Surgery – Means for introducing or removing material from body for... – Infrared – visible light – ultraviolet – x-ray or electrical...
Reexamination Certificate
1999-05-20
2002-05-07
Bockelman, Mark (Department: 3763)
Surgery
Means for introducing or removing material from body for...
Infrared, visible light, ultraviolet, x-ray or electrical...
Reexamination Certificate
active
06385488
ABSTRACT:
BACKGROUND OF THE INVENTION
1. Field of the Invention
The invention is in the field of iontophoresis. In particular, the invention relates to circuits for increasing the reliability of an iontophoretic drug delivery system.
2. Description of Related Art
Iontophoresis is the migration of ions when an electrical current is passed through a solution containing an ionized species, usually the ionic form of a drug or other therapeutic agent (hereinafter referred to as the “drug”). One particularly advantageous application of iontophoresis is the noninvasive transdermal delivery of ionized drugs into a patient using low levels of current. Iontophoretic drug delivery offers an alternative and effective method of drug delivery over other methods such as passive transdermal patches, needle injection, and oral ingestion, and is an especially effective method for children, the bedridden and the elderly. Known advantages of transdermal delivery include avoiding the risks and inconvenience of intravenous delivery. Also, problems associated with oral drug ingestion, such as drug loss caused by digestion and hepatic first pass metabolism are avoided as the gastrointestinal tract and liver (on first pass) are bypassed.
Transdermal delivery advantageously provides continuous drug delivery, easy termination and more convenience.
An iontophoresis transdermal drug delivery system usually includes a patch having multiple reservoirs, one of which, called the active reservoir, contains positively-or negatively-charged drug ions, and another one of which, called the return reservoir, contains an electrolytic solution, such as a saline solution. Located within the reservoirs are electrodes for applying current into the patch. The iontophoresis system also includes a controller device, which is electrically and mechanically connected to the patch. The controller usually contains a power source such as a battery, as well as electrical circuitry required for generating and regulating the current applied to the patch electrodes.
One possible configuration of an iontophoretic delivery device is shown in
FIG. 1. A
controller
80
, including a battery, is respectively connected to an anode
61
and cathode
62
in the patch
60
via the electrical interconnectors
11
and
12
. The anode
61
is arranged in the active reservoir containing a positively-charged drug, while the cathode
62
is arranged in the return reservoir containing the electrolytic (or saline) solution. If the drug is negatively-charged, the anode and cathode arrangement in the reservoirs is reversed, so that when current is applied to the electrodes, drug ions will be repelled from the reservoir of similar polarity. When the patch
60
is placed on the skin of a user and the controller applies current to the patch
60
, the charged drug is forced into the skin of the patient. Other ions are returned to the return reservoir as the body completes the ionic circuit. For example, if the drug is negatively-charged, a AgCl cathode will repel them through the skin, while positively-charged sodium ions are attracted to the cathode. At the same time, negatively-charge chlorine ions will flow from the skin into a return reservoir containing saline toward the anode.
The controller usually includes a microprocessor or state machine to implement numerous control functions. For example, a microprocessor executes software programs which, inter alia, command the current generation and regulation circuitry to provide the required amount of current over a period of time. Because the amount of drug delivered to the patient is directly proportional to the amount of current delivered, the drug dosage can be controlled by regulating the amount of current delivered to the patch.
The microprocessor or the state machine is clocked externally by a counter driven by a crystal oscillator having, for example, a 32.768 kHz frequency (i.e., a watch crystal). This permits the microprocessor or state machine, and thus the system, to cycle through current delivery states, each state defining the current to be delivered over a predetermined time interval. For example, curve A of
FIG. 2
shows a desired current delivery profile. In this profile, the current starts at zero amps. After a first time, t
1
, the current rises to a first current level, after a second time, t
2
, rises to a second, higher current level, after a third time, t
3
, drops back to the first current level, and after a fourth time, t
4
, drops back to zero amps. When the crystal oscillator is operating properly, the microprocessor cycles through each of those current delivery levels over the course of the delivery cycle, thereby directing the current circuitry to generate and deliver the correct amount of current to the patch in accordance with each current level.
However, if the oscillator becomes inoperable during the course of a drug delivery cycle, a drug overdosage or underdosage condition may arise. For example, in curve B of
FIG. 2
, the oscillator has failed at time t
b
. At this time, the microprocessor (or state machine) will become stuck at its last program instruction (or step), that is, the instruction that causes the current circuitry to generate and deliver the second, higher level of current. Accordingly, when the oscillator fails at time t
b
, the system will continue to provide the higher level of current beyond time t
3
, since the microprocessor (or state machine) cannot reach the next program instruction (or step), and thus the next current state. This may result in an inaccurate amount of delivered drug. In the case of curve B, this would be a drug overdosage. In contrast, as shown by curve C, the oscillator has stopped at time t
a
. This failure causes the microprocessor (or state machine) not to reach the instruction (or step) corresponding to the higher current level time interval. Instead, current continues to be delivered at the lower current level, which may result in a drug underdosage or overdosage, depending on when the current is caused to stop.
In addition, the iontophoretic system may employ a voltage reference to provide a highly-accurate output voltage, for example, 1.203 volts, to critical components within the current circuitry. In particular, one way of generating the patch current is to output a digital value from the microprocessor (or state machine) to a D/A converter. The D/A converter in turn converts the digital value to an analog voltage, based on the voltage reference output voltage. That analog voltage is then converted to the patch current using a voltage-to-current converter. An inaccurate voltage reference output voltage, however, will cause both the analog voltage and thus the patch current to be inaccurate. An inaccuracy in patch current may result in a drug overdosage condition, if the patch current is too high, or a drug underdosage condition, if the patch current is too low.
Furthermore, a drug underdosage condition may result if the system's battery power source runs out during a drug delivery cycle. The running down of the battery energy will first cause too little patch current to be produced, and eventually the failure of the device circuitry and no patch current.
SUMMARY OF THE INVENTION
It is thus an object of the present invention to provide circuits for increasing the reliability of an iontophoretic drug delivery system to minimize the possibility of drug overdosage or underdosage conditions.
In one aspect of the present invention, circuits are provided to detect the failure of a crystal oscillator of the system.
In another aspect of the present invention, circuits are provided to detect the failure of a voltage reference of the system.
In yet another aspect of the present invention, a circuit is provided to detect the impending failure of a battery power source of the system.
REFERENCES:
patent: 5499967 (1996-03-01), Teillaud et al.
patent: 5876368 (1999-03-01), Flower
patent: 5899876 (1999-05-01), Flower
patent: 5991655 (1999-11-01), Gross et al.
patent: 6029083 (2000-02-01), Flower et al.
patent: 6035234 (2000-03-01), Riddle e
Flower Ronald J.
Garde Kenneth E.
Walter Steven D.
Bockelman Mark
Kirkpatrick & Lockhart LLP
Vyteris, Inc.
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