Note: Descriptions are shown in the official language in which they were submitted.
2~5181~
~0 94/14406 PCT/~JS93/11786
ORAL COMPOSITIONS CONTAINING
ANTlPLAQUE, ANTICALCULUS AGENTS
This invention relates to oral colllposilio"s, such as dentifrices
and oral solutions, for the treatment or prevention of dental plaque,
calculus, gingivitis, and mouth malodor.
Backqround of the Invention
The mouth is a habilat for microbial growth and colonization.
Within the mouth, the gums, lips, oral mucosa (cheek), palate, tongue
and teeth provide surfaces for the cclo~ dliGn and accumulation of
bacteria. Teeth are unique in the oral cavity be~ ~se they have hard,
non-sl ,eJding surfaces where t~acleria and their products (dental
plaque) can significantly accumulate, especially in ap,uro,~i,,,al areas
and along the gingival crevice.
Dental plaque is a rough sticky film on the teeth that is made up
of saliva, bacteria and food pa~licles which ddl,eles ten~cio!~sly to
teeth at points of irregularity or disconli"uity. Within a few hours of
teeth cleaning, a film of salivary mucins, co"sisli,)g primarily of
proteins, forms on the teeth. Various oral ba.,leria colonize the mucins
and multiply, fo""ing a layer of plaque. Carbohydrate food debris
adl,eres to the mucins and is digested by some types of plaque-
causing bacteria. The digestion prod(l~s both by-products which add
to the plaque, and prodl~ces acid which erodes tooth enamel. The
bacte,ial by-products produced in the oral cavity also include foul
smelling gases which can result in r"alodor of the oral cavity.
If not prevented or removed, plaque may become embedded
with mineral salts, containing calcium and ,~hospl,ate, to form a hard
crusty deposit, c~lcul~ ~s or tartar, on the teeth. Calculus may be white
or yellowish in color or may be slained or discolorecJ by extraneous
agents. ~lcul~s tends to be more unsi!Jl,lly than plaque and much
more difficult to remove from the teeth. The toxins in plaque and
calculus can irritate the gingival tissoes surrounding the coated teeth,
WO 94/14406 PCT/US93/1178~
2is~8l5
causing inflarr,r"alion and destruction of the gums which can lead to
other complicalionc.
Zinc is an anti~lculus agent; however compositions containing
zinc generally taste asll inge,)l and unpleasantly bitter. Like the
chemical and biological activities the negative aesthetics of the zinc
cation are dose depende"l. higher cGncenlralions of zinc exhibit
poorer aesthetics; Ihere~or~ increasing the co"c~ntralion of free zinc
tends to increase errica~ at the ex~pense of aesthetics. This coupled
behavior between efficacy and aesU~elics has limited the utility of zinc
in oral compositions. Pyrophospl-ate is also an antic~lcul~s agent
and likewise has an unpleasant taste which wor~e"s with increased
py, u~,l ,os~l ,ate concerlt, dlion. By carefully formulating zinc and
py, uphospl ,ate~,)taining com~osilions it has been surprisingly
found that the level of zinc in an oral co",posilion can be increased
thus incr~asing the correspond;ng ar,licAIc~ s effect without greatly
inueasing the negative aesthetics of the col"~,osilion. Applicants
have SL~"~ isi, Iyly found that certain ratios of
zinc:citrate:py, upl ,osphale in combination with certain formulation
col"pG"ents unexpectedly provide oral cGI",cosilions which are stable
for longer time periods than are other formulations.
SummarY of tne Invention
This invention involves oral~are w",rosilions col"~,rising.
(a) zinc oxide or zinc nitrate; a source of citrate ions; and
one or more pl,ospho"Js~"lai"ing anticalculus agents
selecte~ from the group consisting of pyrophosphate
pl ,osphonale dipl lospl ,Gnale and phal ",aceutically-
acceptable linear condensed pol~,ul ,osphates of the
general formula: (PnO(3n+1 ))(n+2)- wherein n is an
inlteger from 2 to 21;
wherein a molar ratio of the zinc ions:citrate ions is from about 1:0.1 to
about 1:20; the molar ratio of the zinc ions:~l,ospl,o,.ls~ontaining
a, lliCAIc ~lus agents is from about 1:1 to about 1:20; and
(b) the pha""~ ti~ ly-acceptable topical oral carrier.
~VO 94/14406 21 5 1 ~1 ~ PCT/US93/11786
Detailed Disclosure of the Invention
This invention provides cor",oositions effective against dental
plaque fo",~alion, calculus formation, gingivitis, and mouth malodor.
Such compositions coi"~,ise certain zinc salts and certain molar ratio
amounts of citrate and pyro relative to zinc in a pharmaceutically-
acceplable carrier.
"Pyro", as used herein, refers to pyrophosphate; phospl,G,)ale;
diphos~Jl ,onale; and pl Id~ CeU tic~lly-acceplable polyphosphales
including, but not limited to, linear condensed polyphosphates of the
general formula: (PnO(3n+1))(n+2)~ wherein n is an inleger from 2 to
21 .
"Pharmaceutically-acceptable topical oral carrie~', as used
herein, denotes a carrier for the active co",pounds of this invention
(hereinafter "Actives") co",~risi"g solid or liquid filler diluents s~it~le
for use in contaot with the oral tissues of humans and other ani",als
without undue. toxicity, inco"~ ibility, instability, irritation, allergic
respG"se, and the like, cG",r"e"surate with a reasGI~able benefiVrisk
ratio. Such topical oral carrier, when combinad with Actives of this
invention, results in a composilion which is administered topic~lly to
the oral cavity. r,e~rably such col"~ositions are held in the oral
cavity for a period of time, and then largely eYpectorated rather than
being swallowed. Such ~"~posilions include mouthwashes, mouth
rinses, mouth sprays, dental llealment sol ~tions, tooU~p~stes, liquid
de,ltir,ices and the like and are more fully des~ibed hereinafter.
Del,lir,ices and mouthwashes are the pr~fe"ed c~""~osilions.
"Free pyro", as used herein, refers to pyro that is not bound or
chelated to the transition metal, zinc.
"Free zinc", as used herein, refers to hydlaled zinc cationic
species, such as Zn(H2o)62+.
"Safe and effective amount" as used herein means an amount
of co""~ound or co"~posili~" surricient to induce a significant positive
".odiricalion in the condition to be l,ealed, but low enough to avoid
serious side effects (at a rea-~G"able benefiUrisk ratio), within the
scope of sound medical judgment. The safe and effective amount of
the ~""~ound or co,nrosi(ion will vary with the particular condition
being l,ealed, the age and physical CGndi~iGIl of the patient being
2 ~S PCT/US93/1178~
treated the severity of the condition the duration of the treatment the
nature of concurrent therapy the specific compound or composition
employed the particular pha""aceutically-acceptable carrier utilized
and like factors.
S The term col"prisil"J as used herein means that various
additional cG""~onents can be conjointly employed in the compositions
of this invention.
As used herein percenlages listed are weight percentage of
composition unless otherwise specified.
Zinc:Citrate and Zinc:PYro Ratios
The amounts of pyro and citrate are expressed in terms of a
ratio to the amount of zinc in the oral colnl~osilion. On a molar basis
the amount of citrate relative to zinc is at least 0.1 when the amount of
zinc is 1 (i.e. the ratio of zinc:citrate is at most 1:0.1). Likewise the
amount of pyro relative to to the amcunt of zinc is at least 1 when zinc
is 1 (i.e. the ratio of zinc:pyro is at most 1:1). rl~relled zinc:citrate
ratios are from about 1:0.1 to about 1:20 more preferdbly from about
1:0.5 to about 1:4 more ,ureferably from about 1:1 to about 1:3.
rrefe"ed zinc:pyro ratios are from about 1:1 to about 1:20 more
pr~:ferably from about 1:2 to about 1:6 more prererably from about 1:3
to about 1:5. Also ~,rerer,ed is a zinc:citrate:pyro ratio wherein the
sum of the ratio amounts of citrate and pyro is from about 3 to about 9
more prererdl,ly from about 4 to about 7 when the ratio amount of zinc
is 1 .
The amount of zinc suitable for the purposes of this invention is
from about 0.005% to about 5% Zn; more preferably from about 0.05%
to about 2% Zn; more p~efe(ably still from about 0.1% to about 0.6%
Zn. In denlir,ice co""~ositions the ~,refe"ed amounts of zinc are from
about 0.1% to about 2~6 more prererably from about 0.3% to about
0.6%. In mouthwashes mouth rinses mouth sprays and dental
sol~tions the ~refel,ed amount of zinc is from about 0.005% to about
1% more p~eferably from about 0.01% to about 0.75% more
~, eferably still from about 0.0~% to about 0.5%.
The amount of citrate anion suitable for the purposes of this
invention is from about 0.015% to about 15% citrate. In dentifrice
col"~ositions the prefer,ed amounts of citrate anion are from about
~WO 94/14406 21~1815 PCT/US93/11786
0.2 % to about 8%, more preferably from about 0.4% to about 7%,
more preferably still from about 0.6% to about 6%. In mouthwashes,
mouth rinses, mouth sprays and dental solutions, the prefer, ed
amount of citrate anion is from about 0.01% to about 12%, more
preferably from about 0.1% to about 6%, more prererably still from
v about 0.15% to about 1%.
The amount of pyro anion suitable for the purposes of this
invention is from about 0.5% to about 15% pyro. In dentifrice
compositions, the prer~rled amounts of pyro ion are from about 1% to
about 9%, more ,cr~reral,ly from about 2.5% to about 5%. In
mouthwashes, mouth rinses, mouth sprays and dental solutions, the
prefer,~d amount of pyro anion is from about 0.01% to about 25%,
more preferably from about 0.1% to about 5%.
Suitable sources of zinc ions include zinc oxide and Zn(N03)2.
Zinc sources that are not suitable are zinc
ethylenediaminetel,dacetale (ZnEDTA) and zinc nitrilot,i~cet~te
(ZnNTA). The prere"ed source of zinc ions is ZnO.
Suitable sources of citrate ions include citric acid; alkali metal
salts of citric acid, especi~lly sodium citrate and potassium citrate;
pharm~ce~t~ ly ~ccept~ hydrated and dehydrated salts of any of
the above; and mixtures of any of the above.
Suitable sources of pyro ions are d:sclQsed in U.S. Pat. No.
4,885,155, issued Dece"lber 5, 1989 to Parran & Sakkab; U.S. Pat.
No. 3,678,154, issued July 18, 1972 to Widder et a/.; U.S. Pat. No.
3,737,522, issued June 5, 1973 to Francis et a/.; and U.S. Pat. No.
4,627,977, issued Dec~",ber 9, 1986 to Gaffar et a/.; each is
inco,poratecJ herein by ,efere"ce. Suitable pyro ion sources include
tell~sodi!lm pyrophospl,ale, sodium acid pyrophospl,ale
(Na2H2P207), tet, apot~ssi~ ~m p~, o,GI ,osphale (K4P207); ,uhospl ,ates
3~ including, but not limited to, linear cond~"sed polyphospl ,ates of the
general formula: M(n+2~PnO(3n+1) wherein M is Na or K, and n is an
? integer from 2 to 21; phospl,onates and diphosphonates, such as
EHDP (ethane-1 -hydroxy-1, 1 -diphosphonate) and AHP (azacyclo-
heptane-2,2-diphosphonic acid); pharmaceutically-acceptable alkali
35 metal salts of pyrophosphates, pol~,..l,osphates, phosphonates and
.lipl ,osphonates; and mixtures of any of the above. Preferred
WO 94/14406PCT/US93/1178~
pol~l ,osphate ions are those of the above formula wherein n is 6, 13,
and 21 r,ererfed pyro ions are py,ophosphate ions. P~erer,~:d alkali
metals are sodium and potassium; mixtures of alkali metal salts are
accep~ble. A more preferlad source of pyro ions is a potassium salt
5 of the pyro ion.
ComPositions
Components of the topical, oral carrier are suitable for
administration to the oral cavity of a human or other animal and are
co,l,paliL,le with one another and the other components, especially
10 with the Actives, used in an oral composition of this invention. The
term "co",patiL,le" as used herein, means that the co",ponents are
capable of being co-mingled with one another, in a manner such that
there is no interaction wnich would sul,stA~,lially reduce the efficacy of
the oral co",posilion under ordinary use condiliGr,s.
15r, efe" ed topical, oral carriers provid~ the desired
characteiialics ~or mouthwashes, mouth rinses, mouth sprays, dental
treatment solutions, toothp~-stes, dental gels, tooli ,powders,
prophylaxis pastes, and the like. The topical, oral carriers of this
invention col"~.,ise components typically used in such compositions
20 which are well known to a skilled practitioner. Such co",ponents
include, but ar* not limited to, anlicaries agents, antiplaque agents,
anticalculus agents, dental abrasives, su,ract~-"s, flavoring agents,
sweetening.agents, binders, humectants, thickening agents, buffering
agents, presel./atives, coloring agents and pig",a,lts, ethanol and
25 water.
The pH of oral co,-,~osilions of this invention is critical but can
be varied to some extent. The co""~ositions must be at a pH which is
safe for cG"lact with the tiss~es of the oral cavity, i.e. below a pH of
about 9 for humans, ~.refe,ably below a pH of about 8.5. Otherwise,
30 the pH of the co",posilions is preferably above pH 6, more preferably
above pH 7, more prt:rerably still, above pH 7.5.
During manufacture of a composition of this invention, the r
conditions for addition of each component should be op~ir"i~ed such
that the pH of the mixture does not drop below formulation pH at any
35 time during mixing of the ingredients. To opli"li~e stability of the final
~0 94/14406 21~ 181~ PCT/US93/11786
composition a pH of at least about 7.5 should be maintained at all
times.
Water is a co",ponent of the topical oral carriers of the
compositions of the subject invention. Water employed in the
preparation of the commercially suitable compositions should
~.referably be of low ion col)lel ,t and free of Grgdnic impurities. Water
preferably coi"~,rises from about 2% to about 99% more prererdbly
from about 20% to about 95% of the cor"posilions of the subject
invention. When in the form of tootl ~pasle the cor"positions
prererably con,prise from about 20% to about 99.5% more prererably
from about 30% to about 99% still more ,ure~eral~ly from about 35% to
about 98% more preferdbly still from about 40% to about 97% water.
Mouthwashes co",prise prererably from about 2% to about 99.5%
more preferably from about 45% to about 99% more preferably still
15 from about 75% to about 98% water.
In preparing oral ~",posiliol~s of this invention, it is desirable to
add binders and/or thickening agents particularly to tootl ,pasle
composilions to provide a desired consistency. Suitable binders for
these composilions are those which are non-ionic at the formulation
pH of the co,nposiliG". By 'non-ionic" is meant not more than about
10% ionized. As used herein Yormulation pH means the pH of the
final composition. Suitable binder~ include but are not limited to
natural gums such as gum karaya gum arabic and gum tragaca"ll,;
polysaccha, iJe gums sùch as xantha,) gum; and other natural
products such as calrageenan; chemically modihed natural products
such as those based on cellulose esters that is
~I L,oxylmethylcellulose (CMC) hydroxyethylcellulose (HEC) and
hydroxypropylcellulose (HPC); and synthetic binders such as
polyvinylpyrrolidone; and water soluble salts of cellulose ethers such
as sodium ~, boxymethyl celllJ!ose and sodium ca, Loxymethyl
hydroxyethyl cellulose. Carboxyvinyl polymer binders are less
desirable but may be used. Colloidal magnesium aluminum silicate or
finely divided silica can be used as part of the thickening agent to
further improve texture. Blends and mixtures of the suitable binders
may signirica"lly improve the chara~;te,islics of compositions made
therewith. r~efe"ed binders are chemically modified celluloses such
WO 94/14406 PCT/US93/1178
~,~S~ 8
as CMC or HEC; more prefe~-ed is HEC. Binders and thickening
agents are generally present in the compositions of this invention in
combined amounts of from about 0.1% to 10%, preferably from about
0.25% to about 7.5%, more preferaL)ly from about 0.5% to about 3.5%.
5 OPtional ComPonents
Dental abrasives useful in the topical, oral carriers of the
co""~ositions of this invention include many dirrerel,t materials. The
material selectecl must be one which is coll~ iblQ with the
composition of interest and does not excessively abrade dentin.
10 These include, for example, silicas, including gels and preci,.~ilates,
calcium carbonate, dicalcium o, ll ,opl ,osphate dihydrate, calcium
pyrophosphate, tricalcium phosphate, calcium polymeta-pl ,ospl ,dle,
insoluble sodium polymeta-~Jhospl ,ate, hydrated alumina, and
resinous abrasive r~alelials such as particulate condensation products
15 of urea and ~ormaldehyde, and other materials such as those
disclosed by ~ooley et a/. in U.S. Pat. No. 3,070,510, issued
December 25, 1962, incorporated herein by re~erence. Mixtures of
abrasives may also be used.
Silica dental abrasives, of various types, can provide the unique
20 benefits of excepliGnal dental cleaning and polishing pel rOI " 'ar.ce
without unduly abrading tooth enamel or dentin. For this reason they
are preferred for use herein.
The silica abrasive polishi"g malerials useful herein, as well as
the other abrasives, generally have an average particle size ra"~ing
25 between aboutØ1 and 30 ",icrons, preferably between about 5 and
15 "-i~or,s. The silica abrasive can be precipitated silica or silica gels
such as the silica xerogels desctibed in U.S. Pat. No. 3,538,230,
issued March 2, 1970 to Pader et al., and in U.S. Pat. No. 3,862,307,
issued June 21, 1975 to DiGiulio, both i"c~i ~.Grdted herein by
30 reference. F~f ere~ d are the silica xetc,~els marketed under the
tradename Syloid~ by the W.R. Grace & CGr"pany, Davidson
Chemical Division. rfefe"ed precipitated silica materials include
those marketed by the J. M. Huber C~r,uoralion under the tradename,
7essdentE9~ particularly the silica carrying the designation Zeodent
35 119~). These silica abrasives are desa ibed in U.S. Pat. No.
~0 94/14406 2~ 81~ PCT/US93/11786
4 340 583, Wason issued July 20 1982 incorporated herein by
rererei ,ce.
Mixtures of abrasives may be used. The amount of abrasive in
the co",posiiions desc~ibed herein ranges from about 6% to about
5 70% prt:rerably from about 15% to about 50% more preferably from
about 15% to about 30% when the dentifrice is a toothpaste. Higher
levels as high as 90% may be used if the composition is a tooth
powder.
Flavoring agents can also be added to the oral compositions of
10 this invention to make them more p~l~t~hle. Suitable flavoring agents
include menthol oil of ~inlergreen oil of peppermint oil of spearmint
oil of sassarras and oil of clove. Flavoring agents are generally
included in the slJhject co~,positions in amounts of from 0% to about
3% prererably from about 0.04% to about 2% by weight.
1~ Coloring agents may be added to co,nposilions of this invention
to improve appearance. If present ~lori"g agents typically are
incll~ded at levels of from about 0.001% to about 0.5% by weight.
Sweetening agents are also prefer,ed in the compositions of
this invention to make them more l,A~ le. Sweetening agents which
20 can be used include aspa~ lame acesulfame sacchari,) salts
dexlrose glucose levulose thaumatin D-tryptophan
dihyd~ochalcones and cyclamate salts. Saccl,ari,l salts are prefer,ed.
Sweelenir,g agents are generally used in the subject compositions in
amounts of from 0% to about 6% ,ureferably from about 0.005% to
25 about 5% by weight.
Oral colllposiliG"s can also CGI llain a su, ra~;tanl. Suitable
surfactants are those which are reaso"ably stable and form suds
throughout the pH range suitable for co",positions of this invention
including nonsoap anionic nonionic cationic zwitterionic and
30 a"" l,oteric organic synthetic deterge"ts and cor"palible mixtures
thereof. Many of these suitable su,raclanl~ are disclosed in U.S. Pat.
No. 4 051 234 issued to Gieske et al. on Septe",ber 27 1977 and in
U.S. Pat. No. 3 9~9 458 issued to Agricola Briner Granger and
Widder on May 25 1976 both of which are inco,~orated herein by
35 rerere,)ce. Surfactants are typically present in compositions of this
invention at a level of from 0% to about 20% preferably from about
WO 94/14406 PCT/US93/1178
2~S~8~ 10
-
0.1 more preferably from about 1% to about 4% by weight.
Surfactants may also be used as solubilizing agents to help retain
sparingly soluble co" ,ponents e.g. some flavoring agents in
solutions. Surfactants suitable for this purpose include polysorbales
and poloxamers.
Another optional co",ponent of the oral carriers of the
compositions of this invention is a hu",e~lant. The humectant serves
to keep tootl"~as~e co",posilions from hardeniny upon e.Yros~re to air
and to give mouthwash and tootl,paste composilions a moist feel to
the mouth. Certain hume.la"ls can also impart desirable sweetness
of flavor to mouthwash and tootl"~asle composilions. The humectant
on a pure humectant basis generally com~rises from 0% to about
70% preferably from about 2% to about 55% by weight of the
compositions herein. Suitable hume~ta,)ts for use in co",positions of
this invention include edible polyhydric alcohols such as glycerin
sorbitol xylitol polyethylene glycol and propylene glycol especially
sorbitol and glycerin. rlere"ed humec~a"ts are sorbitol and glycerin;
more prere" ed is sorLilol.
Opacifiers may also be used in toothrA-sles of this invention to
render the tooll"~as~e op~que. Suitable opacifiers include titanium
dioxide and some abrasives including for exa""~le magnesium
aluminum silicate. Opacifiers ge"e(ally comprise from 0% to about
4% preferably from about 0.5% to about 3% by weight of the
w""Josilions herein.
Other optional co",ponenls of the compositions of this invention
are preservatives. The'preservatives prevent microbial growth in the
compositions. Suitable preservatives include methylpa,-a6en
propyJ~arabe" ben7O~tes and ethanol. If the prese, ./ative is ethanol
it generally co",prises from 0% to about 35% by weight prerer~bly
from about 5% to about 15% of the co",posilions herein. Other
preservatives generally coi"prise from 0% to about 5% by weight
preferably from about 0.08% to about 2% of the co"~positions herein.
Anti")icrobial antiplaque agents can also Gptionally be present
in the oral compositions of this invention on the condilion that they are
co",~ ible with the Actives. Such agents may include but are not
limited to triclosan 2 4 4'~ l ,loro-2'-hydroxydiphe, Iyl ether as
215~ 815
~0 94/14406 ^ PCT/US93/11786
11
described The Merck Index. 11 th Ed. (1989), p. 1520 (entry No. 9573);
chlorhexidine, (Merck Index. No. 2090); alexidine (Merck Index, No.
222); hexetidine (Merck Index, No. 4624); sanguinarine (Merck In~ex,
r No 8320); benzalkonium chloride (Merck Index. No. 1066);
salicylanilide (Merck Index. No. 8299); domiphen bromide (Merck
index, No. 3411); cetylpyridinium chloride, (CPC) (Merck Index. No.
2024); tetradecylpyridinium chloride, (TPC); N-tetradecyl-
4-ethylpyridinium chloride (TDEPC); octenidine; delmopinol, octapinol,
and other piperidino derivatives; nicin prepardlions; antibiotics such as
augmentin, amoxicillin, tetracycline, doxycycline, minocycline, and
metronidazole; and peroxides, such as cylium peroxide, hy~rogen
peroxide, and magnesium monoperthalate and its analogs as
described in U.S. Patent No. 4,670,252; and analogs and salts of the
above antimicrobial antiplaque agents. If present, the antimi~obial
antiplaque agents may co"~ ise from 0% to about 6%, preferably from
about 0.1 % to about 5% by weight of the compositions of this
invention.
Bleaching agents can also be present in the oral compositions
of this invention. Suitable bleaching agents include organic and
i"orgal1ic oxidi~i"g agents such as hyd~s~en peroxi-le, alkali metal
peroxides and superoxide and oryanic peroxides such as ."o"oper-
oxyphthalates and pe,Le"~oic derivatives. If pr~ce"l, such bleaching
agents may coi,-~,rise from 0% to about 6%, preferdbly from about 1 %
to about 5% by weight of the co",positions of this invention.
Nutrients can also be present in the oral ~,.,posi~ion of this
invention, on condition that they are co,,,,ualible with the Actives. Such
agents may include folate, retinoids (Vitamin A), Vitamin C, Vitamin E.
If ~Jreselll, the nutrients generally comprise from about 0.001% to
about 10% by weight of the co"~posilions of this invention.
Other optional ingredients include a safe and effective amount
of a fluoride ion source, which typically is in the form of a
water-soluble fluoride ~I "pound. This water-soluble fluoride
compound is typically present in the co",posi~ions of this invention in
an amount sufficient to give a fluoride concentration of from about
3~ 0.0025~ to about 5.0% by weight, preferably from about 0.005% to
about 2.0% by weight. P~efel,ed fluoride sources are sadium fluoride,
-
WO 94/14406 PCT/US93/1178~j_
12 ~
~S~
acid~ ted phospl ,ate fluoride and sodium monofluorophosphate.
U.S. Pat. No. 3678154 issued July 18 1972 to Widder et al.
discloses such salts as well as others and is incorporated herein by
reference.
Other optional ingredients include sy"ll,elic or natural anionic
polymeric polyc:a,boxylates polysaccharides and polysulfates. The
polymers may be present at a weight amount of from about 0.05% to
about 3% more preferably form about 0.05% to about 2% more
l~rererably still from about 0.1% to about 2%. Suitable polymers
include but are not limited to copolmers of maleic acid anhydride or
acid with another polymerizable ethylenically unsaturated ll,onGi"ers
linear polyca, boxylates alginates pec~ins carageenans. Most
prefe"ad are 1:4 to 4:1 copolymers of maleic anhydride or acid with
another poly, neri~able ethylenically unsaturated " ,o"o" ,er ,c,referably
methyl vinyl ether (methoyethylene) having a molcular weight (M.W.)
of about 30 000 to about 1 000 000. These copolymers are available
for exa",~le as Ganlre~ AN 139 (M.W. 500000) A.N. 119 (M.W.
250 000) and ~referably S-97 rl,a""aceutical Grade (M.W. 70 000) of
GAF Co, ~oratiG".
Other operdli~/e polymeric polyca, 6Oxylates include those
disclQsed in U.S. Pat. No. 3956480 such as the 1:1 copolymers of
maleic anhydride with ethyl acrylate hydroxyethyl methacrylate N-
vinyl-2-pyrrolidone or ethylene the latter being available for exa""~le
as l~lqol,s~nto EMA No. 1103 M.W. 10 000 and EMA Grade 61 and
1:1 copolymers of acrylic acid with methyl or hydroxyethyl
methacrylate methyl or ethyl acrylate isobutyl vinyl ether or N-vinyl 2-
pyrrolidone.
~efe"eJ CGIII~OSjl;GIIS
~refe~ composilio"s of this invention are in the form of
de,ltir,ices especially toothr~st~s CGIII~OneI)lS of toothr~stes
generally include a dental abrasive (from about 10% to about 50%) a
su,ractant (from about 0.5% to about 10%) a thickening agent (from
about 0.1% to about 5%) a humectant (from about 10% to about
70%) a flavoring agent (from about 0.04% to about 2%) a sweetening
agent (from about 0.1% to about 3%) a coloring agent (from about
0.01% to about 0.5%) and water (from about 2% to about ~5%).
~o 94/14406 21 S l ~ l S PCT/US93/11786
Other prefe,led compositions of this invention are mouthwashes
mouth sprays and dental solutions. Components of such
mouthwashes and mouth sprays include water (from about 45% to
about 99%) ethanol (from O% to about 25%) humectant (from 0/O to
5 about 50%) su,r~;tanl (from about 0.01% to about 7%) flavoring
agent (from about 0.04% to about 2%) sweetening agent (from about
0.1% to about 3%) and colGring agent (from about 0.001% to about
0.5~). Such mouthwashes and mouth sprays may also include an
antiplaque agent (from about 0.1% to about 5%).
10 Methods of Use
Another aspect of this invention involves methods of l~ealing or
preventing mouth odor dental pl~ql ~e ~ s and gingivitis by
application of compositions comprising a safe and effective amount of
Actives to tissues of the oral cavity. Such c~ ,osilions are desc, ibed
1 5 hereinabove.
These ~lletllods involve administering a safe and effective
amount of Actives ,urererably by adlllillisleri~g an oral cG""~osilion of
this invention as des~ i6ed 1 ,ereinabove to the oral cavity. rl eferably
",ell,ods of this invention co",prise adminisleri"g an amount of
20 co",position ~mp~ising at least about 0.0019 of the Actives. The
teeth and other oral cavity tissues are P~-osed to the Actives.
When the oral col"l~osi~ion is a too~l"~ste ~referal)ly from
about 0.3 grams to about 15 grams preferably from about 0.5 grams
to about 5 grams more prer~rably from about 1 to about 2 grams of
25 tooli"~asle is applied to an appli~AI;llg device e.g. a tooll,~ sh. The
applicating device is then conlacled with the oral cavity surfaces in a
",anner such that the oral ~,npositiGrl is contacted with tissue of the
oral cavity espqc-~lly the teeth and gums. The applicating device may
be further used to effect an even distribution of the oral co"",osilion to
30 the tooth surFace for example by brushing. The application preferably
lasts for a period of from about 15 secG"ds to about 10 minutes more
preferably from about 30 seconds to about 3 minutes more preferably
still from about 1 minute to about 2 minutes. Following arplicPtion the
toothpaste residue is typically removed from the tooth surface by using
35 a liquid acceptable to the oral cavity typically water to rinse and be
sxreGtora~ed from the oral cavity.
\\
WO 94/14406 PCT/US93/1178~
14
When the oral composition is a mouthwash, typically from about
1 ml. to about 20 ml., preferably from about 2 ml. to about 15 ml., most
preferably from about 10 ml. to about 15 ml., of liquid mouthwash
containing the antiplaque Active is introduced to the oral cavity. The
liquid mouthwash is then agitated for from about 10 seconds to about
10 min., preferably from about 15 seconds to about 3 min., more
preferably from about 30 seco,)Js to about 2 minutes, within the oral
cavity to obtain an improved distribution of the mouthwash over the
tissue of the oral cavity. Following agitation, the mouthwash is
typically expectorated from the oral cavity.
Application frequency is prererably from about 3 times weekly to
about 4 times daily, more ,l~refer~bly from about once daily to about 3
times daily, more preferably still from about once to about twice daily.
The period of l,edl",el,l typically ranges from about one day to a
1 5 lifetime.
ExamPles
The following non-li,nilir,i~ e~amples further describe and
demGnsl,dle prefer,ed e",bodi",enls within the scope of this invention.
The examples are given solely for illustration and are not to be
construed as limitations of this invention as many variations are
possible withou~ clel~a, ling from the spirit and scope of this invention.
The co",posilions of this invention can be made using methods
which are c~l"",only used to produce oral care pro~ ct~
EXAMPLES l-VI
The ~ollowing are examples of cJenlirl ice compositions of this invention
and are made using conventional processes. The numbers listed are
weight peroenlages of the c~r~"~osilions. During manufacture, the pH
is maintained at a minimum of ~H 7.5.
~,~.ed ES IEL II E~ E~ EL V E~ VI
~ lV
Sonitol 31.6S 31.65 1.65 3 .6S 31.65 ~ 1.65
PEC-6 3 . ; 3
:~itr c Acid 1.4" 0.088 1 ~.91 0.433 1.0S ~ ~.44
~d um Citrate 3.6~ 0.144 0.8S6 : .28
nc Nitrate Z.g-
Z nc Oxide 0.3?4 0.407 0.407 0.407 0.407
Tc -r 7.12 7.S8 S.78
r h r ~ h~ )uS)
Sodium Acid E~r~ 5~1 0.6Z 0.497
21~1815
~VO 94/14406 ^ PCT/US93/11786
~, ~1;.. ~-ul)h r~ 6.61 4~6 3~39
od um Fluorid~ 0."4 0.' 4 0. ~4 0 ~'4 0 "4 0 ~4
'oc wn Saccharn ~ 60.~6 0.~6 0.~6 0.~6 0.~6
Titanium Dioxice ~ .' f~ O.' O.' O.'
Silica 2" 2- 2~' 22 22 2 '
Glycerin '~ ~ 2.' 1S 2.2 9 2. 5
~ -' . S O.S 0.~
'' ~arthanGum 0.~ 0.~ 0. S 0.4 O.~
.1,~ ~u~,lh~Ilnlnt;ç o
yl Sl~ te 4 ~ 4 4 4 4
(27.9% Aqueous solution~
I;lavor 1.1 1.1 1.1 1.1 1.1 1.1
KOH/HCI/watcr q.s. q.s. q.s. q.s. q.s. q.s.
to to to to to to
pH pH pH pH pH ~H
7.S 8.~i 8.0 8.0 8.0 ~'.0
TOTAL 100 100 100 100 100 00
EXAMPLE Vll
Following dental prophylaxis, a ~,er~on brushes his teeth for
sixty seconcl~ twice daily using 1 9 of a fluoride, non-a"licalculus
tootl "~asle. After eight weeks he receives dental prophylaxis
pe~ru~ ed by his dentist. For the following eight weeks the person
brushes his teeth for sixty seco"~ls twice daily with 1 9 of the
co",position of Example 1. After eight weeks, the person has
sigr,iricar,lly less ~Iculus on his teeth than he did after the first eight
weeks.
EXAMPLE Vlll
Following dental prophylaxis, a ~er~o" brushes his teeth for
sixty seconds twice daily using 1 9 of a fluoride, non-anticalculus
tootl ,~,asle. After one week he receives dental prophylaxis pe, rur---ed
by his dentist. For the following week the person brushes his teeth for
sixty seccl-ds twice daily with 1 9 of the composition of Example IV.
After one week, the person has signir,~anlly less plaque on his teeth
than he did after the first week.
EXAMPLE IX
Following dental prophylaxis, a person brushes his teeth for
sixty seconds twice daily using 1.5 9 of a fluoride, non-anticalculus
tootl .pasle. After nine weeks he receives dental prophylaxis
performed by his dentist. For the following nine weeks the person
brushes his teeth for sixty seconds twice daily with 1.5 9 of the
composition of Example tll. After nine weeks, the person has
WO 94/14406 PCT/US93/117~_
16
2~
significantly less calculus on his teeth than he did after the first nine
weeks.
EXAMPLES X-XIV
The following are ex~ ples of mouthwash and dental rinse
cc, l l,~ositions of this invention and ar~ made usir~g conventinal
proc~ss~s The amounts listed arc weight per~"tages of the
compositions. During manufacture, the pH of the following
col..~osilions is lla;ntaiaed at a mininum of pH '.5.
~omponent Ex.X Ex. ~a Ex.XII Ex.XIII Ex. XIV
Glycerin 10 10 10 10 10
Ethanol 10 10 10 10 10
SodiumCitratc 0.41 3.84 1.28
Citric Acid 11.4 3.8
Zinc Cl .lorid~ 1.36
Zinc Oxide 0.081 1.63 0.81 0.41
T~t~l.ot~csi;~n 1.1 5.51 1.1
Py. v~l ,ospl late
(60% Sol'n)
T~r~so~ n 2.66 0.27
Py- 0~ 05l.ll'ldt~
Sodium 7.36 0.37
Tripoly,~l IGspl ,dta
Sodium Add 6.66 0.22
P~ 5pl ,ata
SodiumLau~yl 0.4 0.4 0.4 0.4 0.4
Sulfate
Sodium Sa~l a- i~l 0.03 0.03 0.03 0.03 0 03
Flavor 0.22 o.æ 0.22 0.22 0.22
NaOH/HCL & q.s. q.s. q.s. q.s. q.s.
Water 100% 100% 100% 100% 100%
at pH at pH at pH at pH at pH
7.5 8.5 8.5 7.5 8.0
2 1 ~
~0 94/14406 PCT/US93/11786
17
EXAMPLE XV
Following dental prophylaxis a person rinses her mouth for
twenty seconds twice daily for a period of eight weeks using 10 ml of a
non-antic~lc~lus mouth rinse. After eight weeks the person received
dental prophylaxis and rinses for twenty seconds twice daily with 10 ml
of the cGr"posilio" of Example Xl. After eight weeks the person has
significantly less C?ICI "- IS on her teeth than she did after the first eight
weeks using the non-anticalculus mouth rinse.
EXAMPLE XVI
Following dental prophylaxis a persol) rinses her mouth for
thirty seco"ds twice daily for a period of one week using 12 ml of a
non-antiplaque mouth rinse. During this week the person does not
brush her teeth. At the end of one week the per~on received dental
prophylaxis and rinses for thirty seco"ds twice daily with 12 ml of the
1~ cG"~.osilion of Example Xlll. During this week the pe,~on does not
brush her teeth. At the end of one week the person has significantly
less plaque on her teeth than she did after the first week using the
non-antiplaque mouth rinse.
EXAMPLE XVII
FollPwing dental prophylaxis a person rinses her mouth for
forty-five seconds twice daily for a period of nine weeks using 15 ml of
a non-anticalculus mouth rinse. After nine weeks the person received
dental prophylaxis and rinses for forty-five seconds twice daily with 15
ml of the co"~posilion of Example XIV. After nine weeks the person
has significantly less r-~'cul! ~s on her teeth than she did after the first
nine weeks using the non-antir~lc~ s toothpaste.
While particular e"l~od;",ents of this invention have been
des~ibecl it will be obvious to those skilled in the art that various
changes and ",odiric~lions to these exc.,,,ples can be made without
depa,ling from the spirit and scope of the invention. It is intended to
cover in the appended claims all such modifications that are within
the scope of this invention.
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