Patent Publication Number: US-2009221951-A1

Title: Iontophoresis device and electric power source for an iontophoresis device

Description:
CROSS-REFERENCE TO RELATED APPLICATIONS 
     This application is the U.S. national stage of international application no. PCT/JP2006/318174, filed Sep. 13, 2006, which claims benefit from Japanese application no. 2005-267588, filed Sep. 14, 2005, which applications are hereby incorporated by reference in their entirety. 
    
    
     BACKGROUND 
     1. Technical Field 
     The present description relates to an iontophoresis device for administering a drug to an organism and an electric power source for the iontophoresis device. 
     2. Description of the Related Art 
     Iontophoresis is one method of permeating a drug into an organism through a biological interface, such as the skin or mucosa. Iontophoresis devices typically include a working electrode assembly having a drug solution holding portion holding a drug solution and a non-working electrode assembly as a counter electrode for the working electrode assembly. A voltage having the same polarity as that of a drug (e.g., a drug ion) in the drug solution holding portion is applied to the working electrode assembly as it is brought into close contact with a biological interface to electrically drive the drug into an organism via the biological interface. 
     A patch-type structure is one possible structure for each of the working electrode assembly and the non-working electrode assembly. 
     The term “patch” conventionally refers to a cloth-like section having adhesive on one surface that may also include a substance such as a drug or an antigen. The patch may have some thickness and may have no adhesiveness in some embodiments. 
     As described in, for example, JP 2002-532540 A, a nicotine patch containing nicotine as an antismoking auxiliary agent is one example of such a patch. In addition, as described in JP 2005-510488 A, some transdermal absorption patches are used to deliver local anesthetics, e.g., using morphine hydrochloride. 
     Drug tapes have also been developed. A film of the drug tape is typically configured such that the amount of drug released reaches its peak at some point in time (e.g., 6 hours) after the tape is placed against the biological interface. 
     Conventionally, the amount of drug administered by such methods cannot be finely controlled. For example, a drug cannot be easily administered in accordance with the daily patterns of a patient, an onset time (for example, dawn, in the case of an asthmatic attack), a circadian rhythm, or otherwise. 
     Oral delivery may apply an excessive load to a patient&#39;s stomach. Meanwhile, if one attempts to manage the amount of drug administered by removing a patch-type iontophoresis device after a predetermined time period, it is relatively easy to forget this manual task and the amount of drug administered may exceed an allowable value. 
     BRIEF SUMMARY 
     One object of the embodiments described herein is to provide an iontophoresis device capable of controlling the amount and timing of drug administration. This may be used to take into consideration the daily patterns of a patient and the circadian rhythm of the drug, for example. 
     In one embodiment, an iontophoresis device may include: a working electrode assembly and a non-working electrode assembly for administering a drug by iontophoresis; an electric power source connected to the working electrode assembly and the non-working electrode assembly; and current control circuitry coupled to the electric power source and operable to programmably control a current that flows to each of the electrode assemblies according to a set pattern; wherein the drug is released based at least in part on the current. 
     In one embodiment, the set pattern of the current control circuitry is rewritable from outside the iontophoresis device without contact. 
     In another embodiment, the working electrode assembly and the non-working electrode assembly are each of a patch-type. 
     In yet another embodiment, the working electrode assembly includes: a working electrode connected to the electric power source with a same polarity as that of a charged ion of the drug; an electrolyte solution holding portion holding an electrolyte solution, the electrolyte solution holding portion adjacent a front surface of the working electrode; a second ion exchange membrane permitting passage of ions having a polarity opposite to that of the charged ion of the drug, the second ion exchange membrane adjacent a front surface of the electrolyte solution holding portion; a drug solution holding portion holding the drug, the drug solution holding portion adjacent a front surface of the second ion exchange membrane; and a first ion exchange membrane permitting passage of ions having the same polarity as that of the charged ion of the drug, the first ion exchange membrane adjacent a front surface of the drug solution holding portion. The non-working electrode assembly may also include: the non-working electrode connected to the electric power source having the polarity opposite to that of the charged ion of the drug; a second electrolyte solution holding portion holding a second electrolyte solution, the second electrolyte solution holding portion adjacent a front surface of the non-working electrode; a third ion exchange membrane permitting passage of ions having the same polarity as that of the charged ion of the drug, the third ion exchange membrane adjacent a front surface of the second electrolyte solution holding portion; a third electrolyte solution holding portion holding a third electrolyte solution, the third electrolyte solution holding portion adjacent a front surface of the third ion exchange membrane; and a fourth ion exchange membrane permitting passage of ions having the polarity opposite to that of the charged ion of the drug, the fourth ion exchange membrane adjacent a front surface of the third electrolyte solution holding portion. 
     In yet another embodiment, an electric power source device for an iontophoresis device including a working electrode assembly and a non-working electrode assembly for administering a drug by iontophoresis is disclosed. The electric power source device may include: a battery; current control circuitry operable to programmably control a current from the battery to each of the electrode assemblies according to a set pattern; and an antenna operable to receive a signal used to rewrite the set pattern of the current control circuitry without contact. 
     In another embodiment, the current control circuitry may be disposed radially outside the battery and side by side next to the battery. 
     In yet another embodiment, the battery is disposed off-center from the working electrode assembly, and the current control circuitry is disposed next to the battery on a side of the battery closer to a center of the working electrode assembly. 
     In still another embodiment, the current control circuitry is disposed on top of the battery. 
     A current amount and a discharge duration may be controlled by using a program to implement a pattern determined by a doctor. The amount of drug administered by an iontophoresis device is proportional to the current, so the amount and timing of drug administered may thereby be controlled. As a result, the drug can be administered in accordance with, for example, the living pattern of a patient and/or a circadian rhythm. 
     In addition, in certain embodiments, an iontophoresis device may be erroneously stuck to a skin for a long time period, while the amount of drug administered is limited to an allowable value or less, by causing the current to go to zero after a predetermined discharge duration (i.e., administration time). 
    
    
     
       BRIEF DESCRIPTION OF THE SEVERAL VIEWS OF THE DRAWINGS 
       In the drawings, identical reference numbers identify similar elements. The sizes and relative positions of elements in the drawings are not necessarily drawn to scale. For example, the shapes of various elements and angles are not drawn to scale, and some of these elements are arbitrarily enlarged and positioned to improve drawing legibility. Further, the particular shapes of the elements as drawn, are not intended to convey any information regarding the actual shape of the particular elements, and have been solely selected for ease of recognition in the drawings. 
         FIG. 1  is a plan view of an iontophoresis device, according to one illustrated embodiment. 
         FIG. 2  is an enlarged cross-sectional view of the iontophoresis device of  FIG. 1  taken along the line II-II. 
         FIG. 3  is an enlarged cross-sectional view of the iontophoresis device of  FIG. 1  taken along the line III-III. 
         FIG. 4  is a circuit diagram representing an electrical system of the iontophoresis device of  FIG. 1 . 
         FIG. 5  is a circuit diagram of current control circuitry of the iontophoresis device of  FIG. 1 , according to one illustrated embodiment. 
         FIG. 6  illustrates a set pattern for a current that flow to electrode assemblies of the iontophoresis device of  FIG. 1 . 
         FIG. 7  is a plan view of an electric power source and current control circuitry according to another illustrated embodiment. 
         FIG. 8  is a cross-sectional view of an electric power source and current control circuitry, according to another illustrated embodiment. 
     
    
    
     DETAILED DESCRIPTION  
     In the following description, certain specific details are set forth in order to provide a thorough understanding of various disclosed embodiments. However, one skilled in the relevant art will recognize that embodiments may be practiced without one or more of these specific details, or with other methods, components, materials, etc. In other instances, well-known structures associated with iontophoresis devices and power sources for iontophoresis devices have not been shown or described in detail to avoid unnecessarily obscuring descriptions of the embodiments. 
     Unless the context requires otherwise, throughout the specification and claims which follow, the word “comprise” and variations thereof, such as, “comprises” and “comprising” are to be construed in an open, inclusive sense, that is as “including, but not limited to.” 
     Reference throughout this specification to “one embodiment” or “an embodiment” means that a particular feature, structure or characteristic described in connection with the embodiment is included in at least one embodiment. Thus, the appearances of the phrases “in one embodiment” or “in an embodiment” in various places throughout this specification are not necessarily all referring to the same embodiment. Further more, the particular features, structures, or characteristics may be combined in any suitable manner in one or more embodiments. 
     As used in this specification and the appended claims, the singular forms “a,” “an,” and “the” include plural referents unless the content clearly dictates otherwise. It should also be noted that the term “or” is generally employed in its sense including “and/or” unless the content clearly dictates otherwise. 
     The headings and Abstract of the Disclosure provided herein are for convenience only and do not interpret the scope or meaning of the embodiments. 
     In one embodiment, as shown in  FIGS. 1 and 4 , an iontophoresis device  10  comprises a working electrode assembly  12  and a non-working electrode assembly  14  for administering a drug (e.g., an ionic drug), and a DC electric power source  16  connected to the electrode assemblies  12 ,  14  with opposite polarities. 
       FIG. 2  shows a cross-section of the working electrode assembly  12  of  FIG. 1 . The working electrode assembly  12  may, in one embodiment, be formed by laminating a working electrode  22 , an electrolyte solution holding portion  24 , a second ion exchange membrane  26 , a drug solution holding portion  28 , and a first ion exchange membrane  30  in that order on a lower side of a base sheet  18 . These layers may form a circle of 10 to 40 mm in diameter. A circular adhesive sheet  20  may also be arranged on the lower surface of the base sheet  18 , so as to substantially surround the working electrode  22 . 
     The base sheet  18  may comprise a variety of materials, including a hard, insulative and elastic resin material, such as a polyethylene terephthalate (PET) resin. The base sheet  18  may be further adapted to help press the working electrode  22  to the first ion exchange membrane  30  against a biological interface of an organism when the adhesive sheet  20  adheres to the biological interface. 
     The working electrode  22  may include a conductive paint applied to one surface of the base sheet  18  blended with a nonmetal conductive filler, such as a carbon paste. In another embodiment, the working electrode  22  may comprise a copper plate or a metal thin film. 
     The electrolyte solution holding portion  24  may, in one embodiment, comprise an electrolytic paint applied to the working electrode  22 . The electrolytic paint may be any paint containing an electrolyte. Examples of suitable electrolytes include: medical agents (e.g., ascorbic acid (vitamin C) and sodium ascorbate), and organic acids (e.g., lactic acid, oxalic acid, malic acid, succinic acid, and fumaric acid and/or salts thereof). The use of such electrolytes may suppress the generation of oxygen or hydrogen. In addition, blending multiple kinds of electrolytes serving as a combination of buffer electrolyte solutions upon dissolution into a solvent may suppress a change in pH during energization. 
     The electrolytic paint may be blended with a hydrophilic polymer (e.g., polyvinyl alcohol, polyacrylic acid, polyacrylamide, or polyethylene glycol) in order to facilitate application and improve the film-forming property of the paint. The electrolytic paint may also be blended with an appropriate amount of solvent, such as water, ethanol, or propanol, for adjusting its viscosity. In some embodiments, the paint may be blended with other components, such as a thickener, a thixotropic agent, a defoaming agent, a pigment, a flavor, or a coloring agent. 
     The second ion exchange membrane  26  may be formed by applying a second ion exchange paint to the electrolyte solution holding portion  24 . 
     The second ion exchange paint may comprise any of a variety of paints containing an ion exchange resin into which an ion exchange group has been introduced, using, for example, an ion having a polarity opposite to that of a drug ion in the drug solution holding portion  28 . For example, if a drug whose drug component dissociates to positive drug ions is used in the drug solution holding portion  28 , the second ion exchange paint may be blended with an anion exchange resin. On the other hand, if a drug whose drug component dissociates to negative drug ions is used, the second ion exchange paint may be blended with a cation exchange resin. 
     The drug solution holding portion  28  may comprise a drug paint applied to the second ion exchange membrane  26 . The drug paint may contain a drug (including a precursor for the drug) whose drug component dissociates to positive or negative ions (drug ions) as a result of, for example, dissolution into a solvent such as water. Examples of drugs whose drug components dissociate to positive ions include lidocaine hydrochloride as an anesthetic drug and morphine hydrochloride, each as an anesthetic. An example of a drug whose drug component dissociates to negative ions is ascorbic acid as a vitamin agent. 
     The first ion exchange membrane  30  may comprise a first ion exchange paint applied to the drug solution holding portion  28 . The first ion exchange paint may contain an ion exchange resin into which an ion exchange group is introduced, using, for example, an ion having the same polarity as that of the drug ion in the drug solution holding portion  28 . Thus, if a drug whose drug component dissociates to positive drug ions is used in the drug solution holding portion  28 , the first ion exchange paint may be blended with a cation exchange resin and vice versa. 
     The above-described ion exchange resins may be obtained by introducing a cation exchange group (i.e., an exchange group using a cation as a counter ion), such as a sulfonic group, a carboxylic group, or a phosphoric group, into a polymer having a three-dimensional network structure, such as a hydrocarbon-based resin (for example, a polystyrene resin or an acrylic resin) or a fluorine-based resin having a perfluorocarbon skeleton. 
     In another embodiment, the ion exchange resin may be obtained by introducing an anion exchange group (i.e., an exchange group using an anion as a counter ion), such as a primary amino group, a secondary amino group, a tertiary amino group, a quaternary ammonium group, a pyridyl group, an imidazole group, a quaternary pyridinium group, or a quaternary imidazolium group, into a polymer having a three-dimensional network structure, similar to that used to form the cation exchange resin. Of course, different ion exchange resins may be used in other embodiments. 
       FIG. 3  shows a cross-section of the non-working electrode assembly  14  of  FIG. 1 . The non-working electrode assembly  14  may, in one embodiment, be formed by laminating a non-working electrode  32 , a second electrolyte solution holding portion  34 , a third ion exchange membrane  36 , a third electrolyte solution holding portion  38 , and a fourth ion exchange membrane  40  arranged on a lower side of a non-working base sheet  19  similar to the base sheet  18  in that order. These layers may form substantially the same shape as that of the working electrode assembly  12 . 
     The non-working electrode  32  may be formed similarly to the working electrode  22  in the working electrode assembly  12 . In addition, the arrangement and composition of the second electrolyte solution holding portion  34  and the third electrolyte solution holding portion  38  may be the same as or similar to those of the electrolyte solution holding portion  24 . 
     The third ion exchange membrane  36  may comprise an ion exchange paint applied to the second electrolyte solution holding portion  34 . The ion exchange paint may be the same as or similar to the first ion exchange paint from which the first ion exchange membrane  30  is formed, and the third ion exchange membrane  36  may function as an ion exchange membrane similar to the first ion exchange membrane  30 . 
     The fourth ion exchange membrane  40  may comprise the same ion exchange paint as that described above with respect to the second ion exchange membrane  26  applied to the third electrolyte solution holding portion  38 . The fourth ion exchange membrane  40  may function the same as or similar to the second ion exchange membrane  26 . 
     A working electrode terminal  42  may be arranged on the upper surface of the base sheet  18  opposite the working electrode  22 , and conduction may be established between the working electrode terminal  42  and the working electrode  22  of the working electrode assembly  12  through a through-hole arranged on the base sheet  18 . 
     Similarly, a non-working electrode terminal  44  may be arranged on the upper surface of the non-working base sheet  19  opposite the non-working electrode  32 , and conduction may be established between the non-working electrode terminal  44  and the non-working electrode  32  of the non-working electrode assembly  14  through a through-hole formed on the non-working base sheet  19 . 
     The DC electric power source  16  may be arranged to cover an upper side of the working electrode terminal  42 . 
     In one embodiment, the DC electric power source  16  comprises a coin battery  46  coupled to current control circuitry  47 , which may include a programmable microprocessor or programmable controller. The current control circuitry  47  may include, for example, a one chip integrated circuit operable to programmably control a current that flows to each of the electrode assemblies  12 ,  14  according to a set pattern. The set pattern may be rewritable from outside based on a signal (e.g., a radio signal) received at a minute antenna  48  (e.g., a loop antenna). A mold resin  50  composed of an insulating material may be used to insulate and integrally mold these electrical components. 
     The coin battery  46  may be arranged at or near substantially the center of the circular working electrode assembly  12  in a plan view, and the current control circuitry  47  may be placed outside the coin battery  46  and laterally next to the coin battery  46 . Each of the coin battery  46  and the current control circuitry  47  may, in one embodiment, be entirely molded within the mold resin into a flat circular shape having an outside diameter substantially equal to that of the circular working electrode assembly  12 . 
     As illustrated in the circuit diagram of  FIG. 4 , the coin battery  46  may be coupled to the current control circuitry  47 , and the cathode side of the circuitry may be connected to the working electrode terminal  42  and the anode side of the circuitry may be connected to the non-working electrode terminal  44  through a lead wire  52 . 
     As shown in detail in  FIG. 5 , the current control circuitry  47  may include: a capacitor  47   a  for accumulating a charge of the coin battery  46 ; a coil  47   b  for collectively discharging the charge accumulated in the capacitor  47   a;  a switching transistor  47   c  for turning an output side of the coil  47   b  on or off; an RC filter  47   d;  a feedback resistor  47   e  for detecting a current flowing between the electrode terminals  42 ,  44  (i.e., through a patient); and a programmable processor  47   f  operating as a boosting converter for turning the switching transistor  47   c  on and off to keep a voltage across the feedback resistor  47   e  at a set value. In  FIG. 5 , reference symbol  47   g  denotes a reverse flow preventing diode, and reference symbol  47   h  denotes a protecting diode. Of course, other analog and digital implementations of the control circuitry  47  may be used in other embodiments. 
     As shown in  FIG. 1 , a coupling belt  54  may couple the base sheet  18  and the non-working base sheet  19  and may be formed of a PET film, for example. The lead wire  52  may be arranged to pass through the inside of the coupling belt  54  or may run along a surface of the belt  54 . 
       FIG. 6  shows an example of a set pattern for a current flowing to the electrode  12 ,  14 , as controlled by the current control circuitry  47 . This set pattern represents an administration pattern for a drug from the iontophoresis device  10 . Thus, in one application, a drug may be administered at a predetermined time (e.g., in accordance with an attack at dawn) even though the patch is put in place at another time (e.g., before sleeping at night). Furthermore, even if a patient forgets to peel the patch off the skin, the amount of drug administered may be limited. In one embodiment, a set pattern for the current may be rewritable from outside the iontophoresis device  10  via the antenna  48 . In another embodiment, the set pattern may be fixed for each patch, and the antenna  48  may be omitted. 
     In one embodiment, an electric power source device includes the coin battery  46  and the electric power source circuitry  47  each molded into a flat shape by the mold resin  50  and each having a diameter substantially equal to that of the working electrode assembly  12  in a plan view. As a result, the patch-type working electrode assembly  12  may be formed without a substantial increase in the entire size of the assembly. 
     In the illustrated embodiment, the DC electric power source  16  is arranged on one side of the working electrode assembly  12 . However, in other embodiments, the DC electric power source  16  may be arranged on one side of the non-working electrode assembly  14 , or may be arranged on both the working electrode assembly  12  and the non-working electrode assembly  14 . 
     In one embodiment, the coin battery  46  is arranged at the center of the working electrode assembly  12  in a plan view, and the current control circuitry  47  is arranged outside and next to the coin battery  46 . However, other embodiments are, of course, possible. For example, as shown in  FIG. 7 , the coin battery  46  may be shifted from the center of the working electrode assembly  12  in a plan view to one side, and the current control circuitry  47  may be arranged on an opposite side. In this embodiment, an outer diameter of the mold resin  50  may be reduced. 
     In yet another embodiment, as shown in  FIG. 8 , the current control circuitry  47  may be arranged and molded on a top side of the coin battery  46 . Such an embodiment may be especially useful where a diameter of the working electrode assembly  12  in a plan view is small. 
     In each of the above embodiments, the iontophoresis device  10  comprises a patch-type working electrode assembly and a non-working electrode assembly. However, other iontophoresis devices may also be used. The DC electric power source is also not limited to a coin battery. In addition, after the current control circuitry  47  has been incorporated, the antenna  48  may be omitted by making the output pattern of the circuitry  47  unrewritable from the outside. 
     DESCRIPTION OF REFERENCE NUMERALS 
     
         
         
           
               10  IONTOPHORESIS DEVICE 
               12  WORKING ELECTRODE ASSEMBLY 
               14  NON-WORKING ELECTRODE ASSEMBLY 
               16  DC ELECTRIC POWER SOURCE 
               18  BASE SHEET 
               19  NON-WORKING BASE SHEET 
               20  ADHESIVE SHEET 
               22  WORKING ELECTRODE 
               24  ELECTROLYTE SOLUTION HOLDING PORTION 
               26  SECOND ION EXCHANGE MEMBRANE 
               28  DRUG SOLUTION HOLDING PORTION 
               30  FIRST ION EXCHANGE MEMBRANE 
               46  COIN BATTERY 
               47  CURRENT CONTROL CIRCUITRY 
               48  ANTENNA 
               50  MOLD RESIN 
           
         
       
    
     The various embodiments described above can be combined to provide further embodiments. All of the U.S. patents, U.S. patent application publications, U.S. patent applications, foreign patents, foreign patent applications and non-patent publications referred to in this specification and/or listed in the Application Data Sheet, are incorporated herein by reference, in their entirety. Aspects of the embodiments can be modified, if necessary to employ concepts of the various patents, applications and publications to provide yet further embodiments. 
     The above description of illustrated embodiments, including what is described in the Abstract, is not intended to be exhaustive or to limit the embodiments to the precise forms disclosed. Although specific embodiments of and examples are described herein for illustrative purposes, various equivalent modifications can be made without departing from the spirit and scope of the disclosure, as will be recognized by those skilled in the relevant art. 
     The various embodiments described above can be combined to provide further embodiments. To the extent that they are not inconsistent with the specific teachings and definitions herein, all of the U.S. patents, U.S. patent application publications, U.S. patent applications, foreign patents, foreign patent applications and non-patent publications referred to in this specification and/or listed in the Application Data Sheet, are incorporated herein by reference, in their entirety. Aspects of the embodiments can be modified, if necessary, to employ systems, circuits and concepts of the various patents, applications and publications to provide yet further embodiments. 
     These and other changes can be made to the embodiments in light of the above-detailed description. In general, in the following claims, the terms used should not be construed to limit the claims to the specific embodiments disclosed in the specification and the claims, but should be construed to include all possible embodiments along with the full scope of equivalents to which such claims are entitled. Accordingly, the claims are not limited by the disclosure.