CA2079322A1 - Copolymers of maleic anhydride and acrylic acid useful in denture adhesives - Google Patents

Abstract

Slurry copolymerization of maleic anhydride with (meth)acrylic acid and, optionally, with C1-C4 alkyl vinyl ether in a cosolvent system of cyclohexane and ethyl acetate yields a pumpable slurry, from which uniform, fine, white powders having a predetermined weight average molecular weight of about 10,000 to one million, preferably about 30,000 to 400,000 are obtained. The copolymers are useful in a denture adhesive composition which is a mixed partial salt of the copolymer.

Description

W~l 91/~4716 PCI-/U~i91/~145~; ~
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1- 2~79322 COPOL~S OF MALEIC A~R~DE A~D ACRYLIC ACID USE
IN DENTVRE ADE~ESIVES

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The prior art has not been entirely successful in providi~g copolymers of maleic anhydride and acrylic acid as Sl) a pumpable slurry of the copolymer in a non-toxic solYent; ( 2) without requiring an excessive degree of agitation; t3~ from which predetermined high molecular weight copolymers can b~i readily obtained; (4) in the form of uni~orm, fine white powders; (5) having ~ubstantially no residual monomers; (6) in a process that does not require a protective colloid; (7) wherein the solvent can be easily recycled;:and which copolymers can be used effectively in denture adhesive compositions~
Accordingly, the slurry polymerization proces~ of the:present invention provides uniform, ~ine white copolymer powders o~ maleic anhydride and acrylic acid or methacrylic acid from;-the copolymerization of predetermined amounts of maleic:anhydride and acrylic acid or methacrylic acid in a cosolvent:system comprising ethyl acetate and an aliphatic:oricycloa~liphatic hydrocarbon. The copolymer powders of:the invention~are particularly useful in denture adhesive compositions.~ J~',: ''' :`;' "~; ~' ~ oilIn~thelprocess-of:l.the:.invention,: from a~out 10 to 70'~ole percent,~pr~ferablyl20`to 60~mole percent,i~ of maleic anhydride~ àndf~30!~tol90 mole`percent,: preferably 20 .to~i~80-mole perc~t~by:;`wei`gh~-o~acrylic àcid or'~
methacrylic acidji; optiona`llyi,?iwith``up-itoi`'aboùt:25-mole ~:
percen~of~i:'a Cl~-C4''~àlkyl`~vinyl`JetXer~ prefièrably:methyl io .-~ !rs~ vinyl~vëther~5~is~copoiymérized in~t~ëlcosolvëint~system of the;~invention,i in:the presence of aipoIymerization initiator, under ~uitable temperatures~andJreaction time conditions.

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W~91/14716 P~T/US91/01~5~

The sequence of addition of these monomers further assures that the polymerization mixture remains in a slurry form in the cosolvent system of the invention at all times during the reaction.
The cosolvent ~ystem of the invention comprises about 5 ~o 80 p~ircent by weight of ~ithyl acetate and ahout 20 to 95 percent by weight of an aliphatic or cycloaliphatic hydrocarhon having a~boiliny point of at least 10C. above the reaction tempera~uxe. Suitable aliphatic and cycloaliphatic hydrocarbons for use herein include h~xane, heptane,.~octa~e, cyclohexane and the like.
Cyclohexane is pre~erred'. ~ost pref~rably, the cosolvent system of ~he invention comprises about lO to 75 percent by weight,of ethyl acetate and about 25 to 90 percent by weight of the aliphatic or cycloaliphatic hydrocarbon.
Most pre~erably, the cosolvent system comprises about ~5 percent by weight of ethyl acetate and about 75 percent by weight of cyclohexane.
The cosolvent system of the invention has a ; synergistic effect on the polymerization as..compared to each solvent.alone.~ Particularly,,~thyl~acetate~itself is . ,.unsuitable solvent for the polymerization because the -- copolymer is soluble-in this solvent,.,.,Furthermore, the .,"~ molecular weight..,of the ,copolymer produced in ethyl acetate ,.,,: -,-; is very low,,and semi-solids product.is produced.
Similarly, cyclohexane alone.is,unsuitable because it ,pr,o,,duces, insolu,ble,pre,cipitates,which":are not readily pu,mpable.-,,F,urthermore,~p,o,lymer,,powders isolated.~rom ,¢";cyclohexane~are.nonuniPor,m~,andjcontains aggregated partic,les..~ In contrast,1a,cosolvent:system.of,ethyl j3 ;' ~3~ ace~tate,,and;,cyclohexane~provides a,;pumpable-~slurry of the -, .~.copoly~er.,withou,t,~requiring e,xcessive agi,tation,or a ,~ ~,tprotective~colloid,~ In~addition,~,~this cosolvent system can remove any".trace of residual, ~a,leic anhydride~monomer from " ~5,,~ the-copoly~er,product.,.,~ ,t7,i ~., .o ,~i ., :

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The use of predetermined ratios of each solvent in the cosolvent will provide copolymPrs having varying molecular weights. Consequently, the amount of ethyl acetate included in the cosolvent system of the invention must be carefully controlled because ethyl acetate has the effect of reduci~g the molecular weight o~ the copolymer : and of solubilizing the copolymer. For example, the use of 66 percent by-weight ethyl:acetate in the cosolvent system will produce a polymer having a weight average molecular weight of about 30,000, while the use of 10 percent by weight ethyl acetate will produce a copolymer with a weight average molecular weight of abou~ 400,000, under similar reaction con~itio~s.
A cosolvent system comprising ethyl acetate and cyclohexane is particularly ad~antageous because their boiling points are very close (76C.:and 80C., respectively), which enables the cosolvent system to be recycled easily by distillation. Mixtures of solvents with boilin~ points far apart are not favored because they would : . become enriched in the lower boiling solvent upon recycle distillation.;~ e~
The boiling points of the solvents used herein usually are at least 10,~ and preferably 20 or more, above the operating polymerization temperature, (preferably about 65C.).' This~difference helps ~o.moderate the e~fect of .the~exothermic~polymerization:reaction upon the solvent and obviates the need ~or..a pressurized reactor.
~ .f.~- s~.The~*otal,-monomer content''in th'e'cosolvent system r.c.of~lthe invention;usually is about~;J10 to 30 percent'by ,;..r~i."':.weight, pre~erably.about 20 ~o 25 percent by weight. In e~ ..".~his~concentration,.'th'e s'lurry~remains~'pumpab'le undier 5~ ;"ordlnary agitation'o~.reac~ants at'ta reàction'tempërature between`about 50;~*o~ 50C;t~ t ~ ,t _. ? ~

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WOg1/147~6 PCT/US91/~1455 2a~322 The polymerization initiator for the process herein preferably is selected from peroxy esters, such as t-butylperoxy pivalate or t-amylperoxy pivalate, or dialkyl peroxides, such as di-decanoyl peroxide, although other initiators known in the art for free radical polymerization may be used as well. . - - .
In operation o~ the polymerization process of the - invention, a solution comprising maleic anhydride reactant, initiator and cosolvent is precharged in a suitiable reactor, and acrylic acid or methacrylic acid is fed contin,uously into the precharged solution, which is maintained at about 60 ~o 80C., over a period of about 0.3 to l0 hours. The optional alkyl vinyl ether monomer is added after the acrylic acid reactant has been added. The polym,erization mixture then is h ld a~ the reaction temperatures for an additional 15 to 90 minutes following completion of addition of all monomers. Several initiator boosters can be introduced during or after feeding of comonomers.
~ The invantion will now be described with reference to the following specific working examples. ~~ .

EXAMPLE_l : . ; ..;.

~ ~ . COPOLYMERIZATION OF ACRYLI~ ACID AND MALEIC
f" 4~ ..7~ . ;"~ ;';,; .ACID-IN-ETHYL ACETATE-CYCLOHEXANE COSOLVENT

~,t~ ,A .l-liter resin kettle;iwas.:.equipped with a cstirrer~ reflux .condenser, N2~inlet~.tube-and an inlet --, closed with~a rubber septum:for.introduction o~-initiator.
.~The ke~ttle~,was charged~with 49..Øg.-i:(0..50 mole) of::maleic anhydriqe.~(~A),s,275v g.-.~ 5iwt.~%)-o~:ethyl;acetate:~EA) and 92 g.:(25 wt. %) of~cyclohexane.^(C~ Agitation-,of the~
mixture was begun and the cyste~ was purged by bubbling in . .' .

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WO~1/14716 P~T/U~91/014~35 ~i';' ~ 5 ~ 2~793`22 N2 for 30 minutes, during which time maleic anhydride dissolved completely. The reaction mixture was then warmed to 65C. and 0.3 ml of Lupersol 11 (Pennwalt) was injected through the ~eptum to initiate polymerization.
Simultaneously, dropwise addition of 7~i.0 g. (1.0 mole) of acrylic acid tAA) was begun and continued over a period of 3 hours. Lupersol 11 was added at a rate of 0.3 ml of initiator for each 30 minutes of AA addition during this period. After completion of all additions, the resulting mixture was maintained at 65C. for 2 hours.
After 15 minutes the reaction mixture became whitish, and, thareafter, a uniformly thick, creamy slurry was for.~ed which was pumped out of the kettle into a filtration unit~ There the slurry was filtered and the polymer product was dried for about.l2 houxs at 65C. in a forced air oven. The polymer product was a uni~orm, fine white powder, having a weig~t average molecular weight (as determined by GPC) of about 47,000. A sample of l g. of the polymer dissolved in 5 ml acetone.was treated with triphenyl phosphine and it indicated that the conversion of maleic anhydride into polymer was complete.
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. EXAMPLES 2-ll .., ,: . . ..... .
~ The procedure of Example l was followed to provide copolymers-.o~lvarying compositions and,molecular. weights.
.The results of Examples l-ll are shown in Table~l below.
In Examples 9.and~lO therein, a third.monomer., either butyl ; vinyl ether or methyl vinyl ether, was introduced after i addition of acrylic acid was completed. I ..

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WO g 1~14716 PCI'/US91/0145! i f:: , _ 7 _ 2~79322 COMP~RATIVE EXAMPLES 12 16 The procedure of Example 1 was followed using different solvents. The following results were obtained and are shown in Table 2 below. It is seen therein that single solvents, including ethyl acetate, cyclohexane, toluene, t-methyl butyl ether and xylene, produced nonuniform slurries and polymer powders, which were difficul~ ~o process and much less advantageous products than thase made in the cosolvent system of the present invention.

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W091~14716 PCT/US91/01455 - , ~
2~79322 g The FIGURE is a graph of adhesive force in lbs.
vs. number of cycles during Instron testing of adhesive compositions of the invention.`

There is provided a denture adhesive which is a mixed partial salt o~ the copolymer of maleic a~hydride and acrylic acid (or ~ethacrylic acid), optionally including a Cl-C4 alkyl vinyl ether, having a weight-average molecular weiyht of about 30,000 to 400,000, preferahly about 50,000 to 350,000. :
Thè copolymer suitably co~prises about lO to 70 mole percen~, preferably 20 to 60 mole percent, of ~aleic anhydride, about 30 to 90 mole percent, preferably 40 to 80 percent, of acrylic acid (or methacrylic acid), and 0 to 25 mole p~rcent of a Cl-C4`alky1 vinyl ether.
The partial mixed salts include calcium/sodium salts wherein the equivalent ratio of calcium to sodium cations may range from 2:1 to 10:1, preferably between 3:1 to:7:1t and the degree-of neutralization of initial carboxyllgroups is-from-~O.S to 0.95, preferably~rom 0.7 to o . g . ~ , . . , 3 -~-~ ~.The adhesive copolymer of this invention-is converted to its ~ixed~par~ial salt,~ which:preferably is employed`as a dry powder having-a~pârticle::size of less thàn:250 ~,^;and,~.morë de~irably, a~particle`:size of.from about~5 t*~about 200 ~ s~l~ 3 J~ ?~ r, ~
7~ Denture~radhesive c*mpositions; are ' provided^ herein by incorporating dry powders of the above~adhesive"i copolymer'asi:mixed:salts`~:~nto a`liquid bat~ë carrier by t3`'' mixing~iùAtii à~hoinogeneous;cream~pastèl:suspénsion~-or collodial;disper`sion:is `obtained,~usuallyrwithin~a~.period o~3from~'~àbou~i~20`'~minutès:to~abouti::5'hours~ ;;The'-resulting --compos`ltionlcontalnstàn~efective-~adhesive amount-of the -~adh`e`sivé copolymer^mix~e~d~salt,`~ge~eraliy'-between~abouk 5 and about 50 wt. %, and preferably between about 10 and about 35 wt. %, of the ~i~al co~position.
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wosl/~471~ PCT/~S91/01455 ,~,.
2~7932~ - lo-Suitable mixed partial salts herein include the calcium/sodium mixed partial salts which are prepared by .
reacting the copolymer with suitable bases. Preferably the equivalent ratio of calcium cations to sodium cations in the mixed partial salts may range from ~i:l to 10:1 and most preferably is between 3:1 and 7:1 (on a mole ratio basis, the range of calcium to sodium cations is from 1:1 to 5:1, most preferably from 1.5:1 to 3.5:1). The s~m total of cations in the mixed partial sialt should be eufficient to give a degree of neutralization o~ from 0.5 to 0.95 and preferably 0.7 ko 0.9 of the total initial carboxyl groups in the copolymer. In the determination of the total initial carboxyl groups in the copolymer, the anhydride radical i9i considered as containing 2 initial carboxyl groups.
rhe base carrier portion of the composition generally includes a water soluble or partially water soluble hydrophilic carrier which is capable of swelling upon exposure to moisture to form a mucilaginous mass.
Such:carrier materia}s include natural and synthetic gums, .: viscous:liquids, ~els and powders.- Among those suitably employed as base carrier in the composition are karaya , gum,~gelatine, gum tragacanth, gum acacia,~gum shiraz, .......... .... ; algin,~sodium alginate,-tragacanth, methyl cellulose, a :...,mixture of~petrclatum.and mineral,oil, glycerine, s~e,polyVinylpyrrolidone,~K-30.and K-90,~carboxymethyl cellulose, ethylene oxid~ polymersj of.,which the.,preferred e..~isia~:mixture~.of petrolatum and mineraljoil~in a ratio o~
~0:60-60:~0.~r..~c~ , ;t~ ?;~
. The..adhesive.copolymer of-.thesinvention can be .employed~asJ:.the~sole,adhesiveijcompQnent i.n"the dent~ure r ,adhesiye composition..or it,pan be.used~asia coadhesiive with another~adhesive~material.~ Such adhesiive~.dditive,~if : :, presentjjwillj.~generally~comprise about~5-~0% by"weight of : ~ithe composition.i r~i Suitable adhesive.~addiitives~:include . _ ~ . . .. . ' ' , WOgltl4716 P~T/US~ltO145~

natural or synthetic polymers such as cellulose, karaya gum, gum tragacanth, gum acacia, carboxymethyl cellulose or salt thereo~, polymethacrylate, polyvinylpyrrolidone, polyvinyl acetate, or any mixture o~ the above.
The compositions of the invention are particularly useful for affixing dentures and can also be used in surgical procedures which require ~emporary displacement of ~issue. As a denture adhesive, the thermal stability of the present composition, over a temperature range which is at least sufficient to embrace all conditions encountered by living ~issue, e.g. 5-50C., is particularly desirable. ~ecause of ~heir increased adhesive strength and thermal stability, ~h~ composi~ion retains its adhesive properties over a long period of ~ime, i.e. up to 24 hours.
. The following illus~rates a few representative formulations-into which the a~dhesive copolymer can be added in ef~ective amounts up to about 50%.

Cream Denture Adheslve Compo ltion . wt.
~ineral Oil ~ 30 Petrolatum 25 Sodium carboxymethyl!cellulsse -- - 20 ....... , ., .. . . . . . .. ~ . .. .. .... . . . .. .... ... . . .. . . .. ..
~adhesive additive) Colorant,........ r,; ' '~
. Flavoring Agent............. m~ . 0.5 atarial.of.Inven~ion ~ jr~'"'~'i-',' ~.``,,~'_''',~.~'~,'- 23.5 .~ iPaste ostomy Adhesi~e.Co ~ ..~,. .,! :.~ 'C' .; 3.~ wt-~
-;Mi~eralr~oil :~heavy)~r~ r~ r '..~ -.` 35 Glycerine~ Q !: 3/.;~ . ~!~,I','';`,",','~ '~` ''~,_~' `'.~,/,' 5 . Polyvinylpyrrolidone ~ : m~ 20 I ... :Carboxymethy~ cellulosem~ ec;. e ~ x~ 5 .Tosylate~nf~quat-~ ~amino.N-propylpyrrolidone~ec~ Ø~5 Matrial:of~.Inv~ntion~3 01;~5)~ r~ jis~ J~.34~5 , .. ... ~ :~ - . - ' ' ' .. . . . : , .
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WO 91/~4716 P~/US91/0145~
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2~79322 - 1~

Denture Adheisive Powder Com~ositi_ Gum tragacanth 40 Gum acacia 20 Spearmint oil 0-05 Material of Tnve~tion ; 39.05 PREPARATION OF DENTURE ADHESIVE COMPOSITIONS

The copolymer was converted to its mixed, partial salts as follows.~ ~5 g. of the copolymer was charged into a 250 ml round bott~m, 3-necked flask together with 90 g.
o~ isopropyl alcohol. The contents were agitated to make a slurry and 9.59 g. o~ calcium hydroxide was added slowly with agita~ion during 15 minutes. Then 2.08 g. of sodium hydroxide.dissolved in 38 g. of water was added with agitation. The mixture was heated at ~5C. with agitation ..
for 1-1/2 hours. The pH of the liquid phase was 4.89. The mixture was filtered and the precipitate was dried in a vacuum oven overnight at 65C.

~ PREPARATION OF ADHESIVE ~COMPOSITIONS FOR - INSTRON TESTING
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: : The dry, mixed salt of the MA/AA copolymer was mill~d to pass through a nu~ber 60 mesh~sieve (250 ~) ahd thei resulting powder was then dispersed at.a ~emperature of 55-65C., followed by cooling to 20-25C., into a ~p*trolatum base using mechanical~stlrring.~~r~The ratio of ~`copolymer to base by w~ight was 1:2.r.~The resulting cream :disper~ion was collected as the desired adhesive !I"';
`ciomposition- ;..i,:ic.~ i s ~
, r- Adhesive compositions.of~the!~dry,~i.mixed~salt of : c.th`e copolymeris,;:i:and~^,GANTREZ!MS-955, which~ls:a~icommercial mixed salt copolymer o~ maleic anhydrlde'and ~et~yl~vinyl ether, also were prepared for testing in the same manner as . described above. ~:

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: ' ' ' . ; . ~ . '' ~: ' . . ' ' . .:: ', 2 y. samples of each of the above prepared compositions were evaluated for adhesion characteristics by Instron testing according to the following procedure:
In the first step, the upper and lower plates of the Instron apparatus were brought together to obtain a zero position. The upper plate was then rais~d 0.06 inch and the upper cycle limit on the Instron indicator is set at this point. The upper plate was then lowered and the lower cycle limit was set. In its lowest position, the upper plate was distanced 0.03 inch above the lower plate.
With these In~tron settings determined, the upper : plate was then raised and 2 g~ of th test sample was unifo~mly spread over the surface of the lower plate in a 1/16 to 1/8 inch thickness; thereafter simulated salivary fluid was applied over ~he sample so ~ha~ it was barely covered.
The Instron crosshead was cycled be~ween the previously set limits at a crosshead speed of 0. 2 in./min.
The Instron chart was set in the continuous mode at a speed of 2 in./min. to record.the compression and adhesion ~orce for each cycle, 5 to 100 cycles. ., -~
At.the end of 100 cycles, the motion.of the upperplate was halted and raised high enough to clean the surface before the next adhesive test.
Each recording was analyzed and t~e adhesional , ,,forces.(lbs.).,for.;,the~.lst,.-5th,~10thj 20th, 40th .... 100th cycles were recorded and then plotted graphically. :~
The results of this study are shown in the FIGURE. This data show significantly better initial stick ,~, . , strength and long.term adhesion,for adhesive formulations contalning.the copolymer..~compositions-,of ~the~invention as compared to a related copolymer composition ~MS-955) useful .as a denture adhe~ive.

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Claims

WHAT IS CLAIMED IS:

1. Copolymers of maleic anhydride and acrylic:
acid or methacrylic acid, optionally including a C1-C4 alkyl vinyl ether, having a predetermined weight average molecular weight of about 10 000 to one million suitable for denture adhesives made by:
copolymerizing about 10 to 70 mole percent of maleic anhydride, about 30 to 90 mole percent of acrylic acid or methacrylic acid, and from 0 to 25 mole percent of a C1-C4 alkyl vinyl ether, in the presence of a free radical initiator, at about 50° to 150°C., in a cosolvent system comprising about 5 to 80 percent by weight of ethyl acetate and about 20 to 95 percent by weight of an aliphatic or cycloaliphatic hydrocarbon having a boiling point at least 10°C. above the reaction temperature, to produce a pumpable slurry of said copolymer in said cosolvent system, and recovering the copolymer therefrom as a uniform, fine power having substantially no residual maleic anhydride.

2. A denture adhesive composition containing the copolymer of claim 1.

3. A denture adhesive according to claim 2 which comprises a mixed partial salt of the copolymer of

claim 1.