WO 97/11741 PCT~US96/15513 IONTOPHORETIC DRUG DELIVERY
SYSTEM,-INCLUDlNG REUSABLE DEVICE
FIELD OF T~E lNv~llON
The present invention generally relates to iontophoretic systems ~or delivering drugs, medicines and the like to patients transdermally, i.e., through the skin, and more speci~ically relates to a reusable iontophoretic drug delivery device such as a controller attachable to a disposable drug-~illed patch.
8AC~GROUND OF THB lN V ~:N'l lON
Transdermal drug delivery systems have, in recent years, become an increasingly important means o~ administering drugs and like therapeutic agents.
Presently, there are two types o~ trans~rm~l drug delivery systems, i.e., "Passive" and "Active." Passive systems deliver drug through the skin o~ the user unaided, an example o~ which would involve the application o~ a topical anesthetic to provide localized relie~, as disclosed in U.S.
Patent No. 3,814,095 (Lubens) Active systems on the other hand deliver drug through the skin o~ the user using, ~or example, iontophoresis, which according to Stedman's Medical Dictionary, is de~ined as "the introduction into the tissues, by means o~ an electric current, o~ the ions o~ a chosen medicament." Such systems o~er advantages clearly not achievable by any other methods o~ administration, such as avoiding introduction o~ the drug through the gastro-intestinal tract or punctures in the skin to name a ~ew Conventional iontophoretic devices, such as those described in U S Patent Nos 4,820,263 (Spevak et al.), 4,927,408 (~aak et al.) and ~,084,008 (Phipps), the disclosures o~ which are hereby incorporated by re~erence, ~or delivering a drug or medicine transdermally- through iontophoresis, basically consist o~ two electrodes, which are in contact with a portion o~ a patient's body. A ~irst - SUBSTITUTE SHEET (P~UL~ 26) =
WO97/11741 PCT~S96/15513 electrode, generally called the active electrode, delivers the ionic substance or drug into the body by iontophoresis. The second electrode, generally called the counter electrode, closes an electrical circuit that includes the ~irst electrode and the patient's body Generally, the circuit includes a source o~ electrical energy, such as a battery. The ionic substance to be driven into the body may be either positively charged or negatively charged In the case o a positively charged ionic substance, the anode o~ the iontophoretic device becomes the active electrode and the cathode serves as the counter electrode to complete the circuit. Alternatively, i~
the ionic substance to be iontophoretically delivered is negatively charged, the cathode will be the active electrode and the anode will be the counter electrode.
In practice, this process is typically achieved by placing the ionic drug either in solution or in gel ~orm on a carrier and placing the drug-containing carrier, ~or example, in the ~orm o~ a drug-~illed adhesive patch, into contact with t-he skin. The pair o~ electrodes is placed in contact with the skin and with the carrier. Direct current is applied between the two electrodes. Under the in~luence o~ the electric ~ield present, the drug molecules migrate through the skin. As current ~lows between the two electrodes placed at spaced apart locations on the skin, the current path carries the drug with it.
In order to dellver the drug to the patient, the adhesive patch may be applied to the desired portion o~ the patient's body and the controller attached to the patch. O~tentimes the controller is as large as, or larger than, the patch. It also should be somehow secured in place o~ the patient so that the patient may remain mobile and carry both the patch and controller with him as he moves about Delivery o~ a drug to the patient iontophoretically may be accomplished either at a constant rate over a long period o~ time, or periodically at various intervals and in some situations, upon demand. As can be seen, it may be necessary SUBSTITUrE SHEET (RULE 26) W O 97/11741 PCT~US96/1~513 Lor the drug-cont~;n~ng carrier to be maintained in contact with the patient's skin over a long period o~ time, either ~or continuous drug delivery, or to permit ~requent interval delivery over a period o~ time.
S One o~ the problems with an iontophoretic drug delivery device such as described above, especially one that is compact and portable to provide patient mobility, is how to attach the controller to the patient and yet be as unobtrusive as possible and com~ortable ~or the patient where the system is to be applied ~or an extended period o~ time A side-by-side arrangement o~ patch and controller may occupy too much space on the patient's skin and limit the choices where the transdermal device may be attached to the patient. Also, the controller may then have to be ~astened to the patient's skin by adhesive or a strap, ~or example, which may be uncom~ortable to the user As previously noted, it may be necessary to use an iontophoretic drug delivery device over an extended period o~
time i.e., longer than 24 hours to delivery the necessary dosage o~ drug. As the length o~ delivery time increases, there is a need to develop small, unobtrusive iontophoretic delivery devices which can be easily worn on the skin under clothing.
In addition to the need ~or developing smaller iontophoretic devices, there is need to reduce the cost o~
these devices in order to make them more competitive with conventional ~orms o~ therapy such as pills and subcutaneous injections. One manner o~ improving cost e~ectiveness is to have a reusable controller which includes the costly electronics that provides the current to drive the patch.
Also, it is envisioned that the controller, which may contain sophisticated electronics besides ~ust a power source to control and monitor the delivery o~ drug to the patient, is repeatedly used while the patch is discarded a~ter use and replaced with new patches. The replaceable patches and controller should be so structured as to make it easy and SUBSTITUTE SHEET (RULE 26) W O 97/11741 PCT~US96/15513 convenient ~or the patient to replace used patches with new patches on the controller.
Thus, there has been a need ~or an iontophoretic drug delivery system, particularly a controller which would eliminate the problems and limitations associated with the prior devices discussed above, most signi~icant o~ the problems being reusability, unobtrusiveness and ease o~ use.
SnMM~RY OF T~E lNV~NllON
In contrast to the prior devices discussed above, it has been ~ound that a iontophoretic drug delivery system includiny a controller which may be constructed in accordance with the present invention is particularly suited ~or reuse In addition, the controller ~or the system o~ the present invention pre~erably can be used with disposable patches to easily attach the system to the patient ~or delivering the drug, medicament or the like.
The controller o~ the present invention ~or use in c~mbination with a drug-~illed patch to ~orm an operable iontophoresis drug delivery system includes a housing having an upper portion and a lower portion pivotably interconnected, with the upper=portion and the lower portion being biased towards one another at a openable ~ront end by biasing means, and the housing including electronic means ~or monitoring and controlling electrical current and electrical connection means positioned within the ~ront end o~ the housing and electrically connected to the electronics so that when su~icient ~orce is applied to the housing to overcome the biasing means, the upper portion and the lower portion are ~orced away ~rom one another to open the ~ront end and expose the electrical connection array whereby the electrical connection array may be interconnected with the drug-~illed patch In the pre~erred embodiment, the connection means is adapted to include an electrical array and also adapted so that upon opening the ~ront end the patch may be inserted into the open ~ront end in electrical contact with the connection means.
SUBSTITUTE SHEET (RULE 26) WO 97/11741 PCT~US96/15513 In addition, the open end o~ the housing includes a notch for keying the controller and the patch to insure proper interconnection and orientation.
The iontophoretic drug delivery system o~ the present invention includes a drug-~illed patch removably attachable to the skin o~ a patient ~or iontophoretically delivery at least one drug to the patient, with the patch including conductive pad means ~or interconnection with the reusable controller, and a reusable controller removably, electrically connectable to the patch, the controller providing su~icient energy to the patch to drive the ionized medicament into the skin o~ the patient, with the controller including housing means having an upper portion and a lower portion pivotably interconnected, with the upper portion and the lower portion being biased towards one another at a openable ~ront end by biasing means, and the housing including electronic means ~or monitoring and controlling electrical current, and with the ~ront end o~ the controller housing means adapted to including electrical cannection means positioned within the ~ront end o~ the housing and electrically connected to the electronics so that when su~icient ~orce is applied to the housing to overcome the biasing means, the upper portion and the lower portion are ~orced away ~rom one another to open the ~ront end and expose the electrical connection array whereby the electrical connection array may be interconnected with the conductive pad means o~ the drug-~illed patch.
BRIEF DESCRIPTION OF THE DRAWINGS
The various ~eatures, objects, bene~its, and advantages o~ the present invention will become more apparent upon reading the ~ollowing detailed description o~ the pre~erred embodiment along with the appended cl ~m~ in conjunction with the drawings, wherein like re~erence numerals identi~y corresponding components, and:
SUBSTITUTE SHEET (RULE 26) - Figure 1 is a perspective, schematic view of the control;erof the present invention illustrating opening of the controller for interconnecting to the patch;
Figure 2 is a perspective view of the controller shown in Figure 1 illustrating interconnection of the controller and the patch;
Figure 3 is plan view of the patch for interconnection with the controller of the present invention;
Figure 4 is an perspective view of the controller having a member for attaching the patch thereto, whereby the patch having a corresponding member may be folded and the two members brought into contact with one another; and Figure 5 is a perspective bottom view of the controller illustrating attachment of the patch to the controller.
DETAIT~n D~SC~IPTION OF T~ PREFERRED EMBODIMENT
The iontophoretic drug deliver system of the present invention is illustrated in Figure 1-5, with the controller generally designated 10 and the patch generally designated 12.
Referring to Figures 1, 2 and 3, the controller 10 of the present invention for use in the iontophoretic drug delivery system is electrically connectable to the patch 12 to form the operable system, with the patch being attachable to the skin o~
a patient 14. The patch typically includes an active electrode assembly 16 and a counter electrode assembly 18. If a positively charged medicament is to be delivered to the skin 14, the medicament would be positioned in the active electrode assembly.
In the preferred embodiment, an third or adjunct electrode assembly 19 is provided so that when delivering a local anesthetic such a Lidocaine, the local anesthetic may be delivered beneath the counter electrode as well as the active electrode as disclosed, for example, in International Publication No. WO 95/09032, published 6 April 1995, entitled "IONTOPHORETIC
DRUG DELIVERY SYSTEM AND METHOD FOR USING SAME," which is hereby incorporated in its entirety.
As illustrated in Figures 1-4, the controller 10 is coupled to the patch 12 using well known means, for example, by printed ~EN~ED S~ET
"~ '~ ' . ,,. '',;
flexible circuits, metal foils, wires, tabs or electrically conductive adhesives as disclosed for example in International Publication No. WO 96/10442, entitled "IONTOPHORESIS ASSEMBLY
INCLUDING PATCH/CONTROLLER ATTACHMENT," published 11 April 1996, the disclosure of which is hereby incorporated by reference in its entirety.
Referring to Figures 3 and 4, the patch 12 is a generally planar flexible member and may be adhesively supported on the skin 14 of the patient (Figure 5). The patch 12 includes an enlarged patch body 20 and an extending narrow tab 22. The patch body 20 includes opposed planar surfaces 24 and 26, with the planar surface 24 disposed for skin contact and including a drug reservoir 28 typically in a gel form which contains at least one drug, medicament or like active agents (hereinafter collectively referred to simply as drugs), preferably in an ionic form. While the drug reservoir 28 is shown, any other known iontophoretic drug reservoir structure for placing a medicament in contact with the skin in an iontophoretic patch may be employed, as disclosed for example in International Publication No. WO 95/09031 entitled "IONTOPHORETIC DRUG DELIVERY DEVICE AND RESERVOIR AND METHOD OF
MAKING SAME," published 6 April 1995, the disclosure of which is hereby incorporated by reference in its entirety.
Each of the electrode assemblies 16 and 18 are positioned to be in contact with the skin once the patch 12 is secured, as shown in Figure 5. The positioning of the electrode assemblies 16 and 18 is such that an electrical current path is established between the electrode assemblies 16 and 18 through the skin of the patient 14. A direct current source in combination with the electrode assemblies 16 and 18 and the patient's body 14 completes the circuit and generates an electric field across the body surface or skin to which the iontophoretic device is applied, with the drug reservoir 28 assumes the same charge as the ionized drug contained in the reservoir 28. Under the influence of electrical current passing from the electrode assembly 16 through the skin 14 to the electrode assembly 18, the drug contained in the drug reservoir 28 is transcutaneously AMENDED SHEET
delivered into the body of the patient by the process of iontophoresis.
Referring to Figure 4, the electrical current is supplied from the controller 10 to the electrode assemblies 16 and 18 on the patch via the electrical traces or leads 32 and 34 shown in Figure 3. Each of the traces 32 and 34 may be one or more conductive paths extending from the electrode assemblies 16 and 18 to exposed conductive pads 36 (Figure 3) positioned on a marginal edge of the patch tab 22. As described in further detail below, the pads 36 are positioned for electrical connection to the controller 10, which provides a source of electrical current.
The particular construction of the patch 12 is not essential to the present invention, and may be formed of woven or non-woven textiles or polymers or may be any other construction well known in the art. However, it is preferred that the electrode assemblies 16, 18, the electrical traces 32, 34 and the conductive pads be printed or otherwise formed on a polymeric substrate as disclosed, for example, in International Publication No. WO 94/17853 entitled "ACTIVE DRUG DELIVERY DEVICE, ELECTRODE
AND METHOD FOR MAKING SAME," published 18 August 1994, the disclosure of which is hereby incorporated by reference in its entirety.
As illustrated in Figures 1 and 2, the controller 10 includes a controller housing 40 having an upper portion 42 and a lower portion 44 pivotably interconnected, with the portions being biased towards one another by a biasing means such as a spring 46. In this way, the housing 40 has a general clothespin shape and includes an biasingly openable front end 48 which accommodates the tab 22 of the patch 12. The housing 40 further accommodates a connection array 50 adjacent the electronics 52 contained within the housing 40 and schematically shown in phantom in Figure 2. The connection array 50 and the electronics 52 are preferably mounted to a common printed circuit board (not shown). The connection array 50 may include plural electrical terminals in electrical connection with the electronics 52 and may be connectable to the pads 36 of the tab 22 extending from _ 8 A~EN~)E~ S~tEET
~ the patch 12. In the p~esent illustrative embodiment, the connection array 50 is an electrical connection member having plural spaced-apart, exposed conc~uctive surfaces separated by an insulating material. As p~evio~sly discussed, it may be S appreciated that any suitable electrical interconnection device may be employed in accordance with the present invention.
Re~erring back to Figure 2, the controller 10 houses the electronics 52 that monitor and control the supply of electric current to the electrode assemblies 16 and 18 and the user interfaces. As is known in the art, the electrical components may include a source of electrical power such as a battery and additional electronic components, such as an application speci~ic integrated circuit, a microprocessor, used to send a controlled electrical current to electrode assemblies 16 and 18. It should be appreciated that the particular electrode assemblies and the electronic array are not essential to the present invention, with the electrode assemblies including, for example, those disclosed in International Publication No. WO 96/10440 entitled "IONTOPHORETIC DRUG DELIVERY DEVICE HAVING IMPROVED CONTROLLER,"
published 11 April 1996 and International Publication No.
97/07854 published 6 March 1997 entitled "IONTOPHORETIC DRUG
DELIVERY DEVICE HAVING HIGH-EFFICIENCY DC-TO-DC ENERGY CONVERSION
CIRCUIT," the disclosures of which are hereby incorporated by re~erence in their entirety.
In the preferred embodiment, as illustrated in Figures 1 and 2, the controller may be easily interconnected with the patch 12 under thumb actuation to an open position exposing the connection array 50 for electrical connection with the pads 36 of the tab 22. Specifically, by pressing the rear end 49 of the housing with sufficient force to overcome the spring 46 to open front end 48 of housing 42 (Figure 1). The tab 22 of the patch 12 may then be inserted in the open end, with the conductive pads 36 slidably engageable with the connection array 50 and the housing returned to a closed position by releasing the rear portion to cover the connection array 50 with the pads clamped or otherwise held there between.
In order to assure accurate alignment of the pads 36 of the tab 22 with the connection array 50 supported within the housing 40, the tab 22 is keyed to the housing 40. Specifically, the tab 22 includes an extending leg or like portion 38 on one side which is designed to fit in a corresponding notch 54 formed in at least one side of the front end 48 of the lower portion 42 of the housing 40. The notch 54 and the leg 38 are of similar shape so as to provide keyed accommodation of the tab 22 and the leg 38.
The key structure included on both the housing front end 48 and the leg 38 insures proper orientation of the patch 12 and the controller 10 by preventing incorrect positioning of the patch 12 with respect to the controller 10. In the present embodiment, both the front end 48 and the notch 54, and the corresponding tab 22 and the leg 38 have a generally L-shaped cross-section, however, any other mating shape which would prevent incorrect alignment may be employed.
Referring to Figures 4 and 5, the controller 10 and the patch 12 include attachment means for permitting the releasable support of the controller 10 on the patch 12 after interconnection between the pads 36 and the connective array 50 is established.
The surface 24 of patch 12, and the exposed upper portion 42 include cooperating fastening elements 56 and 58 thereon. In the present illustrative embodiment, the ;~
W O 97/11741 PCT~US96/15513 cooperative ~astening elements 56, 58 include conventional hook and loop ~asteners o~ the type sold under the trademark VELCRO.
Any other cooperating type ~asteners may be employed to achieve the same objective. One cooperating ~astening element 56 is secured adhesively or otherwise to patch 12 on sur~ace 24 while the other cooperating ~astening member 58 is secured by adhesive or otherwise to the exposed sur~ace o~ upper portion 42 o~ the housing 40. As described in ~urther detail below, attachment o~ the mating hook and loop ~asteners 56 or 58 provide removable support ~or controller 10 on patch 12. It may be appreciated by those skilled in the art that the patch and controller may take any known ~orm. The only requirement is that the patch be capable o~ being physically and electrically connected to the controller 10.
SUBSTITUTE SHEET (RULE 26) CA 02233l97 l998-03-26 Operation and Use Having described one embodiment of iontophoretic drug delivery system, including the controller 10 and the patch 12, of the present invention, its operation and use is described below.
As illustrated in Figure 5, the controller 10 and patch 12 may be adhesively secured to the skin 14 of the patient, with surface 24 of patch 12 placed in intimate contact with the skin 14 so that the electrode assemblies 16 and 18, as well as the drug containing reservoir 28, are supported in intimate contact with the skin 14. In order to iontophoretically deliver the medicament from reservoir 28 transcutaneously through the skin 14, the reusable controller 10 of the present invention is electrically connected to patch 12. The housing 40 is opened and the tab 22 of the patch 12 is inserted into the open front end 48 of the housing 40. Proper planar orientation is assured between the patch 12 and the controller 10 due to the key mateability between the notch 54 in the open front end 48 of the housing 40 and the extending leg 38 of the patch tab 22. As the controller 10 is designed to be maintained in electrical connection with the patch 12 during iontophoretic delivery of the drug contained in the reservoir 28, the controller lo may be fastened or otherwise attached to the patch 12 so that it will be conveniently retained on the skin of the patient.
As shown in Figures 4 and 5, once the patch 12 is connected to controller 10, the controller may be flipped up so that the mating hook and loop fasteners 56 and 58 engage each other to removably fasten the controller 10 to the patch 12 as shown in Figure 5.
The controller 10 is comfortably retained on the skin of the patient during iontophoretic drug delivery. At such time as a particular application of the drug is completed, the controller 10 and the patch 12 may be removed from the skin of the patient, and by separating the mating hook and loop fasteners 56 and 58, and pressing on the rear end of the housing 40, the controller 10 and the patch 12 may be AMENOED ~tEET
W O 97/11741 PCT~US96/15~13 separated In this way, the controller may be disconnected and placed aside until the next administration o~ the drug is needed, when it can be reused with a new patch.
In the pre~erred embodiment, the patch 12 o~ the present invention contains Lidocaine (a local anesthetic) and Epinephrine or Adrenaline (vasoconstrictors) In this way, the device can be used ~or anesthetizing the applied area to m; n~m; ze sensation ~rom the insertion o~ a needle or the like.
However, it should be appreciated that other substances suitable ~or being applied to the area may be utilized which are well known to those skilled in the art.
Active agent, drug, ~ormulation, medication, medicament and active compound have been used herein to mean any ethical pharmaceutlcal compound or agent, such as therapeutic compounds, diagnostic agents, anesthetic agents and the like.
As is well known within the ~ield, the device can be situated on the area o~ the patient to which the active agent is to be applied (the applied area) such as the skin and a v~ltage impressed across the electrode assemblies 16, 18 to cause electrical current to flow through the skin o~ the patient to drive or otherwise transport the drug pre~erably in the ~orm o~ an ionic active agent into the skin and the tissue to be absorbed by the body o~ the patient. The electric ~ield lines are su~iciently long, however, so that the active agent is transported to the desired depth within the skin, and possibly to the vasculature, to provide the desired e~ect, e.g., anesthetic, therapeutic or diagnostic It should also be appreciated that the device o~ the present invention can be applied to other areas o~ the body such as mucus membranes depending upon the desired therapy and drugs to be delivered.
In addition, while the present invention has been described in connection with iontophoresis, it should be appreciated that it may be used in connection with other principles o~ active introduction, i.e , motive ~orces, such as electrophoresis which includes the movement o~ particles in an electric ~ield toward one or other electric pole, anode, or - SUBSTITUTE SHEET (RULE 26) cathode and electro-os~osis which includes the transport o~
uncharged compounds due to the bulk ~low o~ water induced by an electric ~ield Also, it should be appreciated that the patient may include humans as well as ~n;m~l S
While the pre~erred embodiment o~ the present invention has been described so as to enable one skilled in the art to practice the device o~ the present invention, it is to be understood that variations and modi~ications may be employed without departing ~rom the concept and intent o~ the present invention as de~ined in the ~ollowiny claims. The preceding description is intended to be exemplary and should not be used to limit the scope o~ the invention. The scope o~ the invention should be det~rm; ne~ only by re~erence to the ~ollowing claims What is claimed is:
SUBSTITlJTE SHEEr (RULE 26)