Patent Abstract:
An iontophoresis patch is equipped with a donor gel and a reference gel which are disposed to contact an external conductor, for example, the skin of a patient and thereby output current from a current-carrying device to the external conductor. The iontophoresis patch includes: a donor portion having the donor gel containing a medical agent to be penetrated into the external conductor; a reference portion having a reference gel, mounted with the current-carrying device on the surface on the side opposite to the reference gel, and disposed on the external conductor apart from the donor portion; and an electrode film for supplying current from the current-carrying device to the donor gel and the reference gel.

Full Description:
TECHNICAL FIELD 
       [0001]    The present invention relates to an iontophoresis patch for use with an ionic drug permeation device which operates on the principles of iontophoresis for transdermally administrating a drug such as a local anesthetic or the like by passing a low electric current through the skin of a human being. 
       BACKGROUND ART 
       [0002]    Local anesthetic patches such as lidocaine are widely used for the purpose of removing a pain which is caused upon puncture. Particularly, local anesthetic patches find widespread use in hemodialysis. Hemodialysis patients are treated with dialysis three times a week, for example, by having two dialysis needles, each having a diameter ranging from 17 to 18 G (gauge), inserted through their skin for an extracorporeal blood circulation to remove waste materials from the blood. Such local anesthetic patches are used to remove the pain caused upon puncture. 
         [0003]    Lidocaine patches take a long time, e.g., 2 hours, prior to the onset of their effect. Therefore, the skin area to which a lidocaine patch is applied is likely to be irritated. In addition, the efficacy of lidocaine patches tends to be insufficient because they fail to deliver the drug deeply into the tissue. 
         [0004]    On the other hand, iontophoresis is advantageous in that it takes a shorter time until the onset of the drug efficacy and it can deliver the drug more deeply into the tissue. The above problems can be solved by combining local anesthetic patches such as lidocaine with iontophoresis. Specifically, iontophoresis refers to a process wherein positive and negative electrodes are placed at two spaced points on a skin and an electric current is passed from one of the electrodes across the stratum corneum to the other electrode thereby to move a charged drug based on the principle of electrophoresis for facilitating transdermal drug absorption. Iontophoresis provides a basis for a transdermal drug administration system. Usually, one of the positive and negative electrodes is held in contact with a gel containing the drug and referred to as a donor portion, and the other electrode is held in contact with a gel containing salt solution and referred to as a reference portion. 
         [0005]    According to iontophoresis, the charged drug is subjected to facilitation of absorption in principle. There has been a report stating that since a water flow is developed in the patient&#39;s body due to an electric current, even a non-charged drug or even a high-molecular-weight drug exhibits increased skin permeability. 
         [0006]    Japanese Laid-Open Patent Publication No. 2007-532193 (PCT) discloses an electrically assisted delivery device utilizing iontophoresis which includes an electrode assembly having positive and negative electrodes containing a drug and a controller for supplying an electric current to the electrode assembly. The disclosed electrically assisted delivery device is problematic in that it is not small enough to make the controller integral with a patch and is highly costly. 
         [0007]    Japanese Laid-Open Patent Publication No. 09-510387 (PCT) discloses an electrically operated administration device having a structure wherein a flexible substrate and a button cell for energizing a pair of electrode means to be applied to the skin of a patient are disposed on upper portions of the electrode means. 
       SUMMARY OF INVENTION 
       [0008]    The structure disclosed in Japanese Laid-Open Patent Publication No. 09-510387 (PCT) is reduced in size to a certain extent because the button cell and the flexible substrate are employed to make an energizing unit integral with a patch to be applied to the skin. However, since the substrate and the cell are stacked on the entire surface of the patch in planar view, the patch is inflexible in its entirety. Particularly, like a hemodialysis patient, if the blood vessel in a puncture area (shunt portion on an arm) is highly raised from the puncture area, then it is difficult to apply the inflexible patch in fully intimate contact with the raised blood vessel. 
         [0009]    The present invention has been made in view of the above problems. It is an object of the present invention to provide an iontophoresis patch which is flexible enough to be stably placed on a raised portion of an external conductor such as a human skin or the like. 
         [0010]    According to the present invention, there is provided an iontophoresis patch having a first contact member and a second contact member for outputting an electric current from an energizing unit to an external conductor upon being placed in contact with the external conductor, comprising a donor portion having the first contact member, the first contact member containing a drug to permeate into the external conductor, a reference portion having the second contact member and which is placed on the external conductor away from the donor portion, the energizing unit being placed on a surface of the second contact member which is opposite to a surface thereof to be held in contact with the external conductor, and an electrode body having a first electrode and a second electrode for supplying electric currents from the energizing unit respectively to the first contact member and the second contact member, the electrode body being disposed over the donor portion and the reference portion. 
         [0011]    With the above arrangement, the iontophoresis patch has the donor portion which holds a drug to permeate into the external conductor, e.g., a human body, the reference portion disposed away from the donor portion, and the electrode body having the first electrode and the second electrode for supplying electric currents to the first contact member and the second contact member, the energizing unit being placed on the reference portion. Thus, since the energizing unit is not placed on the donor portion which holds the drug, the donor portion is more flexible than the reference portion. Therefore, even with respect to, for example, a skin of a hemodialysis patient having a highly raised blood vessel, the donor portion with the drug can easily conform closely to the shape of such a skin, and thus the donor portion can be placed stably in intimate contact with the skin of the hemodialysis patient. 
         [0012]    The electrode body may have a one-sided interconnect structure in the donor portion wherein the first electrode is disposed on one surface of a flexible base, and the electrode body has a double-sided interconnect structure in the reference portion wherein the second electrode is disposed on a surface of the base, while a first contact terminal line and a second contact terminal line for interconnecting the energizing unit and the first electrode and the second electrode are disposed on another surface of the base. Thus, since the donor portion is thinner and more flexible than the reference portion, the donor portion can be held in increased intimate contact with the external conductor. 
         [0013]    The electrode body may have a one-sided interconnect structure in the donor portion wherein the first electrode is disposed on one surface of a flexible bas, and the electrode body may have a double-sided interconnect structure in the reference portion wherein after the second electrode, and a first contact terminal line and a second contact terminal line for interconnecting the energizing unit and the first electrode and the second electrode are formed on the same surface of the base as the surface on which the first electrode is disposed, the base in the reference portion is folded back on itself into a two-layer structure, so that the second electrode is disposed on a surface of the reference portion, and terminal bases connecting the first contact terminal line and the second contact terminal line to the energizing unit are disposed on another surface of the reference portion. Thus, since the reference portion can be made into a double-sided interconnect structure simply by performing an interconnect forming process on one side of the base, the production efficiency is increased. 
         [0014]    The first contact terminal line and the second contact terminal line include wider portions disposed on a portion of the reference portion that includes a folding portion of the base, the wider portions being wider than other portions of the first contact terminal line and the second contact terminal line. When the base is folded back on itself along the folding portion, the wider portions are effective to prevent the first contact terminal line and the second contact terminal line from being broken or buckled. Thus, the first contact terminal line and the second contact terminal line are made more durable and reliable. 
         [0015]    The iontophoresis patch may include a bridge portion interconnecting the donor portion and the reference portion, wherein the first electrode and the first contact terminal line are electrically connected to each other in the bridge portion, and the second electrode and the second contact terminal line are electrically connected to each other in the bridge portion. Owing thereto, joints between the interconnections, e.g., through holes, are not disposed in the donor portion and the reference portion. Therefore, the electrode body in the donor portion and the reference portion can be made flat, thereby providing increased intimate contact between the first contact member and the second contact member, and the first electrode and the second electrode. 
         [0016]    It is effective to provide a protective layer covering and electrically insulating the bridge portion for reliably insulating the joints between the interconnections. 
         [0017]    The first contact terminal line connected to the first electrode and the second contact terminal line connected to the second electrode may be juxtaposed on the surfaces of the bridge portion and the reference portion, and the contact terminal lines may have respective ends electrically connected respectively to the first electrode and the second electrode in the bridge portion and respective other ends electrically connected respectively to connection terminals connected to the energizing unit in the reference portion. With this arrangement, the one-sided interconnect structure in the donor portion can be constructed more easily, and the electrode body can be reduced in outer shape for making the iontophoresis patch smaller in size. 
         [0018]    The iontophoresis patch may include a manually grippable grip projectingly formed on a side of at least one of the donor portion and the reference portion. The applier can grip the grip to apply the iontophoresis patch more easily to the external conductor. 
         [0019]    The donor may have, on a surface thereof opposite from the first contact member, a central mark indicative of the center of the first contact member as viewed in plan and an angle mark indicative of a rotational angle of the first contact member as viewed in plan. For example, the central mark allows the applier to apply the first contact member holding the drug to the external conductor more easily at a desired area of the external conductor. Owing to the angle marks, after determining the position to which the donor portion is to be applied, and when determining a position to which the reference portion is to be applied, the applier can turn the reference portion around the center of the angle mark to make it possible to apply the reference portion to a more stable position. Further, the supervisor can easily and accurately instruct the applier as to a position where to apply the reference portion. 
         [0020]    According to the present invention, the iontophoresis path includes the donor portion holding the drug to permeate into the external conductor, e.g., a human body, the reference portion disposed away from the donor portion, and the electrode body having the first electrode and the second electrode for supplying electric currents to the first contact member and the second contact member, the energizing unit being placed on the reference portion. Thus, since the energizing unit is not placed on the donor portion which holds the drug, the donor portion is more flexible than the reference portion. Therefore, even with respect to, for example, a skin of a hemodialysis patient having a highly raised blood vessel, the donor portion with the drug can easily conform closely to the shape of such a skin, and thus the donor portion can be placed stably in intimate contact with the skin of the hemodialysis patient. 
     
    
     
       BRIEF DESCRIPTION OF DRAWINGS 
         [0021]      FIG. 1  is a perspective view showing the overall configuration of an ionic drug permeation device incorporating therein an iontophoresis patch according to a first embodiment of the present invention; 
           [0022]      FIG. 2  is an exploded perspective view of the iontophoresis patch shown in  FIG. 1 ; 
           [0023]      FIG. 3  is a cross-sectional view of an electrode film taken along line III-III of  FIG. 2 ; 
           [0024]      FIG. 4  is an enlarged cross-sectional view of portion IV encircled by the broken line in  FIG. 3 ; 
           [0025]      FIG. 5A  is a plan view of the electrode film; 
           [0026]      FIG. 5B  is a bottom plan view of the electrode film; 
           [0027]      FIG. 6  is a side elevational view showing the manner in which the ionic drug permeation device shown in  FIG. 1  is placed in intimate contact with a patient&#39;s arm; 
           [0028]      FIG. 7  is a plan view of a modification of the iontophoresis patch shown in  FIG. 1 ; 
           [0029]      FIG. 8  is an exploded perspective view of an iontophoresis patch according to a second embodiment of the present invention; 
           [0030]      FIG. 9A  is a bottom plan view of an electrode film shown in  FIG. 8  before a reference-side region thereof is folded back on itself; 
           [0031]      FIG. 9B  is a bottom plan view of the electrode film shown in  FIG. 9A  with an insulative resist layer placed on the face side thereof; 
           [0032]      FIG. 10A  is a bottom plan view of the electrode film shown in  FIG. 9A  after the reference-side region thereof is folded back on itself; 
           [0033]      FIG. 10B  is a plan view of the electrode film shown in  FIG. 10A ; and 
           [0034]      FIG. 11  is a cross-sectional view taken along line XI-XI of  FIG. 10B . 
       
    
    
     DESCRIPTION OF EMBODIMENTS 
       [0035]    Iontophoresis patches according to preferred embodiments of the present invention in connection with an ionic drug permeation device which can incorporate such an iontophoresis path will be described in detail below with reference to the accompanying drawings. 
         [0036]      FIG. 1  shows in perspective the overall configuration of an ionic drug permeation device  12  incorporating therein an iontophoresis patch  10  according to a first embodiment of the present invention. In  FIG. 1 , the iontophoresis patch  10  and an energizing unit  14 , which jointly make up the ionic drug permeation device  12 , are shown as separate from each other.  FIG. 2  shows in exploded perspective the iontophoresis patch  10  shown in  FIG. 1 . 
         [0037]    The ionic drug permeation device  12  (hereinafter also referred to as “device  12 ”) is a medical instrument used to remove a pain caused upon puncture on a hemodialysis patient, for example, and also to administer a local anesthetic, e.g., an ionic anesthetic including lidocaine, to permeate into a patient&#39;s arm. The iontophoresis patch  10  (hereinafter also referred to as “patch  10 ”) is applied to the skin of the patient, which is an external conductor, and is energized by the energizing unit  14  to cause the ionic anesthetic included in the patch  10  into the living body. The patch  10  may be applied to a device for administrating a drug other than the ionic anesthetic to a patient, and may be used for iontophoresis to deliver various drugs. 
         [0038]    As shown in  FIGS. 1 and 2 , the device  12  includes the patch  10  and the energizing unit  14  placed on and connected to the face side (upper surface) of the patch  10 . 
         [0039]    The patch  10  has a donor portion  16  in the form of a circular thin sheet (film) and a reference portion  18  in the form of a rectangular thin sheet (film) with an arcuate side, the reference portion  18  being spaced from the donor portion  16 . An electrode film (electrode body)  20  connected to the energizing unit  14  is placed over the donor portion  16  and the reference portion  18 . The electrode film  20  includes a donor-side region  22  and a reference-side region  24  (see  FIG. 2 ) which are shaped coextensively with the donor portion  16  and the reference portion  18 , respectively, and a narrow bridge portion  26  disposed between the donor-side region  22  and the reference-side region  24  and joining the donor portion  16  and the reference portion  18 . 
         [0040]    The donor portion  16  has a circular donor application member  28  corresponding in shape to the outer shape of the donor portion  16 , and a donor gel (first contact member)  30  which fills an opening defined in the donor application member  28 . The donor-side region  22  of the electrode film  20  is electrically connected to the surface (upper surface in  FIG. 2 ) of the donor gel  30 . The reference portion  18  has a reference application member  32  of an oblong shape substantially corresponding in shape to the outer shape of the reference portion  18  and a reference gel (second contact member)  34  which fills an opening defined in the reference application member  32 . The reference-side region  24  of the electrode film  20  is electrically connected to the surface (upper surface in  FIG. 2 ) of the reference gel  34 . 
         [0041]    Each of the donor application member  28  and the reference application member  32  is made of a sticky elastic material which can adhere to a human skin or the like with a certain strength, and is electrically insulative. The donor gel  30  contains therein the ion anesthetic, and the reference gel  34  contains therein a solvent or a solution of an electrolyte, e.g., buffer salt, common salt, or the like, which is not harmful to living bodies, such as saline. Since a medical professional with sufficient puncture skills finds it easy to insert a needle into a puncture area of 2.5 (cm 2 ) for drug delivery, the surface (lower surface in  FIG. 2 ) of each of the donor gel  30  and the reference gel  34  for contact with the skin should be of an area of about 2.5 (cm 2 ). 
         [0042]    The donor gel  30  is inserted into the opening in the donor application member  28  and the reference gel  34  is inserted into the opening in the reference application member  32 . Then, the donor application member  28  and the reference application member  32  are applied to the skin of a patient, thereby bringing the donor portion  16  and the reference portion  18  substantially simultaneously into contact with the skin. Therefore, the patch  10  can simply be applied to the skin in one operation. The surfaces of the donor gel  30  and the reference gel  34  for contact with the skin may be made sticky. 
         [0043]      FIG. 3  is a cross-sectional view of the electrode film  20  taken along line III-III of  FIG. 2 . For an easier understanding of the electrode film  20 , the thickness of the electrode film  20  is illustrated as exaggerated.  FIG. 4  is an enlarged cross-sectional view of portion IV encircled by the broken line in  FIG. 3 .  FIG. 5A  is a plan view (top plan view) of the electrode film  20 , and  FIG. 5B  is a bottom plan view of the electrode film  20 . In  FIGS. 4 ,  5 A, and  5 B, a cover lay  36  to be described later is omitted from illustration for an easier understanding of the electrode film  20 . 
         [0044]    The electrode film  20  comprises a flexible substrate having a flexible base  21  which defines the outer shape thereof and which includes portions constructed respectively as the donor-side region  22 , the reference-side region  24 , and the bridge portion  26 . The base  21  comprises, for example, a thin flexible film of a resin such as polyester, polyimide, or the like. 
         [0045]    As shown in  FIGS. 3 through 5B , the donor-side region  22  includes a circular first electrode  38  disposed on the bottom surface of the base  21  and held in contact with and electrically connected to the donor gel  30 . A connection line  38   a  extends from the first electrode  38  along one side of the bridge portion  26  to a substantially central portion thereof. 
         [0046]    The reference-side region  24  includes an oblong second electrode  40  disposed on the bottom surface of the base  21  and held in contact with and electrically connected to the reference gel  34 . A first contact terminal line  42  and a second contact terminal line  44  are juxtaposed on the surface of the base  21 . A connection line  40   a  extends from the second electrode  40  along one side of the bridge portion  26  to the substantially central portion thereof in parallel to the connection line  38   a  (see  FIG. 5B ). The first and second contact terminal lines  42 ,  44  have a pair of respective circular terminal bases  42   a ,  44   a  juxtaposed on the face side of the reference-side region  24  and a pair respective connection lines  42   b ,  44   b  extending from the terminal bases  42   a ,  44   a  and bent to the substantially central portion of the bridge portion  26  parallel to each other. 
         [0047]    The interconnections of the electrode film  20 , i.e., the first electrode  38  (connection line  38   a ), the second electrode  40  (connection line  40   a ), and the first and second contact terminal lines  42 ,  44  (connection lines  42   b ,  44   b , terminal bases  42   a ,  44   a ), are formed, for example, by printing an electrically conductive ink containing silver/silver chloride on the face side and reverse side of the base  21 . The interconnections have exposed surfaces sealed by an electrically insulative adhesive  45  (see  FIGS. 3 and 4 ). However, the bottom surfaces (contact surfaces) of the first electrode  38  and the second electrode  40  which are held in contact with the donor gel  30  and the reference gel  34  are not coated with the adhesive  45  (see  FIG. 5B ). The electrically conductive ink may have its thickness increased by being printed in a plurality of layers for reliably preventing conduction failures from occurring. 
         [0048]    As shown in  FIGS. 3 through 5B , the connection line  38   a  of the first electrode  38  and the connection line  42   b  of the first contact terminal line  42  are aligned with each other in the thicknesswise direction of the bridge portion  26  (see  FIGS. 3 and 5B ), and have their respective distal ends electrically connected to each other by a through hole  46  which extends through the bridge portion  26  in the thicknesswise direction thereof (see  FIG. 4 ). Similarly, the connection line  40   a  of the second electrode  40  and the connection line  44   b  of the second contact terminal line  44  are aligned with each other in the thicknesswise direction of the bridge portion  26 , and have their respective distal ends electrically connected to each other by a through hole  48  which extends through the bridge portion  26  in the thicknesswise direction thereof. 
         [0049]    With the electrode film  20 , as described above, the base  21  of the donor-side region  22  is of a one-sided interconnect structure having the first electrode  38  only, and the base  21  of the reference-side region  24  is of a double-sided interconnect structure having the second electrode  40 , the first contact terminal line  42  and the second contact terminal line  44 . Therefore, the donor portion  16  including the donor-side region  22  of the one-sided interconnect structure is more flexible than the reference portion  18  including the reference-side region  24  of the double-sided interconnect structure. The bridge portion  26  has the various interconnects and the through holes  46 ,  48  lumped together on its substantially central portion. However, since the bridge portion  26  is of the one-sided interconnect structure having the connection line  38   a  only near the donor-side region  22 , the bridge portion  26  is also flexible near the donor portion  16 . 
         [0050]    As shown in  FIGS. 2 and 3 , the bridge portion  26  is surrounded by cover lays (protective layers)  36 , each in the form of an electrically insulative sheet, for preventing the connection lines  38   a ,  40   a ,  42   b ,  44   b  and the through holes  46 ,  48  from being exposed outwardly. Instead of the cover lays  36 , electrically insulative coatings (resist layers) may be used. However, if the bridge portion  26  should have more flexibility and durability, then the cover lays  36  in the form of sheets are more effective. 
         [0051]    As shown in  FIG. 4 , the electrode film  20  comprises a thin film wherein, for example, the base  21  has a thickness t 1  ranging from 12.5 μm to 250 μm, preferably from about 12.5 μm to 50 μm, each of the interconnections made of an electrically conductive ink, such as the first electrode  38 , the connection line  38   a , etc. has a thickness t 2  of about 20 μm, the adhesive  45  has a thickness t 3  ranging from about 20 μm to 30 μm, and each of the through holes  46 ,  48  has a thickness t 4  of about 140 μm. If the thickness of the donor portion  16  is represented by the sum of 25 μm as the thickness of the base  21 , 20 μm as the thickness of the first electrode  38 , and 20 μm as the thickness of the adhesive  45 , then the donor portion  16  is of a thin shape that is sufficiently flexible. 
         [0052]    The thickness t 4  of the through holes  46 ,  48  tends to be the greatest in the entire electrode film  20 . With the patch  10  according to the present embodiment, the through holes  46 ,  48  are disposed in the bridge portion  26 , thereby making the donor-side region  22  and the reference-side region  24  flat by preventing them from having bulges which would otherwise be produced by through holes. Therefore, increased intimate contact is achieved between the donor gel  30  and the reference gel  34  and the first electrode  38  and the second electrode  40 . Depending on the conditions in which the patch  10  is used, the through holes  46 ,  48  may be disposed in the donor-side region  22  or the reference-side region  24 . 
         [0053]    As shown in  FIG. 2 , connection terminals (hooks)  50 ,  52  are mounted on the respective terminal bases  42   a ,  44   a  that are electrically connected to the first electrode  38  and the second electrode  40 , by respective electrically conductive members (e.g., silver paste). The connection terminals  50 ,  52  have respective projections  50   a ,  52   a , each in the form of a small-diameter cylinder, projecting upwardly. The other portions of the connection terminals  50 ,  52  than the projections  50   a ,  52   a , together with the terminal bases  42   a ,  44   a , and the connection lines  42   b ,  44   b  are covered with an insulating film (hook cover)  54 . The insulating film  54  has a pair of holes defined therein through which the projections  50   a ,  52   a  penetrate. With only the projections  50   a ,  52   a  being exposed from the insulating film  54 , the face sides of the other members of the reference-side region  24  are covered with the insulating film  54 . 
         [0054]    As described later in a second embodiment, by use of fasteners (grommets), the connection terminals may be fixed to the base by crimping the connection terminals and the fasteners with the base sandwiched therebetween. 
         [0055]    As shown in  FIG. 1 , the energizing unit  14  has connection holes  14   a ,  14   b  defined in the bottom surface thereof for connection to the projections  50   a ,  52   a  of the connection terminals  50 ,  52 . The energizing unit  14  houses therein two series-connected cells  56  and an electric circuit which comprises a plurality of parallel-connected constant-current diodes, not shown. 
         [0056]    The energizing unit  14  includes an insulating sheet  58  held against the cathode of the cells  56 . Prior to use of the device  12 , the insulating sheet  58  prevents an electric current from flowing from the cells  56  to the constant-current diodes. When the device  12  stars to be used, the insulating sheet  58  is pulled away to electrically connect the cathode of the cells  56  to the electrode film  20 . An electric current then flows from the cells  56  through the electrode film  20  to the donor gel  30 , the body of the patient, and the reference gel  34 . Alternatively, a power supply switch may be used instead of the insulating sheet  58 . 
         [0057]    The device  12  thus constituted provides a current path along which the energizing unit  14  supplies an electric current from the connection terminal  50  connected to the connection hole  14   a  through the terminal base  42   a , the connection line  42   b , the connection line  38   a , and the first electrode  38  to the donor gel  30 , and the electric current supplied to the donor gel  30  flows through the body of the patient, the reference gel  34 , the second electrode  40 , the connection line  40   a , the connection line  44   b , the terminal base  44   a , and the connection terminal  52 , and then from the connection hole  14   b  back to the energizing unit  14 . 
         [0058]    The patch  10  according to the present embodiment has the first contact terminal line  42 , the second contact terminal line  44 , and the connection terminals  50 ,  52  for connecting and placing the energizing unit  14 , only on the face side of the reference portion  18 . 
         [0059]    Therefore, of the pair of gels functioning as a pair of electrodes to be applied to the skin of the patient, the donor portion  16  including the donor gel  30  which holds the drug is free of the energizing unit  14 , and hence has its flexibility not impaired by the energizing unit  14 . Therefore, as shown in  FIG. 6 , the donor portion  16  which contains the drug can easily conform closely to surface irregularities of a patient&#39;s arm or a highly raised blood vessel of a hemodialysis patient and thus the donor portion  16  can be secured in intimate contact with the surface irregularities of the patient&#39;s arm or the highly raised blood vessel of the hemodialysis patient. Since the donor portion  16  and the reference portion  18  are spaced from each other with the bridge portion  26  interposed therebetween, the donor portion  16  is highly flexible for better freedom with which to apply itself to the patient&#39;s body. Furthermore, as the energizing unit  14  can be connected directly to the patch  10 , the device  12  is reduced in overall size and is easy to handle, advantageously. 
         [0060]    The donor portion  16  and the reference portion  18  may be spaced from each other in a configuration without the bridge portion  26  being interposed therebetween. For example, the bridge portion  26  may be integral with the reference portion  18 , and thus the bridge portion  26  may be omitted in appearance. 
         [0061]    With respect to the electrode film  20  of the patch  10 , the donor portion  16  is of a one-sided interconnect structure and the reference portion  18  is of a double-sided interconnect structure, thereby making the donor portion  16  thinner and more flexible than the reference portion  18  for more intimate contact with the patient. 
         [0062]    With the patch  10 , furthermore, the through holes  46 ,  48  which connect the first electrode  38  and the second electrode  40  that contact the donor gel  30  and the reference gel  34  with the first and second contact terminal lines  42 ,  44  that are connected to the energizing unit  14 , i.e., connecting between the connection lines  38   a ,  40   a  and the connection lines  42   b ,  44   b , are disposed in the bridge portion  26 . Therefore, the donor-side region  22  and the reference-side region  24  of the electrode film  20  are made flat by preventing them from having bulges which would otherwise be produced by through holes. Therefore, increased intimate contact is achieved between the donor gel  30  and the first electrode  38 , and between the reference gel  34  and the second electrode  40 , thereby for preventing conduction failures from occurring. 
         [0063]    Since the first contact terminal line  42  connected to the first electrode  38  and the second contact terminal line  44  connected to the second electrode  40  are disposed parallel to each other on the face sides of the bridge portion  26  and the reference portion  18 , the one-sided interconnect structure can be easily provided on the donor portion  16 , and the electrode film  20  can be smaller in outer shape. 
         [0064]    As shown in  FIG. 7 , the patch  10  may have grips  60 ,  62 , each in the form of a small ear-shaped member, projecting on respective outer side surfaces of the donor portion  16  and the reference portion  18 . The grips  60 ,  62  are shaped so as to be easily gripped by the index fingers and thumbs of the right and left hands of a doctor, a nurse, or the like who applies the patch  10  to the patient, for example. Owing to the grips, when the applier applies the patch  10  to the skin of the patient, its fingertips are prevented from touching the donor gel  30 , the reference gel  34 , the donor application member  28 , and the reference application member  32 , and hence the adhering capability of the patch  10  is prevented from being lowered before the patch  10  is applied. When the patch  10  is to be applied, the applier may lightly pull the patch  10  in directions to space the donor portion  16  and the reference portion  18  apart from each other, thereby elongating the patch  10  straight to make it possible to bring the patch  10  accurately and easily into intimate contact with a target area. 
         [0065]    As shown in  FIG. 7 , the patch  10  may have, on the face side of the donor portion  16 , a central mark  64  indicative of the center of the donor gel  30  as viewed in plan and a plurality of angle marks  66  indicative of rotational angles of the donor gel  30  around the central mark  64 . The central mark  64  and the angle marks  66  may be represented by electrically nonconductive characters and symbols drawn on the face side of the donor-side region  22  of the electrode film  20  by silk screen printing or ink jet printing. The central mark  64  and the angle marks  66  have a thickness of about 17 μm, for example. The angle marks  66  serve as, for example, radial spider lines angularly spaced at 30 degrees around the central mark  64 . 
         [0066]    The central mark  64  allows the applier to apply the patch  10  to the skin easily at a desired area of the skin by aligning the center of the donor gel  30  with the desired area. Owing to the angle marks  66 , after determining the position to which the donor portion  16  is to be applied by using the central mark  64 , and when determining a position to which the reference portion  18  is to be applied, the applier can turn the reference portion  18  around the central mark  64  to make it possible to apply the reference portion  18  to a more stable position. Further, the supervisor can easily and accurately instruct the applier as to a position where to apply the reference portion  18 . As the energizing unit  14  is not placed on the donor portion  16 , advantageously the central mark  64  and the angle marks  66  can easily be formed on the donor portion  16 . 
         [0067]    Only one of the central mark  64  and the angle marks  66  may be used, for example. In the case where the angle marks  66  are provided, even if the central mark  64  may be omitted, the center of the angle marks  66  may essentially function as a central mark. 
         [0068]    The grips  60 ,  62 , and the central mark  64  and the angle marks  66  may be provided altogether, as shown in  FIG. 7 . Alternatively, either one of the grips  60 ,  62 , and the central mark  64  and the angle marks  66  may be used. If all of them are used as shown in  FIG. 7 , then advantageously while the applier is gripping the grips  60 ,  62 , the applier can easily and stably position the patch  10  using the central mark  64  and the angle marks  66 . 
         [0069]      FIG. 8  shows in exploded perspective an iontophoresis patch  100  according to a second embodiment of the present invention. 
         [0070]    As with the iontophoresis patch  10  according to the first embodiment, the iontophoresis patch  100  (hereinafter also referred to as “patch  100 ”) according to the present embodiment, and the energizing unit  14  (see  FIGS. 1 and 11 ) jointly make up an ionic drug permeation device. Those parts of the patch  100  according to the present embodiment which have identical or similar functions and advantages to those of the patch  10  according to the first embodiment are denoted by identical reference characters, and will not be described in detail below. 
         [0071]    As shown in  FIG. 8 , the patch  100  is substantially the same as the patch  10  shown in  FIG. 1 , etc. in that it has a donor portion  16  in the form of a circular thin sheet (film) and a reference portion  18  in the form of a rectangular thin sheet (film) with an arcuate side, the reference portion  18  being joined to the donor portion  16  by a bridge portion  26 . However, an electrode film (electrode body)  102  that is placed over the donor portion  16  and the reference portion  18  has structural details different from those of the electrode film  20  shown in  FIGS. 1 through 5B . 
         [0072]    The electrode film  102  includes a donor-side region  104  and a reference-side region  106  which are shaped so as to correspond to the donor portion  16  and the reference portion  18 , respectively, and has an outer shape defined by a base  108  which has a single-layer structure in the donor-side region  104  and a double-layer structure (two-layer structure) in the reference-side region  106  which is folded back on itself along a folding portion (bending portion)  110 . The reference-side region  106  comprises a first reference-side region  106   a  (bottom side) to be applied to the skin and a second reference-side region  106   b  which is folded along the folding portion  110  so as to overlap the reverse side of the first reference-side region  106   a  (see  FIG. 8 ). With the electrode film  20  of the patch  10 , the donor-side region  22  and the reference-side region  24  are formed by the base  21  which is of a single-layer structure (see  FIG. 3 ). 
         [0073]    In the donor portion  16  of the patch  100 , the donor-side region  104  of the electrode film  102  is electrically connected to the face side (lower surface in  FIG. 8 ) of the donor gel  30 . Similarly, in the reference portion  18 , the reference-side region  106  of the electrode film  102  is electrically connected to the face side (lower surface in  FIG. 8 ) of the reference gel  34 . 
         [0074]      FIG. 9A  is a bottom plan view of the electrode film  102  before the reference-side region  106  is folded back on itself, and  FIG. 9B  is a bottom plan view of the electrode film  102  shown in  FIG. 9A  with an insulative resist layer  112  placed on the face side thereof. Specifically,  FIG. 9A  is a bottom plan view of the electrode film  102  with the resist layer  112  (represented by the dashed cross-hatched pattern in  FIG. 9B ) omitted from illustration. In  FIGS. 9A and 9B , most of the face side of the electrode film  102  (the donor-side region  104  and the first reference-side region  106   a ) is shown as a bottom surface to be applied to the skin. In an actual product, the second reference-side region  106   b  folded back along the folding portion  110  provides an upper surface on which the energizing unit  14  is placed. 
         [0075]    As shown in  FIG. 9A , the electrode film  102  before the reference-side region  106  is folded back on itself (while the assembly is in a production process) comprises a flexible substrate which has the single base  108  wherein the reference-side region  106  is of a symmetrical shape with respect to the folding portion  110 . As with the base  21 , the base  108  comprises a thin flexible film of a resin such as polyester, polyimide, or the like. 
         [0076]    The single base  108  has an outer shape which is substantially L-shaped before the reference-side region  106  is folded back on itself. On the single base  108 , various electrodes and interconnections of the donor-side region  104  and the reference-side region  106  are formed. 
         [0077]    The donor-side region  104  includes a circular first electrode  38  disposed on the bottom surface of the base  108  and held in contact with and electrically connected to the donor gel  30 . The reference-side region  106  includes an oblong second electrode  40  disposed on the bottom surface of the base  108  (the face side of the first reference-side region  106   a ). The first electrode  38  and the second electrode  40  are connected to the energizing unit  14  respectively by a first contact terminal line  114  and a second contact terminal line  116  which are wired on the base  108 . 
         [0078]    The first contact terminal line  114  includes a terminal base  114   a  disposed on the face side of the second reference-side region  106   b  and a connection line  114   b  extending from the terminal base  114   a  in a bent pattern along the face sides of the first reference-side region  106   a  and the bridge portion  26  and connected to the first electrode  38 . The terminal base  114   a  has a small-diameter hole  115   a  defined centrally therein and extending therethrough in a thicknesswise direction thereof. The hole  115   a  also extends through the base  108 . 
         [0079]    The second contact terminal line  116  includes a terminal base  116   a  disposed on the face side of the second reference-side region  106   b  side by side with the terminal base  114   a , and a connection line  116   b  extending from the terminal base  116   a  in a bent pattern to a substantially central area of the first reference-side region  106   a  so as to be connected to the second electrode  40 . The connection line  116   b  has a small rectangular electrode mounting plate  116   c  on an end thereof remote from the terminal base  116   a . The second electrode  40  is held in contact with the electrode mounting plate  116   c  in an electrically conductive state. As with the terminal base  114   a , the terminal base  116   a  has a hole  115   b  defined centrally therein and extending therethrough and also through the base  108 . 
         [0080]    As shown in  FIG. 9A , in the electrode film  102 , the first electrode  38 , the first contact terminal line  114 , and the second contact terminal line  116  are formed by printing an electrically conductive ink containing silver, for example, on the face side of the base  108  before the reference-side region  106  is folded back on itself. After the electrode mounting plate  116   c  of the second contact terminal line  116  is formed, the second electrode  40  is formed by printing an electrically conductive ink containing silver/silver chloride on the upper surface of the electrode mounting plate  116   c . The second electrode  40  may be made of the same material as the first electrode  38 , etc. If the second electrode  40  is made of the same material as the first electrode  38 , etc., then the electrode mounting plate  116   c  may be dispensed with, and the first electrode  38 , the first contact terminal line  114 , the second contact terminal line  116 , and the second electrode  40  may be formed altogether. 
         [0081]    The interconnections have exposed surfaces which is sealed, for example, by a resist layer  112  made of an electrically insulative adhesive, a coating, or the like, as shown in  FIG. 9B  after the first electrode  38 , the first contact terminal line  114 , and the second contact terminal line  116  have been formed. The surfaces of the first electrode  38  and the second electrode  40  which are held in contact with the donor gel  30  and the reference gel  34  are not coated with the resist layer  112 , and holes  117   a ,  117   b  which are not coated with the resist layer  112  are defined around the respective holes  115   a ,  115   b . The holes  117   a ,  117   b  are of a circular shape greater in diameter than the holes  115   a ,  115   b . The electrically conductive ink may have its thickness increased by being printed in a plurality of layers for reliably preventing conduction failures from occurring. The exposed surfaces of the interconnections may be covered with an electrically insulative sheet applied thereto, instead of the resist layer  112 . 
         [0082]    The connection lines  114   b ,  116   b  of the first contact terminal line  114  and the second contact terminal line  116  have respective portions corresponding to the folding portion  110 , i.e., respective portions including the folding portion  110 , which are formed as wider portions  114   c ,  116   d  (see  FIG. 9A ) which are wider than the other portions of the connection lines  114   b ,  116   b  on both sides of the wider portions  114   c ,  116   d . When the first reference-side region  106   a  and the second reference-side region  106   b  are folded back on each other along the folding portion  110 , the wider portions  114   c ,  116   d  are effective to reliably prevent the connection lines  114   b ,  116   b  from being broken or buckled. Thus, the connection lines  114   b ,  116   b  can be made more durable and reliable at the time the first reference-side region  106   a  and the second reference-side region  106   b  are folded back on each other. 
         [0083]    A process of constructing the patch  100  using the electrode film  102  thus constituted will be described below. 
         [0084]    First, the first electrode  38 , the second electrode  40 , the first contact terminal line  114 , and the second contact terminal line  116  are formed on one face of the base  108 , and thereafter the reference-side region  106  is folded back on itself along the folding portion  110 , as shown in  FIGS. 10A and 10B . Then, the first reference-side region  106   a  and the second reference-side region  106   b  are fixed to each other by an adhesive or the like with their reverse sides held in close contact with each other. On the reference-side region  106 , the second electrode  40  is disposed on the same surface as the surface on which the first electrode  38  is disposed (see  FIG. 10A ), and the terminal bases  114   a ,  116   a  are disposed on the other surface which is the reverse side thereof (see  FIG. 10B ). 
         [0085]    Prior to the folding process, as shown in  FIG. 11 , connection terminals (hooks)  118 ,  120  are fixed to the upper surfaces of the respective terminal bases  114   a ,  116   a  by fasteners (grommets)  118   b ,  120   b  which are inserted from the reverse side of the base  108  into the respective holes  115   a ,  115   b . The connection terminals (hooks)  118 ,  120  and the fasteners  118   b ,  120   b  are now securely fixed to the second reference-side region  106   b , and the connection terminals  118 ,  120  are electrically connected to the terminal bases  114   a ,  116   a . The connection terminals  118 ,  120  may be substantially identical in structure to the connection terminals  50 ,  52  (see  FIG. 2 ) except that they have small holes in which the fasteners  118   b ,  120   b  are fitted. The connection terminals  118 ,  120  have projections  118   a ,  120   a , respectively, each in the form of a small-diameter cylinder, projecting upwardly from their upper surfaces for connection to the connection holes  14   a ,  14   b  (see  FIG. 1 ) of the energizing unit  14 . In  FIG. 11 , for an easier understanding of the electrode film  102 , the thickness of the electrode film  102  is illustrated as exaggerated, and the base  108  of the first reference-side region  106   a  and the base  108  of the second reference-side region  106   b  are illustrated as spaced from each other. Actually, however, the base  108  of the first reference-side region  106   a  and the base  108  of the second reference-side region  106   b  are held in intimate contact with each other. 
         [0086]    Then, as shown in  FIGS. 8 and 11 , the donor application member  28 , the reference application member  32 , the donor gel  30 , and the reference gel  34  are placed in respective given positions on the electrode film  102  folded back on itself as described above, thereby producing the patch  100 . 
         [0087]    The thus-constituted patch  100  provides a current path along which an electric current is supplied from the connection terminal  118  connected to the connection hole  14   a  of the energizing unit  14  through the terminal base  114   a , the connection line  114   b , and the first electrode  38  to the donor gel  30 , and the electric current supplied to the donor gel  30  flows through the body of the patient, the reference gel  34 , the second electrode  40 , the electrode mounting plate  116   c , the connection line  116   b , the terminal base  116   a , and the connection terminal  120 , and then from the connection hole  14   b  back to the energizing unit  14 . Thus, by using the patch  100 , an ionic drug permeation device which can be used in substantially the same manner as the device  12  shown in  FIG. 1  can be constituted. 
         [0088]    When the patch  100  according to the present embodiment is manufactured, as shown in  FIG. 9A , the interconnect forming process on the electrode film  102  can be finished simply by forming the first electrode  38 , the second electrode  40 , the first contact terminal line  114 , and the second contact terminal line  116  on one surface of the base  108 . Thereafter, the reference-side region  106  is folded back on itself along the folding portion  110 , thereby producing the electrode film  102  of a desired constitution. 
         [0089]    With the electrode film  20  of the patch  10  according to the first embodiment, it is necessary to perform the interconnect forming process on both surfaces of the base  21 . In contrast thereto, with the electrode film  102  of the patch  100  according to the second embodiment, simply by performing the interconnect forming process on one surface of the base  108 , and then folding the reference-side region  106  back on itself along the folding portion  110 , the reference-side region  106  can be made into a double-sided interconnect structure. Therefore, the interconnect forming process is simplified for increased production efficiency, and the printing of the interconnections requires only one plate (original plate) for one-sided printing, and thus the cost thereof can be reduced. As with the patch  10 , the donor-side region  104  to be brought into intimate contact with a patient&#39;s arm can be of a flexible one-sided interconnect structure, thereby making it possible to bring the donor portion  16  into sufficiently intimate contact with the patient. 
         [0090]    The folded-back structure of the reference-side region  106  of the patch  100  makes it unnecessary to provide the through holes  46 ,  48 , etc. (see  FIGS. 3 and 4 ) between the first electrode  38  and the second electrode  40 , and the first and second contact terminal lines  114 ,  116  that are connected to the energizing unit  14 . Consequently, the bridge portion  26  in particular is highly flexible, so that the ability of the patch  100  to be applied to the patient is further increased. 
         [0091]    The patch  100  may also have not only the grips  60 ,  62  but also the central mark  64  and the angle marks  66  (see  FIG. 7 ). 
         [0092]    The present invention is not limited to the above embodiment, but may adopt various arrangements and processes without departing from the scope of the invention. 
         [0093]    For example, the energizing unit  14  may be of another arrangement than the above arrangement insofar as it is capable of energizing the patches  10 ,  100  as desired. 
         [0094]    The donor gel  30  and the reference gel  34 , and the donor portion  16  and the reference portion  18  may be of shapes other than those described above, and their shapes may be changed depending on the applications and specifications of the patches  10 ,  100 .

Technology Classification (CPC): 0