The term "electrotransport" as used herein refers generally to the delivery of an agent (eg, a drug) through a membrane, such as skin, mucous membrane, or nails, which delivery is induced by application of an electrical potential. For example, a beneficial therapeutic agent may be introduced into the systemic circulation of a human body by electrotransport delivery through the skin. A widely used electrotransport process, iontophoresis, involves the electrically induced transport of charged ions. Another type of electrotransport, electroosmosis, involves the flow of a liquid, which liquid contains the agent to be delivered, under the influence of an electric field. Still another type of electrotransport process, electroporation, involves the formation of transiently-existing pores in a biological membrane by the application of an electric field, through which pores an agent can be delivered either passively (ie, without electrical assistance) or actively (ie, under the influence of an electric potential). However, in any given electrotransport process, more than one of these processes may be occurring simultaneously to a certain extent.
Accordingly, the term "electrotransport", as used herein, should be given its broadest possible interpretation so that it includes the electrically induced or enhanced transport of at least one agent, which may be charged, uncharged, or a mixture thereof. regardless of the specific mechanism or mechanisms by which the agent actually is transported.
Electrotransport devices generally use at least two electrodes which are in electrical contact with some portion of the skin, nails, mucous membrane, or other surface of the body. One electrode, commonly referred to as the "donor" or "active" electrode, is the electrode from which the agent is delivered into the body. The other electrode, typically termed the "counter" or "return" electrode, serves to close the electrical circuit through the body. For example, if the agent to be delivered is positively charged, ie, a cation, then the anode is the active or donor electrode, while the cathode serves to complete the circuit. Alternatively, if an agent is negatively charged, ie, an anion, the cathode is the donor electrode. Additionally, both the anode and cathode may be considered donor electrodes, for example, if both anionic and cationic agent ions are to be delivered from the cathode and anode, respectively.
Furthermore, electrotransport delivery systems generally require at least one reservoir or source of the agent to be delivered to the body. Examples of such donor reservoirs include a pouch or cavity, a porous sponge or pad, and a hydrophilic polymer or a gel matrix. Such donor reservoirs are electrically connected to, and positioned between, the anode or cathode and the body surface, to provide a fixed or renewable source of one or more agents or drugs. Electrotransport devices also have an electrical power source such as one or more batteries. Typically, one pole of the power source is electrically connected to the donor electrode, while the opposite pole is electrically connected to the counter electrode. In addition, some electrotransport devices have an electrical controller which controls the current applied through the electrodes, thereby regulating the rate of agent delivery. Furthermore, passive flux control membranes, adhesives for maintaining device contact with a body surface, insulating members, and impermeable backing members are some other potential components of electrotransport devices.
As used herein, the terms "agent" and "drug" are used interchangeably and are intended to have broad application and to refer to any therapeutically active substance that is delivered to a living organism to produce a desired, usually beneficial, effect. In general, this includes therapeutic agents in all of the major therapeutic areas including, but not limited to: anti-infectives such as antibiotic and antiviral agents; analgesics, and analgesic combinations; anesthetics, anorexics; antiarthritics; antiasthmatic agents; anticonvulsants; antidepressants; antidiabetic agents; antidiarrheals; antihistamines; anti-inflammatory agents; antimigraine preparations; antimotion sickness preparations; antinauseants; antineoplastics; antiparkinson drugs; cardiostimulants; antipruritics; antipsychotics; antipyretics; antispasmodics, including gastrointestinal and urinary; anticholinergics; sympathomimetrics; xanthine derivatives; cardiovascular preparations, including calcium blockers; beta blockers; beta-agonists; antiarrythmics; antihypertensives; ACE inhibitors; diuretics; vasodilators, including general, coronary, peripheral and cerebral; central nervous system stimulants; cough and cold preparations; decongestants; diagnostics; hormones; hypnotics: immunosuppressives; muscle relaxants; parasympatholytics; parasympathomimetrics; prostaglandins; proteins; peptides; psychostimulants; sedatives and tranquilizers.
All electrotransport agent delivery devices utilize an electrical "power network" to electrically connect the power source (eg, a battery) to the electrodes. In very simple devices, such as those disclosed by Ariura et al in U.S. Pat. No. 4,474,570, the power network is merely the battery and a conductive wire used to connect the battery to an electrode. Other devices use a variety of electrical components to control the amplitude, polarity, timing, waveform shape, etc. of the electric current supplied by the power source. See, for example, U.S. Pat. No. 5,047,007, issued to McNichols et al.
Commercial transdermal electrotransport drug delivery devices (eg, the Phoresor, sold by Iomed, Inc. of Salt Lake City, Ut.; the Dupel Iontophoresis System sold by Empi, Inc. of St. Paul, Mn.; the Webster Sweat Inducer, sold by Wescor, Inc. of Logan, Ut) generally utilize a desk-top electrical power supply unit and a pair of skin contacting electrodes. The donor electrode contains a drug solution while the counter electrode contains a solution of a biocompatible electrolyte salt. Examples of "satelite" electrode assemblies which are adapted for use with a desk-top electrical power supply unit are disclosed in Lloyd et al U.S. Pat. 5,236,412; Hillman et al U.S. Pat. No. 5,088,978; Patelenz et al U.S. Pat. No. 5,087,242; Mathiesen et al 5,087,241; Jacobsen et al U.S. Pat. No. 5,037,380; LaPrade U.S. Pat. No. 5,006,108; Stephen et al U.S. Pat. No. 4,979,938; Johnson et al U.S. Pat. No. 4,973,303; Jacobsen et al U.S. Pat. No. 4,968,297; and elsewhere. The satelite electrodes are connected to the electrical power supply unit by long (e.g., 1-2 meters) electrically conductive wires. In this type of design configuration, there is no danger of the liquid drug/salt solutions contaminating the electrical circuitry in the desk-top power supply unit since they are far removed from one another. In general, the satelite electrodes are comprised of a receptacle or a matrix for holding the drug/salt solution, a current distributing member and a means for connecting the current distributing member to the long electrically conductive wire/cable. In general, the satelite electrodes contain no electrical components for generating or controlling the electric current applied by the device.
More recently, small self-contained electrotransport delivery devices adapted to be worn on the skin, sometimes unobtrusively under clothing, for extended periods of time have been proposed. The electrical power networks in such miniaturized electrotransport drug delivery devices are also preferably miniaturized, and may be in the form of either integrated circuits (i.e., microchips) or small printed flexible circuits. Conventional printed circuits are formed by printing or otherwise depositing electrically conductive pathways on a flexible substrate, usually in the form of a polymer sheet. Electronic components, such as batteries, resistors, pulse generators, capacitors, etc., are electrically connected to form an electrical power network which generates and/or controls the amplitude, polarity, timing, waveform shape, etc. of the electric current which is the driving force for the delivery of the drug or other beneficial agent. Such small self-contained electrotransport delivery devices are disclosed for example in Tapper U.S. Pat. No. 5,224,927; Haak et al U.S. Pat. No. 5,203,768; Gyory et al U.S. Pat. No. 5,169,383; Watanabe U.S. Pat. No. 5,032,110; Sibalis U.S. Pat. No. 5,167,617; Bannon et al U.S. Pat. No. 5,135,480; Sibalis et al U.S. Pat. No. 5,135,479; Sibalis U.S. Pat. No. 4,883,457 and Ariura et al U.S. Pat. No. 4,474,570. One design problem which is inherent in any small wearable electrotransport device is that the electrical network which powers the device and controls the level of applied current must be adequately protected from contamination from external liquids such as water from bathing. The prior art recognized this and water-proof backings have been used to prevent contamination from external liquids. See Haak et al U.S. Pat. No. 5,158,437. Sibalis U.S. Pat. No. 4,883,457 also teaches an adhesive seal surrounding an entire assembly of batteries and liquid containing electrodes in order to separate them from the external environment.
While the prior art has recognized the need to prevent the electrotransport drive/control power networks from being contaminated from contacting external liquids, there is still the potential problem of contamination from contacting the (usually aqueous) drug solution contained in the donor electrode reservoir and/or the salt solution contained in the counter electrode reservoir. What is needed is an electrotransport device, and a method of making same, which provides better insulation of the power supply and other electrical components from the wet (ie, liquid containing) portions of the device.