CA2343893C - Iontophoretic drug delivery electrodes - Google Patents
Iontophoretic drug delivery electrodes Download PDFInfo
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- CA2343893C CA2343893C CA002343893A CA2343893A CA2343893C CA 2343893 C CA2343893 C CA 2343893C CA 002343893 A CA002343893 A CA 002343893A CA 2343893 A CA2343893 A CA 2343893A CA 2343893 C CA2343893 C CA 2343893C
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- medicament
- electrode
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- skin
- substrate
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- 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
Abstract
Non-reusable, medicament-dispensing applicator electrodes (10) adapted for u se with an iontophoresis device or an ionosonic device for facilitating delivery of medication across the cutaneous membrane into adjacent underlying tissues, and blood vessels. The embodiments of the iontophoresis electrode include an open mesh (12) having cells (12a) in the medicament dispensing portions (11) of the electrode which retain a medicament in the form of liquid, gel or ointment. The cells are adapted to contain, to iontophoretically dispense, and deliver medicament. The medicament-dispensing electrodes (70) are composite or unita ry in construction and may be useful in the treatment of acne, and also genital herpes simplex infection. The delivery electrode (71), when used in accordance with the medicated electrode, and method described herein, demonstrated > 90 % treatment efficacy in clinical trials for the treatment of genital herpes. The applicator electrode may also be used with an ionosonic handpiece (40).
Description
2 TITLE: IONTOPHORETIC DRUG DELIVERY ELECTRODES
4 INVENTOR: JULIAN L. HENLEY, M.D.
lo 1 Field of the Invention:
l l This invention relates generally to the transdermal electrokinetic mass transfer 12 of medication into a diseased tissue, and, more specifically, to a iontophoresis 13 electrode for the transdermal delivery of medication into diseased tissues and blood 14 vessels adjacent to the delivery site.
2. Prior Art:
16 lontophoresis has been employed for several centuries as a means for applying 17 medication locally through a patient's skin and for delivering medicaments to the eyes 18 and ears. The application of an electric field to the skin is known to greatly enhance 19 the skin's permeability to various ionic agents. This permeability change has been used, for example, to enhance transcutaneous transport of glucose for monitoring 21 blood glucose levels. The use of iontophoretic transdermal delivery techniques has 22 obviated the need for hypodermic injection for many medicaments, thereby eliminating 23 the concomitant problems of trauma, pain and risk of infection to the patient.
24 lontophoresis involves the application of an electromotive force to drive charged ions into the dermal layers comprising or overlying a target tissue.
26 Particularly suitable target tissue includes tissues adjacent to the delivery site for 27 localized treatment or tissues remote therefrom in which case the medicament enters 28 into the circulatory system and is transported to a tissue by the blood.
Positively 29 charged ions are driven into the skin at an anode while negatively charged ions are 3o driven into the skin at a cathode. Studies have shown increased skin penetration of SUBSTITUTE SHEET (RULE 26) 1 drugs at anodic or cathodic electrodes regardless of the predominant molecular ionic 2 charge on the drug. This effect is mediated by polarization and osmotic effects.
4 INVENTOR: JULIAN L. HENLEY, M.D.
lo 1 Field of the Invention:
l l This invention relates generally to the transdermal electrokinetic mass transfer 12 of medication into a diseased tissue, and, more specifically, to a iontophoresis 13 electrode for the transdermal delivery of medication into diseased tissues and blood 14 vessels adjacent to the delivery site.
2. Prior Art:
16 lontophoresis has been employed for several centuries as a means for applying 17 medication locally through a patient's skin and for delivering medicaments to the eyes 18 and ears. The application of an electric field to the skin is known to greatly enhance 19 the skin's permeability to various ionic agents. This permeability change has been used, for example, to enhance transcutaneous transport of glucose for monitoring 21 blood glucose levels. The use of iontophoretic transdermal delivery techniques has 22 obviated the need for hypodermic injection for many medicaments, thereby eliminating 23 the concomitant problems of trauma, pain and risk of infection to the patient.
24 lontophoresis involves the application of an electromotive force to drive charged ions into the dermal layers comprising or overlying a target tissue.
26 Particularly suitable target tissue includes tissues adjacent to the delivery site for 27 localized treatment or tissues remote therefrom in which case the medicament enters 28 into the circulatory system and is transported to a tissue by the blood.
Positively 29 charged ions are driven into the skin at an anode while negatively charged ions are 3o driven into the skin at a cathode. Studies have shown increased skin penetration of SUBSTITUTE SHEET (RULE 26) 1 drugs at anodic or cathodic electrodes regardless of the predominant molecular ionic 2 charge on the drug. This effect is mediated by polarization and osmotic effects.
3 Regardless of the charge of the medicament to be administered, a 4 iontophoretic delivery device employs two electrodes (an anode and a cathode) in conjunction with the patient's skin to form a closed circuit between one of the 6 electrodes (referred to herein alternatively as a "working" or "application"
or 7 "applicator" electrode) which is positioned at the site of drug delivery and a passive or 8 "grounding" electrode affixed to a second site on the skin to enhance the rate of 9 penetration of the medicament into the skin adjacent to the applicator electrode.
lo Ultrasonic vibrations may be used in conjunction with iontophoresis to facilitate 1 t iontophoretic deliver of a drug. An apparatus employing both iontophoresis and 12 ultrasonic vibrations to transdermally deliver medicament is referred to herein as an 13 ionosonic apparatus.
14 Recent interest in the use of iontophoresis for the transdermal delivery of drugs to a desired cutaneous or subcutaneous treatment site has stimulated a redesign 16 of many of such drugs with concomitant increased efficacy of the drugs when 17 delivered transdermally. As iontophoretic delivery of medicaments become more 18 widely used, the opportunity for a consumer/patient to iontophoretically self-19 administer a transdermal dosage of medicaments simply and safely at non-medical or non-professional facilities would be desirable and practical. Similarly, when a 21 consumer/patient travels, it would be desirable to have a personal, easily transportable 22 apparatus available which is operable for the iontophoretic transdermal delivery of a 23 medication packaged in a single dosage applicator. A problem which presents an 24 impediment to potential users is the necessity for reformulating medicaments for iontophoretic delivery. Such reformulations must be approved by cognizant 26 regulatory agencies prior to sale. This requires delay and additional expense for the 27 manufacturer, which additional expense may be passed along to consumers.
The 28 present invention provides a disposable medicament dispensing electrode for use with 29 a portable iontophoretic medicament delivery apparatus in which the electrode is adapted for use with the apparatus for self-administering medicament. The SUBSTITUTE SHEET (RULE 26) 1 medicament dispensing portion of the electrode can accept, store and dispense 2 presently approved medicament formulations.
The present invention discloses a unit dosage medicament applicator electrode 6 adapted for use with a portable iontophoretic transdermal or transmucoscal 7 medicament delivery apparatus for the self-administration of a unit dose of a 8 medicament into the skin. While the discussion to follow refers to iontophoretic 9 devices, it is understood that an ionosonic device is included within the meaning of iontophoretic devices. The electrode and current supply apparatus is particularly 11 suited for the localized treatment of herpes infections. The established treatment for 12 recurrent genital herpetic lesions has been primarily supportive; including local topical 13 application of anesthesia. Severe cases have been treated with systemic Acyclovir , 14 Zovirax (Glaxo -Wellcome) or Famvir (SmithKline Beecham). Some cases the condition is managed with prophylactic long-term dosing administration with a 16 suitable anitviral agent at great expense. Systemic treatment of acute herpetic flare-17 ups may reduce the normal 10-12 day course of cutaneous symptoms into a 6-8 day 18 episode. Topical treatment of lesions with Acyclovir has not been as effective as in 19 vitro studies would suggest. A compound which is not presently available to clinicians but has demonstrated significant anti herpetic activity is 5-iodo-2 deoxyuridine 21 (IUDR). Both of those agents have shown limited clinical efficacy when applied 22 topically to the herpetic lesion. It is the present inventor's contention that the limited 23 efficacy of topical administration previously observed is, at least in part, due to the 24 poor skin penetration of these medicaments when applied topically. The present invention discloses a mesh-like iontophoresis electrode, which contains and dispenses 26 pre-approved formulations of those medicaments and provides improved transdermal 27 delivery of these medicaments. The device and associated medicament dispensing 28 electrodes may be used to treat such diverse conditions as herpes, warts, acne and 29 psoriasis.
Genital herpes (usually herpes simplex II infection) afflicts many people, cause 31 discomfort, shame, and may contribute to more severe and costly illnesses such as SUBSTITUTE SHEET (RULE 26) 1 cervical cancer, prostate cancer, and perinatal blindness from herpetic conjunctivitis.
2 Certain formulations containing anti-viral and/or anti-microbial drugs have been 3 approved for topical application by the cognizant regulatory agency.
Reformulation 4 of such compositions for iontophoretic transdermal drug delivery entails significant delays before such technology is available to the public for general use. The present 6 invention discloses a medicated iontophoresis electrode for the portable transdermal 7 delivery of Acyclovir (9-[(2-hydroxyethoxy)methyl]guanine) or similar anti-viral 8 agent formulations which have already received (or may in the future receive) 9 regulatory approval to greatly benefit these afflicted patients. In a second preferred embodiment of the invention, the medicament delivery electrode is attached to a user-i l wearable glove having one or more fingers or merely a finger cot covering at least a 12 portion of one or more fingers of a user's hand.
13 It is an object of the present invention to provide an iontophoretic medicament 14 delivery electrode which is adapted to be used with an iontophoresis device operable for self-administration of inedicament into the skin of a person.
16 It is another object of the present invention to provide an improved 17 iontophoretic transdermal drug delivery apparatus having a medicament-containing 18 application electrode which dispenses and transdermally delivers a single dosage and 19 which is disposable and non-reusable.
It is a further object of the present invention to provide an iontophoresis 21 electrode meeting the above objectives which can receive and retain a previously 22 approved drug formulation for dispensation by ionosonic transdermal delivery.
23 It is still another advantage of the present invention to provide an improved 24 disposable iontophoretic medicament applicator which meets the above objectives and which is inexpensive, safe to use and greatly increases the therapeutic efficacy of a 26 medicament administered thereby.
27 The medicament-containing electrode in accordance with the present 28 invention, together with an iontophoresis or ionosonic apparatus, provides a means 29 for transdermally administering medicament dispersed in a variety of previously approved formulations directiy and with high efficiency into a diseased tissue thereby 31 providing a novel method for treating clinical conditions presenting cutaneous and/or SUBSTITUTE SHEET (RULE 26) mucocutaneous symptoms such as warts, acne, superficial fungus infections, hyperprolifer-ative diseases such as psoriasis, and particularly mucocutaneous Herpes simplex viral eruptions and sequelle associated therewith.
The invention thus provides according to a first aspect for a medicament dispensing iontophoresis applicator electrode comprising a generally thimble-shaped electrically conductive member and an overlying medicament dispensing portion of an electrically non-conducting elastomer having a cell or plurality of cells in at least a portion thereof and wherein the thimble-shaped conductive portion is dimensioned to fit over and conform to the shape of the distal end of a finger.
According to a second aspect, the invention provides for a medicament-dispensing applicator electrode for use with an electrokinetic device to transdermally deliver a medica-ment to an individual, comprising: a substrate having a first surface and a second surface opposite the first surface, the substrate including a medicament-dispensing portion com-prising a cell or a plurality of cells forming an aperture or a plurality of apertures between the first surface and the second surface, the cell or plurality of cells containing the medica-ment; and a layer of adhesive covering at least a portion of the second surface of the sub-strate opposite the first surface for releasably attaching the substrate to an electrokinetic device containing an electrical power source for electrokinetically driving the medicament through the first surface and into the individual's skin upon application of an electrical current to effect delivery of the medicament in the cell or plurality of cells to the individual's skin.
According to a third aspect, the invention provides for a medicament-dispensing applicator electrode for use with an electrokinetic device to transdermally deliver a medica-ment to an individual, comprising: a substrate having a first surface and a second surface opposite the first surface, the substrate including a medicament-dispensing portion com-prising a cell or a plurality of cells forming an aperture or a plurality of apertures between the first surface and the second surface, the cells or plurality of cells containing the medica-ment; and a layer of adhesive covering at least a portion of the first surface of the substrate opposite the second surface for releasably attaching the substrate to an individual's skin, the aperture or plurality of apertures being open along the second surface such that the medica-ment is electrokinetically driven through the first surface and into the individual's skin upon - 5a-electrically contacting an electrokinetic device containing an electrical power source with the second surface of the medicament-dispensing portion to generate an electrical current to effect delivery of the medicament in the cell or plurality of cells to the individual's skin.
According to a fourth aspect, the invention provides for a medicament-dispensing applicator electrode for use with an electrokinetic device to transdermally deliver a medica-ment to an individual, comprising: a substrate having a first surface and a second surface opposite the first surface, the substrate including a medicament-dispensing portion between the first surface and the second surface and defining a reservoir for containing the medica-ment; and a layer of adhesive covering at least a portion of one of the first surface and the second surface of the substrate for releasably attaching the substrate to one of an electro-kinetic medicament-delivery device containing an electrical power source or an individual's skin, the second surface of the medicament-dispensing portion being pervious to enable electrical contact through the second surface with the medicament or a carrier therefor such that the medicament is electrokinetically driven from the reservoir through the first surface and into the individual's skin upon transmission of an electrical current through the second surface, the reservoir and the first surface.
According to a fifth aspect, the invention provides for an apparatus for the trans-dermal delivery of a medicament to an individual, comprising: a medicament-dispensing applicator electrode including a substrate having a first surface and a second surface opposite the first surface, the substrate including a medicament-dispensing portion comprising a cell or a plurality of cells forming an aperture or a plurality of apertures between the first surface and the second surface, the cell or plurality of cells containing the medicament; an electro-kinetic device comprising a housing having a portion thereof shaped for grasping within an individual's hand for manual manipulation by the individual, and a first electrode formed of electrically conductive material and in electrical contact with the substrate and with a portion of an individual's skin upon application of the device to the individual's skin with the sub-strate interposed therebetween; a power source contained within the housing having first and second terminals, the first terminal being in electrical contact with the first electrode; a tactile electrode in electrical contact with the second terminal of the power source and having a surface for electrical contact with another portion of an individual's skin;
and the device being operable to electrokinetically drive the medicament from the applicator electrode to - 5b -effect delivery of the medicanient in the cell or plurality of cells to the portion of the individual's skin in contact with the substrate on one side thereof in response to completion of an electrical circuit between the first terminal through the first electrode and the substrate via the individual's skin portion and the second terminal via the tactile electrode and the another portion of the individual's skin.
According to a sixth aspect, the invention provides for an apparatus for the trans-dermal delivery of a medicament to an individual, comprising: a medicament-dispensing applicator electrode; an electrokinetic device; the medicament-dispensing applicator elec-trode including a substrate having a first surface and a second surface opposite the first surface, the substrate including a medicament-dispensing portion comprising a cell or a plurality of cells forming an aperture or a plurality of apertures between the first surface and the second surface, the cell or plurality of cells containing the medicament, the substrate having a portion thereof for releasably coupling the substrate to the device;
the device comprising a housing having a portion thereof shaped for grasping within an individual's hand for manual manipulation by the individual, and a first electrode formed of electrically conductive material and exposed for contact with the substrate upon releasable connection to the device; a power source contained within the housing having first and second terminals, the first terminal being in electrical contact with the first electrode; a tactile electrode in electrical contact with the second terminal of the power source and having a surface for contact with the individual's skin; and the device being operable to electrokinetically drive the medicament from the applicator electrode to effect delivery of the medicament in the cell or plurality of cells to a portion of the individual's skin in contact with the substrate on one side thereof in response to completion of an electrical circuit between the first terminal through the first electrode and the substrate via the individual's skin and the second terminal via the tactile electrode and another portion of the individual's skin.
According to a seventh aspect, the invention provides for a medicament-dispensing electrokinetic applicator for delivering medicament to a large area of an individual's skin, comprising: a glove-shaped body containing a medicament for application through an outer surface thereof; and a conductive layer formed within the glove-shaped body for connection with an electrical power source and electrokinetically driving the medicament from the body onto an area of the individual's skin overlaid and in contact with the glove-shaped body upon - 5c -application of an electrical current to effect delivery of the medicament contained in the body to the large area of the individual's skin in contact with the overlying glove-shaped body, wherein the conductive layer comprises a multi-channel electrode.
According to a eighth aspect, the invention provides for an apparatus for the trans-dermal delivery of medicament to an individual, comprising: a medicament-dispensing electrode; an electrokinetic device; the medicament-dispensing electrode including a sub-strate having a first surface and a second surface opposite the first surface, the substrate including a medicament-dispensing portion having a cellular structure with one or a plurality of cells dimensioned to retain a medium including the medicament within the confines of the cellular structure for electrokinetically transporting the medicament from the cell or plurality of cells through the first surface into the individual's skin upon flowing an electrical current between the first surface and the second surface; a tactile conductive portion carried by the substrate having a second cell or a plurality of cells electrically insulated from the medica-ment-dispensing portion, the second cell or plurality of cells containing an electrically con-ductive material for electrical connection through the second surface with a conductive portion on the electrokinetic device; and the electrokinetic device including a housing having a portion thereof shaped for manual manipulation by the individual's hand, and a first elec-trode exposed for contact with the second surface of the substrate upon engagement of the substrate and the device with one another, a power source within the housing and having first and second terminals, the first terminal being in electrical contact with the first electrode, a tactile electrode in electrical contact with the second terminal of the power source and having a surface for electrical contact with the tactile conductive portion of the applicator electrode, the device being operable to deliver the medicament from the applicator electrode to a por-tion of the individual's skin in contact with the first surface in response to completion of an electrical circuit between the first terminal through the first electrode and the substrate via the individual's skin and the second terminal via the tactile electrode, the tactile conductive portion and another portion of the individual's skin.
According to a ninth aspect, the invention provides for a use of a hand-held ionto-phoretic device comprising an electrode and a medicament dispensing reservoir containing an antiviral agent, the reservoir being in electrical communication with the electrode, for treating lesions associated with cold sore and genital herpes, wherein the medicament - 5d-dispensing reservoir is in contact with the lesions and a voltage gradient between the elec-trode and the lesion is present.
According to a tenth aspect, the invention provides for a use of a hand-held ionosonic device comprising an electrode and a medicament dispensing reservoir containing an anti-viral agent, the reservoir being in electrical communication with the electrode, for treating lesions associated with cold sore and genital herpes, wherein: the medicament dispensing reservoir is in contact with the lesions; ultrasonic vibration in a tissue comprising the lesion is present; and a voltage gradient between the electrode and the lesion is present.
According to a eleventh aspect, the invention provides for a use of a hand-held iono-sonic device comprising an electrode and a medicament dispensing reservoir containing an ionic compound in electrical communication with the electrode, for treating lesions associ-ated with acne, wherein: the medicament dispensing reservoir comes into contact a the lesion; ultrasonic vibration in a tissue comprising the lesion is present; and a voltage gradient between the electrode and the lesion is present.
According to a twelfth aspect, the invention provides for a disposable medicament dispensing applicator electrode for an iontophoretic drug delivery device adapted for the self-administration of a medicament into a person's skin, the device comprising a base assembly having an active terminal adapted to receive and make electrical contact with a detachable medicament dispensing applicator electrode wherein the base assembly comprises: a case having an elongate, substantially cylindrical outer surface having a size and shape adapted to be comfortably grasped within a person's hand and wherein at least a portion of the outer surface is a tactile electrode formed of an electrically conductive material;
and a bipolar electrical power means having a first pole and a second pole; the electrical power means being enclosed within the case and wherein the first pole is in electrical communication with the tactile electrode; wherein the medicament dispensing applicator electrode comprises: a module containing unit dose of medicament, an electrically conductive working electrode and means thereon adapted for releasably attaching the working electrode to the second pole of the electrical power means wherein the working electrode further comprises an elongate strip constructed of a substantially electrically non-conductive substrate material, the strip having a central portion containing a medicament in an electrically conductive substrate and laterally symmetric end portions having cutouts therewithin.
- 5e-The above objects, features and advantages of the invention are realized by the im-proved iontophoretic medicament applicator electrode of the present invention.
The objects, features and advantages of the invention will become apparent upon consideration of the following detailed disclosure of the invention, especially when it is taken in conjunction with the accompanying drawings wherein:
BRIEF DESCRIPTION OF THE DRAWINGS
FIG. 1 is a top plan view of a first embodiment of the disposable iontophoretic medi-cament containing applicator electrode adapted for attachment to an iontophoresis handpiece wherein the medicament dispensing portion of the electrode is an open mesh.
FIG. 2 is a side elevational view of a preferred embodiment of the disposable non-reusable iontophoretic applicator electrode for use with an iontophoresis handpiece adapted for self-administration.
FIG. 3 is a top plan view of the iontophoresis applicator electrode in accordance with claim 2.
FIG. 4 is a horizontal cross-sectional plan view of an iontophoresis handpiece adapt-ed for use with the embodiments of the medicament dispensing applicator electrode of the present invention shown in Figures 1 - 3.
FIG. 5 is a perspective view showing the applicator electrode of Figures 1- 3 releas-ably affixed to an iontophoresis handpiece in accordance with Figure 4.
FIG. 6 shows a patient preparing to self-administer medicament to a treatment site.
FIG. 7 is a top plan view of an embodiment of a medicament dispensing applicator electrode having unitary construction and an open mesh medicament dispensing portion similar to the embodiment shown in Figures 1 - 3 and adapted for attachment to the skin of a patient.
or 7 "applicator" electrode) which is positioned at the site of drug delivery and a passive or 8 "grounding" electrode affixed to a second site on the skin to enhance the rate of 9 penetration of the medicament into the skin adjacent to the applicator electrode.
lo Ultrasonic vibrations may be used in conjunction with iontophoresis to facilitate 1 t iontophoretic deliver of a drug. An apparatus employing both iontophoresis and 12 ultrasonic vibrations to transdermally deliver medicament is referred to herein as an 13 ionosonic apparatus.
14 Recent interest in the use of iontophoresis for the transdermal delivery of drugs to a desired cutaneous or subcutaneous treatment site has stimulated a redesign 16 of many of such drugs with concomitant increased efficacy of the drugs when 17 delivered transdermally. As iontophoretic delivery of medicaments become more 18 widely used, the opportunity for a consumer/patient to iontophoretically self-19 administer a transdermal dosage of medicaments simply and safely at non-medical or non-professional facilities would be desirable and practical. Similarly, when a 21 consumer/patient travels, it would be desirable to have a personal, easily transportable 22 apparatus available which is operable for the iontophoretic transdermal delivery of a 23 medication packaged in a single dosage applicator. A problem which presents an 24 impediment to potential users is the necessity for reformulating medicaments for iontophoretic delivery. Such reformulations must be approved by cognizant 26 regulatory agencies prior to sale. This requires delay and additional expense for the 27 manufacturer, which additional expense may be passed along to consumers.
The 28 present invention provides a disposable medicament dispensing electrode for use with 29 a portable iontophoretic medicament delivery apparatus in which the electrode is adapted for use with the apparatus for self-administering medicament. The SUBSTITUTE SHEET (RULE 26) 1 medicament dispensing portion of the electrode can accept, store and dispense 2 presently approved medicament formulations.
The present invention discloses a unit dosage medicament applicator electrode 6 adapted for use with a portable iontophoretic transdermal or transmucoscal 7 medicament delivery apparatus for the self-administration of a unit dose of a 8 medicament into the skin. While the discussion to follow refers to iontophoretic 9 devices, it is understood that an ionosonic device is included within the meaning of iontophoretic devices. The electrode and current supply apparatus is particularly 11 suited for the localized treatment of herpes infections. The established treatment for 12 recurrent genital herpetic lesions has been primarily supportive; including local topical 13 application of anesthesia. Severe cases have been treated with systemic Acyclovir , 14 Zovirax (Glaxo -Wellcome) or Famvir (SmithKline Beecham). Some cases the condition is managed with prophylactic long-term dosing administration with a 16 suitable anitviral agent at great expense. Systemic treatment of acute herpetic flare-17 ups may reduce the normal 10-12 day course of cutaneous symptoms into a 6-8 day 18 episode. Topical treatment of lesions with Acyclovir has not been as effective as in 19 vitro studies would suggest. A compound which is not presently available to clinicians but has demonstrated significant anti herpetic activity is 5-iodo-2 deoxyuridine 21 (IUDR). Both of those agents have shown limited clinical efficacy when applied 22 topically to the herpetic lesion. It is the present inventor's contention that the limited 23 efficacy of topical administration previously observed is, at least in part, due to the 24 poor skin penetration of these medicaments when applied topically. The present invention discloses a mesh-like iontophoresis electrode, which contains and dispenses 26 pre-approved formulations of those medicaments and provides improved transdermal 27 delivery of these medicaments. The device and associated medicament dispensing 28 electrodes may be used to treat such diverse conditions as herpes, warts, acne and 29 psoriasis.
Genital herpes (usually herpes simplex II infection) afflicts many people, cause 31 discomfort, shame, and may contribute to more severe and costly illnesses such as SUBSTITUTE SHEET (RULE 26) 1 cervical cancer, prostate cancer, and perinatal blindness from herpetic conjunctivitis.
2 Certain formulations containing anti-viral and/or anti-microbial drugs have been 3 approved for topical application by the cognizant regulatory agency.
Reformulation 4 of such compositions for iontophoretic transdermal drug delivery entails significant delays before such technology is available to the public for general use. The present 6 invention discloses a medicated iontophoresis electrode for the portable transdermal 7 delivery of Acyclovir (9-[(2-hydroxyethoxy)methyl]guanine) or similar anti-viral 8 agent formulations which have already received (or may in the future receive) 9 regulatory approval to greatly benefit these afflicted patients. In a second preferred embodiment of the invention, the medicament delivery electrode is attached to a user-i l wearable glove having one or more fingers or merely a finger cot covering at least a 12 portion of one or more fingers of a user's hand.
13 It is an object of the present invention to provide an iontophoretic medicament 14 delivery electrode which is adapted to be used with an iontophoresis device operable for self-administration of inedicament into the skin of a person.
16 It is another object of the present invention to provide an improved 17 iontophoretic transdermal drug delivery apparatus having a medicament-containing 18 application electrode which dispenses and transdermally delivers a single dosage and 19 which is disposable and non-reusable.
It is a further object of the present invention to provide an iontophoresis 21 electrode meeting the above objectives which can receive and retain a previously 22 approved drug formulation for dispensation by ionosonic transdermal delivery.
23 It is still another advantage of the present invention to provide an improved 24 disposable iontophoretic medicament applicator which meets the above objectives and which is inexpensive, safe to use and greatly increases the therapeutic efficacy of a 26 medicament administered thereby.
27 The medicament-containing electrode in accordance with the present 28 invention, together with an iontophoresis or ionosonic apparatus, provides a means 29 for transdermally administering medicament dispersed in a variety of previously approved formulations directiy and with high efficiency into a diseased tissue thereby 31 providing a novel method for treating clinical conditions presenting cutaneous and/or SUBSTITUTE SHEET (RULE 26) mucocutaneous symptoms such as warts, acne, superficial fungus infections, hyperprolifer-ative diseases such as psoriasis, and particularly mucocutaneous Herpes simplex viral eruptions and sequelle associated therewith.
The invention thus provides according to a first aspect for a medicament dispensing iontophoresis applicator electrode comprising a generally thimble-shaped electrically conductive member and an overlying medicament dispensing portion of an electrically non-conducting elastomer having a cell or plurality of cells in at least a portion thereof and wherein the thimble-shaped conductive portion is dimensioned to fit over and conform to the shape of the distal end of a finger.
According to a second aspect, the invention provides for a medicament-dispensing applicator electrode for use with an electrokinetic device to transdermally deliver a medica-ment to an individual, comprising: a substrate having a first surface and a second surface opposite the first surface, the substrate including a medicament-dispensing portion com-prising a cell or a plurality of cells forming an aperture or a plurality of apertures between the first surface and the second surface, the cell or plurality of cells containing the medica-ment; and a layer of adhesive covering at least a portion of the second surface of the sub-strate opposite the first surface for releasably attaching the substrate to an electrokinetic device containing an electrical power source for electrokinetically driving the medicament through the first surface and into the individual's skin upon application of an electrical current to effect delivery of the medicament in the cell or plurality of cells to the individual's skin.
According to a third aspect, the invention provides for a medicament-dispensing applicator electrode for use with an electrokinetic device to transdermally deliver a medica-ment to an individual, comprising: a substrate having a first surface and a second surface opposite the first surface, the substrate including a medicament-dispensing portion com-prising a cell or a plurality of cells forming an aperture or a plurality of apertures between the first surface and the second surface, the cells or plurality of cells containing the medica-ment; and a layer of adhesive covering at least a portion of the first surface of the substrate opposite the second surface for releasably attaching the substrate to an individual's skin, the aperture or plurality of apertures being open along the second surface such that the medica-ment is electrokinetically driven through the first surface and into the individual's skin upon - 5a-electrically contacting an electrokinetic device containing an electrical power source with the second surface of the medicament-dispensing portion to generate an electrical current to effect delivery of the medicament in the cell or plurality of cells to the individual's skin.
According to a fourth aspect, the invention provides for a medicament-dispensing applicator electrode for use with an electrokinetic device to transdermally deliver a medica-ment to an individual, comprising: a substrate having a first surface and a second surface opposite the first surface, the substrate including a medicament-dispensing portion between the first surface and the second surface and defining a reservoir for containing the medica-ment; and a layer of adhesive covering at least a portion of one of the first surface and the second surface of the substrate for releasably attaching the substrate to one of an electro-kinetic medicament-delivery device containing an electrical power source or an individual's skin, the second surface of the medicament-dispensing portion being pervious to enable electrical contact through the second surface with the medicament or a carrier therefor such that the medicament is electrokinetically driven from the reservoir through the first surface and into the individual's skin upon transmission of an electrical current through the second surface, the reservoir and the first surface.
According to a fifth aspect, the invention provides for an apparatus for the trans-dermal delivery of a medicament to an individual, comprising: a medicament-dispensing applicator electrode including a substrate having a first surface and a second surface opposite the first surface, the substrate including a medicament-dispensing portion comprising a cell or a plurality of cells forming an aperture or a plurality of apertures between the first surface and the second surface, the cell or plurality of cells containing the medicament; an electro-kinetic device comprising a housing having a portion thereof shaped for grasping within an individual's hand for manual manipulation by the individual, and a first electrode formed of electrically conductive material and in electrical contact with the substrate and with a portion of an individual's skin upon application of the device to the individual's skin with the sub-strate interposed therebetween; a power source contained within the housing having first and second terminals, the first terminal being in electrical contact with the first electrode; a tactile electrode in electrical contact with the second terminal of the power source and having a surface for electrical contact with another portion of an individual's skin;
and the device being operable to electrokinetically drive the medicament from the applicator electrode to - 5b -effect delivery of the medicanient in the cell or plurality of cells to the portion of the individual's skin in contact with the substrate on one side thereof in response to completion of an electrical circuit between the first terminal through the first electrode and the substrate via the individual's skin portion and the second terminal via the tactile electrode and the another portion of the individual's skin.
According to a sixth aspect, the invention provides for an apparatus for the trans-dermal delivery of a medicament to an individual, comprising: a medicament-dispensing applicator electrode; an electrokinetic device; the medicament-dispensing applicator elec-trode including a substrate having a first surface and a second surface opposite the first surface, the substrate including a medicament-dispensing portion comprising a cell or a plurality of cells forming an aperture or a plurality of apertures between the first surface and the second surface, the cell or plurality of cells containing the medicament, the substrate having a portion thereof for releasably coupling the substrate to the device;
the device comprising a housing having a portion thereof shaped for grasping within an individual's hand for manual manipulation by the individual, and a first electrode formed of electrically conductive material and exposed for contact with the substrate upon releasable connection to the device; a power source contained within the housing having first and second terminals, the first terminal being in electrical contact with the first electrode; a tactile electrode in electrical contact with the second terminal of the power source and having a surface for contact with the individual's skin; and the device being operable to electrokinetically drive the medicament from the applicator electrode to effect delivery of the medicament in the cell or plurality of cells to a portion of the individual's skin in contact with the substrate on one side thereof in response to completion of an electrical circuit between the first terminal through the first electrode and the substrate via the individual's skin and the second terminal via the tactile electrode and another portion of the individual's skin.
According to a seventh aspect, the invention provides for a medicament-dispensing electrokinetic applicator for delivering medicament to a large area of an individual's skin, comprising: a glove-shaped body containing a medicament for application through an outer surface thereof; and a conductive layer formed within the glove-shaped body for connection with an electrical power source and electrokinetically driving the medicament from the body onto an area of the individual's skin overlaid and in contact with the glove-shaped body upon - 5c -application of an electrical current to effect delivery of the medicament contained in the body to the large area of the individual's skin in contact with the overlying glove-shaped body, wherein the conductive layer comprises a multi-channel electrode.
According to a eighth aspect, the invention provides for an apparatus for the trans-dermal delivery of medicament to an individual, comprising: a medicament-dispensing electrode; an electrokinetic device; the medicament-dispensing electrode including a sub-strate having a first surface and a second surface opposite the first surface, the substrate including a medicament-dispensing portion having a cellular structure with one or a plurality of cells dimensioned to retain a medium including the medicament within the confines of the cellular structure for electrokinetically transporting the medicament from the cell or plurality of cells through the first surface into the individual's skin upon flowing an electrical current between the first surface and the second surface; a tactile conductive portion carried by the substrate having a second cell or a plurality of cells electrically insulated from the medica-ment-dispensing portion, the second cell or plurality of cells containing an electrically con-ductive material for electrical connection through the second surface with a conductive portion on the electrokinetic device; and the electrokinetic device including a housing having a portion thereof shaped for manual manipulation by the individual's hand, and a first elec-trode exposed for contact with the second surface of the substrate upon engagement of the substrate and the device with one another, a power source within the housing and having first and second terminals, the first terminal being in electrical contact with the first electrode, a tactile electrode in electrical contact with the second terminal of the power source and having a surface for electrical contact with the tactile conductive portion of the applicator electrode, the device being operable to deliver the medicament from the applicator electrode to a por-tion of the individual's skin in contact with the first surface in response to completion of an electrical circuit between the first terminal through the first electrode and the substrate via the individual's skin and the second terminal via the tactile electrode, the tactile conductive portion and another portion of the individual's skin.
According to a ninth aspect, the invention provides for a use of a hand-held ionto-phoretic device comprising an electrode and a medicament dispensing reservoir containing an antiviral agent, the reservoir being in electrical communication with the electrode, for treating lesions associated with cold sore and genital herpes, wherein the medicament - 5d-dispensing reservoir is in contact with the lesions and a voltage gradient between the elec-trode and the lesion is present.
According to a tenth aspect, the invention provides for a use of a hand-held ionosonic device comprising an electrode and a medicament dispensing reservoir containing an anti-viral agent, the reservoir being in electrical communication with the electrode, for treating lesions associated with cold sore and genital herpes, wherein: the medicament dispensing reservoir is in contact with the lesions; ultrasonic vibration in a tissue comprising the lesion is present; and a voltage gradient between the electrode and the lesion is present.
According to a eleventh aspect, the invention provides for a use of a hand-held iono-sonic device comprising an electrode and a medicament dispensing reservoir containing an ionic compound in electrical communication with the electrode, for treating lesions associ-ated with acne, wherein: the medicament dispensing reservoir comes into contact a the lesion; ultrasonic vibration in a tissue comprising the lesion is present; and a voltage gradient between the electrode and the lesion is present.
According to a twelfth aspect, the invention provides for a disposable medicament dispensing applicator electrode for an iontophoretic drug delivery device adapted for the self-administration of a medicament into a person's skin, the device comprising a base assembly having an active terminal adapted to receive and make electrical contact with a detachable medicament dispensing applicator electrode wherein the base assembly comprises: a case having an elongate, substantially cylindrical outer surface having a size and shape adapted to be comfortably grasped within a person's hand and wherein at least a portion of the outer surface is a tactile electrode formed of an electrically conductive material;
and a bipolar electrical power means having a first pole and a second pole; the electrical power means being enclosed within the case and wherein the first pole is in electrical communication with the tactile electrode; wherein the medicament dispensing applicator electrode comprises: a module containing unit dose of medicament, an electrically conductive working electrode and means thereon adapted for releasably attaching the working electrode to the second pole of the electrical power means wherein the working electrode further comprises an elongate strip constructed of a substantially electrically non-conductive substrate material, the strip having a central portion containing a medicament in an electrically conductive substrate and laterally symmetric end portions having cutouts therewithin.
- 5e-The above objects, features and advantages of the invention are realized by the im-proved iontophoretic medicament applicator electrode of the present invention.
The objects, features and advantages of the invention will become apparent upon consideration of the following detailed disclosure of the invention, especially when it is taken in conjunction with the accompanying drawings wherein:
BRIEF DESCRIPTION OF THE DRAWINGS
FIG. 1 is a top plan view of a first embodiment of the disposable iontophoretic medi-cament containing applicator electrode adapted for attachment to an iontophoresis handpiece wherein the medicament dispensing portion of the electrode is an open mesh.
FIG. 2 is a side elevational view of a preferred embodiment of the disposable non-reusable iontophoretic applicator electrode for use with an iontophoresis handpiece adapted for self-administration.
FIG. 3 is a top plan view of the iontophoresis applicator electrode in accordance with claim 2.
FIG. 4 is a horizontal cross-sectional plan view of an iontophoresis handpiece adapt-ed for use with the embodiments of the medicament dispensing applicator electrode of the present invention shown in Figures 1 - 3.
FIG. 5 is a perspective view showing the applicator electrode of Figures 1- 3 releas-ably affixed to an iontophoresis handpiece in accordance with Figure 4.
FIG. 6 shows a patient preparing to self-administer medicament to a treatment site.
FIG. 7 is a top plan view of an embodiment of a medicament dispensing applicator electrode having unitary construction and an open mesh medicament dispensing portion similar to the embodiment shown in Figures 1 - 3 and adapted for attachment to the skin of a patient.
1 FIG. 8 is a horizontal cross-sectional view of the applicator electrode of 2 Figure 7 taken along section line 8-8.
3 FIG. 9 is a bottom plan view of the applicator electrode of Figure 7.
4 FIG. 10 is a perspective view of an embodiment of an iontophoresis device and a medicament dispensing applicator electrode adapted to be releasably affixed to a 6 finger of a patient wherein the medicament dispensing portion of the electrode is an 7 open mesh.
3 FIG. 9 is a bottom plan view of the applicator electrode of Figure 7.
4 FIG. 10 is a perspective view of an embodiment of an iontophoresis device and a medicament dispensing applicator electrode adapted to be releasably affixed to a 6 finger of a patient wherein the medicament dispensing portion of the electrode is an 7 open mesh.
8 FIG. 11 is a perspective view of the iontophoresis device and applicator 9 electrode of Figure 10 wherein the thimble-like applicator electrode has been removed 1o from the patient's finger.
t 1 FIG. 12 is a partially cut-away view of the iontophoresis applicator electrode 12 of Figures 10 and 11 showing the relationship between the applicator electrode, an 13 insulating finger cot and a wrist-worn adaptation of the iontophoresis device shown in 14 Fig.4.
FIG. 13 is a plan view of a glove embodiment of the applicator electrode in 16 accordance with the present invention having a large area for medicament delivery.
17 FIG. 14 is a perspective view of a patient using the glove embodiment of FIG.
18 13 to self-administer a medicament to a relatively large portion of skin underlying the 19 glove, as in, for example, the treatment of acne.
FIG. 15 is a schematic elevational view of a hand-held ionosonic handpiece 21 having an applicator electrode in accordance with the present invention attached 22 thereto.
FIG 1 shows, in top plan view, a first preferred embodiment of the hand-held 26 iontophoretic transdermal medicament delivery apparatus of the present invention.
27 The first preferred embodiment of the iontophoretic medicament-containing 28 application electrode is shown at 10. The application electrode 10 is preferably 29 disposable and non-reusable. The electrode 10 is suitable, for example, for transdermally delivering anti-viral agents such as Acyclovir for the treatment of cold 31 sores or genital herpes. The applicator electrode 10 is adapted for use with an SUBSTITUTE SHEET (RULE 26) 1 iontophoresis handpiece such as the handpiece shown in Figures 4 and 5. In use, the 2 applicator electrode 10 is detachably affixed to a hand-held iontophoresis handpiece 3 40 which handpiece presents a first electrically conductive surface 41 and a second 4 electrically conductive surface 42. The handpiece 40 comprises a current driver 45 which receives an electrical voltage from a voltage multiplier 46 which is in electrical 6 communication with one electrode 47 of an electrical power source 48 such as a 7 battery. The other electrode 49 of the battery is in electrical communication with a 8 tactile electrode 42 on the surface of the handpiece 40 which electrode is, in use, in 9 contact with the skin of one or more fingers of a user. The electrical current from the current driver 45 is conducted through a wire or conductive strip 44 to the first 11 electrically conductive surface 41. When the applicator electrode 10 is attached to the 12 handpiece 40, the current passes through the conductive applicator electrode to the 13 skin of the user, returning to the second electrically conductive element 42, or "tactile 14 electrode" to drive the medicament 23 through the mesh-like matrix material 12 and into the user's skin. The medicament or treatment agent is contained within a viscous 16 fluid vehicle which, in turn, is contained within a plurality of cellular apertures 12a 17 comprising the mesh 12.
18 The applicator electrode 10 comprises a substantially flat elongate strip having 19 lateral ends extending from a central medicament dispensing portion 12. The central medicament dispensing portion 12 is of mesh-like construction and has vertical cells 21 dimensioned to accommodate a viscous fluid within the confines of the cellular 22 structures. The viscous fluid contained within each of the plurality of cells 12a 23 includes a medicament (not shown) which is in a form suitable for transport under the 24 influence of an electrical current. The lateral ends of the applicator electrode 10 may include a mesh-like tactile conductive portion 11 which contains an electrically 26 conductive gel therewithin. The applicator electrode 10 has a skin-facing surface 13 27 and a device-facing surface 14. One or a plurality of cells 12a form one or a plurality 28 of apertures between the upper skin-facing surface 13 and the lower device-facing 29 surface 14. The device-facing surface 14 may further include an adhesive layer 18 applied thereto suitable for releasably adhering the applicator electrode 10 to the 31 positive (anode) or negative (cathode) pole of a iontophoresis handpiece.
The SUBSTITUTE SHEET (RULE 26) 1 positioning of the electrode's tactile conductive portion I1 on the surface of the 2 handpiece is such that tactile conductive portion 11 makes electrical contact with the 3 tactile electrode 42 on the handpiece. When the applicator electrode 10 is correctly 4 positioned on the handpiece, the medicament dispensing reservoir 12 is in electrical communication with the electrically contacting element 41 on the handpiece. In 6 addition, one or more small magnets 15 disposed within the applicator electrode 10 7 may be positioned on the handpiece to activate a switch within said handpiece which 8 turns the handpiece on and/or off. The relatively narrow, flexible areas 16 on the 9 electrode 10 enable the applicator electrode 10 to be bent and formed around the handpiece. Figure 2 shows a cross-sectional view of the applicator electrode 10 of 11 Figure 1 taken along section lines 2-2. The material 17 forming the structural portion 12 of the applicator electrode 10 is preferably a non-electrically conducting elastomer. A
t 1 FIG. 12 is a partially cut-away view of the iontophoresis applicator electrode 12 of Figures 10 and 11 showing the relationship between the applicator electrode, an 13 insulating finger cot and a wrist-worn adaptation of the iontophoresis device shown in 14 Fig.4.
FIG. 13 is a plan view of a glove embodiment of the applicator electrode in 16 accordance with the present invention having a large area for medicament delivery.
17 FIG. 14 is a perspective view of a patient using the glove embodiment of FIG.
18 13 to self-administer a medicament to a relatively large portion of skin underlying the 19 glove, as in, for example, the treatment of acne.
FIG. 15 is a schematic elevational view of a hand-held ionosonic handpiece 21 having an applicator electrode in accordance with the present invention attached 22 thereto.
FIG 1 shows, in top plan view, a first preferred embodiment of the hand-held 26 iontophoretic transdermal medicament delivery apparatus of the present invention.
27 The first preferred embodiment of the iontophoretic medicament-containing 28 application electrode is shown at 10. The application electrode 10 is preferably 29 disposable and non-reusable. The electrode 10 is suitable, for example, for transdermally delivering anti-viral agents such as Acyclovir for the treatment of cold 31 sores or genital herpes. The applicator electrode 10 is adapted for use with an SUBSTITUTE SHEET (RULE 26) 1 iontophoresis handpiece such as the handpiece shown in Figures 4 and 5. In use, the 2 applicator electrode 10 is detachably affixed to a hand-held iontophoresis handpiece 3 40 which handpiece presents a first electrically conductive surface 41 and a second 4 electrically conductive surface 42. The handpiece 40 comprises a current driver 45 which receives an electrical voltage from a voltage multiplier 46 which is in electrical 6 communication with one electrode 47 of an electrical power source 48 such as a 7 battery. The other electrode 49 of the battery is in electrical communication with a 8 tactile electrode 42 on the surface of the handpiece 40 which electrode is, in use, in 9 contact with the skin of one or more fingers of a user. The electrical current from the current driver 45 is conducted through a wire or conductive strip 44 to the first 11 electrically conductive surface 41. When the applicator electrode 10 is attached to the 12 handpiece 40, the current passes through the conductive applicator electrode to the 13 skin of the user, returning to the second electrically conductive element 42, or "tactile 14 electrode" to drive the medicament 23 through the mesh-like matrix material 12 and into the user's skin. The medicament or treatment agent is contained within a viscous 16 fluid vehicle which, in turn, is contained within a plurality of cellular apertures 12a 17 comprising the mesh 12.
18 The applicator electrode 10 comprises a substantially flat elongate strip having 19 lateral ends extending from a central medicament dispensing portion 12. The central medicament dispensing portion 12 is of mesh-like construction and has vertical cells 21 dimensioned to accommodate a viscous fluid within the confines of the cellular 22 structures. The viscous fluid contained within each of the plurality of cells 12a 23 includes a medicament (not shown) which is in a form suitable for transport under the 24 influence of an electrical current. The lateral ends of the applicator electrode 10 may include a mesh-like tactile conductive portion 11 which contains an electrically 26 conductive gel therewithin. The applicator electrode 10 has a skin-facing surface 13 27 and a device-facing surface 14. One or a plurality of cells 12a form one or a plurality 28 of apertures between the upper skin-facing surface 13 and the lower device-facing 29 surface 14. The device-facing surface 14 may further include an adhesive layer 18 applied thereto suitable for releasably adhering the applicator electrode 10 to the 31 positive (anode) or negative (cathode) pole of a iontophoresis handpiece.
The SUBSTITUTE SHEET (RULE 26) 1 positioning of the electrode's tactile conductive portion I1 on the surface of the 2 handpiece is such that tactile conductive portion 11 makes electrical contact with the 3 tactile electrode 42 on the handpiece. When the applicator electrode 10 is correctly 4 positioned on the handpiece, the medicament dispensing reservoir 12 is in electrical communication with the electrically contacting element 41 on the handpiece. In 6 addition, one or more small magnets 15 disposed within the applicator electrode 10 7 may be positioned on the handpiece to activate a switch within said handpiece which 8 turns the handpiece on and/or off. The relatively narrow, flexible areas 16 on the 9 electrode 10 enable the applicator electrode 10 to be bent and formed around the handpiece. Figure 2 shows a cross-sectional view of the applicator electrode 10 of 11 Figure 1 taken along section lines 2-2. The material 17 forming the structural portion 12 of the applicator electrode 10 is preferably a non-electrically conducting elastomer. A
13 bottom view of the applicator electrode 10 of Figures 1 and 2 is shown in Figure 3.
14 Figure 5 is a perspective view of the applicator electrode 10 attached to the handpiece 40 in position for use. Figure 6 shows a patient preparing to use the 16 iontophoresis device for administering medicament to herpes lesions on the face. The 17 patient 60 grasps the tactile electrode 42 with a finger 61 to make electrical 18 communication therewith. The patient then touches the tip 12 of the applicator 19 electrode 10 to the lesion 63 thereby completing the electrical circuit and the resulting current flow driving the medicament into the skin.
21 Turning next to Figure 7, a second preferred embodiment of a medicament 22 dispensing applicator electrode in accordance with the present invention is shown at 23 70. The centrally located medicament dispensing portion 71 has cells 72 therewithin 24 which cells provide an aperture between the upper surface 73 and the lower, skin-contacting surface 74 of the electrode 70. The applicator electrode 70 is shown in 26 cross-section along section lines 8-8 in Figure 8. The central medicament dispensing 27 portion 71 of the electrode 70 is mesh-like in construction. A plurality of vertical cells 28 72 are molded within the elastomer strip comprising the applicator electrode to form 29 apertures which communicate between the upper surface 73 and the lower surface 74.
A fluid or semi-fluidic vehicle containing a medicament is placed within the cells 72 31 which cells are dimensioned to retain the medicament therewithin until an electrical SUBSTITUTE SHEET (RULE 26) 1 current is passed therethrough. An adhesive layer 75 is coated upon the lower surface 2 74 of the applicator electrode. The adhesive is chosen to be hypoallergenic, 3 biocompatible and to releasably affix the electrode 70 to the skin.
4 A bottom view of the applicator electrode 70 of Figures 7 and 8 is shown in Figure 9. In use, the embodiment of the applicator electrode 70 shown in Figures 7 -6 9 is affixed to the skin via the adhesive surface 75. The iontophoresis handpiece 40 is 7 grasped between the fingers of the patient such that the tactile electrode (42 in Fig. 5) 8 is in contact with at least one of the patient's fingers. The handpiece is then advanced 9 to the medicament dispensing portion 71 of the applicator electrode 70 until it makes contact therewith. The circuit formed between the fingers grasping the tactile 11 electrode 42 portion of the handpiece 40 and the lesion is made through the mesh 12 surface of the medicament dispensing portion of the applicator electrode.
Current 13 flows through the handpiece to the medicament dispensing electrode and into the skin 14 of the patient to return to the handpiece via the fingers and the tactile electrode to close the circuit. As the current flows through the medicament dispensing electrode 16 the current drives the medicament into the skin of the patient.
17 Turning now to Figure 10, a thimble-like medicament dispensing applicator 18 electrode 100 is shown attached to a finger 105 of a patient. The applicator electrode 19 100 is in electrical communication with one pole (cathode or anode) of a wrist-wom, bipolar iontophoresis device 101 by means of a wire 102. The bottom 106 or wrist-21 facing, skin-contacting surface of the bipolar iontophoresis device 101 is the other 22 pole (anode or cathode) comprising a conductive electrode. The iontophoresis device 23 101 is releasably affixed to the wrist by means of a strap 103. The iontophoresis 24 device 101 may be constructed similarly to the iontophoresis handpiece 40 except that the working electrode 41 is attached to the wire 102 and the tactile electrode 26 replaced with a conductive electrode 106 forming the skin-contacting portion of the 27 device 101 which is in contact with the wrist of the patient. The applicator electrode 28 100 is electrically isolated from the finger 105 by means of an insulating finger cot 29 104. Current from the iontophoresis device 101 passes through the conductive wire 102 to an inner electrically conductive thimble 110 (Figure 11) to which the wire is 31 conductively attached by means of solder. The electrically conductive thimble 110 has SUBSTITUTE SHEET (RULE 26) 1 an overlying silicone elastomeric thimble 111. The elastomeric thimble 111 is 2 homogenous in composition and has an upper surface 112 and a lower surface 3 which comprises a mesh 113 a. The mesh 113 a has integral therewith a plurality of 4 retaining cells 114 which cells extend between the electrically conductive thimble 110 and the lower surface 113 and are dimensioned to contain a medicament. In 6 operation, current from the iontophoresis device 101 passes through the wire 102 to 7 the electrically conductive thimble 110 of the applicator electrode. The voltage 8 applied to the surface of the electrically conductive thimble 110 drives medicament 9 contained within the cells 114 of the mesh 113 into the skin of a user's body. The current passes through the user's body to the conductive electrode (not shown) which I 1 comprises the wrist-facing portion of the iontophoresis device 101. The iontophoresis 12 device 101 preferably includes a power source, a voltage multiplier, a driver and an 13 on/off switch as shown in the handpiece 40, but reconfigured to be worn on the wrist.
14 An enlarged perspective view of the applicator electrode 100 overlying a finger cot is shown in structural relationship in Figure 12.
16 The simple design is capable of retaining and dispensing existing medicament 17 formulations in various viscosities because the size of the retaining cells 72 in the 18 mesh portion of the electrode may be varied. The structural matrix of the applicator 19 electrode is a flexible, preferably hypoallergenic, nonelectrically-conductive material.
A suitable material is Silastic , a silicone elastomer which is biocompatible, non-21 conductive, flexible and possessing sufficient structural rigidity to contain 22 medicaments and a delivery vehicle within the retaining cells 114. Further, Silastic 23 silicone elastomer is inert so that medicaments will not oxidize or otherwise have their 24 chemical structures damaged. An electrode constructed from silicone elastomer has a prolonged shelf-life, is soft and pleasant on contact, is hypoallergenic and sufficiently 26 flexible to adhere to any anatomical contour such as presented by a thimble. Such 27 anatomical plasticity is a key advantage to the foregoing design. Other polymers, such 28 as polyurethane, are suitable as well. A hydrated hydrophilic cotton layer (not shown) 29 may be interposed between the medicament dispensing portion 71 and the electrically conductive surface 41 of the handpiece 40 to provide pretreatment hydration of the SUBSTITUTE SHEET (RULE 26) 1 medicament dispensing portion or the mesh may be hydrated by the patient 2 immediately prior to use.
3 With reference to the embodiment of an iontophoresis applicator electrode 4 shown in Figures 7 - 9, the electrode is easily manufactured using mold technology wherein uncured silicone elastomer is either poured into a complementary mold or 6 pressure-mold injected. The lower surface 74 of the non-medicament dispensing 7 portion of the electrode is coated with skin adhesive. The medicament dispensing 8 portion 71 functions as a medicament reservoir and is preferably between lnun and 9 4mm thick, depending upon the amount of medicament required to be stored in the cells 72. The medicament-retaining cells 72, which are preferably a hexagonal, honey 11 comb-like structure, retain the medicament therein through their surface tension.
12 Hexagonal cells also lessen cross channel conductivity by means of their vertical 13 orientation. The size and geometry of these cells can vary. The smallest cells, for 14 instance, would be more suited to retaining liquid medicaments while the larger cells are better adapted to retain ointment-based medicaments. Medium cells are more 16 suited to retaining and dispensing gel medicaments and lotions. The silicone walls of 17 the cells can be chemically modified to change the hydrophobic surface characteristics 18 thereof and further improve retention of specially formulated liquid medicaments. For 19 additional cell stability and retention capabilities, the skin-facing surface of the cells can be covered with non-wicking, fibrous and porous materials commonly used in 21 electrodes. A composite or unitary construction from a single mold can be used 22 depending on production cost, it is inexpensive to manufacture and it offers both a 23 compartment for storage of existing formulations as well as a structural backbone for 24 the application electrode. The surface treatments of the retaining material bounding each of the cells to create hydrophilic or hydrophobic surface effects depending on the 26 formulation to be utilized is well known in the art. An example of such technology is 27 disclosed, for example, in US patent 5,589,563. For ointments and hydrophobic 28 materials, silicone is preferred. For water or gel medicaments, surface treatment such 29 as doping the elastomeric cell surface with hydrophilic molecules can be of additional benefit, as described herein. The embodiments disclosed herein present the following 31 advantages:
SUBSTITUTE SHEET (RULE 26) 1 Inexpensive manufacture;
2 Use of either injection or pour molding production;
3 Use of composite sheet cutout assembly;
4 Anatomically conforming;
Elastomer surface modification for optimum retention of medicament;
6 Variable retaining cell size;
7 Variable retaining cell geometry;
8 Ability to utilize existing medicament formulations;
9 May use a cotton or (other hydrophilic matrix) layer for rapid pre-treatment hydration.
11 May be used with single or multi-channel dispersive iontophoretic drivers;
and 12 May be used with iontophoretic or ionosonic devices.
13 An embodiment of the present invention adapted for delivering medicament to 14 a large area of skin is shown in Figure 13. The iontophoresis electrode is contained within a glove adapted to conform to and be worn upon a patient's hand. The glove 16 embodiment 130 of the iontophoresis drug delivery electrode comprises an 17 elastomeric glove 131 having a plurality of holes or open pores 132 in the palmar 18 surface 133 thereof. Underlying the palmar surface 133 and disposed within the glove 19 between the skin 134 and glove is an electrically insulating sheet 135 having an inner surface 136 and an outer surface 137, both of which surfaces are coated with an 21 electrically conductive layer 138. The inner conductive layer 136 is, in use, in 22 electrical communication with the skin. The outer conductive layer 137 is in contact 23 with the interior surface of the glove and the pores 132. A medicament 139 capable 24 of iontophoretic transdermal delivery is contained within the pores. A
bipolar power source 140 has a working electrode 141 in electrical communication with the outer 26 conductive layer 137 coating the electrically insulating sheet 135, and a ground 27 electrode (not shown) which is in electrical communication with the inner conductive 28 layer coating the electrically insulating sheet. When the power source 140 is 29 energized, an electrical current flows between the inner conductive layer and the outer conductive layer, which layers are separated by the electrically insulating sheet, via the 31 patient's skin. The polarity and amplitude of the current flowing through pores into SUBSTITUTE SHEET (RULE 26) 1 the user's skin facilitates entry of the medicament into the skin. The glove 2 embodiment, shown in use in Figure 14, is particularly useful for transdermally 3 delivering medicament to large areas of skin.
4 The advantages of a unitary iontophoresis electrode and a glove and finger cot embodiment of an iontophoresis electrode for drug delivery have been presented. It is 6 noted that similarly constructed electrodes may be employed for non-invasively 7 collecting molecular species from the blood. For example, the mesh may be 8 impregnated with an electrically conductive gel. The polarity of the gel, with respect 9 to the skin, may be employed to transport blood components through the skin into the gel where such components may be detected and/or quantitated. Such measurements lI are useful for monitoring blood levels of compounds such as glucose or drugs.
12 The hand held iontophoretic device 40 (Figure 4)may be modified to include a 13 piezoelectric element operable for imparting ultrasonic vibrational motion to the 14 applicator electrode 12 to further facilitate transdermal delivery of certain iontophoretically transportable compounds. A schematic view of such a modified 16 handpiece similar to the handpiece 40 of Figure 4 is shown at 150 in Figure 15. The 17 applicator electrode 160 includes all embodiments of the applicator electrode 18 described for the iontophoresis handpiece discussed above. One side of an annular 19 ultrasonic piezoelectric element 151 is disposed rearwardly to the applicator electrode 160 containing a medicament. Power is supplied to energize the piezoelectric element 21 151 by means of conductive elements 157 and 152 which are in electrical 22 communication with an ultrasonic driver 163. An optional current sensitive switching 23 element (not shown) may be used to energize the piezoelectric element only when 24 current passes through the applicator electrode circuit. The applicator electrode 160 may include any applicator electrode heretofore described for use with an 26 iontophoretic handpiece. The applicator electrode 160 may contain an ionic 27 medicament or a biologically inactive ionic solution which penetrates the skin and 28 opens clogged pores under the influence of iontophoretically driven transport assisted 29 by ultrasonic waves in the cutaneous tissue. Stephen et al. have shown in US Patent 4,979,938 that the iontophoretic delivery of hydroxyl ions into the skin can be used to 31 treat acne. The ionosonic delivery of a similar anion may provide improved opening SUBSTITUTE SHEET (RULE 26) 1 of pores in the skin for treating acne. The combination of iontophoretic delivery of a 2 compound into a tissue, together with inducing ultrasonic vibration in the tissue, may 3 enable the removal of coloration (such as a blemish, freckle or tattoo) within the skin 4 by the delivery of a suitable bleaching agent While the invention has been described above with references to specific 6 embodiments thereof, it is apparent that many changes, modifications and variations in 7 the materials, arrangements of parts and steps can be made without departing from the 8 inventive concept disclosed herein. For example, an impregnated conductive gel can 9 also be used to as medicament containing medium to increase the physical stability and the tissue adhering characteristics of the electrode. The applicator electrode described 11 herein, when used with an ionosonic or iontophoretic handpiece can deliver 12 medicaments for treating diverse medical conditions including, but not limited to acne, 13 hyperproliferative diseases of the skin, superficial fungal infections, warts, and herpes 14 type viral infections. Accordingly, the spirit and broad scope of the appended claims is intended to embrace all such changes, modifications and variations that may occur 16 to one of skill in the art upon a reading of the disclosure. All patent applications, 17 patents and other publication cited herein are incorporated by reference in their 18 entirety.
21 Turning next to Figure 7, a second preferred embodiment of a medicament 22 dispensing applicator electrode in accordance with the present invention is shown at 23 70. The centrally located medicament dispensing portion 71 has cells 72 therewithin 24 which cells provide an aperture between the upper surface 73 and the lower, skin-contacting surface 74 of the electrode 70. The applicator electrode 70 is shown in 26 cross-section along section lines 8-8 in Figure 8. The central medicament dispensing 27 portion 71 of the electrode 70 is mesh-like in construction. A plurality of vertical cells 28 72 are molded within the elastomer strip comprising the applicator electrode to form 29 apertures which communicate between the upper surface 73 and the lower surface 74.
A fluid or semi-fluidic vehicle containing a medicament is placed within the cells 72 31 which cells are dimensioned to retain the medicament therewithin until an electrical SUBSTITUTE SHEET (RULE 26) 1 current is passed therethrough. An adhesive layer 75 is coated upon the lower surface 2 74 of the applicator electrode. The adhesive is chosen to be hypoallergenic, 3 biocompatible and to releasably affix the electrode 70 to the skin.
4 A bottom view of the applicator electrode 70 of Figures 7 and 8 is shown in Figure 9. In use, the embodiment of the applicator electrode 70 shown in Figures 7 -6 9 is affixed to the skin via the adhesive surface 75. The iontophoresis handpiece 40 is 7 grasped between the fingers of the patient such that the tactile electrode (42 in Fig. 5) 8 is in contact with at least one of the patient's fingers. The handpiece is then advanced 9 to the medicament dispensing portion 71 of the applicator electrode 70 until it makes contact therewith. The circuit formed between the fingers grasping the tactile 11 electrode 42 portion of the handpiece 40 and the lesion is made through the mesh 12 surface of the medicament dispensing portion of the applicator electrode.
Current 13 flows through the handpiece to the medicament dispensing electrode and into the skin 14 of the patient to return to the handpiece via the fingers and the tactile electrode to close the circuit. As the current flows through the medicament dispensing electrode 16 the current drives the medicament into the skin of the patient.
17 Turning now to Figure 10, a thimble-like medicament dispensing applicator 18 electrode 100 is shown attached to a finger 105 of a patient. The applicator electrode 19 100 is in electrical communication with one pole (cathode or anode) of a wrist-wom, bipolar iontophoresis device 101 by means of a wire 102. The bottom 106 or wrist-21 facing, skin-contacting surface of the bipolar iontophoresis device 101 is the other 22 pole (anode or cathode) comprising a conductive electrode. The iontophoresis device 23 101 is releasably affixed to the wrist by means of a strap 103. The iontophoresis 24 device 101 may be constructed similarly to the iontophoresis handpiece 40 except that the working electrode 41 is attached to the wire 102 and the tactile electrode 26 replaced with a conductive electrode 106 forming the skin-contacting portion of the 27 device 101 which is in contact with the wrist of the patient. The applicator electrode 28 100 is electrically isolated from the finger 105 by means of an insulating finger cot 29 104. Current from the iontophoresis device 101 passes through the conductive wire 102 to an inner electrically conductive thimble 110 (Figure 11) to which the wire is 31 conductively attached by means of solder. The electrically conductive thimble 110 has SUBSTITUTE SHEET (RULE 26) 1 an overlying silicone elastomeric thimble 111. The elastomeric thimble 111 is 2 homogenous in composition and has an upper surface 112 and a lower surface 3 which comprises a mesh 113 a. The mesh 113 a has integral therewith a plurality of 4 retaining cells 114 which cells extend between the electrically conductive thimble 110 and the lower surface 113 and are dimensioned to contain a medicament. In 6 operation, current from the iontophoresis device 101 passes through the wire 102 to 7 the electrically conductive thimble 110 of the applicator electrode. The voltage 8 applied to the surface of the electrically conductive thimble 110 drives medicament 9 contained within the cells 114 of the mesh 113 into the skin of a user's body. The current passes through the user's body to the conductive electrode (not shown) which I 1 comprises the wrist-facing portion of the iontophoresis device 101. The iontophoresis 12 device 101 preferably includes a power source, a voltage multiplier, a driver and an 13 on/off switch as shown in the handpiece 40, but reconfigured to be worn on the wrist.
14 An enlarged perspective view of the applicator electrode 100 overlying a finger cot is shown in structural relationship in Figure 12.
16 The simple design is capable of retaining and dispensing existing medicament 17 formulations in various viscosities because the size of the retaining cells 72 in the 18 mesh portion of the electrode may be varied. The structural matrix of the applicator 19 electrode is a flexible, preferably hypoallergenic, nonelectrically-conductive material.
A suitable material is Silastic , a silicone elastomer which is biocompatible, non-21 conductive, flexible and possessing sufficient structural rigidity to contain 22 medicaments and a delivery vehicle within the retaining cells 114. Further, Silastic 23 silicone elastomer is inert so that medicaments will not oxidize or otherwise have their 24 chemical structures damaged. An electrode constructed from silicone elastomer has a prolonged shelf-life, is soft and pleasant on contact, is hypoallergenic and sufficiently 26 flexible to adhere to any anatomical contour such as presented by a thimble. Such 27 anatomical plasticity is a key advantage to the foregoing design. Other polymers, such 28 as polyurethane, are suitable as well. A hydrated hydrophilic cotton layer (not shown) 29 may be interposed between the medicament dispensing portion 71 and the electrically conductive surface 41 of the handpiece 40 to provide pretreatment hydration of the SUBSTITUTE SHEET (RULE 26) 1 medicament dispensing portion or the mesh may be hydrated by the patient 2 immediately prior to use.
3 With reference to the embodiment of an iontophoresis applicator electrode 4 shown in Figures 7 - 9, the electrode is easily manufactured using mold technology wherein uncured silicone elastomer is either poured into a complementary mold or 6 pressure-mold injected. The lower surface 74 of the non-medicament dispensing 7 portion of the electrode is coated with skin adhesive. The medicament dispensing 8 portion 71 functions as a medicament reservoir and is preferably between lnun and 9 4mm thick, depending upon the amount of medicament required to be stored in the cells 72. The medicament-retaining cells 72, which are preferably a hexagonal, honey 11 comb-like structure, retain the medicament therein through their surface tension.
12 Hexagonal cells also lessen cross channel conductivity by means of their vertical 13 orientation. The size and geometry of these cells can vary. The smallest cells, for 14 instance, would be more suited to retaining liquid medicaments while the larger cells are better adapted to retain ointment-based medicaments. Medium cells are more 16 suited to retaining and dispensing gel medicaments and lotions. The silicone walls of 17 the cells can be chemically modified to change the hydrophobic surface characteristics 18 thereof and further improve retention of specially formulated liquid medicaments. For 19 additional cell stability and retention capabilities, the skin-facing surface of the cells can be covered with non-wicking, fibrous and porous materials commonly used in 21 electrodes. A composite or unitary construction from a single mold can be used 22 depending on production cost, it is inexpensive to manufacture and it offers both a 23 compartment for storage of existing formulations as well as a structural backbone for 24 the application electrode. The surface treatments of the retaining material bounding each of the cells to create hydrophilic or hydrophobic surface effects depending on the 26 formulation to be utilized is well known in the art. An example of such technology is 27 disclosed, for example, in US patent 5,589,563. For ointments and hydrophobic 28 materials, silicone is preferred. For water or gel medicaments, surface treatment such 29 as doping the elastomeric cell surface with hydrophilic molecules can be of additional benefit, as described herein. The embodiments disclosed herein present the following 31 advantages:
SUBSTITUTE SHEET (RULE 26) 1 Inexpensive manufacture;
2 Use of either injection or pour molding production;
3 Use of composite sheet cutout assembly;
4 Anatomically conforming;
Elastomer surface modification for optimum retention of medicament;
6 Variable retaining cell size;
7 Variable retaining cell geometry;
8 Ability to utilize existing medicament formulations;
9 May use a cotton or (other hydrophilic matrix) layer for rapid pre-treatment hydration.
11 May be used with single or multi-channel dispersive iontophoretic drivers;
and 12 May be used with iontophoretic or ionosonic devices.
13 An embodiment of the present invention adapted for delivering medicament to 14 a large area of skin is shown in Figure 13. The iontophoresis electrode is contained within a glove adapted to conform to and be worn upon a patient's hand. The glove 16 embodiment 130 of the iontophoresis drug delivery electrode comprises an 17 elastomeric glove 131 having a plurality of holes or open pores 132 in the palmar 18 surface 133 thereof. Underlying the palmar surface 133 and disposed within the glove 19 between the skin 134 and glove is an electrically insulating sheet 135 having an inner surface 136 and an outer surface 137, both of which surfaces are coated with an 21 electrically conductive layer 138. The inner conductive layer 136 is, in use, in 22 electrical communication with the skin. The outer conductive layer 137 is in contact 23 with the interior surface of the glove and the pores 132. A medicament 139 capable 24 of iontophoretic transdermal delivery is contained within the pores. A
bipolar power source 140 has a working electrode 141 in electrical communication with the outer 26 conductive layer 137 coating the electrically insulating sheet 135, and a ground 27 electrode (not shown) which is in electrical communication with the inner conductive 28 layer coating the electrically insulating sheet. When the power source 140 is 29 energized, an electrical current flows between the inner conductive layer and the outer conductive layer, which layers are separated by the electrically insulating sheet, via the 31 patient's skin. The polarity and amplitude of the current flowing through pores into SUBSTITUTE SHEET (RULE 26) 1 the user's skin facilitates entry of the medicament into the skin. The glove 2 embodiment, shown in use in Figure 14, is particularly useful for transdermally 3 delivering medicament to large areas of skin.
4 The advantages of a unitary iontophoresis electrode and a glove and finger cot embodiment of an iontophoresis electrode for drug delivery have been presented. It is 6 noted that similarly constructed electrodes may be employed for non-invasively 7 collecting molecular species from the blood. For example, the mesh may be 8 impregnated with an electrically conductive gel. The polarity of the gel, with respect 9 to the skin, may be employed to transport blood components through the skin into the gel where such components may be detected and/or quantitated. Such measurements lI are useful for monitoring blood levels of compounds such as glucose or drugs.
12 The hand held iontophoretic device 40 (Figure 4)may be modified to include a 13 piezoelectric element operable for imparting ultrasonic vibrational motion to the 14 applicator electrode 12 to further facilitate transdermal delivery of certain iontophoretically transportable compounds. A schematic view of such a modified 16 handpiece similar to the handpiece 40 of Figure 4 is shown at 150 in Figure 15. The 17 applicator electrode 160 includes all embodiments of the applicator electrode 18 described for the iontophoresis handpiece discussed above. One side of an annular 19 ultrasonic piezoelectric element 151 is disposed rearwardly to the applicator electrode 160 containing a medicament. Power is supplied to energize the piezoelectric element 21 151 by means of conductive elements 157 and 152 which are in electrical 22 communication with an ultrasonic driver 163. An optional current sensitive switching 23 element (not shown) may be used to energize the piezoelectric element only when 24 current passes through the applicator electrode circuit. The applicator electrode 160 may include any applicator electrode heretofore described for use with an 26 iontophoretic handpiece. The applicator electrode 160 may contain an ionic 27 medicament or a biologically inactive ionic solution which penetrates the skin and 28 opens clogged pores under the influence of iontophoretically driven transport assisted 29 by ultrasonic waves in the cutaneous tissue. Stephen et al. have shown in US Patent 4,979,938 that the iontophoretic delivery of hydroxyl ions into the skin can be used to 31 treat acne. The ionosonic delivery of a similar anion may provide improved opening SUBSTITUTE SHEET (RULE 26) 1 of pores in the skin for treating acne. The combination of iontophoretic delivery of a 2 compound into a tissue, together with inducing ultrasonic vibration in the tissue, may 3 enable the removal of coloration (such as a blemish, freckle or tattoo) within the skin 4 by the delivery of a suitable bleaching agent While the invention has been described above with references to specific 6 embodiments thereof, it is apparent that many changes, modifications and variations in 7 the materials, arrangements of parts and steps can be made without departing from the 8 inventive concept disclosed herein. For example, an impregnated conductive gel can 9 also be used to as medicament containing medium to increase the physical stability and the tissue adhering characteristics of the electrode. The applicator electrode described 11 herein, when used with an ionosonic or iontophoretic handpiece can deliver 12 medicaments for treating diverse medical conditions including, but not limited to acne, 13 hyperproliferative diseases of the skin, superficial fungal infections, warts, and herpes 14 type viral infections. Accordingly, the spirit and broad scope of the appended claims is intended to embrace all such changes, modifications and variations that may occur 16 to one of skill in the art upon a reading of the disclosure. All patent applications, 17 patents and other publication cited herein are incorporated by reference in their 18 entirety.
What I claim is:
SUBSTITUTE SHEET (RULE 26)
SUBSTITUTE SHEET (RULE 26)
Claims (37)
1. A medicament dispensing iontophoresis applicator electrode comprising a generally thimble-shaped electrically conductive member and an overlying medicament dispensing portion of an electrically non-conducting elastomer having a cell or plurality of cells in at least a portion thereof and wherein said thimble-shaped conductive portion is dimensioned to fit over and conform to the shape of the distal end of a finger.
2. The applicator electrode of claim 1 wherein said cell or plurality of cells contain a medicament.
3. The applicator electrode of claim 2 wherein said thimble-shaped electrically conduct-ive member has a first end of an electrically conductive wire affixed thereto.
4. The applicator electrode of claim 3 wherein said electrically conductive wire has a second end in opposition to said first end and includes means for attaching said second end to a pole of a current source.
5. The applicator electrode of claim 2 wherein said medicament dispensing portion further comprises a hydrophilic matrix layer overlying said cell or plurality of cells for pre-treatment hydration by a user immediately prior to use when used with non-ionic medica-ment formulation.
6. The applicator electrode of claim 5 wherein said hydrophilic matrix layer is hydrated.
7. The applicator electrode of claim 2 further comprising an electrically insulating layer underlying said thimble-shaped electrically conductive member.
8. A medicament-dispensing applicator electrode for use with an electrokinetic device to transdermally deliver a medicament to an individual, comprising:
a substrate having a first surface and a second surface opposite said first surface, said substrate including a medicament-dispensing portion comprising a cell or a plurality of cells forming an aperture or a plurality of apertures between said first surface and said second surface, said cell or plurality of cells containing the medicament; and a layer of adhesive covering at least a portion of said second surface of said substrate opposite said first surface for releasably attaching said substrate to an electrokinetic device containing an electrical power source for electrokinetically driving said medicament through said first surface and into the individual's skin upon application of an electrical current to effect delivery of said medicament in said cell or plurality of cells to the individual's skin.
a substrate having a first surface and a second surface opposite said first surface, said substrate including a medicament-dispensing portion comprising a cell or a plurality of cells forming an aperture or a plurality of apertures between said first surface and said second surface, said cell or plurality of cells containing the medicament; and a layer of adhesive covering at least a portion of said second surface of said substrate opposite said first surface for releasably attaching said substrate to an electrokinetic device containing an electrical power source for electrokinetically driving said medicament through said first surface and into the individual's skin upon application of an electrical current to effect delivery of said medicament in said cell or plurality of cells to the individual's skin.
9. The applicator electrode of claim 8 further comprising a tactile conductive portion carried by said substrate having a second cell or a plurality of cells electrically insulated from said medicament-dispensing portion, said second cell or plurality of cells containing an electrically conductive fluid for electrical connection through said second surface with a conductive portion on the electrokinetic device.
10. An applicator electrode according to claim 8 wherein said substrate comprises a strip, said medicament-dispensing portion being substantially centrally located along said strip, said layer of adhesive disposed along said second surface on opposite sides of said medica-ment-dispensing portion for securing the strip to the device.
11. An applicator electrode according to claim 8 wherein said second surface is pervious to enable electrical contact from the electrokinetic device through said second surface with the medicament or a carrier therefor.
12. An applicator electrode according to claim 8 including a switch-actuating member carried by said substrate to enable the electrokinetic device upon attaching said strip to said device.
13. An applicator electrode according to claim 8 in combination with the electrokinetic device wherein said device comprises a housing having a portion thereof shaped for grasping within an individual's hand for manual manipulation by the individual, and a first electrode exposed for contact with said second surface of said substrate upon application of said sub-strate to said device, the power source being contained within said housing and having first and second terminals, said first terminal being in electrical contact with said first electrode, a tactile electrode in electrical contact with said second terminal of said power source and having a surface for electrical contact with the individual's skin;
said device being operable to deliver said medicament from said applicator electrode to a portion of the individual's skin in contact with said first surface in response to comple-tion of an electrical circuit between said first terminal through said first electrode and said substrate via the individual's skin and said second terminal via said tactile electrode and another portion of the individual's skin.
said device being operable to deliver said medicament from said applicator electrode to a portion of the individual's skin in contact with said first surface in response to comple-tion of an electrical circuit between said first terminal through said first electrode and said substrate via the individual's skin and said second terminal via said tactile electrode and another portion of the individual's skin.
14. A medicament-dispensing applicator electrode for use with an electrokinetic device to transdermally deliver a medicament to an individual, comprising:
a substrate having a first surface and a second surface opposite said first surface, said substrate including a medicament-dispensing portion comprising a cell or a plurality of cells forming an aperture or a plurality of apertures between said first surface and said second surface, said cells or plurality of cells containing the medicament; and a layer of adhesive covering at least a portion of said first surface of said substrate opposite said second surface for releasably attaching said substrate to an individual's skin, said aperture or plurality of apertures being open along said second surface such that the medicament is electrokinetically driven through said first surface and into the individual's skin upon electrically contacting an electrokinetic device containing an electrical power source with said second surface of said medicament-dispensing portion to generate an elec-trical current to effect delivery of said medicament in said cell or plurality of cells to the individual's skin.
a substrate having a first surface and a second surface opposite said first surface, said substrate including a medicament-dispensing portion comprising a cell or a plurality of cells forming an aperture or a plurality of apertures between said first surface and said second surface, said cells or plurality of cells containing the medicament; and a layer of adhesive covering at least a portion of said first surface of said substrate opposite said second surface for releasably attaching said substrate to an individual's skin, said aperture or plurality of apertures being open along said second surface such that the medicament is electrokinetically driven through said first surface and into the individual's skin upon electrically contacting an electrokinetic device containing an electrical power source with said second surface of said medicament-dispensing portion to generate an elec-trical current to effect delivery of said medicament in said cell or plurality of cells to the individual's skin.
15. An applicator electrode according to claim 14 wherein said substrate comprises a strip, said medicament-dispensing portion being centrally located along said strip, said layer of adhesive disposed along said first surface on opposite sides of said medicament-dispens-ing portion for releasably securing the strip to the individual's skin.
16. An applicator electrode according to claim 14 in combination with the electrokinetic device wherein said device comprises a housing having a portion thereof shaped for grasping within an individual's hand for manual manipulation by the individual, and a first electrode exposed for contact with said second surface of said substrate upon application of said device to the substrate, the power source being contained within said housing and having first and second terminals, said first terminal being in electrical contact with said first elec-trode, a tactile electrode in electrical contact with said second terminal of said power source and having a surface for electrical contact with the individual's skin;
said device being operable to deliver said medicament from said applicator electrode to a portion of the individual's skin in contact with said first surface in response to comple-tion of an electrical circuit between said first terminal through said first electrode and said substrate via the individual's skin and said second terminal via said tactile electrode and another portion of the individual's skin.
said device being operable to deliver said medicament from said applicator electrode to a portion of the individual's skin in contact with said first surface in response to comple-tion of an electrical circuit between said first terminal through said first electrode and said substrate via the individual's skin and said second terminal via said tactile electrode and another portion of the individual's skin.
17. An applicator electrode according to claim 14 including a switch-actuating member carried by said substrate to enable the electrokinetic device and thereby generate an electric current to effect delivery of the medicament.
18. A medicament-dispensing applicator electrode for use with an electrokinetic device to transdermally deliver a medicament to an individual, comprising:
a substrate having a first surface and a second surface opposite said first surface, said substrate including a medicament-dispensing portion between said first surface and said second surface and defining a reservoir for containing the medicament; and a layer of adhesive covering at least a portion of one of said first surface and said second surface of said substrate for releasably attaching said substrate to one of an electro-kinetic medicament-delivery device containing an electrical power source or an individual's skin, said second surface of said medicament-dispensing portion being pervious to enable electrical contact through said second surface with the medicament or a carrier therefor such that the medicament is electrokinetically driven from said reservoir through said first surface and into the individual's skin upon transmission of an electrical current through said second surface, said reservoir and said first surface.
a substrate having a first surface and a second surface opposite said first surface, said substrate including a medicament-dispensing portion between said first surface and said second surface and defining a reservoir for containing the medicament; and a layer of adhesive covering at least a portion of one of said first surface and said second surface of said substrate for releasably attaching said substrate to one of an electro-kinetic medicament-delivery device containing an electrical power source or an individual's skin, said second surface of said medicament-dispensing portion being pervious to enable electrical contact through said second surface with the medicament or a carrier therefor such that the medicament is electrokinetically driven from said reservoir through said first surface and into the individual's skin upon transmission of an electrical current through said second surface, said reservoir and said first surface.
19. The applicator electrode of claim 18 further comprising a tactile conductive portion carried by said substrate having an electrically conductive fluid electrically insulated from said medicament-dispensing portion for electrical connection through said second surface with a conductive portion on the electrokinetic device.
20. An applicator electrode according to claim 18 wherein said substrate comprises a strip, said medicament-dispensing portion being centrally located along said strip, said layer of adhesive disposed along said second surface on opposite sides of said medicament-dis-pensing portion for securing the strip to the device.
21. An applicator electrode according to claim 18 in combination with the electrokinetic device wherein said device comprises a housing having a portion thereof shaped for grasping within an individual's hand for manual manipulation by the individual, and a first electrode exposed for contact with said second surface of said substrate upon application of said sub-strate to said device, the power source being contained within said housing and having first and second terminals, said first terminal being in electrical contact with said first electrode, a tactile electrode in electrical contact with said second terminal of said power source and having a surface for electrical contact with the individual's skin;
said device being operable to electrokinetically deliver said medicament from said applicator electrode to a portion of the individual's skin in contact with said first surface in response to completion of an electrical circuit between said first terminal through said first electrode and said substrate via the individual's skin and said second terminal via said tactile electrode and another portion of the individual's skin.
said device being operable to electrokinetically deliver said medicament from said applicator electrode to a portion of the individual's skin in contact with said first surface in response to completion of an electrical circuit between said first terminal through said first electrode and said substrate via the individual's skin and said second terminal via said tactile electrode and another portion of the individual's skin.
22. Apparatus for the transdermal delivery of a medicament to an individual, comprising:
a medicament-dispensing applicator electrode including a substrate having a first surface and a second surface opposite said first surface, said substrate including a medica-ment-dispensing portion comprising a cell or a plurality of cells forming an aperture or a plurality of apertures between said first surface and said second surface, said cell or plurality of cells containing the medicament;
an electrokinetic device comprising a housing having a portion thereof shaped for grasping within an individual's hand for manual manipulation by the individual, and a first electrode formed of electrically conductive material and in electrical contact with said sub-strate and with a portion of an individual's skin upon application of said device to the individual's skin with said substrate interposed therebetween;
a power source contained within said housing having first and second terminals, said first terminal being in electrical contact with said first electrode;
a tactile electrode in electrical contact with said second terminal of said power source and having a surface for electrical contact with another portion of an individual's skin; and said device being operable to electrokinetically drive said medicament from said applicator electrode to effect delivery of said medicament in said cell or plurality of cells to the portion of the individual's skin in contact with said substrate on one side thereof in response to completion of an electrical circuit between said first terminal through said first electrode and said substrate via the individual's skin portion and said second terminal via said tactile electrode and the another portion of the individual's skin.
a medicament-dispensing applicator electrode including a substrate having a first surface and a second surface opposite said first surface, said substrate including a medica-ment-dispensing portion comprising a cell or a plurality of cells forming an aperture or a plurality of apertures between said first surface and said second surface, said cell or plurality of cells containing the medicament;
an electrokinetic device comprising a housing having a portion thereof shaped for grasping within an individual's hand for manual manipulation by the individual, and a first electrode formed of electrically conductive material and in electrical contact with said sub-strate and with a portion of an individual's skin upon application of said device to the individual's skin with said substrate interposed therebetween;
a power source contained within said housing having first and second terminals, said first terminal being in electrical contact with said first electrode;
a tactile electrode in electrical contact with said second terminal of said power source and having a surface for electrical contact with another portion of an individual's skin; and said device being operable to electrokinetically drive said medicament from said applicator electrode to effect delivery of said medicament in said cell or plurality of cells to the portion of the individual's skin in contact with said substrate on one side thereof in response to completion of an electrical circuit between said first terminal through said first electrode and said substrate via the individual's skin portion and said second terminal via said tactile electrode and the another portion of the individual's skin.
23. Apparatus applicator electrode according to claim 22 including a switch-actuating member carried by said substrate to enable said device and thereby complete the electrical circuit.
24. Apparatus for the transdermal delivery of a medicament to an individual, comprising:
a medicament-dispensing applicator electrode;
an electrokinetic device;
said medicament-dispensing applicator electrode including a substrate having a first surface and a second surface opposite said first surface, said substrate including a medica-ment-dispensing portion comprising a cell or a plurality of cells forming an aperture or a plurality of apertures between said first surface and said second surface, said cell or plurality of cells containing the medicament, said substrate having a portion thereof for releasably coupling said substrate to said device;
said device comprising a housing having a portion thereof shaped for grasping within an individual's hand for manual manipulation by the individual, and a first electrode formed of electrically conductive material and exposed for contact with said substrate upon releas-able connection to said device;
a power source contained within said housing having first and second terminals, said first terminal being in electrical contact with said first electrode;
a tactile electrode in electrical contact with said second terminal of said power source and having a surface for contact with the individual's skin; and said device being operable to electrokinetically drive said medicament from said applicator electrode to effect delivery of said medicament in said cell or plurality of cells to a portion of the individual's skin in contact with said substrate on one side thereof in response to completion of an electrical circuit between said first terminal through said first electrode and said substrate via the individual's skin and said second terminal via said tactile electrode and another portion of the individual's skin.
a medicament-dispensing applicator electrode;
an electrokinetic device;
said medicament-dispensing applicator electrode including a substrate having a first surface and a second surface opposite said first surface, said substrate including a medica-ment-dispensing portion comprising a cell or a plurality of cells forming an aperture or a plurality of apertures between said first surface and said second surface, said cell or plurality of cells containing the medicament, said substrate having a portion thereof for releasably coupling said substrate to said device;
said device comprising a housing having a portion thereof shaped for grasping within an individual's hand for manual manipulation by the individual, and a first electrode formed of electrically conductive material and exposed for contact with said substrate upon releas-able connection to said device;
a power source contained within said housing having first and second terminals, said first terminal being in electrical contact with said first electrode;
a tactile electrode in electrical contact with said second terminal of said power source and having a surface for contact with the individual's skin; and said device being operable to electrokinetically drive said medicament from said applicator electrode to effect delivery of said medicament in said cell or plurality of cells to a portion of the individual's skin in contact with said substrate on one side thereof in response to completion of an electrical circuit between said first terminal through said first electrode and said substrate via the individual's skin and said second terminal via said tactile electrode and another portion of the individual's skin.
25. A medicament-dispensing electrokinetic applicator for delivering medicament to a large area of an individual's skin, comprising:
a glove-shaped body containing a medicament for application through an outer surface thereof; and a conductive layer formed within said glove-shaped body for connection with an electrical power source and electrokinetically driving the medicament from the body onto an area of the individual's skin overlaid and in contact with said glove-shaped body upon application of an electrical current to effect delivery of said medicament contained in the body to the large area of the individual's skin in contact with the overlying glove-shaped body, wherein said conductive layer comprises a multi-channel electrode.
a glove-shaped body containing a medicament for application through an outer surface thereof; and a conductive layer formed within said glove-shaped body for connection with an electrical power source and electrokinetically driving the medicament from the body onto an area of the individual's skin overlaid and in contact with said glove-shaped body upon application of an electrical current to effect delivery of said medicament contained in the body to the large area of the individual's skin in contact with the overlying glove-shaped body, wherein said conductive layer comprises a multi-channel electrode.
26. Apparatus for the transdermal delivery of medicament to an individual, comprising:
a medicament-dispensing electrode;
an electrokinetic device;
said medicament-dispensing electrode including a substrate having a first surface and a second surface opposite said first surface, said substrate including a medicament-dispensing portion having a cellular structure with one or a plurality of cells dimensioned to retain a medium including the medicament within the confines of the cellular structure for electrokinetically transporting the medicament from said cell or plurality of cells through said first surface into the individual's skin upon flowing an electrical current between said first surface and said second surface;
a tactile conductive portion carried by said substrate having a second cell or a plural-ity of cells electrically insulated from said medicament-dispensing portion, said second cell or plurality of cells containing an electrically conductive material for electrical connection through said second surface with a conductive portion on the electrokinetic device; and said electrokinetic device including a housing having a portion thereof shaped for manual manipulation by the individual's hand, and a first electrode exposed for contact with said second surface of said substrate upon engagement of said substrate and said device with one another, a power source within said housing and having first and second terminals, said first terminal being in electrical contact with said first electrode, a tactile electrode in elec-trical contact with said second terminal of said power source and having a surface for electrical contact with the tactile conductive portion of the applicator electrode, said device being operable to deliver said medicament from said applicator electrode to a portion of the individual's skin in contact with said first surface in response to completion of an electrical circuit between said first terminal through said first electrode and said substrate via the individual's skin and said second terminal via said tactile electrode, said tactile conductive portion and another portion of the individual's skin.
a medicament-dispensing electrode;
an electrokinetic device;
said medicament-dispensing electrode including a substrate having a first surface and a second surface opposite said first surface, said substrate including a medicament-dispensing portion having a cellular structure with one or a plurality of cells dimensioned to retain a medium including the medicament within the confines of the cellular structure for electrokinetically transporting the medicament from said cell or plurality of cells through said first surface into the individual's skin upon flowing an electrical current between said first surface and said second surface;
a tactile conductive portion carried by said substrate having a second cell or a plural-ity of cells electrically insulated from said medicament-dispensing portion, said second cell or plurality of cells containing an electrically conductive material for electrical connection through said second surface with a conductive portion on the electrokinetic device; and said electrokinetic device including a housing having a portion thereof shaped for manual manipulation by the individual's hand, and a first electrode exposed for contact with said second surface of said substrate upon engagement of said substrate and said device with one another, a power source within said housing and having first and second terminals, said first terminal being in electrical contact with said first electrode, a tactile electrode in elec-trical contact with said second terminal of said power source and having a surface for electrical contact with the tactile conductive portion of the applicator electrode, said device being operable to deliver said medicament from said applicator electrode to a portion of the individual's skin in contact with said first surface in response to completion of an electrical circuit between said first terminal through said first electrode and said substrate via the individual's skin and said second terminal via said tactile electrode, said tactile conductive portion and another portion of the individual's skin.
27. Use of a hand-held iontophoretic device comprising an electrode and a medicament dispensing reservoir containing an antiviral agent, said reservoir being in electrical com-munication with said electrode, for treating lesions associated with cold sore and genital herpes, wherein the medicament dispensing reservoir is in contact with said lesions and a voltage gradient between the electrode and the lesion is present.
28. Use of claim 27 wherein said medicament comprises (2 amino-1,9-dihydro-9-[(2-hydroxyethoxy) methyl]-6H-purin-6-one) or iontophoretically transportable analogs thereof.
29. Use of a hand-held ionosonic device comprising an electrode and a medicament dispensing reservoir containing an antiviral agent, said reservoir being in electrical com-munication with said electrode, for treating lesions associated with cold sore and genital herpes, wherein:
the medicament dispensing reservoir is in contact with said lesions;
ultrasonic vibration in a tissue comprising the lesion is present; and a voltage gradient between the electrode and the lesion is present.
the medicament dispensing reservoir is in contact with said lesions;
ultrasonic vibration in a tissue comprising the lesion is present; and a voltage gradient between the electrode and the lesion is present.
30. Use of claim 29 wherein said medicament comprises (2 amino-1,9-dihydro-9-[(2-hydroxyethoxy)methyl]-6H-purin-6-one) or ionosonically transportable analogs thereof.
31. Use of a hand-held ionosonic device comprising an electrode and a medicament dispensing reservoir containing an ionic compound in electrical communication with said electrode, for treating lesions associated with acne, wherein:
the medicament dispensing reservoir is in contact with a said lesion;
ultrasonic vibration in a tissue comprising the lesion is present; and a voltage gradient between the electrode and the lesion is present.
the medicament dispensing reservoir is in contact with a said lesion;
ultrasonic vibration in a tissue comprising the lesion is present; and a voltage gradient between the electrode and the lesion is present.
32. Use of claim 31 wherein said ionic compound is anionic.
33. Use of claim 31 wherein said ionic compound is a hydroxyl ion.
34. Use of claim 31 wherein said ionic compound is cationic.
35. A disposable medicament dispensing applicator electrode for an iontophoretic drug delivery device adapted for the self-administration of a medicament into a person's skin, said device comprising a base assembly having an active terminal adapted to receive and make electrical contact with a detachable medicament dispensing applicator electrode wherein said base assembly comprises: a case having an elongate, substantially cylindrical outer surface having a size and shape adapted to be comfortably grasped within a person's hand and wherein at least a portion of said outer surface is a tactile electrode formed of an electrically conductive material; and a bipolar electrical power means having a first pole and a second pole; said electrical power means being enclosed within said case and wherein said first pole is in electrical communication with said tactile electrode; wherein said medicament dis-pensing applicator electrode comprises: a module containing unit dose of medicament, an electrically conductive working electrode and means thereon adapted for releasably attaching said working electrode to said second pole of said electrical power means wherein said working electrode further comprises an elongate strip constructed of a substantially electric-ally non-conductive substrate material, said strip having a central portion containing a medicament in an electrically conductive substrate and laterally symmetric end portions having cutouts therewithin.
36. The disposable medicament dispensing applicator electrode of claim 35 wherein said cutouts in said laterally symmetric end portions contain an electrically conductive material.
37. The disposable medicament dispensing applicator electrode of claim 36 wherein said electrically conductive material is a gel.
Applications Claiming Priority (5)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| US09/153,640 | 1998-09-15 | ||
| US09/153,640 US6148231A (en) | 1998-09-15 | 1998-09-15 | Iontophoretic drug delivery electrodes and method |
| US09/205,751 US6385487B1 (en) | 1996-05-08 | 1998-12-04 | Methods for electrokinetic delivery of medicaments |
| US09/205,751 | 1998-12-04 | ||
| PCT/US1999/011440 WO2000015120A1 (en) | 1998-09-15 | 1999-05-24 | Iontophoretic drug delivery electrodes |
Publications (2)
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|---|---|
| CA2343893A1 CA2343893A1 (en) | 2000-03-23 |
| CA2343893C true CA2343893C (en) | 2008-12-30 |
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|---|---|---|---|
| CA002343893A Expired - Fee Related CA2343893C (en) | 1998-09-15 | 1999-05-24 | Iontophoretic drug delivery electrodes |
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| EP (1) | EP1121059A4 (en) |
| JP (1) | JP4297401B2 (en) |
| AU (1) | AU763197B2 (en) |
| CA (1) | CA2343893C (en) |
| WO (1) | WO2000015120A1 (en) |
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| US6792306B2 (en) * | 2000-03-10 | 2004-09-14 | Biophoretic Therapeutic Systems, Llc | Finger-mounted electrokinetic delivery system for self-administration of medicaments and methods therefor |
| US6477410B1 (en) * | 2000-05-31 | 2002-11-05 | Biophoretic Therapeutic Systems, Llc | Electrokinetic delivery of medicaments |
| US20040236269A1 (en) * | 2002-09-25 | 2004-11-25 | Marchitto Kevin S. | Microsurgical tissue treatment system |
| BRPI0511604A (en) * | 2004-05-28 | 2008-01-02 | Jan De Geest | electrical communication unit, electrical communication system, and, use of electrical communication unit or electrical communication system |
| NZ575920A (en) | 2006-09-15 | 2012-08-31 | Stephen John Ralph | Pro-oxidant anti-cancer compounds |
| AU2016369628B2 (en) * | 2015-12-17 | 2021-06-10 | Hg Medical Technologies Llc | Electro kinetic transdermal and trans mucosal delivery accelerator device |
Family Cites Families (18)
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|---|---|---|---|---|
| US279524A (en) * | 1883-06-19 | Thimble | ||
| US3163166A (en) * | 1961-04-28 | 1964-12-29 | Colgate Palmolive Co | Iontophoresis apparatus |
| US4838273A (en) * | 1979-04-30 | 1989-06-13 | Baxter International Inc. | Medical electrode |
| US4856188A (en) * | 1984-10-12 | 1989-08-15 | Drug Delivery Systems Inc. | Method for making disposable and/or replenishable transdermal drug applicators |
| US4765343A (en) * | 1985-01-29 | 1988-08-23 | Biosonics, Inc. | Apparatus for transferring electrical energy to and from living tissue |
| JPH0647026B2 (en) * | 1986-07-11 | 1994-06-22 | 美智士 谷 | Electromagnetic therapy device |
| JPS63135179A (en) * | 1986-11-26 | 1988-06-07 | 立花 俊郎 | Subcataneous drug administration set |
| IL86076A (en) * | 1988-04-14 | 1992-12-01 | Inventor S Funding Corp Ltd | Transdermal drug delivery device |
| JP2788307B2 (en) * | 1989-11-30 | 1998-08-20 | 住友ベークライト株式会社 | Drug dosing device |
| US5318510A (en) * | 1991-06-11 | 1994-06-07 | Deknatel Technology Corporation, Inc. | Collection device |
| US5589563A (en) | 1992-04-24 | 1996-12-31 | The Polymer Technology Group | Surface-modifying endgroups for biomedical polymers |
| JPH0591693U (en) * | 1992-05-22 | 1993-12-14 | 恒 福村 | Electrotherapy equipment |
| US5667487A (en) * | 1993-04-07 | 1997-09-16 | Henley; Julian L. | Ionosonic drug delivery apparatus |
| US5458569A (en) * | 1993-06-08 | 1995-10-17 | Becton Dickinson And Company | Wearable iontophoresis system |
| JP2818999B2 (en) * | 1993-11-22 | 1998-10-30 | ドラッグ デリバリー システムズ インコーポレイテッド | Transdermal drug applicator |
| JPH07194711A (en) * | 1993-12-28 | 1995-08-01 | Tokyo Iken Kk | Gloves for electric treating instrument |
| JPH09103496A (en) * | 1995-10-12 | 1997-04-22 | Etsuko Nozoe | Iontophoresis device |
| US5676648A (en) * | 1996-05-08 | 1997-10-14 | The Aps Organization, Llp | Iontophoretic drug delivery apparatus and method for use |
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1999
- 1999-05-24 EP EP99924478A patent/EP1121059A4/en not_active Withdrawn
- 1999-05-24 CA CA002343893A patent/CA2343893C/en not_active Expired - Fee Related
- 1999-05-24 WO PCT/US1999/011440 patent/WO2000015120A1/en active IP Right Grant
- 1999-05-24 AU AU40966/99A patent/AU763197B2/en not_active Ceased
- 1999-05-24 JP JP2000569706A patent/JP4297401B2/en not_active Expired - Fee Related
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| WO2000015120A1 (en) | 2000-03-23 |
| JP4297401B2 (en) | 2009-07-15 |
| AU4096699A (en) | 2000-04-03 |
| JP2002524184A (en) | 2002-08-06 |
| EP1121059A1 (en) | 2001-08-08 |
| EP1121059A4 (en) | 2006-04-05 |
| AU763197B2 (en) | 2003-07-17 |
| CA2343893A1 (en) | 2000-03-23 |
| WO2000015120A8 (en) | 2001-10-04 |
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| Date | Code | Title | Description |
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| EEER | Examination request | ||
| MKLA | Lapsed |
Effective date: 20130524 |