CA1324419C

CA1324419C - Transdermal drug delivery device

Info

Publication number: CA1324419C
Application number: CA000596618A
Authority: CA
Inventors: Chana Reller; Joseph Gross
Original assignee: INVENTOR'S FUNDING CORP. LTD.
Current assignee: INVENTOR'S FUNDING CORP Ltd
Priority date: 1988-04-14
Filing date: 1989-04-13
Publication date: 1993-11-16
Anticipated expiration: 2010-11-16
Also published as: EP0337642A2; JPH0236885A; IL86076A; ZA892541B; AU611791B2; AU3275089A; EP0337642A3; IL86076A0; US5053001A; US5002527A

Abstract

ABSTRACT

An iontophoretic device is taught which is positionable on skin or a recipient. An insulating member includes therethrough at least one reservoir containing a drug between outer and inner (recipientwise) electrodes adhered to surface of the insulating member. The inner elctrode preferably is spaced from a rim of the drug reservoir by the same distance as the depth and width of the reservoir,the electrodes are connected to field generating means which draw the ionic drug into the patient and outward from the rim of the reservoir.

Description

T~ANSDERMAL DRUG DELIVERY D~VICE

2 by ! Chana ~eller and Joseph Gros~

BACKGROUND OF THE INVENTION
, Tne present inventlon relates to a devlce ~or dell~ery o~ cbar~ed dru~ molecules throush the skln, employln~ sn ionto~horesi~ Phenomen~.
'' ''.

Recentl~, lontoP~ore61s has ~alned lncreased attentlon as ~n e~ective method ~or toplcal appllcation o~ ionlc a~ents or dru~ b~ Promotln~
ab-orption throu~n kin o~ a human or snlmal~
Iontopbore-ls tec~nl~ue~ are dlsclosed ln, ~or ``
exam~lo, ~la88 JM Qt al., Int. J. ~Qrmstol. 19,519 ~ i (1980); Ru-~o, J.., A., J. Ho~. Pb~rm. 37,843 - ~ ~ (1980); G n~aros- LP et al., J. Pbarmacol. Exp.~Ther.
2~2,377 (1980~; Hlll JM et ~ nn. NY. ~csd. Scl. ;~
28~,60~ (1977~.~

Ionto~horesis ~- b-en used ~or trsnsdermsl delivery r ch r~ed molocule dru~s lnto the skin. The method om~loY- a dc volt-~e botween two elQctrodes, attached ; to tbo ~kln. and under one o~ said electrodes there Provided a laYer o~ t~e dru~ to be lntroduced. ~he dr~ mi~2rat-d lnto tho s~in dùé to the applled ~ . . : ,.
~ lootric ~i-ld. ` `~

132~19 Bec~u~e o~ im~dance o~ t~e outer la~ers o~ the s~ln, tne dru~ ~enetrates the bodY's lnter~tltlal ~lulds, ~rom whlc~ it 18 dl~used into the bodY

These electrl~ Pleld~ contain a lar~e amount oP ions, by whlc~ electrlc current i8 Passed lnto the bodY A
msln dlssdvanta~e ~ound ln lontoPhoresls is the ~act that it causes burns and lrritatlon to the skln Thls e~ect can be ex~lalnad b~ the hi~h im~edance between the two electrodes whlc~ result~ in the develoPment o~ a very hl~h ~owQr converted lnto heat t~usl~
causln~ skln burn~ In order to ellmlnàte these s~ln burns t~e lmDe~ance between t~e two electrodes must be decreased In an e~uivalent clrcuit ~to that descr1bed above ~uch a- ehe hum-n membr-ne) Pllla et al de~cribe ln the Journal o~ hlectro Chemical Soclet~ 124 (1977) ;`
1698, a circult contalnin~ ca~acltors and resl~tors S~U~ t~y concluded that ln order to lncrease ml~ration current, the lm~edance o~ the capacitors and re-l-tor- should be decreasQd~

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~ 1324~19 T~e lmPedance o~ a caPa~1tor ls ln~er~elY
~roportlonal to tBe rr~<;lu~ncy. Incr~asin~: tl~e rrequency decreases the lmPedsnce o~ the capacltor and decreases the impedance o~ the human body.

ExDerlments ~howed tnat ap~lYln~ square w~ve ~ulse~
Or o volts to ~ and a dut~ cYcle o~ 1:1 at 50-500 kHz, and havin~ a ~e~k curr~nt o~ 50mA, wlth an avera~e current o~ 12mA, ~assed throu~h the ~uman bod~, without causin~ burns. T~e rOre~oin~ su~e~t t~at appllcation or pul~e~ at 8 current or volta~e or ~ariou- ~napes, at ~l~h ~re~uencY wlll àccomplis~ the deslred ob~Qctlves.
"

~notner wsy to reduce t~e bodY~s impedance ls to deorea~e tne o~mlc resistance. The ohmlc resistance betweQn two electrod~s depends on the con~i~uratlon ~ or t~e electrlc-l cell. In 8 pl~nar con~l~uratlon.
w~ic~ con~i~t- o~ two Planar ~arallel electrodes. t~e resi-tance dePends on the ~aP beeween thq electrodes.
By decreasln~ t~e ~a~ tne electrlcal ~leld lncre~se~i, cau~ln~ a decrea~e ln reslstance.
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In a concentrlc cylinder conrl~uratlon, mcst o~ the ohmic Potentlal dro~ occur~ near the lnner cyllnder and doe~ not dePend solelY on the electrode ~ap In a circular planar electrode, most Or the ohmlc pot~nti~l dro~ occurs st a reslon o~ the sa~e order Or ma~nitude as the radlus o~ thQ olectrode, and 18 ~roportlonal to the rsdlus By chan~ln~ the conri~uration o~ the electrode~, tn~ ohmlc reslstanoe can b~ cnan~ed too, thl~ 18 ~hown bY J Newman et al in ~lectroc~Qmical SYstems~ ~ubll~hed bY ~rentice-Hall, ~n~lewood cllr~8. ~w Jer~ 1973) Th~r~ 18 no convenient w Y to Produce ~lanar or cyllndrlcal conrl~uratlon-,;usln~ the human body as th~ ~le~trlcal medium ~he clrcular planar electrode 1- mor~ conv~nlent However, ie wa- hown b~ aoki et al~ ~lectro chQmlc~l Journal~ th~t thln lon~itudlnal electrod~- rece~bla tho b~bavlor Or cYlinders~ This ~act al-o enable- U80 0~ t~in recean~ular electrodes . -stron~ o~rec~ ot cell con~i~uràtion~in iR (current x r~ t nce~ dro~ wa- nown bY Bond Qt al, ~-lectron-l Ch~ (~9a4 ~ 257 TheY were àble to take el~ctroch~ical ~ m~a-urement- Or ~xtre~elY non :. - ~ . ` . . .
oonductlve electrol~t~-, at tQmperatures down to the rr a~ln~ ~olnt o~ tn~ olv~nt (Qut-ctr1c mixtures) olv~nt~ uch a-; acontonltr~le and Rcetono -- b~
usln~ mall clrcular elQctrodes 1324~19 At these low temperatures measurement lar~e electrode~ cannot be utillzed because ohmic reslstance ls very ~l~h~

The electrolYte i8 non-unl~orm and may contaln even insulatln~ re~ions Even thou~h the ~uman body ls non-unl~orm and has hl~h s~ecl~lc rQs1stance~ the e~ect o~ size and s~ape o~ the electrodeQ in~luences the reslstance between t~e electrode~
. . .

Other ~tructures and dQsl~ns o~ lontophoretlc transdermal dovlccs were descrlbed in the rollowin~
pat~nts 1~ Unlted ~ln~dom Patent Ga21043a8 de~crlbin~ a li~t `-devlce con-l~tln~ Qssentiall~ o~ two electrodes, a current bein~ conducted betwe~n thes~ Qlectrodes throu~n a ~ati-nt~a bodY~ cau~ln~ an lonl~ed ~ru~
- : :~ . .
~ to ba ~orced tnrou~h ehe kln - ~ .
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2 Unltad Stato- Patent 4,141,359 dQsorlbes an lonto~nore-i- d~vlco, havin~ means ~or ;~
predeeermined settln~ o~ llmlts o~ im~edance , ~ ~ enablin~ control o~ currQnt~ hence control o~
~ dru~ rlow. : : .
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1324~19 Unlted State-~ Patent 4,164,226 de8~ribe8 ln~lbitlon o~ persPlratlon~ slt~ou~h lt al80 ~alntalns ~eneral lonto~oretlc a~pllcatlons.
Burns on t~e skln are ellmlnated by lnterpoQln~ a rel~tively tnlck Dorous and pre~erably molstened materlsl b~tween a ne~atlve electrode and t~e skln~ ElectrodQs wlt~ se~arate conductive areas are su~ested.
..

4~ unltQd States Patent 4,~19, og2 descrlbes a structure o~ nn ~l~Qtrode ror use ln eleotro~oratlc devloqs ~-vln~ ;
a membranq throu~b whlch ions can ~l~rate lnto kln~ and in~lude an eleotrode mount~d on toP o~ a ~.
re-orvolr oonnected to an ener~ source. .~.

, 5. Unlted State- Patent- 4. 55r. 724 and 4, 64a, 689 as lt- c~ntlnuatlon ln part do-cribQ 8y8tem8 whereb~ `
dru~- re obar~ed elqctrlcallY ln a reservoir and ~ ~ drlven toward- t~o kln lnto t~e ~lood Jtream b~
:~ . , - .
~a-sln~ a ourrant tbrou~ t`~e skln between two ; olectrodQ~ wblC~ are connocted to a Power ~ource. . ;~

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132~419 6 Unlted State~ Patent 4 764 16~ de0crlbes a devl~e ~or iontoPhoresl~ w~lc~ lncludes a Dul~e senerstor a wor~lns ~lectrode ~nd a counter electrode T~e devlce ~as means ~or dlschar~lng and c~ar~ln~ the c~ar~es accumulated ln t~e electrodes durins lntermlssion periods between t~e pulse~ senersted b~ the pul~e s~nerator T~e devlce clalms to ellmlnate the lrrltatlon and burns Or t~e ~in T~e e~ectlve oPeratlon time o~
t~Q devlce 18 20X o~ t~e total tlme applied at relatively ~ls~ currQnts o~ 10-30mA ~e maJor ~eature o~ sald Datent 18 reduction o~ skin capacitor l~Dedance b~ uslns a ~ls~ ~requency pul~

T~e loto~orotic devlce dlsclosed ln Drlor art known to u- ~onerall~ include connectln~ and output ter~inal or a contlnuous dlrect current ~enerator or ~ul-- ~enerator to a workln~ olectrode composQd o~ a aatal ~late or ot~er conductlve substances T~ese la-t mont~oned electrodec are covered wlt~ a sel or a mol-t n~d ~ad or ~orous matQrial lmPre~nsted wlt~
an ~u.ou- olutlon, lncludln~ an ionlc drus and a counter l-ctrode tructured ~lmllar to t~e worklns ~ erod~ oot ~1e~oot tb~ dro~

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~32~19 - From the Sore$olnsc descrlPt10n . lt .Qhould be clear that the actual arplicatlon o~ lontoP~eresls t~rou~h these ~rlor art tec~nl~es hss maJor dl~d~ant~es lncludln~ but not llmited to low e~Plcienc~ ~nd skln burns ~lthou~h iontoP~orsls 16 a very e~ectlve met~od ~or dru~ aP~llcatlon tbese dlsad~anta~es ~a~e li~lted lts wldespre~d use By way o~ exPl~natlon, ln all o~ these ~ore~oln~
iontopherQsls ap~roacbes tba ~ollowln~ maJor ~roblems recur Becau-e o~ the Al~n im~edance o~ a buman or anlmal body, an appllcatlon oP electric CUrrQnt C8U es a l-r~ar Dower to d~welo~ wblcb convert- into beat w~e~ ro~ultant ~urn- an~ lrrltation to the skln o~
t~e reci~lent u-~n~ t~e devlce~

2 ~locerode de-len- ln device de-crlbed ln tbe ~rlor are known to u- dO not teach s~eciflc ~eometric - r latlon- to olve t~1- burn ~roblem by roductlon o~ o~mlc re-i-tance o~ the Jkln Tbls insdRquacv overCome bY t~e devl¢e~ wnlcb aro thQ su~Ject o~ t~l~ invontlon .:

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- 132~19 Accordingly, it is an object of the present invention to eliminate the above mentioned problems in the prior art by providing an iontophoretic deYice capable o~ sufficiently 5 decreasing the skin's total impedance (ohmic resistance and capacitor impedance) thereby allowing ~ .
an iontophoretiC device to be used under a :
relatively low voltage and a relatively high electric current, also permitting the iontophoretic device to be applied safely to the human or animal skin under a hig~ current without causing irritation, burns and rubefaction of the skin. ~
Another o~ject of the present invention is to provide an iontophoretic device which is light in 15 weight, easily manufactured and assembled and : .
capable of direct and simple application to a ; ~ `
recipient's skin and which can be operated over a long period of time. ~
In accordance with a particular embodiment .:
of t~e invention there is provided an iontophoretic ;~.
device comprising in combination: `
an insulating member hàving an inner ` `
surface positionable adjacent skin of a recipient, at least one reservoir in the insulating --member and adapted to contain an ionic drug and terminating in a rim formed by said inner surface, ..
an outer electrode in contact with the ~ ``
drug, .
an inner electrode on the inner surface ""
and spaced from the rim to define a gap ;`.
therebetween, :;`"
field between generating means for ~
energizing the electrodes to draw the drug ``, ` `
recipientwise and outward from the rim. :

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- 9a -In accordance with a further particular embodiment of the invention there is provided an iontophoretic device comprising in combination:
an insulating member having an inner 5 surface positionable adjacent skin of recipient, at least one reservoir in the insulating member and adapted to contain a drug and, terminating in a rim formed by said inner surface, an outer electrode in contact with the lo drug, . .
the reservoir having a depth measured from the outer electrode to the inner surface, an inner electrode on the inner surface and spaced from the rim to define a gap 5 therebetween, the gap of similar dimension to the depth, field generating means for energizing the electrodes to draw the drug recipientwise and .
outward from the rim.
DESCRIPTION OF THE DRAWINGS
Figure 1 is a schematic plan view of an embodiment of the invention in the form of a patch and having fork like grooves as drug reservoirs, and ;
~lso shows complementary multi electrodes. `
Figure 2 is a schematic end view of the patc~ shown in Figure 1.

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132~419 -10- ~, Fl~. 3 1~ a plan vl~w showln~ another and pre~erred embodlment o~ the inventlon includln~ circular holes .
88 t~e dr~ ~e~er~olrs, Bnd 8 contlnuous lnner electrode s~sced ~rom the holes.

Fl~. ~ ls a cross sectional vlew taken on llne 4-~ o~
~1~. 3 ,'' .

Fi~. 5 ls a plan vi~w s~owln~ anot~er embodlment havln~ rin~ llke ~rooves Pormlns dru~ reservoirs wlt~
contlnuous lnner rln~ llko electrodes spaced ~rom the eroove-~ ~

. :,` `' Fl~. 6 18 a cross sectlonal vlew taken on llne~ 6-6 o~ Fi~. 5. ~`
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Fl~. 7 1- a Plan vlew lllustratin~ anot~r embodlment o~ the inventlon ~avln~ s~uare ~rooves ~ormln~ dru~
r~-Qrvolrs, with a contlnuous lnner electrode s~aced ~rom th~ holes.
Fl~. 8 1- a ~lan ViQW lllustratin~ anot~er embodlment . .:
~avln~ a snail likQ ~rOovQ ~ormln~ a dru~ reservoir.

and a snall llke inner electrode spaced ~rom t~c ~ ' . ~, .
~roove.
., . ''.' ' Fl~. 9 lllustrat~s sc~ematlcall~ an electrlcal dia~ram o~ a pre~erred ~ower suPPly unlt.

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-11- i~2J,~ 9 Fl~. 10 lllustrates schematlcall~ a ~re~errc~
~re~uency wave-len~tn sequence 0~ the Pulse ~enerator.

FiS~ a ~rau~ 0~ current enterln~ the reclplent' Q bodY.

FiS. 12 show~ 8 plan v~ew o~ a ~atch accordlns to this inventlon.

Fl~. 13 is a cross ~Qctional vlew o~ the ~atch member ~`
tak~n on llne ~3-13 o~ ~lS. 12.

Fi~. ~ i~ a Cro-8 octlonal vlow o~ t~e Power su~ly unit taken on llne 1~ . 15.
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FiS. 15 1- a pl~n viow`o~ t~e power Jup~l~ unlt.

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Fl~. 16 18 a croaa a~ctlonal vlew o~ the ~atch wlth t~e power u~ly unit a~-embled t~erewlt~, and ~hown ~lled to a reclplent~8 akln. i`

F~ ~. 17 18 a Cro-s sQctional vlew o~ a patch with t~e power upplY unlt, ~a~lns an srran~ement s~ecl~lcally ;~

de-i~ned ~or u-e oX li~uld dru~ olutlons.
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-12- i32~19 DESCRIP~ION OF THE INVENTION
An lontopboretlc device accor~ln~ to t~e present lnvention comprlse~ a gup~ortln~ member ln~ludln~
mean~ ~or attachln~ same to a human or anl~al reclplent w~o ls to receive a dru~ T~e lonto~horetlc devlce 18 covered by a relesse protectln~ ~oll on lts slde to be attac~e~ to t~e recl~ent'~ skln Connected to t~e sUDDortin~ member 1~ a contlnuous thln conductive sbeet ad~ered tC an lnsul~tin~ l~yer ~avin~ cavltles ~oln~ tnrou~ the lnsulstln~ la~er pre~erabl~ at varlous lo~at~ions T~ere are ~olar solutions or ~el- oP lonic dru~s lneroduced into the CaVltlQ8. On an Inner sur~ace o~ tbe lnsulatln~ laYer i8 a t~ln ~re~erabl~ contlnuous conductlve s~eet ~ormln~ n electrode connectable to an electrlcal DowQr 8u~1y Dre~erabl~ consistin~ o~ a power source, oPtiona~ a~ln~ a ~ulse ~enerator, and 8 current control means ~11 o~ratlvel~ connected to sald multi electrode~ bY two conneQtor~ 80 that when the electrlc ~o~er ~ource i- switcbed on t~e pulsln~
~enerator ~up~l~e~ Pulses Or hl~h ~requency, wa~e~orm- ln a de-lred dut~ c~cle, under volta~e ~rom the ~ow r ~ource T~e ourrent caU-es ml~ratlon o~ the , .
~ol r lon~ o~ tbe dru~ beln~ ap~lled lnto t~è

r cl~lent tbrou~b lt- kin ~be combination oP the . ', '.

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-hl~b ~re~uency o~ the ~ulse and the specl~lc electrode system oP thls lnventlon reduces the bO~Y
t ~pedance and increaseS the CUrrent mi~ratlon at relatively low volta~e~ This electrode Porm snd mode 0~ o~eratlon increase the devloe'~ e~iciency wlthout csusln~ undeslrable lr~ltatlon or burn~ to the human sX~n. ...

In onQ embodlment o~ t~è lnvention the electrodes are in a ror~ or contlnuous thin conductivo layers adhered to an lnsulatln~ ~late havln~ ~ork shaPed ~rooves ~llled wleh a ~el or a cellular spon~e ab~orbin~ ~aterlal contalnln~ t~e dru~ ln solutlon T~re 1- al80 ~rovlded a thin conductlve la~er in the rm Or a co~lomontarY ~orm to said ~roove~ and lntorme-hed betw~ôn tbo ~roo~Q~ To acbleve hlSh e~lcien~ o~ t~Q devl~Q the Wldtb o~ ehe ~rooves and tbo wldtb o~ t~e conductlvo layer and the dlstance betwoon e~Q laYer nd t~o ~roovQ or ~roove~ sbould ~11 bo o~ual in c180 to t~o ~opt~ or t~e ~ellul~r a~on~e ~l~Yer or ~el contalnln~ the dru~

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In another snd moQt Pre~erred embodiment o~ tbe in~ention tne ~lectrode~ are ln the ~orm o~ a ~ontlnuous thln conductlve l~Yer connected to an lnsulaeln~ layer whlc~ has punched clrcular holes throu~h lt T~e ~oles a~e ~llled wlth a ~el or a cellular spon~e absorbln~ materlal contalnin~ the drus solutlon Thls embodlment lncludes also a complementary circular thin conductl~e layer connectQd on top Or sald ~nsulatln~ la~er Sald clrcular la~er beln~ lar~er in sl~e than t~e punched nOle8. To scbiQ~R e~icienc~ o~ the devlce the de~th and dia~eter o~ t~e sald cellular s~on~Q materlal or ~el contalnin~ t~e dru~, ln tne ~ormed or punobed ~ole, ~rererably ~ould be e~ual to the radiu~
d~ ~erentlal or tbe punc~ed thln to~ conductive layer~ and the radiu8 Or the PunchQd hole .
In anothor ~mbodlment o~ tne lnv-ntion the electrode ~y-t~m i8 in the rorm or a serles o~ concentric clrcul r ~rooves ~oln~ t~rou~h sld lnsulatln~ layer contalnln~ t~e cellular absorbent mstQrlal or ~el wltn enQ dru~ and navln~ complQmQntary ~or~ed rln~s o~ a thln conductive la~er. For e~lciencY oP the d~vlc~ e~ wldt~ o~ the rln~s, t~e width or the ~roo~e- and the di~tance between th~ rln~ and the sroovQ~ Pre~erably snould be Q~ual or clo~e in slze to t~ de~t~ o~ t~e cellular màterial or ~el contalnln~ tn- dru~

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~2~

In ~notner em~odlment or tne lnventlon ~he inner electrode 1~ in the ~orm o~ ~unc~ed ~mall -Q~uares ln the ln8ulstln~ laYer lnto whic~ the cellular materlal or ~el contalnln~ t~e dru~ 1~ lntroduced A t~lnl~
~ormed conduct~ve laYer connected to thQ lnner sur~ace o~ tne lontop~oreslo member i8 ln the ~orm o~
complementsriv lar~er ~uares surroundin~ tne puncned squares Tne best eP~lclenc~ o~ the devlce wlll occur wnen t~e dept~ o~ the said celiular materl~l or ~el ln tne Punc~ed ~oles 18 slmllsr ln sl~e to tne sl~e o~ tne puncned s~uare and sl~ilar ln 81~e to tne dlstance bet~een t~e tnin to~ conductlve la~er to tne ~uare, nd t~e wldtn or t~e conductl~ s~Uare ~rld~

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In not~r ~bodl~ant o~ tna lnventlon tne electrode y-te~ 1- in tne rorm o~ a continuous snall llke ~roova ~uncned tnrOu~ tne ln~ulstin~ laYer and rlll - d witn ~ld cellular mstarial or ~el oontainln~
. . .
tna dru~ Tna tnin~conductiva laYar i- ~ormed as a com~l-~ent o~ t~e ~n~ll llk- ~roove ~nd conneoted ln tne Pace betwa-n tn- ~rooveg on top o~ tne .....
ln-ulatln~ laYer~ E~icl~ncY io lmProved when thQ
d~t~ o~ tne c~llul-r ~terlal or ~el 18 si~llar or ual to tne ~roov~ wldt~ the wldt~ o~ t~e lnner oloctro~do, and tne dl-tanco between the rlm of the ~roovo and ~ald oloctrodo i .. . . .
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i -16- 132~19 The electrl~ power sup~ly unlt and the ~lel~
~ener~tin~ me~ns mav conslst o~ a Power source the ~orm Or a batterY havln~ 8 volta~e or 3 to 9 volts Tbe batterY can either be a dry-cell b~tterY a lithlum bstter~ or ~ rechsrseable nlckel-cadmlum batterv enablln~ t~e user to have a minlmum o~ 8 to lo ~ours at a re~ulred current ran~e o~ 5-50mA
Optionallv t~erQ ~an be a pulse ~enerator prerersbly bavin~ a rre~uencv ran~e or 50-500 kH~ and a swltch mec~anlsm ~laced in Parallel between tb~ electrodes mlcroProcessor enables t~e usQr to establls~ a tberaDeutlc ~ro~ram and 18 ln serles wlt~ the ~ulse ~enerator.

In a ~urtber e~bodlmQnt Or tbe in~entlon t~e dru~
re~r~oir are arr-n~ed ln one or more ~oles or ~roo~a~ rormed rrOm t~ ln-ulatln~ laYer anq eitber lll-d ~ltb a dru~ containln~ sel or com~r~se a cellul r or ~mllar ab~orb~nt ~on~e materlal ~oaked wltb tb~ dru~ solutlon S~e re-ervolr~ can be m~de o~
~lt~er-- cellulo-e ~ rlbrous elastomerlc or ~la~tic o~m~d ~at~rlal S~ ln-ulatln~ layer between the l-ctroda- can be mad~ or a Dllable rlastlc or~ -la-tom ric ln-ulator material actln~ also as a ~`
bolder ~or t~ c~llular s~on~e or material sosked `~ ~

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-17- ~32~

wlth the dru~ or rOr sald ~el contalnin~ t~e dru~.
T~e thln conductlve electrode sheet~ csn be made o~
thin alumlnum ~oll or anY other sultable metal ~oll or oP a t~ln carbon layer or c~rbon ~lber non woven web or woven carbon ~iber mattin~ Tbe conductlve electrodes can pre~erablY be made oP a sultable substrate coated wltb sllver or anotner sultable conductln~ materlal Pre~erablY at a coatln~ thlcknes~
ln t~e order o~ 5M~
' '.

In anotber ~mbodlment o~ tbe lnventlon t~e ~ower suD~ly unit or ~leld ~eneratin~ mQans i~ mounted on a se~arate me~ber connected (~or example) to t~e eloctrode and dru~ carryln~ member b~ two ~ulck connector8, one to eacb o~ t~e eleQtrodes ~reciplentwise inner catbode or outer anode) ~his ~mbodt~ nt onables USQ oP tbe electrode and dru~
carr~in~ m~ber ~or a sln~lQ trQatmQnt and ~or any re~uired lQn~tb o~ tlme or ~or anY re~ulred 8~ecl~ic dru~ Onc~ tbe treatment l~ completed or t~e dru~ ln t~e res rvoir i8 exb~u~ted tbe electrodQ member (wlth all tbe related comPOnents~ can be dlsposQd o~ and t~e ~oWQr 8u~1y un~lt or ~iold ~neratin~ mean~ can be di-connected and reused ~or a next treat~ent untll tbo ~ownr sourco or batterY ls ex~austed ;~ : '`. ' . ' ". -:
'."','.:, ,'`''''',""',' ': ' ~".',.: .' ' '...'. '. ' ....
~ ~, ,` -18- 132~419 In another embodlment o~ the inventlon the dru~
re~ervolr 1~ ~peclricallY ~esl~ned to sdmlnlster 8 ll~uld solution o~ the dru~ w~lc~ wlll be 81r8t absorbed in ~ caDillar~ cellular absorbent laYer, an~
t~rou~h t~at layer, will enter tbe skln The construction o~ the lontoPhoretic devioe comprlses 8 supportin~ member wlth me~sns to attach s~me to the reclplent; The de~lce 18 co~ered b~ a rele~se protectln~ ~oil on the side to ~e attached;
Connected to t~e supPortln~ member 18 a continuous tnln conductlve ~heet ~ormln~ an electrode sdhered to a layor o~ a ca~illar~ ab~orbent material placed between t~e conductlvo sn~et and an insulatin~ la~er ~avin~ cavitles ~oln~ throu~h it at variou~
locationr~ On tbe lnner ~ur~ace o~ the insulatln~
1 Yer 1~ a thin coneinuou- conductivo sheet ~ormln~
n electrodo conn-ce-ble to an eloctrlcal power u~p~Y ~na ab-orb~nt l-Yar placad between tho Pirst ~lectrod~ and thQ ln-ulatln~ laYor i~ connected to a ~laxlblo soaled ll~uid rosorvoir contalnln~ t~e dru~ olution ~laced alon~ tne sldo or the upportln~ me~mber The resQrvolr has a tear o~P
~Qcbanls~ whlcb can be aP~lied b~ the recipient Prior u~e of the device, o that when the mechanlsm ls o~orated tho ll~uid olution in the reservolr is allow d out onto tbo ca4111ar~ absorbin~ laYer~ whlch , .. .
ab-orb- the solutlon and distrlbutes lt equ811~

~ rou~b the cavlties Or the lnsulatln~ laYer onto the `, `~ ~in of the recipient ~ ~, .
-19- i32~19 DE~:cRIPTIoN OF THE; PREF~RRE;D ~M80DIMENT

Fl~ 1 illu~trateg a devlce accordln~ to the ~resent inventlon and havln~ a ~lat contlnuous reclplentwlse outer met81 ~oll 2~ sdnered to the boetom (o~ter) sid~ o~ an lnsulatin~ ~e~ber 22 ~avln~ a ~roove 21 ~lll~d wit~ a ~el or a cellular absorbent materlal cont~lnin~ sn lonic dru~ The ~roove 21 i8 in t~e ~orm o~ a ~ork ln lts Plain ViQW a~ shown in Fl~ 1 ~n inn~r thln electrode 23 i~ ~or~ed a~ a mattin~
, . . .
~ork to ~roove 21 to ~ate wlth tines o~ the ~roove 21 ~nd 1~ connQ~tQd on the lnner slde o~ tbe lnsulatln~
laYar 22 The width or t~o ~roove 21 18 Q~U8l or ~ilar ln sl~e to th~ wldtbs o~ the clectPode 23 and tho dl-tance b~twecn tb~ o~cctrodQ 23 ~rom the rlm o~
tb~ ~roov~ 21 ~l-o the distance between the aloctrodo 23 ~nd tno rlm o~ tne ~roove 21 should be e~ual or imilar ln ~lze to the de~th o~ tbe cellular layer ~on~c or ~el wblCb contain8 the dru~ Leads 25 and 27 connect ~etal ~olls to connQotors 26 and 28 wnlcn r- connectad to thQ power 8up~1~ or Pleld ~-noratin~ ~ -n-~(not hown~

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132~19 Fl~ 3 lllustrates a prererred devlce ~ccordin~ to the preBent lnventlon havln~ a contlnuo~s metal ~oil 18 (wbich mAY be al~minum or a sll~er coated substrate) an lnsulstln~ laver 12 navln~ Punched holes 11 contalnln~ the dru~ in an absorbent cellular medlum or a ~Ql~ A thin contlnuous inner metal ~oil 13 18 connected on the lnslde (reciplentwlse) lnsulatln~
laver 12 wire leads 14 and 16 connect the metal roils 18 and 13 to a Power sup~lY unlt or ~ield ~eneratln~ mean8 (not shown) bv the two connectors 15 and 17 re~Pectlvel~ T~e de~th o~ the holes 11 i8 o~
t~e same or slmllar slz~ to the radiUs dl~Perentlal between t~e ~ole sl~e and ~oil as wlll be clear ~rom Fi~ ~

Fl~- 5 and 6 illustrateB a device accordln~ to the ~r~-ent lnventlon ~a~ln~ a rln~ shaPed electrode ~Y-t~m A ~etal ~oll 3~ 18 connected to the outslde Or n ln-ulatlon l-Y~r 32 h~vin~ r~n~ sna~ed ~roove~
31 rllled ~lth Qellular absorbent materlàl or ~el contalnin~ dru~ ~ ~cond metal ~oll member 33 also ln t~- ~or~ o~ a rln~ 1~ mount-d on the lnner sur~ace o~ ln-ulatin~ l~y~r 32 between the ~rooves 31 S~lckne-a Or t~e ~roov~ e~ual or simllar in slze to the di-t nce~ beeween the lnsulat~on la~er and roov~ and al80 t~ dlstance between the inner~
electrode nd the ~roove-` ~ ' ''.'',"' ' "", ,' -Zl- 132~419 Fl~. 7 illustrates an electrode Wlth s~u~re reservoirs ln ~lan view. Fi~ 8 lllustrstes an electrode Wlth a snall llke reservolr and ~om~lementln~ u~per (lnner electrode). Rererrln~ to ~1~8. 7, 8 ~nd 9, lt ~nould be noted that t~ey s~ow an embodlment o~ tbe Pre~ent lontoPboretlc device a~
a bloc~ dlB~ram ror slmPllcitY Or illustrstlon. -~

Fi~. 9 comPriSeS a power ~ource or ~leld ~eneratin~ -means 2 ~e.S~. a dr~ element bstterY havln~ a volta~e 0~ ~ V), a pul~e ~enerator 3 capable o~ ~eneratinL a voltB~ Pulse ~avlo~ a Pre~uencY Or 50-500ka~ as ` ^"
s~own in Fi~. 10. ~ wor~ln~ ele¢trode 4 containln~ an lonlc ~ent, a counter electrod~ 5, a buman or anlmal body decl~nated 6 connec~ed to t~e workln~ counter Qlectrode- ~ and 5~ and B 8wltc~ mechani~m 7. A
~icro~roce--or unlt 8 is lnc~uded Sor introdu~ln~ a o~e-et t~era~eutlc ~ro~ram.
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:. ' ~ -22- 132~19 The swltch mechanlsm 7 ls ln parallel to the human or anlmal bodY 6 ~or de~olarlzln~ the potentlals o~ the co~nter electrodes ~ and 5, prererabl~ ror brln~ln~
the polarl~ed potentials or the electrode~ ~ and 5 to an e~ual level simultaneouslY with sto~pa~e Or therspeutic pulses 9 ~enerated ~rom the rul~e ~enerator 3 That 18 sccordln~ to thls mechanism the resldual c~ar~e ~i Q Polarlzation~ in the polarlzatlon caPscltY 1~ dlsc~ar~ed or derolsrized by :
s~ortclr~ultln~ t~e electrode~ ~ and 5 When thls ~leld ~eneratin~ mean~ 18 aPplled to the numan or anlmal body 6, t~Q CUrrent passln~ lnto the bodY ls hown in Fl~ 11 Tnat 1~, durln~ output tlme ~eriod T or tn~ t~era~eutic ~ul-e s~own ln Fl~. 11. t~e curr~nt ~1 e , ~ul~e current Ia) Plows mslnl~ lnto ` k t~o ~ol ri~ation i~Podance o~ the skln Or the bod~ 6, ~nd t~ ionlc aSent conealnQd ln the workln~
oloctrodo ~ lc ~alnl~ endermlc~llY ab~orbed Stated dl~torontl~ tho rleld ~on-ratln~ mQans drsws the lonic dru~ lnto t~o Patlent and outward rrom the ra-orvolr Fl~ 12, ~3, 1~ 15 and 16 illustrato dirrerent views Or a comPlete ~atch m~mber b-rore u~e and when PPll-d to kln o~ a reciPient~

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-23- 1~2~19 Fls 12 shows a top vlew o~ a ~atch illustratln~ th~
member 45 connected to the recirlent not shown) and the powQr suPplY unlt or ~ield ~enerstlns means 51 havln~ two connectors 50 snd ~ connectln~ unlt 51 to member ~5 Fl~ 13 18 a Cross sQctlonal vlew o~ the devlce ~hown in ~ 12 The member ~S carryin~ the unit whlcn connects to t~e ~ower ~u~ly member 51 b~ connector~
50 and ~8, tnrou~n leads 4? and 4g al80 is connected to both t~ln mQtsl ~oil~ ~3 and ~
''`'', ~e insulatlns la~er ~2, snd tne dru~ reservolrs 41 re srooves ln the lnsulstln~ l~Yer contalnln~ either ~-llular materlal 80sked With ehe dru~ solutlon or a ~el contalnlne th~ drus ~ ~roeectlve dQt~chsble ~oll ~~
~6 oPtlonally ~rotects t~e devlce and thQ dru~ durin~
l~Pln~ and tora~e Fl~ 1~ and 15 lllustrate the ~`
Dow~r u~lY unlt or ~-ld ~eneratln~ means 51, witn :
two conncctors 50 snd ~a. Fl~ 16 lllustr~tes the devlc~ ~en pplled to ~um~n or ~nl~al skin 52 arter r~o~ln~ a dQtschablo ~oll ~6 . " ,:
: ~ ' . ' ,`''~' ' "
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i -Z4~ 132~19 T~e power su~lY unlt or ~ield ~ener~tln~ m~ans 51 1s connected to the member ~5 bY connectors 50 and 48 throu~ losds 47 and 49, w~ic~ are connected to thin metal ~oll electrode~ 43 and 44 resPectlvelv The dru~ solutlon 18 stored in the ~roo~es or reser~olrs) 4~ elther ln cellulsr ab~orbln~ material, or ln 8 ~el. Tbe member ~5 i8 attsc~ed to the skln 52 o~ a reci~lènt a~ bY a suitable adhestve ,~`` ``'~ .
When t~e batterY not snown 1~ switched on and t~e ~ulsln~ ~enerator starts to 8UPPl~ Qlectric Pulse8 at tne re~ulred ~re~uencY~ t~e current ~a-ses throu~h ono or t~e ~ole~ o~ the battor~ throu~h the connector 50 to load 49 lnto the outor ~oil eloctrode 44, tben trou~ t~e dru~ ros~rvoir~ ~1 lnward into the ~uman or ani~l body, returnln~ to ehe inner conductlve ~
roll eloctrodo ~3 tnence t~rou~h the load 47 an~ ` -connector 48 to tne Otner ~ole o~ tho batterY T~u31y tho curr nt ~a~-ln~ t~rou~ tho loni~ed dru~ solution in t~e reservoir, drawln~ ~ne ions ~atlentwl~e ~rOu~ tne ~kln and outward o~ the re~ervolr lnto tn~ bodY ` "

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-25- 132~419 Fl~. ~7 lllustrates a cross 8ectlon 0~ a ~atch Wlth a power Yu~ly, h~vln~ an arran~ement sPecl~icallY
desi~ned ~or use o~ uid dru~ solutlons; Tn~
supportln~ memb~r 45 c~r~lny the unlt w~lc~ connects tne power supplY unlt 51 b~ connector8 50 and 48 .
t~rou~ leads ~7 and 49, also 18 connected to both electrode l~Yers 43 and 44 T~e insulstln~ layer 42 has ~rooved ~ole~ in lt snd the ca~lllary absorbin~
lsyer ~1 is placed between the lnBulatln~ laYer 41 and t~e bottom electrode ~4 and comes throu~b the ~rooved holes o~ the insulatln~ lsyer ~2~ A
urotectl~e detac~able ~oll ~6 ~rotqcts the devlce nnd dru~ ~rior U8Q~ Flexible trou~ed contalner 53 contalns the dru~ solutlon and the nYlon ysrn 54 18 u~ed ~or Dunceurln~ t~e contalner 53 w~en pulled So ~ehat wh~n nylon Yarn 54 18 ~ulled the oontalner 53 1- ~unctured an~ t~e dru~ solution ~lows oue Or t~e contaln~r 53 on to t~e extended trou~ o~ the re~orvolr~ w~ero lt meets t~e ca~lllary sbsorbln~
laYor ~1 The ~olutlon 18 absorbed and dlstrlbute~
throu~h eo all ~ rt~ o~ the laY~r 41 w~lo~ a~ts as the dru~ resQr~olr durln~ the iontop~or~tle deliverY

to tl~ reclPlent.

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' -26- 1324~19 It should be understood t~st specl~lc Porm~ or t~e ln~entlon hereln lllustrated and descrl~ed ~re lntended to be re~resèntatlve onlY as certaln c~an~es may be made ln the lnventlon wlt~out dePartln~ ~rom t~e teacht n~ o~ t~l~ dlsclosure. Accordln~ly, re~erence s~ould be made to t~e ~ollowln~ clalms -.
determ~nin~ the rull scoPe o~ thls invention.

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Claims

1. An iontophoretic device comprises in combination:

an insulating member having an inner surface positionable adjacent skin of a recipient, at least one reservoir in the insulating member and adapted to contain an ionic drug and terminating in a rim formed by said inner surface, an outer electrode in contact with the drug, n inner electrode on the inner surface and spaced from the rim to define a gap therebetween, field between generating means for energizing the electrodes to draw the drug recipientwise and outward from the rim.

2. The iontophoretic device in Claim 1 with the reservoir having a depth measured from the outer electrode to the inner surface, the gap of similar dimension to the depth.

3. The iontophoretic device of Claim 2 with the reservoir having a width or similar dimension to the depth.

4. An iontophoretic device comprising in combination:

an insulating member havikng an inner surface positionable adjacent skin of resipient, at least one reservoir in the insulating member and adapted to contain a drug and, terminating in a rim formed by said inner surface, an outer electrode in contact with the drug, the reservoir having a depth measured from the outer electrode to the inner surface.

an inner electrode on the inner surface and spaced from the rim to define a gap therebetween.

the gap of similar dimension to the depth, field generating means for energizing the electrodes to draw the drug recipientwise and outward from the rim.

5. The iontophoretic device of Claim 4 With the gap equal to the depth.

6. The iontophoretic device of Claim 5 with the reservoir having a width equal to the depth.

7. The iontophoretic device of Claim 6 the insulating member a flat plate having an outer surface.

the reservoir passing completely through the insulating member from the outer surface to the inner surface.

the outer electrode adhered on the outer surface, the inner electrode adhered on the inner surface.

8. The iontophoretic device of Claim 7 with the drug in a gel form.

9. The iontophoretic device of Claim 7 with the drug in a cellular absorbing material.

10.The iontophoretic device of Claim 7 with the field generating means comprising a power source operatively connected to the pulse generator and arranged to supply pulses of high frequency wave forms in a predetermined duty cycle for pulsing current through the drug to cause the drawing of the drug to be at reduced impedance and resistance.

11.The iontophoretic device of Claim 7 with the reservoir substantially cylindrical.

12.The iontophoretic device or Claim 11 with a plurality or the reservoirs.

13. The iontophoretic device or Claim 12 with each of the reservoirs arranged substantially equidistant from any adjacent reservoir.

14.The iontophoretic device of Claim 7 with the reservoir substantially a right parallepiped.

15.The iontophoretic device of Claim 14 with a plurality of the reservoirs.

16. The iontophoretic device of Claim 15 with each of the reservoirs arranged substantially equidistant from any adjacent reservoir

17.The iontophoretic device of Claim 7 with the reservoir elongated.

18.The iontophoretic device of Claim 17 with the reservoir worked in its plan view.

the inner electrode a complementary fork to the reservoir.

19.The iontophoretic device of Claim 17 with both the reservoir and the inner electrode snail like in plan view.

20. The iontophoretic device of Claim 17 with a plurality of the reservoirs spaced about each other in plan view.

21. The iontophoretic device of Claim 20 with reservoirs concentric to plan view.

22. The iontophoretic device of claim 21 with the reservoirs square in plan view.

23. The iontophoretic device of Claim 22 with the reservoirs circular in plan view.

24. The iontophoretic device of Claim 1 with a detachable protective covering on the inner surface.

25. The iontophoretic device of claim 1 with the electrode comprising conductive metal sheets

26.The iontophoretic device of Claim 1 with the electrodes comprising a thin coating or silver on a substance.

27.The iontophoretic device of Claim 26 with the coating approimately 5m.

28. The iontophoretic device of Claim 1 with the field generating means connected to the electrodes by means of detachable connectors.

29.The iontophoretic device of Claim 1 wherein the field generating means comprises a power source in form of a battery having a voltage of 3 to 9 volts.

30.The iontophoretic device of Claim 29 wherein the said battery is dry cell battery.

31.The iontophoretic device of Claim 29 wherein the said battery is lithium battery.

32.The iontophoretic device of Claim 29 wherein the said battery is a rechargeable nickel-cadmium battery.

33.The iontophoretic device of Claim 29 wherein the battery is selected to enable the recipient a minimum of 8 to 10 service hours at a current level of 5-10mA.

34.The iontophoretic device of Claim 29 wherein the field generating means include a pulse generator with a frequency range of 50-500 KHz.

35.The further iontophoretic device of Claim 27 wherein the field generating means includes a current control means in the form of a microprocessor placed in series with the pulse generator to enable an operator to program a therapeutic program.

36.The iontophoretic device of Claim 1 wherein the energizing means is mounted on a separate member connected to the electrodes quick connectors, each connected to either one of the electrodes.

37.The iontophoretic device as in claim 1 wherein a liquid solution of the drug is stored in a flexible container having a trough extending from it; and said container can be punctures by a yarn or other mechanism extended out of said device;
and when said container is punctured said drug solution is absorbed in a capillary absorbing layer provided between said outer electrode and said insulating layer which then becomes the drug reservoir.