Patent Publication Number: US-2011060268-A1

Title: Nail treatment device

Description:
FIELD 
     The present invention relates to a nail treatment device. Moreover, the present invention is of a nail treatment device for active delivery of an active substance to the nail. 
     BACKGROUND 
     A variety of infections are known to affect the nail. Nail infections include fungal infection, bacterial infection, viral infection, psoriasis infection and combinations thereof. 
     Onychomycosis is a fungal infection of the nail and surrounding skin. In the most common form of onychomycosis, the fungus invades the nail bed under the nail plate, beginning at the hyponychium and then migrates proximally through the underlying nail matrix. Onychomycosis causes nails to thicken, split, discolor and disfigure and may cause pain. 
     Psoriasis of the nails occurs in about half the people affected with psoriasis. Nail psoriasis manifests itself with pitting and deformation of the nail, thickening of the nail, onycholysis and discoloration. 
     It has been found by the inventors that iontophoresis promotes the delivery of active agents into the nail and provides an effective method of treating nail infections including onychomycosis. 
     A substance to be delivered by iontophoresis should preferably be disposed in close proximity to the delivery electrode of an iontophoresis device. In iontophoretic treatment of a nail infection, a drug in contact with the delivery electrode, which is disposed on an infected nail area may be delivered into the nail. The inventors observed that if the drug in contact with the nail is also in contact with the surrounding skin, at least some if not most of the drug may be delivered through the skin instead of through the nail. This problem appears to be unique to active delivery to the nail. Presumably, this may be a result of the typically lower resistance exhibited by skin compared to nail and because a drug which is actively delivered will typically be delivered through the current pathway of least resistance. 
     In order to optimize delivery of an active agent into the nail, short circuiting through the skin should be avoided. 
     It would therefore be advantageous to have an iontophoresis device and method of use thereof which prevents delivery of the active agent through the skin and optimizes delivery of the active agent through the nail and into the nail, such as is provided by the present invention. 
     SUMMARY 
     Aspects of the invention include a nail treatment device for active delivery of an active substance to the nail. One aspect relates to a nail treatment device comprising an active delivery device for disposing on the nail and for promoting delivery of an active agent into the nail to treat a nail infection and at least one means for preventing delivery of the active agent to the skin. The device may be worn by a user and may deliver the active agent when mobile and/or when stationary. The device may include a skin mask. The skin mask may be integrally formed with the device or may be part of a kit comprising the skin mask and the nail treatment device. The skin mask may include a locator for accurate placement on the digit of a user. The treatment device may include a locator for disposing and/or suitably interconnecting with the skin mask locator for accurate application of the treatment device. 
     A further aspect relates to a nail treatment device comprising an active delivery device for disposing on the nail and for promoting delivery of an active agent into the nail to treat a nail infection and at least one means for preventing delivery of the active agent to the skin, wherein the at least one means for preventing delivery of the active agent to the skin comprises an electrode and/or formulation displacement prevention means. 
     An additional aspect relates to a nail treatment device comprising an active delivery device for disposing on the nail and for promoting delivery of an active agent into the nail to treat a nail infection and at least one means for preventing delivery of the active agent to the skin, wherein the at least one means for preventing delivery of the active agent to the skin comprises a means for separating the nail from the skin 
     In a still further aspect, the at least one means for preventing delivery of the active agent to the skin comprises an electrode and/or formulation displacement prevention means and a means for separating the nail from the skin. 
     Another aspect relates to a method of treating a nail infection comprising applying a nail treatment device on an infected nail, the nail treatment device comprising an active delivery device for disposing on the nail and for promoting delivery of an active agent into the nail to treat a nail infection and at least one means for preventing delivery of the active agent to the skin. In one aspect a skin mask with a locator means may be first applied onto the digit, after which the nail treatment device with a corresponding device locator may be applied over the skin mask such that the skin mask locator and the device locator correspond with each other and may be suitably interconnected and the treatment device is accurately placed on the digit. 
    
    
     
       BRIEF DESCRIPTION OF THE DRAWINGS 
       The various features of the invention will best be appreciated by simultaneous reference to the description which follows and the accompanying drawings and in which: 
         FIG. 1  shows schematically a device for iontophoretic delivery of an active agent into the nail according to one aspect of the present invention; 
         FIG. 2  shows schematically a device for iontophoretic delivery of an active agent into the nail according to one aspect of the present invention; 
         FIG. 3  shows schematically a device for iontophoretic delivery of an active agent into a nail, wherein the device is attached to a toe according to one aspect of the present invention; 
         FIG. 4  shows schematically a device for iontophoretic delivery of an active agent into the nail according to one aspect of the present invention; 
         FIG. 5  shows schematically a nail delivery device attached to a non-big toe according to one aspect of the present invention; 
         FIG. 6  shows schematically a kit including a device and a skin mask according to one aspect of the present invention; 
         FIG. 6   a  shows schematically a skin and nail separating means according to one aspect of the present invention; 
         FIG. 6   b  shows a schematic cross sectional view of part of the nail delivery device on the nail according to one aspect of the present invention; 
         FIG. 6   c  shows schematically a frame disposed on a toe of a user according to one aspect of the present invention; 
         FIG. 7   a  shows a schematic cross sectional view of part of the nail delivery device on the nail according to one aspect of the present invention; 
         FIG. 7   b  shows a schematic cross sectional view of part of the nail delivery device on the nail according to an aspect of the present invention; 
         FIG. 7   c  shows a schematic cross sectional view of part of the nail delivery device on the nail according to an aspect of the present invention; 
         FIG. 7   d  shows a schematic cross sectional view of part of the nail delivery device on the nail according to an aspect of the present invention; 
         FIG. 7   e  shows a schematic cross sectional view of part of the nail delivery device on the nail according to an aspect of the present invention; 
         FIG. 8  shows schematically a method of use of an iontophoretic delivery device for treatment of a nail infection according to one aspect of the present invention; 
         FIG. 9  shows schematically a method of use of an iontophoretic delivery device for treatment of a nail infection according to one aspect of the present invention; 
         FIG. 10  shows graphical representation of average changes in healthy toenail growth (mm) between each visit to visit 1 in Group A (Terbinafine &amp; Patch) and Group B (Terbinafine); 
         FIG. 11  shows graphical representation of frequency (N, %) of patients with distance changes above 1.5 mm from visit 1 by visit and treatment group; 
         FIG. 12  shows graphical representation of frequency (N, %) of patients with fungal elements in their nail specimen by visit and treatment group; and 
         FIG. 13  shows graphical representation of Terbinafine content (μg/cm 2 ) in nails at visit 4 and visit 5 by treatment group. 
     
    
    
     DETAILED DESCRIPTION 
     It was discovered that iontophoretic delivery of an antifungal agent into the nail is effective in the treatment of nail fungal infection such as but not limited to onychomycosis. In the context of the present application, the term “iontophoresis” means any method of electrical delivery of substances, including electrotransportation, iontophoresis, electroosmosis, electroporation, and/or a combination thereof. The term ‘antifungal’ as used herein refers to any substance or composition including same which is effective in treatment of a fungal infection. The term ‘active agent’ or ‘active substance’ as used herein refers to any pharmaceutical, drug, homeopathic agent, herb, vitamin, cosmetic or cosmeceutical. The term includes any substance which has a therapeutic, biological or aesthetic effect. The term ‘nail’ as used herein refers to a toenail or fingernail. The term may also refer to a claw, talon or animal nail equivalent. 
     As described above, a problem of active delivery of a substance to the nail using current when compared to active delivery of a substance to the skin is that due to the lower resistance of the skin, if the substance to be delivered or the delivery electrode is contacted with skin in addition to nail, the substance or most of the substance will be delivered to the skin and not to the nail. In order to optimize active delivery of an active substance to the nail, it is advantageous to avoid or limit contact of the main electrode and/or substance to be delivered with the skin. This problem is not encountered when the target delivery site is the skin and the formulation or the delivery electrode contacts the nail region. In addition, this problem is not characteristic of passive delivery of a drug to the nail, wherein the nail resistance and current pathway are not relevant. An additional problem, associated with contact of the main electrode with the skin, is that due to the relatively high resistance of the nail compared with the skin, a higher current density than used and tolerated on skin may be necessary in order to deliver an active substance into the nail. As such, if the electrode which is in contact with the nail also contacts the skin, the high current density may be harmful to the skin, causing burns. 
     Before explaining at least one embodiment of the invention in detail, it is to be understood that the invention is not limited in this application to the details of construction and the arrangement of the components set forth in the following description or illustrated in the drawings. The invention is applicable to other embodiments of being practiced or carried out in various ways. Also, it is to be understood that the phraseology and terminology employed herein is for the purpose of description and should not be regarding as limiting. 
     The principles and operation of a device according to the present invention may be better understood with reference to the figures. The figures show exemplary embodiments of the present invention and are not limiting. 
       FIG. 1  shows schematically a device for active delivery of an active agent to the nail  10  according to one aspect of the present invention. The device may be an iontophoresis delivery device. As can be seen from  FIG. 1 , the device  10  includes at least one power source  12 , at least one main electrode  14 , at least one counter electrode  16  and at least one means for preventing delivery of the active agent to the skin. The device may include at least one drug reservoir  20 . 
     The device  10  may be thin and flexible. The device  10  may be lightweight. In some aspects the device  10  may be less than about 1 mm thick. In one aspect, the device  10  may be less than about 0.5 mm thick. The device  10  may be flexible in order that it can conform to the contours of the digits and surrounding areas. In one aspect, the device  10  is for application for prolonged periods of time such as more than several hours. As such, the device  10  may be configured in order for the user to have substantially full mobility. In an alternative aspect, the device  10  may be any suitable active delivery device suitable for delivery of an active agent to the nail wherein the device further features at least one means for preventing delivery of the active agent to the skin.  FIG. 2  shows schematically a device for iontophoretic delivery of an active agent to the nail according to one aspect of the present invention, wherein the device is a plaster like patch device  10 . 
     The device  10  may be powered by any suitable power source  12 . A suitable power source may include at least one galvanic couple, which may comprise the at least one main electrode  14  and the at least one counter electrode  16  and/or at least one battery which may be integral to the device  10  or may be an external component. The power source  12  may be at least one thin and flexible battery. In one aspect the power source  12  may be a non-thin and flexible battery such as but not limited to a button battery or any type of battery. The power source  12  may be of any suitable voltage. In one aspect the power source  12  may provide up to about 40V. In one aspect the power source  12  is configured to supply any suitable current density, such as a current density of up to about 1000 μA/cm 2 . The power source  12  may be in electrical connection by any suitable means  22  with the counter electrode  16  and the main electrode  14 , which are disposed in spaced apart relation on a device body  24  or device frame  24 . The power source  12  may be disposed in any suitable region of the device  10 . In one aspect the power source  12  may be disposed in a part of the device to be disposed on the foot area. The size of the device  10  may be configured to accommodate the size of the power source  12  used. 
     The device may include any additional suitable electronic circuitry  25 , such as but not limited to a chip. The electronic circuitry may control the current and voltage. In one aspect the circuitry may facilitate constant current or constant voltage. In a further aspect, the circuitry may facilitate providing current which is not above a predetermined value. The device may be configured to provide any suitable current such as direct current, alternating current or pulsed current. 
     The main delivery electrode  14  and the counter electrode  16  may be any suitable electrode, made by any suitable technique. In one aspect, the main electrode  14  may include one or a plurality of holes  27  or other suitable openings. The hole  27  may facilitate releasing excess surplus formulation, when the device  10  is disposed on the nail. The device  10  may further includes a type of pad of absorbent material (not shown in  FIG. 1 ) disposed between the device frame  24  and main electrode  14 , which may absorb the released excess formulation. In such a way the excess formulation may be prevented from leaking from the nail to the skin. The size of the hole and the number of holes may be chosen so as not to affect the electrode function. In one aspect, the main delivery electrode  14  is for disposing on the infected nail and for delivering the active agent into the nail. The counter electrode  16  may be disposed on the device  10  such that on application onto a user it is disposed on any suitable non-nail area. In the device  10  shown in  FIG. 1 , the counter electrode  16  is disposed in the device  10  such that it will be disposed on the skin of the digit in the same plane as the active delivery electrode  14 . In one aspect, the counter electrode  16  may be configured such that it is in the same plane in a linear arrangement with the active electrode  14  and is further disposed to at least one side of the delivery electrode  14 . The size of the counter electrode  16  may be configured so that the electrode is thin and flexible and less prone to damage. In view that the device it not only wearable and configured for a user when stationary, but is also configured for full mobility of a subject, it is desirable that the electrode is sized for optimal thinness for comfort and also for the subject to be able to wear footwear such as a sock and shoe or equivalent over the device. If the counter electrode  16  is smaller, it may be bulky in order to facilitate the desired electrical requirements. Further, a counter electrode  16  which is configured around the sides as well as in a linear arrangement from the active electrode  14  facilitates optimal direction of current and multidirectional current for delivery of the active agent to a plurality of areas in the nail. In one aspect, hydrogel  26  (not shown in  FIG. 1 ) may be disposed on the main delivery electrode  14  and the counter electrode  16 . 
     The at least one means for preventing delivery of the active agent to the skin may comprise any suitable means for preventing contact of the main electrode  14  and formulation with the skin. The means for preventing contact of the main electrode  14  and formulation with the skin may include a movement electrode and/or formulation displacement prevention means  28 , for preventing displacement of the main electrode  14  and/or formulation on movement of the toe or foot. The means for preventing contact of the main electrode  14  and formulation with the skin may in addition feature a means for preventing contact of the formulation with the skin when pressure is applied to the affected region. The means for preventing delivery of the active agent to the skin may be configured such that the means does not hinder or prevent delivery of the active agent into the nail. 
     The device  10  may be configured so that when applied to a user, the user is able to be mobile or move the treated area. The device  10  may be of any suitable size, and on application of the device  10  on the nail, toe and foot regions of a user, the device may be disposed on the joints of the toes used in movement and walking. It was observed that a delivery device, which is configured so that it is disposed on the part of the toe and/or foot which is flexed on movement, resulted in pulling of the main electrode and/or formulation downwards, when the toe or foot was flexed or moved. This problem was especially prevalent with the big toe. A result of such movement was that the formulation was displaced and undesirably contacted with the surrounding skin area resulting in delivery of the active agent into the skin instead of the nail. One non limiting example of a suitable means for preventing displacement of the main electrode and/or formulation is a device aperture  28  or suitable opening in the device frame  24 , which on application of the device  10  on a user is disposed about the toe movement joint, such as the first metatarsal phalange joint of the toe. The device aperture  28  provides a solution to the movement displacement problem, resulting in a user being able to flex or move the foot and/or toe joint without putting strain on the device  10  and preventing displacement of the main electrode or formulation from the nail to the skin. The device aperture  28  may be sized and positioned in order that it does not interfere with the desired function of the device. 
       FIG. 3  shows schematically a device for iontophoretic delivery of an active agent into the nail  10  such as shown in  FIG. 2 , wherein the device  10  is attached to a toe  30  and the surrounding foot area  31  of a user. The device  10  shown in  FIG. 3  is attached to the big toe  30 . As can be seen from  FIG. 3  the device may include a device aperture  28 , which may be disposed in device  10 , such that when the device is applied to a user, the device aperture  28  will be disposed about the joint  33  of the toe  30 . 
     Other suitable means for enabling movement of the foot whilst ensuring that the delivery electrode and formulation are not displaced and contacted with the skin include use of elastic and stretchable material in at least the region of the device disposed on the toe foot joint. In an aspect wherein the device  10  includes stretchable material, the stretchable material may preferably not be placed on regions of the device where it may interfere with the desired function of the device, such as in the region of the main electrode or in any region of the device such that it will promote delivery of the formulation into the skin. 
     In an alternative aspect, the device  10  may be constructed such that the device is not disposed over the toe or foot movement joints. In such an aspect, the device may not need a movement electrode and/or formulation displacement prevention means  28 . 
     The joints in the smaller toes are not moved to the same extent as the big toe joint and therefore an aperture movement electrode/formulation displacement prevention means as described hereinabove may not be essential in the devices for treatment of the nails of the smaller toes.  FIG. 4  shows schematically a device  50  for iontophoretic delivery of an active agent to the nail according to a further aspect of the present invention. As can be seen from  FIG. 4 , the plaster like device  50  does not include an aperture electrode/formulation displacement prevention means for enabling movement of the foot as shown in the device of  FIGS. 1 ,  2  and  3 . The device  50  of  FIG. 4  is intended for application on one of the non-big, smaller toes. The other components of the device  50  are substantially as described for 10 hereinabove and below. The shape of the device  50  for the smaller toes may differ according to the ergonometry of the relevant foot area.  FIG. 5  shows the device  50  attached to the second toe. 
     One suitable means for preventing contact of the main electrode and/or formulation with the skin may feature at least one skin mask  32 . The skin mask  32  allows contact of the main electrode and/or formulation with the nail. As can be seen in  FIG. 1 , device  10  may include a skin mask  32 . A skin mask  32  may be any suitable means or separator for separating and/or preventing contact of the skin from the nail. In one aspect the skin mask may be disposed to cover and mask at least some of the skin surrounding a nail. In one aspect the skin mask or any alternative separator means may be disposed to mask some or all the skin surrounding the nail, but in such a way as to enable electrical contact between the power source and the counter electrode which may be disposed on the skin. The suitable means for separating and/or preventing contact of the skin with the nail may be disposed such that on use it would not be applied to the area of the toe where the counter electrode is to be contacted as this may prevent closing of the circuit with the counter electrode. In some embodiments, the skin mask will be disposed on the nail perimeter and the skin. Non-limiting examples of a suitable separator means or other means for separating and/or preventing contact of the skin with the nail include masking tape, a nail frame, nail varnish and combinations thereof. In one non-limiting example non-conductive nail varnish may be applied around the skin of the nail. The suitable separator or other means for separating and/or preventing contact of the skin with the nail may be constructed from a non-conductive material, which is substantially impermeable to the active agent formulation. 
     The skin mask or other suitable separator means may be an integral part of the device as shown in  FIG. 1 . Alternatively, the skin mask may be part of a kit as shown in  FIG. 6 . In an aspect wherein the skin mask is part of a kit, such as shown in  FIG. 6 , the skin mask  32  may be applied to the digit by a user before application of the device  10 . The skin mask  32  may include an aperture  52  which is suitable for exposing the nail part of the digit. The skin mask may include any suitable attachment means to attach to the skin, such as adhesive. The adhesive underside of the skin mask  32  may be protected before use by a liner (not shown in  FIG. 6 ). The skin mask may include a locator  54  and/or other suitable markings such that a user may correctly apply the skin mask  32  onto the toe. In one embodiment the locator  54  may be for placing on the perimeter of the nail and skin below the lunala, such as on the eponychium. The locator  54  may be a raised portion (a male part of the locator) of the mask. The skin mask  32  may be placed such that the raised portion  54  points upwards away from the digit. The device  10  may include a corresponding locator  56 , for corresponding and fitting with the skin mask locator  54 , for example an insert or aperture into which the raised portion of the skin mask locator  52  may fit. The type of locator is not intended to be limiting and any complimentary suitable locators may be used in the skin mask  32  and the device  10 . Use of a skin mask  32  as part of a kit may be advantageous, as it facilitates covering skin regions of the digit before application of the formulation. When the skin mask  32  is an integral part of the device  10 , the formulation may for any number of reasons contact the underside of the skin mask, before the device  10  has been applied to the user. Such contact would negate the function of the skin mask  32 . Use of a skin mask  32  with a locator  54  is advantageous as it aids a user to correctly apply the skin mask  32  and the device  10  to the nail and the digit. The skin mask locator  54  enables correct positioning of the skin mask  32  for optimal covering of the skin, while facilitating an uncovered nail region. The skin mask locator  54  further enables correct positioning of the device  10  on top of the mask  32  such that the electrodes and formulation are correctly disposed on the nail region. If the skin mask  32  or the device  10  is not applied accurately, the active electrode and/or the formulation may be placed such that they are disposed on the skin. Such incorrect positioning may prevent the device  10  from producing the desired therapeutic effect. Accurate positioning is therefore very important, however the small size of the nails on the digits prevents such precise positioning without the use of a suitable locator means. 
       FIG. 1  shows the device comprising a drug reservoir  20 . The suitable means for separating the skin from the nail may be integrated with the drug reservoir  20 . In an alternative aspect, the suitable means for separating and/or masking the skin from the nail may not be part of the drug reservoir  20 . 
     The drug reservoir  20  may be an integral part of the device  10 , such that the drug reservoir  20  may be built in to the device  10  or the device  10  may be supplied with the drug reservoir  20  attached in any suitable way to the device  10 . In one aspect the drug reservoir  20  is supplied separately from the device  10  and may be attached by a user to the device  10  or the nail before using the device  10 . The drug reservoir  20  may be disposed on the main delivery electrode  14 . The drug reservoir  20  may be disposed on a hydrogel  26  which is disposed on the main delivery electrode. 
       FIG. 6   a  shows schematically a skin and nail separating means according to one aspect of the present invention. The skin and nail separating means may be configured as a drug reservoir  20 . The reservoir  20  may include a nail frame  34  which may be in a ring conformation with a central nail frame aperture  36 . In some aspects, the nail frame  34  may not be part of the drug reservoir  20 . A skin and/or nail contacting surface  38  of the nail frame  34  may include any suitable adhesive for adhering the nail frame  34  to the area surrounding the nail to be treated. The nail frame  34  may be a means for framing or separating the skin from the nail in order to prevent the formulation and/or delivery electrode from contacting the skin. The nail frame  34  may be constructed from a non-conductive material, which is substantially impermeable to the active agent formulation. In one aspect, the nail frame  34  is made from polystyrene type foam. The nail frame  34  may be of any suitable dimensions such that the formulation can not seep under and/or over the sides of the nail frame  34  and such that the nail treatment area is not covered by the nail frame  34 . In one aspect the height  35  of the nail frame  34  is less than about 2 mm. In some aspects the height  35  is less than about 1 mm. The volume capacity of the nail frame aperture  36  may be up to about 5 cm 3 . In one aspect the volume capacity may be up to about 1 cm 3 . The nail frame  34  may include or have attached thereto tape  40  disposed on the sides of the nail frame  34  and/or around the nail frame  34 . In one aspect, the nail frame may be disposed on tape  40 . When the nail frame is disposed on tape  40 , it enables more facile removal of the device. The tape  40  may function in place of mask  32  described in  FIG. 1 . The tape  40  may be adhesive tape and may be one sided adhesive tape. In an aspect wherein the tape  40  functions instead of mask  32 , the tape  40  may be applied such that it covers and masks the skin on either side of the nail and may also function to further anchor the nail frame  34  around the nail. Alternatively, as shown in  FIG. 6   b  the tape  40  may function in addition to mask  32 . In the event of formulation  48  leakage, tape  40  which is suitable for disposing about mask  32  may restrict the leaked formulation between the mask  32  and tape  40  and prevent the formulation from contacting any of the device components. The masking tape  40  may be non-conductive and may be impermeable to the drug formulation. 
       FIG. 6   c  shows schematically the nail frame  34  disposed on a digit  30 . The device  10  or  50  may be disposed on the patient, such that the nail frame  34  is in contact with only the nail part  42  of the nail perimeter and the nail frame aperture  36  is disposed on the nail. The main delivery electrode and the active agent may be disposed within the nail frame aperture  36 . Optionally, in some aspects, the device  10  or  50  may be disposed on a user, such that the nail frame  34  is in contact with only the skin  44  surrounding the nail perimeter, or the nail frame  34  may be disposed such that it contacts part of the surrounding skin  44  around the nail and part of the nail part  42  of the nail perimeter. The position of the nail frame  34  on the digit  30  and nail  46  is very important and needs to be applied with precision. The device  10  and  50  may include markings and locator means on the non-body contacting surface of the device to enable easy correct application of the device including the nail frame  34 . 
       FIG. 7   a  shows a schematic cross sectional view of part of the nail delivery device on the nail according to one aspect of the present invention. From  FIG. 7   a , it can be seen that a nail frame  34  may be disposed on the nail  46  about a hydrogel  26 , wherein the hydrogel may be disposed on the main electrode  14 . The hydrogel  26  may be configured to absorb the applied formulation  48  and prevent the formulation  48  from contacting the skin area  44 . A mask  32  may be disposed at the sides of the nail frame  34 , such that the mask  32  covers at least part of the skin  44  and separates the skin from the nail  46 . 
       FIG. 7   b  shows a schematic cross sectional view of part of the nail delivery device on the nail according to an alternative aspect of the present invention. From  FIG. 7   b , it can be seen that the nail frame  34  is disposed on the mask  32 , such that the mask contacts the nail perimeter. 
       FIG. 7   c  shows a schematic cross sectional view of part of the nail delivery device on the nail according to a further alternative aspect of the present invention. From  FIG. 7   c , it can be seen that the part of the nail frame  34  is disposed on the mask  32 , such that part of the nail frame  34  and part of the mask  32  contact the nail perimeter. 
       FIG. 7   d  shows a schematic cross sectional view of part of the nail delivery device on the nail according to a further alternative aspect of the present invention. From  FIG. 7   d , it can be seen that the device includes a nail frame  34 , but does not include an additional mask  32 . 
       FIG. 7   e  shows a schematic cross sectional view of the part of the nail delivery device on the nail according to a still further aspect of the present invention. From  FIG. 7   e , it can be seen that a hydrogel  26  is disposed in such a way that it is disposed on the nail frame  34 . The hydrogel may be of a size such that it may be longer than the main electrode  14  or nail frame aperture. Part of the hydrogel which is disposed on the nail frame may not contact the nail or formulation. In such a way, the hydrogel  26  may be configured as a type of cover or cap to further prevent the formulation from leaking over the sides of the nail frame. 
     The formulation may be applied to the infected nail. Care must be taken that the formulation is not contacted with the skin. The formulation may be a gel, which may be applied accurately to the nail area, without contacting the surrounding skin area. Alternatively, the formulation may be preapplied to the device or may be applied to the device by a user, such that it is disposed within the nail frame. 
     In an aspect wherein the drug reservoir or formulation is supplied separately by a user, the invention provides a kit featuring the device and the separate formulation and/or reservoir and/or skin mask. 
     In one aspect the present invention provides a method of treating a nail infection. The terms ‘treatment’ ‘treat’ and ‘treating’ as used herein encompass any treatment of a nail infection, such as onychomycosis or psoriasis and includes: preventing the infection or disease from occurring in a subject which may be predisposed to the disease; inhibiting the infection or disease, i.e. arresting its development; and/or relieving the disease, i.e. causing regression of the disease. Relieving the disease means attaining improvement in the subject&#39;s condition, including, but not limited to clinical improvement, microbiological improvement and aesthetic improvement. 
     Non-limiting examples of active agents used to treat onychomycosis and which may be used with the present invention include terbinafine, naftifine, ketoconazole, fluconazole, itraconazole, terconazole, natamycin, nyastin, amphotericin B, 5-Fluorocytosine, bifonazole, chlortrimazole, econazole, fenticonazole, miconazole, oxiconazole, tolnaftate, ciclopirox, undecylenic acid, sulbentine and amorlifine in free base, ionic form, salt form or a derivative thereof. 
     Non-limiting examples of active agents used to treat psoriasis and which may be delivered to the nail with the device of the present invention include clobetasol, salicylic acid, tazarotene, calcipotriene, methotrexate, acitretin, cyclosporine, ibuprofen, naproxen, sulfasalazine, fluocinonide and triamcinolone in free base, ionic form, salt form or a derivative thereof. 
     The nail infection, such as onychomycosis or psoriasis may be treated by applying an iontophoresis device as described herein to the infected nail area. The device may include the formulation. In an aspect, wherein the formulation is not attached to the device, the formulation may be applied to the main electrode of the device or applied directly to the nail region to be treated. In one aspect, the formulation may be applied to a hydrogel disposed on the main electrode. After the formulation has been applied, (in an aspect where the device does not include the formulation), the device may be applied to the nail and foot area. The device is applied by ensuring that the nail frame as previously described is disposed on the digit and that the nail frame covers the perimeter of the nail. Slight pressure on the nail frame may adhere the nail frame to the area of the toe. The nail frame may include any additional adhesive means to ensure the correct positioning of the nail frame and formulation. The device may include adhesive means in order for the user to adhere the device to the surrounding skin. In a device for use with the big toe, wherein the device is to be disposed over a movement joint of the toe and/or foot, the means about the movement joints, such as a device aperture may be correctly positioned by a user. In some aspects, the device includes wings or other attachment means which can be disposed and adhered around the toe and foot. In an aspect wherein a skin mask is not integral with the device, the skin mask may be applied and adhered to the digit, such that the skin mask locator may be positioned on the eponychium. The mask may be adhered to the digit by adhesive or other attachment means on the device frame. In an aspect, wherein the formulation is not preapplied, the formulation may be applied to the reservoir of the device or to the nail. The device may then be applied to the digit, such that the device locator interlocks or equivalent thereof with the skin mask locator and the reservoir and main electrode are positioned on the nail. 
     In some aspects, the contact of the device with the body area causes closing of the circuit of the device with the nail and the current promotes delivery of the active agent from the formulation onto and into the nail for treatment of the nail. 
     The device may be removed from the body area at the end of the device application time. Time of application and frequency of treatment may vary and may be according to a treatment regimen. 
     In some aspects a pretreatment can be applied prior to use of the device. Non-limiting examples of pretreatments include applying a cleanser, applying a moisturizing composition, cutting nail, removing dry skin, hair removal, bathing, softening treatment, applying an anti-irritant, applying a permeation enhancer, heating, microporation, electrical stimulation, applying a formulation comprising a pharmaceutically active ingredient, applying a formulation comprising a cosmetically active ingredient or a combination thereof. 
     In some aspects a post treatment can be applied to the body area after application of the device. Non-limiting examples of post treatments include applying an occlusion formulation, applying a cleanser, cooling, applying a nail varnish, applying a formulation comprising a pharmaceutically active ingredient, applying a formulation comprising a cosmetically active ingredient or a combination thereof. 
     Use of the present invention can facilitate alleviation and elimination of the nail infection. Duration of effect can be affected by time and frequency of application, type and amount of current used, severity of condition and inactivation of the active agent delivered and present in the nail and matrix. The duration of the effect of the treatment may vary. Repeated use may have a synergistic effect on duration and extent of treatment result. 
       FIG. 8  shows schematically a typical treatment according to the present invention. The treatment area may be optionally pretreated ( 100 ) as described hereinabove. A device such as  10  or  50  or as described hereinabove may be provided. In an aspect, wherein the device does not include the formulation, the formulation may be applied onto the main electrode or onto an optional hydrogel disposed on the main electrode of the device and/or the formulation may be applied to the treatment area of the nail ( 200 ). The device may then be applied to the treatment area of the nail and/or surrounding skin area, such that a device nail frame is disposed around the perimeter of the nail to frame the nail and separate the skin surrounding region from the nail region and wherein the nail frame aperture is not disposed on the skin ( 300 ). At least one additional means for masking the skin from the nail may be applied, such as a masking tape for applying to the skin surrounding the nail and/or nail varnish. The device may be applied such that a digit or toe joint movement means if incorporated in the device is disposed about the movement joint of the digit, such as the toe ( 400 ). The device may be applied and adhered to the toe and foot area, such that the active electrode is disposed on the nail and the counter electrode is contacted with the skin and a circuit is completed through the nail, so that current promotes delivery of an active agent to the nail ( 500 ). The treatment device is contacted with the digit for a treatment time ( 600 ). The device and/or formulation may be removed from the treatment area after the treatment time ( 700 ). The treatment area may be optionally treated with a post treatment as described hereinabove. The same device, a different device or a different sample of the same device may again be applied and the treatment may be repeated at a suitable time interval ( 800 ). The treatment and the application of the device and/or formulation may be repeated according to need. 
       FIG. 9  shows schematically a treatment according to an aspect of the present invention. The treatment area may be optionally pretreated ( 900 ) as described hereinabove. A device such as  10  or  50  or as described hereinabove may be provided. In an aspect, wherein the device does not include the formulation, the formulation may be applied to the device reservoir and/or the formulation may be applied to the treatment area of the nail ( 910 ). A skin mask may be applied and adhered to the skin surrounding the nail, such that the nail region is exposed. The skin mask may be applied such that a locator on the skin mask is disposed about a suitable place on the digit, such as the eponychium ( 920 ). The device may then be applied over the skin mask. The device may be positioned such that a locator on the device fits into or onto the locator of the skin mask. The device may be applied such that a digit or toe joint movement means if incorporated in the device is disposed about the movement joint of the digit, such as the toe ( 930 ). The device may be applied and adhered to the toe and foot area, such that the active electrode is disposed on the nail and the counter electrode is contacted with the skin and a circuit is completed through the nail, so that current promotes delivery of an active agent to the nail ( 940 ). The treatment device is contacted with the digit for a treatment time ( 950 ). The device and/or formulation may be removed from the treatment area after the treatment time ( 960 ). The treatment area may be optionally treated with a post treatment as described hereinabove. The same device, a different device or a different sample of the same device may again be applied and the treatment may be repeated at a suitable time interval ( 970 ). The treatment and the application of the device and/or formulation may be repeated according to need. 
     In one aspect, the treatment may be configured for home use or any other non-supervised use. In other aspects, the treatment may be conducted in a supervised environment. 
     The device of the present invention is configured for optimal delivery of an active agent by iontophoresis to the nail and for preventing delivery of the active agent to the skin facilitating improved treatment of the nail infection. 
     Example 1 
     A clinical trial was conducted to evaluate delivery of terbinafine HCl with an iontophoretic device according to an aspect of the present invention in patients with toenail onychomycosis. 38 patients suffering from distal and lateral subungual toenail onychomycosis were enrolled into the study and were divided randomly into group A (20 subjects) and group B (18 subjects). Onychomycosis was confirmed by both KOH examination and mycological culture, wherein samples were taken from the distal parts of the nail. Nail samples were divided, one part being used for direct KOH examination and the second part for fungal culture using Sabouraud&#39;s Dextrose agar (Novamed, Jerusalem, Israel). The identification of the fungus was done on the basis of morphologic characteristics. 
     Group A was tested with 1% terbinafine HCl and an iontophoretic patch using a constant current density of 100 μA/cm 2 . Group B was tested with 1% terbinafine HCl without iontophoresis. Treatment period was overnight wear, every day, five days per week, for 4 weeks. During the treatment period visits were conducted every 10 days (visits 2-4). The follow-up period was 10 weeks from the end of treatment (visit 5). At each visit nail photography and KOH examination were performed. Routine blood test; complete blood count and liver functions tests were performed at the before study initiation, at the end of the treatment and at the end of the follow-up period. Terbinafine content in affected nail samples was determined by clipping nails at visits 4 &amp; 5. Nails were then weighed and cut into symmetric shapes in order to estimate their area. Symmetric shapes of nails were then cut into small pieces and inserted into tubes with 0.5 ml DDW. Subsequently, methanol 0.5 ml was added and tubes were sonicated. The eluted solution was analysed by HPLC. 
     A significant clinical response was recorded in group A patients treated with terbinafine under a constant current density of 100 μA/cm 2 . Patients from the active group A showed significant growth of healthy toenails ( FIGS. 10 and 11 ). The percentage of patients having healthy toenail growth above 1.5 mm at the end of treatment in group A was 40% compared to 11% in patients treated with terbinafine without current (passive group B). A significant mycological improvement was observed during and after treatment in patients in Group A, ( FIG. 12 ) whereby the percentage of patients having fungal elements (KOH) in nail specimens decreased significantly 10 weeks following the completion of treatment (15% in the active group A versus 53% in the passive group B). 
     Terbinafine (TBF) nail content was much higher at visit 4 among patients in the active group A (5.69 μg/cm 3 ) than in patients from the passive group B (1.34 μg/cm 2 ). Statistically significant differences were observed in mean values of terbinafine content in nail samples between treatment groups at visit 5 (p&lt;0.05) ( FIG. 13 ). At the end of the follow up period terbinafine nail content in the active group A was found to be 2.41 μg/cm 2 , compared to 0.15 μg/cm 2  in the passive group B. It was noted that the terbinafine content in Group A even at the end of the follow up period was considerably higher than terbinafine&#39;s minimal inhibition concentration (MIC) against dermatophytes (0.1 to 1.0 μg/cm 2 ). 
     The device of the present invention appears to deliver terbinafine in clinically effective amounts into the nail and is efficacious, safe and well tolerated for the treatment of nail onychomycosis. 
     Example 2 
     A nail treatment device without means for preventing delivery of the active agent to the skin was applied onto the big toes of a group of about 10 subjects. The subjects were allowed to move and walk about. The majority of the subjects suffered from burns on the skin, resulting from contact of high current density with the skin. The active electrode and/or formulation were found to have been displaced from the nail and to have contacted the skin of these subjects. A nail treatment device including means for preventing delivery of the active agent to the skin, such as a skin mask and an electrode and/or formulation movement displacement prevention means according to an aspect of the present invention was also tested on the big toes of a group of about 10 subjects. It was observed that none of the subjects suffered from burns or hot spots, indicating that the main electrode and formulation did not contact the skin. 
     Example 3 
     A nail treatment device was supplied to a group of subjects to self apply to the big toe. It was observed that each subject applied the device in a different way with non-accurate placement of the active electrode and formulation on the digit. The group of subjects was then give a nail treatment device with locator means according to an aspect of the present invention and it was observed that all the subjects applied the device and mask correctly, such that the active electrode and formulation were disposed on the nail and not on the skin of the digit. 
     One skilled in the art can appreciate from the foregoing description that the broad devices and techniques of the aspects of the present invention can be implemented in a variety of forms. Therefore, while the aspects of this invention have been described in connection with particular examples thereof, the true scope of the aspects of the invention should not be so limited since other modifications will become apparent to the skilled practitioner upon a study of the specification, and following claims.