Note: Descriptions are shown in the official language in which they were submitted.
wo ss/3343~ 2 1 9 2 1 8 0 PCTIUS95107280
DENTURE STABILIZING COIviPOSITIONS
s
BAI'.K('~OUND
Ordinary removable dentures, dentai plates and the like, comprise teeth
mounted in a suitabie plate or base. Aithough dentures generally are skillfully
0 prepared, often they do not fit perfectly. Moreover, no matter how ~a~i~r~ u,y at
first, afier a period of time the fit of the denture becomes loose and imperfect due to
natural shrinkage and changes in the gums, mucous tissues, and the like. Loose and
imperfectly fitted dentures usually are corrected and stabilized by the use of a denture
stabiiizer. Denture stabilizers are used to fiii the interstices between the dentures and
15 the gums or tissues. Prior to placement of the denture in the orai cavity, a denture
stabiiizer is appiied to the denture-plate surface which, for a perfect fit, should
uniformiy contact the gums and mucous tissues. The denture stabiiizer is formulated
not oniy for its adherent properties, but aiso to provide a cushion or gasket between
the denture and the gums or tissues, thereby positioning the denture securely in the
20 orai cavity.
Severai d fi~ that commoniy exist with denture stabiiizing or adhesive
-- are phaæ æparation, the need for more than one application of the
adhesive per day and oozing of the adhesive from under the dental plate. Oozing is
particularly I ' ' ' because of the resuiting unpleasant taste, unpleasant
2s mouthfeel, and loss of adhesive from under the dentai plate.
C~lnci~l~r~hl~ effort has been made over the years to develop improved
denture adhesive , Both synthetic and naturai polymers and gums have
been uæd singiy, in ' , and in ~ ' with various adhesives in an
attempt to lesæn the ' " noted above. However, the need still exists for
30 improved denture stabiiizing ~ - which offer a secure hold, are ~
pleasing to the user, which ooze less than currently available products, and which are
easy to clean from the mouth and/or denture.
It has been discovered, in accordance with the present invention, that a
denture stabiiizer can be formulated having excellent adhesive quality while oozing
35 less and providing pleasing aesthetics to the user. The invention adhesive
r '- may aiso be effectively used as a wound dressing, ulld~ d~el adhesive,
bio-adhesive, and/or as a delivery vehicle for other actives.
woss/3343~ 2 1 92 l 80 PCT/US9~/07280
It is an object of the present invention to provide a denture stabilizing
which effectively holds dentures in place for prolonged periods of time
yet allows for easy removal of the denture on demand. It is also an object of the
invention to provide an improved denture stabilizing cu~ which oozes less
s than currently avaiiable stabilizers and is ' '1~ pleasing to the user. It is a
further ûbject that the hydrophilic nature of the invention ~,u~ o~;Liu.~s will provide
adhesive ~ that are easier to clean from the mouth and/or denture than
currently available products.
These and other objects of the present invention will become readily apparent
0 from the detailed description which follows.
SUMMA~Y OF THE INVENTION
The present invention . ....~ adhesive ..(. ~ , a)
from about I û% to about 8û% of an unmixed partial sait of a lower aiicyl vinyl ether-
maieic acid copolymer consisting essentiaily of the repeated structural unit:
_ ~
I R
--CH2 ~:H--CH--f H--
O=C C--O
~O OH n
wherein R represents a Cl to C4 aiicyl radicai, n is an integer greater than oneq,.~ ~ the number of repeated O~,~,ul~ .. of the structural unit in a molecule
of the copolymer and n is iarge enough to ~,llo a~,L~il;.._ the copolymer as having a
20 specific viscosity larger than 1.2, the specific viscosity being determined in methyl
ethyl ketone at 2~C, and wherein the partiai sait contains a cationic salt function of
from about û.1% to about 6û~/. zinc or strontium cations, ofthe totai initiai carboxyl
groups reacted; and b) from about 20% to about 90% of ~vl~ , glycol having
an average molecuiar weight above about lû0 and eciuai to or below about 60û.
DI~T~TFn DESC~ ON OF THE INVENTION
The adhesive . . of the present invention comprise lower alicyl
vinyl ether-maieic acid copolymers consisting of unmixed zinc or strontium salts, and
~c,l~_Lh,l~...c giycol . ru~ giycol having an average molecular weight of
about 4ûû iS most preferred for use in the present invention ~ l.c~ The
present, . may be formulated âS creams, pastes, powders, liquids,
W095/33434 21 921 80 PCT/US95/0728n
ointments, and lotions. A detailed deseription of essential and optional ~ u~ vuof the present invention is given beiow.
s Lower Aiijyl Vinyl Ether-Maleie Aeid Covolymer Saits
The present adhesive ~ eomprise an unmixed partial salt of a
lower aikyl vinyl ether-maieie acid ("AVE/MA") eopolymer eonsisting essentially of
the repeated structurai unit:
(I)
fR
--CH2--CH--CH--fH--
O=C C=o
I
:~O OH
- n
wherein R represents a Cl to C4 aiicyl radieal, n is an integer greater than one.~.. _ the number of repeated oc~,u.,~ of the struetural unit in a molecule
of the eopolymer and n is large enough to .~ the eopolymer as having a
speeiffc viscosity larger than 1.2, the speciffc viscosity being determined in methyl
ethyl ketone at 25C, and wherein the partiai saits eontain a cationic salt function of
from about û. 1% to about 60% zinc (preferred) or strontium cations, preferably from
about 10% to about 60%, and most preferably from about 2û% to about 50%, of the
totai initiai earboxyl groups reaeted.
The term "unmixed eopolymer saits" as used herein refers to zinc and
strontium partiai saits of lower aiicyl vinyl ether-maieic acid CU~Vlr~ wherein the
zinc or strontium eations are unmixed with any other ester funetions or r..,...~...l;.
eations on the same eopolymer, the remaining earboxyl groups being unreacted.
The term "mixed eopolymer saits" as used herein refers to zine and/or
strontium partiai saits of lower aikyl vinyl ether-maieic acid ~,u~.ul~ wherein the
zinc and strontium are mixeo on the same eopolymer with each other, or with other
ester funetions or ' ' eations selected from the group consisting of caleium,
sodium, _ , potassium, ~ , and mixtures thereo
It is preferred that the present ~ further comprise from about
0.1% to about 75% of one or more mixed partial salts of lower alicyl vinyl ether-
maieic acid copolymers wherein the partiai saits eontain a eationie salt funetion
selected from the group eonsisting of eaieium, sodium, _ , potassium,
wo ss/33434 2 1 9 2 1 8 ~ Pcr/uss~/07280
ammonium, zinc, strontium, and mixtures thereo Most preferred are mixed
copolymer salts containing zinc, calcium, or sodium cations, or mixtures thereof.
Zinc cations may be present at a level of from about 0.1% to about 65%, preferably
from about 10% to about 45%, and most preferably rom about 15% to about 30%,
s of the total initial carboxyl groups reacted. Calcium ions may be present at a level of
from about 10% to about 75%, preferably from about 25% to about 60%, and most
preferably from about 40% to about 60%, of the total initial carboxyl groups reacted.
Sodium cations may be present at a level of from about 1% to about 20%, preferably
from about 1% to about 15%, and most preferably from about 1% to about 10%, of
o the total initial carboxyl groups reacted.
The subject polymeric salts are ad~,r l ~3, u ~l~ prepared by the interaction ofthe AVEIMA copolymer (I) with cationic zinc or strontium ~ having a
functional group typical of reactants of a carboxylic acid, such as, for example, the
hydroxide, acetate, halide, lactate, etc. in an aqueous medium. In a preferred
5 L ' t, mixed AVE/MA copol5~mer salts are prepared by the interaction of the
AVEIMA copolymer (I) with cationic calcium, sodium, lg , potassium,
zinc, strontium (and mixtures thereofl , ' having a functional
group as specifed above for cationic zinc or strontium ~ r ~' In a preferred
mixed AVE/MA copolymer e L- ' t, the oxide of zinc and the hydroxide of
~o calcium are utilized.
Since zinc hydroxide is not uun~ c~ "S, available, its use as a reactant is
readily and more 'lS. e ,' ' ' by employing an aqueous slurry of
particular zinc oxide which, although practically irlsoluble in water, provides
hydration to zinc hydroxide on the particulate surface. Strontium hydroxide, on the
2s otber hand, is available in either crystalline or powder form and is soluble in about 50
parts water. Aqu~ous solutions of strontium oxide, however, which forms the
hydroxide when treated with water (caution: heat evolution), may also be used.
Anions that form toxic, irritating or, ~, by-products should be
avoided, or special ~ liu.... and treatment provided to assure the removal and
30 absence of such by-produhs from the polymeric salt end-produh The particular
compound used should be ' '1~ pure to assure obtaining a ' '~S pure,
'~ off-white polymeric salt end-produh~
The lower alxyl vinyl ether maleic acid ~AVE/MA) co~ are readily
obtained by ~,upul~ a lower alkyl vinyl ether monomer, such as methyl vinyl
35 ether, ethyl vinyl ether, divinyl ether, propyl vinyl ether and isobutyl vinyl ether, with
maleic anhydride to yield the ,u-,~ r '- ~, lower alkyl vinyl ether-maleic anhydride
copolymer which is readily l~ ul~Lablc tû the acid copolymer (I). Both anhydride
.. ....
wo ssl33434 2 1 q ~ 1 8 0 PCT/US9S/07280
and acid forms are also available from commercial suppliers. For example, the GAF
Corporation, Wayne, N.J. provides both the polyrneric free acid form (I) and theLUllL_r " _ anhydride form under its "GANTREZ" trademark as the "GANTREZ
S Series" and "GANTREZ AN Series", l~ .Li~ . In the forrner acid series, the
s GANTREZ S-97 (M. W. TM 5û,00û) is particularly suitable, and, in the latter
anhydride series, the GANTREZ AN-149 (M. W. = 50,000) the GANTREZ AN-169
(M. W = 67,000) and the GANTREZ AN-179 (M. W. = 80,000) cu~ùlyll~ are
particularly suitable. The acid and anhydride forrns of AVE/MA .,u~.ul~....,.~, having
an average molecular weight of from about 50,000 to about 80,000 (as measured byo membrane osmometry in 2-butanone 1-10 grarns/1000 ml solution), are also
by having the previously described specific viscosity parameter of more
than 1.2. When the anhydride copolymer dissolves in water, the anhydride linkage is
cleaved so that the highly polar, polymeric free acid (I) is forrned. Accordingly, the
anhydride form, which is relatively less expensive than the acid form, may be used as
a convenient and cheaper precursor for the acid. Elevated le~ LLIlct may be
a i v - ~ O. .r . ~l y employed to enhance the rate of ', J. i~c to-acid hydrolysis.
In general, the lower alkyl vinyl ether-maleic acid copolymer (I), or its
cullL-r ' _ anhydride, is added to water preheated to about 70-80C. with
vigorous stirring to form a l~.,. h.-~ru~ mixture. If the anhydride precursor isutilized, it is . ~.. \ l ~l that the aqueous mixture be further heated to about 90
C. with stirring to ensure complete hydrolysis of the anhydride to the acid form.
Heating is then ~' l aithough mixing is continued untii the batch turns clear
with a ' decrease in viscosity (about 65-75C.). An aqueous solution of
the cationic zinc or strontium sait forming compound, or, for example, an aqueous
25 dispersion of particulate zinc oxide in the form of a slurry, in an amount sufficient to
provide the desire cationic content desired in the end-product, is separately prepared
at arnbient i , I; and slowly added to the hot polyrneric acid solution with
continuous vigorous mixing so as to prevent locaiized IJlC~.;,Ll;LdL;L.~ of the cationic
polyrneric sait. After addition is complete, mixing is continued to ensure that all the
30 sait forming compound is rcacted with the copolymer.
, an aqueous soiution containing the zinc or strontium source is
preheated to 70-80C. with vigorous stirring to forrn a 1, ~. u~ slurry. The
lower aikyl vinyl ether-maieic acid copolymer (I) or its ~OIl~_r ~' _ anhydride is
then added to the slurry while further heating to 90C. and stirring tû ensure
35 complete hydrolysis.
The reaction batch is then dried such as by shallow drying trays in a
convection oven maintained at about 70C. with hot air circulation to evaporate the
WO 95/3343~1 2 1 9 2 1 8 0 PCT/US95107280
water content and recover the polymeric salt product in dry form. Altematively, the
reaction batch is then transferred to 5 drum dryers maintained at 80-100 PSIG with
hot steam to evaporate the water content and recover the polymeric salt in the flake
fomm.
s The resulting flakes may be subjected to milling and screening to yield thedesired physical properties to provide satisfactory denture stabilizing properties.
The salts are ~iable so that ~Iyyl~y~;at~, particle size and bulk density can be
obtained. For best results, particles should be capable of passage through a 140- to
200-mesh sieve (U.S.B.S. series) and preferably are less than 0.74 millimeter in their
0 largest dimension.
The subject zinc or strontium AVE/MA copolymer salts have exceptional
adhesive qualities when contacted with water or saliva such that they are extremely
useful as denture adhesive materials in denture stabilizing ~ c For such
use the salt in particulate fomm is preferably cl.~..~.,i.,.i,.~,~ by a particle size of at least
5 minus 140-mesh U.S.B.S. sieve; a bulk density greater than 0.3 gram per cubic
centimeter and preferably higher than 0.6 gram per cubic centimeter; and a pH
between 3 and 7.0, the pH being detemlined on a one percent by weight dispersion in
water.
The subject zinc or strontium AVE/MA copolymer salts may be utilized in
20 effective adhesive amounts, preferably at least 20 percent by weight, as the sole
adhesive component or as a co-adhesive in joint usage with other active adhesive - r ' in denture stabilizing . Preferably, the unmixed zinc or
strontium AVE/MA copolymer salts may be utilized with mixed AVEIMA copolymer
salts containing cations such as calcium, sodium, magnPcil~m potassium, r - -
2Jr zinc, strontium, and mixtures thereo
r~5~-lh~ - Glycol
The invention .~ also comprise pGl.~lh/l~ glycol. In general,
yO1~ ,,~ glycols are polymers with the general fommula (OCH2CH2)nOH, where
n is greater than or equal to 4. The pul.~..h,!~ glycols are designated by a number
30 that represents the average molecular weight ~Merck Index. Tenth Edition, No. 7441, 1983]
The present , comprise p~ . glycol having an average
molecular weight above about 100 and equal to or below about 600. Preferred is
p~ glycol having an average molecular weight of equal to or greater than
3s about 300 and equal to or below about 600. rul~,.l./l, .. , glycol having an average
molecular weight of about 400 is most preferred. The -y.Jl~.,lhjl~,..e glycols suitable
-
wo ss/33434 2 1 9 2 1 8 0 PCTIUS95107280
for use in the present inYention are well known and ~ available, such as
those marketed by Union Carbide Corporation under the trademark "Carbowax".
The level of pol~ hJ ' giycol that is useful in the present invention is based
on ' ~' 'I"'`'I;fJ''` containing AVE/MA copolymer saits ..l, -,- .Irl;~d by a particle size
s of at least minus 140-mesh U.S.B.S. sieve. Therefore, P~JI~ hYI~ ; glycol having an
average molecular weight above about 100 and equal to or below about 600 is
present at a level of from about 20% to about 90%, preferably from about 30/0 to
about 80%, and most preferably from about 35% to sbout 75%, by weight of the
invention '
Optional ,; . , . ~
The present invention , may also include a safe and adhesively
effective amount of a co-adhesive. The term "safe and adhesively effective amount"
as used herein means an amount sufficient to provide adherence of a denture or
dental prosthesis to the orai cavity.
Preferred co-adhesives include a water-soluble hydrophilic colloid or polymer
having the property of swelling upon exposure to moisture to form a
mass. Such adhesive materiais include natural gums, synthetic polymeric gums,
adhesive materiais commoniy employed in denture stabilizing ~ ,- and
compatible with the subject AVE~A copolymer salts, synthetic poiymers,
saccharide derivatives, cellulose derivatives, and mixtures thereo Examples of such
materiais include karaya gum, guar gum, gdatin, algin, sodium alginate, tragacanth,
h,' " ' , acrylamide polymers, ethylene oxide polymers, pul~
cationic ~fJI~ ~' ' ' polymers, ~bu~ ' ~ II,ulù~e, sodium
.~i,uA~....,I~.~l~,eiiui~se and mixed partiai saits of poly(vinyl methyl-ether maleate).
25 Sodium ~ " ' is most preferred for use in the present invention. In
generai, the co-adhesives may be present at a level of from about 5% to about 70%
by weight of the ~ .
Other suitable optionai ingredients include colorants; preservatives such as
methyl and propyl parabens; thickeners such as silicon dioxide, and pfJI.~
30 giycol having an average molecular weight of 8000; and vehicles such as liquid
, petrolatum, minerai oil, and giycerin. Preferred are ~JIJ~ l.., glycol
having an average molecular weight of 8000, minerai oil, and petrolatum. Colorants,
..,I va~ , thickeners, and vehicles may be present at levels of from about 0% to about 20%, by weight of the c~
The , - of the present invention may optionally include from about
0.01% to about 5% of one or more c , which provide the user with sensory,
including flavor, benefits. Suitable r include natural or artificial
w095/3343.1 21/~2180 r~u~
sweetening agents, menthol, methyl lactate, ~ , oil, peppermint oil,
spearmint oil, leaf alcohol, as well as coolants 3~ ,.u~,~u.G-1,2-diol and
~.~ ' c~ u~_ ' agents such as N-ethyl-p ' -3-~ bu~ idc
which is described in U.S. Patent 4,136,163 to Watson et. al., which is i~.~,ul~o~cd
5 by reference herein in its entirety.
The ~ . of the present invention are ~ ur~ ulcJ in an art-
recognized manner icnown to those sicilled in the art, such as powder, cream,
ointment, liquid, or paste r".. l ~; Suitable examples of such r.... ~ ;.. are
disclosed in U.S. Patent 4,518,721, issued May 21, 1985, and U.S. Patent 4,514,528,
o issued April 30, 1985, both to Dhabar et ai., and both ;..vu.~u-~c~ by reference
herein in their entirety.
The foliowing l~o,~ l ~ examples ii~ustrate ...~l~v~ of the subject
invention wherein both essentiai and optionai ingredients are combined. These
examples are given solely for the purpose of illustration and are not to be construed
5as limiting the scope of the invention
F.XAMpi.F I
Inyredients. Weight %
17.5% Zinc unmixed partiai sait of
AVEIMA copolymer(a) 33.0
~orul~_L~.,!c.. ~, Glycol 400 40.5
Sodium Gubu~ yl~,ellulu ~ 17.3
Petrolatum 8.0
ru~ ......... c Glycol gO00 1.2
(a) AVE/MA copolymer salt having about 17.5% ' with zinc.
2s FXA.~PLE 11
~ Weight %
20.0% Strontium unmixed partiai salt of
AVE/MA copolymer(a) 10.0
47.5% Caicium/17.5% Zinc mixed partial
salt of AVE/MA copolymer(b) 28.1
rUl~ ,J!~ . Glycol 40û 39.0
Sodium C.u~v~ ' ,1~1h.1~se 12.1
Petrolatum 10.0
Minerai Oii 0.8
(a) AVE/MA copolymer sait having about 20% : ' with strontium.
(b) AVE/MA copolymer sait having about 47.5% ' with caicium
and about 17.5% 1 ' with zinc.
WO 95/33434 2 1 9 2 1 ~3 0 PCTIUS95/07280
9
EXAMPLE III
Wei~ht %
25% Zinc unmixed partial salt of
AVEIMA copolymer(a) 11.9
s 65% Calcium panial salt of
AVE/MA copolymer (b) 24.1
rul~Lh,~ Glycol 400 42.2
Sodium COIbu~y~ h.~,dl~uL~se 12.8
Petrolatum 8.0
o rU~ h.~,.. , Glycol 8000 1.0
(a) AVE/MA copolymer salt having about 25% ' with zinc.
(b) AVEJMA copolymer salt having about 65% . _~. ' with calcium.
Examples l-m are prepared as follows. Combine P~IJ~,.I,J~ glycol 400,
petrolatum, (and mineral oil if present) and heat to SS-65C until liquid. Add sodium
15 hu~u~.. ~.h,1~ " ' , pul~,.l.. ,l~.. ~ glycol 8000, and AVE/MA copolymer salts.
Stir until well mixed. Cool to room i . ~.
