
In the preEerred practice oE this invention an oral composition i3~93~1 ~
accordlng to thia lnventlon ~uch a8 a mouthwash or dentlfrlce contslnlng the compusltlon of the present lnventlon ls preferably applled regularly to dentsl enamel, such as every day or evety second or thlrd dsy or prefersbly from I to 3 tlmes dally, at A ptl of nbuut 4.5 to about 9, generally about 5.5 tu about 8, preferably about 6 to 8, for at least 2 weeks up to 8 weeks or more up tu llfetlme.
The compusltlons of thls lnvention cfln be lncorporated In lozenges, or ln cl-ewlng gum or other products, e.g. by stlrrlng lnto a warm gum base or coating the outer surface of a gum base, lllustrative of which may be mentloned ~elutone, rubber latex, vlnylite reslns, etc., deslrably with conventlonal plastici7ers or softeners, sugar or other sweeteners or carbohydrates sucl~ as glucose, sorbltol and the llke.
The followlng examples are further Illustratlve of the nature uf the present lnvention, but it is understood that the invention is not limlted thereto. ~11 amounts and proportions referred to hereln and in the appended clalms are by welght.
.. D
133~301 E~ample l Slurtle~ and solutlons described below are prepared to determlne ef~ectlveness ln terms of mlnlmum lnhlbltory concentratlon (MIC) of varlous antlbscterlal ngents sgalnst 8 varlety of oral bActerlnl urganlsms lmpllcated in formation of plaque and leadlng to glnglvltis on dental surfaces. Soft plsque contalns about,1.7 x lOIl organlsm/gm.
(net welght). The antlbacterlal agent6 are admlxed wlth anlonlc materlals, particularly anionlc surfsce active agent often commonly employed ln oral composltions and polyphosphate antlcalculus sgent.
Minlmum inhlbltory concentrfltlon (MIC) of antibacterlal agent' 18 used to evaluate the efflcacy of the agent ln vltro. MIC 18 deflned 25 the mlnlmum concentratlon ln mlcrogramstml of antlbacterlal agent at whlch the growth of bacterla 18 completely lnhiblted by the agent. The smaller the MIC value the greate~ 18 the efflcacy of the antlbacterlal agent to lnhlblt the growth of the bacterla. The ln vltro MIC data ls rel~ted to the efflcacy of the dentlfrlce ln vlvù since retention nnd release of antlbacterlal agent lnto the oral cavlty after toothbrushlng 18 ln the rsnge of mcg/ml.
In the Tsbles, followlng dlsclosure and followlng E~amples, the sgent Trlclossn, 2,4,4'-trlchloro-2'-hydro~ydlphenyl ether 18 lndlcated as "TCIIE"; the quaternary smmonlum antlbacterlal agents ben~thonlum chlorlde 18 lndlcated as "BTC"; The blguanlde chlothexldlne dlgluconate is lndicated AS "CU-', sodium lauryl sulfate is lndlcated 8S "SLS"; the copolymer of mslelc anhydrlde and methyl vlnyl ether avallable from GAF
corporstlon 88 "Gnntrez S-97" i8 ldentlfled 86 "Gsntrez"; tetrasodlum pyrophosphste 18 Identlfled as "pyrophosphate"; and sodlum fluorlde 18 ldentlfled as "NaF".
TABLE I 1~39301 . ,, '' .. .
Hlnimum Inhlbltlon Concentratlon Test (MIC) Solutlon in mcg/ml Bacterlodes Bacteriodes Actlnobaclllus Streptococcus glnglvalls lntermedlus actlnomycetem- mutans comltans I. O.S% TCIIE nncI 2.5 2.S 5.0 2~.0 1~ SLS ln wster 2. 0.5X ICIIE, 2.5 2.5 S.0 25.0 lX SLS, 1~ Gnntrez, 2Z PytophospIIate and 0.2X NaF ln WAter 3. 12 SLS ln NE NE NE NE
water 4. 1% SLS, NE NE NE NE
1~ Ga--trez nIld 22 PyroplIosphate ~- ~ ~ ~ -c ln wster note: NE - not effectlve The results lndlcate that TCIIE ln the presence of anlonlc surfactant inhlblted four dentsl plaque orgsnl6ms, Bacterlodes glnglvalls, Bacteroldes lntermedlus, Actlnobaclllus actln~mycetemcomltans and Strep. mutAns ~t 2.5 mcg/ml and 2.5 mcg/ml, 5.0 mcg/ml ~nd 25.0 mcg/ml respectlvely(l). Slmllsr antlbacterlAl effect ls seen ln the presence of Gantrez/pyropho~pItAte/flùorlde(2).
SIS per se and a combln~tlon of SLS/Gsntrez/pyropI-osphAte/Eluorlde was lneffectlvet3 snd 4).
It 1R noteworthy that ln human cllnlcRl tests wlth catlonlc ~~ sntlbacterlal flgentS, 0.075% BTC dlssolved ln water ls e~fectlve ln reduclng plaque formatlon whlle 0.075% BTC snd I% pyrosphosphAte dlssolved ln water 18 not. Slmllarly, O.OI~ CH dlssolved ln water 18 effectlve ln reduclng plaque formatlon whlle 0.01~ nd 1% sodlum N-lRuroyl s~rcoslnnte dls601ved ln water 18 not.
1~9301 Example Z
The sdsorptlon to and relesse from tOOt11 mlnetal~ for ~nt~,nlaque/ sntltQrtar efflcacy of agents is ssseRsed by adsotptlon of anLIbA(Lerlal ~gent to sallva coAted tootl~ mlneral hydroxyspatlte In the pre6ence and the absence oE pyropho~phate (~oluble tetrflsodlum pyrorllosphQte)/GAntre2/NaF.
200 mg. of hydruxyapatlte (IIA) ls treAted wlth human sQllva for 2 hours. The excess sallva ls washed o[f with n burrcr at1<1 8al;.V~ coatc<1 11 18 used Eor adsorptlon studles. Varlous concentratlona of TCIIE In SLS
or ln SLS/pyrop11osp11ate/GQt1trez/NAF are mlxed wlth the coated llA and lucubated At 37~ for 3 hours under contlnuous agltatlon. At the end of lncubatlun perlod, the mlxtures are centrlfuged, 1~ separated and the amounts oE TCIIE adsorbed determlned by e~tlmatlng TCIIE ln the supetnatant at 283nM ln a Gllford ~pectrophotometer. The amounts sdsorbed are ca]culated by tlle dlfference between the amount Added and tl1e amount left ln tl1e supernat~nt aEter tl1e lncubatlon wltl1 coated llA.
Tl1e table below summarlzes the data.
,., 13333~1 ~
r~t~mln~!lents and Concentratlons Z of TCIIE Adsorbed to Coated H~
0.005~ TCHE ln IX SLS 80~
O.OIY TCHE ln 1% SLS 85X
0.015% TCHE ln IX SLS 85Z
0.02% TCHE ln 1~ SLS 88Z
0.005X TCI1~ ln 1~ SLS; 0.5X 80X
Gantrez; 2% pyrophosphate/
0.24% NaF
' 0.01% TCIIE " 85Z
~ 0.015% TCHE " 86X
0.02X TCHE " 81X
The data lndltates that the addltlon of pyrophofiphatet Gantrez/NsF doefi not lmpalr adfiorptlon of TCHE to fiallva coated tooth n,lnetals.
.
1~39301 Example 3 Dentlfrlce ComPosltlons A ~ C
Parts Parts Parts Glycerlne 15.00 10.20 15.00 Polyethylene Glycol 6005.00 3.00 5.00 Iota Carrageenan 0.60 - 0.60 Sodlum CarboYymethyl Cellulose - l.00 Sodlum Saccharln 0.40 - 0.40 Sodlum Cyclamate - 3.00 Sodlum Fluorlde 0.243 0.243 0.243 : Delonlzed water 15.08 29.90723.657 Tltanlum Dloxlde - - 0.50 Sodlum ~enzoate - 0.50 FD&C ~lue No. 1(1% Solutlon) 0.400 - -Sorbltol t70%) 19.807 22.50 22.50 Gantrez S-97 8.330( ) 1.00l )1.00~ ) Tetrasodlum Pyrophosphate 1.50 1.50 1.50 Tetrapotasslum Pyrophosphate 4.50 4.50 4.50 Preclpltated Amorph. Hydrated Slllca 16.00 19.50 Preclpltated Amorp. S111CA
contalnlng comblned alumlna - - 16.00 Slllc~ Thlckener 7.00 - 5.50 Flavor 1.10 0.95 1.10 Sodlum Lauryl Sulfate 1.20 1.20 1.20 TCHE 0.50 o 50 0 50 1 iqu ld powder - 1339~01 ExA~ple 4 The dentlfrice descrlbed ln Example 3A 18 compared wlth the same compusltlun except wlthout sny TCIIE snd wlth sdded 0.50 pstt6 of wlter. Aqueous extrActs uf esch dentlfrlce are prepsred A8 follow6: 50 ml of dlstllled wster 16 added to 1.0 ~m of esch dentlfrlce, ~lxed well ror a cuuple oE hour~ wlth 6tlrrlng bar ~nd centrlfuged, sfter uhlch the ~upernntsnt 16 collected ns Aqueuu6 extrsct. Antlbncterlal Actlvlty of the dentlfrlce extrncts sre evnluated on Bacterludes ginglv8118.
Result6 Are 6ummarlzed belo~.
IAB~E 3 Inhlbltlon of Growth of Bacterlode6 Glnglvall6 Trestment %
Extract from dentlfrlce contalnlng 100.0 TCHE ~1:500) Extract from dentlfrlce wltlIout o.O
TCHE (I:500) TCHE (5.0 mcg/ml) by ltself100.0 These re6ults lndlcate thst TCHE sntlbacterial antlplaque a8ent 16 compatlble ln a dentlfrlce composltlon contAInlng anlonlc surfactsnt plus pyrophoAphAte sntlcAlculus lngred1ents wlth en2yme lnhlbltor6 C~ntrer and NaF. Slmllsr compsrsble effects prevall when esch of hexyl resurclnol, 2,2'-methylene bls~4-chloru-6-bromophenol)/
replsce TCHE.
133930~
Example 5 Mouthrlnse Parts Tetrasodlum Pyrophosphate 2.00 Gantrez S-97 0.25 Glycerlne 10.00 Sodlum Fluoride 0.05 Fluronlc F108 2.00 ~Polyoxyethylelle/Polyoxypropylene Block Copolymer) TCHE 0.10 Flavor 0.90 Water Q.S. to 100.00 Example 6 Lozenye 75-80% Sugar 1-20% Corn Syrup 0.1-1.0 Flavor 2~. Tetrasodlum Pyrophosphate 0.25% Gantrez S-97 0.01 to 0.05% MaF
0.01 to 0.1% TCHE
1 to 5~i Magneslum Stearate Lubrlcant 0.01 to 0.2~ Wate~
Trade-mark 27 X
1~39301 Example 7 Chewlng G~m .Parts Gum base 25.00 S~tbltol (70~) 17.00 TCIIE 0.50 to 0.10 Tetrasodlum Pyrophosophate 2.00 Gantrez S.97 0.25 Na~ 0.05 Glycerlne O.S0 Ct-y~talllne Sutbitul 53.00 ~1avor And WAter Q.S. to 100.00 Thls lnventlun has been described wlth respect to certain preferred embodlments and lt wlll be understood that modiflcatlon6 and varlAtluns thereof obvlous to those skllled in the Art sre to be lncluded wlthln the purvlew of thls appllcat~on snd the scope of the appended claims.
Claims
THE EMBODIMENTS OF THE INVENTION IN WHICH AN EXCLUSIVE
PROPERTY OR PRIVILEGE IS CLAIMED ARE DEFINED AS FOLLOWS:
1. 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 polyphosphate salt selected from the group consisting of water-soluble alkali metal or ammonium tripolyphosphates and hexametaphosphates 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, alkylphenols, halophenols, alkylhalophenols, aromatic halophenols, resorcinols and bisphenolic compounds) and halogenated carbanilides, and a fluoride ion source.
2. An oral composition as claimed in Claim 1 wherein the said tripolyphosphate is sodium tripolyphosphate.
3. An oral composition as claimed in Claim 1 wherein the said hexametaphosphate is sodium hexametaphosphate.
4. An oral composition as claimed in Claim 1 which contains about 10-80% by weight of a liquid phase comprising water and humectant.
5. The oral composition as claimed in Claim 1 in which the said oral composition contains about 70-99.9% by weight of a mixture of wetter and alcohol in a weight ratio of from substantially 1:1 to about 20:1.
6. The oral composition as claimed in Claim 5 in which the said alcohol is ethanol.
7. An oral composition comprising in an orally acceptable vehicle, an effective anticalculus amount of anticalculus material, a water-soluble alkali metal hexametaphosphate and an effective antiplaque amount of a substantially water-insoluble non-cationic antibacterial agent 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.
8. The oral composition as claimed in Claim 7 wherein the fluoride ion source is sufficient to release 300 to 2000 ppm of fluoride ion.
9. The oral composition as claimed in Claim 7 in the form of a dental gel, toothpaste, dental cream, toothpowder or dental tablet.
10. The oral composition as claimed in Claim 7 in which the hexametaphosphate salt is present in an amount of 0.1-7%
by weight.
11. The oral composition as claimed in Claim 7 in which the said antibacterial agent is present in an amount of 0.01-5% by weight.
12. The oral composition as claimed in Claim 7 in which the said antibacterial agent is a halogenated diphenyl ether.
13. The oral composition as claimed in Claim 12 in which the halogenated diphenyl ether is a 2,4,4'-trichloro-2'-hydroxydiphenyl ether.
14. The oral composition as claimed in Claim 7 wherein the said hexametaphosphate is sodium hexametaphosphate.
15. The oral composition as claimed in Claim 13 in which the 2,4,4'-trichloro-2'-hydroxydiphenyl ether is present in an amount of about 0.03-1% by weight.
16. The oral composition as claimed in any one of Claims 1 to 3 and 11 to 15 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.
17. The oral composition as claimed in Claim 16 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.
18. The oral composition as claimed in Claim 16 in which the said polishing agent is a silica polishing material.
19. An oral composition comprising in an orally acceptable vehicle, an effective anticalculus amount of at least one polyphosphate salt selected from the group consisting of water-soluble alkali metal, tripolyphosphates and hexametaphosphates, as essential anticalculus agent and an effective antiplaque amount of a substantially water-insoluble non-cationic antibacterial compound as essential antiplaque agent.
20. The oral composition according to Claim 19 further containing as essential inhibitor of salivary enzymatic hydrolysis of the sodium tripolyphosphate about 0.05% to about 3% of a water-soluble synthetic anionic polymeric polycarboxylate salt having a molecular weight of about 1,000 to about 1,000,000.
21. The oral composition according to Claim 20 wherein said water-soluble polycarboxylate salt is an alkali metal or ammonium salt of a copolymer of vinyl methyl ether and maleic acid or anhydride having a molecular weight of about 30,000 to about 500,000.
22. The oral composition according to Claim 21 in the form of a toothpaste containing a dentally acceptable water-insoluble polishing agent.
23. The oral toothpaste composition according to Claim 22 containing a silica polishing agent.
24. Use of an oral composition according to any one of Claims 1 to 23 to combat calculus and plaque in a mammal.
25. An oral composition comprising, in an orally acceptable vehicle, an effective anticalculus amount of at least one water-soluble linear molecularly dehydrated polyphosphate salt as essential anticalculus agent and an effective antiplaque amount of a substantially water-insoluble non-cationic antibacterial compound as essential antiplaque agent, wherein said substantially water-insoluble non-cationic antibacterlal compound is other than a parahydroxybenzoic acid ester.
26. An oral composition according to Claim 25 wherein said polyphosphate salt comprises a pyrophosphate salt.
27. An oral composition according to Claim 26 wherein said pyrophosphate salt comprises a mixture of sodium pyrophosphate and potassium pyrophosphate.
28. An oral composition according to Claim 27 wherein said pyrophosphate salt comprises a mixture of tetrasodium pyrophosphate and tetrapotassium pyrophosphate.
29. An oral composition according to Claim 25 wherein the substantially water-insoluble non-cationic antibacterial compound is a halogenated diphenyl ether.
30. An oral composition according to Claim 29 wherein the substantially water-insoluble non-cationic antibacterial compound is triclosan.
31. An oral composition according to any one of Claims 25 to 30, further containing as essential inhibitor of salivary enzymatic hydrolysis of the water-soluble linear molecularly dehydrated polyphosphate salt an effective amount of a water-soluble synthetic anionic polymeric polycarboxylate salt.
32. An oral composition according to any one of Claims 25, 28, 29 and 30, in the form of a toothpaste containing a dentally acceptable water-insoluble polishing agent.
33. An oral composition according to Claim 32 in the form of a toothpaste containing a silica polishing agent.
34. An oral composition comprising, in an orally acceptable vehicle, an effective anticalculus amount of pyrophosphate as essential anticalculus agent, an effective antiplaque amount of a substantially water-insoluble non-cationic antibacterial compound as essential antiplaque agent and as essential inhibitor of salivary enzymatic hydrolysis of the polyphosphate salt a fluoride ion-providing source in an amount sufficient to supply about 25 ppm to about 2,000 ppm of fluoride ions, wherein said substantially water-insoluble non-cationic antibacterial compound is other than a parahydroxy-benzoic acid ester.
35. An oral composition according to Claim 25, wherein said polyphosphate salt comprises sodium tripolyphosphate.
36. An oral composition according to any one of Claims 25 and 26, wherein the substantially water-insoluble non-cationic antibacterial compound is a phenolic compound.
37. An oral composition according to Claim 36 wherein said antibacterial phenolic compound comprises hexyl resorcinol.
38. An oral composition according to Claim 37 wherein said polyphosphate salt comprises sodium tripolyphosphate.
39. An oral composition comprising, in an orally acceptable vehicle, a dentally acceptable silica polishing agent, an effective anticalculus amount of at least one water-soluble linear molecularly dehydrated polyphosphate salt as essential anticalculus agent, an effective antiplaque amount of a substantially water-insoluble non-cationic antibacterial compound as essential antiplaque agent and a mixture of (A) an amount of a fluoride ion-providing source sufficient to supply about 25 ppm to about 2,000 ppm fluoride ions; and (B) about 0.05% to about 3% of a water-soluble synthetic anionic polymeric polycarboxylate.
40. An oral composition comprising, in an orally acceptable vehicle, a dentally acceptable silica polishing agent, an effective anticalculus amount of at least one water-soluble linear molecularly dehydrated polyphosphate salt as essential anticalculus agent, an effective antiplaque amount of a substantially water-insoluble non-cationic antibacterial compound as essential antiplaque agent and a mixture of (A) an amount of a fluoride ion-providing source sufficient to supply about 25 ppm to about 2,000 ppm fluoride ions; and (B) about 0.05% to about 3% of a water-soluble synthetic anionic polymeric polycarboxylate;
wherein said substantially water-insoluble non-cationic antibacterial compound is other than a parahydroxybenzoic acid ester.
41. Use of an oral composition according to any one of Claims 25 to 40 to combat calculus and plaque in a mammal.
PROPERTY OR PRIVILEGE IS CLAIMED ARE DEFINED AS FOLLOWS:
1. 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 polyphosphate salt selected from the group consisting of water-soluble alkali metal or ammonium tripolyphosphates and hexametaphosphates 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, alkylphenols, halophenols, alkylhalophenols, aromatic halophenols, resorcinols and bisphenolic compounds) and halogenated carbanilides, and a fluoride ion source.
2. An oral composition as claimed in Claim 1 wherein the said tripolyphosphate is sodium tripolyphosphate.
3. An oral composition as claimed in Claim 1 wherein the said hexametaphosphate is sodium hexametaphosphate.
4. An oral composition as claimed in Claim 1 which contains about 10-80% by weight of a liquid phase comprising water and humectant.
5. The oral composition as claimed in Claim 1 in which the said oral composition contains about 70-99.9% by weight of a mixture of wetter and alcohol in a weight ratio of from substantially 1:1 to about 20:1.
6. The oral composition as claimed in Claim 5 in which the said alcohol is ethanol.
7. An oral composition comprising in an orally acceptable vehicle, an effective anticalculus amount of anticalculus material, a water-soluble alkali metal hexametaphosphate and an effective antiplaque amount of a substantially water-insoluble non-cationic antibacterial agent 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.
8. The oral composition as claimed in Claim 7 wherein the fluoride ion source is sufficient to release 300 to 2000 ppm of fluoride ion.
9. The oral composition as claimed in Claim 7 in the form of a dental gel, toothpaste, dental cream, toothpowder or dental tablet.
10. The oral composition as claimed in Claim 7 in which the hexametaphosphate salt is present in an amount of 0.1-7%
by weight.
11. The oral composition as claimed in Claim 7 in which the said antibacterial agent is present in an amount of 0.01-5% by weight.
12. The oral composition as claimed in Claim 7 in which the said antibacterial agent is a halogenated diphenyl ether.
13. The oral composition as claimed in Claim 12 in which the halogenated diphenyl ether is a 2,4,4'-trichloro-2'-hydroxydiphenyl ether.
14. The oral composition as claimed in Claim 7 wherein the said hexametaphosphate is sodium hexametaphosphate.
15. The oral composition as claimed in Claim 13 in which the 2,4,4'-trichloro-2'-hydroxydiphenyl ether is present in an amount of about 0.03-1% by weight.
16. The oral composition as claimed in any one of Claims 1 to 3 and 11 to 15 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.
17. The oral composition as claimed in Claim 16 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.
18. The oral composition as claimed in Claim 16 in which the said polishing agent is a silica polishing material.
19. An oral composition comprising in an orally acceptable vehicle, an effective anticalculus amount of at least one polyphosphate salt selected from the group consisting of water-soluble alkali metal, tripolyphosphates and hexametaphosphates, as essential anticalculus agent and an effective antiplaque amount of a substantially water-insoluble non-cationic antibacterial compound as essential antiplaque agent.
20. The oral composition according to Claim 19 further containing as essential inhibitor of salivary enzymatic hydrolysis of the sodium tripolyphosphate about 0.05% to about 3% of a water-soluble synthetic anionic polymeric polycarboxylate salt having a molecular weight of about 1,000 to about 1,000,000.
21. The oral composition according to Claim 20 wherein said water-soluble polycarboxylate salt is an alkali metal or ammonium salt of a copolymer of vinyl methyl ether and maleic acid or anhydride having a molecular weight of about 30,000 to about 500,000.
22. The oral composition according to Claim 21 in the form of a toothpaste containing a dentally acceptable water-insoluble polishing agent.
23. The oral toothpaste composition according to Claim 22 containing a silica polishing agent.
24. Use of an oral composition according to any one of Claims 1 to 23 to combat calculus and plaque in a mammal.
25. An oral composition comprising, in an orally acceptable vehicle, an effective anticalculus amount of at least one water-soluble linear molecularly dehydrated polyphosphate salt as essential anticalculus agent and an effective antiplaque amount of a substantially water-insoluble non-cationic antibacterial compound as essential antiplaque agent, wherein said substantially water-insoluble non-cationic antibacterlal compound is other than a parahydroxybenzoic acid ester.
26. An oral composition according to Claim 25 wherein said polyphosphate salt comprises a pyrophosphate salt.
27. An oral composition according to Claim 26 wherein said pyrophosphate salt comprises a mixture of sodium pyrophosphate and potassium pyrophosphate.
28. An oral composition according to Claim 27 wherein said pyrophosphate salt comprises a mixture of tetrasodium pyrophosphate and tetrapotassium pyrophosphate.
29. An oral composition according to Claim 25 wherein the substantially water-insoluble non-cationic antibacterial compound is a halogenated diphenyl ether.
30. An oral composition according to Claim 29 wherein the substantially water-insoluble non-cationic antibacterial compound is triclosan.
31. An oral composition according to any one of Claims 25 to 30, further containing as essential inhibitor of salivary enzymatic hydrolysis of the water-soluble linear molecularly dehydrated polyphosphate salt an effective amount of a water-soluble synthetic anionic polymeric polycarboxylate salt.
32. An oral composition according to any one of Claims 25, 28, 29 and 30, in the form of a toothpaste containing a dentally acceptable water-insoluble polishing agent.
33. An oral composition according to Claim 32 in the form of a toothpaste containing a silica polishing agent.
34. An oral composition comprising, in an orally acceptable vehicle, an effective anticalculus amount of pyrophosphate as essential anticalculus agent, an effective antiplaque amount of a substantially water-insoluble non-cationic antibacterial compound as essential antiplaque agent and as essential inhibitor of salivary enzymatic hydrolysis of the polyphosphate salt a fluoride ion-providing source in an amount sufficient to supply about 25 ppm to about 2,000 ppm of fluoride ions, wherein said substantially water-insoluble non-cationic antibacterial compound is other than a parahydroxy-benzoic acid ester.
35. An oral composition according to Claim 25, wherein said polyphosphate salt comprises sodium tripolyphosphate.
36. An oral composition according to any one of Claims 25 and 26, wherein the substantially water-insoluble non-cationic antibacterial compound is a phenolic compound.
37. An oral composition according to Claim 36 wherein said antibacterial phenolic compound comprises hexyl resorcinol.
38. An oral composition according to Claim 37 wherein said polyphosphate salt comprises sodium tripolyphosphate.
39. An oral composition comprising, in an orally acceptable vehicle, a dentally acceptable silica polishing agent, an effective anticalculus amount of at least one water-soluble linear molecularly dehydrated polyphosphate salt as essential anticalculus agent, an effective antiplaque amount of a substantially water-insoluble non-cationic antibacterial compound as essential antiplaque agent and a mixture of (A) an amount of a fluoride ion-providing source sufficient to supply about 25 ppm to about 2,000 ppm fluoride ions; and (B) about 0.05% to about 3% of a water-soluble synthetic anionic polymeric polycarboxylate.
40. An oral composition comprising, in an orally acceptable vehicle, a dentally acceptable silica polishing agent, an effective anticalculus amount of at least one water-soluble linear molecularly dehydrated polyphosphate salt as essential anticalculus agent, an effective antiplaque amount of a substantially water-insoluble non-cationic antibacterial compound as essential antiplaque agent and a mixture of (A) an amount of a fluoride ion-providing source sufficient to supply about 25 ppm to about 2,000 ppm fluoride ions; and (B) about 0.05% to about 3% of a water-soluble synthetic anionic polymeric polycarboxylate;
wherein said substantially water-insoluble non-cationic antibacterial compound is other than a parahydroxybenzoic acid ester.
41. Use of an oral composition according to any one of Claims 25 to 40 to combat calculus and plaque in a mammal.
Priority Applications (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CA000616760A CA1339301C (en) | 1987-01-30 | 1993-11-04 | Antibacterial antiplaque, anticalculus oral composition |
Applications Claiming Priority (4)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| US890187A | 1987-01-30 | 1987-01-30 | |
| US008,901 | 1987-01-30 | ||
| CA000557661A CA1327942C (en) | 1987-01-30 | 1988-01-29 | Antibacterial antiplaque, anticalculus oral composition |
| CA000616760A CA1339301C (en) | 1987-01-30 | 1993-11-04 | Antibacterial antiplaque, anticalculus oral composition |
Related Parent Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| CA000557661A Division CA1327942C (en) | 1987-01-30 | 1988-01-29 | Antibacterial antiplaque, anticalculus oral composition |
Publications (1)
| Publication Number | Publication Date |
|---|---|
| CA1339301C true CA1339301C (en) | 1997-08-19 |
Family
ID=25671683
Family Applications (3)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| CA000616608A Expired - Lifetime CA1328623C (en) | 1987-01-30 | 1993-04-01 | Antibacterial antiplaque, anticalculus oral composition |
| CA000616610A Expired - Lifetime CA1328081C (en) | 1987-01-30 | 1993-04-01 | Antibacterial antiplaque, anticalculus oral composition |
| CA000616760A Expired - Lifetime CA1339301C (en) | 1987-01-30 | 1993-11-04 | Antibacterial antiplaque, anticalculus oral composition |
Family Applications Before (2)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| CA000616608A Expired - Lifetime CA1328623C (en) | 1987-01-30 | 1993-04-01 | Antibacterial antiplaque, anticalculus oral composition |
| CA000616610A Expired - Lifetime CA1328081C (en) | 1987-01-30 | 1993-04-01 | Antibacterial antiplaque, anticalculus oral composition |
Country Status (1)
| Country | Link |
|---|---|
| CA (3) | CA1328623C (en) |
-
1993
- 1993-04-01 CA CA000616608A patent/CA1328623C/en not_active Expired - Lifetime
- 1993-04-01 CA CA000616610A patent/CA1328081C/en not_active Expired - Lifetime
- 1993-11-04 CA CA000616760A patent/CA1339301C/en not_active Expired - Lifetime
Also Published As
| Publication number | Publication date |
|---|---|
| CA1328623C (en) | 1994-04-19 |
| CA1328081C (en) | 1994-03-29 |
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Legal Events
| Date | Code | Title | Description |
|---|---|---|---|
| MKEX | Expiry |
Effective date: 20140819 |