Note: Descriptions are shown in the official language in which they were submitted.
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WO 97/11741 PCT~US96/15513
IONTOPHORETIC DRUG DELIVERY
SYSTEM,-INCLUDlNG REUSABLE DEVICE
FIELD OF T~E lNv~llON
The present invention generally relates to iontophoretic
systems ~or delivering drugs, medicines and the like to
patients transdermally, i.e., through the skin, and more
speci~ically relates to a reusable iontophoretic drug delivery
device such as a controller attachable to a disposable drug-
~illed patch.
8AC~GROUND OF THB lN V ~:N'l lON
Transdermal drug delivery systems have, in recent years,
become an increasingly important means o~ administering drugs
and like therapeutic agents.
Presently, there are two types o~ trans~rm~l drug
delivery systems, i.e., "Passive" and "Active." Passive
systems deliver drug through the skin o~ the user unaided, an
example o~ which would involve the application o~ a topical
anesthetic to provide localized relie~, as disclosed in U.S.
Patent No. 3,814,095 (Lubens) Active systems on the other
hand deliver drug through the skin o~ the user using, ~or
example, iontophoresis, which according to Stedman's Medical
Dictionary, is de~ined as "the introduction into the tissues,
by means o~ an electric current, o~ the ions o~ a chosen
medicament." Such systems o~er advantages clearly not
achievable by any other methods o~ administration, such as
avoiding introduction o~ the drug through the gastro-
intestinal tract or punctures in the skin to name a ~ew
Conventional iontophoretic devices, such as those
described in U S Patent Nos 4,820,263 (Spevak et al.),
4,927,408 (~aak et al.) and ~,084,008 (Phipps), the
disclosures o~ which are hereby incorporated by re~erence, ~or
delivering a drug or medicine transdermally- through
iontophoresis, basically consist o~ two electrodes, which are
in contact with a portion o~ a patient's body. A ~irst
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electrode, generally called the active electrode, delivers the
ionic substance or drug into the body by iontophoresis. The
second electrode, generally called the counter electrode,
closes an electrical circuit that includes the ~irst electrode
and the patient's body Generally, the circuit includes a
source o~ electrical energy, such as a battery. The ionic
substance to be driven into the body may be either positively
charged or negatively charged In the case o a positively
charged ionic substance, the anode o~ the iontophoretic device
becomes the active electrode and the cathode serves as the
counter electrode to complete the circuit. Alternatively, i~
the ionic substance to be iontophoretically delivered is
negatively charged, the cathode will be the active electrode
and the anode will be the counter electrode.
In practice, this process is typically achieved by
placing the ionic drug either in solution or in gel ~orm on a
carrier and placing the drug-containing carrier, ~or example,
in the ~orm o~ a drug-~illed adhesive patch, into contact with
t-he skin. The pair o~ electrodes is placed in contact with
the skin and with the carrier. Direct current is applied
between the two electrodes. Under the in~luence o~ the
electric ~ield present, the drug molecules migrate through the
skin. As current ~lows between the two electrodes placed at
spaced apart locations on the skin, the current path carries
the drug with it.
In order to dellver the drug to the patient, the adhesive
patch may be applied to the desired portion o~ the patient's
body and the controller attached to the patch. O~tentimes the
controller is as large as, or larger than, the patch. It also
should be somehow secured in place o~ the patient so that the
patient may remain mobile and carry both the patch and
controller with him as he moves about
Delivery o~ a drug to the patient iontophoretically may
be accomplished either at a constant rate over a long period
o~ time, or periodically at various intervals and in some
situations, upon demand. As can be seen, it may be necessary
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Lor the drug-cont~;n~ng carrier to be maintained in contact
with the patient's skin over a long period o~ time, either ~or
continuous drug delivery, or to permit ~requent interval
delivery over a period o~ time.
S One o~ the problems with an iontophoretic drug delivery
device such as described above, especially one that is compact
and portable to provide patient mobility, is how to attach the
controller to the patient and yet be as unobtrusive as
possible and com~ortable ~or the patient where the system is
to be applied ~or an extended period o~ time A side-by-side
arrangement o~ patch and controller may occupy too much space
on the patient's skin and limit the choices where the
transdermal device may be attached to the patient. Also, the
controller may then have to be ~astened to the patient's skin
by adhesive or a strap, ~or example, which may be
uncom~ortable to the user
As previously noted, it may be necessary to use an
iontophoretic drug delivery device over an extended period o~
time i.e., longer than 24 hours to delivery the necessary
dosage o~ drug. As the length o~ delivery time increases,
there is a need to develop small, unobtrusive iontophoretic
delivery devices which can be easily worn on the skin under
clothing.
In addition to the need ~or developing smaller
iontophoretic devices, there is need to reduce the cost o~
these devices in order to make them more competitive with
conventional ~orms o~ therapy such as pills and subcutaneous
injections. One manner o~ improving cost e~ectiveness is to
have a reusable controller which includes the costly
electronics that provides the current to drive the patch.
Also, it is envisioned that the controller, which may
contain sophisticated electronics besides ~ust a power source
to control and monitor the delivery o~ drug to the patient, is
repeatedly used while the patch is discarded a~ter use and
replaced with new patches. The replaceable patches and
controller should be so structured as to make it easy and
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convenient ~or the patient to replace used patches with new
patches on the controller.
Thus, there has been a need ~or an iontophoretic drug
delivery system, particularly a controller which would
eliminate the problems and limitations associated with the
prior devices discussed above, most signi~icant o~ the
problems being reusability, unobtrusiveness and ease o~ use.
SnMM~RY OF T~E lNV~NllON
In contrast to the prior devices discussed above, it has
been ~ound that a iontophoretic drug delivery system includiny
a controller which may be constructed in accordance with the
present invention is particularly suited ~or reuse In
addition, the controller ~or the system o~ the present
invention pre~erably can be used with disposable patches to
easily attach the system to the patient ~or delivering the
drug, medicament or the like.
The controller o~ the present invention ~or use in
c~mbination with a drug-~illed patch to ~orm an operable
iontophoresis drug delivery system includes a housing having an
upper portion and a lower portion pivotably interconnected,
with the upper=portion and the lower portion being biased
towards one another at a openable ~ront end by biasing means,
and the housing including electronic means ~or monitoring and
controlling electrical current and electrical connection means
positioned within the ~ront end o~ the housing and electrically
connected to the electronics so that when su~icient ~orce is
applied to the housing to overcome the biasing means, the upper
portion and the lower portion are ~orced away ~rom one another
to open the ~ront end and expose the electrical connection
array whereby the electrical connection array may be
interconnected with the drug-~illed patch
In the pre~erred embodiment, the connection means is
adapted to include an electrical array and also adapted so that
upon opening the ~ront end the patch may be inserted into the
open ~ront end in electrical contact with the connection means.
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In addition, the open end o~ the housing includes a notch for
keying the controller and the patch to insure proper
interconnection and orientation.
The iontophoretic drug delivery system o~ the present
invention includes a drug-~illed patch removably attachable to
the skin o~ a patient ~or iontophoretically delivery at least
one drug to the patient, with the patch including conductive
pad means ~or interconnection with the reusable controller,
and a reusable controller removably, electrically connectable
to the patch, the controller providing su~icient energy to
the patch to drive the ionized medicament into the skin o~ the
patient, with the controller including housing means having an
upper portion and a lower portion pivotably interconnected,
with the upper portion and the lower portion being biased
towards one another at a openable ~ront end by biasing means,
and the housing including electronic means ~or monitoring and
controlling electrical current, and with the ~ront end o~ the
controller housing means adapted to including electrical
cannection means positioned within the ~ront end o~ the
housing and electrically connected to the electronics so that
when su~icient ~orce is applied to the housing to overcome
the biasing means, the upper portion and the lower portion are
~orced away ~rom one another to open the ~ront end and expose
the electrical connection array whereby the electrical
connection array may be interconnected with the conductive pad
means o~ the drug-~illed patch.
BRIEF DESCRIPTION OF THE DRAWINGS
The various ~eatures, objects, bene~its, and advantages
o~ the present invention will become more apparent upon
reading the ~ollowing detailed description o~ the pre~erred
embodiment along with the appended cl ~m~ in conjunction with
the drawings, wherein like re~erence numerals identi~y
corresponding components, and:
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- Figure 1 is a perspective, schematic view of the control;erof the present invention illustrating opening of the controller
for interconnecting to the patch;
Figure 2 is a perspective view of the controller shown in
Figure 1 illustrating interconnection of the controller and the
patch;
Figure 3 is plan view of the patch for interconnection with
the controller of the present invention;
Figure 4 is an perspective view of the controller having a
member for attaching the patch thereto, whereby the patch having
a corresponding member may be folded and the two members brought
into contact with one another; and
Figure 5 is a perspective bottom view of the controller
illustrating attachment of the patch to the controller.
DETAIT~n D~SC~IPTION OF T~ PREFERRED EMBODIMENT
The iontophoretic drug deliver system of the present
invention is illustrated in Figure 1-5, with the controller
generally designated 10 and the patch generally designated 12.
Referring to Figures 1, 2 and 3, the controller 10 of the
present invention for use in the iontophoretic drug delivery
system is electrically connectable to the patch 12 to form the
operable system, with the patch being attachable to the skin o~
a patient 14. The patch typically includes an active electrode
assembly 16 and a counter electrode assembly 18. If a positively
charged medicament is to be delivered to the skin 14, the
medicament would be positioned in the active electrode assembly.
In the preferred embodiment, an third or adjunct electrode
assembly 19 is provided so that when delivering a local
anesthetic such a Lidocaine, the local anesthetic may be
delivered beneath the counter electrode as well as the active
electrode as disclosed, for example, in International Publication
No. WO 95/09032, published 6 April 1995, entitled "IONTOPHORETIC
DRUG DELIVERY SYSTEM AND METHOD FOR USING SAME," which is hereby
incorporated in its entirety.
As illustrated in Figures 1-4, the controller 10 is coupled
to the patch 12 using well known means, for example, by printed
~EN~ED S~ET
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"~ '~ ' . ,,. '',;
flexible circuits, metal foils, wires, tabs or electrically
conductive adhesives as disclosed for example in International
Publication No. WO 96/10442, entitled "IONTOPHORESIS ASSEMBLY
INCLUDING PATCH/CONTROLLER ATTACHMENT," published 11 April 1996,
the disclosure of which is hereby incorporated by reference in
its entirety.
Referring to Figures 3 and 4, the patch 12 is a generally
planar flexible member and may be adhesively supported on the
skin 14 of the patient (Figure 5). The patch 12 includes an
enlarged patch body 20 and an extending narrow tab 22. The patch
body 20 includes opposed planar surfaces 24 and 26, with the
planar surface 24 disposed for skin contact and including a drug
reservoir 28 typically in a gel form which contains at least one
drug, medicament or like active agents (hereinafter collectively
referred to simply as drugs), preferably in an ionic form. While
the drug reservoir 28 is shown, any other known iontophoretic
drug reservoir structure for placing a medicament in contact with
the skin in an iontophoretic patch may be employed, as disclosed
for example in International Publication No. WO 95/09031 entitled
"IONTOPHORETIC DRUG DELIVERY DEVICE AND RESERVOIR AND METHOD OF
MAKING SAME," published 6 April 1995, the disclosure of which is
hereby incorporated by reference in its entirety.
Each of the electrode assemblies 16 and 18 are positioned to
be in contact with the skin once the patch 12 is secured, as
shown in Figure 5. The positioning of the electrode assemblies
16 and 18 is such that an electrical current path is established
between the electrode assemblies 16 and 18 through the skin of
the patient 14. A direct current source in combination with the
electrode assemblies 16 and 18 and the patient's body 14
completes the circuit and generates an electric field across the
body surface or skin to which the iontophoretic device is
applied, with the drug reservoir 28 assumes the same charge as
the ionized drug contained in the reservoir 28. Under the
influence of electrical current passing from the electrode
assembly 16 through the skin 14 to the electrode assembly 18, the
drug contained in the drug reservoir 28 is transcutaneously
AMENDED SHEET
CA 02233197 1998-03-26
,,~
delivered into the body of the patient by the process of
iontophoresis.
Referring to Figure 4, the electrical current is supplied
from the controller 10 to the electrode assemblies 16 and 18 on
the patch via the electrical traces or leads 32 and 34 shown in
Figure 3. Each of the traces 32 and 34 may be one or more
conductive paths extending from the electrode assemblies 16 and
18 to exposed conductive pads 36 (Figure 3) positioned on a
marginal edge of the patch tab 22. As described in further
detail below, the pads 36 are positioned for electrical
connection to the controller 10, which provides a source of
electrical current.
The particular construction of the patch 12 is not essential
to the present invention, and may be formed of woven or non-woven
textiles or polymers or may be any other construction well known
in the art. However, it is preferred that the electrode
assemblies 16, 18, the electrical traces 32, 34 and the
conductive pads be printed or otherwise formed on a polymeric
substrate as disclosed, for example, in International Publication
No. WO 94/17853 entitled "ACTIVE DRUG DELIVERY DEVICE, ELECTRODE
AND METHOD FOR MAKING SAME," published 18 August 1994, the
disclosure of which is hereby incorporated by reference in its
entirety.
As illustrated in Figures 1 and 2, the controller 10 includes
a controller housing 40 having an upper portion 42 and a lower
portion 44 pivotably interconnected, with the portions being
biased towards one another by a biasing means such as a spring
46. In this way, the housing 40 has a general clothespin shape
and includes an biasingly openable front end 48 which
accommodates the tab 22 of the patch 12. The housing 40 further
accommodates a connection array 50 adjacent the electronics 52
contained within the housing 40 and schematically shown in
phantom in Figure 2. The connection array 50 and the electronics
52 are preferably mounted to a common printed circuit board (not
shown). The connection array 50 may include plural electrical
terminals in electrical connection with the electronics 52 and
may be connectable to the pads 36 of the tab 22 extending from
_ 8
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~ the patch 12. In the p~esent illustrative embodiment, the
connection array 50 is an electrical connection member having
plural spaced-apart, exposed conc~uctive surfaces separated by an
insulating material. As p~evio~sly discussed, it may be
S appreciated that any suitable electrical interconnection device
may be employed in accordance with the present invention.
Re~erring back to Figure 2, the controller 10 houses the
electronics 52 that monitor and control the supply of electric
current to the electrode assemblies 16 and 18 and the user
interfaces. As is known in the art, the electrical components
may include a source of electrical power such as a battery and
additional electronic components, such as an application speci~ic
integrated circuit, a microprocessor, used to send a controlled
electrical current to electrode assemblies 16 and 18. It should
be appreciated that the particular electrode assemblies and the
electronic array are not essential to the present invention, with
the electrode assemblies including, for example, those disclosed
in International Publication No. WO 96/10440 entitled
"IONTOPHORETIC DRUG DELIVERY DEVICE HAVING IMPROVED CONTROLLER,"
published 11 April 1996 and International Publication No.
97/07854 published 6 March 1997 entitled "IONTOPHORETIC DRUG
DELIVERY DEVICE HAVING HIGH-EFFICIENCY DC-TO-DC ENERGY CONVERSION
CIRCUIT," the disclosures of which are hereby incorporated by
re~erence in their entirety.
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In the preferred embodiment, as illustrated in Figures 1 and
2, the controller may be easily interconnected with the patch 12
under thumb actuation to an open position exposing the connection
array 50 for electrical connection with the pads 36 of the tab
22. Specifically, by pressing the rear end 49 of the housing
with sufficient force to overcome the spring 46 to open front end
48 of housing 42 (Figure 1). The tab 22 of the patch 12 may then
be inserted in the open end, with the conductive pads 36 slidably
engageable with the connection array 50 and the housing returned
to a closed position by releasing the rear portion to cover the
connection array 50 with the pads clamped or otherwise held there
between.
In order to assure accurate alignment of the pads 36 of the
tab 22 with the connection array 50 supported within the housing
40, the tab 22 is keyed to the housing 40. Specifically, the tab
22 includes an extending leg or like portion 38 on one side which
is designed to fit in a corresponding notch 54 formed in at least
one side of the front end 48 of the lower portion 42 of the
housing 40. The notch 54 and the leg 38 are of similar shape so
as to provide keyed accommodation of the tab 22 and the leg 38.
The key structure included on both the housing front end 48 and
the leg 38 insures proper orientation of the patch 12 and the
controller 10 by preventing incorrect positioning of the patch
12 with respect to the controller 10. In the present embodiment,
both the front end 48 and the notch 54, and the corresponding tab
22 and the leg 38 have a generally L-shaped cross-section,
however, any other mating shape which would prevent incorrect
alignment may be employed.
Referring to Figures 4 and 5, the controller 10 and the patch
12 include attachment means for permitting the releasable support
of the controller 10 on the patch 12 after interconnection
between the pads 36 and the connective array 50 is established.
The surface 24 of patch 12, and the exposed upper portion 42
include cooperating fastening elements 56 and 58 thereon. In the
present illustrative embodiment, the
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cooperative ~astening elements 56, 58 include conventional hook
and loop ~asteners o~ the type sold under the trademark VELCRO.
Any other cooperating type ~asteners may be employed to achieve
the same objective. One cooperating ~astening element 56 is
secured adhesively or otherwise to patch 12 on sur~ace 24 while
the other cooperating ~astening member 58 is secured by
adhesive or otherwise to the exposed sur~ace o~ upper portion
42 o~ the housing 40. As described in ~urther detail below,
attachment o~ the mating hook and loop ~asteners 56 or 58
provide removable support ~or controller 10 on patch 12. It
may be appreciated by those skilled in the art that the patch
and controller may take any known ~orm. The only requirement
is that the patch be capable o~ being physically and
electrically connected to the controller 10.
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Operation
and Use
Having described one embodiment of iontophoretic drug
delivery system, including the controller 10 and the patch 12,
of the present invention, its operation and use is described
below.
As illustrated in Figure 5, the controller 10 and patch 12
may be adhesively secured to the skin 14 of the patient, with
surface 24 of patch 12 placed in intimate contact with the skin
14 so that the electrode assemblies 16 and 18, as well as the
drug containing reservoir 28, are supported in intimate contact
with the skin 14. In order to iontophoretically deliver the
medicament from reservoir 28 transcutaneously through the skin
14, the reusable controller 10 of the present invention is
electrically connected to patch 12. The housing 40 is opened and
the tab 22 of the patch 12 is inserted into the open front end
48 of the housing 40. Proper planar orientation is assured
between the patch 12 and the controller 10 due to the key
mateability between the notch 54 in the open front end 48 of the
housing 40 and the extending leg 38 of the patch tab 22. As the
controller 10 is designed to be maintained in electrical
connection with the patch 12 during iontophoretic delivery of the
drug contained in the reservoir 28, the controller lo may be
fastened or otherwise attached to the patch 12 so that it will
be conveniently retained on the skin of the patient.
As shown in Figures 4 and 5, once the patch 12 is connected to
controller 10, the controller may be flipped up so that the mating
hook and loop fasteners 56 and 58 engage each other to removably
fasten the controller 10 to the patch 12 as shown in Figure 5.
The controller 10 is comfortably retained on the skin of the
patient during iontophoretic drug delivery. At such time as a
particular application of the drug is completed, the controller
10 and the patch 12 may be removed from the skin of the patient,
and by separating the mating hook and loop fasteners 56 and 58,
and pressing on the rear end of the housing 40, the controller 10
and the patch 12 may be
AMENOED ~tEET
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separated In this way, the controller may be disconnected and
placed aside until the next administration o~ the drug is
needed, when it can be reused with a new patch.
In the pre~erred embodiment, the patch 12 o~ the present
invention contains Lidocaine (a local anesthetic) and
Epinephrine or Adrenaline (vasoconstrictors) In this way,
the device can be used ~or anesthetizing the applied area to
m; n~m; ze sensation ~rom the insertion o~ a needle or the like.
However, it should be appreciated that other substances
suitable ~or being applied to the area may be utilized which
are well known to those skilled in the art.
Active agent, drug, ~ormulation, medication, medicament
and active compound have been used herein to mean any ethical
pharmaceutlcal compound or agent, such as therapeutic
compounds, diagnostic agents, anesthetic agents and the like.
As is well known within the ~ield, the device can be
situated on the area o~ the patient to which the active agent
is to be applied (the applied area) such as the skin and a
v~ltage impressed across the electrode assemblies 16, 18 to
cause electrical current to flow through the skin o~ the
patient to drive or otherwise transport the drug pre~erably in
the ~orm o~ an ionic active agent into the skin and the tissue
to be absorbed by the body o~ the patient. The electric ~ield
lines are su~iciently long, however, so that the active agent
is transported to the desired depth within the skin, and
possibly to the vasculature, to provide the desired e~ect,
e.g., anesthetic, therapeutic or diagnostic It should also
be appreciated that the device o~ the present invention can be
applied to other areas o~ the body such as mucus membranes
depending upon the desired therapy and drugs to be delivered.
In addition, while the present invention has been
described in connection with iontophoresis, it should be
appreciated that it may be used in connection with other
principles o~ active introduction, i.e , motive ~orces, such
as electrophoresis which includes the movement o~ particles in
an electric ~ield toward one or other electric pole, anode, or
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cathode and electro-os~osis which includes the transport o~
uncharged compounds due to the bulk ~low o~ water induced by
an electric ~ield Also, it should be appreciated that the
patient may include humans as well as ~n;m~l S
While the pre~erred embodiment o~ the present invention
has been described so as to enable one skilled in the art to
practice the device o~ the present invention, it is to be
understood that variations and modi~ications may be employed
without departing ~rom the concept and intent o~ the present
invention as de~ined in the ~ollowiny claims. The preceding
description is intended to be exemplary and should not be used
to limit the scope o~ the invention. The scope o~ the
invention should be det~rm; ne~ only by re~erence to the
~ollowing claims
What is claimed is:
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