Patent Publication Number: US-2009221954-A1

Title: Iontophoresis device

Description:
CROSS REFERENCE TO RELATED APPLICATION 
     This is a continuation-in-part application of PCT/JP2007/062027 filed on Jun. 14, 2007, the contents of which are incorporated herein by reference in its entirety. 
    
    
     BACKGROUND 
     1. Technical Field 
     The present application relates to iontophoresis devices for administering a drug ion to an organism by applying a voltage. 
     2. Description of the Related Art 
     PCT patent application publication WO 0303742 describes an iontophoresis device as including a DC power supply, a working side electrode assembly, and a non-working side electrode assembly, for administering a drug solution to skin or mucosa from an ion exchange membrane of the working side electrode assembly. 
     The working side electrode assembly is described as being formed by stacking a first ion exchange membrane constituting an organism contact surface to contact the skin or mucosa, a drug solution holding portion, a second ion exchange membrane, a first electrolyte solution holding portion, and a working side electrode assembly in the stated order. 
     The non-working side electrode assembly is described as being formed by stacking a fourth ion exchange membrane constituting an organism contact surface to contact the skin or mucosa, a third electrolyte solution holding portion, a third ion exchange membrane, a second electrolyte solution holding portion, and a non-working side electrode in the stated order. 
     It is naturally required for the organism contact portions of the working side electrode assembly and the non-working side electrode assembly to be in contact with the skin or mucosa in order to effectively administer the drug solution. However, on the working side electrode assembly side, administration efficiency of the drug solution ion is largely varied depending on dryness of the skin, quantity of sebum, thickness of stratum corneum, or the like. 
     To address such, it is conceivable to bring the working side electrode assembly and the non-working side electrode assembly into contact with the skin or mucosa after removing the sebum and the stratum corneum from the skin as much as possible. 
     No difficulty occurs if the sebum and skin removing operation is conducted by a nurse or the like at a medical institution. However, the above-mentioned removing operation is difficult if the iontophoresis device is used by a user by himself at his home, or the like, and will not likely be conducted. 
     BRIEF SUMMARY 
     In view of the above-mentioned problem, applicants described herein various embodiments of an iontophoresis device which is constructed so that the iontophoresis device may be used after removing the sebum and the stratum corneum partially or fully at a region for administering the drug solution ion on the skin. 
     An iontophoresis device may be summarized as including: a power source; and a working side electrode assembly and a non-working side electrode assembly connected to the power source, for administering a drug ion held in the working side electrode assembly to an organism from an organism contact surface at a tip of the working side electrode assembly through voltage applied from the power source, in which: the iontophoresis device further includes a release liner which is attached so as to cover the organism contact surface and is peelable by pulling the release liner in one direction along the organism contact surface; and on a front surface side of the release liner, in the organism contact surface, a base film, which is connected to the release liner at a vicinity of an end portion opposite to the pulling direction side and which covers at least a front surface region of the organism contact surface, and a paste layer attached to the front surface of the base film, the paste layer having an adhesive force which is peelable with respect to the skin by pulling the base film toward the pulling direction. Thus, the above-mentioned problem may be addressed by mounting the device after removing even a little amount of the stratum corneum and the sebum of the skin prior to use of the device. 
    
    
     
       BRIEF DESCRIPTION OF THE SEVERAL VIEWS OF THE DRAWINGS 
       In the drawings, identical reference numbers identify similar elements or acts. 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 an exploded perspective view illustrating an iontophoresis device according to Embodiment 1. 
         FIG. 2  is a sectional view of the iontophoresis device of  FIG. 1 . 
         FIG. 3  is a sectional view schematically illustrating a process of exfoliating a base film in Embodiment 1. 
         FIG. 4  is a sectional view schematically illustrating an iontophoresis device according to Embodiment 2. 
         FIG. 5  is a sectional view schematically illustrating an iontophoresis device according to Embodiment 3. 
         FIG. 6  is a sectional view schematically illustrating an iontophoresis device according to Embodiment 4. 
         FIG. 7  is a sectional view schematically illustrating an exfoliating process for a paste layer in Embodiment 4. 
     
    
    
     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 drug delivery devices, transdermal devices and 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. 
     Hereinafter, description is made of Embodiments 1 to 4. 
     Embodiment 1 
     An iontophoresis device  10  according to an Embodiment 1 will be described in detail with reference to  FIGS. 1 to 2 . 
     The iontophoresis device  10  comprising a DC electric power source  12 , a working electrode assembly  20  connected to one of an anode or cathode of the DC electric power source  12 , and a non-working electrode assembly  40  connected to the other of the anode or cathode. The device administers a drug ion held by the working electrode assembly  20  to an organism with a voltage from the DC electric power source  12  through an organism contact surface  20 A which being a tip surface of the working electrode assembly  20 . 
     In the iontophoresis device  10 , each of the working electrode assembly  20  and the non-working electrode assembly  40  is constructed by interposing constituent members such as a drug solution holding portion between a base end support  14  and an intermediate support  16 , which are overlapped and are each formed of a resin sheet, for example, polyurethane foam sheet, or by receiving the constituent members in through-holes formed in the intermediate support  16  and a tip support portion  18 . The base end support  14  and the intermediate support  16  are formed into the same size, and the tip support  18  is formed so as to be larger than the supports  14  and  16 . 
     With reference to  FIG. 2 , the base end support  14 , the intermediate support  16 , and the tip support  18  each have respective pressure-sensitive adhesive layers  14 A,  16 A, and  18 A, respectively, at the lower surfaces thereof so as to be stuck to one another. At the same time, the pressure-sensitive adhesive layer  18 A of the tip support  18  may be selectively stuck to the skin or mucosa in use. 
     Here, the intermediate support  16  is a single sheet-like member which forms a part of the working electrode assembly  20  and a part of the non-working electrode assembly  40 . 
     Similarly, the tip support  18  is a single sheet-like member which forms a part of the working electrode assembly  20  and a part of the non-working electrode assembly  40 . 
     The organism contact surface  20 A of the working electrode assembly  20  and the organism contact surface  40 A which being a tip surface of the non-working electrode assembly  40  are arranged flush with each other and with a gap there between. Further, there is provided a release liner  60  so as to cover the organism contact surfaces  20 A and  40 A which, as previously noted, are flush with each other. 
     The release liner  60  is peelable by pulling in one direction along the organism contact surfaces  20 A and  40 A, for example, in a right direction in  FIG. 1 . 
     Further, on a front surface side of the release liner  60 , in the organism contact surfaces  20 A are provided, a base film  62 , which is connected to the release liner  60  at a vicinity of an end portion  20 B opposite to the pulling direction side and has a size capable of covering at least a front surface region of the organism contact surfaces  20 A and  40 A, and a paste layer  64  attached to the front surface of the base film  62 . 
     The paste layer  64  has an adhesive force which is peelable with respect to the skin S by pulling the base film  62  toward the pulling direction, and is constructed so that a part of the stratum corneum and the sebum of the surface of the skin S may be simultaneously peeled off when the paste layer  64  is peeled off from the skin S. 
     The base film  62  is formed by bending the release liner  60  into a U shape at the vicinity of the end portion  20 B and by extending the release liner. Here, the paste layer  64  is preferably made of a material which adheres to the skin S but is hard to adhere to the organism contact surfaces  20 A and  40 A. 
     The structures of the working electrode assembly  20  and the non-working electrode assembly  40  are further described in detail. 
     The working electrode assembly  20  is formed by stacking a working electrode  24  connected to an anode and a cathode in a DC electric power source  12 , which is the same polarity with a drug ion, a separator  26  arranged on a front surface of the working electrode  24 , a second ion selective membrane  28  arranged on a front surface of the separator  26 , selectively passing an ion opposite in polarity to the drug ion, a drug solution holding portion  30  arranged on a front surface of the second ion selective membrane  28 , for holding a drug which is different from the drug ion, a first ion selective membrane  32  arranged on a front surface of the drug solution holding portion  30 , selectively passing an ion which is the same polarity as the drug ion, and a working organism contact portion  34  which is formed by applying a viscous liquid containing a drug which is the same with the drug on a front surface of the first ion selective membrane  32  in the stated order. A front end surface of the working organism contact portion  34  is constituted as the working organism contact surface  20 A which is brought into contact with the skin or mucosa. 
     The working electrode  24  comprises: a working collector  24 A connected to the DC electric power source  12  and including a carbon-printed electrode formed by printing on the front surface of a resin sheet  36 ; and a working polarizable electrode  24 B electrically connected to the front surface of the working collector  24 A. 
     It should be noted that the phrase “electrically connected” comprehends not only the case where the electrode is directly connected to the front surface but also the case where the electrode is connected to the front surface through an electric conductor such as a conductive adhesive (the same holds true for the following). 
     The intermediate support  16  is formed of a resin material having a thickness substantially equal to that of the working polarizable electrode  24 B, and has a working intermediate through-hole  21 A of substantially the same shape as that of an external shape in a plane shape of the working polarizable electrode  24 B. The working polarizable electrode  24 B is received in the working intermediate through-hole  21 A. 
     In addition, the tip support  18  is formed of a resin material having a thickness substantially equal to that of the drug solution holding portion  30 , and has a working tip through-hole  22 A of substantially the same shape as that of an external shape in the plane shape of the working polarizable electrode  24 B. The drug solution holding portion  30  is received in the working tip through-hole  22 A. 
     The non-working electrode assembly  40  is formed by stacking, from the base end support  14  in the following order, a non-working electrode  44  connected to an anode or a cathode in a DC electric power source  12 , which is of an opposite polarity to that of the drug ion, a separator  46  arranged on a front surface of the non-working electrode  44 , an electrolyte solution holding portion  48  for holding an electrolyte solution, a third ion selective membrane  50  selectively passing an ion opposite in polarity to a polarity of the drug ion, and a non-working organism contact portion  52  which is formed by applying a viscous liquid containing an electrolyte solution which is the same type as the electrolyte solution which is held in the electrolyte solution holding portion  48 . A front end surface of the non-working organism contact portion  52  is constituted as the non-working organism contact surface  40 A. 
     The non-working electrode  44  comprises: a non-working collector  44 A which is formed of a material containing carbon and printed in a film shape on the front surface of the resin sheet  36  so as to be distinct from the working collector  24 A of the working electrode  24 ; and a non-working polarizable electrode  44 B provided so as to contact the non-working collector  44 A. 
     The non-working polarizable electrode  44 B has a thickness equal to that of the intermediate support  16 , and is received in a non-working intermediate through-hole  41 A formed in the intermediate support  16 . In addition, the electrolyte solution holding portion  48  has a thickness equal to that of the tip support  18 , and is received in a non-working tip through-hole  42 A formed in the tip support  18 . 
     In Embodiment 1, each of the through-holes  22 A,  21 A,  41 A, and  42 A is of a circular shape, and, furthermore, each of the working electrode  24 , the separator  26 , the second ion selective membrane  28 , the drug solution holding portion  30 , the first ion selective membrane  32 , and the working organism contact portion  34  is of a circular membrane shape or a sheet shape. 
     Similarly, each of the non-working electrode  44 , the separator  46 , the electrolyte solution holding portion  48 , the third ion selective membrane  50 , and the non-working organism contact portion  52  is of a circular membrane shape or a sheet shape. 
     As illustrated in  FIG. 1  by a broken line, in the resin sheet  36 , a working wire  19 A and a non-working wire  19 B which are formed of a material containing carbon and printed continuously in a film shape are connected to the working collector  24 A in the working electrode  24  and the non-working collector  44 A in the non-working electrode  44 , respectively 
     In Embodiment 1, as shown in each of  FIGS. 1 and 4 , the respective circular members are overlapped in each of the working electrode assembly  20  and the non-working electrode assembly  40  in the thickness direction of each assembly, and are integrated to constitute the iontophoresis device  10 . 
     Here, the intermediate support  16  is interposed between other members from above and below the support in a state where the working polarizable electrode  24 B and the non-working polarizable electrode  44 B are received in the working intermediate through-hole  21 A and non-working intermediate through-hole  41 A of the intermediate support  16 , respectively. Similarly, the tip support  18  is interposed between other members from above and below the support in a state where the drug solution holding portion  30  and the electrolyte solution holding portion  48  are stored in the working tip through-hole  22 A and non-working tip through-hole  42 A of the tip support  18 , respectively. Further, a member between the base end support  14  and the intermediate support  16  is positioned and fixed by being interposed between them, and a member between the intermediate support  16  and the tip support  18  is positioned and fixed by being interposed between them. 
     Each of outer diameters of the working collector  24 A and the non-working collector  44 A in the working electrode  24  and the non-working electrode  44  is slightly larger than each of diameters of the working intermediate through-hole  21 A and non-working intermediate through-hole  41 A. Outer peripheral portions thereof are arranged so as to be sandwiched between the base end support  14  and the intermediate support  16 . 
     Reference numeral  56  of  FIG. 1  and  FIG. 2  represents an adhesive. The adhesive  56  is placed across an intermediate portion between the working and non-working collectors  24 A and  44 A in the insulating film  19 D to bind the insulating film  19 D and the intermediate support  16  so that the area between the insulating film  19 D and the intermediate support  16  is partitioned into a working side and a non-working side. 
     In addition, reference numeral  60  of  FIG. 1  represents a release liner attached to the front surface of the tip support  18  in a peelable fashion so as to cover the working organism contact portion  34  and the non-working organism contact portion  52 . 
     Next, materials, components, and the like for the above respective constituent elements are described. 
     In Embodiment 1, the drug solution holding portion  30  is constructed by impregnating a polypropylene (PP) non-woven fabric with a viscous liquid containing the drug. In addition, the drug solution holding portion  30  is impregnated with a drug, the drug effect component of which dissociates into a positive or negative ion by, for example, dissolution in a solvent such as water (drug which dissociates into a drug ion (a precursor for the drug is also permitted)). A drug, the drug effect component of which dissociates into a positive ion is, for example, lidocaine hydrochloride as a narcotic or morphine hydrochloride as a narcotic. A drug, the drug effect component of which dissociates into a negative ion is, for example, ascorbic acid which being a vitamin agent. 
     In addition to the foregoing, a hormone, DNA, RNA, a protein, an amino acid, and minerals are also included in the category described above. 
     The separator  46  in the non-working electrode assembly  40  is obtained by impregnating a PP non-woven fabric with a viscous liquid containing the electrolyte solution (details about the electrolyte solution are described later). Further, the electrolyte solution holding portion  48  is obtained by impregnating a PP non-woven fabric with a viscous liquid containing the same electrolyte solution. 
     The electrolyte solution to be used in each of the separator  46  and the electrolyte solution holding portion  48  is mainly formed of an electrolyte, and electrolytes each of which is oxidized or reduced more readily than the electrolytic reaction of water (oxidation at an anode and reduction at a cathode) such as: pharmaceuticals such as ascorbic acid (vitamin C), and sodium ascorbate; and organic acids such as lactic acid, oxalic acid, malic acid, succinic acid, and fumaric acid and/or salts of the acids are each particularly preferably used as the electrolyte. As a result, the generation of an oxygen gas or hydrogen gas may be suppressed. In addition, a fluctuation in pH of the electrolyte solution during energization may be suppressed by blending such a combination of multiple kinds of electrolytes as to provide a buffer electrolyte solution when being dissolved in a solvent. 
     Such viscous liquid containing the drug or electrolyte solution described above may be produced by, for example, mixing water (ion exchange water) with 2 mass % or more of a tacky material such as hydroxypropylcellulose (HPC) (for example, H-Type manufactured by NIPPON SODA CO., LTD.) or a Metolose as a water-soluble polymer obtained by chemically treating a water-insoluble cellulose (for example, 90SH-10000SR manufactured by Shin-Etsu Chemical Co., Ltd.). 
     The working polarizable electrode  24 B in the working electrode  24  and the non-working polarizable electrode  44 B in the non-working electrode  44  are either constructed of as a main component or a conductive base, which is formed of active carbon, preferably, a carbon fiber or carbon fiber paper. If only an active carbon fiber is used as the working and non-working polarizable electrodes  24 B and  44 B, it is preferred to form a layer by combining cloth and felt formed of the active carbon fiber. Beside, for the conductive base, for example, layers in which the active carbon is dispersed within a binder polymer may be laminated. Active carbon having a specific area of 10 m 2 /g or more may be used. 
     The working polarizable electrode  24 B is impregnated with a viscous liquid containing a drug identical to the drug held by the drug solution holding portion  30 . In addition, the non-working polarizable electrode  44 B is impregnated with a viscous liquid containing an electrolyte solution identical to the electrolyte solution held by the separator  46 . 
     Each of the working collector  24 A in the working electrode  24  and the non-working collector  44 A in the non-working electrode  44  may be a printed electrode obtained by printing a polyethylene terephthalate (PET) material mixed with carbon and an adhesive. 
     It should be noted that, any electrically conductive material may be used for the working collector  24  and the non-working collector  44 A, for example, a metal such as gold, platinum, silver, copper, or zinc other than carbon may be used. Alternatively, a conductive material such as carbon or gold itself may be used as a collector without reliance on printing. In addition, as a material for the working wire  19 A and the non-working wire  19 B, the same may be applied. 
     The separator  26  is obtained by impregnating a PP non-woven fabric with a viscous liquid containing a drug identical to the drug held by the drug solution holding portion  30 , and is interposed between the working polarizable electrode  24 B and the second ion selective membrane  28  to prevent physical contact between them. 
     The first ion selective membrane  32  is constructed by incorporating an ion-exchange resin into which an ion-exchange group is introduced so that an ion having the same polarity as the drug ion selectively substantially passes through the resin while ions of the opposite polarity are substantially blocked. Specifically, the first ion selective membrane  32  contains a cation exchange resin when the drug solution of the drug solution holding portion  30  dissociates into a cation, and contains an anion exchange resin when the drug solution dissociates into an anion. 
     The second ion selective membrane  28  is constructed by incorporating an ion-exchange resin into which an ion-exchange group is introduced so that an ion of opposite polarity as the drug ion selectively substantially passes through the resin while ions of the same polarity as the drug are substantially blocked. Specifically, the second ion selective membrane  28  contains an anion exchange resin when the drug solution of the drug solution holding portion  30  dissociates into a cation, and contains the cation exchange resin when the drug solution dissociates into the anion. 
     As in the case of the second ion selective membrane  28 , the third ion selective membrane  50  is constructed by incorporating an ion exchange resin into which an ion exchange group is introduced so that an ion opposite in polarity to the drug ion selectively passes through the resin. That is, when the drug solution of the drug solution holding portion  30  dissociates into a cation, the third ion selective membrane  50  contains an anion exchange resin, and when the drug solution dissociates into an anion, the membrane contains a cation exchange resin. 
     As the above cation exchange resin, there may be used, without any limitation, an ion exchange resin obtained by introducing a cation exchange group (exchange group the counter ion of which is a cation) such as a sulfonic group, a carboxylic group, or a phosphonic group into a polymer having a three-dimensional network structure such as a hydrocarbon-based resin such as a polystyrene resin or an acrylic acid-based resin, or a fluorine-based resin having a perfluorocarbon skeleton. 
     In addition, as the above anion exchange resin, there may be used, without any limitation, an ion exchange resin obtained by introducing a cation exchange group (exchange group, the counter ion of which is an anion) such as a primary, secondary, or tertiary amino group, a quaternary ammonium group, a pyridyl group, an imidazole group, a quaternary pyridium group, or a quaternary imidazolium group into the same polymer having a three-dimensional network structure as that in the case of the cation exchange resin. 
     The working organism contact portion  34  is constructed by applying a viscous liquid, identical to a liquid with which the drug solution holding portion  30  is impregnated, to the front surface of the first ion selective membrane  32 . In addition, the non-working organism contact portion  52  is constructed by applying a viscous liquid containing an electrolyte solution identical to that used in the electrolyte solution holding portion  48  to the front surface of the third ion selective membrane  50 . It should be noted that each of those viscous liquids is desirably applied in an amount as small as 7 μL in order that the spread of each of the applied viscous liquids due to the attachment of the release liner  60  on each of the viscous liquids may be suppressed. 
     At the time of the assembly of the iontophoresis device  10 , in a state shown in  FIG. 1 , the respective constituent members are arranged like a laminate or stored in through-holes, and the base end support  14 , the intermediate support  16 , and the tip support  18  are sequentially overlapped on the release liner  60 , and are fixed by being stuck to one another with the pressure-sensitive adhesive layers  16 A and  14 A. Thus, the assembly is completed. 
     A button cell or a thin cell disclosed in, for example, Japanese Patent Application Laid-Open No. Hei 11-067236, US Patent Publication No. 2004/0185667 A1, or U.S. Pat. No. 6,855,441 may be used as the DC electric power source  12 , although other types of power sources may be employed in this embodiment. 
     When the above-mentioned iontophoresis device  10  is used, as illustrated in  FIG. 2 , the paste layer  64  of the base film  62  is adhered to a contact region Si, which is a portion of the skin S, with which the working organism contact surface  20 A and the non-working organism contact surface  40 A (hereinafter, referred to as organism contact surfaces  20 A and  40 A) are brought into contact. 
     Next, the release liner  60  is pulled (e.g., toward the right as viewed in  FIG. 2 ) substantially parallel to the organism contact surfaces  20 A and  40 A. In this case, for example, a user grasps the whole iontophoresis device  10 , to thereby fix its position with respect to the skin S. 
     With this, the release liner  60  moves along the organism contact surfaces  20 A and  40 A, and the base film  62  is also pulled through the movement of the release liner  60 , with the result that the paste layer  64  is, as illustrated in  FIG. 3 , peeled from the skin S sequentially from the left side. A part of the stratum corneum or sebum of the skin S is adhered to the paste layer  64 . This means that the stratum corneum or sebum is peeled from the contact region Si of the skin S. 
     The paste layer  64  peeled from the skin S moves along the organism contact surfaces  20 A and  40 A (toward the right as viewed in the figure), and when the ends (right ends in the figure) of the base film  62  and the paste layer  64  pass through the organism contact surfaces  20 A and  40 A, the peeling of the release liner  60  and the base film  62  are finished. 
     In this state, the iontophoresis device  10  is mounted so that the organism contact surfaces  20 A and  40 A are brought into contact with the skin S. 
     In the contact region Si with which those organism contact surfaces  20 A and  40 A are brought into contact, the part of the stratum corneum or sebum has been peeled as described above, and hence impedance of the skin is small and the drug ion may be administered efficiently. 
     Embodiment 2 
     An iontophoresis device  70  according to Embodiment 2 will be described with reference to  FIG. 4 . 
     The iontophoresis device  70  comprises the release liner  60 , a release liner  72  and a base film  74 , each having a different structure from the base film  62 . The other structure is the same as the structure of the iontophoresis device  10  according to Embodiment 1, and hence the detailed description of such is not repeated. 
     The release liner  72  according to Embodiment 2 is, as illustrated in  FIG. 4 , formed as a separate member from the base film  74 , and at least a portion of the base film  74  is integrally formed on a front surface of the release liner  72 . In addition, the base film,  74  is bent into a U-shape at the vicinity of an end portion  20 B to be extended, and the paste layer  76  is formed on the extended portion. 
     In Embodiment 2, when the release liner  72  and the base film  74  which is integrally formed therewith are pulled (toward the right as viewed in  FIG. 4 ), while supporting the iontophoresis device  70 , the paste layer  76  is sequentially peeled from the contact region Si of the skin S from a left end (as viewed in  FIG. 4 ). At this time, a part of the stratum corneum or sebum of the skin S may be peeled off. 
     In contrast to Embodiment 1, in Embodiment 2 the peeled paste layer  76  is free from contact with the organism contact surfaces  20 A and  40 A, and hence the peeling of the release liner  72  from the organism contact surfaces  20 A and  40 A advantageously may be performed more smoothly, and a range of material suitable for the paste layer  76  advantageously becomes wider. 
     Embodiment 3 
     An iontophoresis device  80  according to Embodiment 3 will be discussed with reference to  FIG. 5 . 
     The iontophoresis device  80  is constructed by adding a second release liner  82 , a second base film  84 , and a second paste layer  86  with respect to the iontophoresis device  70  of Embodiment 2 ( FIG. 4 ), and the other structures are the same as the iontophoresis device  70  according to Embodiment 2. Accordingly, the detailed description thereof is not repeated. 
     The second release liner  82  in Embodiment 3 is provided on a lower side (with respect to the orientation illustrated in  FIG. 5 ) of the paste layer  76  which is attached to the base film  74 . The second base film  84  is integrally formed with respect to the second release liner  82  on the front surface of the second release liner  82 , and the second base film  84  is also bent into a U-shape at the vicinity of the end portion  20 B to be extended. 
     Specifically, the second release liner  82 , the second base film  84 , and the second paste layer  86  each have the same structure as the release liner  72 , the base film  74 , and the paste layer  76 , respectively, of Embodiment 2, are additions to the stack structure of Embodiment 2. 
     To use iontophoresis device  80  of Embodiment 3, first, the second release liner  82  and the second base film  84  on the skin S side are pulled toward the right (as viewed in  FIG. 5 ), thereby peeling off the second paste layer  86  from the skin S, and the second release liner  82  is peeled off from the paste layer  76  above the second release liner  82 . 
     Next, after adhering the paste layer  76  of the base film  74  onto the skin S, the release liner  72  and the base film  74  are pulled toward the right (as viewed in  FIG. 5 ), whereby the paste layer  76  peels off a part of the stratum corneum or sebum from the skin S as described above. 
     Like this, the part of the stratum corneum or sebum of the skin S are peeled off two times by the paste layers  86  and  76 , respectively, and hence, compared to a case where the peeling is conducted one time, the impedance of the skin may be made even smaller. 
     In Embodiment 3 ( FIG. 5 ), the part of the stratum corneum or the like is peeled off two times from the skin S, respectively, by two layers of the paste layers  86  and  76 . However, embodiments of the present invention are not limited thereto, and a combination of the release liner, base film, and the paste layer may be provided in three layers. 
     Embodiment 4 
     An iontophoresis device  90  according to Embodiment 4 will be discussed with reference to  FIG. 6 . 
     The iontophoresis device  90  has a substantially same shape and size (a total of the organism contact surfaces  20 A and  40 A), and includes: a release liner  92  having one side end  92 A which is attached at a right end portion of the non-working organism contact surfaces  40 A (as viewed in  FIG. 6 ); and a winding member  94  attached to another side end  92 B, which is opposite to the one side end  92 A of the release liner  92 , capable of winding the release liner  92 , while rotating, from the another side end  92 B toward the one side end  92 A. 
     The release liner  92  has a paste layer  96  formed on a surface which is opposite to a surface which is brought into contact with the winding member  94 , and constitutes a paste-attached liner. The paste layer  96  is constructed so as to have an adhesive force which is peelable with respect to the skin when the paste layer-attached release liner is rolled up. 
     In the iontophoresis device  90  according to Embodiment 4, the paste layer  96  outside the winding member  94  is brought into contact with the contact region Si of the skin S, with which the organism contact surfaces  20 A and  40 A are to be brought into contact, from a left side (as viewed in  FIG. 6 ), and then the winding member  94  is rotated, for example, toward the right (as viewed in  FIG. 6 ). 
     If the winding member  94  is rotated toward the right (as viewed in  FIG. 6 ), the outside paste layer  96  is brought into contact with the contact region Si, and further, when the paste layer  96  is taken up by the winding member  94 , a part of the stratum corneum or sebum of the contact region Si is peeled off through the adhesive force of the paste layer  96 . 
     Through a way as described above, when the winding member  94  is caused to advance while taking up the release liner  92  along the contact region Si, as illustrated in  FIG. 7 , the part of the stratum corneum or sebum in an entire area of the contact region Si is peeled off by the paste layer  96 . 
     At a time of finish of the peeling, the organism contact surfaces  20 A and  40 A are positioned on an upper side of the contact region Si. If electrification is conducted after removing the release liner  92  or as it is, without removing, and bringing the organism contact surfaces  20 A and  40 A into contact with the contact region Si, the drug ion may efficiently be administered. 
     It should be noted that, in each of the iontophoresis devices  10 ,  70 ,  80 , and  90  according to the above-mentioned embodiments, each of the paste layers  64 ,  76 ,  86 , and  96  peels off a part of the stratum corneum, or the like from the contact region Si of the skin S in an area where the both the organism contact surfaces  20 A and  40 A are brought into contact with the paste layers  64 ,  76 ,  86 , and  96 , but the embodiments of the present invention are not limited to this. The part of the stratum corneum, or the like may only be peeled off from the skin S in at least an area with which the working contact surface  20 A of the working electrode assembly is brought into contact. 
     Further, the structure of the iontophoresis device main body is not limited to the structures according to Embodiments 1 to 4, but may be applied, in the working electrode assembly, to a case of including at least a working electrode and a drug solution holding portion. 
     Further, the structure of the iontophoresis device main body may be applied to a case where, without using the working organism contact portion  34  or non-working organism contact portion  52 , the ion selective film constitutes the organism contact surface. 
     A transdermal drug delivery devices allows a user or patient themselves to selectively remove a base film which is adhered with respect to the skin or mucous membrane through an adhesive or paste layer, by using a release liner covering an organism contact surface at least at a tip of a working electrode assembly and a non-working electrode assembly, and thereby peel off part of a stratum corneum or sebum from a drug solution ion administering area by causing the stratum corneum or sebum to be attached to the adhesive or paste layer. As a result, the device is easy to use. 
     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 teachings provided herein of the various embodiments can be applied to other drug delivery devices, not necessarily the exemplary iontophoresis delivery device generally described above. 
     The various embodiments described above can be combined to provide further embodiments. 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.