Patent Publication Number: US-2005143686-A1

Title: System and method for iontophoretic transdermal delivery of one or more therapeutic agents

Description:
RELATED APPLICATIONS  
      This application is a continuation of U.S. patent application Ser. No. 10/626,439 entitled “System and Method for Iontophoretic Transdermal Delivery of One or More Therapeutic Agents” filed Jul. 24, 2003, which claims benefit to U.S. Provisional Patent Application No. 60/399,618 entitled “System and Method for Iontophoretic Transdermal Delivery of One or More Therapeutic Agents” filed Jul. 29, 2002. 
    
    
     TECHNICAL FIELD OF THE INVENTION  
      This invention relates generally to iontophoresis and more particularly to a system and method for iontophoretic transdermal delivery of one or more therapeutic agents.  
     BACKGROUND  
      Iontophoresis (i.e. electrically assisted transdermal delivery of a therapeutic agent) has become an increasingly important technique for administering therapeutic agents such as analgesics, steroids, and the like. Iontophoretic transdermal delivery systems offer advantages that are not typically achievable using any other means of administration, such as introduction of the agent through mucosal absorption or skin puncture. However, such systems are known to have a number of undesirable side affects, such as skin injury ranging from redness of the skin to actual iontophoretic burns to the treated area due to fluctuations in current density. In addition, where multiple agents are contained in a reservoir of such a system, in the form of different ions, these agents may enter into competition with one another during iontophoresis, meaning that the actual transport of the charge associated with the current flow is effected through the flow of these different charge carriers. This may make it more difficult to control the dosage rates of the multiple agents individually.  
     SUMMARY OF THE INVENTION  
      In one embodiment, a system for iontophoretic transdermal delivery of one or more therapeutic agents into a user&#39;s skin includes a first end including a first reservoir for containing one or more therapeutic agents, a second end including a second reservoir for containing one or more therapeutic agents, and a connecting portion coupling the first end to the second end. The connecting portion houses a self-contained power source for generating electric current, the power source having a first terminal and a second terminal. The connecting portion also houses: (1) at least a portion of a first electrode for electrically coupling the first terminal of the power source to the first reservoir, the first electrode operable to conduct electric current between the power source and the first reservoir to ionize the one or more therapeutic agents contained within the first reservoir for iontophoretic transdermal delivery into the user&#39;s skin; and (2) at least a portion of a second electrode for electrically coupling the second terminal of the power source to the second reservoir, the second electrode operable to conduct electric current between the power source and the second reservoir to ionize the one or more therapeutic agents contained within the second reservoir for iontophoretic transdermal delivery into the user&#39;s skin. The system is adapted to be used in an extended or non-extended state.  
      In another embodiment, a method for manufacturing a system for iontophoretic transdermal delivery of one or more therapeutic agents into a user&#39;s skin includes providing a first reservoir for containing one or more therapeutic agents, providing a second reservoir for containing one or more therapeutic agents, and providing a self-contained power source for generating electric current. The power source includes a first terminal and a second terminal. The method further includes providing a first electrode for electrically coupling the first terminal of the power source to the first reservoir. The first electrode conducts electric current between the power source and the first reservoir to ionize the one or more therapeutic agents contained within the first reservoir for iontophoretic transdermal delivery into the user&#39;s skin. The method further includes providing a second electrode for electrically coupling the second terminal of the power source to the second reservoir. The second electrode conducts electric current between the power source and the second reservoir to ionize the one or more therapeutic agents contained within the second reservoir for iontophoretic transdermal delivery into the user&#39;s skin. The system may be used in an extended or non-extended state.  
      In another embodiment, a method for delivering one or more therapeutic agents to a user through the user&#39;s skin includes positioning an iontophoretic transdermal delivery system about a portion of the user&#39;s body to receive treatment. The system may be used in an extended or non-extended state. The system includes a first end having a first reservoir for containing one or more therapeutic agents, a second end having a second reservoir for containing one or more therapeutic agents, and a connecting portion coupling the first end to the second end. The connecting portion may house a self-contained power source for generating electric current. The power source may include a first terminal and a second terminal. The connecting portion may also house a first electrode for electrically coupling the first terminal of the power source to the first reservoir. The first electrode may conduct electric current between the power source and the first reservoir to ionize one or more therapeutic agents contained within the first reservoir for iontophoretic transdermal delivery into the user&#39;s skin. The connecting portion may further include a second electrode for electrically coupling the second terminal of the power source to the second reservoir. The second electrode may conduct electric current between the power source and the second reservoir to ionize the one or more therapeutic agents contained within the second reservoir for iontophoretic transdermal delivery into the user&#39;s skin. The system may be used in an extended or non-extended state. The method further includes applying electrical current to the therapeutic agents contained in the reservoirs using the power source and delivering the therapeutic agents to the user through the user&#39;s skin in response to the electrical current.  
      Particular embodiments of the present invention may provide one or more technical advantages. Certain embodiments provide a simple and effective technique for administering drugs or other therapeutic agents. Certain embodiments provide two separate reservoirs each containing one or more drugs or other therapeutic agents. Certain embodiments provide the opportunity to treat more than one area of the body at a time with more than one drug or other therapeutic agent, without being limited to using ionized or ionizing agents. Certain embodiments provide an extendable, multi-function, multi-purpose system that may be used as a single bandage or as two separated bandages in delivering drugs or other therapeutic agents iontophoretically through the skin. Certain embodiments provide a fully self-contained iontophoresis system completely encased in a hypoallergenic adhesive bandage, while maintaining a shallow profile that may, in particular embodiments, be less than one sixteenth of an inch thick. Certain embodiments combine a power source, electrodes, reservoirs, and a flex-circuit to form a single applicator or, when extended, possibly to form two separate applicators. Certain embodiments provide a complete iontophoretic system in which the system and all of its components are suitable for a single patient use and are disposable after a single use.  
      Certain embodiments may provide all, some, or none of these technical advantages. Certain embodiments may provide one or more other technical advantages, one or more of which may be readily apparent to those skilled in the art from the figures, description, and claims included herein.  
    
    
     BRIEF DESCRIPTION OF THE DRAWINGS  
      To provide a more complete understanding of the present invention and certain features and advantages thereof, reference is made to the following description taken in conjunction with the accompanying drawings, in which:  
       FIG. 1  illustrates a top view of an example system, in an extended state, for iontophoretic transdermal delivery of one or more therapeutic agents;  
       FIG. 2  illustrates a top view of an example system, in a non-extended state, for iontophoretic transdermal delivery of one or more therapeutic agents;  
       FIG. 3  illustrates an exploded perspective view, bottom side up, of an example system for iontophoretic transdermal delivery of one or more therapeutic agents;  
       FIG. 4A  illustrates a detailed view, looking up at the top, of an example first electrode of an example power strip;  
       FIG. 4B  illustrates a detailed view, looking down at the bottom, of an example second electrode of an example power strip;  
       FIG. 5A  illustrates a top view of an example power strip;  
       FIG. 5B  illustrates a cross-sectional view of the example power strip of  FIG. 5A ;  
       FIG. 6A  illustrates a top view of an example system for iontophoretic transdermal delivery of one or more therapeutic agents;  
       FIGS. 6B and 6C  illustrate cross-sectional views of the example system for iontophoretic transdermal delivery of one or more therapeutic agents of  FIG. 6A ;  
       FIG. 7  illustrates a bottom view of an example system for iontophoretic transdermal delivery of one or more therapeutic agents, depicting a pair of exposed reservoir pads and surrounding gaskets when the system is in an extended state;  
       FIG. 8  illustrates a bottom view of an example system for iontophoretic transdermal delivery of one or more therapeutic agents, depicting a pair of exposed reservoir pads and surrounding gaskets when the system is in a non-extended state; and  
       FIG. 9  illustrates an example method for treating at least one portion of a user&#39;s body with one or more therapeutic agents using an example iontophoretic transdermal delivery system.  
    
    
     DESCRIPTION OF EXAMPLE EMBODIMENTS  
       FIG. 1  illustrates a top view of an example system  2 , in an extended state, for iontophoretic transdermal delivery of one or more therapeutic agents. In certain embodiments, system  2  provides an extendable, multi-function, multi-purpose iontophoretic transdermal delivery system that may be used as a single bandage or as two separated bandages in delivering one or more therapeutic agents iontophoretically through the user&#39;s skin. In a particular embodiment, system  2  provides a complete iontophoretic system in which system  2  and all of its components are suitable for a single patient use and are disposable after a single use.  
      As shown in  FIG. 1 , system  2  includes an outer strip  10  that includes a positive end  10   a  associated with a positive electrode, a negative end  10   b  associated with a negative electrode, and a connecting portion  10   c  coupling positive end  10   a  to negative end  10   b . Outer strip  10  may be made from an FDA-approved hypoallergenic material, which may be either woven or non-woven, with a hypoallergenic adhesive on its bottom surface for removably coupling the system to the user&#39;s skin. In certain embodiments, outer strip  10  is preferably soft, flexible, foldable, and moldable to the surface of the user&#39;s skin.  
      System  2  includes one or more reservoirs  40  containing one or more therapeutic agents for application to the user&#39;s skin. In certain embodiments, system  2  provides two separate reservoirs  40 , each containing one or more therapeutic agents. The use of two separate reservoirs  40  provides the opportunity to treat more than one area of the user&#39;s body at a time and may be desirable when more than one therapeutic agent is to be applied. In certain embodiments, system  2  includes protective tabs  60  which may be made from a paper material and removably coupled to a hypoallergenic adhesive on the bottoms of reservoir gaskets associated with reservoirs  40  to protect and provide protection from the therapeutic agents in reservoirs  40  prior to application of system  2  to the user&#39;s skin. As shown in  FIG. 1 , in an extended state, system  2  has an extended length L and a width W. In a particular embodiment, extended length L is approximately 10.375 inches and width W is approximately 2.559 inches, although system  2  may have any suitable length and width according to particular needs.  
      Where system  2  is extendable from a non-extended state to an extended state shown in  FIG. 1 , outer strip  10  may provide a “hidden” pocket  70  on one end, such as negative end  10   b , to house connecting portion  10   c  and associated components when system  2  is in a non-extended state. In certain embodiments, such components may include a power source, electrodes, and an associated flex-circuit as discussed in more detail below.  
       FIG. 2  illustrates a top view of example system  2  in a non-extended state. As shown in  FIG. 2 , in a non-extended state, system  2  has a non-extended length L′. In a particular embodiment, non-extended length L′ is approximately 5.500 inches, although system  2  may have any suitable non-extended length according to particular needs. As discussed above, when system  2  is in a non-extended state, connecting portion  10   c  and associated components may be housed in pocket  70 .  
       FIG. 3  illustrates an exploded perspective view, bottom side up, of example system  2 . In certain embodiments, each reservoir  40  includes a reservoir gasket  20  and a reservoir pad  30 . Thus, where system  2  includes two reservoirs  40   a  and  40   b , one for each end  10   a  and  10   b , reservoir gaskets  20   a  and  20   b  and reservoir pads  30   a  and  30   b  are provided. Reservoir gaskets  20  are used to help contain the one or more therapeutic agents within associated reservoirs  40  to prevent leakage to other parts of the user&#39;s skin during application of system  2  and subsequent treatment. In a particular embodiment, reservoir gaskets  20  may be made from a soft, flexible, foldable, FDA-approved, hypoallergenic foam material. In certain embodiments, reservoir pads  30  are used to absorb the one or more therapeutic agents to contain them in reservoirs  40  prior to treatment. In a particular embodiment, reservoir pads  30  may be made from a soft, flexible, foldable, absorbent, FDA approved, hypoallergenic material.  
      In certain embodiments, system  2  includes a power strip  50  having a first electrode  51 , a second electrode  55 , and a power source  59  to positively and negatively ionize or otherwise charge the one or more therapeutic agents within reservoir pads  30  for delivery of the therapeutic agents through the user&#39;s skin. Power strip  50  is described more fully below with reference to  FIGS. 4A, 4B ,  5 A, and  5 B. Power source  59  may have a negative terminal and a positive terminal. Power source  59  may be self-contained. For example, in a particular embodiment, power source  59  is a 1.55 volt battery. Although example system  2  is discussed as having a power source  59  for ionizing the therapeutic agents, the present invention contemplates using system  2  without using ionized or ionizing therapeutic agents.  
      Where system  2  is in a non-extended state, “hidden” pocket  70  may be used to house the flex-circuit portions of power strip  50 , discussed below with reference to  FIGS. 4A, 4B , and  5 , and power source  59 . In certain embodiments, all components associated with connecting portion  10   c  fold over themselves in the direction of negative end  10   b  and, once in their folded state, slide into hidden pocket  70 . Although hidden pocket  70  is described as associated with negative end  10   b , the components associated with connecting portion  10   c  may fold in either direction (i.e. toward positive end  10   a  or negative end  10   b ) depending on the configuration of system  2 . To extend system  2  from a non-extended state, the components are removed from hidden pocket  70  and unfolded in a reverse manner. Among other benefits, the extendable nature of certain embodiments of system  2  allows for a sequential separation of the therapeutic agents to be administered through the user&#39;s skin by way of the electric current from power source  59 . Another benefit of the extendable nature of certain embodiments of system  2  is the ability to treat two areas of a user&#39;s body at one time, with the same or different therapeutic agents.  
       FIG. 4A  illustrates a detailed view, looking up at the top, of an example first electrode  51  of an example power strip  50 . In certain embodiments, first electrode  51  includes a first electrode end  52  and a first conductor  53  coupled to first electrode end  52 . First conductor  53  and first electrode end  52  may each comprise an electrically conductive material such as silver, copper, silver chloride, zinc, or any other material suitable to conduct and deliver an electrical current to the therapeutic agents. In certain embodiments, first conductor  53  and first conductor end  54  may comprise part of a flex circuit portion of power strip  50 . First conductor  53  may be disposed between insulating layers  80   a  and  80   b . Insulating layer  80   b  may be of a sufficiently shorter length than insulating layer  80   a  such that first conductor end  54  is at least partially uncovered to enable proper electrical contact with power source  59 . The contact between power source  59  and first conductor end  54  is described more fully below with reference to  FIG. 5B . Insulating layer  80   a  may be disposed on the top side (i.e. the side facing the viewer in  FIG. 4A ) of first electrode end  52 . In certain embodiments, insulating layers  80  may include any appropriate soft, flexible insulating material.  
       FIG. 4B  illustrates a detailed view, looking down at the bottom, of an example second electrode  55  of an example power strip  50 . Second electrode  55  includes a second electrode end  56  and a second conductor  57  coupled to second electrode end  56 . Second conductor  57  and second electrode end  56  may each comprise an electrically conductive material such as silver, copper, silver chloride, zinc, or any other material suitable to conduct and deliver an electrical current to the therapeutic agents. In certain embodiments, second conductor  57  and second conductor  58  may comprise part of the flex-circuit portion of power strip  50 . Second conductor  57  may be disposed between insulating layers  80   c  and  80   d . Insulating layer  80   d  may be of a sufficiently shorter length than insulating layer  80   c  such that second conductor end  58  is at least partially uncovered to enable proper electrical contact with power source  59 . The contact between power source  59  and second conductor end  58  is described more fully below with reference to  FIG. 5B . Insulating layer  80   d  may be disposed on the top side (i.e. the side facing away from the viewer in  FIG. 4B ) of second electrode end  56 . In certain embodiments, insulating layers  80  may include any appropriate soft, flexible insulating material.  
       FIG. 5A  illustrates a top view of an example power strip  50  and its associated components. In certain embodiments, power source  59  is a self-contained power source, such as a battery, that may lie within and be insulated by a protective covering  90 . In a particular embodiment, protective covering  90  may be made from a polymer or gel-like substance, although any appropriate insulating material may be used.  
      As shown in  FIG. 5A , in certain embodiments power strip  50  has an extended-state length M. In a particular embodiment, length M is approximately 8.3438 inches, although power strip  50  may have any suitable length according to particular needs. Furthermore, first electrode end  52  and second electrode end  56  of first electrode  51  and second electrode  55 , respectively, each have a length N and a width X. In certain embodiments, first electrode end  52  and second electrode end  56  are substantially square in shape, such that length N and width X are substantially the same. In a particular embodiment, length N and width X of first electrode end  52  and second electrode end  56  are each approximately 0.4375 inches, although electrodes  52  and  53  may have any suitable lengths and widths according to particular needs. The distance from an approximate centerline of first electrode end  52  to an approximate centerline of power source  59  is represented by extended-state length O. The distance from an approximate centerline of second electrode end  56  to and the approximate centerline of power source  59  is represented by extended-state length P. In a particular embodiment, length O is approximately 5.3875 inches and length P is approximately 2.5188 inches, although lengths O and P may be any suitable lengths according to particular needs.  
       FIG. 5B  illustrates a cross-sectional view of an example power strip  50  and its associated components.  FIG. 5B  shows the details of the various layers of certain embodiments of power strip  50 , including insulating layers  80 . In certain embodiments, insulating layers  80   a  and  80   c  cover first electrode end  52  and second electrode end  56  on only one side, as described above with reference to  FIGS. 4A and 4B , such that first electrode end  52  and second electrode end  56  make sufficient electrical contact with reservoirs pads  30 , as shown in  FIG. 6C  described below.  FIG. 5B  shows first conductor end  54  and second conductor end  58  each extending beyond layers  80   b  and  80   d , respectively, such that first conductor end  54  and second conductor end  58  each make sufficient electrical contact with power source  59 .  
       FIG. 6A  illustrates a top view of example system  2  in an extended state.  FIGS. 6B and 6C  illustrate cross sectional views of example system  2  cut along section B-B of  FIG. 6A .  
       FIG. 6B  illustrates system  2  including a protective covering  45 , preferably made of a hypoallergenic woven or non-woven material, to protect the self-contained power source  59  and power strip  50  from the user&#39;s skin and also to further prevent battery leakage, should it occur, into the user&#39;s skin. The positioning of reservoir gasket  20   b , reservoir pad  30   b , and protective tab  60   b , according to a particular embodiment, is also illustrated. In certain embodiments, system  2  maintains a shallow profile. In a particular embodiment, for example, thickness T of system  2  is less than approximately one-sixteenth of an inch, although system  2  may have any suitable thickness according to particular needs.  
      In certain embodiments, as shown in  FIG. 6C , first electrode end  52  is positioned such that it makes sufficient electrical contact with reservoir pad  30   a  to enable the transfer of electrical current to reservoir pad  30   a . As discussed above, protective tab  60   a  may be made from paper removably coupled to adhesive on the bottom of reservoir gasket  20   a  to protect and provide protection from the therapeutic agents in reservoir pad  30   a  prior to application of system  2  to the users skin. When protective tab  60   a  is removed, reservoir pad  30   a  and the associated therapeutic agents may make sufficient contact with the user&#39;s skin to allow the electrical current flowing from power source  59  through first electrode end  52  to flow through reservoir pad  30   a  to ionize the therapeutic agents contained in reservoir  40   a  so as to facilitate absorption of the one or more associated therapeutic agents through the user&#39;s skin. While the details of the positive portion of system  2  are illustrated and described with reference to  FIGS. 6B and 6C , the operation and arrangement of components on the opposing negative portion of system  2 , such as second electrode end  56 , reservoir gasket  20   b , reservoir pad  30   b , and protective tab  60   b , are substantially similar.  
       FIG. 7  illustrates a bottom view of example system  2 , depicting a pair of exposed reservoir pads  30  (i.e. with protective tabs  60  removed), reservoir gaskets  20 , and protective covering  45  when system  2  is in an extended state. The details of power strip  50 , which is hidden behind protective covering  45 , reservoir gaskets  20 , and reservoir pads  30 , are omitted for clarity.  
       FIG. 8  illustrates a bottom view of example components of example system  2 , depicting a pair of exposed reservoir pads  30  and surrounding reservoir gaskets  20  when system  2  is in a non-extended state. As described above, in certain embodiments, all components associated with connecting portion  10   c , including protective covering  45  and portions of power strip  50  including power source  59 , fold over themselves in the direction of negative end  10   b  and, once in their folded state, slide into hidden pocket  70 . The components associated with connecting portion  10   c  may fold either towards negative end  10   b  or positive end  10   a  depending on the configuration of system  2 . Hidden pocket  70 , and the components of power strip  50  which fold into pocket  70  when system  2  is in its non-extended state, are omitted for clarity.  
       FIG. 9  illustrates an example method for treating at least one portion of a user&#39;s body with one or more therapeutic agents using an example iontophoretic transdermal delivery system  2 . The example method begins at step  202 , where protective covering  45  and protective tabs  60  are removed. At step  204 , system  2  is positioned about the portion of the user&#39;s body that is to receive the therapeutic agents. At step  206 , an electrical current is applied to the therapeutic agents contained in reservoirs  40 , using power source  59  for example. At step  208 , the therapeutic agents are delivered to the user through the user&#39;s skin.  
      Although an example method is illustrated, the present invention contemplates two or more steps taking place substantially simultaneously or in a different order. In addition, the present invention contemplates using methods with additional steps, fewer steps, or different steps, so long as the steps remain appropriate for using an iontophoretic transdermal delivery system  2  for delivery of one or more therapeutic agents to at least one portion of user&#39;s body.  
      Furthermore, although the present invention has been described with several embodiments, a multitude of changes, substitutions, variations, alterations, and modifications may be suggested to one skilled in the art, and it is intended that the invention encompass all such changes, substitutions, variations, alterations, and modifications as fall within the spirit and scope of the appended claims.