WO1991015261A1 - Activity controlled electrotransport drug delivery device - Google Patents
Activity controlled electrotransport drug delivery device Download PDFInfo
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- WO1991015261A1 WO1991015261A1 PCT/US1991/002160 US9102160W WO9115261A1 WO 1991015261 A1 WO1991015261 A1 WO 1991015261A1 US 9102160 W US9102160 W US 9102160W WO 9115261 A1 WO9115261 A1 WO 9115261A1
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- activity
- patient
- control signal
- current generator
- generating
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Classifications
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61N—ELECTROTHERAPY; MAGNETOTHERAPY; RADIATION THERAPY; ULTRASOUND THERAPY
- A61N1/00—Electrotherapy; Circuits therefor
- A61N1/02—Details
- A61N1/04—Electrodes
- A61N1/0404—Electrodes for external use
- A61N1/0408—Use-related aspects
- A61N1/0428—Specially adapted for iontophoresis, e.g. AC, DC or including drug reservoirs
- A61N1/0432—Anode and cathode
- A61N1/044—Shape of the electrode
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61N—ELECTROTHERAPY; MAGNETOTHERAPY; RADIATION THERAPY; ULTRASOUND THERAPY
- A61N1/00—Electrotherapy; Circuits therefor
- A61N1/18—Applying electric currents by contact electrodes
- A61N1/20—Applying electric currents by contact electrodes continuous direct currents
- A61N1/30—Apparatus for iontophoresis, i.e. transfer of media in ionic state by an electromotoric force into the body, or cataphoresis
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61N—ELECTROTHERAPY; MAGNETOTHERAPY; RADIATION THERAPY; ULTRASOUND THERAPY
- A61N1/00—Electrotherapy; Circuits therefor
- A61N1/02—Details
- A61N1/04—Electrodes
- A61N1/0404—Electrodes for external use
- A61N1/0408—Use-related aspects
- A61N1/0428—Specially adapted for iontophoresis, e.g. AC, DC or including drug reservoirs
- A61N1/0448—Drug reservoir
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61N—ELECTROTHERAPY; MAGNETOTHERAPY; RADIATION THERAPY; ULTRASOUND THERAPY
- A61N1/00—Electrotherapy; Circuits therefor
- A61N1/18—Applying electric currents by contact electrodes
- A61N1/32—Applying electric currents by contact electrodes alternating or intermittent currents
- A61N1/325—Applying electric currents by contact electrodes alternating or intermittent currents for iontophoresis, i.e. transfer of media in ionic state by an electromotoric force into the body
Definitions
- the present invention relates to transdermal electrotransport drug administration devices and, more particularly, to a patch system which includes a current generator and a sensor for feedback control of the patients activity level to regulate the rate of drug delivery.
- drug and “therapeutic agent” are used interchangeably and are intended to have their broadest interpretation as any therapeutically active substance which is delivered to a living organism to produce a desired, usually beneficial, effect.
- this includes therapeutic agents in all of the major therapeutic areas 5 including, but not limited to, anti-infectives such as antibiotics and antiviral agents, analgesics and analgesic combinations, anesthetics, anorexics, antiarthritics, antiasthmatic agents, anticonvulsants, antidepressants, antidiabetic agents, antidiarrheals, antihistamines, anti-
- anti-infectives such as antibiotics and antiviral agents, analgesics and analgesic combinations, anesthetics, anorexics, antiarthritics, antiasthmatic agents, anticonvulsants, antidepressants, antidiabetic agents, antidiarrheals, antihistamines, anti-
- cardiovascular preparations including calcium channel blockers, beta-blockers, antiarrythmics, antihypertensives, diuretics, vasodilators, including general, coronary, peripheral and cerebral, central nervous system stimulants, cough and cold preparations,
- the invention is also useful in the controlled
- U.S. Patent 4,808,152 - teaches an adjustable iontophoretic generator with programmable output.
- U.S. Patent 4,141,359 - teaches a feedback controlled current source with automatic shutdown in the presence of excessive voltage buildup. « J
- U.S. Patent 4,292,968 - teaches a an iontophoretic generator which operates in a constant current mode, but which may operate in a constant voltage mode if in the presence of high electrode impedance.
- PCT patent application WO 88/08729 teaches an iontophoretic drug delivery system which provides closed loop control of the driving current.
- European patent application 0 309 093 EPA - teaches low frequency oscillator for the application of drugs.
- the device uses a waveform having rapid rise time and a slow fall off time.
- the present invention provides open loop feedback control of the rate of drug delivery as a function of a measurement of patient activity.
- FIG. 3 is an exploded view of the iontophoretic patch depicting structural relationships between the elements of the device.
- transdermally deliverable drugs should be administered at a rate which takes into account the underlying metabolic state or activity level of the recipient.
- a variety of activity sensors may be used to access the patient's physical activity level. However, it is preferred to use a piezoelectric sensor of the type taught by the Anderson reference. It should be appreciated that other forms of activity sensing such as myoelectric sensing, may be used as well.
- the physical activity of the patient is detected by the sensor which is responsive to the body motion proximate the treatment site.
- the current supplied to the patch electrode is regulated, which in turn controls the rate of drug administration.
- the rate of drug delivery should increase with increasing physical activity.
- the rate of drug delivery should decrease with increasing activity.
- the illustrative embodiment increases drug delivery with increases in activity.
- FIG. 2 is a functional block diagram showing the electronic portion of the invention.
- the electronic portion 1 of the invention is composed of several interconnected modules.
- An activity monitoring module 20 switches between a high and a low state with increasing frequency as activity • increases. These level changes are applied to the trigger module 21.
- the trigger module contains a leading edge detector circuit to convert activity level changes to narrow trigger pulses. These trigger pulses trigger the one shot module 22 which in turn generates fixed pulse width pulses of approximately 10 ms.
- the output of the one shot module is low pass filtered by filter module 23.
- the output of the averager 23 is compared to a reference signal in comparator module 24.
- the switching module 25 switches the output current source 28 in response to the activity level of the patient.
- the circuitry shown operates at a lower basal delivery rate and a higher activity based delivery rate.
- the activity module In the absence of patient activity, the activity module generates essentially no activity counts. In this instance, the one shot module 22 output goes to a logic zero. After a brief delay related to the time constant of the averager module 23 the delivery rate drops to a minimum basal rate. In the presence of high patient activity the one shot operates at the activity based rate to establish a maximum drug delivery rate.
- the activity module 20, includes a piezo sensor 27 which is coupled to the patient. This type of transducer deflects in response to patient activity. This sensor is coupled to an integrated circuit 26 which incorporates certain circuit functions more fully described in the incorporated reference. However, in general the activity sensor tracks the activity motion signal of the body, and generates an output which is linearly proportional to the excitation frequency supplied to the sensor by the body. It has been found that this type of activity signal correlates well with the oxygen consumption of the patient over a wide range of activities. In operation the circuitry of module 20 generates activity counts which are supplied to trigger pulse generator 21.
- the trigger pulse generator serves to buffer and square up the activity count pulses. It is preferred to use CMOS logic connected as a leading edge detector to perform this detection and trigger pulse stretching function.
- the one shot module 22 receives the output of the trigger pulse generator.
- This trigger pulse generator 21 output signal is used as a triggering input to a triggerable one-shot multivibrator contained in one-shot module 22.
- the output of the one-shot is a fixed pulse width pulse.
- the - output frequency of the one-shot module 22 tracks the triggering input frequency. In the absence of a trigger input the one-shot 22 output is at a logic zero state.
- pulses are supplied to an averager 23 at an increasing rate. The averager accumulates or integrates these pulses.
- the function of the averager 23 is to prevent rapid excursions in the output current source 28 electrode drive circuit.
- the comparator 24 compares the averaged output of the averager 23 with a reference value and toggles a switching circuit 25. Slight hysteresis is provided to ensure that rapid excursions of the current output do not take place.
- the switching circuit 25 controls the output current source module 28.
- field effect transistor 29 operates in a constant current mode, sinking current from the 9 volt battery supply 30, through the reservoirs and electrodes.
- Field effect transistor 19 operates as a switch to shunt resistor 18 to increase the delivery rate to the higher activated determined value.
- FIG. 3 is an exploded view of the iontophoretic "patch" depicting structural relationships between the Q elements of the device. It is preferred to dispense the patch as a unitary, disposable, single use drug delivery system. However it should be apparent that certain modifications may be made to the device described to render it reusable.
- an adhesive is used to mount the patch to the patient.
- This adhesive is attached to a conformal reservoir housing 41 on its under side 43.
- the separator 16 between the two reservoirs should have sufficient adhesive to isolate the two reservoirs 31, and 32 to prevent short circuiting of-the patch.
- the upper surface 44 of the reservoir housing 41 may be adhesively attached to the flex circuit 36.
- a foam circuit housing 35 may be used to locate and protect the batteries 33 and other high profile circuit components. These electronic structures may be sealed by the use of a thin cover 34. The foam circuit housing 35 may be adhesively attached directly to the reservoir housing thus sealing the flex board within the patch.
- a single gelled drug reservoir 32 is stored in a suitable cavity 39.
- the drug reservoir 32 is connected to one of the circuit electrodes 45.
- a salt may be gelled with a suitable material to form the a gelled counter- reservoir 31 skin connection.
- This other tissue connection is located proximate to the drug delivery .
- ⁇ - reservoir to establish the current path of the circuit.
- the two reservoirs have different surface areas. It may be preferred to use the larger area reservoir 31 as the negative interface to reduce skin 5 irritation.
- a cationic drug may be placed in the first cavity while the second cavity may contain an anionic drug.
- the activity sensor may switch the polarity in response to increased activity, thereby delivering a first cationic drug at a basal activity level and a second cationic drug in response to increased activity levels.
- Suitable switch reversal current sources are known from U.S.
- Patent 4,406,658 which is incorporated by reference. This configuration may also be applied to two drugs in anionic form.
- the patch is activated by closing a suitable switch 17 which supplies current to the circuitry.
- the mounting adhesive on surface 43 may be exposed by removing a suitable wrapper. At this point the patch is placed on the skin of the patient.
- the patch may be used on the upper torso or other area where activity based measurements of patient activity are most accurately
Abstract
Description
Claims
Priority Applications (8)
Application Number | Priority Date | Filing Date | Title |
---|---|---|---|
AU75868/91A AU649439B2 (en) | 1990-03-30 | 1991-03-29 | Activity controlled electrotransport drug delivery device |
EP91907606A EP0522062B1 (en) | 1990-03-30 | 1991-03-29 | Activity controlled electrotransport drug delivery device |
JP50741491A JP3300953B2 (en) | 1990-03-30 | 1991-03-29 | Body movement control type drug delivery device |
CA002079007A CA2079007C (en) | 1990-03-30 | 1991-03-29 | Activity controlled electrotransport drug delivery device |
DE69121885T DE69121885T2 (en) | 1990-03-30 | 1991-03-29 | DEVICE FOR THE IONTOPHORETIC ADMINISTRATION OF DRUGS CONTROLLED BY PHYSICAL ACTIVITY |
NO19923787A NO321603B1 (en) | 1990-03-30 | 1992-09-29 | Apparatus for iontophoric delivery of drugs to a patient |
FI924376A FI111131B (en) | 1990-03-30 | 1992-09-29 | Activity-controlled electronic delivery drug delivery device |
KR1019920702375A KR100192161B1 (en) | 1990-03-30 | 1992-09-30 | Activity controlled electrotransport drug delivery device |
Applications Claiming Priority (3)
Application Number | Priority Date | Filing Date | Title |
---|---|---|---|
US50242290A | 1990-03-30 | 1990-03-30 | |
US502,422 | 1991-03-18 | ||
US671,267 | 1991-03-18 |
Publications (1)
Publication Number | Publication Date |
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WO1991015261A1 true WO1991015261A1 (en) | 1991-10-17 |
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Application Number | Title | Priority Date | Filing Date |
---|---|---|---|
PCT/US1991/002160 WO1991015261A1 (en) | 1990-03-30 | 1991-03-29 | Activity controlled electrotransport drug delivery device |
Country Status (2)
Country | Link |
---|---|
KR (1) | KR100192161B1 (en) |
WO (1) | WO1991015261A1 (en) |
Cited By (14)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
WO1993024178A1 (en) * | 1992-06-02 | 1993-12-09 | Alza Corporation | Iontophoretic drug delivery apparatus |
EP0586666A1 (en) * | 1992-03-17 | 1994-03-16 | Becton Dickinson Co | User activated iontophoretic device and method for using same. |
US5445609A (en) * | 1993-05-28 | 1995-08-29 | Alza Corporation | Electrotransport agent delivery device having a disposable component and a removable liner |
WO1996031251A1 (en) * | 1995-04-07 | 1996-10-10 | Novartis Ag | Iontophoretic transdermal system for the administration of at least two substances |
US5603693A (en) * | 1993-09-10 | 1997-02-18 | Asulab S.A. | Three part device for the transdermic administration of drugs by electrophoresis or iontophoresis |
EP0776677A2 (en) * | 1992-12-31 | 1997-06-04 | Alza Corporation | Electrotransport system |
WO1997039742A1 (en) * | 1996-04-23 | 1997-10-30 | Pharmacia & Upjohn Ab | Transdermally administered dextromethorphan as antitussive agent |
US5817044A (en) * | 1992-11-05 | 1998-10-06 | Becton Dickenson And Company | User activated iontophoertic device |
US5879322A (en) * | 1995-03-24 | 1999-03-09 | Alza Corporation | Self-contained transdermal drug delivery device |
US5899876A (en) * | 1997-08-27 | 1999-05-04 | Becton, Dickinson And Company | Multiple site drug delivery system |
US6035234A (en) * | 1995-06-02 | 2000-03-07 | Alza Corporation | Electrotransport delivery device with voltage boosting circuit |
WO2003059160A1 (en) * | 2002-01-03 | 2003-07-24 | Israel Yerushalmy | Apparatus for treating bruxism |
US7596407B2 (en) | 2004-03-26 | 2009-09-29 | Solvay Pharmaceuticals, B.V. | Transdermal iontophoretic delivery of piperazinyl-2(3H)-benzoxazolone compounds |
EP3061492A1 (en) * | 2002-03-11 | 2016-08-31 | Nitto Denko Corporation | Transdermal drug delivery patch system, method of making same and method of using same |
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US4406658A (en) * | 1981-03-06 | 1983-09-27 | Medtronic, Inc. | Iontophoretic device with reversible polarity |
FR2562800A1 (en) * | 1984-04-11 | 1985-10-18 | Fournier Laboratoires | Device for percutaneous administration of medicaments |
EP0191404A1 (en) * | 1985-02-04 | 1986-08-20 | Telectronics N.V. | Activity sensor for pacemaker control |
WO1986007269A1 (en) * | 1985-06-10 | 1986-12-18 | Drug Delivery Systems Inc. | Programmable control and mounting system for transdermal drug applicator |
US4725263A (en) * | 1986-07-31 | 1988-02-16 | Medtronic, Inc. | Programmable constant current source transdermal drug delivery system |
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Cited By (24)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
EP0586666A1 (en) * | 1992-03-17 | 1994-03-16 | Becton Dickinson Co | User activated iontophoretic device and method for using same. |
EP0586666A4 (en) * | 1992-03-17 | 1994-08-03 | Becton Dickinson And Company | |
WO1993024178A1 (en) * | 1992-06-02 | 1993-12-09 | Alza Corporation | Iontophoretic drug delivery apparatus |
US5817044A (en) * | 1992-11-05 | 1998-10-06 | Becton Dickenson And Company | User activated iontophoertic device |
EP0776677A2 (en) * | 1992-12-31 | 1997-06-04 | Alza Corporation | Electrotransport system |
EP0776677A3 (en) * | 1992-12-31 | 1998-03-25 | Alza Corporation | Electrotransport system |
US5445609A (en) * | 1993-05-28 | 1995-08-29 | Alza Corporation | Electrotransport agent delivery device having a disposable component and a removable liner |
US5603693A (en) * | 1993-09-10 | 1997-02-18 | Asulab S.A. | Three part device for the transdermic administration of drugs by electrophoresis or iontophoresis |
US5879322A (en) * | 1995-03-24 | 1999-03-09 | Alza Corporation | Self-contained transdermal drug delivery device |
US6032073A (en) * | 1995-04-07 | 2000-02-29 | Novartis Ag | Iontophoretic transdermal system for the administration of at least two substances |
WO1996031251A1 (en) * | 1995-04-07 | 1996-10-10 | Novartis Ag | Iontophoretic transdermal system for the administration of at least two substances |
AU701737B2 (en) * | 1995-04-07 | 1999-02-04 | Novartis Ag | Iontophoretic transdermal system for the administration of at least two substances |
US6842640B2 (en) | 1995-06-02 | 2005-01-11 | Alza Corporation | Electrotransport delivery device with voltage boosting circuit |
US6035234A (en) * | 1995-06-02 | 2000-03-07 | Alza Corporation | Electrotransport delivery device with voltage boosting circuit |
US7708731B2 (en) | 1995-06-02 | 2010-05-04 | Alza Corporation | Electrotransport delivery device with voltage boosting circuit |
AU714942B2 (en) * | 1996-04-23 | 2000-01-13 | Mcneil Ab | Transdermally administered dextromethorphan as antitussive agent |
US6335030B1 (en) | 1996-04-23 | 2002-01-01 | Pharmacia & Upjohn Ab | Transdermally administered dextromethorphan as antitussive agent |
WO1997039742A1 (en) * | 1996-04-23 | 1997-10-30 | Pharmacia & Upjohn Ab | Transdermally administered dextromethorphan as antitussive agent |
US5899876A (en) * | 1997-08-27 | 1999-05-04 | Becton, Dickinson And Company | Multiple site drug delivery system |
WO2003059160A1 (en) * | 2002-01-03 | 2003-07-24 | Israel Yerushalmy | Apparatus for treating bruxism |
AU2003207944B2 (en) * | 2002-01-03 | 2007-04-05 | Israel Yerushalmy | Apparatus for treating bruxism |
EP3061492A1 (en) * | 2002-03-11 | 2016-08-31 | Nitto Denko Corporation | Transdermal drug delivery patch system, method of making same and method of using same |
US9486616B2 (en) | 2002-03-11 | 2016-11-08 | Nitto Denko Corporation | Transdermal integrated actuator device, methods of making and using same |
US7596407B2 (en) | 2004-03-26 | 2009-09-29 | Solvay Pharmaceuticals, B.V. | Transdermal iontophoretic delivery of piperazinyl-2(3H)-benzoxazolone compounds |
Also Published As
Publication number | Publication date |
---|---|
KR100192161B1 (en) | 1999-06-15 |
KR930700180A (en) | 1993-03-13 |
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