Note: Descriptions are shown in the official language in which they were submitted.
~78~
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
- : .
''
,' ' ' '
,
. .
~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
'' ' ' ~ " , ............................ ~
-
~7~3~V~
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.
~L~7~
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
,,--
//
/ / ..................... . . . . . . . .. . .. .. . . . . . . . .. . .. .
- 7a
~78~
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
-,, . .
,: .
~a~7~
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
.. . .
.
~L~7~
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~
~ - .
~ ~7~
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
.
~8~
~ 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~
'. ' ' . ' ' : ~ ,
,
,
~'~7~
14
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.
~'~781~
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 .()
'
'' ' ' '
:
.
,
.
,
~27~
16
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
. . . _... : . . ,
.
..
~7~5
17
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
~ '
' .
,
.
~L'æ7~ 5
18
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
,: .
'
7~ 5
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21
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.
. ..
' ' ' ' ' , ' ,
.
~;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.
