Arrangements for providing transdermal delivery pathways into skin

Abstract

The present specification relates to arrangements for modifying a skin barrier provide transdermal pathways into the skin Such pathways can be used to improve ease of delivery of a wide variety of actives into the skin. In one aspect there is an arrangement for modifying a skin barrier, the arrangement comprising: - a substrate and a first skin modifier comprising a first and second electrode supported by the substrate, each of the first and second electrodes electrically isolated from one another; and - a second skin modifier, the second skin modifier different to the first skin modifier.

Description

[0001] TITLE

[0002] Arrangements for Providing Transdermal Delivery Pathways into Skin

[0003] BACKGROUND

[0004] The present specification relates to arrangements for modifying a skin barrier provide transdermal pathways into the skin. Such pathways can be used to improve ease of delivery of a wide variety of actives into the skin. Actives may comprise as examples only pharmaceutical compositions and anaesthetics.

[0005] Electroporation has previously been typically carried out by high voltage pulses applied to a pair of electrodes which are applied to a tissue surface. It has been thought that the electric pulses cause disruption to the tissue thereby providing new pathways through which a charged active applied topically to the skin can penetrate.

[0006] Aspects of the present invention provide improvements or at least provide a useful alternative.

[0007] SUMMARY

[0008] Aspects of the present disclosure are set out in the accompanying independent and dependent claims and in the following statements of invention. Combinations of features from the dependent claims may be combined with features of the independent claims as appropriate and not merely as explicitly set out in the claims. Combinations of preferred features described with respect to one aspect may also be combined with another aspect.

[0009] According to an aspect of the present disclosure there is an arrangement for modifying a skin barrier, the arrangement comprising a layered structure comprising:

[0010] a first electrode;

[0011] an insulator disposed onto the first electrode to leave the first electrode partially exposed;

[0012] a second electrode disposed onto the insulator;wherein the insulator is arranged to form an electrically insulating zone between the first and second electrodes.

[0013] Each of the first electrode, insulator and second electrode may comprise a respective skin contact surface or skin contact zone. A skin contact surface of the arrangement may be defined by at least the first electrode, insulator and second electrode.

[0014] Modification of the skin barrier enables improved ease of delivering an active through the skin barrier. Modification of the skin barrier may cause pathways to form through the skin barrier. The pathways may form by the effect of electroporation. The formation of the pathways is temporary and the pathways contract after terminating of application of a voltage across the first and second electrode. The arrangement therefore reduces the resistance to passage of substances into the adjacent tissue at least during application of current between the electrodes.

[0015] In any of the aspects according to the present disclosure an electric field is generated across a skin barrier which modifies the skin barrier. Current flows through the skin between the electrodes.

[0016] A benefit of such a configuration as defined having the layered structure is the ability to maximise the surface area occupied by either first or second electrodes. This in turn increases the current flow pathways between the respective first and second electrodes and thereby increases the disruption to the skin meaning an increased number of pathways present to allow more uniform delivery of the active.

[0017] The electrodes may have a thickness of from about 0.10 to about 0.30 mm.

[0018] The insulator may be printed onto the first electrode, and the second electrode may be printed onto the insulator. Printing enables electrodes and insulators to be deposited having minimal thickness, and this is beneficial in that surface variations in the skin contact surface of the arrangement is minimised. Alternative manufacturing techniques may be etching or laminating.The first electrode may be disposed onto a substrate. The first electrode is preferably printed onto a substrate.

[0019] The substrate may comprise a patch. The patch may be arranged to sit onto a wearer’s skin. The patch may be arranged to conform to the geometry of the body portion of the wearer. The patch is therefore beneficially arranged to be worn. The patch may be formed to accommodate a certain area of the body, for example in a complex body area such as a face. The patch may comprise a wrap or sock.

[0020] A plurality of patches may be connected in series for treating larger body areas.

[0021] The electrodes may be gold plated to be suitable for skin contact.

[0022] The arrangement may further comprise a power source comprising a first terminal electrically connected to the first electrode and a second terminal electrically connected to the second electrode. The power source may be connected to the first and second electrodes by a flexible umbilical. Thus, in some embodiments the power source may be moveable separately to the layered structure.

[0023] The power source may comprise an electrochemical cell. The voltage of the electrochemical cell may be between 0.5 and 10V, preferably 0.5 and 5V.

[0024] In some embodiments, it may be beneficial to enable modification of the applied electrical energy. This may be useful for efficacy for different user’s or may be beneficial to modify the feel for each user. For example, some users may find that a lower voltage is preferable to avoid any irritation, whereas other users may find that a higher voltage is comfortable without irritation, and thereby find that efficacy can be improved at higher voltages. A controller may be provided to enable modification of the delivery of the electrical energy (for example of the electrochemical cell (if present)).

[0025] The power source, preferably an electrochemical cell, may be disposed on the substrate.The arrangement may comprise a patch, and the power source such as the electrochemical cell may be disposed on the patch. It will be appreciated that one or more electrochemical cells may be provided as required.

[0026] At least one of the first and second electrodes may comprise an active deposited thereon. The active may be deposited onto the first and / or second electrodes by printing. The active can be deposited specifically on the skin contacting surface of the first and / or second electrodes. The active may further be provided on the insulator.

[0027] The active capable of being delivered may be charged and not charged substances. Electroporation does not deliver a charged substance, but rather reduces the resistance to passage of substances into the adjacent tissue. The active may take a variety of forms depending on the desired outcome for the user. The active may be a topical active.

[0028] The active may comprise one or more of:

[0029] a local pain relief such as EMLA;

[0030] a systemic pain relief active such as an opioid;

[0031] a vaccine;

[0032] a muscle relaxant such as BOTOX

[0033] a hair growth stimulator such as a topical vasodilator (e.g. minoxidil);

[0034] a sleep modifier such as melatonin;

[0035] a lypolytic fat burning compound such as caffeine; and / or

[0036] a collagen promoting substance such as retinol.

[0037] The active may comprise a first active and a second active, the second active different to the first active. The first and second actives may be deposited in first and second zones respectively, the first and second zones being separate from one another. The first and second zones may be adjacent one another. There may comprise multiple first and second zones. For example, it may be beneficial for the deposition of a first active comprising a vasodilator and a second active comprising a pain relief medication in generally adjacent locations. This may be for the purpose of firstly opening blood vessels to assist in absorption of the pain relief medication.The layered structure may comprise an adhesive deposited thereon. It will be appreciated that the adhesive should be biocompatible. An adhesive can be utilised to ensure that the patch skin contact surface.

[0038] The arrangement may comprise a third electrode, where the polarity of the third electrode is the same as one of the first or second electrodes.

[0039] The arrangement may further comprise a controller for controlling the electrical energy supplied to the first and second electrodes (meaning the electric field across the electrodes is controlled). The controller may be operable upon receipt from a remote signal, for example from an input from a user or medical practitioner. The arrangement may therefore further comprise a receiver for receipt of a signal for effecting operation of the controller.

[0040] Controlling of applied electrical energy may comprise switching between an on and an off state and / or changing the polarity and / or modification of the voltage across the electrodes and / or modification of the current and / or modification of the frequency.

[0041] The arrangement may further comprise a third electrode, the controller arranged to control applied electrical energy between the first electrode and the second or third electrode. The controller may be arranged to switch the current to selectively enable a current flow pathway between the first electrode and the second electrode or first and third electrode. The controller may be configured to enable a current flow pathway between the first electrode and second electrode and first electrode and third electrode concurrently. The controller may be configured to enable a current flow pathway between the first electrode and second electrode and first electrode and third electrode sequentially.

[0042] It will be appreciated that the arrangement may comprise further electrodes. This plurality of electrodes (whether three or more) effectively enables multiple different zones to be activated at different times or with different electrical potential or in varying sequences.

[0043] The third electrode if present may be disposed on the insulator. The third electrode may be disposed in a side-by-side configuration relative to the second electrode.The first active may be disposed on the second electrode and the second active may be disposed on the third electrode. This effectively enables different actives to be administered using the same arrangement (such as a patch) by controlling current pathways.

[0044] The insulator may be disposed on the first electrode such that a plurality of first electrode skin contact zones are exposed. The plurality of first electrode skin contact zones are beneficially distinct from one another.

[0045] The insulator may be disposed across the first electrode in a plurality of insulating regions, wherein the second electrode is disposed on one or more of the plurality of insulating regions. This has the effect of separating the first electrode into a plurality of distinct first electrode skin contact zones.

[0046] The insulator may comprise a primary insulator, and wherein the layered structure comprises a secondary insulator disposed onto the second electrode, primary insulator and first electrode such that at least a part of the first electrode and second electrode is exposed.

[0047] A part of the second electrode may be disposed on the secondary insulator. A third electrode may be disposed on the secondary insulator.

[0048] The arrangement may further comprise a sensor for sensing a parameter of the skin. On the basis of such sensed parameter, operation of the arrangement may be modified. For example, the power source may be disconnected from the electrodes either temporarily or permanently, or the voltage may be modified. The sensor may be carried by (and may be printed onto) the layered structure. An example sensor may be arranged to measure the Trans Epidermal Water Loss (TEWL). This is a standard process that measures the amount of water vapour being released via the skin. Higher water vapour means the skin barrier has been compromised; less water vapour means good barrier function. This could be a closed-loop system, and as the water vapour increases, the power delivered could be altered or removed.

[0049] The controller may control modification of operation of the arrangement.

[0050] The sensor may comprise a diagnostic sensor, and on the basis of the sensed input, operation of the arrangement may be modified.The first and second electrode may comprise a first skin modifier, and the arrangement may comprise a second skin modifier different to the first skin modifier. The second skin modifier may be supported by the substrate. The second skin modifier may comprise a heating arrangement and / or a microneedle portion and / or a light emitter. The second skin modifier may further assist action of delivery of an active into the skin.

[0051] According to a second aspect, there is an arrangement for modifying a skin barrier, the arrangement comprising:

[0052] o a plurality of electrodes;

[0053] o a power source for supplying a voltage across a first electrode pair and a second electrode pair of the plurality of electrodes;

[0054] o a controller configured to control the voltage across the first electrode pair and second electrode pair.

[0055] Preferred features of the first aspect are equally applicable to the second aspect, as are the associated benefits described. As examples, the plurality of electrodes and optionally the power source are disposed on a substrate. The substrate may comprise a patch. The power source may comprise an electrochemical cell. The applied voltage is suitable for generating an electric field between the first and second electrodes.

[0056] The controller may control the voltage to selectively enable a current pathway between the power source and the first electrode pair or between the power source and the second electrode pair.

[0057] The first and / or second electrode pair may comprise an active deposited thereon.

[0058] One or both of the electrodes of the first electrode pair may comprise a first active thereon, and one or both of the second electrode pair may comprise a second active thereon, the first active different to the second active.

[0059] Suitable actives are described elsewhere in the specification and are equally applicable for this aspect.The first electrode pair may comprise a first electrode and a second electrode, and the second electrode pair may comprise the first electrode and a third electrode. The second and third electrode may be disposed (preferably printed) onto the first electrode.

[0060] The first, second and third electrodes may define a skin contact surface. The skin contact surface may further be defined by an insulator arranged to electrically insulate the first, second and third electrodes from each other.

[0061] The controller may be arranged to modify the current to control a current flow pathway between the first electrode and the second electrode and / or the first electrode and the third electrode.

[0062] The controller may be configured to selectively enable a current flow pathway between the first electrode and the second electrode or the first electrode and the third electrode. The controller may include a switching arrangement to control current flow between the first electrode and the second electrode or the first electrode and the third electrode.

[0063] Such a configuration enables independent control in terms of zones of the arrangement such as a patch and the time that these zones are activated.

[0064] According to a third aspect there is an arrangement for enabling improved delivery of an active through skin, the arrangement comprising:

[0065] o a substrate;

[0066] o a first and second electrode supported by the substrate, each of the first and second electrodes electrically isolated from one another;

[0067] o an active for delivery through the skin, the active printed onto the first and / or second electrodes.

[0068] Suitable actives are described elsewhere in the specification and are equally applicable for this aspect.By printing the active onto the first and / or second electrodes the amount of active can be carefully controlled. Furthermore, the location on the arrangement can also be carefully controlled.

[0069] Optional features described elsewhere in the statements of invention presented with respect to other aspects are equally applicable to this aspect. As an example only, the substrate may comprise a patch.

[0070] According to a fourth aspect an aspect of the present disclosure there is an arrangement for modifying a skin barrier, the arrangement comprising:

[0071] o a first electrode wound helically having a plurality of turns with a separation gap between the turns, the first electrode defining a skin contact surface; o a second electrode would helically and disposed in the separation gap between the turns of the first electrode, the second electrode defining a second skin contact surface, the second electrode electrically isolated from the first electrode;

[0072] o a substrate for supporting the first and second electrodes.

[0073] The second electrode may comprise a plurality of turns. The turns of the first and second electrodes are electrically insulated from one another. The first and second electrodes may be printed onto the substrate. The first electrode may be deposited onto the substrate, an insulator may be deposited onto the first electrode having a plurality of helical turns, and the second electrode may be deposited onto the insulator, The structure may therefore be layered.

[0074] The substrate may comprise a patch as described with respect to other embodiments and may further comprise a power source.

[0075] According to a fifth aspect of the present disclosure there is a hairbrush comprising a body having an array of bristles extending therefrom, the bristles each having a distal end, wherein a plurality of the distal ends comprise first electrodes and a plurality of the distal ends comprise second electrodes, the first and second electrodes being electrically isolated from one another, the hairbrush being configured in use to generate an electric field between the first and second electrodes.The hairbrush may comprise a first terminal for connection to the plurality of first electrodes and a power source and a second terminal for connection to the plurality of second electrodes and the power source. The hairbrush may further comprise a power source. The power source may comprise an electrochemical cell. The voltage of the electrochemical cell may be between 0.5 and 5V.

[0076] The first and / or second electrodes may comprise an active thereon.

[0077] According to a sixth aspect, there is a bristle for a hairbrush comprising a proximal end for engagement with a hairbrush body extending to a distal end, where the bristle comprises a first electrode and a second electrode electrically isolated from the first electrode.

[0078] The bristle is arranged to enable an electric field between the first and second electrodes when the first and second electrodes are connected to a power source.

[0079] The first and second electrodes may extend axially between at least a portion of the distance between the proximal and distal ends. An insulator may extend axially intermediate the first and second electrodes. The first electrode may comprise an external surface of at least a portion of the bristle. The second electrode may comprise a core region, having an exposed region at the distal end. The first electrode may comprise a first outer annulus. The insulator may comprise a second annulus radially inwardly of the first annulus. The second electrode may comprise a core. The second electrode may have an axially exposed surface. The second electrode may have no exposed radial surface. The first and second electrodes may each have a respective first and second terminal for connecting to a power source.

[0080] There may further comprise a hairbrush comprising a plurality of bristles as defined.

[0081] According to a seventh aspect of the present disclosure there is an arrangement for modifying a skin barrier, the arrangement comprising:

[0082] a band;

[0083] a first electrode supported by the band;

[0084] a second electrode supported by the band and being electrically isolated from the first electrode;the arrangement being configured in use to generate an electric field between the first and second electrodes.

[0085] The band may comprise a loop. The band may be elastically deformable. The band may be arranged to deform to accommodate the body geometry of a wearer.

[0086] Preferred features of other aspects are equally applicable to the sixth aspect.

[0087] According to an eighth aspect, there is an arrangement for modifying a skin barrier, the arrangement comprising:

[0088] o a substrate;

[0089] o a first and second electrode supported by the substrate, each of the first and second electrodes electrically isolated from one another;

[0090] o a controller for controlling delivery of electrical energy to the first and second electrodes.

[0091] The voltage across the first and second electrodes is therefore controlled. The electric field across the electrodes is therefore also controlled, and thus the current through the skin is also controlled). Control of the electrical energy delivery enables control of delivery of an active. The active may be applied to at least the first and / or second electrodes. The first and second electrodes define respective skin contact surfaces.

[0092] The controller may be operable upon receipt from a remote signal, for example from an input from a user or medical practitioner. The arrangement may therefore further comprise a receiver for receipt of a signal for effecting operation of the controller.

[0093] Controlling of applied electrical energy may comprise switching between an on and an off state and / or changing the polarity and / or modification of the voltage across the electrodes and / or modification of the frequency of applied voltage.

[0094] The arrangement may further comprise a sensor for sensing a parameter of the skin. On the basis of such sensed parameter, operation of the arrangement may be modified. For example, the power source may be disconnected from the electrodes either temporarily or permanently, or the voltage may be modified. The sensor may be carried by (and may beprinted onto) the substrate. An example sensor may be arranged to measure the Trans Epidermal Water Loss (TEWL). This is a standard process that measures the amount of water vapour being released via the skin. Higher water vapour means the skin barrier has been compromised; less water vapour means good barrier function. This could be a closed-loop system, and as the water vapour increases, the power delivered could be altered or removed.

[0095] The sensor may comprise a diagnostic sensor, and on the basis of the sensed input, operation of the arrangement may be modified.

[0096] The arrangement may comprise a second skin modifier supported by the substrate different to the first skin modifier. The second skin modifier may comprise a heating arrangement and / or a microneedle portion and / or a light emitter. The secondary skin modifier may further assist action of delivery of an active into the skin. The light emitter may comprise one or more LED light sources.

[0097] The substrate may comprise a patch. The patch may be for positioning onto a user and may be arranged to be flexible to accommodate the contours of the body.

[0098] According to a ninth aspect, there is an arrangement for modifying a skin barrier, the arrangement comprising:

[0099] o a substrate and a first skin modifier comprising a first and second electrode supported by the substrate, each of the first and second electrodes electrically isolated from one another; and

[0100] o a second skin modifier, the second skin modifier different to the first skin modifier.

[0101] The second skin modifier may be supported by the substrate.

[0102] The second skin modifier may comprise a heating arrangement and / or a microneedle portion and / or a light emitter. The secondary skin modifier may further assist action of delivery of an active into the skin.

[0103] It will be appreciated that features of the other aspects are equally applicable to being preferred features of the ninth aspect. For example, an active may be applied to at least thefirst and / or second electrodes. The first and second electrodes may be positioned and configured as per preferred features of any other aspects.

[0104] The arrangement may comprise a device such as handheld device, and preferably a handheld portable device. The device may be termed a skin treatment device. The substrate may be defined by a device body, and the first and second electrodes are supported by the body. The device body may be handheld and may include control functionality of the first and second skin modifiers.

[0105] The second skin modifier may comprise one or more Light Emitting Diodes (LEDs). The second skin modifier may comprise an LED array. It has been determined that the combined provision of LED light together with the first and second electrodes capable of generating an electric field therebetween enhances the ability for an active to provide its associated beneficial effect to the skin. This has been determined to be greater than either the application of an electric field or LED light alone. The electric field provides the pathways into the skin barrier, and the LED energises the skin cells thereby improving uptake of an active.

[0106] The LEDs may emit light having a wavelength range including one or more of 630-660nm (red), 400-470nm (blue), and 590-620nm (orange / yellow). The effect of LED light on the skin energises skin cells, and the specific effect varies depending on the wavelength. For example, LED light in the red wavelength range has particularly beneficial effect upon collagen production through known mechanisms such as increased ATP production. LED light in the orange / yellow region penetrates the upper dermis and provides energy to skin cells, with blue LED light having similar effects.

[0107] According to any aspect, the active may be carried by a carrier, where the carrier is releasably connectable to the substrate. The carrier may for example secure to the substrate to maintain the active in contact with the electrodes.

[0108] It will be appreciated that arrangements as described with respect to any aspect may further comprise further functionality. For example, the arrangements such as patches, hairbrush, band or alternatives may include LED’s, microneedles, radio frequency emitters, vibration modules and or thermal sources for application of either heat or cooling effects.BRIEF DESCRIPTION OF THE DRAWINGS

[0109] Embodiments of this disclosure will be described hereinafter, by way of example only, with reference to the accompanying drawings in which like reference signs relate to like elements and in which:

[0110] Figure 1 shows a cross sectional schematic representation viewed from the side demonstrating the effect of use of an arrangement according to an embodiment of this disclosure on the skin;

[0111] Figure 2 is a schematic cross sectional representation viewed form a side of an arrangement according to an embodiment of the present disclosure;

[0112] Figure 3 is a schematic cross sectional representation viewed form a side of an arrangement according to an embodiment of the present disclosure;

[0113] Figure 4 is a schematic plan view viewed from a skin contact side of an arrangement according to an embodiment of the present disclosure;

[0114] Figure 5 is a schematic representation of an arrangement according to an embodiment of the present disclosure;

[0115] Figure 6 is a schematic representation of an arrangement according to an embodiment of the present disclosure as presented in Figure 5 with an active deposited thereon;

[0116] Figure 7 is a schematic representation of an arrangement according to an embodiment of the present disclosure as presented in Figure 5 with active deposited in zones thereon;

[0117] Figure 8 a schematic representation of an arrangement according to an embodiment of the present disclosure;

[0118] Figure 9 a schematic representation of an arrangement according to an embodiment of the present disclosure;Figure 10 a schematic representation of an arrangement according to an embodiment of the present disclosure;

[0119] Figure 11 is a schematic representation of an arrangement according to an embodiment of the present disclosure;

[0120] Figure 12 is a schematic representation of an arrangement according to an embodiment of the present disclosure;

[0121] Figure 13 is a schematic representation of an arrangement according to an embodiment of the present disclosure;

[0122] Figures 14 a and b are a schematic representation of an arrangement according to an embodiment of the present disclosure in a first and second operable configuration;

[0123] Figure 15 a schematic representation of an arrangement according to an embodiment of the present disclosure;

[0124] Figure 16 a schematic representation of an arrangement according to an embodiment of the present disclosure;

[0125] Figure 17 a schematic representation of an arrangement according to an embodiment of the present disclosure;

[0126] Figures 18a and b are a schematic representation of arrangements according to an embodiment of the present disclosure;

[0127] Figure 19 is a schematic representation of an arrangement according to an embodiment of the present disclosure;

[0128] Figure 20 is a schematic representation of a hairbrush bristle;Figure 21 a schematic representation of an arrangement according to an embodiment of the present disclosure;

[0129] Figure 22a and b are schematic representations of an arrangement according to an embodiment of the present disclosure.

[0130] Figure 23 is a schematic representation of an arrangement according to an embodiment of the present disclosure.

[0131] DETAILED DESCRIPTION

[0132] Embodiments of this disclosure are described in the following with reference to the accompanying drawings.

[0133] Figure 1 shows a cross-sectional schematic representation viewed from the side of an article demonstrating the effect of use of an article on the skin. The article may be referred to as a patch, however it will be understood that a patch may take numerous different forms and encompasses any article that is suitable for being positioned against a user’s skin. Such articles may comprise for example sheets, bandages, sleeves or pads.

[0134] A purpose of patch 2 is to enable improved transdermal delivery of an active such as a a drug or anaesthetic. The active may be anything that is desired to penetrate the barrier provided by skin. The movement of actives transdermally is improved by a process believed to be electroporation. Electroporation is typically carried out by a voltage applied across a pair of electrodes which are in communication with the skin. The applied voltage and current pathway through the skin providing improved pathways for the passage of actives. Utilising the effects of electroporation actives do not need to be charged, although charged actives are capable of passing through the skin barrier utilising the present invention.

[0135] Referring to Figure 1 the effect of application of a voltage to the skin and delivery of actives is shown. The patch 2 has been shown as a layered structure, however it will be appreciated that this is not essential for all embodiments, where instead electrodes can be in a spaced apart side by side configuration. However, Figure 1 is used to demonstrate the effect of electroporation on the skin. It will be appreciated that Figure 1 is schematic in nature, andin reality the electrodes will be in contact with the skin and there are no spaces between the layers.

[0136] The patch shows a positively charged first electrode 4 acting as the anode spaced apart from a negatively charged second electrode 6 acting as the cathode with an insulator 8 therebetween. A topical active 10 is disposed between one or both of the first and second electrodes 4,6, and the layers of the skin are presented with dashed lines 12. The insulator and first and second electrodes define a skin contact surface. Application of a voltage across the first and second electrodes 4,6 causes current to flow through the skin 12 and active 10 as indicated by the arrows 14 having the effect of temporarily disrupting the skin barrier and providing pathways into the skin. Active 10 can then pass through these pathways and into the skin barrier as indicated by arrows 16. Whilst it has been described that the first electrode is positively charged and the second electrode negatively charged, this polarity can readily be reversed without affecting the efficacy of the patch 2.

[0137] Figure 2 is a schematic representation of a cross-sectional side view of a patch 2 with the insulator 8 printed onto the first electrode 4, and the second electrode 6 printed onto the insulator 8. The active 10 is then printed onto a skin contact surface defined by the first and second electrodes 4,6 and insulator 8.

[0138] Figure 3 is a schematic cross sectional side view of an embodiment including a substrate 20 onto which the first electrode 4 is printed. Further presented is a power source comprising an electrochemical cell 22 electrically connected by first and second terminals to the respective first and second electrodes 4,6. Again it will be appreciated that the thickness of the printed electrodes, insulator and active is minimal and the substrate, electrodes and insulator together define a substantially planar skin contact surface.

[0139] Figure 4 is a schematic representation of a patch 2 viewed in plan from the direction of the skin contact surface of the patch 2. The electrode and insulator arrangement providing the regions for modifying the skin barrier are schematically represented as the region 24. An active may be deposited on the region 24. In this embodiment, there is an onboard power source in the form of an electrochemical cell 22. The arrangement can therefore form a standalone patch that can be adhered to a user’s skin (by for example a strap or adhesive) without impeding a user’s mobility.Figure 5 is a schematic representation of an arrangement according to an embodiment of the present disclosure. In this embodiment there is a first electrode 4, second electrode 6, with an insulator 8 electrically isolating the first and second electrodes 4,6 from each other. In such an embodiment the arrangement can be layered such that either the first electrode 4 and insulator 8 is disposed for example by printing onto the second electrode 6. Alternatively, the second electrode 6 and insulator 8 can be disposed for example by printing onto the first electrode 4. In the alternative, layering is not required and the electrodes are disposed onto a separate substrate (not shown).

[0140] In this embodiment, insulator 8 wholly encircles the first electrode, and the second electrode wholly encircles the second electrode. In this way, there are multiple short current pathways between the first and second electrodes, and it has been determined that the effect of barrier disruption is not limited to the area directly adjacent to the border but occurs across the area of the first electrode 4.

[0141] A power source (not shown) will be connected to the first and second electrodes respectively. The polarity can be selected and permanently set or may be modified as appropriate with a controller such as described with respect to another embodiment.

[0142] It will be further appreciated that an active may be disposed onto the complete or part of the first electrode 4, complete or part of the second electrode 6, or any other combination. This is schematically presented in Figure 6 where active 10 is applied (by printing for example) across the entirety of the first and second electrodes and insulator. It will be appreciated that an active can be applied in this way to any of the other embodiments described herein.

[0143] Referring to Figure 7 and 8, there is a schematic representation of the same arrangement as presented in Figures 5 and 6, however in this embodiment active is deposited onto the first and / or second electrodes in distinct zones. It will be appreciated that these zones can be selected as appropriate for the user and the active to be delivered. Again, it will also be appreciated that active can be printed onto the arrangement. Such zones can also be utilised with any of the other embodiments presented.The active 10 may comprise multiple different actives having different effects. For example, as presented in Figure 8, there is a first active 10a and a second active 10b, the second active 10b different to the first active 10a. The different zones in which the actives 10a, b are deposited are schematically presented as being separate from one another and distinct, however they may be adjacent. An example of this would be enhancing the activity of a systemic pain medication or CBD type active 10a. A vasodilator active 10a such as niacin can be applied to the first zone 10a to open up the blood vessels ready for increased speed of delivery of the second active 10b such as a pain relief medication or CBD type active.

[0144] Another example could be where active 10a is anti-inflammatory and active 10b could be a lypolytic compound (breaks down fat). Caffeine is a good example. It is a proven lypolytic but poorly absorbed into skin. To get enough into the skin, a very high concentration has to be applied to the surface of the skin - but this causes inflammation and irritation. So, active 10a could be a corticosteroid to suppress inflammation and irritation then caffeine 10b delivered as active 10b.

[0145] Another example could be in skin rejuvenation whereby it is desirable for multiple different effects. It is desirable to recruit and activate fibroblasts in the skin to produce new collagen. This can be achieved by triggering the release of TGF Beta from the blood cells via a retinoic acid (retinol). Once the fibroblasts have been recruited and activated, it is desirable to maintain activity for as long as possible and this can be done by applying vitamin C. Active 10a may therefore be retinol and active 10b could be vitamin C.

[0146] Referring to Figure 9, a schematic representation of an arrangement for increasing delivery of an active through skin is presented. In this embodiment the arrangement comprises a layered structure which may be achieved by printing the layers. This embodiment is similar to that described with respect to Figure 5, however in this embodiment the insulator 8 is disposed on the first electrode 4 such that a plurality of first electrode skin contact zones 4a, 4b are exposed. The zones 4a, 4b are separated from one another by an insulating region 36 printed onto the first electrode 4 which is in addition to the insulating region 8. Additional second electrode 38 is then printed onto the insulating region 36 and electrically communicates with the surrounding second electrode region 8. By separating theelectrode regions, there are more current pathways between the positively and negatively charged electrodes, thereby modifying the effect of the arrangement on the skin barrier.

[0147] As with other embodiments presented, active(s) may be printed on the whole or part of the skin contact surface of the arrangement as presented schematically. It will further be understood that the polarity can be changed as desired.

[0148] Referring now to Figure 10 which builds on the embodiment presented in Figure 9, the insulator is disposed across the first electrode 4 in a plurality of insulating regions 36a-d, wherein the second electrode 6 is disposed on the plurality of insulating regions. This has the effect of separating the first electrode 4 into more (five as shown in Figure 10) distinct first electrode skin contact zones 4a-e. This further increases the current pathways and therefore the consistency of modifying the skin barrier to enable improved transdermal delivery of active.

[0149] Referring to Figure 11, there is a further development on the embodiment of Figure 10. In this illustrative embodiment, the insulator 8 comprises insulating regions 36a-d as shown in Figure 10. The second electrode 6 is disposed, preferably by printing, onto the insulating regions 36a-d which may be termed a primary insulator. Over the layered structure formed is provided, again via printing, a secondary insulator 38a-d disposed onto the second electrode, primary insulator and first electrode 4 such that at least a part of the first electrode and second electrode 6 is exposed. The secondary insulator is presented in the illustrative embodiment as five insulating strips perpendicular to the strips of the primary insulator 36a-d, however there are numerous alternative configurations available. The second electrode 6 is printed onto the strips of the secondary insulator, thereby adding further current flow pathways between the first and second electrodes.

[0150] In an alternative configuration, the electrode printed onto the strips of the secondary insulator may be a third electrode and may be independently connected to a common or different power source and may be operated either concurrently or at different timings to the second electrode 6. Again, active may be disposed over part or the entire skin contact surface of the arrangement presented.Referring now to Figure 12, the same features are generally present and as described with respect to Figure 5 comprising a first electrode 4. Onto the first electrode 4 is printed a insulator 8 and onto the insulator 8 is printed a second electrode 6. In the illustrative embodiment of Figure 12, there is a further electrode 40 also printed onto an insulator having the same polarity as the second electrode 6. Such a configuration provides numerous current pathways between the first and second electrodes and also first and third electrodes, thereby enabling consistency of modification of the skin barrier across the skin contact surface enabling improved consistency of transdermal active delivery.

[0151] Referring to Figure 13, a controller 44 is provided for controlling current between a power source 22 and the first and second electrodes 4,6. In this embodiment, there is an electrode configuration as presented in Figure 12, where there is an additional third electrode, and where the controller controls the current between the power source 22 and the second electrode and the current between the power source 22 and the third electrode 40.

[0152] A current pathway is defined from the power source to both the second and third electrodes 6,40 and in an implementation the controller 44 is arranged to operate switches 46 within these current pathways to selectively enable a current flow pathway between the first electrode 4 and the second electrode 6 or third electrode 40. This functionality allows different areas of a patch having the respective electrodes to be activated at different times for example. The different electrodes can carry a different active.

[0153] The controller 44 may also be configured to modify the voltage across the power source 22 thereby affecting the current passing between the first electrode 4 and the second and / or third electrode 6,40. This can be beneficial to tailor the treatment for a specific individual for example if the individual feels discomfort.

[0154] It will be appreciated that the controller 44 has been introduced with respect to this embodiment having both second and third electrodes 6,40, however a controller 44 is beneficial in arrangements utilising first and second electrodes 4,6 for switching the power source 22 on and off which may be at predetermined times and / or time intervals for example. The controller 22 may also be used to modify the voltage.Referring to Figure 14a and b, in such a configuration the controller enables the polarity of the first electrode 4 relative to the second and third electrodes 6,40. The controller issues control signals to the switches 46 at the power source such that in Figure 14a for example the first electrode 4 is the anode and the second and third electrodes are the cathodes. In Figure 14b the switches 48 are switched upon receipt of an input from the controller 44 thereby enabling the electrodes 6,40 to become the anode and electrode 4 to become the cathode.

[0155] Referring to Figure 15, an arrangement according to an illustrative embodiment is presented. In this embodiment there is a patch having at least a first and second electrode structure as described elsewhere. Further provided is a controller 44 and power source 22. In this embodiment, presented is a communication link between the controller 44 and external communications represented by arrow 50. The external communications may communicate via a wired or wireless link to enable input to the controller to affect the activity of the patch. Accordingly, based on an external input, the patch may be switched between an on and an off configuration that causes current to flow between the electrodes. This may be desirable for example based on a user input (whether patent or medical practitioner for example) as to whether an active should be delivered at that time.

[0156] It will be appreciated that in any of the embodiments described the power source may be formed as part of a patch that sits in an arrangement against a wearer allowing ease of portability and mobility for the user. In an alternative the power source may be connected via a flexible umbilical. If forming part of a patch particularly, it is beneficial if the power source is printed for reduced size and weight. In some embodiments the patch is disposable or single use.

[0157] A further feature of any of the embodiments provided with the provision of control facility is the ability to sense parameters of the current for example. Based on the sensed information, operational parameters can be modified. Such operational parameters could be connecting and disconnecting the power source from the electrodes, connecting and disconnecting for specific time frames, and active voltage control as examples only. An example of this is presented in Figure 16, which is a schematic side view representation of a layered structure having a further sensor arrangement 54. The sensor arrangement may be printed onto one or more of the layers and further defines a portion of the skin contact surfaceof the arrangement. The sensor arrangement comprises one or more sensors for measuring a skin parameter as indicated by arrows 56, and based on this an operational parameter may be modified. As an example only, the sensor may monitor skin temperature, and if a threshold skin temperature is reached then the power source is disconnected from the electrodes.

[0158] Referring to Figure 16, a layered structure is shown with a first electrode 4, second electrode 6 separated by an insulator (not shown) onto which is printed an active 10. This is illustrative only however and any other electrode configurations could be utilised without printed active.

[0159] Further provided in the illustrative embodiment of Figure 17 is a diagnostic sensor 58 and on the basis of the input to the sensor 58 the current pathway or output to the electrodes can be modified by the controller (not shown). The sensor could be printed onto the layered structure. An example sensor may be arranged to measure the Trans Epidermal Water Loss (TEWL). This is a standard process that measures the amount of water vapour being released via the skin. Higher water vapour means the skin barrier has been compromised; less water vapour means good barrier function. This could be a closed-loop system, and as the water vapour increases, the power delivered could be altered or removed. Another sensor could be optical measuring the skin colour for blood flow. A topical cream such as EMLA ™ is applied to the surface for reducing pain from needle insertion and contains two active substances called lidocaine and prilocaine. As the EMLA becomes active in the skin, it acts as a vaso-constrictor reducing blood flow in the area. By sensing the change in colour from the lack of blood, the power can be controlled or switched off. A third example could be an assay for particular compounds in the interstitial fluids. If the skin barrier is compromised, interstitial fluids could be drawn out via vacuum and analysed for different components. An example would be the detection of Type III procollagen peptide (PIIINP) levels in the tissue fluids. PIIINP are terminal ends of collagen strands that get released when new collagen strands bind together to create bigger collagen bundles. Measuring the levels of PIIINP is an indicator of new collagen production.

[0160] Referring to Figure 18a and b, alternative electrode configurations are shown, where the electrodes 4, 6 are helically wound. In these illustrative embodiments the electrodes are disposed onto a patch 2 however as described elsewhere the patch can take a variety of different forms.Referring to Figure 18a, the first and second electrodes are shown supported on a substrate and presenting respective skin contact surfaces. It will be appreciated that the electrodes can be deposited in various forms including in a printed form. The electrodes 4,6 each define multiple turns and are spaced apart from one another. Such a configuration presents multiple different conductive pathways between the electrodes thereby achieving a large surface area that is effectively activated to disrupt a skin barrier to assist in delivery of an active. An active may be deposited on a whole or part of the patch 2.

[0161] Referring to Figure 18b, the electrode 4 is deposited onto the substrate via printing for example. An insulator 8 is then deposited onto the electrode 4, and a second electrode 6 is then deposited onto the insulator 8. This provides a layered structure.

[0162] A user of any of the embodiment presented may include, but is not limited to, a patient or an individual administering the treatment where the treatment involves delivery of an active through skin.

[0163] There are multiple different applications for arrangements as described and falling within the scope of the appended claims.

[0164] In skincare and beauty treatment there is effective improvement in the enablement of delivery of topical actives effective for skin beauty therapy. In such an embodiment a self-contained patch would be particularly beneficial.

[0165] In pain relief a patch which delivers accelerated pain relief in a number of applications would have significant benefits. For example a patch could be utilised for a time period until the active had fully transferred through the dermal layer in chronic pain applications.

[0166] The speed of delivery of a local anaesthetic may be improved compared to known techniques without causing a patient any pain or even discomfort. An example of this application would be prior to cannulation, particularly beneficial for children.For sleep applications a patch may readily and obtrusively deliver controlled administration of accepted molecules for sleep aid. For anxiety treatment a patch may deliver controlled administration of accepted molecules for the treatment for anxiety. Additional applications may delivery of vaccines or hormones. Other medical skin applications may be a patch for the treatment of conditions such as pre-cancerous lesions.

[0167] Other applications may be in hair care and restoration. The patch may enable delivery of a topical active to stimulate hair growth to penetrate through the skin barrier more effectively. There are also veterinary applications for a variety of treatments.

[0168] Referring now to Figure 19, there is a schematic representation of a hair growth brush that utilises the same technology as described throughout the present specification but is designed to disrupt the skin barrier on the scalp to assist in delivery of a topical to the scalp suitable for encouraging hair growth. Represented in Figure 20a are two adjacent bristles of a hairbrush showing the effect upon the skin. Figure 20b shows multiple bristles in an array indicating how the brush comprising the multiple bristles may move, and Figure 20c shows the bristles in plan view.

[0169] Each of the bristles 80 is at least electrically charged at the tip 82 effectively presenting positively and negatively charged tips 82a, 82b respectively. This results in generation of an electric field across the scalp 86 between the respective bristles 82 as presented by lines 84 in Figure 20a. The appearance of the bristles in end view is shown in Figure 20c. Referring to Figure 20b, the brush can be drawn across the scalp 86 represented by arrow 88 thereby generating an electric field across the scalp and disrupting the skin barrier and stimulating hair growth. The effectiveness can be further increased by inclusion of an active onto the tips 82a or applied directly to the scalp before application.

[0170] The brush may comprise a power source such as an electrochemical cell with a voltage of between 0.5 and 5V. The power source can be either mounted onto the brush or provided separately. If separate, the brush comprises first and second terminals for connection to the respective first and second electrodes.

[0171] Figure 20 is a schematic cross sectional representation of a hairbrush bristle according to an illustrative embodiment. The bristle 100 comprises proximal end 101 for engagementwith a hairbrush body extending to a distal end 103, where the bristle 101 comprises a first electrode 104 and a second electrode 104 electrically isolated from the first electrode by an insulator 108. The bristle is arranged to enable an electric field between the first and second electrodes 104,106 when the first and second electrodes are connected to a power source such that there is a current flow through the skin between the first and second electrodes in use.

[0172] The first and second electrodes 104,106 extend axially between the proximal and distal ends and comprise terminals at the proximal end for connection to a power source (not shown). The insulator 108 extends axially intermediate the first and second electrodes 104,106. The first electrode presents an external surface of the bristle. The second electrode effectively comprises a core region, having an exposed region at the distal end. The first electrode 104 comprises a first outer annulus. The insulator 108 comprises a second annulus radially inwardly of the first annulus. The bristles may be integrated into a hairbrush.

[0173] Referring now to Figure 21, an illustrative embodiment is presented wherein the patch 2 is in the form of a cover that may cover a portion of a wearer’s head. Electrodes in the various forms as described in the present specification present skin contact surfaces to the user’s scalp, and an electrical field is applied between the oppositely charged electrodes causing disruption of the skin on the scalp. An active applied topically to the scalp or applied to the at least part of the electrodes can then have increased mobility to enter into the scalp for the purpose of stimulating hair growth for example.

[0174] Referring now to Figure 22a and b, an illustrative embodiment is presented whereby the electrodes are carried by a band 90 arranged to be worn by a user. The band may be a ring, wrist band, or may be incorporated into a watch for example. The band may be elastically deformable to conform to the geometry of a wearer. Figure 22a shows an active 10 applied to the electrodes 4,6, and Figure 22b shows an embodiment without applied active 10.

[0175] In each embodiment control of operating parameters such as timings of delivery with connection and disconnection of the power source with the electrodes may be beneficial to tailor to the specific factors of a user such as weight, gender or age. It will be appreciated that in any of the described embodiments a controller can be utilised to modify the power deliver to the electrodes. Such control can be based on time, activity of different zones, power output1

[0176] from the power source etc. Connection may therefore be achieved to smart wearables to both monitor and control power delivery which in turn affects the rate or location of delivery of the active(s).

[0177] In any of the described embodiments, the provision of first and second electrodes may be termed a first skin modifier, and the arrangement may comprise a second skin modifier different to the first skin modifier. For example, a second skin modifier can be provided on the same substrate such as a patch. The second skin modifier may take various forms and may be microneedles, a heating element to supply heat, and / or a light emitting element (or array of light emitting elements) to deliver light to the skin. Each secondary skin modifier may be specifically designed to assist with delivery of an active into the skin. This may depend on the specific active for example, where delivery of some active types is assisted with a secondary action, for example the application of heat.

[0178] Referring to Figure 23 a further illustrative embodiment is presented. In this embodiment there is a schematic illustration of a further embodiment showing an arrangement for modifying a skin barrier comprising a handheld skin treatment device body 100 having a forward face defining a skin contact surface 102. Provided within the device body 100 is a control system and power source (not shown). A user operable actuator 104 is provided for activating the device.

[0179] The device is designed for improved delivery of actives into the skin surface, and the embodiment presented shows at the skin contact surface first and second electrodes 4, 6 electrically insulated from one another by an insulator 8. It will be appreciated that there are numerous other suitable electrode configurations that would be equally suitable for enabling improve delivery of active into the skin. Further provided is an array of LEDs 106 which are arranged to deliver LED light onto the skin. The LEDs may emit light having a wavelength range including one or more of 630-660nm (red), 400-470nm (blue), and 590-620nm (orange / yellow).

[0180] In operation, the control system is configured to provide a voltage across the first and second electrodes thereby presenting an electric field across the skin and further deliver an output from the second skin modifier concurrently. This has a synergistic effect, whereby the applied electric field provides pathways into the skin, and the LED light energises the cells.Together, the effect is improved ability for the cells to absorb an active compound. As described elsewhere, the active may comprise various forms. It may be presented onto the skin as a topical by a user prior to treatment or may be pre-disposed onto the electrodes. It will be appreciated that further beneficial functionality may be provided such as described elsewhere, which may include for example the provision of a skin tone sensor based on which the output from the LEDs and / or the voltage across the electrodes may be modified.

[0181] Although particular embodiments of this disclosure have been described, it will be appreciated that many modifications / additions and / or substitutions may be made within the scope of the claims.

Claims

29CLAIMS1. An arrangement for modifying a skin barrier, the arrangement comprising:o a substrate and a first skin modifier comprising a first and second electrode supported by the substrate, each of the first and second electrodes electrically isolated from one another; ando a second skin modifier, the second skin modifier different to the first skin modifier.

2. An arrangement according to claim 1 where the second skin modifier is supported by the substrate.

3. An arrangement according to any preceding claim wherein the arrangement comprises a device body and the substrate comprises a skin contact surface of the device body.

4. An arrangement according to any preceding claim where the second skin modifier comprises one or more Light Emitting Diodes (LEDs).

5. An arrangement according to claim 4 wherein the one or more LEDs emit light having a wavelength range including one or more of 630-660nm, 400-470nm, and 590- 620nm.

6. An arrangement according to any preceding claim comprising an insulator disposed onto the first electrode to leave the first electrode partially exposed and the second electrode disposed onto the insulator; wherein the insulator is arranged to form an electrically insulating zone between the first and second electrodes.

7. An arrangement according to claim 6 wherein the insulator is printed onto the first electrode, and the second electrode is printed onto the insulator.

8. An arrangement according to any preceding claim further comprising a power source comprising a first terminal electrically connected to the first electrode and a second terminal electrically connected to the second terminal.

309. An arrangement according to any preceding claim wherein at least one of the first and second electrodes comprises an active deposited thereon.

10. An arrangement according to claim 9 wherein the active comprises a first active and a second active, the second active different to the first active.

11. An arrangement according to claim 10 wherein the first and second actives are deposited in first and second zones respectively, the first and second zones being separate from one another.

12. An arrangement according to any preceding claim further comprising a controller for controlling voltage applied across the first and second electrodes and operation of the second skin modifier.

13. An arrangement according to claim 12 wherein controlling of voltage comprises switching between an on and an off state and / or changing the polarity of the current and / or modification of the voltage across the electrodes.

14. An arrangement according to any preceding claim wherein the insulator is disposed on the first electrode such that a plurality of first electrode skin contact zones are exposed.

15. An arrangement according to claim 14 wherein the insulator is disposed across the first electrode in a plurality of insulating regions, wherein the second electrode is disposed on one or more of the plurality of insulating regions.

16. An arrangement according to any preceding claim further comprising a sensor for sensing a parameter of the skin.

17. An arrangement according to claim 12 and 16 wherein control system is configured to control one or both of the voltage across the first and second electrodes and / or operation of the second skin modifier dependent upon the sensed parameter.

19. An arrangement according to claim 12 wherein the control system is configured to provide a voltage across the first and second electrodes and deliver an output from the second skin modifier concurrently.

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