Note: Descriptions are shown in the official language in which they were submitted.
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1
ELECTROTRANSPORT DEVICE AND METHOD OF SETTING OUTPUT
TECHNICAL FIELD
s The present invention relates to delivery of therapeutic agents through a
body surface by electrotransport. More particularly, the invention relates to
a
two-part electrotransport delivery device comprised of an electronic
controller
adapted to be coupled to, one at a time, a plurality of therapeutic agent (eg,
drug) containing units.
BACKGROUND ART
The transdermal delivery of drugs, by diffusion through the epidermis,
offers improvements over more traditional delivery methods, such as
~s subcutaneous injections and oral delivery. Transdermal drug delivery avoids
the
hepatic first pass effect encountered with oral drug delivery. Transdermal
drug
delivery also eliminates patient discomfort associated with subcutaneous
injections. In addition, transdermal delivery can provide more uniform
concentrations of drug in the bloodstream of the patient over time due to the
2o extended controlled delivery profiles of certain types of patches. The term
"transdermal" delivery, broadly encompasses the delivery of an agent through a
body surface, such as the skin, mucosa, or nails of an animal.
The skin functions as the primary barrier to the transdermal penetration of
2s materials into the body and represents the body's major resistance to the
transdermal delivery of therapeutic agents such as drugs. To date, efforts
have
been focussed on reducing the physical resistance or enhancing the
permeability of the skin for the delivery of drug by passive diffusion.
Various
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methods for increasing the rate of transdermal drug flux have been attempted,
most notably using chemical flux enhancers.
Others have attempted to increase the rates of transdermal drug delivery
s using alternative energy sources such as electrical energy and ultrasonic
energy. The present invention relates specifically to electrically assisted
transdermal delivery, also referred to as electrotransport. The term
"electrotransport" as used herein refers generally to the delivery of an agent
(eg,
a drug) through a membrane, such as skin, mucous membrane, or nails. The
delivery is induced or aided by application of an electrical potential. For
example, a beneficial therapeutic agent may be introduced into the systemic
circulation of a human body by electrotransport delivery through the skin. A
widely used electrotransport process, electromigration (also called
iontophoresis), involves the electrically induced transport of charged ions.
~s Another type of electrotransport, electroosmosis, involves the flow of a
liquid,
which liquid contains the agent to be delivered, under the influence of an
electric
field. Still another type of electrotransport process, electroporation,
involves the
formation of transiently-existing pores in a biological membrane by the
application of an electric field. An agent can be delivered through the pores
Zo either passively (ie, without electrical assistance) or actively (ie, under
the
influence of an electric potential). However, in any given electrotransport
process, more than one of these processes, including at least some "passive"
diffusion, may be occurring simultaneously to a certain extent. Accordingly,
the
term "electrotransport", as used herein, should be given its broadest possible
is interpretation so that it includes the electrically induced or enhanced
transport of
at least one agent, which may be charged, uncharged, or a mixture thereof,
whatever the specific mechanism or mechanisms by which the agent actually is '
transported.
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Electrotransport devices use at least two electrodes that are in electrical
contact with some portion of the skin, nails, mucous membrane, or other
surface
of the body. One electrode, commonly called the "donor" electrode, is the
electrode from which the agent is delivered into the body. The other
electrode,
' s typically termed the "counter" electrode, serves to close the electrical
circuit
through the body. For example, if the agent to be delivered is positively
charged, ie, a cation, then the anode is the donor electrode, while the
cathode is
the counter electrode which serves to complete the circuit. Alternatively, if
an
agent is negatively charged, ie, an anion, the cathode is the donor electrode
and
~o the anode is the counter electrode. Additionally, both the anode and
cathode
may be considered donor electrodes if both anionic and cationic agent ions, or
if
uncharged dissolved agents, are to be delivered.
Furthermore, electrotransport delivery systems generally require at least
~s one reservoir or source of the agent to be delivered to the body. Examples
of
such donor reservoirs include a pouch or cavity, a porous sponge or pad, and a
hydrophilic polymer or a gel matrix. Such donor reservoirs are electrically
connected to, and positioned between, the anode or cathode and the body
surtace, to provide a fixed or renewable source of one or more agents or
drugs.
2o Electrotransport devices also have an electrical power source such as one
or
more batteries. Typically at any one time, one pole of the power source is
electrically connected to the donor electrode, while the opposite pole is
electrically connected to the counter electrode. Since it has been shown that
the
rate of electrotransport drug delivery is approximately proportional to the
electric
2s current applied by the device, many electrotransport devices typically have
an
electrical controller that controls the voltage and/or current applied through
the
electrodes, thereby regulating the rate of drug delivery. These control
circuits
use a variety of electrical components to control the amplitude, polarity,
timing,
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waveform shape, etc. of the electric current and/or voltage supplied by the
power
source. See, for example, McNichols et al US Patent No 5,047,007.
To date, commercial transdermal electrotransport drug delivery devices
s (eg, the Phoresor, sold by loured, Inc. of Salt Lake City, UT; the Dupel
lontophoresis System sold by Empi, Inc. of St. Paul, MN; the Webster Sweat
Inducer, model 3600, sold by Wescor, Inc. of Logan, UT) have generally
utilized
a desk-top electrical power supply unit and a pair of skin contacting
electrodes.
The donor electrode contains a drug solution while the counter electrode
contains a solution of a bio-compatible electrolyte salt. The power supply
unit
has electrical controls for adjusting the amount of electrical current applied
through the electrodes. The "satellite" electrodes are connected to the
electrical
power supply unit by long (eg, 1-2 meters) electrically conductive wires or
cables. The wire connections are subject to disconnection and limit the
patient's
~s movement and mobility. Wires between electrodes and controls may also be
annoying or uncomfortable to the patient. Other examples of desk-top
electrical
power supply units which use "satellite" electrode assemblies are disclosed in
Jacobsen et al US Patent 4,141,359 (see Figures 3 and 4); LaPrade US Patent
5,006,108 (see Figure 9); and Maurer et al US Patent 5,254,081
More recently, small self-contained electrotransport delivery devices
adapted to be worn on the skin, sometimes unobtrusively under clothing, for
extended periods of time have been proposed. Such small self-contained
electrotransport delivery devices are disclosed for example in Tapper, US
Patent
2s 5,224,927; Sibalis, et al US Patent 5,224,928; and Haynes et al US Patent
5,246,418.
There have recently been suggestions to utilize electrotransport devices
having a reusable controller which is adapted to by used with multiple drug-
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containing units. The drug-containing units are simply disconnected from the
controller when the drug becomes depleted and a fresh drug-containing unit is
thereafter connected to the controller. In this way, the relatively more
expensive
hardware components of the device (eg, batteries, LED's, circuit hardware,
etc)
s can be contained within the reusable controller, and the relatively less
expensive
donor reservoir and counter reservoir matrices can be contained in the single
use/disposable drug-containing unit thereby bringing down the overall cost of
electrotransport drug delivery. Examples of electrotransport devices comprised
of a reusable controller adapted to be removably connected to a drug-
containing
~o unit are disclosed in Sage, Jr. et al, US Patent 5,320,597; Sibalis, US
Patent
5,358,483; Sibalis et al, US Patent 5,135,479 (Fig. 12); and Devane et al UK
Patent Application 2 239 803. The Devane Application discloses a two-part
electrotransport system comprised of a controller and a drug-containing unit.
The two parts are electrically and mechanically coupled to form a complete
~s electrotransport device. One of the Devane devices has cooperating
electrical
contacts on the controller and drug unit, specifically projections on the drug
unit
engage microswitches on the controller, to select a given therapeutic
program/electrotransport current. Another of the Devane electrotransport
devices has a bar code on the drug unit which can presumably be scanned by a
2o scanner in the controller (eg, by passing the scanner over the bar code) to
signal
the controller the type of drug-containing unit that is being connected
thereto.
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DISCLOSURE OF THE INVENTION
In accordance with one aspect of the present
invention, there is provided an electrotransport device
comprising: a therapeutic agent-containing unit having a
reservoir containing the therapeutic agent to be delivered;
a controller for providing one of a plurality of
electrotransport current outputs to the therapeutic agent-
containing unit; a coupler for reparably coupling the
controller and the therapeutic agent-containing unit, the
coupler providing electrical connection between the
controller and the therapeutic agent-containing unit; the
therapeutic agent-containing unit comprising a signaling
mechanism which provides a signal to the controller, said
controller comprising a predetermined set of outputs
corresponding to a plurality of dosing regimens for said
agent and further comprising a receiver for receiving the
signal and setting an output in response to the signal,
wherein the controller includes means to deliver said agent
at multiple rates, which rate is determined by selection of
a therapeutic agent-containing unit.
In accordance with a second aspect of the present
invention, there is provided a method of setting an
electrical output of an electrotransport controller which is
to be coupled to one of a plurality of different therapeutic
agent-containing units so that the output matches a
predetermined output suitable for the particular unit,
comprising: selecting one of the plurality of different
therapeutic agent-containing units; coupling the selected
unit to the controller; providing a signal from the selected
unit to the controller, said signal being related to a
parameter selected from the group consisting of the amount
of therapeutic agent in the unit, the concentration of the
therapeutic agent in the unit, and combinations thereof;
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receiving the signal by the controller; and setting the
output of the controller to the predetermined output in
response to the received signal, whereby a single agent can
be delivered at multiple rates by selection of an
appropriate therapeutic agent-containing unit.
In accordance with a third aspect of the present
invention, there is provided an electrotransport device
comprising: a therapeutic agent-containing unit having a
reservoir containing the therapeutic agent to be delivered;
a controller for providing one of a plurality of
electrotransport current outputs to the therapeutic agent-
containing unit; a coupler for separably coupling the
controller and the therapeutic agent-containing unit, the
coupler providing electrical connection between the
controller and the therapeutic agent-containing unit; the
therapeutic agent-containing unit comprising a first circuit
portion, said first circuit portion including a resistance
or capacitance portion of a predetermined magnitude; the
controller comprising a second circuit portion for coupling
to said first circuit portion wherein said second circuit
portion provides at least one logic input, said logic input
determined by comparing said predetermined magnitude of the
resistance or capacitance to at least one reference
parameter, said reference parameter having a range of values
associated therewith; wherein the controller sets the
controller output from among said plurality of
electrotransport current outputs in accordance with said
logic input.
In accordance with a fourth aspect of the present
invention, there is provided a kit for electrotransport
agent delivery comprising: a first set of therapeutic agent-
containing units comprising a reservoir containing the
therapeutic agent to be delivered at a first predetermined
~ ~ CA 02218713 2006-02-03
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dosage rate; a second set of therapeutic agent-containing
units comprising a reservoir containing the therapeutic
agent to be delivered at a second predetermined dosage rate;
a controller for controlling electrotransport delivery of
the agent; a coupler for reparably coupling the controller
and the therapeutic agent-containing unit, the coupler
providing electrical connection between the controller and
the therapeutic agent-containing unit; each of said
therapeutic agent-containing units comprising a signaling
mechanism which provides a signal to the controller, said
controller comprising a predetermined set of outputs
corresponding to said first and second dosage rates for said
therapeutic agent and further comprising a receiver for
receiving the signal and setting an output in response to
the signal; whereby said agent can be administered at
multiple rates by appropriate selection of a therapeutic
agent-containing unit.
In another aspect of the invention, there is
provided a two-part electrotransport delivery device, the
device having an electronic controller with a plurality of
predetermined electronic outputs (eg, electric current
and/or voltage outputs), which controller is adapted to be
coupled to a plurality of different therapeutic agent-
containing units, one at a time, for administering the
therapeutic agent through a body surface (eg, skin) by
electrotransport.
In a further aspect of the present invention,
there is provided a reliable means for signaling to the
electronic controller the particular type of therapeutic
agent-containing unit which is being coupled thereto and for
selecting a specific controller output which is suited for
the coupled unit in order to achieve a predetermined
therapeutic agent delivery regimen.
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The present invention is directed to a two-part
electrotransport device for delivering a therapeutic agent.
The first part of the device is an electronic controller
which is adapted to be coupled (ie, mechanically and
electrically connected) to a plurality of different
therapeutic agent-containing units, one at a time. For
example, the "different" therapeutic agent-containing units
may contain different therapeutic agents (ie, different
drugs), different concentrations of the same
drug/therapeutic agent, or different loadings (ie, amounts)
of the same drug/therapeutic agent.
The controller is capable of providing one of a
plurality of different electrical outputs to any particular
therapeutic agent-containing unit that is coupled thereto.
The number and type of "different" electrical outputs will
depend in large part on the different types of therapeutic
agent-containing units which are adapted to be used with the
controller. For example, the controller
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could be adapted to be used with (ie, coupled to) two different drug units,
one
unit containing a narcotic analgesic drug for treating chronic pain and the
other
unit containing an anti-migraine drug for treating a migraine headache. In
such
a device, the controller would be designed to have two different electrical
s outputs. In connection with the narcotic analgesic-containing unit, the
controller
applies electrotransport current over a relatively extended period of time
(eg, 24
hours) to (eg, continuously) administer the narcotic analgesic to treat the
chronic pain. In connection with the anti-migraine drug-containing unit, the
controller applies electrotransport current over a relatively short (eg, 30
minutes
~o or less) period of time at the onset of a migraine attack. In addition to
the timing
of the applied electrotransport currents being different in the two above-
exemplified examples, the magnitude, polarity, waveform shape (eg, whether
pulsed or constant DC), etc, of the applied electrotransport current and/or
voltage may also be different between the two different applications (ie,
narcotic
~s analgesic for treating chronic pain and the anti-migraine for treating
migraine
headaches).
Another example of different drug-containing units and different controller
outputs concerns an electrotransport controller adapted to be used to deliver
a
Zo single drug at multiple dosing rates. One example of this mode of operation
is
an electrotransport device for delivering a narcotic analgesic drug to control
chronic and/or acute pain. When delivering analgesics to control pain, it is
not
unusual to provide different dosing levels for different patients. For
example,
adult patients typically require higher doses of analgesic that children in
order to
2s achieve the same level of analgesia. Also, analgesic drug-tolerant patients
typically require higher doses than patients who are not drug tolerant. Thus,
the
controller is designed to apply electrotransport currents of different
magnitudes,
one output current having a higher magnitude to deliver a higher dose of
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analgesic drug compared to an output current having a lower magnitude for
delivering a lower dose of analgesic drug.
In all of the above-described examples where the controller has a plurality
s of different outputs and is adapted to be connected to one of a plurality of
different drug-containing units, the output of the controller must be reliable
set to
meet the needs of the particular therapeutic agent-containing unit which is
coupled thereto. In accordance with this invention, the therapeutic agent-
containing unit provides a signal to the controller. The signal is received by
the
controller and the output of the controller is selected in accordance with the
received signal in order to appropriately match the controller output to the
coupled therapeutic agent-containing unit. The selection of the controller
output
is accomplished automatically without the need for any manual setting or other
human intervention. Thus, the controller output can be reset simply by having
15 the patient or medical technician couple the particular drug unit to the
controller,
without the need to take any other action.
In one embodiment of the invention, the signal provided by the
therapeutic agent-containing unit to the controller is an optical signal
comprised
zo of light reflected from a light reflective surface on the drug unit. The
light
reflective surtace is provided with one of a plurality of different
reflectivities
which can be read by an optical sensor in the controller. The light reflective
surtace and the optical sensor are aligned when the therapeutic agent-
containing unit and the controller are coupled. The optical sensor provides a
2s control signal which sets the output of the controller responsive to the
level of
reflected light.
In another embodiment of the present invention, the signal provided by
the selected therapeutic agent-containing unit to the controller is an
electrical
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resistance signal. The controller applies a test current through the resistor
in the
drug unit when the controller and the unit are coupled together. The
resistance
value of (ie, voltage drop across) the resistor is sensed by the controller
which
then sets its output responsive to the sensed resistance signal.
In another embodiment of the present invention, the signal provided by
the selected therapeutic agent-containing unit to the controller is an
electrical
capacitance signal. The controller has a capacitance sensor which receives the
capacitance signal upon the controller and the unit being coupled together.
The
~o capacitance sensor provides a control signal which sets the output of the
controller responsive to the received capacitance signal.
In still another embodiment of the present invention, the signal is provided
by a an electro-mechanical connector which connects when the controller and
the therapeutic agent-containing unit are coupled together. The electro-
mechanical connector is comprised of two parts, a "universal" part on the
controller and a "unit-specific" part on the therapeutic agent-containing
unit.
Thus, the unit specific part will have one of a plurality of configurations
depending upon how many different drug units are adapted to be used with the
2o controller. For example, electro-mechanical connector may be comprised of a
series of male members (eg, posts on the therapeutic agent-containing unit)
which are adapted to be inserted in, and make electrical contact with, a
corresponding number of female members (eg,sockets on the controller). For
example, the controller is designed with a plurality (eg, 4) of sockets,
whereas
2s four different therapeutic agent-containing units are designed to carry
one, two,
three or four posts, respectively. When the selected unit is coupled to the
controller, the controller's output is set depending upon the number of posts
which are engaged in the four sockets on the controller.
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An additional embodiment of the invention uses magnets) in the drug unit
and a magnetic field sensor leg, a hall-efFect device) in the controller.
Another
embodiment uses pieces of metal in the drug unit and a metal detector in the
control ler.
s '
BRIEF DESCRIPTION OF THE DRAWINGS
For a further understanding of the objects and advantages of the present
invention, reference is made to the following detailed description, taken in
conjunction with the accompanying drawings, in which like parts are given like
reference numerals and wherein;
Fig. 1 is a perspective view of an electrotransport device comprised of a
reusable controller and a drug-containing unit, in an uncoupled configuration,
in
~s which the controller and drug-containing unit communicate by means of an
optical signal;
Fig. 2 is an exploded view of the device shown in Fig. 1;
zo Fig. 3 is a schematic diagram of the optical sensing and control circuit of
the device shown in Figs. 1 and 2;
Fig. 4 is a schematic diagram of another two-part electrotransport device
having a resistance signal sensing and control circuit;
zs
Fig. 5 is a perspective view of another two-part electrotransport device, in
which the controller and the drug unit communicate by means of an electro-
°
mechanical connector;
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Fig. 6 is a schematic diagram of the signal sensing and control circuit of
the device shown in Fig. 5;
Fig. 7 is a schematic diagram of another two-part electrotransport device
s in which the controller and drug unit, shown in an uncoupled configuration,
communicate by means of a capacitance signal;
Fig. 8 is a schematic diagram of portions of the deice shown in Fig. 7, with
the drug unit coupled to the controller;
Fig. 9 is a schematic diagram of the same portions of the device shown in
Fig. 8, with the drug unit attached to the body surface of a patient; and,
Fig. 10 is a schematic diagram of another two-part electrotransport device
,s in wh~cht~econtroller and-drug-unit comn-!unlcat~-by-means-ova-magnetic
signal.
MODES FOR CARRYING OUT THE INVENTION
Zo Fig. 1 is a perspective view of electrotransport device 20 having a
reusable electronic controller 22 which is adapted to be coupled to and
uncoupled from, drug-containing unit 24. The controller 22 is reusable, ie, it
is
adapted to be used with a plurality of drug units 24, eg, a series of similar
and/or
very different drug units 24. On the other hand, drug unit 24 typically has a
more
Zs limited life and is adapted to be discarded after use, ie, when the drug
contained
therein has been delivered or has been depleted. Thus, after the drug
contained
in drug unit 24 becomes depleted after a predetermined operational life (eg,
24
hours), the drug unit 24 is uncoupled from the controller 22 and replaced with
a
fresh drug unit 24 of the same or difFerent structure and/or composition. The
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controller 22 is designed to provide one of a plurality of different
predetermined
electrical outputs, which outputs are preferably set at the time the
controller is
manufactured. The different electrical outputs of the controller 22 are
designed
to be used with different drug units 24. For purposes of illustration, the
s controller 22 can be designed to be used with two different drug units 24,
both of
which units are adapted to be used with the same controller 22 to continuously
deliver drug over a period of 12 hours. The two different drug units 24
contain
the same drug in their respective donor reservoirs but each contains a
different
amount of the drug. The drug unit 24 which contains a greater amount of drug
is
a "high dose" drug unit which is adapted to be used with a higher DC current
(eg, 2 mA) output from the controller 22. The drug unit 24 which contains a
lesser amount of drug is a "low dose" drug unit which is adapted to be used
with
a lower DC current (eg, 1 mA) output from the controller 22. Thus, the
controller
22 is designed to apply one of two different DC currents (ie, 1 mA or 2 mA)
~s depending upon whether a low dose or a high dose drug unit 24 is coupled
thereto. The present invention provides a means for signaling to the
controller
22 which type of drug unit (eg, either a high dose or a low dose drug unit) is
being coupled thereto and for appropriately setting the output of the
controller
(ie, setting either the high current output or the low current output) to
match the
zo coupled drug unit. In the device illustrated in Figs. 1 and 2, the drug
unit 24
signals the controller 22 by means of an optical signal, which optical signal
is
automatically sent and then read (ie, decoded) by the controller 22 upon
coupling the drug unit 24 thereto (ie, by means of the snap connectors 26,
28).
Upon reading the signal, the controller appropriately selects the correct
electrical
2s output to apply to the coupled drug unit 24.
With reference to Fig. 2, there is shown an exploded view of both the
drug unit 24 and the controller 22. The controller 22 is comprised of an upper
housing 68 and a lower housing 50, both typically formed of a molded plastic
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such as polypropylene. The upper housing 68 is joined to the lower housing 50
by a contiguous splash proof and preferably water proof peripheral seal. The
seal can be made by heat sealing or ultrasonic welding of the joint between
housings 50, 68, by gluing the housings together at their common joint using a
s water proof adhesive, and the like. The lower housing 50 has an opening 52
for
receiving the battery 54. Battery contacts 64, 66 are provided to make
electrical
contact with the respective poles of battery 54. A removable cover 60 screws
into the opening 52 to retain the battery 54 in place. The cover 60 has a slot
62
for inserting a coin or a screw driver blade to turn the cover 60 and remove
it
~o from the opening 52 in order to access (ie, replace) the battery 54. The
controller 22 includes a battery 54, eg a button cell battery, for powering
the
electrical circuit (not shown) on circuit board 59. The circuit board 59 is
formed
in a conventional manner, having conductive traces patterned for
interconnecting electrical components) thereon which control the magnitude,
15 timing, frequency, waveform shape, etc., of the electrical output (eg,
voltage
and/or current) of controller 22. The conductive traces on circuit board 59
may
be deposited with a conventional silk screen printing process or a
conventional
solder coated copper plated mask and etch process. The insulating substrate of
circuit board 59 may be made of standard FR-4 or the like. Although not
critical
2o to the invention, controller 22 includes a push button switch 74 which can
be
used to start operation of device 10 and a liquid crystal display 56 (Fig. 1 )
which
can display, through window 58 (Fig. 2), system information such as the
particular type of drug unit 24 that is coupled to the controller, the applied
current level, the dosing level, number of doses delivered, elapsed time of
Zs current application, battery strength, etc.
The lower housing 50 is provided with holes 75a, 75b which hold
electrically conductive receptacles 30, 32. The receptacles 30, 32 protrude
through respective holes 75a, 75b in lower housing 50. The ends of receptacles
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30, 32 are held in place in by, and make electrical contact with the outputs
of the
electronic circuit on circuit board 59, by respective conductive gripping
fasteners
76a, 76b.
s The drug unit 24 is configured to be removably coupled to the controller '
22, with the top of drug unit 24 adjacent to and facing the bottom of the
controller
22. The top of drug unit 24 is provided with the male parts of two snap type
connectors, the male parts being posts 26 and 28 which extend upwardly from
drug unit 24. Receptacle 30 is positioned and sized to receive donor post 26
and receptacle 32 is positioned and sized to receive counter post 28. One snap
connector pair, for example receptacle 32 and post 28, may be made larger than
the other snap connector pair (ie, receptacle 30 and post 26) in order to
provide
a polarity specific connection of the drug unit 24 to the controller 22.
Receptacles 30, 32 and posts 26, 28 are made from an electrically conductive
~s material (eg, a metal such as silver, brass, stainless steel, platinum,
gold, nickel,
beryllium-copper, etc or a metal coated polymer, eg, ABS with a silver
coating).
The donor post 26 is electrically connected to the donor electrode 90, which
in
turn is electrically connected to the donor reservoir 101 which typically
contains
a solution of the therapeutic agent (eg, a drug salt) to be delivered. The
counter
Zo post 28 is electrically connected to the counter electrode 88, which in
turn is
electrically connected to the counter reservoir 99 which typically contains a
solution of a biocompatible electrolyte (eg, buffered saline). The electrodes
88
and 90 are typically comprised of electrically conductive materials, most
preferably a silver (eg, silver foil or silver powder loaded polymer) anodic
2s electrode and a silver chloride cathodic electrode. The reservoirs 99 and
101
typically include hydrogel matrices which hold the drug or electrolyte
solutions
and are adapted to be placed in contact with the body surface (eg, skin) of a
patient (not shown) when in use. The electrodes 88, 90 and the reservoirs 99,
101 are isolated from each other by foam member 96. The bottom (ie, patient
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contacting) surface of foam member 96 is preferably coated with a skin contact
adhesive in order to secure drug unit 24 on the patient's body. A release
liner
102 covers the body contacting surfaces of the two reservoirs 99 and 101 and
the adhesive coated surface of foam member 96 before the drug unit 24 is put
in
s use. The release liner 102 is preferably a silicone coated polyester sheet.
The
release liner 102 is removed when the device 20 is applied to the skin of a
patient (not shown).
Thus, the post 26 and the receptacle 30 comprise a snap type connector
~o which electrically connects an output 78a of the circuit on circuit board
59 to the
electrode 90 and the reservoir 101. Similarly, the post 28 and the receptacle
32
comprise a snap type connector which electrically connects an output 78b of
the
circuit on circuit board 59 to the electrode 88 and the reservoir 99. In
addition to
providing the above described electrical connections, the two snap connectors
~s also provide a separable (ie, not permanent) mechanical connection of the
drug
unit 24 to the controller 22. Thus, the electrically conductive snap
connectors
26, 30 and 28, 32 simultaneously provide the functions of (i) mechanically
coupling the drug unit 24 to the connector 22, and (ii) electrically
connecting the
electrical output of controller 22 to the drug unit 24.
2o
In accordance with this embodiment of the present invention, the drug unit
24 provides an optical signal to the controller 22 in order to properly set
the
electrical output of the controller to a predetermined output which is
appropriate
for the specific drug unit 24 and the specific drug contain therein. As is
clearly
is shown in both Figs. 1 and 2, the mating surface of drug unit 24 has two
surface
areas 40, 42. Surface area 40 is shown as "white" for high light reflectivity
while
surface area 42 is shown as "black" for low light reflectivity. Areas 40, 42
may
be provided (eg, by printing or painting) directly on the backing layer 44 of
drug
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16
unit 24 or alternatively on a thin strip of paper or mylar 43 which is mounted
on
the backing layer 44 by a suitable adhesive.
Controller 22 has a pair of light reflection switches 34, 36 mounted on
s circuit board 59 and oriented so as to project through holes 37a, 37b in
lower
housing 50. The switches 34, 36 are directed toward and adjacent to the drug
unit 24. The reflective areas 40, 42 are positioned on drug unit 24 such that
areas 40, 42 are located closely adjacent to the reflection switches 36, 34,
respectively, when the controller 22 and drug unit 24 are coupled.
The light reflection switches 34, 36 are arranged to illuminate the light
reflective areas 40, 42 respectively. The reflective areas 40, 42 are arranged
such that the illumination from the switch 34 is independently reflected by
the
area 42 back to the switch 34. Similarly, the illumination from switch 36 is
1s independently reflected by the area 40 back to the switch 36. In a
preferred
embodiment, the switches 34 and 36 are each provided with a respective
illumination source in the form of a photo emitter, 46a and 46b, and a
respective
matching light sensitive photodetector in the form of a phototransistor, 48a
and
48b, such as the SFH901 or SFH902 available from Siemens Optoelectronics
2o Division, Cupertino, CA. The phototransistors 48a and 48b are connected in
a
circuit (described below) which generates signals responsive to incident
light.
The switches 34, 36 are mounted on the circuit board 59 and respective
traces (not shown) by conventional means such as through holes and solder
Zs connections. The electrical connections between the circuit board 59
respective
conductive traces (not shown) and the photoemitters 46a, 46b and
phototransistors 48a, 48b of the switches 34, 36 are explained in detail with
reference to Fig. 3, below.
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17
The flexible backing layer 86, which is preferably made of a material (eg,
polyethylene sheet) which is impermeable to the passage of liquid water, forms
the top-most layer of the drug unit 24. Holes 84a, 84b are provided through
the
backing layer 44 and perforations 82a, 82b through strip 43 in an aligned
s arrangement. The conductive base rivets 26a, 28a project through the
openings
84a, 84b and the perforations 82a and 82b, respectively, and engage the posts
26, 28 to fix the backing layer 44 therebetween.
Electrodes 88, 90 are composed of electrically conductive materials such
~o as a carbon powder/fiber loaded polymer matrix, a metal powder loaded
polymer
matrix or a metal foil. Electrodes 88, 90 make contact with the base rivets
26a,
28a. A carbon filled or silver particle filled conductive adhesive is used to
bond
the electrodes 88, 90 to the base rivets 26a, 28a. The electrodes 88, 90 are
in
electrical contact with reservoirs 99, 101, respectively. An insulating closed
cell
~s foam layer 96 has cavities 98, 100 therein, which cavities contain
reservoirs 99,
101, respectively. Typically, one of the reservoirs 99, 101 is the donor
reservoir
which contains a liquid solution of the therapeutic agent to be delivered by
electrotransport while the other is the counter reservoir which contains a
solution
of a bio-compatible electrolyte (eg, saline). The matrix of reservoirs 99, 101
is
2o preferably a gel.
Transmitting information about the drug unit 24, via the optical signal
transmitted to the controller 22, is accomplished by providing the reflective
areas
40, 42 with different levels of reflectivity. For example, area 40 may be a
is standard white having about 90% reflectivity, while area 42 may be a flat
black
having between about 10 to 15% reflectivity at the wavelength of illumination
from the switches 34, 36. With two light reflective surface areas, each area
having one of two possible light reflectivities, the drug unit 24 may transmit
to
controller 22 up to four differently coded optical signals based on the
following
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18
"reflectivity code"; (1 ) a first optical signal when both areas 40 and 42
have low
reflectivities; (2) a second optical signal when both areas 40 and 42 have
high
reflectivities; (3) a third optical signal when area 40 has a low reflectivity
and '
area 42 has a high reflectivity; and (4) a fourth optical signal when area 40
has
s a high reflectivity and area 42 has a low reflectivity. The areas 40, 42 may
be
encoded by simply painting with a paint having suitable reflectivity. The
areas
40, 42 may also be encoded by printing or by applying adhesive tape with
suitable reflectivity.
~o Fig. 3 is a schematic diagram of one example of an electrical circuit which
can be used to read the optical signal provided by drug unit 24 to controller
22
and to decode the signal in order to appropriately set the electrical output
of
controller 22. Those skilled in the electrical arts will appreciate that other
electrical circuits may be used to perform the functions of circuit 200 shown
in
~s Fig. 3 and that the details of circuit 200 are shown for purposes of
illustration
only.
Circuit 200 is carried on the circuit board 59 (shown in Fig. 2) of controller
22. The battery 54 is connected to system ground 58 and by conductive circuit
Zo trace 202 to switch 74. When the switch 74 is actuated (ie, closed), the
trace
202 is connected to a circuit trace 204. One end of resistors Ra, Rb, Rp1, Rp2
and one terminal of a large capacitor Cr, (eg about 0.1 micro Farad) are
connected to trace 204. One end of a large (eg. about 1 meg ohm) resistor Rr
is
connected to the other terminal of capacitor Cr. The other end of resistor Rr
is
2s connected to ground. The resistor Rr and capacitor Cr comprise a circuit to
debounce the actuation of the switch 74.
A field effect transistor (FET) Q1 gate is connected to a D-type latch U7 Q
output. The FET Q1 drain is connected to the other end of resistor Ra. The FET
-
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Q1 source is connected to the anode of photoemitter 46a. The FET Q1, acting
as a switch between the FET Q1 drain and source, connects the other end of
resistor Ra to the anode of photoemitter 46a when the FET Q1 gate is activated
by a high level on the latch U7 Q output. The cathode of photoemitter 46a is
s connected to system ground. The other end of resistor Rb is connected to the
common point of FET Q1 source and the photoemitter anode 46a.
The collector of phototransistor 48a is connected to the other end of
resistor Rp1. The collector of phototransistor 48a is also connected to
inverter
o U1 input, to an input of a finro input NAND gate U5 and an input of a two
input
AND gate U6. The emitter of phototransistor 48a is connected to system ground.
The common point of FET Q1 source and the anode of photoemitter 46a
are also connected to the anode of photoemitter 46b. The cathode of
~s photoemitter 46b is connected to system ground. The collector of
phototransistor
48b is connected to the other end of resistor Rp2, an inverter U2 input, one
input
of a two input NAND gate U4, and the other input of the two input AND gate U6.
Inverter U2 output is connected to a first input of a three input NAND gate
Zo U3, to the other input of the two input NAND gate U5, and a first input of
a three
input NAND gate U8. Inverter U1 output is connected to the second input of the
three input NAND gate U3, the other input of the two input NAND gate U4 and a
second input of the three input NAND gate U8. The third input of the three
input
NAND gate U8 is connected to the U7 latch Q output. The third input of the
Zs three input NAND gate U3 is connected to the U7 latch Q\ output.
D latch U7 clock, C, and Data, D, inputs are connected to system ground.
The D latch U7 set input, S, is connected to the AND gate U6 output. The D
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latch U7 reset input, R, is connected to the common point of capacitor Cr and
resistor Rr.
The respective NAND gates U3, U4, U5 and U8 outputs drive
s corresponding P-channel FETs Q2, Q3, Q4, and Q5 gate inputs. The FETs Q2,
Q3, Q4, Q5 respective source terminals are connected to one end of a resistor
Rs1 and to a non-inverting input of a high gain operational amplifier A1 which
functions as a differential amplifier in circuit 200. The other end of
resistor Rs1
is connected to system ground.
One end of resistors R1, R2, R3, R4 are connected to a common point at
the trace 204. The other end of R4 connects to FET Q5. The other ends of
respective resistors R1, R2, R3 and R4 are connected to corresponding P-
channel FETs Q2, Q3, Q4, Q5 drain terminals.
The electrode 88 and the reservoir 99 are electrically connected through
the mated snap connectors 28, 32, to the amplifier A1 output. The electrode 90
and the reservoir 101 are connected through the mated snap connectors 26, 30,
to the inverting input of amplifier A1. One end of a resistor, RS2, is also
Zo connected to the inverting input of A1. The amplifier A1 supplies an
electrotransport current, I, to the electrodes 88, 90 and the reservoirs 99,
101
based on the action of the circuit 200 as described below.
The circuit 200 operates as follows. After application of the device 20 to
Zs the skin, the switch 74 is actuated, connecting circuit trace 202 to trace
204.
The connection between traces 202 and 204 causes the battery 54 voltage to be
connected to trace 204. The high voltage on trace 204 is momentarily passed
through the capacitor C1 to the R input of U7 which causes U7 to reset with
the
Q output low and the Q\ output high. The low level on the Q output turns off
the
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21
transistor Q1 thereby disconnecting resistor Ra from the anodes of
photoemitters 46a and 46b. The value of Rb is chosen to cause sufficient
illumination from the anode of photoemitters 46a such that light reflected
from
the white area 40 causes the phototransistor 48a to saturate, thereby pulling
s Rp1, and the input to inverter U1 essentially to system ground, ie a low
level.
The resistance value of resistor Rb is also chosen to be small enough such
that
light reflected from the black area 42 will not saturate the phototransistor
48b
causing a high level to remain at the input to inverter U2.
A low level on the inverter U1 input and a high level on inverter U2 input
cause the inverter U1 output to go high and the inverter U2 output to go low.
The NAND gate U4 will have both inputs high, and will therefore turn on
transistor Q3. All other NAND gates will remain off, thereby disabling the
other
FETs Q2, Q4, and Q5. Transistor Q3 connects resistor R2 to the non-inverting
~s input of amplifier A1 and one side of resistor Rs1. Resistors Rs1, Rs2, and
level
setting resistors R1, R2, R3, and R4 are selected to be much larger than the
typical electrical resistance of the body surface (eg, skin) to which the two
reservoirs 99, 101 are applied. Human skin resistance is typically in the
range
of about 5 to 30 kohms.
zo
Since the gain of amplifier A1 is very large, the voltage difference
between the non-inverting and the inverting inputs of amplifier A1 will be
essentially zero. Resistors Rs1 and R2 will therefore act essentially as a
voltage
divider with the voltage across resistor Rs1 set by the resistance ratio of
zs resistors R2 and Rs1. The current, I, will flow through the snap connectors
26,
30 and 28, 32, the electrodes 90, 88, the reservoirs 101, 99, and the skin.
The
current, I, will be the same in the resistor Rs2 since it is the same value as
resistor Rs1. The current, I, therefore is determined by the voltage across
resistor Rs1 and the voltage from the battery 54. The current delivered by
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22
amplifier A1 to the electrodes 88, 90, can therefore be determined by the
resistance values of the resistors R1, R2, R3, and R4 relative to the
resistance
values of resistors Rs1, Rs2, and the reflectivity of the areas 40, 42 on the
specific drug unit 24.
s
Similar logic follows for the case of (i) both areas 40, 42 being white,
which selects resistor R1, and (ii) area 40 being black and area 42 being
white,
which selects resistor R3.
~o In the event that both the areas 40, 42 are black, neither phototransistor
48a or 48b will saturate causing the respective collectors to both remain
high.
The inputs to AND gate U6 will be high, causing the output of AND gate U6 and
the S input of U7 latch to go high. The latch U7 will be set causing the Q
output
to go high. The N-channel transistor Q1 will be switched on, connecting the
~s resistor Ra to the anodes of photoemitters 46a and 46b.
The resistor Ra is selected so that illumination from the photoemitters 46a
and 46b is sufficient to provide enough light reflected from a black surface
areas
40 and 42, to saturate the phototransistors 48a and 48b. The resulting low
level
Zo on the collectors of phototransistors 48a and 48b will cause a high level
to the
first and second input of NAND gate U8. The third input of NAND gate U8 will
also be high, as it receives the high level from the U7 Q output. The output
of
NAND gate U8 will go low, thereby turning on P-channel FET Q5. The other
NAND gates U3, U4, U5 remain off. Resistor R4 is thereby connected to the
2s non-inverting input of amplifier A1, selecting the current, I, according to
the
values of resistors R4 and Rs1.
In the event that the switch 74 is activated when no drug unit 24 is
coupled to controller 22, no light will be reflected back to the
phototransistors
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23
48a, 48b. The voltage at the collectors of phototransistors 48a, 48b will
remain
high. Again, the AND gate U6 high output will cause the set input S of latch
U7
to go high, thereby setting the Q output high. This time however, the first
two
inputs to NAND gate U8 will be low causing the output of U8 NAND gate to
s remain high and the P-channel transistor Q5 turned off. The other NAND gates
will also be off since at least one input to each NAND gate U3, U4, U5, U8, is
low. The amplifier A1 therefore will not be driven to supply current 1.
In summary, the circuit 200 selects one of four current setting resistors R1
~o through R4 for delivering one of four different (ie, different magnitude)
DC
currents to the electrodes 88, 90 and the reservoirs 99, 101 as a function of
the
coding combination of white and black on the areas 40 and 42 of drug unit 24.
In other embodiments of the present invention, additional light reflective
~s areas, light reflective switches and additional decoding logic may be
provided in
the controller 22 and drug unit 24 to select one of a larger number of desired
controller outputs.
Although circuit 200 only has the ability to select one of four different
2o constant magnitude DC electrotransport currents based on the optical signal
received from the drug unit 24, it should be noted that the outputs of NAND
gates U3, U4 , U5 and U8 can also be used to select other electrical currents
besides a constant DC current. For example, the NAND outputs could select
different pulsed DC or AC current generators, or DC current generators having
is different waveforms (eg, pulsed DC current), duty cycles and the like.
Furthermore, the circuit 200 can also be modified to include a mechanism for
selecting different time intervals for application of electrotransport
current, or
repetitive application of a predetermined current according to different
therapeutic regimens.
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24
Fig. 4 illustrates a 2-part electrotransport delivery device 300 comprised
of a controller 314 adapted to be coupled to one of a plurality of different
drug
units 301. Each drug unit 301 provides an electrical signal to the controller
314,
s the electrical signal being provided by a "test current" which is applied,
by the
controller 314 through the "identifying resistor" Rx in drug unit 301, when
the
drug unit 301 is first coupled to the controller 314. A sensing circuit within
the
controller 314 senses the value of resistor Rx (which resistor has a different
resistance value in the different drug units 301 ) in order to identify which
drug
unit 301 is being coupled thereto and to appropriately select the one
electrical
output (of a plurality of electrical outputs) which is matched to the
particular drug
unit 301.
Similar to device 20 illustrated in Figs 1 to 3, device 300 includes a pair
~s of electrically conductive snap connectors 306, 310 and 308, 312 for
simultaneously (i) mechanically coupling drug unit 301 to controller 314 and
(ii)
electrically coupling the electrical output of controller 314 to the drug unit
301.
Drug unit 301 is provided with an identifying resistor Rx connected
Zo between the electrode assemblies 302 and 304. The resistance of resistor Rx
is
chosen to be much larger (eg. at least three times and preferably at least
about
20 times) the typical electrical resistance of the body surtace (eg, skin) to
which
the device is adapted to be applied. In the case of human skin, the electrical
resistance of human skin is typically in the range of 5 to 15 kohms and hence
the
Zs resistance of resistor Rx will typically be chosen to be at least about 50
kohms.
The controller 314 includes a current measuring resistor Rm having one
end connected to the receptacle 312 and to a very high impedance +sense input
of a logic-current control device 316. The +sense input impedance is
sufficiently
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high that no significant current will flow into the +sense input when current
is
flowing in resistor Rm. The other end of resistor Rm is connected to a low
impedance -sense input of the control device 316. The -sense input acts as a
current, I, return line for the resistor Rm. The resistance value of resistor
Rm is
' s typically a low value relative to the electrical resistance of the animal
body
surFace (eg, 5 to 15 kohm for human skin) to which drug unit 301 is applied.
The
controller 314 also includes four voltage comparators A5, A6, A7 and A8 each
having a plus (+) input, a minus (-) input and a comparator output.
The respective minus input of each comparator A5 through A8 is
connected to a corresponding reference voltage Vref1, Vref2, Vref3 and Vref4
and is derived from a voltage divider (not shown) relative to the receptacle
312.
Such voltage dividers are well known in the art. The respective plus input of
each comparator A5 through A8 is connected to a common point at the
1!S receptacle-310:--T~e-re~pe~i,,/e-06;~pvit~refrea~h cvmparator ~i5 throng h
Ae-are
connected to corresponding logic inputs 320, 322, 324, and 326 of the circuit
316.
The circuit 316 includes a current enable output signal OE, a read enable
20 output signal RE and an output control voltage Vb. The output control
voltage Vb
is connected to N-channel FETs Q10 and Q11 drain terminals. Signal OE is
connected to the FET Q10 gate input and signal RE is connected to the FET
Q11 gate input. The FET Q10 source terminal is connected to the anode of
blocking diode D1. The FET Q11 source terminal is connected to one terminal
is of a constant current source, Iref. The other terminal of Iref is connected
to the
anode of blocking diode D2. The current source Iref provides a known reference
- current of predetermined value. Iref is typically set to a low value, eg, 1-
2 uA,
relative to the applied electrotransport drive current I. The cathodes of
diodes D1
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26
and D2 are connected to the common point of the plus inputs of comparators A5
through A8 and the receptacle 310.
Circuit 316 operates as follows. Upon coupling the drug unit 301 to the
s controller 314, but before placing the electrode assemblies 302, 304 on the
skin,
the circuit 316 is activated. The activation of circuit 316 can be
accomplished
automatically upon connecting the snap connectors 306, 310 and 308, 312 or
manually, for example by the closure of switch 74 on the controller 22.
Activation of the circuit 316 initiates a first timing circuit (not shown)
that begins
a timing period Te. The timing period Te enables a high level voltage Vte on
the
RE output. The high level Vte on the RE output turns on FET Q11 which
connects the current source Iref, to the receptacle 310. The current Iref
flows
through the snap connector 310, 306, through the resistor Rx (no current Iref
flows through the electrode assemblies 302, 304 since the electrode assemblies
~s have not yet been placed on the body of the patient) and returns through
the
snap connector 308, 312 and the resistor Rm to the low impedance -sense
return input of circuit 316.
Voltage developed across Rx by the current Iref is compared to the
2o reference voltages Vref1 through Vref4 by the comparators A5 through A8
during the period Te. One or more of the comparators will output high levels
on
their respective outputs according to the value of Rx and the value of the
corresponding reference voltage, Vref1-Vref4. The circuit 316 decodes the
resulting logic inputs 320-326 and provides an amplifier means (not shown) for
2s controlling the signal, Vb. The signal Vb is controlled such that the FET
Q11 will
deliver the predetermined value of electrotransport drive current, I,
according to
the value of resistor Rx, when enabled by the signal OE.
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27
After the end of the enable period Te, the electrode assemblies 302, 304
are then placed against the skin of the patient. Upon another activation of
the
controller 314, for example, by another switch actuation (not shown) or by
detecting the change of voltage across the electrode assemblies 302, 304 when
s the device 300 is placed on the skin, the circuit 316 enables the beginning
of an
output period, To. At the beginning of time period To, the output signal OE
goes
high thereby causing the circuit 316 to begin controlling the voltage Vb.
During the output period To, the voltage Vb from the circuit 316 is
~o responsive to the voltage across the resistor Rm as sensed by the +sense
and -
sense inputs and to the circuit 316. Circuit 316 is provided with suitable
negative
feed back and gain, when the output signal OE is high, such that Vb is
controlled
to provide a constant current, I, to flow in the sense resistor Rm,
independent
over the expected range of the electrical resistance of the skin. The value of
~s current in the resistor Rm will be the same as that flowing through the
electrode
assemblies 302, 304 and the skin, since they are effectively in series.
Again, although the circuitry which selects and controls the outputs of
controller 314 has been shown in terms of selecting one of four alternative
Zo constant currents by sensing (ie, decoding) the value of resistor Rx, the
circuit
316 may provide other output currents besides constant DC current, including
pulsed DC currents, intermittent DC currents, time-varying (ie, non-constant)
DC
currents, intermittent polarity reversing currents, and even AC currents.
Furthermore, additional comparators and control logic may be provided in order
zs to select from an increased number of such alternate currents or waveforms.
Figs. 5 and 6 illustrate a perspective view of a two-part electrotransport
drug delivery device 350 comprised of a controller 352 and a drug unit 358
which are coupled by electro-mechanical connectors which simultaneously
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28
provide mechanical and electrical coupling of the drug unit 358 to the
controller
352 and a means for providing a signal to the controller 352 as to the
particulars
of the drug unit 358 which is being coupled thereto.
s The controller 352 has a strap 354, 356 (which strap includes
conventional buckle, tongue-and-hole elements, not shown) for attaching device
350 to the limb of a patient for treatment. The body proximal side of
controller
352 contains a plurality of electrically conductive receptacles (eg, in the
form of
female parts of two-part snap connectors) 360, 362, 364, 366 and 368.
The drug delivery unit 358 has a body distal surface with one or more
posts 370, 372, 374, 376 and 378 (eg, in the form of male parts of two-part
snap
connectors) which are positioned to be in alignment with one or more of
receptacles 360, 362, 364, 366 and 368, respectively. In the case of the
~s particular drug unit 358 shown in Fig. 5, only posts 370 and 374 are
present.
Thus, post 370 and receptacle 360 comprise one mating snap connector pair
and post 374 and receptacle 364 comprise a second mating snap connector
pair. Posts 372, 376 and 378 are not present on the drug unit 358 shown in
Fig.
5, although their locations are aligned with receptacles 362, 366 and 368,
Zo respectively, on controller 352.
The populated locations of posts 370, 374 and unpopulated post locations
372, 376 and 378 can be seen to comprise a position code. With the five
stud/receptacle location pairs, a unique one out of four selection may be made
25 between a reference post/receptacle pair, eg post 370 and receptacle 360,
and
a second post/receptacle pair, eg post 374, receptacle 364, by populating only
one of the other four post locations on the drug unit 358.
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29
When the controller 352 and the drug unit 358 are aligned and mated,
post 370 mates with receptacle 360 and post 374 mates with receptacle 364.
receptacles 362, 366 and 368 are left unconnected. Different drug units may be
made having the second post positioned alternatively in one of the locations
s 372, 376, or 378.
It is apparent that the posts 370, 374 and receptacles 360, 364 co-act to
provide electrical connection and signal encoding means between the controller
352, and the drug unit 358. Optionally, the snap connectors 360, 370 and 364,
~0 374 also provide a mechanical coupling of the drug unit 358 to the
controller
352, although the mechanical coupling may be accomplished by other means
such as mechanical coupler 394, 396.
Fig. 6 shows a schematic diagram of device 350 with the controller 352
~s mechanically coupled to the drug unit 358. The controller 352 includes a
power
source (eg, one or more batteries) 380 and four current control sources 382,
384, 386 and 388. The drug unit includes two electrode assemblies 390, 392, at
least one of which contains a therapeutic agent with the other acting as a
counter electrode assembly. The electrode assemblies 390, 392 are mounted
2o as before described on the bottom of the delivery unit 358 to make contact
with
the body surface (eg, skin) 391 of a patient when the device 350 is attached
to
patient's limb. One terminal of each current control source 382 through 388 is
electrically connected to a common terminal of the power source 380, the other
terminal of each respective current control source 382 through 388 is
electrically
zs connected to the respective receptacle 362 through 368. The other terminal
of
the power source 380 is electrically connected to the remaining receptacle
360.
When the controller 352 is connected to the drug unit 358, and the
device 350 is attached to the patient's limb with the electrode assemblies
390,
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392 in contact with the patient's skin 391, a complete electrical circuit is
formed
by the power source 380, the current control source 384, the snap connector
pair 364, 374, the electrode 392, the patient's skin 391, the electrode 390
and .
the snap connector pair 360, 370. The electrotransport current delivered to
the
s drug unit 358 is therefore selected by the location of the post 374 which
mates '
with receptacle 364 and is thereby controlled by current control source 384
which is electrically connected to the "selected" receptacle 364.
The receptacle 360 acts as a reference point for the system of location
coding receptacles and posts. The selection of different control currents
specific
to drug units having different therapeutic treatment regimens is made by the
location of the posts on the drug unit 358. The specific post location 374
provided on the drug unit 358, provides a connection to the receptacle 364 on
the controller 352. This particular connection returns a signal to the
controller
~s 352, in the form of the current delivered to the drug unit 358 by the
current
control source 384. The signal, or current returned to the controller 352, is
specific to the coupled drug unit 358 and the therapeutic agent contained
therein. In the case shown, one of four different control currents may be
provided. Device 350 can be modified to have more receptacles connected to
2o different current control sources to provide a greater range of choices for
treatment.
In order to avoid mistakes in connection of the controller 352 and drug
unit 358, the snap connector pair 360, 370 may have a different size and/or
2s shape from that of the other snap connector pair 364, 374. Alternatively, a
cooperating ridge 394 and slot 396 combination or other cooperating guide
means on the two connecting units 352, 358 could be provided to prevent mis-
orientation. Although device 350 has been explained in regard to snap type
connectors, other types of electrically conductive, releasable
fastener/connector
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31
combinations are contemplated for use in this invention. For example, in place
of
snap connectors, the controller and drug unit could each hold an array of
mechanically interlocking male and female members, respectively, which could
be formed of a molded plastic material or the like. The male members (eg, on
s the drug unit) can be arranged in a pattern which allows the drug unit to be
connected to the controller in only one orientation. One or more of the male
members (eg, pins) could be coated with an electrically conductive material
(eg,
silk-screened using a conductive ink). When fitted into the corresponding
female members (eg, sockets) in the controller, the pins would complete one or
more electrical connections (in a manner similar to that disclosed in Fig. 6)
which
would comprise a coded signal to be read by the controller. In this case, the
code is provided by the particular pin which are coated to be electrically
conductive. For example, using an array of 4 pins, each of which can be
.either
coated (ie, conductive) or non-coated (ie, non-conductive), there is a
possible 16
15 (ie, 24) different coded signals which can be configured using the electro-
mechanical connector. This electro-mechanical connector also acts to both
mechanically and electrically couple the drug unit to the controller, thereby
performing a dual function.
zo Figs. 7, 8 and 9 all illustrate a 2-part electrotransport delivery device
400
comprised of a controller 414 which is adapted to be coupled to one of a
plurality
of different drug units 401, one at a time. Each drug unit 401 provides an
electrical capacitance signal to the controller 414, the capacitance signal
being
provided by a capacitor 441, 430 formed when the drug unit 401 is first
coupled
is to the controller 414. When the drug unit 401 is first coupled to the
controller
414, a "test current" is applied by the controller 414 through the
"identifying
capacitor" formed by the parallel plates 430, 441. A sensing circuit within
the
controller 414 senses the value of the identifying capacitor (which capacitor
has
a different capacitance value in the different drug units 401 ) in order to
identify
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32
which drug unit 401 is being coupled thereto and to appropriately select the
one
electrical output (of a plurality of electrical outputs) which is matched to
the
particular drug unit 401. Like the device 20 shown in Figs. 1 to 3, device 400
includes finro snap connector pairs 406, 410 and 408, 412 which function to
both
s mechanically couple the drug unit 401 to the controller 414 and to
electrically
couple the output of controller 414 to the drug unit 401. Receptacles 410, 412
may optionally be provided with internal peripheral ridges which are
configured
to removably engage into respective complementary peripheral grooves on the
posts 406, 408 when the drug unit 401 is pressed into aligned contact with
controller 414. The engaged ridges and grooves thereby mechanically couple
the drug unit 401 more securely to the controller 414.
The Figs. 7, 8 and 9 illustrate the device 400 in three different conditions.
Fig. 7 shows the device 400 in an uncoupled configuration, ie, before the drug
~s unit 401 is coupled to the controller 414. Fig. 8 shows the drug unit 401
coupled
to the controller 414 but before the device 400 is placed on the patient. Fig.
9
shows the device 400 with the drug unit 401 coupled to the controller 414 and
the device 400 applied to the body surface (eg, skin) 407 of a patient and
applying an electrotransport drive current I'.
2o
With reference to Fig. 7, there is shown an insulating wall 434 of the
control unit 414 which defines planar, parallel, spaced apart internal and
external faces 432 and 436. Receptacles 410, 412 are outwardly mounted on
the external face 436 of the insulating wall 434. Controller 414 includes a
switch
is 474, a power source (eg, one or more batteries) 456, FET's Q10' and Q11'
each
having a drain, gate and source terminal, a reference AC voltage source Vx', a
reference capacitor C1, a blocking diode D1, a rectifier diode D2, a filter
resistor
Rf, a sense resistor Rm', a filter capacitor Cf, four threshold comparators
A5',
A6', A7' and A8' each having a positive (+) compare input, a negative compare
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(-) input and an output, a logic and current control circuit 416 and four
voltage
reference sources Vref1', Vref2' Vref3' and Vref4'. The magnitude and
frequency of Vx' is typically set to generate a sinusoidal test current (eg,
having
a frequency of about 10-20 kHz) of suitably low magnitude (eg, about 10-20
N.A)
s relative to the electrotransport drive current, I'.
The circuit 416 includes a current enable output signal OE, a read enable
output signal RE, an output control voltage Vb', and an activation input 464
connected to the power source 456 through the switch 474. The opposite pole
of the power source 456 is connected to system ground. The circuit 416 is
connected to system ground by a return terminal 468. The output control
voltage Vb' is connected to N-channel FETs Q10' and Q11' drain terminals.
Output enable signal OE is connected to the FET Q10' gate input and read
enable signal RE is connected to the FET Q11' gate input. The FET Q10'
~s source terminal is connected to the anode of blocking diode D1. The FET
Q11'
source terminal is connected to one terminal of the AC voltage source, Vx. The
voltage source Vx' provides a known reference voltage of predetermined value.
The other terminal of voltage source Vx' is connected to capacitor C1.
2o The comparators A5' through A8' are high gain, high input impedance
threshold detectors which output a high logic level on the respective output
when
the difference between the respective (+) input and (-) input is positive,
otherwise the respective output is a low logic level. The voltage references,
Vref1' through Vref4', provide unique reference voltages for each of the
2s comparators A5' through A8', respectively. The voltage references Vref1'
through Vref4' are derived from a voltage divider and reference source (not
shown) in the controller 414. Voltage reference Vref1' is connected to the (-)
input of comparator A5', Vref2' to the (-) input of comparator A6', Vref3' to
the (-)
input of comparator AT, and Vref4' to the (-) input of comparator A8'. Each
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34
positive (+) input of the comparators A5' through A8' are connected to a
compare
node 452 and to the cathode terminal of rectifier diode D2 and joined to one
terminal of the filter capacitor Cf. Each respective output of each comparator
A5'
through A8' is connected to corresponding logic inputs 420, 422, 424, 426 of
the
s circuit 416. The other terminal of capacitor Cf is connected to system
ground.
The anode terminal of diode D2 is connected to one end of the filter resistor
Rf.
The other terminal of filter resistor Rf is connected to a sense terminal 450
formed by the union of one terminal of capacitor C1, the cathode of blocking
diode D1 and the receptacle 410.
An AC signal on the sense terminal 450 is peak detected by the diode D2
and filtered by the resistor Rf, capacitor Cf series combination which acts as
a
low pass filter. The values of resistor Rf and capacitor Cf are arranged such
that
the AC components of the signal of the sense terminal 450 are essentially
1s attenuated to zero at the frequency of interest, fs, and above, leaving
only a DC
voltage component at the cathode of diode D2 and the node 452. The DC
voltage output at the node 452 will be essentially the peak value of the AC
voltage on the terminal 450. For example, a value of about 100 kohm for
resistor Rf and a value of about 1 microfarad (uF) for capacitor Cf are
suitable
zo for a 6000 to one reduction of AC amplitude for a signal frequency, fs, of
about
10 kHz.
The other terminal of capacitor C1 is connected to one terminal of the AC
source Vx'. The other terminal of Vx' is connected to the source terminal of
FET
is Q11'. The drain of FET Q11' is connected to a controlled voltage output,
Vb', of
the circuit 416. The gate of FET Q11' is connected to an enable output, RE, of
the circuit 416. The FET Q11' acts as a voltage controlled switch to close the
circuit path from Vb' to sense node 450 through the action of a logic high
value
on the RE enable output as explained further below.
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When the RE output is a logic high, the circuit path from Vb' to the node
. 450 is closed and the AC voltage from Vx' is impressed therein. The
capacitor
C1, the stray capacitance Cs, and any coupling capacitance (Cx) of the
parallel
s plates 430 and 440, on the node 450 act as a voltage divider according to
the
relation
ho = C I
V~ (CI+Cs+Cx)
where Cs is the stray capacitance at the node 450, and Cx is the unknown, or
added capacitance at the node 450. Therefore, by coupling a predetermined
~o value of capacitance, Cx, to the node 450, the voltage, Vx', can be divided
by
the predetermined ratio resulting in the AC output voltage Vo , on the sense
node
450. The AC voltage Vo is peak detected and filtered by the resistor Rf,
capacitor CF, diode D2 circuit to yield a DC voltage on the input compare node
452 essentially equal to the peak value of Vo. Thus, the controller 414 is
~s signaled according to the value of the coupling capacitance, Cx, which is
coupled to the sense node 450. For suitable incremented values of Cx, and
suitable values of reference voltages Vx', Vref1' through Vref4', the drug
unit 401
signals the controller 414 which unique one of a predetermined set of drug
units
has been coupled thereto. Circuits for generating such AC and DC reference
20 voltages are well known by those skilled in the art of electronic circuit
design.
The drain of FET Q10' also connects to the Vb' output. The gate of FET
Q10' is connected to the output enable signal, OE, of the circuit 416. The
. source of FET Q10' is connected to the anode terminal of the blocking diode
D1.
Zs The FET Q10' acts as a voltage controlled switch to close the circuit path
from
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36
Vb' to the sense node 450 through the action of a logic high value on the OE
enable output.
Once the unique one of the predetermined set of delivery units 401 has
s been determined by the control circuit 416, the circuit 416 controls the
bias
voltage Vb' to control the electrotransport drive current delivered to the
drug unit
401 to a predetermined amount. The sequence of the operation of RE and OE
signals is similar to that described for the embodiment of Fig. 4.
The signal provided by drug unit 401 to controller 414 is a capacitance
signal provided by the coupling capacitor, Cx, formed by electrodes 441 and
430
upon coupling the drug unit 401 to the controller 414. Grounding electrode 430
is disposed on the inside face 432 of the insulating wall 434 of controller
414.
The electrode 430 is spaced away from the snap receptacles 410 and 412
~s sufficiently to minimize effects of stray capacitance. The grounding
electrode
430 comprises one half of the coupling capacitor, Cx, (see Fig. 8) formed by
mechanically connecting the delivery unit 401 adjacent to the control unit 414
as
described below. The grounding electrode 430 is formed by coating a portion of
the inside of the wall 434 with an electrically conductive coating, such as
silver
zo ink or the like. The electrode 430 may be applied by spraying, brushing,
plating,
evaporation, plasma deposition or the like.
The physical configuration or circuit layout of the diodes D1, D2, the
capacitor C1 and their location relative to the snap receiver 410 are arranged
to
zs minimize stray capacitance, represented by the symbol, Cs, with respect to
system ground. This minimizes the influence of stray capacitance Cs on the
sensitivity of the sense node 450 to changes in capacitance coupled through
the
snap receptacle 410 and thereby to the change in peak AC voltage at node 450
and to the DC voltage on the compare node 452
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The drug unit 401, in addition to the electrode assemblies 402, 404, also
contains a coupling electrode 440, and a protective insulating layer 441. The
coupling electrode 440 extends laterally over the face 442 to cover a
s predetermined area, Ac. The coupling electrode 440 is covered with the layer
441 as protection against scratching or inadvertent wear. The layer 441 is
preferably made of a thin (eg, about .01 mm thickness) sheet material such as
cellophane.
Electrode 440 is preferably a thin conductor such as a silver foil
adhesively attached to the controller facing side 442 of the drug unit 401.
The
electrode 440 is electrically connected to the electrode assembly 402 and to
the
post 406.
15 Post 406 is electrically connected to electrode assembly 402. Post 408 is
electrically connected to the electrode assembly 404. The electrical
connection
of the posts to the electrode assemblies may be made by conventional means
such as wires, deposited or plated conductive traces, conductive adhesives or
by overlapping layers of conductive foil, deposited or plated layers. Through
Zo holes (not shown) may be provided to connect conductive layers on opposite
sides of the insulating wall 442 in the manner shown in Fig. 2.
The two electrode assemblies 402, 404 are spaced apart and insulated
from one another by a rear facing insulating wall 445. Wall 445 may have a
2s construction similar to foam layer 96 described earlier and shown in Fig.
2, with
cavities for containing the electrode assemblies 402, 404. Alternatively, the
wall
445 and wall 442 may be merged into one layer of insulating material having
front and rear facing surfaces having cavities for the electrode assemblies
and
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posts. A suitable material for the insulating wall 442 is a closed cell
polypropylene foam.
The wall 445 is adapted to hold the electrode assemblies 402, 404 in
s spaced apart relationship in contact with the skin 407 when the drug unit
401 is
attached to the patient's body. The body proximal surface of wall 445 is
preferably coated with a skin contact adhesive which can adhere the entire
device 400 to the patient's skin.
The coupling electrode 440 is aligned with the studs 406, 408 such that
the area, Ac, of the coupling electrode 440 is entirely within the perimeter
of the
area, Ag, of the grounding electrode 430 when the drug unit 401 is coupled to
the controller 414.
15 The laminated structure of the coupling electrode 440 and protective layer
441 are compressively held in contact with the face 436 of the controller wall
434. The series combination of the grounding electrode 430, the dielectric
wall
434, and the laminate of the layer 441 and electrode 440 form the coupling
capacitor, Cx. The value of Cx will depend on the thickness and the dielectric
Zo constant of the dielectric layers between the two electrodes 430 and 440,
and
the area Ac of the coupling electrode 440. If the layer 441 is the same for
all of
the different drug units which are adapted to be coupled to controller 414,
then
the area, Ac, of the electrode 440 that is on the delivery unit 401, is the
only
variable which controls the capacitance value of the capacitor Cx. If the area
of
is electrode 440 is halved or doubled, the capacitance, Cx, changes
proportionally.
Thus the voltage, on the node 450 changes also. The capacitance value of the
capacitor Cx, then is '
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Cx -= A~ K' eo
t
' where K is the relative dielectric constant of the materials between the
electrodes, so is the permittivity of free space, and t is the thickness of
the
dielectrics.
For a wall 434 made of closed cell foam polypropylene (dielectric
constant of about 2.25) and a thickness of about 1.5 mm (1/16 inch) and an
area, Ac of about 0.75 cm2, a capacitance of about 1 picofarad (pF) is
expected.
Thus a range of capacitances, from about 1 to about 8 pF can be obtained with
an area, Ac, from about 0.75 to about 6 cm2. This range for area Ac is
acceptable for small "wearable" electrotransport delivery devices which tend
to
have skin contact areas in the range of about 10 to 100 cm2. The insulating
layer 441 is sufficiently thin to have substantially no effect on the value of
Cx.
~s A practical selection of capacitance values for Cx is about 1, 2, 4 and
about 8 pF. A practical value for capacitor C1 is about mid-way between the
minimum and maximum range of Cx and thus is about 4 pF. Large or smaller
values of Cx may be achieved and utilized with the device 400 with advances in
the art of fabrication and with the use of other materials. A controller 414
with
Zo greater and lesser numbers of detectors may be made to detect more or fewer
unique capacitances Cx to provide different alternative therapies.
Device 400 operates as follows. In the uncoupled relationship of Fig. 7,
' before the controller 414 and the drug unit 401 are connected, no electrical
zs currents flow between the units or from the units to the patients skin. In
use, the
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switch 474 is closed and the power source 456 is connected to an activation
input terminal 464 of the control circuit 416.
Activation of the circuit 416 enables an output, RE, which is connected to
s a gate input of the FET Q11'. The RE output signal turns on the FET Q11' and
'
connects the Vx' AC source in the circuit path from Vb' to node 450. In the
absence of the connection of the drug unit 401 to the controller 414, the
capacitance on the sense node 450 is only the stray capacitance, Cs. The
resulting DC voltage on the compare node 452 is then
h~cCl
(CI+Cs+Cx)
The values of Vref1' through Vref4' are chosen so that the circuit 416
remains in the state with RE signal high supplying Vx' to node 450.
With reference to Fig. 8, the drug unit 401 is connected to the controller
414 by engaging the posts 406, 408 with receptacles 410, 412, respectively.
~s When the snap connector pairs 406, 410 and 408, 412 ar connected, the
coupling electrode 440 and insulating layer 441 are engaged adjacent to the
surface 436 of the wall 434. The coupling capacitance Cx is thereby formed
between the sense node 450 and system ground. With the additional coupling
capacitance, Cx, in place, the voltage on the compare node 452 drops to
h%CI
(CI+Cs+Cx)
Zo The values of Vref1' through Vref4' and detection logic (not shown) within
the circuit 416 are arranged such that the logic circuit 416 detects a
condition
code specific to the value of Cx which has been connected, stores the
condition
code in a memory element (not shown), disables the RE logic high, and enables
,
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41
the OE logic output. The time of detection, To, of the condition code may be
determined by the elapse of delay time, Te, from an internal timer (not shown)
or by detecting the rate of change of voltage, dVc/dt, on the compare node 452
and storing the condition code when dVc/dt is sufficiently small.
s
The FET Q11' is turned off by the disabled RE output signal and removes
the Vx' reference voltage from the circuit path Vb' through FET Q11' and
capacitor C1 to node 450. The enabled OE logic output turns on the Q10' FET
and connects Vb' through the blocking diode D1 to the node 450. The device
400 is now in an output condition ready to deliver electrotransport drive
current
through the electrode assemblies 402, 404. The logic circuit 416 controls the
value of Vb' and attempts to drive a therapeutic current, I', through the
electrode
assemblies 402, 404, of the specific coupled drug unit 401. The controller 414
is preprogrammed to supply a specific current to the electrode assemblies
,s d~per>~ng-on-the-value-sf the-capacitans~; fix; detected.- ~o cur rent
Y"ifl flov~,
however, until the electrode assemblies 402, 404 are placed in contact with
the
skin 407, as shown in the Fig. 9.
After the capacitance, Cx, has been detected, a visual or audio display
Zo (not shown) may be used to signal to the patient or clinician that the
device 400
is ready to be attached to the skin. For example an LED or LCD display 56 (see
Fig. 1 ) may be turned on by the control circuit 416, or an audio annunciator
sounded. Alternatively, a fixed delay time may be preprogrammed into the
controller 414, allowing the clinician time to attach the connected units 401,
414
is to the patient's skin.
Once the electrode assemblies 402, 404 are placed in contact with the
skin 407, the preprogrammed current, I', will begin to flow through the
patient's
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42
skin, carrying the therapeutic agent (which agent is contained in at least one
of
the two electrode assemblies 402, 404) by electrotransport.
Again, although device 400 has been shown in terms of selecting one of
s four alternative constant currents by reading (ie, decoding) the value of
capacitor
Cx, the circuit 416 may provide alternative output current waveforms, such as
AC, pulsed and non-constant DC, etc. based on such decoding and selection.
Furthermore, additional comparators and control logic may be provided in order
to select from an increased number of such alternative currents or waveforms.
Although the capacitive sensing embodiment of device 400 has been
described with a coupling capacitor Cx connected between the receptacle 410
and system ground, other connector structures having detectably different
capacitive values are contemplated in this invention. For example, The posts
406, 408 may themselves include extended flanges (not shown) of overlapping
conductive sheets separated by a thin dielectric layer, in which the
capacitance
is selected by the area of overlap or thickness of the intervening dielectric.
Alternatively, the coupling capacitor, Cx, may be electrically isolated from
Zo the snap connectors 406, 410 and 408, 412, and the detection circuitry and
therapeutic current delivery circuit path may be separate paths.
Other known methods of capacitive sensing also may be employed in this
invention, including those disclosed in Calvin US Patent 4,345,167; Maier US
2s Patent 4,122,708; Kronberg US Patent 5,135,884; Fudaley US Patent
3,445,835;
and Boie et al US Patent 5,337,353.
Another type of signal which can be used in the present invention is a
magnetic signal. For example, small magnets can be placed in the drug unit,
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with different drug units containing magnets of differing magnetic field
strengths.
The controller contains a magnetic field strength sensing device, such as a
Hall-
effect device, which are known in the electro-magnetic arts. The Hall-effect
device senses the strength of the magnetic field produced by the magnets) in
the drug unit, and sets the controller electrical output according to the
sensed
magnetic signal.
Fig. 10 shows one example of a magnetically actuated electrotransport
device 500 comprised of a separable controller 502 and drug unit 508 in
accordance with the present invention. The controller 502 contains a sensor
and logic circuit 504 and a current control circuit 506. The controller 502 is
adapted to be removably coupled to a plurality of disposable drug units 508,
one
at a time in succession. In use, the device 500 is affixed to the skin of a
patient
with the electrodes 510, 512 placed in ion-transmitting contact with the skin.
A surface 514 of the drug unit 508 is configured with two spaced apart
permanent magnets 516 and 518. Suitable permanent magnets 516, 518 may
be formed from a flexible permanent magnetic material known as
"PLASTIFORM", part no. 81030, available from Arnold Engineering Company,
Zo Norfolk, NE, having a thickness of 0.1 cm (0.05 inches), and a length and
width
of 0.6 cm (0.25 inches). Other permanent magnetic materials may be used in
place of magnets 516, 518, such as metallic strips of PERMALLOY (magnetic
iron-base alloys containing 45-80% nickel) and the like. The magnets 516, 518
may be attached to or embedded in the surface 514 of the drug unit 508, or may
is be mounted inside a magnetically transparent covering.
A pair of electrically conductive mechanical snap connectors 520 and 522
are provided to releasably couple, both mechanically and electrically, the
drug
unit 508 to the controller 502. Snap connectors 520 and 522 are comprised of a
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post 520a and 522a and a corresponding socket 520b, 522b, respectively. The
electrodes 510, 512 in drug unit 508 are electrically connected to the posts
520a, 520b by wires or conductive traces.
s The controller 502 contains a pair of magnetically actuated sensor
switches 524, 526. The switches 524, 526 are disposed relative to the sockets
520b and 522b such that they are actuated by the permanent magnets 516, 518
when the snap connectors are mechanically coupled. Suitable magnetic sensor
switches 524, 526 are the "UNIPOLAR HALL EFFECT" switches, SS141A,
~o available from Honeywell Microswitch Division, Freeport, IL. The switches
524,
526 each contain a Hall effect sensor element 524a and 526a and an N-channel
transistor switch 524b and 526b, respectively. The sensor elements 524a and
526a each have a common terminal connected to the respective source
terminals of transistors 524b and 526b, respectively, which are connected to
~s system ground of the controller 502. The elements 524a and 526a also have
respective bias terminals 524d and 526d and output terminals 524c and 526c.
The output terminals 524c and 526c are connected to respective gate terminals
of transistors 524b and 526b.
2o A pull-up resistor, R1, is connected from the drain of each transistor
524b,
526b to a power source, eg such as a battery (not shown), in the controller
502,
which provides system power, V+.
A P-channel transistor 530 has a drain terminal connected to the bias
is output terminals 524c and 526c. The power supply provides system power, V+,
to the source of the transistor 530. The transistor 530 has an active low gate
terminal 531 connected to an inverting output of an inverter 532.
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The transistor 530 is sized such that, when the transistor gate 531 is
pulled low, bias currents will flow in the Hall effect elements 524a and 526a.
The bias currents are selected such that, when the elements 524a and 524b are
close to a sufficiently intense magnetic field, the elements 524a and 524b
send
s output signals on terminals 524c and 526c sufficient to switch on the
transistors
524b and 526b.
Inverter 532 has an input connected to an output 534 of a low duty cycle
pulse timer 536.
Set/Rest flip-flops 544 and 546 have active high clock inputs, CLK,
connected to the timer output 534.
Drain terminals 524b and 526b are connected to inputs of logic inverters
~s 540 and 542 respectively, and also connected to respective reset inputs
544a
and 546a of S-R flip-flops 544 and 546. Inverter output 540 is connected to
set
input 544b of flip-flop 544. Inverter output 542 is connected to set input
546b of
flip-flop 546. Flip-flop outputs 544c and 546c are connected to logic inputs
506a
and 506b of the current control circuit 506.
2o
The current control circuit 506 has outputs 506c and 506d electrically
connected to the sockets 520b and 522b, respectively. The current control
circuit 506 delivers an electrotransport current, I, through the outputs 506c
and
506d, the coupled snap connectors 520 and 522, electrodes 510, 512 and
25 through the body of the patient when activated by the logic inputs 506a and
506b.
The magnitude of the current I is controlled by the circuit 506 as a
function of logic levels A, B (not shown in Fig. 10) at the inputs 506x, 506b.
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The size, shape, spacing and location of the magnets 516, 518 are
configured such that, with the snap connectors 520 and 522 coupled, the Hall
effect elements 524a and 526a are actuated by the magnetic field provided by
s the proximity of the elements 524a, 526a to the magnets 516, 518 as
described
below.
Operation of the device 500 is as follows. The disposable drug unit 508
is attached to the skin of a patient in the conventional manner, eg with
straps or
adhesives, such that the electrodes 510, 512 are in suitable contact for
electrotransport of the therapeutic agent or agents contained in at least one
of
the electrodes 510, 512.
The controller 502 is activated, for example, by a switch (not shown) and
~s electrical power, eg V+, is supplied to the circuit elements therein. The
timer
circuit 536 is arranged to output at least one positive going, low duty cycle
pulse
on the output 534. At each high level on output 534, the CLK inputs of the
flip-
flops 544, 546 are enabled, such that the logic state on the SR inputs
544a,544b
and 546a,546b are transferred to the outputs 544c and 546c.
zo
The output of inverter 532 goes low at this time, causing the p-channel
device 530 to supply bias current to the Hall effect elements 524a and 526a.
In
the presence of a sufficiently strong magnetic field, supplied by the magnets
516
and 518, the Hall effect element outputs 524c and 526c go high and turn on the
zs transistors 524b, 526b. When transistors 524b, 526b turn on, the inputs to
inverters 540 and 542 go low and apply a low level to the reset inputs 544a
and
546x. The inverter 540 and 542 outputs transfer the opposite logic level to
the
SR flip-flop set inputs 544b and 546b. The flip flops 544, 546 will remain in
that
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47
state indefinitely, holding the control inputs 506a and 506b in the state
determined by the detection of presence or absence of the magnets 516, 518.
Table I shows the relation between the presence (designated by "yes"
and "1" in Table 1 ) or absence (designated by "none" and "0" in Table 1 ) of
magnets 516, 518, the logic levels output at points A, B and several exemplary
current levels which can be delivered by the circuit 506.
Table I
16 18 506a B/506b urrent
one one 0 0
es one 1 100
none es 1 150
es es 1 1 00
The details of the circuitry for outputting different values of current under
control of one of a set of logic levels or for generating narrow pulse width,
low
duty cycle pulses is known by those skilled in the art.
In other embodiments of this invention, additional magnets and sensors
can be provided to increase the range of selectable currents, or for other
control
functions. As an example, an additional pair of magnets similarly coupled to
magnetic sensors connected to a current control circuit, can provide control
over
Zo the timing or duration of therapeutic current delivery.
Still another type of signal which can be used in the present invention is a
signal which can be sensed by a metal detector. For example, small pieces of
metal can be placed in the drug unit, with different drug units containing
different
zs metals or differing amounts of the same metal. The controller contains a
metal
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WO 96/38198 PCT/US96/08242
48
detector, which are known in the electro-magnetic arts. The metal defector
senses the signal produced by the metals) in the drug unit, and sets the
controller electrical output according to the sensed signal.
s While the foregoing detailed description has described several
embodiments in accordance with this invention, it is to be understood that the
above description is illustrative only and not limiting of the disclosed
invention. It
will be appreciated that it is possible to modify the type, location and
number of
mechanical fasteners, and electrical connectors, the materials, shape and form
of the controller and drug unit or to include or exclude various elements
within
the scope and spirit of this invention. Thus the invention is limited only by
the
claims as set forth below.
