CA1278125C - Silicone pressure sensitive adhesive and uses - Google Patents

Abstract

SILICONE PRESSURE SENSITIVE ADHESIVE AND USES

ABSTRACT OF THE DISCLOSURE
Pressure sensitive adhesive having favorable adhesive, shear, liquid permeability, and release characteristics. The adhesive is a crosslinked polymerization product of a methyl/phenyl siloxane gum, dimethyl siloxane gum and a polysiloxane resin. The resulting product provides suitable adhesion to a large number of surfaces and has particular utility as an adhesive between plastic film and human skin, especially for use with transdermal therapeutic devices. The adhesive characteristic mitigates damage to underlying surfaces such as human skin tissue during adhesive removal.

Description

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SI~ICONE PRESSURE ~ENSITIVE ADIIESIVE ~ND USES

l. Pleld of the Invent~on Ihe present invention relntes to pre~sure sensltive adhesive~ which p~ovide suitable aclherence of obJects to the human skin. ~he invention relates more partlcularly to sillcone based pressure sensitive ndhesiveY whlch are of particular use in transdermal therapeutic devices for nttachr~ent to the human skln.

2 Descri tlon of tlle Prior ~rt P ~ .., __ Pre~sure sensitive adhesives for use on human skln are used typically in bRndages or other therapeutic devices which must adhere to the skln for n prescribed period of time. Such devices are typically comprlaed of a plAstic or cloth film layer conted with a pressure sensitive ndllesive. lhe pres~ure sensltlve nllleslve la ~rotected wlth n release substrate wllich in rendily peelable Ero-n the ndhesive contlng. 111e pressure sensitive adheslve for use ln connection with such - bandages ~r other thernpeutic device must sAti~fy an nrrny of specific physical chnracterlstlc~. Importantly the release substrate must be easily peelable from the ndhesive coatin~ and the adhesive must have sufflcient cohesion to keep the bnnda~e or therapeutic ob~ect in adlleslve contnct with the skln for A prescrlbed period of time. ~180 the ndheslve mu~t not cau~e skln inflnmmntion nnd must be nontoxlc.
~ddltlonally a pressure sensltive adllesive as ~pplied to a transdermal therapeutic devlce must meet other strict performance requlrements. A transdermal device is a medicinal pouch which contalns a liquld medlclne or other dru~s which must be abnorbed pradually into the ~klr over n Ealrly long pertod of time. Jllese devices typically contain A semipermeable membrane and Are advnntageously used wlth drugs whicJl are best ~bsorbed into tlle h nnan body gradually, 8UCIl as nitroglycerine or other drug~
useful in treating cardiQc impAirment. lhus, the pre~sure sensltive adllesive which 18 coated onto tl-e therApeutlc device mu~t not ACt a9 a barrier to interrupt the flow of fluld from the device and lnto the human blood ~tream.
Speclflcally, the pressure sen~itive Adhesive must be permeable to the drug being used. Furthermore, nince the therapeutic device must remain ln close adllesive contnct with the slcin over a perlod of time typicnlly nt least up to 24 hour3, the ndhesive should keep essentially all of the contact surface of the therapeutic device ln adheslve contact wlth the patient 8 skin ovet this entlre period.
lhe pressure sensitive adhesive should also permlt the therapeutic device to be peeled from the skLn without causing discomfort and without leaving an adhesive resldue on the skin which i~ not easily removeable.
U.S. Paten~ Nos. 2,857,356 and 4,039,707 nre illustrative of prior art sllicone-based pressure sen~itlve adhesives. U.S. Patent No. 2,857,356 dl6closes pressure sensitive adhesive formed from tlle polymerl7~tlon of 2 silicate resin and an ~5 organopolyslloxane fluid. llle silicate resin is obtnined by interconden~ing a mixture comprising a cohydrolysis product of a trialkyl hydrolyzable silAne and an alkyl 6ilicate, said cohydrolysis product contalnirlr, n plurality of 811icone-bonded hydroxy groups. ~he formulation disc]osed ln tlli~ reference is directed ~rincipally to forming n pressure sensltive adhesive wl-lcll retains ~ high degree of tsck and cohesion over a wlde temperflture rarlge for example between nhout -75C and 250C. lhe pressure sensitlve Adhesive product disclosed in tllls - : .
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~L ~ 7 ~ 5 reference is dlrected to npplication princlpa1ly as an adllesive coating for u~e ln contacting polymeric material such næ gln~s a wide range of plastics such a8 polyethylyene and also for use in connection wlth the manufncture of pressure sensltlve tapes. Ihere is no reference ma(le in this disclosure to 6uitability oE the ndhesive product Eor application to lluman skin. In order to achieve tlle high degree of t~ck and cohesive strength patentees tlisc]ose that the weigllt ratio of tlle sllicnte renin to the organopolyniloxane Fluid should be between about 0.5/1 to 6/1 more preferably between about 1/1 to 3/1. (Collmmn 7 lines 21 to 28). lhe rnnge of forn~lations disclosed ln this reerence could not be suitnble for npplication to A tr~nsdermal therapeutic device becnuse of insufficient tnck for npplicntion to human skln and too grent a time lapse required to achieve maximum bonding.
U.S. Patent No. 4 039 707 dlscloses a siloxane-type pressure nensltive adhesive which is composed of the intercondensatlon product of a mixture containing an orgAnopolysilo~ane resin and nt least one alkylaryl polyslloxane gum. Ihe org~nopoly~iloxnne resin 1B deflned nt Column 6 lines 5 to 10 ns having the formula:
(011)q (OR2)rR2SiO4qr8t2 It is also disclosed ns essentla1 that tlle organopolysiloxane gum contaln nryl groups such ns phenyl groups to obtain optimum pre~sure sensitive a(lheslve properties. If a mixture of phenyl and methyl groups 18 employed thls reference tenches that the number of silicone-bonded phenyl group6 should be malntnined wlth such a range that for ench 2 to 75 phenyl groups att~ched directly to silicone by a cnrbon silicone linknge there nre present from 98 to 25 sllicone-borded methyl groups wlth the preferred rnnge for instance from nbout 5 to 15 '' ' ' ~ " , ............................ ~

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pllenyl groups per 95 to 85 methyl groups. (Column 5, line 59 to Column 6, llne 2). lhis reference nlso dlscloses a use of a release substrate covering the pressure sensitive adhesive. lhe release sub~trate may typlcslly be n paper 5 or polymer flltn coated wlth n release coating such a~ a sllanol-stopped dimethylpolyslloxane fluld. Another releaae coating which 18 disclo~ecd in this reference 18 hflsed on dlmethylvinyl-stopped dimethyl poly~iloxnne fluld. I~ddltionally, the reference disclo~es that the 10 allcylaryl polyslloxane gum should have a vlscoslty from nbout 200,000 to 15 million centlpolse at 25C and contain an average from about 1,85 to 2.01 silicone-bonded alkj~l and aryl radlcals per silicone atom.
Although use of an alkylaryl polysiloxane p,um with an 15 organopolysiloxAne resin is dlsclosed in this reference, the reEerence does not dlsclo~e or su~,gest use of 6peclflc combinations of alkylnryl polysiloxane gums to lmprove the product 8 adhesive, shear and liquid permeabillty charneteristlcs 80 that tlle adhesive product may be used 20 with transdermal therapeu' ic devlces.
~ ccordlngly, it 18 an ob~ect of the present lnvention to provlde an improved pres6ure senslLlve adhesive wllich has partlcular u~e as an adlleslve for retnining ~ plastlc film or therapeutlc device in adheslve contact wlth the 25 hurnan ~kln an 1 wl ich ndhesive 18 nontoxlc and easlly removeable from the skin.
~ n important obJect of the lnventlon 18 to provide pressure sensltlve adheslve for pnrticular use in transdermal tllerapeutlc clevlces. A relnte l oblect 18 to 30 provide pressure sensitlve aclheslve whlcl retnlns tile therapelltic devlce ln adlleslve contact wlth the h~llnnll skin over ~ prolonged perlocl of time ancl cloe8 not lnterfere wlth the absorptlon of medlclnal Eluld from the transdermal clevlce througll the adheslve alld lnto the skln.

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SUM~RY OF ~IE INVFNIlON
l~)e pres~ure sensitlve ~lheslve of the inventlon ha~
been formul~ted to satisfy atl array of speclflc perFormance requirements 80 thnt the product has a particular sultablllty for use as a pressure sen~itlve ndheslve for tralls(lermal ther~peutic devices whLch are applled ln fl<lhesive contact wltll the skln. lhe pressure sensltlve ndheslve formulAtion 18 composed of the combination of n methyl/pllenyl slloxane preferably dimetllyl dlpllenyl siloxane gum wlth a dlmethyl siloxane gum and an organopolysiloxane resin. Preferably, the resin 1~ composed of monofunctlonnl and quadrAfunctionAl ~lloxane unlts, deslgnated herelnafter as an MQ regin.
~ppllcants h~ve found thnt such a formulatlon provideg a polymerized pressure sensitlve ndhe~lve having the requl~ite array of performance characteristics for use in connectlon with transdermal thernpeutic device6.
suit~ble catalyst such a8 ~ diaryl peroxide catalyst 18 advantageously included in the mixture to initiate polymerizntion between the siloxane gum and resin to form the pressure sensitlve adllesLve product. Alternatively, the catalyst may be omitted and the polymerization lnltlated by other meRns.
~lthough lt 18 conventlonal wlsdom th~t dimethyl dlphenyl 8l10xane gurn 18 lmcomp~tlble wlth dlmethyl sllo~Ane gum, nppllcsnt~ have found that over ~ speclfied range ln concentration of these component6 ln the presence of an MQ resln, a pressure senffitive ndllesive product can be formed. ~le resulting ndheslve product hag an arrny of 6pecifLc performance characteristics which make the product partlcularly sultable for use a~ a pressure sensitive a(ll)egLve for tran~dermal therapeutlc devlces. 11e ~elght ratlo o~ a dlrnetllyl diphelyl siloxalle ~8~

gum to dimethyl siloxane gum should preferably be in a range between 1/3 to 3/1. In the embodiment lncluding a catalyst, A diaryl peroxide catalyst may be used comprising between about 0.1 to 2 percent by weight of the polymerized pressure sensitlve adheslve product. ~
preferred catalyst oE this type i~ composed oE 2, 4, dichloro benzoyl peroxide contaLning A phlegmatic ngent such as dibutylphthalate. I~e pre6~ure sensitive sdhesive formulatlon mi~y addltionally include polybutene resln ln an amount of up to approxlmately 15 percent by weight of the pol~nerized adhesive product.
An fllterl1~tive formulation for tlle polymerlzed ~dhesive product of the invention is composed oE dimethyl dlphenyl siloxane gum, an organopolysiloxane resin (preferably ~IQ re6in~, arld a suitable catalyst 8uch as a dinryl peroxide catalyst as above de~cribed. lhe catnlyst typically 6hould be between about 0.1 to 5 percent by weight of the adhesive product. ~lthough this formulation produces ~n acceptable product for use in connection wlth a transdermal therapeutic device, the product exhlbits somewllat less satisfactory release charncteristics ln removing the relea3e ~ubstrate from the Rdheslve as compared with the preferred formulation containing both dimethyl/diphenyl siloxAne gum and dimethyl siloxane gum.
Ihe polymerized pressure sensltive ndhe~ive product is preferably prepared by forming a raw ndhesive solution composed of the reQctflnts ~et forth above, and solvents such as toluene, naphtha, xylene and n-butyl ncetate. In the alternative formulations polybutene resin may be included, or as above-mentioned, the dimethyl siloxalle gum may be omitted from the preferred formulation. 1~1e raw ~dlleslve solution 18 prepared by mixing the siloxane gum, MQ resin, catalyst and solvents until R llOmOgeneOU8 solution 18 formed. The solutlon is co~ted onto ft relea~e '~Z~

sub.~trate ~typicnlly n paper sheet overcoated wlth a sllicone releaAe conting~, thus forming ~n Ad11esive lamlnflte. Ihe a(111esive lamlnflte ln dried to vflpori~e the solvents flEter whlc11 the laminate is heflted to temperatures nece~sary to initlAte n polymerl7,ation reactlon between the siloxane gum and MQ resin.
n1e nd11esive lamlnflte may be transferre(1 to n surfnce of D trnllBdermal device BO that the ndheslve contlng comes into direct contnct with the device. Prefernbly, the ndhe~ive coflting come~ into dlrect contnct wlt11 a semlpermeable membrane component of the transdermal device. lhe user need only peel oEf the release substrate to expose the adhesive lnyer prior to pressing the transdermnl device onto his skin. It has been found that the pre~sure sensitive adheslve formulfltion of the invention exhibits unique liquid permeabllity characteri6tlcs flnd a h~gh degree of ndhesion to humfln skln, yet causes negligible skin lrritation or redness and has excellent release properties permittin~ easy removal of a releflse substrate from the adhesive.

In view of the foregoing discussion, in one broad aspect, the present invention relates to an adhesive that is permeable to medicinal fluids comprising the polymerization product of a methyl/phenyl siloxane with a dimethyl siloxane gum and an organosiloxane resin.

In a Eurther aspect of the present invention, the said adhesive may be provided in combination with a polyfunctional derivative of a polyfunctional alcohol applied thereon.

In another broad aspect, the present invention relates to the method of preparing an adhesive for the transdermal passage of medicinal substances, which comprises (a~ providing an aryl polysiloxane; (b) providing an alkyl polyslloxane; (c) providing an MQ organopolysiloxane with multifunctional siloxane units; and (d) polymerizing the mixture of said aryl polysiloxane, said alkyl polysiloxane and said MQ polysiloxane ,,--//

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I~E~AILED DrSCRIPTlOM
111e prensure sensitive ndheslve of the lnvention is preEernbly composed of the comblnatlon of a methyllpherlyl 6110xane gum; a dimethyl siloxane gum; an orgnnopolyslloxane resin, advant~tgeously MQ resin; and suitnble catalyst. A sultable methyl/pllenyl slloxane gum is a dlmethyl diphenyl siloxnne. Ihe term "gum" n~ used herein denotes Q hlgll visco~ity, e.g. grenter thnn about 20,000 centlpolse, linear nlkyl/nryl poly3110xnne or polydiorgnnosiloxnne thnt cnn be converted from n highl viscous plAstlc stAte into the predomirlnntly eln~tic stnte by crossllnklng. See, W. Noll, "Chemistry nnd Technology of Silicones", ~cademic Press, New York (1958), p. 387.
nle term "organosiloxnne ela~tomer" i8 herelnafter deEined a8 synonymous nnd interchnngenble with the term "gum" n~
nbove-defined. See. W. Noll, suprn, p. 387. ~e term "resin" as used in this patent ~pplicatlon iR synonymous with "polymer". ~he pres~ure sensitlve adhesive iB
pnrticularly useEul Eor ~ttnchlng n transdenn.ll ZO therapeutic device t~ h~an skln for n period of up to ~bout 24 hours. nle ndlleslve exhiblts Envorable peel releAse chnracterlstics and a high degree of adhesion over a prolonged period. nle ~dhe~ive i8 particulArly 6uited to medical Applicntlons in thnt it is easily removed from Z5 the skin and nonirritating, and permits the medication in the transdermal device to pa6s from the device, throug}
the ndhesive, nnd thence into the skin.
Transdermal devices nre well known in the art. ~ley are composed of a semipermeable mlcroporous membrane or membrnne~ Eor storing a supply of liquid medicntlon and causing relea~e of the medicntion there~rom nt COtl~tttlt rate over n prolonged period of time. Ihe trnn~dermal device contninlng the llquid medication is apl)lied I

-,, . .
,: .

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dlrectly to the slcln ln the form oE a banda~e lhe semlpermc~ble membralle ln cont~ct wlth thc sicln must be providecl wltll a pre~sure sensitlve ndheslve layer ln order ~o aclllere to tlle 6kln. ll1e references U.S. Patent Mos.
~,200,093 ~n(l (~,201,211 are merely representRtive of transdermal tllerapeutic devlces to whic11 tlle adllesive of tlle Inventio~ uppllc~le. 111e adl~esive of the ltlVelltlOn htl~'3 gerleral ~ppllcn~L]lty to e~sentlally nny tr~ns~1erlna] devlce whlc11 muDt be ~d1)e~lvely p1Acec1 in colltact wltll the n1cin, and there~ore the lnventlon ls not intended to be ]imlted to the foregoi1lg re~erences A sultable adl1esive for trnnsdertnal therapeutic devlces should ~atlsfy ~ number of specific requlrements.
~le adhesive mu~t nllow the liquid medicine to flow uninterrupte~l over a prolonged period of time, e .r,. up to nt least 6 hour6 alld preferably up to at least 24 to 3G
hours and longer, at constant rate, through the ~emlpermeRble membrane and into the skin. l11erefore, the adheaive cannot form n barrier between the membrane nnd the skin during the required prolonged period oE use so as to measurably retard the constant rate of flow of tlle medlclne from the membrane into the human slcin. It has been found that the adhesive formulation of the lnvention satisfies all tlle aforesald requirements, wherea~
conventional pressure sensltive adhesives have been founcl to signiflcantly retnrd the free flow of llquids therethroug11, especlally over a prolonged period.
~dditlonally, the adhe3ive shol1ld not c~use UlldUC
lrrltation to the skin, including 6welling, redtlens or itching on prolonged contact (typlcally up to at least 2 hours). I11e ndhesive should also allow for relntively ' 78~

e~sy removnl of the tra~sdermal device from the skin without causlng great dlscomfort to the patient~ In order to provide a suitable ndhesive for use with a tran~dermal devtce, the ndhesive should not signlficnntly deteriorate ln strength or tend to peel or toonen over the 24 hour period. ~dditionally, there 6hould be very llttle or no ndhe6ive renidue remalning on the skln after the trnns(lermal device 18 peeled from the skin.
~ pressure sensltlve ~dheslve formulation which has been founcl to sntlsfy tlle ~bove requlrernents is presented n3 formulation ~ ln Table I. ll~e pressure sen~itlve adheslve formulfltlon A is composed of n raw ndhesive solutlon whlch 18 drled to evapornte the solvents nnd then cured to form the polymeri~ed presnure sensltlve ndhe~ive product A, having n composition shcwn in Tnble I.
Raw ndhe6ive solutlon A a8 shown in ~able I is composed of a metl-yl/phenyl slloxane gum ~uch as dimethyl dlphenyl ~iloxane gum, and organopolysiloxane resln, preferably MQ resln, dimethyl siloxane gum, suitnble catAlyst~ nnd solvent~. The methyl/phenyl siloxane gum such as dimethyl dlphenyl si10xane ~um as well ns the dimethyl s110xnne gum may typicalLy have A vlscoslty between about 20,000 nnd 10,000,000 centipolse at 25C, preferably between about 20,000 and 1,000,000 centipoise at 25C. ~le MQ resin lncluded in formulntion A is compo6ed of monofunctional and quadrofunctional ~iloxnne units and has the generlc chemlcAl Eormula: MxQy~
where M = R3SiOl/2i Q ~ SiO4/2; and R prefer~bly in n methyl group. Ilowever, R may include any other fllkyl group particularly Cl to C4 nlkyl groups, l.e. methyl, ethyl, pr~pyi nnd butyl ~lkyl groups.
~ le molnr ratio of phenyl groups to methyl p,roupæ in the dimethyl dlpl~enyl siloxane Kurn is at least nbout 0.1/1 .. . .

.

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nlld preferably between about o.l/l nnd 0.2/1. Mlxtures of dimettlyl diphenyl siloxane gum and sulta~le MQ resin may , be purchased under the trndename SILGRIP SR6574 ~r~ manufactured by the General Electrlc Company of Waterford, New York. lhe MQ resin ls commerclally available in dry powdery partl,culate form. ~ preferrecl rlQ resin to be added to thls mlxture 1~ commerclally nval],able under the tradename CR5~2 from ~enernl Electric Company. ~notller MQ
resln suitable for use in ndhesive solutlon ~ is colmnercinlly 801(l under the tradename C~2-2109 deslgnated as a controlled release sdditive frcm Dow Corning Co. of Mldland, Mlchigan. ~ suitable mixture of dimethyl siloxane gum nnd MQ resin 18 available under the trade deslgnation 280 A adhesive from Dow Corning Co.
nle preferred catalyst 18 a diaryl peroxlde type catalyst, such as that contalning 2, 4, dichloro benzoyl peroxide, which contalns fl phlegmatlc agent such as dibutyl phthalate. ~ catalyst of thls type 1.~ available under the tradename C~ W X~TDP, nvallable from Noury Chemical Company oE Burt, New York. 111e raw adhesive ~olution ~ a8 set forth in Table I further contains solvents, preferably toluene, naphtha, xylene, and n-butyl acetate ln the proportions llsted.
~n alternate pressure sensitive adhesive formulatlon B 18 tabulated ln l'able II. ltlis formulation llflB also been found to satlsfy the above-referenced requirements.
~le pressure 6en6itlve ndheslve formulation B 18 compo~ed of a raw adhesive ~olutlon whlch 18 dried to evaporate the solvents contained therein nnd then cured to form the polylnerlzed pressure sensltlve adlleslve product B hnvlng a composition shown in Table II.
l~le composltlon of formulatlon B ls slmllar to that of formulntion ~ except that n small nmoullt oE polybutene ~d~r~ote~ t~a~

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re~in was found to be desirable because lt produced greater tack nnd Aomewhat better adlleslon. A suitAble polybutene renin i8 avAilable under the tradename INDDPOL
(medium molecular welght) available from ~moco Company of Chlcago, Illlnols. 111e MQ resin included in formulation n ha~ tl-e eeneric formulfl r~Qy where M ~ R3S101/2, Q Si4/2; nncl R preferably is ~ methyl group. Ilowever, R may be composed of nny otller alkyl group, particulsrly Cl to C~ alkyl groups 8uCh a~ methyl, ethyl, propyl ~0 nnd butyl'alkyl groups. 111e dlmethyl dlphenyl poty~iloxane gum lncluded in raw adhesive solution B
preferably hAs a molar rntio of phenyl groups to methyl groups ~t least about O.ltl nnd preferably between about O.l/t to 0.2~1.
A preferred formulation containing both dimethyl dlphenyl ailoxane gum and MQ resin for use in adllesive solution B i~ SILG~IP SR65~4, available froln tlle ~eneral ~,lectric Company. ~ preferred MQ re~in to be added to adllesive solutlon B ln avallAble under the tradename CR542 2a from Gener~l Electric Company. Another MQ resln sultable for u~e in adheslve solution B is ~old under the tradename C42-2109~from Dow Corning'Co. A preferred formulntion contnlning both dimethyl ~iloxane gum and MQ resin for use in ndhesive solution B may be purchased under the tradename 280 A~adhesive from Dow Corning CompAny.
A suitable catalyst for formulation B i8 a diaryl peroxide type cataly~t, nuch an tllat containlng 2, 4 dichloro benzoyl peroxide WlliCh contalnB a phlegmatlc agent such a8 dlbutyl phthalate~ A catalyst of this type may be purchflsed under tlle trfldename CADDX TDP from Noury Chemical Company. 111e raw adheslve solutlon a~ set forth itl 'I'able II furtl)er contains solvents toluene, nnphLIl~, xylene nnd'n-butyl acetAte in the proportions liste(l.
o~Qv~o'~es .

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~ lthougll tlle pre~erred cntQlyst shown in Table~q I arld II 18 ~ dlnryl peroxide, such ns 2, 4, dichloro benzoyl peroxlde, otller cntaly~tq may be employed. Other catalysts lnclude, for example, diacyl peroxide; amlno ~qilanes; secontlflry or tertiary ~mlnes; or ~n orgnnic titana~e nuch as te~t;abutyl titanate available under the tradename rryzoR T~r from DuPont Compnny of Wilmlngton, Delaware. ~lternat~vely, the c~talynt may be omitted and the polymerl~ntlon reactlon lnltlated by other means such as electron benm contact.
Although the ~olvents ll~qted ln Tables I nnd II nre most deslrable, other solvents may be used, such an, for exnmple toluene, naphths and esterq quch ns ethyl acetMte and butyl ncetate.
Although dimethyl dlphenyl polysiloxnne gum ls preferred any methyl/phenyl polyslloxane gum may be used.
Prefernbly, the methyl/phenyl polysiloxane gum has n rtlolar ratio of phenyl group~ to methyl groups between about 0.1/1 and 0.2/1. When employing n8 a basic ingredlent one 2~ of the gum/resin mixtures recited above, the polymeri~ed pressure sensitive adhes~ve product ndvantageously ncludes between about 0.1 to 15 weight percent of additionnl MQ ~esln nnd between about 0.1 to 2.0 weight percent catalyst. Typically the welgllt ratio of rne~hyl/phenyl siloxane gum to dimethyl siloxane gum is in a range between nbout 1/3 to about 3/1 nlthough a weigllt ratio npproaclling 3/1 is preferred.
Either oE the adhe~ive ~olution~ A or B may be made by mlxing the constituents listed ~n Table I ln a conventlon~l closed mixing vat until a hornogeneouq sc-lution is achieved. Although the vnriou~q components may be added ln nny order, lt is adv~ntageotnq to premlx the catalyst and ~qolvents followed by additloll of the ~ ~QI~oteS tl`Qd~ ~a~

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remaining compollents. 11le homogeneou8 raw solutlon is then coated onto n releAse substrate, typlcally composed of a paper sheet overcoated with fl release coatlng 6uch a8 conventionnl silicone release fluirls; e.g.
5 polyclimethylvlnyl siloxAne fluld containing npproprlnte catalysts sucll a8 one containing a noble metal complex.
Ihe overco~ted release substrate forms an Adhesive lamlnate sheet which is tllen drletl, typicAlly ln convention~l convectlve drlers operatinp, between 10 approxlmately 100F l:o 200F', in or-3er to evaporate tlle solvents contained ln the raw adheRlve coating. The dried adhenive lamin~te 58 then pnssed througll a curing oven operatlng nt n tempernture level of between about 200F to 350F, wherein n crosslinking type 15 polymerization re~ctlon occurs between the ~iloxane gurns, the MQ resin, ~nd the catalyst.
~ le adllesive lnminate slleet contalnlng the cured pressure 6ensitive adhesive product may be tran~ferred dlrectly to a surface of the semipermeable membrane of a 20 transderrnal thernpeutic device. T~-an~fer may be sccomplished by passing t:he Rdhes~ve lflminate slleet nnd the semipermeable membr~ne' film tllrough a conventional laminator. lhe adheslve coated semlpermeable membrane m~y then be cut into deslred shapes for use ln manufacture of 25 transdermal thernpeutic devlce~. In use oE the tr~snsdermal device, the patient will peel off the release substrate portion of the fldhe6ive laminate sheet thus expo6ing the adhe6ive coated semipermeable membrnlle 80 that direct contact can be m~de between the ndhesive 30 coated semlpermeable membrane and the human slcin.
Varlous performance tests for the polymeri~ed pressure sensitive adlleslve product were mn(le for formul~tlons tabulated in Table I nnd lIo Ille results of the performance tests nre tnbulnted in Tnble III.

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I'ABLE I
Pressure Sensitlve Adhesive (PoS~A~ ormul tion Raw Aclhe~ive Solution A

Mlxtllre of Dimethyl-DIpllenyl 36.9 Slloxane Gum Plus MQ Resln (e.g. SILGRIP SR 6574) ~ddition~l MQ Resin 0.5 (e.g. CR 542) Mixture oE Dlmethyl 12.5 Siloxane Gum Plus M~
Resin (e.g. 280 A ~dhesive) C~t~ly~t (e.g. Diaryl Peroxlde and Phlegmatlc A~ent a8 in CADOX TDP30.2 Solvent 1 Toluene 15.4 Solvent 2 Naphtha 15.1 Solvent 3 Xylene B.3 Solvent 4 n-Butyl Acetate 11.1 1 00 .() ' '' ' ' ' :
.

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I~BLE I (CON'r.) ~rl~d ~ Sensitive Adl1esive_Product A
R~w ~dhesive Solution A

S MLxture of Dlmethyl Diphenyl 73.6 , Slloxnne Gu~ Plu8 MQ Re~in (e.g. SILGRIP SR 6574) Additlonal MQ Resin 1.t (e.g. CR 542) Mixtu~e of Dimethyl Siloxane Gum 24~9 Plu~ MQ Re~in (e.g. 280A Adhesive) Cntnlyst ~e.g. CADOX ~DP) 0.4 1 00 .0 . . . _... : . . , .
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~7~5 1`ABLE II

Pre~sure Sensitive Ad~!e~ive (POS.~ Formulation 8 Raw ~dheslve Solution B

Comp., Wt.%
MLxtu~e of Dimethyl Dlphenyl 34.9 Siloxane Cum Plus MQ Re~ln (e.g. ~8 in SII,GRIP 6574) Additional MQ Resln0.9 (e.g. CR 542~
Mixture of Dlmethyl Slloxane Gum ` 12.6 Plus MQ Renin (e.g. 280A Adhesive) CatAlyst 0.2 (e.~. CADOX TDP) Polybutene Reflin l.7 (e.g. Indopol 300) Solvent 1 14.8 Toluene Solvent 2 14.2 Naphtha Solvent 3 8.3 Xylene Solvent 4 n-Butyl Acetatel2.4 100.0 ~ ' ' .
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~L'æ7~ 5 T~LE II ~CONT ) ~olymerized Pre~sure Sensitive Ad1!esive Product B

Comp , ~t~70 , Mixture of Dimetl1yl Dlpl1enyl Siloxane 69.4 - 5 (:um nnd MQ Resin (e.p,. SILGXIP 6574) ~dditionAl MQ Resin . 1.8 (e.g. CR 542) Mixture of Dimetl1yl Slloxane Gum and 25.0 MQ Resin (e.g. 280A Ad11esive) Catalyst 0.4 (e.g. CADOX TDP) Polybutene Resin 3.4 (e.g. Indopol 300) 100.0 ,: .
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._ - .- , ' ' 111e production of a pressure sensitive adhesive in accordance with the inventlon lb further illustrated by the followin~ nonlimitln~ example:

EX~1PLE
~ batch of raw adhe~ive solution wa~ prepared in accor(lance wlth either of the formulations oE Tables I and II. Ille catalyst was dlRpersed flrst lnto the solvents and the solvent6 with disper~ed catnlyst therein were then stlded to"the siloxane gurn nnd MQ resin constituents.
Disperslng the cataly~t flrst in the solvents retluced the rnixing time requlred to nchleve n homogeneou~ solution.
~fter the raw ndhe61ve solution hnd been formed in accordance with the forrnulation shown in Table I the solution was mlxed within a closed senled drum with n hlgh speed air driven agltnting mlxer.
The mixing wns contlnued under ambient condition6 until a homogeneous raw adhesive solution wn6 obtnined.
~le raw adhe~ive solutlon wa~ then coated onto a release substrate which was composed of a psper sheet precoated with a polydimethylvinyl 6iloxane fluid with the noble metnl complex catalyst 7p48 of ~ow Corning Co. Ille raw adhe~ive was coated onto the release substrnte u~ing conventional three roll reverse rollers to achieve a coating thlckness of about 3.5 mils. Ihe release substrate coated with the raw adhesive solution formed nn adheslve laminate sheet.
The adheslve laminate sheet wa~ then passed throu~h a conventional convective coater drier, opernted under four temperature zone~. The flrst zone lncluded temperatures between about 80 to 125F; the second zone between about 125 to 200F; the third zone between about 200 to 250F and the fourth zone at about 350F.

. ..

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~;27~

~he adhesive laminate sheet pAsAed continuously through the convectlve drier at ahout 40 feet per minute. The total length of the four zones was about 100 feet. As the adhesive laminate passed through the first two ~ones of the convective oven the solvents evapornted from the raw adheslve solution which Wfl9 coated onto the release substrate. Ihen as the adhesive lamlnate continued through zones 3 nn(l 4 i.e. the curing zones cro6s-linking ~olymerlzatlon reactlon occurred formlng the polymerized pressure sensltive ndheslve product.
lhe a(llle61ve lamlnate nheet contalning the polymerized pressure sensitive adhesive coating wa~
transferred onto A surface of a ~emipermeable membrane for use within a trAnsdermal therapeutic devlce of which V.S.
Patent No6. 4 200 098 and 4 201 211 are merely illustratlve. A conventional laminator was used to transfer the adhesive laminate onto the surface of the semipermenble membrane. The semipernieable membrane sheet with the attacl~ed adhesive laminate was then cut ln predesignated shapes or stored in rolls for use in connectinn with the manufacture of transdermal therapeutic devices.
It will be appreclated that other formulations for the pres6ure sensitive adhesive product may be prepared in a manner similar to that set forth above without departing from the splrit and scope of the lnvention.

Claims (6)

1. An adhesive that is permeable to medicinal fluids comprising:
the polymerization product of a methyl/phenyl siloxane with a dimethyl siloxane gum and an organosiloxane resin.

2. An adhesive as claimed in Claim 1, wherein said resin is composed of monofunctional and quadrafunctional siloxane units.

3. An adhesive as claimed in Claim 1 or 2, further including a catalyst.

4. An adhesive as claimed in Claim 1 or 2, further including a diaryl peroxide catalyst.

5. An adhesive as claimed in Claim 1 or 2, in combination with a polyfunctional derivative of a polyfunctional alcohol applied thereon.

6. The method of preparing an adhesive for the transdermal passage of medicinal substances, which comprises:

(a) providing an aryl polysiloxane;

(b) providing an alkyl polysiloxane;

(c) providing an MQ organopolysiloxane with multifunctional siloxane units; and (d) polymerizing the mixture of said aryl polysiloxane, said alkyl polysiloxane and said MQ polysiloxane.