Note: Descriptions are shown in the official language in which they were submitted.
WO 95/17158 2 1 7 9 3 1 ~ PCTIUS94/14662
Tooth Whi~ . ;..~ r~ dliOns
Scope of the I.~
This invention relates to a system for whitcning natural teeth and dental
The whitening is achieved through the use of an alkali metsl
S hi~ at about between 5 to 25 percent by weight in a dentslly acceptable
carrier when used alone. The ~ol~ can be combined with a compound
which provided active oxygen and/or an enzymatic hydrolytic agent; the
, may be present in 1 to 25 percent by weight when combined with
one or both of these agents. Any orslly accephble I or one suitable for
10 dental prostheses, can be utilized in this invention.
Area of the I-, . . ' -
Several factors contribute to e=l ." but the three main factors
are believed to be: i) formation of plsque and tartsr mat~ices on the tooth surface
which then entraps stains, ii) ingestion of certain drugs during tooth formadon, and
15 iii) t~; ..1. .., ;..-- due to ~al cavity i following which blood break-
down products seep into the 1i7~ area of the teeth during ensmel formation.
This invention is primarily cor;cerned with the first factor or cause of tooth
that is the nahlral stain which ' on teeth.
Over-the-counter teeth whitening 1 1 p ~ - have been developed to
20 address the cosmetic preference of rnany to restore luster to tooth enamd discolored
by surface entrapped materials; the term lighterling may also be used in .
with the hd~. ~ and ssle of these products. While all dentifrices and
contain some cleaning and polishing agents some enamel deposits
may become intractable to be fully removed by these agenLs under normal use
25 conditions. Also these I , may not be formulated with the amount or type
of agent required to fully remove the amount of stairls and ~; - . .1. .., - ~ which build
up due to e~cessive exposure to the staining agenL For example, smokers often
develop discolored enamd because thc tars and particulate in exhaled cigarette
smoke collect on the teeth. And a number of ' can stain or discolor tooth
30 enamel, tea being one cxsmple of a bcverage where the tannins in the tea deposit on
thc tooth enamel. Some medicinal agcnts may cause staining or ~ , via
t, though this is not a usual common cause of this type of staining.
Threc ~!'`^h~C to enamel whitening are currently in general use. They are
based on using abrasives, employ oxidi7ing agents or utili_e a hydrolytic entity to
35 brcak down the staining matcrial, e.g. en_yme-based product .
I
WO 95/17158 ~ PCI~/US94/14662
One approach is basically a physical abrading of the stain to effect removal.
Harsher abrasives, which might also be called polishing agents, than what are
nolmally used in tooth paste ~ are employed in this approach. Most if
not all of these ~ , are i hl . gels or powder dentifrices as they
5 require close contact with the teeth. And brushing or similar scrubbing or polishing
action is required as a A ' to successful stain removal. Examples of such
products are Smokers Topol made by Topol-Dep C'n~-inn and maliceted to
smolcers and tea drin~ers as a means for removing slains caused by smoking and
drinlc tea or similar beverages.
Oxidizing agent represent the most widely distributed and utilized agent in
oral ~ , marlceted as enamel whiteners in the U.S. All of these products
are pastes or gels. Urea peroxide, hydrogen peroxide or calcium peroxide are most
often found in these p~ducts. Currendy there are more dhan thirty such products
marlceted over the counter in dhe U.S. The oxidizing agents apparendy worl~s viathe release of a radical which brealcs down dhe ~ / complex to a product
which can be flushed away or removed by an abrasive. These treatments require
quite a bit of time to whieve good results; ~ ' ~ to dght days, or 2-3
mondhs depending on the peroxide source and its
Recendy catalytic systerns have come baclc into favor and have been
pac~aged and m~rl~et du~ugh retail oudets in paralld widh odher oral care products.
Proteolytic enzymes are the catalyst of choice, I ' ~, papain. A second active
such as a citric acid salt has been used by at least one ~ These products
fire presented in a paste or gel. They claim to whiten teedh by removing the plaque
which has entrapped dhe stain.
This invention provides a unique alternative. It utilizes a allcali metal
h;~ ' , ' salt, optionaDy widh a peroxide arldlor a hydrolytic agent, to effect
stain removal and whiten tooth enamel.
S ~ of the I~
This invention comprises a . , for reducing v~ U~;..6 sutface
30 deposited stains from natural teeth and dental prostheses comprising a dentally
acceptable l ~ ~ about S to 25% by weight of a water soluble
al~ali metal hi~.yl ' . '
In a second aspect dlis invention relates to a ~ for reducing or
removing surface deposited stains from natural teeth and dental prostheses
35 . , ' ~adentallyacceptablel ~ ~;- comprisingaboutI to25%byweight
of a water soluWe allcali metal hi~ul~l an effecive amount of a source of
WO g5/17158 21 7 g 31 7 PCT/US94/14662
active oxygen, and~or an effective amount of an enzymatic hydrolytic agent.
Tn addition this invention relates to a means ru. I~dU~ or removing
surface deposited stains from natural teeth and dental prostheses which method
comprises contacting teeth or dental prostheses which have surface stsins with a5 dentally acceptable ~ , lg at least about 5 to 15% by weight of a
water soluble al~ali metal lli~l,~ ' . '
If yet another . 1 t, this invention relates to a method for reducing or
removing surface deposited stains from teeth and dental prostheses which method
comprises contacting said teeth or dental prostheses which have surface stains with a
10 dentally acceptable . - . ~ at least about I to 25* by weight of a
water soluble aLIcali metal ~ ' , ' and an effective amount of a source of
active oxygen, and/or an effective arnount of an enzymadc hydrolydc agent.
Detailed r - of the I..~ '
The fo~us of this invendon is on that of removing stains which are adhered
15 to, or entrapped in materials on, the surface of teeth r)r dental prostheses. Nadve
teeth and dental prostheses, e.g., false teeth, can be treated with this invendon. This
invendon can also be used to prevent build-up of surface attached stains. In essence
this is a matter of removing ~l;~I.call~ srnall amounts of newly deposited
malerials be they stains themselves or matrices which can trap colared materials.
20 Deposit prevendon per se may not be involved here but that has not been ruled out.
That is, treadng teeth with these l , ' may prevent the attachment of stains
or tbe ~ , of stains in some fashion. Whether one or both of these
' is going on is not so important as the fact thu regular use of these
can achieve a state where the user does not perceive thu her or his
25 teeth are stained. And regular use can prevent a A~ of that condidon.
The le~m stain or staining is used ' , ' ' with ~' ' ~ and
generally means that the surface of the enamel (or prostheses) has tal~en on some
unwanted or unnatural coloradon distinct from the color of the underlying enamel.
These words are intended to be given the same meaning as here as would be
accorded to them in their . ~ usage in the oral and dental care arts.
These r ~ ' and the methods disclosed herein are directed toward
human use though these l... ~ can be used in other species as well, for
example in pet care products.
The primary acdve , - of this invention comprises a water soluble
35 aLcali metal L,i~l~, ' . ' - The sodium form of this salt is preferred, though the
potassium or mixed sodium and potassium salts could be used as a preferred
WO 95/171~8 2sl 7~ 7 ~ PCT/US94/1466Z
as well. All physical forms can be used, e.g. a hydrate or the
dehydrated form.
The amount of hi~,~,lJ, ' . ' salt will be between about 5 and 15% by
weight of the, , when it is used alone in a solid r , , that is ndther
5 of the other two actives are present in the defined ranges. A solid I
includes a paste, gd, powder and the lilce. A preferred amount of said salt, again
when used alone in a solid, , is about 10% by ~. . ,.' .~ _'
As regards liquid I , e.g., h~ ' or rinses, the
h;~ can be used in amounts ranging between 0.1 to 15% by0 ...~' J~ ' Amorepreferredrangeis1toabout10%by. ~' h~' ina
h~ ' orrinse.
When a peroxy compound or a hydrolytic enzyme is added in with the
h;r,l~ i in a solid I , . or a liquid r , such as a I h~ . h,
the phosphate may be used in amounts ranging between I and 25% by
5 ~ h~ in solid l r - and in a range of about QI to 15%
in liquid ~ , A preferred amount of the phosphate in the
solid I , is between 5 and 10% (w/w), most preferably
about 10%.
A sou~ce of wtive oxygen means material containing an O-O bond which
20 can brealc down to give an active oxygen specie(s). The peroxtdes a~d
h~ ' r ' are preferred for use in this invention. Examples of prefer~ed
peroxides are inorganic peroxides such as hydrogen pe~xide, the alicali metal
such as sodium, potassium and calcium r ' , sodium,
calcium, strontium, barium, zinc or I _ peroxide, and the perborates. Also
25 inorganic r ' which contain hydrogen peroxide of .,.~ " . such as 2
Na2CO3-3H2O2 and Na4P2O7.nH2O2 can be used. In addition several organic
peroxides can be used herein. For exarnple peroxy - r ' such as peracetic
acid, benzoyl peroxide, _ , , ' ' m-l ' ' ' add and
cumyl h~ can be used in this invention. This is a , ~ Iist and
30 is not intended to limit in any way or fashion the practice of this invention vis-à-vis
what comp~ises an active oxygen compound.
The; of these active oxygen r (AOCs), that is the
effective amount, will valy between about 0.01% and 20% in the final folm of theas measured just before it is contacted with the teeth orprosthesis.
35 These I ~ may be calculated on the basis of weight where the AOC is a
solid and the dentifrice is a solid. If the AOC is a liquid and the dentifrice a solid,
then the l _ will be baæd on a ~ inn Likewiæ where
~ WO9SI17158 217~;3~7 PCI'IUS94/14662
the AOC is a solid and is being added to a liquid, i.e., a ' ~aaL~ the ~
will be based on a wdght and volume ' ' If the AOC and the final product
are both liquids, then the percentage will be based on a ~ J~. ' ll '
For .. ' herein, recitation of a percentage for an AOC should be read to include all four of these instances; i~ will be left to the I to select the
calculation based on what I . she is '
r~nnes which brealc down proteins, lipids or sugars can be added to these
Herein the phrase "enzymatic hydrolytic agent" is used as a short-
handed rneans for refernng to these types of enzyrnes. These enzymes are well
10 Icnown in the art of e~J,.,~ . They are usually referred to as proteases, lipases
and atnylases .~ . Numerous papers and reviews have been written on the
activity of these enzytnes and their physical and biological L~ - r ;~ See forexample "AdYances m L~ and Related Subjects, John Wiley 8~ Sons, Inc.
all editions and Methods im r,,,~ ~ll~y, Acadernic Press, New Yorl~, all editions.
The hydrolylic agent rnay comprise a single enz-yme or a mixture of a given
type of enzyrne or still further a mixture of two or three types of enzymes. It is
preferred to use a protease in singular c ' with the other active(s). And it
is most prefe~red to use just one protease. But an amylase or a lipase could be
combined with the protease, or both could be added in with the protease, to provide
20 a means for e~ degrading proteins, fats and sugars.
All hydrolytic agents may be combined with the ~ ' , ' with no
adverse affect on the activity of the agents or on the activity of the phosphate per se
Certain ' ' ~ such as pH, may affect the activity of a given
enzyme. It is well l~nown that enzyme activity is influenced by pH. For example
'~5 sotne enzyrnes are more active at a pH below 7, some are most active at a neutral
pH and others are most active at a pH higher than 7. r. with a particular
enzyme must necessarily take into ' the pH u which the target enzyme
is most active. And in addition, the pH of the product du;ing use may have an
influence on selecting an enzyme. Certain of the al~ali metal h;~lrl ' , '
30 which can be used im this invention are most stable at an all~aline pH. So it is
preferred to use an enzyme which retains its activity when exposed to ali~line pH,
or to protect the enzyme in some fashion such as ~ . ' , it or presening it in
a separate container for ' with the phosphate at time of use.
Certain enzymes which require a heavy metal ion to function may not be
35 l ' 1~ useful in this invention given the presence of the hi~ ' . ' But
it rnay be possible to . . ' the ~ ; with that ion, thereby providing it
in adequate to maintain the activity of the enzyme while not
WO 95/171~8 ; ~ 7 PCT/US94/14662
adversely impacdng the acdon of the ~ VI~I ' , ' on stains.
In another e L - t, certain enzymes may be combined with the acdve
oxygcn component to provide a dentifrice with three acdves. Oxidizing agents such
as peroxides degrade enzyme, inacdvate them, rather rapidly. But it has bcen found
5 that the rate of ~ ;- for certain enzymes is not so rapid that they lose all
hydt~lydc crf~~ , c.g. in less than a minute. And it has bcen
found thu this residual wtivity is ~ high to pr~vide far protein and other
stain hydrolysis over five to ten minutes. Since the methods of this invention will
normally be cartied out over one to ten minutes, the invention also: , ' a
10 tripardte I r '' combining the ~ l ' , ' . a source of active oxygen and
a hydrolydc agent which retains useful wdvity within this dme frarne. These
reladvely stable enzymes are termed peroxide-acdve enzytnes herein.
A peroxide-acdve enzyme is any enzyme having ' ' acdvity at 3%
(wlv) hydrogerl pcroxide in aqueous soludon at standard; , and pressure
15 ' ' ' by such ~ ; assays as the Azocoll method, Tomarelli, R
M.,et al., J. Lab. Clin. Med., 34, 428 (1949), or the dimethyl casein method
proteolydc activity as descriLled by Yaun Lin, et aL, J P:-l r
244: (4) 789-793, (190).
These stable enzymes rnay be derived from any piant or animal source,
20 including rnicrobial atld " sources. They may be neutral, acidic or all~alineenzymes. A proteolytic enzyme will have in patt or in total the capacity to
hydrolyze pepdde atnide bonds. Such enzymes may also have some inherent
liplydc aDdlor amylolytic acdviq associated with the proteolytic acdvity.
Preferrcd proteolydc enzymes are those which are '1~ free of sulfhydryl
25 groups or disulfide bonds, whose presence may react with the acdve oxygen to the
detriment of both the acdvity of the acdve oxygen and which may result in the
undmely ' ~uu.. of the enzyme. r ' " ".ut~ ., those enzymes which
contain a divalent metal ion such as calcium, _ or zinc bound to the
protein, may also be used, with the foregoing caveat that the phosphate may have an
30 affect on the acdviy of such enzymes. A more prefe~red group of ~""u id"-~a~ lP
proteolydc enzymes are the serine pro~ac~c,p ~ those derived from Bacillus
and ~ bacte~ia and ~ . ,'v "' molds. Within this grouping, the more
preferred enzymes are the Bacillus derived all~aline proteases generically called
subdlisin enzymes. Reference is made to Deayl, L, Moser, P. W. and Wildi, B. S.,35 "Proteases of theGenus Bacillus. II all~aline Proteases." r. ' ~ and
P --nv . Vol.XlI, pp 213-249 tl970) and Keay, L. and Moser, P. W.,
'~ '' of All~aline Proteases fromBacil~u~ Species" P;(r 1 , l and
WOg5/17158 21 79~1 7 PCrlUSg4114662
Biu~ ' Research Comm., Vûl 34, No. 5, pp 600 604, (1969). The subtilisin
en~ymes at~e bloken down into two sub-cl~tsses, subtilisin A and subtilisin B. In t~te
subttlisin A grouping are enzymes detived from such species ate B. sublilis, B.
I ' ', and B. pumilis. Orga~itsms in thts sub-class produce little or no neutral
5 pt~tease or amylase. The subttlisin B sub-cl~tss is made up of enzymes f~m such
organt;sms as B. subnlis, B. subn~is vat.L~ t ;~ B. ~
nd B. sub~tlis NRRL B3411. These organisms produce neutral proteases and
Itmylases on a level about cu- ~ t~ to thcir allcaltne pt~otease I In
addttion other preferred enzymes at e, for exitmple, pattcreatin, ttgpsitl, . " ~- .
10 Icerattnase, ~hu~' ~ , , ' elast~tse, and aspergillo-peptltdase A atqd B,
pt~tase E (from S. griseus) altd dispase ~ n ~ po~xa).
Prefd proteases are papatn, bromelin, and the var'tous subtilistns
mentioned above.
The ' - ~ separation attd I of enzymes is att old ~
15 Many ' - ~ - atld isolation techniques exist in the general scientific literature
for t}te isolation of enzymes, includtng those enzymes having proteolytic and mixed
'~ lul~ ~ or l..utwl~ ~ activi~y. The enzymes: , '
by this invelttion catt be treadily obtained by known techniques from plant, animal or
tDicrobial sources. ~It}t the advent or ' DNA ~1 ' . . it is
20 anticipated that new soutces and types of enzymes will become available. These
newly tntnted enzymes should be considered to fall within the scope of this
inventton so long as they meet the criteria for stability and activity set forth herein.
An effective amount of cnzyme is to be used in t}te prac~ice of thts invention.
The amount of enzyme required to malce an effective dentifrtce will depend on
25 several factoR, including the inherent activity of the enzyme, pH, salt - -
attd if combined wit~t a peroxide, its , ' ' y to attack by peroxides. As a
basic yatdsticlc, the wor~tng ' ' - should cont~tin sufficieM enzyme to
provide between about 0.001 to 5 Anson units of activity, preferably ~.~
û.Ol and I Anson units, per single tteatment. Higher or lower atnounts may be used.
30 Enzyme t lower than these stated here p~bably will serve to assist in
reving surf~tce materials which statn, I - ' '~, if used to clean prostheses
wltich can be removed from t~te mouth and soaked for some extended period such ~ts
overnight. ~n ~ ' or ~. ,,' ~ 'v. ' terlus, since enzyme ~
seldom pure, it is expected that the enzyme source will be used in amounts between
35 aboutQ003tol5%oftheftnalworkingl -~ ~'; Theptreciseamountwillvary
with t~te pur'tty of t~te enzyme and will need to be finally ~' ' on a lot-by-lot
basis.
-7-
WO 95/17158 21~ ~ 3 ~ 7 `1 PCTIUS94/14662
S ~
These ~.~i, will be presented in a fortn which is safe for use in the
oral caviy and which will not have a de~eterious effect if ~ , swallowed.
The oral care asrt has developed a substasqtial body of r, ,", ,1 l ;. .. ypes asld has
identified and tested a large listing of ingreoients which can be used in these
5 l , in a safe and efficacious manner. Confecting or ' ~ these
and there safe packaging and storage is also well ;~ ' in these
arts.
For achieving optimum whitening results the r ~ " as used should
have a pH of between about 7.0 to 9Ø Optimum cleaning results are achieved with
l0 a pH of about 8 with reference to how the ~ is used for b~ushing teeth in
the mouth. For example a toothpaste I , will usually be diluted in the
mouth by about I plus 2 or I plus 3 volumes of . /~ while brushing. Thus a
paste or gel, for example, optimrzed for whitening will be formulated to achievc ~
pH between about 7 and 9 when it is bcing actuarsy used to brush or tteat teeth. An
lS acid or base may be used to adjust the pH of the l , the choice is within the
s~ll of the art concerned with oral I , Tlqe optimum pH for stability
pulposes in a particular, , prior to use, may vary from this range and may
have a different optimum pH, dcpendin~ on cxcipients and additives.
While the ~ , can be presented in any form, it is , ' ' that
20 certain ~ ' as compared witlq ingredient mixes, will provide better and
faster results, and will be morc user friendly. By example, one can provide
in the form of an o~l rinse, a gum, a dentifrice such as a paste, gd or
powder, or one can . ~ the active into a toothpick or dental floss. Appli~ués
and uth pieces can also be used, that is ~ , which are appred to the teeth
25 and left in place for scveral hours with or without a covering membrane to secure
them in place. While the method can be practiced in a ~l~ ' ' setting, it is
intended primarily in a self-treatment rcgimen.
In addition, a course of care may include using two or more of these
Say for example a ' .. . ' can be used in ~; with a
30 tooth paste where both contained t~qe two _ ' Such a regimen can
contribute to optimizing the effect of this oral care regimen, i ' 'S, in those
consumers who normally use both products. Flossing in ; with using
tooth paste can also comprise an effective treatment reginqen.
It is . ' ' that the l , used in this invention would be
35 formulated in a way which permitted them to be used in the fashion and for the time
the consumer would normally associate with the use of that I For
e_~le~ if the acives were pre_ted as ~ mouth wash, ~ woul~ be form~lated ~o
wo 95117158 2~ 7 3 j PCTIUS94114662
that the directions for use would be consonant with the normal and accepted practice
of using mouth washes. The same applies for ~i~ntifrir~, toothpicks, or dental floss
and chcwing or bubble gums. No special tirne , ate , ' ' for
the practice of this invention. If an appliqué or mouth pie~e approach is used, that
5 n~ entails l~eeping the rnaterials on the teeth for up lo several hours, or
re. That is the only context where extended treatment is the norm.
Preferably the active will be formulated into a tooth paste, liquid paste or
gel. So for example 109~ sodium L~IJI ' . ' (STP) will be mixed with other
orally acceptable ingredients to make a paste or gel which will be packaged in a10 usual fashion. The consurner will then put some of this gd or paste on a tooth brush
and brush her tccth for a discrcte time, just as if she was using any other t~otn paste.
Most dentists and rcsearchcrs ~ brushing ones teeth for at least three
minutcs per btushing to achieve maximum results, though; . ' with this
standard is not univcrsal. A similar standard is ' for the instant pastes
15 and gds, though it is cxpccted that non~ . ' will still provide the desired
rcsults with rcgular use, i.e. daily use.
Any orally acccptablc ca~ricr or calricrs can be used, with the limitation that
' ~ ' mctal ions should be climinated or 1, othcrwise these ions will
form a complex with the active and could I '~ rendcr it par~ally or wholly
20 ineffective. In addition, oxidizing agents should not be used lest they rcact with the
educing agcnt . Othcrwise, the two activcs can be formulated with any compatiblecxcipicnts which are also acccptable for use in the oral cavity.
oral F~ ~r
D ~
r~ for i ~i liquid pastes, gds and
tL ~ . ' which can be used in this inventions will have the usual calriers,
binders, s ' .1 . coloring agents, pigments, antiplaque agents, anti-
bacterial agents, ' " ~-type agents, abrasives, anticaries agents, flavorings,
sweeteners, bulking agents and the like which can bc used in preparing pastes and
30 powders. Gels and pastes contain water or can be anhydrous.
Dental abrasives are useful with these actives as a means for providing
physical rcmoval of matcrials which have been acted on by the phosphate. Classicexamples of dental abrasives are calcium ~IJ . ' . ' , silica abrasives, alumina,
insoluble , ' , patticulate ~ ,.i~l rcsins, and sodium
35 ' ' The patent and scientific literature is replete with cxamples of such
abrasives. One such example is U.S. patent 4,822,599 which list a setics of
wo g~/17158 2 1 7 9 3 1 7 ~ PCT/US94/14662 ~
dentifrice abrasives and references .~ .. . . 1 sources and literature references on
their 1 . Most if not all of dental abrasives are available from
sources.
A selected abrasive should be compatible with the phosphate active, as well
5 as any t1dditives which may bc actives in their own right, such as fluo~ide ions and
' agents. But as with any other paste, gel or powder, the selection of an
abrasive can be influenced by the , of combining a particular ab}asive
with another additive. For exdmple if fluoride ions and calcium ~.r , ' , ' ions~re to be included in these r ~ '- the p.~ , ' , ' should be converted from
10 its ~phase to its ~phase by heating the ~phdse to 700-900 C as per tbe teachings
of U.S.patent3,112,247. Alsocertainquaternary I '~ ' '
agents may not be compatible with some silica abtasives. Silica is a preferred
abr~sive for this worl~.
Abrdsive can cover a very broad range. r , are
15 described with abrasive rarlging in from 5 to 80% by weight
depending on the abrasive. A secondary ~ range is that of 10 to 50%
depending on the abrasive selected. Herein the preferred abrasive, silica, is
employed in amounts between 10 and 20% by weight.
A source of fluoride ion may be included in these l r~ ''1 ---` Fluoride ion
20 sources are nutnerous. For exdmple see U.S. patent 3,535,421 which lists numerous
salts which can be used in the dental arts. While any one of these sources could be
used sodium fluoride, stannous fluoride and sodium '' I - . ' have
emerged as the preferred ion sources in most dentifrices.
Fluotide ions are routindy added into dentiftices in an amount sufficierlt to
25 provide up to 3500 ppm, preferably 1100 ppm of the fluoride ion. Where a
is formulated such that the fluoride ion is confined to one ~ , of
the I , . but is tr~ixed with the other . , at the time of use, the
fluolide ion source should be adjusted upward in an amount sufficient to provide a
of up to about 3500 ppm, but preferably 1100 ppm, in the prQduct as
30 used.
As for other - , flavorings, coloring agents, ..
. thickening agents, binders and surfactants are most commonly used in
dentiftices.
Taste is provided by adding a small amount of a flavoring agent; this
35 component also leaves a perception of mouth freshness. Numerous r~inty flavored
agents are available for use in dentifrices and it is well known in the art how to go
about selecting a flavoting and testing its consumer ~r~-~rr~hil;ty. Flavoring agents
-10-
~ wo 95/171~8 21 7 ~ 31 ~ ~ ` . PCT/US94/14662
are routindy used at levds of between about 0.1 to 5% by weight.
Dyes, la~es and titanium dioxide are routinely used in the dcntifrice arts for
imparting color, in the case of titanium dioxide a white paste or powder is obtained.
These materials are widely available, have been oft used in such r ~ ' and are well l~nown to the dental artisan. Coloring agents are usually present in
ranging between 01. and 5%.
Sweeteners are routine~y added to increase consumer ar~tq~l;ty. So
called ar~ficial sweeteners are used today to avoid the cariogentc poterltial of most
sugars and other .. ~ agents. Examples of non-cariogentc sweeteners now in
10 routine use are saccharin, aspartame. D-~ .' ' ' c~. '
xylitol and r '' Sweeteners comprise about 0.1 to 5% of the r ~ .
TT are added to gels and pastes to prevent their drying out on
exposure to air, and they impart a "moist" feel to the mouth when brushing. Somehumectant, e.g. sorbitol, are perceived as sweet. Examples of - - r useful as15 l in dentifrices are the polyhydric alcohols such as glycerin, sorbitoL and
hyl~ , glycols. Sorbitol (usually 70% ~ ) and glycerin are
preferred. In pastes and gels one or two I are usually used in amounts
between about 20 and 40%.
Binders ~nd thickening agents can be added to assure physical integrity in
20 pasres, gds and liquid pastes. E~amples of these are gums such as xanthan and acacia gum, r---gT . the celluloses such as carboxy methyl cellulose,
~I.~v~ . " ~I polymers such as the Pluronics polymers, PVP materials, and certain
polymers r _ yJ~ 1 by the calbu~ 1 polymers (Gantrez and the lilce). These
latter po~ymers, and perhaps some of the others, have an additional benefit in that
25 their adhesive nature which makes them useful as binders also can serve the
additional purpose of adhering to the teeth surface and thereby binding the active
to the teeth for a longer period. Gantrez is a example of a ~vl.~.~'
lbVA.~ ' material which serves such a dual purpose.
Binders are usually added in amounts n~nging between Q1 and 55 by
30 weight.
S r ' normally are added to dentifrices to assist with removing debris.
All classes of r ', anionics, cationics, ~ h ;~ ~ nonionics and zwitterion-
based r . can be used in these ~ These; . ' . and those
which are most useful in the dental arts, are well ~ 1 in the lih rature.5 Reference is made to U.S. patent 4,~22,59g for a detailed listing of useful
are available through any number of
or can be make by well ~ ' processes.
WO 95/17158 21 i 9 317 PCT/US94114662
S r are norrnaily used in amounts between about 0.5 and 5% in
pastes and gels but may be used at higher in some dental i~owders.
Sulfactants can also be used as geiiing agents.
Breath freshening agents (eg. sodium ~- ~ ) could be included, dther
S with the phosphate ~ , or as an adjunct a described in the preceding
paragraph, i.e. a two chamber delivery device.
App]iqués can provide an effective means for removing stains as per ~his
invention. These can be prepared in the form of a doughy or taclcy rnaterial which
can be readily molded to conform to the teeth. It can then be manually
10 on tne teeth as is or placed in a plastic retainer, inserted into the mouth and bitten
into, and left in place of a some time, for example 15 to 30 rninutes. When the
appliqué is removed the debris causing the stain wili be remove~ Ille appliqué is
tnen discardeL
The active(s) can be formuiated as a ' ' or mouth rinse as weil. A
15 mouth wash or rinse wiil contain up to 95% water, up to 30 % aicohol, flavor,polyhydric alcohols, anti-caries agents, piaque removing agents, .. . dyes
and laices, and a ~ in some instances, and sufficient water to maice
volume. The active could aiso be , ' into currentiy existing r .
such as Cepacol (Laiceside r ), Plax, (Pfizer), Listerine (Warner-
Lambert), Scope ~Procter ~ Gamble), and the iiice.
C - of the active phosphate in these products wouid be in the
range of about 1 to 15% (~ ' ), preferably 1 to 5%. An AOC could be
mixed with the phosphate, or presented in a separate dispenser for combirling with
the 1 , containing I , at time of use. Liicewise, an enzyme couid be
mixed with the phospilate or pacicage separately for mixing with the phosphate at
time of use. If ali three ingrcdients are to be presented in a ~ ~h or rinse, it is
, ' ' that the enzyme will be i~acicaged separately. Any one of tnese
ingredients tDaybe pacicaged as a powder for mixing and then diiuted up in a iiquid
containing the otner _ ~(c) just before use.
A soaking and cleatling solution for dentai pieces can aiso be prepared with
these two active c ' It is . , ' ' that such l. . l.r Ah. . c wouid
contain water, a surfactant, an e~Fc. ~, ~ agent, and other optional
Dental prostheses wouid be removed and placed in a solution containing the
t~ ' , sait and soalced for several hours, then either brushed with a
' ' denDfrice or simply rinsed and reinserted into the mouth. The
of phosphate active here vr21 b~ about 1-20%.
WO 95/17158 ~17 9 317 PCTNS94/14662
The following exarnples are provided by way of illustration and are not
intended to lirnit the scope of the invendon.
ExamDle I
r~ nfT~th w~ ~T~nt~ te
S A toot_paste ,.~ , of what may be prepared for the practice of this
invention was prepared as per the ingredient profile and ~ ~ in Tables I and
II.
0/1 ~% STP)
(~ ~ti~n nV/W%)
Water, DI . 28.402 23.402
SQrbitol, 70% 26.410 26.410
Abrasive siL;ca 14.00 14.00
Sodiurn T, ~l ' , ' (STP) 10.00 15.00
Glycerin 10.000 lQ000
Tl ' silica 4.00 4.00
I~l~,~,l.,.. ~ glycol 4~0, NF 3.00 3.00
Sodium Lauryl Sulfate 1.150 1.150
rltanium Dioxide 0.995 0.995
Sodiu~n Saccar_in 0.20 0.20
Xant_an Gurn 0.800 Q800
rlavor 0.800 Q800
Sodium Fluoride 0.243 0.243
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WO 95117158 PCTIUS94/14662
~17g31~ ~
~i
(10% STP ~ ~n PernYi~l
Ingredient Pa~t A Part B
Sobitol Solution (USP 70%) 23.0901 ---
Glycerin 99.5~o, USP lQ000 88.00
PEG 8 3.00 --
Silicon Dioxide, (Zeofree 153) 4.500
Silicon Dioxide, (Zeodent 113) 10.000 ---
Titanium DioYide 1.447 ---
Sodium Lauryl Sulfate NF 1.150 ---
Saccharin, Sodium Powder USP 0.40 ---
Sodium benzoate, NF 0.100 ---
Xantban Gum 0.700 ---
Sodium Tripoly phosphate 20.000 ---
Sodium Hydroxide S0~ solution 0.900 ---
C~lrbopol 974P --- 2.000
Hydrogen PeroYide (359ro) --- 10.000
Flavor (not to eYceed) 1.5
Wa~r QS
Total 100.00 100.00
These two ~ ' will oe pacl~ages in containers which dispense an
5 equal volume of each; the l-to-l ratio of Pa~t A and Pa~t B comprise the product to
be used for brushing the teeth or dental prostheses.
-14-
WO 95/17158
21 7~31 ~ PCT/US94114662
l~kl~lII
(5% STP ~?tinn~lly w]th ~ n
~ ~ ' (WIW%~
Water, DI 28.402 28.302
Sorbitol, 70% 31.410 31.410
Ablasivc silica 14.00 14.00
Sodium T~ r ' , ' (STP) 5.00 5.00
Glycerin 10.000 10.000
Thiclccning silica 4.00 4.00
r~ yl~,~ glycol 400, NF 3.00 3.00
Sodium Lauryl Sulfate 1.150 1.150
Titanium Dioxide 0.995 Q995
Sodium Saccarhin 0.200 Q200
Xanthan Gum 0.800 0.800
Flavor 0.800 Q800
Sodium Fluoride 0.243 Q243
Papain Q100
Total 100.00 100.00
S 1~
Tooth whitelung was measured by the following process:
Whitcning was !~ using a ~ -- to a system normally
employed ~n the dental alts for ~' g the abrasivity of dentifrices.
Bovine jaws wcrc obtained at a local abattou and the tecth werc extracted in
10 t_eir naive state; no prc-clc~ning was done. Teeth were mounted in a cap with dental acrylic so as to fit the format of a ~ and the brushing ; a
detailed ~ rtinn is given below. An initial brushing was done with a slu~ry of
Crest Regular toothpaste and an 0~ B40, medium bristle, ~ ' ' ' Then an
iniial L value was ~' ' on a ~,~1. ,.; -- ~ (Hunter). This was designated as
15 the initial w_iteness value. The wear tester device was ~ ' by Ramè-Ha~,
of Mountain Lal~es, New Jersey. This machine has often been used to test the
abrasivity of dental ~ - p ~ Tooth brushes were mounted and the teeth and
brushes aligned. A 1:3 slurry of paste and water was poured into the trays and
brusbing ~' for a total of six hours. The slurry was replaced hourly. At 3
20 and 6 hours L value ' were made. This was done by first rinsing the
teeth with deionized water, then placing them in a closed container at 100%
-15-
wo 95/17158 ~17 ~ 31~ PCT/US94/14662
humidity for I hours, then tal~ing a reading on the ~ . to obtain a 3 hour and
6 hour L valuc.
Toothpaste slurries were tcsted for their whitening effect. An exemplary
slurry was prepared as follows:
S The placebo was prepared usi~g the ingredjents listcd in Table l, but without
any STP. To a portion of this was added STP, either 5, 10 or 15 percent, and theSTP and the base paste were mixed till all were combined. The pH of this
, that is with the STP, was 3~ 8.5. Where higher pH slurries
wcrC prepaTcd, 3M NaOH was used to adjust the pH and where the pH was to be
lowered, 3M HQ was used. ,AII slu~ics were used " ' '!v- The rcsults
showed that 10% or highcr STP provided superior tooth whitening as compared
with the placebo base and that the best rcsults were obtained at a pH of around 8Ø
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