Note: Descriptions are shown in the official language in which they were submitted.
- -~ 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
1339301
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~.
1 339301
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
- 1339301
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.
--10--
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
-- 1 1 --
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.
-13-
~ 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
- - ~
1339301
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~
~ ===
1339301
..,
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
-18-
!'
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.
-20-
.. 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".
-21-
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.
-22-
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.
,.,
-23-
13333~1 ~
TABLE 2
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.
.
-24-
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.
-26-
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.
-28-
