US20080195035A1 - Collapsible Patch and Method of Application - Google Patents

Abstract

A microneedle patch (30) includes a base (32), at least one collapsible side wall (34) extending from the base, and a lip (36) disposed along the at least one collapsible sidewall and opposite the base. An adhesive (38) is disposed along the base, and a microneedle array (40) is affixed to the base.

Description

CROSS-REFERENCE TO RELATED APPLICATIONS
• The present application claims priority to U.S. Provisional Application Ser. No. 60/693,901, filed on Jun. 24, 2005, which is incorporated herein in its entirety.
FIELD
• The present invention relates to microneedle patches and patch assemblies, and more particularly to collapsible microneedle patches and patch assemblies for carrying and delivering microneedle arrays.
BACKGROUND
• Only a limited number of molecules with demonstrated therapeutic value can be transported through the skin via unassisted or passive transdermal drug delivery. The main barrier to transport of molecules through the skin is the stratum corneum (the outermost layer of the skin).
• Devices including arrays of relatively small structures, sometimes referred to as microneedles or micro-pins, have been disclosed for use in connection with the delivery of therapeutic agents, vaccines and other substances through the skin and other surfaces. The devices are typically pressed against the skin to deliver molecules to a particular location. Microneedles of these devices pierce the stratum corneum upon contact, making a plurality of microscopic slits which serve as passageways through which molecules of active components can be delivered into the body. In delivering an active component, the microneedle device can be provided with a reservoir for temporarily retaining an active component in liquid form prior to delivering the active component through the stratum corneum. In some constructions, the microneedles can be hollow to provide a liquid flow path directly from the reservoir and through the microneedles to enable delivery of the therapeutic substance through the skin. In alternate constructions, active component(s) may be coated on the microneedle array and delivered directly through the skin after the stratum corneum has been punctured.
• Microneedle arrays can be used in conjunction with an applicator device capable of being used a number of different times. The microneedle arrays are generally used once and then discarded.
• Microneedles can be delivered using a patch that carries the microneedles. The patches are typically manufactured in a flat sheet-like configuration, carrying the microneedles. Patches may be temporarily attached to a disposable collar for an applicator device using, for example, an adhesive. The disposable collar may then be temporarily attached to the applicator using, for example, a mechanical snap-fit.
• Patches, with or without a microneedles, can have fragile and sanitary characteristics. It is generally desired that the patch and array not be touched before application to a target site. This presents difficulties in storing and transporting patches to desired locations for eventual application. The patches may be stored along with the collars. However, the collars are large, and storage of disposable collars takes up excessive space and generates excessive waste.
• Thus, the present invention provides an alternative microneedle patch and patch assembly.
BRIEF SUMMARY
• In a first aspect of the present invention, a microneedle patch includes a base, at least one collapsible side wall extending from the base, and a lip disposed along the at least one collapsible sidewall and opposite the base. An adhesive is disposed along the base, and a microneedle array is affixed to the base.
• In another aspect of the present invention, a microneedle patch system includes a collapsible patch element having a base and at least one side wall extending from the base. The base of the collapsible patch element has an upper face and an opposite bottom face, and the at least one side wall generally extends from the bottom face of the base. A microneedle array is affixed to the bottom face of the base of the collapsible patch element, and a first carrier is disposed adjacent to the collapsible patch element and relative to the bottom face of the base. The first carrier covers the microneedle array, and is separable from the collapsible patch element.
• In another aspect of the present invention, a microneedle patch assembly includes a web of material having an upper face and a lower face, an adhesive disposed along the lower face of the web of material, and a microneedle array affixed to the lower face of the web of material. The patch has a first state where the web of material defines a first volume relative to its lower face and the microneedle array is spaced from a target site. The patch also has a second state where the web of material defines a second volume that is less than the first volume and the microneedle array contacts the target site.
• In another aspect of the present invention, a method of microneedle array deployment includes positioning a patch carrying a microneedle array relative to a target site and collapsing at least a portion of the patch while moving the microneedle array toward the target site.
• In another aspect of the present invention, a method of microneedle array deployment includes positioning a patch carrying a microneedle array near a target site. The patch is initially in an expanded state and the microneedle array is spaced from the target site. The microneedle array is moved toward the target site by placing the patch in a collapsed state, where at least a portion of the patch is collapsed and the microneedle array contacts the target site. The patch is also adhered to the target site with an adhesive disposed on the patch.
• In another aspect of the present invention, a microneedle patch assembly includes a patch element having, in an initial expanded state, a first skin contacting surface and a second surface spaced from the first surface. A microneedle array is affixed to the second surface of the patch element.
• In another aspect of the present invention, a microneedle patch system includes a plurality of collapsible patch elements nested together to form a package. Each collapsible patch element includes a base having an upper face and an opposite bottom face, at least one side wall extending from the base, and a microneedle array affixed to the bottom face of the base. The at least one side wall generally extends from the bottom face of the base.
• The above summary is not intended to describe each disclosed embodiment or every implementation of the present invention. The figures and the detailed description, which follow, more particularly exemplify illustrative embodiments.
BRIEF DESCRIPTION OF THE DRAWINGS
• FIG. 1 is a perspective bottom view of a microneedle patch.
• FIG. 2A is a side view of the microneedle patch ofFIG. 1 in an expanded state.
• FIG. 2B is a cross-sectional view of the microneedle patch ofFIGS. 1 and 2A in an expanded state.
• FIG. 2C is a side view of another embodiment of a microneedle patch in an expanded state.
• FIG. 3A is a side view of the microneedle patch ofFIGS. 1-2B in a collapsed state.
• FIG. 3B is a cross-sectional view of the microneedle patch ofFIGS. 1-2B and3A in a collapsed state.
• FIG. 4 is a perspective bottom view of another embodiment of a microneedle patch having slots defined therethrough.
• FIG. 5 is a top view of the microneedle patch ofFIG. 4.
• FIG. 6 is a side view of another embodiment of a microneedle patch having a channel defined therethrough.
• FIG. 7 is a side view of another embodiment of a microneedle patch having a rib disposed thereon.
• FIG. 8 is a bottom view of a microneedle patch showing possible venting feature locations.
• FIG. 9 is a cross-sectional view of a microneedle patch assembly.
• FIG. 10 is a cross-sectional view of another embodiment of a microneedle patch assembly.
• FIG. 11 is a cross-sectional view of another embodiment of a microneedle patch assembly.
• FIG. 12 is a cross-sectional view of a stack of nested microneedle patch assemblies.
• FIG. 13 is a cross-sectional view of a microneedle patch according to the present invention adhered to an application surface, and a microneedle patch applicator.
• FIG. 14 is a cross-sectional view of a microneedle patch according to the present invention held in a microneedle patch applicator.
• FIG. 15 is a cross-sectional view of a microneedle patch according to the present invention positioned relative to an application surface prior to microneedle deployment, and a microneedle patch applicator.
• FIG. 16 is a cross-sectional view of a microneedle patch according to the present invention positioned relative to an application surface after microneedle deployment, and a microneedle patch applicator.
• FIG. 17 is another cross-sectional view of a microneedle patch according to the present invention adhered to an application surface after microneedle deployment, and a microneedle patch applicator.
• FIG. 18 is a schematic representation of a manufacturing system for producing microneedle patches according to the present invention.
• FIG. 19 is a cross-sectional view of another embodiment of a microneedle patch in an expanded state.
• FIG. 20 is a cross-sectional view of another embodiment of a microneedle patch in a collapsed state.
• While the above-identified drawing figures set forth several embodiments of the invention, other embodiments are also contemplated, as noted in the discussion. In all cases, this disclosure presents the invention by way of representation and not limitation. It should be understood that numerous other modifications and embodiments can be devised by those skilled in the art, which fall within the scope and spirit of the principles of the invention. The figures may not be drawn to scale. Like reference numbers have been used throughout the figures to denote like parts.
DETAILED DESCRIPTION
• Patches can be used for transdermal delivery of molecules, and can carry microneedle arrays, which have utility for the delivery of large molecules that are ordinarily difficult to deliver by passive transdermal delivery. As used herein, “array” refers to the medical devices described herein that include one or more structures capable of piercing the stratum corneum to facilitate the transdermal delivery of therapeutic agents or the sampling of fluids through or to the skin. “Microstructure,” “microneedle” or “microarray” refers to the specific microscopic structures associated with the array that are capable of piercing the stratum corneum to facilitate the transdermal delivery of therapeutic agents or the sampling of fluids through the skin. By way of example, microstructures can include needle or needle-like structures as well as other structures capable of piercing the stratum corneum. The microneedles are typically less than 500 microns in height, and sometimes less than 300 microns in height. The microneedles are typically more than 20 microns in height, often more than 50 microns in height, and sometimes more than 125 microns in height.
• FIGS. 1-2B and3A-3B show a first embodiment of acollapsible microneedle patch30 according to the present invention that has a first, expanded state and a second, collapsed state.FIG. 1 is a perspective view of themicroneedle patch30 in the expanded state.FIG. 2A is a side view of themicroneedle patch30 in the expanded state.FIG. 2B is a cross-sectional view of themicroneedle patch30 in the expanded state.
• Themicroneedle patch30 has a collapsible patch element comprising a generallycircular base portion32, at least oneside wall34 extending from thebase portion32, and aperimeter lip36 extending from theside wall34 opposite thebase portion32. Thebase portion32, theside wall34 and theperimeter lip36 can be formed integrally. An adhesive38 is disposed on thebase portion32, and amicroneedle array40 is supported by the base portion32 (individual microneedles of thearray40 are not visible in the figures). As seen inFIG. 2B, theside wall34 is disposed at an angle between the perimeter of thebase portion32 and the inner diameter of theperimeter lip36, such that the inner diameter of theperimeter lip36 is larger than the perimeter (i.e., the outer diameter) of the base portion32 (measured with respect to anaxis42 defined at a center of the patch30). In an alternative embodiment (not shown) the side wall may be generally perpendicular to the base and the lip, such that the inner diameter of theperimeter lip36 would be about the same size as the perimeter of thebase portion32. In still another embodiment (not shown) the side wall may be angled such that the inner diameter of theperimeter lip36 would be smaller than the perimeter of thebase portion32, although the inner diameter of the perimeter lip should be large enough to allow themicroneedle array40 to contact a target surface. Theside wall34 also generally has a smaller thickness T_SWthan thicknesses T_Band T_Lof thebase portion32 and theperimeter lip36, respectively. The patch may further comprise an adhesive (not shown inFIGS. 1-2B) disposed along the surface of the lip opposed to the base.
• In one embodiment, the side wall thickness T_SWis about 0.0001 inches (0.00254 mm) to about 0.010 inches (0.254 mm), and is preferably about 0.0005 inches (0.0127 mm) to about 0.005 inches (0.127 mm). The outer diameter of theperimeter lip36 is typically about 1 inch (2.54 cm) to about 3 inches (7.62 cm), the outer diameter of thebase portion32 is typically about 0.5 inches (1.27 cm) to about 2.5 inches (6.35 cm). An overall height H_Eof the patch30 (in the expanded state) is typically about 0.1 inches (0.254 cm) to about 1 inch (2.54 cm). In one embodiment, the base thickness T_Bis about 0.005 inches (0.127 mm) to about 0.050 inches (1.27 mm). In one embodiment, the lip thickness T_Lis about 0.005 inches (0.127 mm) to about 0.050 inches (1.27 mm).
• Thebase portion32 and theperimeter lip36 are each generally planar. When thepatch30 is in the expanded state, thebase portion32 and theperimeter lip36 are spaced from one another (i.e., are not coplanar). Thebase portion32, theperimeter lip36 and theside wall34 define a volume V_Erelative to a bottom face of thepatch30. Thepatch30 has enough rigidity to remain in the expanded state without undesired collapse prior to application, due to external factors such as gravity and slight inadvertent contact.
• InFIGS. 1-2B, themicroneedle array40 is affixed to thebase portion32 by the adhesive38. Furthermore, the adhesive38 extends along thebase portion32 beyond themicroneedle array40 and surrounds themicroneedle array40. Themicroneedle array40 can also be connected to thebase portion32 in other ways.FIG. 2C is a side view of another embodiment of a microneedle patch30C in the expanded state. As shown inFIG. 2C, themicroneedle array40 is connected to thebase portion32, without adhesive disposed therebetween. Such a connection can be made by processes such as welding and directly forming themicroneedle array40 on thebase portion32. As shown inFIG. 2C, the adhesive38 is disposed on thebase portion32 around themicroneedle array40.
• FIG. 3A is a side view of themicroneedle patch30 in the collapsed state.FIG. 3B is a cross-sectional view of themicroneedle patch30 in the collapsed state. In the collapsed state, thebase portion32 and theperimeter lip36 are closer together than in the expanded state. In the collapsed state shown inFIGS. 3A and 3B, themicroneedle array40 extends at least as far, and preferably beyond, a skin-contactingface44 of theperimeter lip36 of thepatch30. Thebase portion32, theperimeter lip36 and theside wall34 define a volume V_C, which is less than a volume V_Edefined in the expanded state.
• Collapsing of thepatch30 involves deformation of a portion of thepatch30, for example, deforming theside wall34. The relatively thin wall thickness T_SWof theside wall34 facilitates collapse of thepatch30, and allows increased predictability in the deformation pattern (i.e., the characterization of deformation of thepatch30 resulting from collapse) for increasing reliability ofmicroneedle array40 deployment. This deformation may take many forms, andFIGS. 3A and 3B are merely exemplary of this result. It should be recognized that other deformation patterns are possible.
• At least thecircular base portion32, theside wall34, and theperimeter lip36 of thepatch30 are preferably formed of a thermoplastic material, such as polypropylene, polybutylene terephthalate, polystyrene, polyethylene, polythermide, polyethylene terephthalate, polystyrene, polyvinyl chloride, polymethylmethacrylate, acrylonitrile-butadiene styrene, polycarbonate, and blends thereof. Other possible materials include metal foils, such as aluminum, steel, and stainless steel. Thebase32,side wall34, andperimeter lip36 may be made of a single material or they may be formed using separate materials.
• FIG. 4 is a perspective view of another embodiment of amicroneedle patch50 having a plurality ofslots52A-52D defined therethrough to form venting features. Themicroneedle patch50 is generally similar to those shown and described with respect toFIGS. 1-3B. Theslots52A-52D are each generally elongated in shape, and extend from thebase portion32, along theside wall34 and into theperimeter lip36.FIG. 5 is a top view of themicroneedle patch50. In one embodiment, theslots52A-52D may be spaced equally aboutaxis42. As shown inFIGS. 4 and 5, there are fourslots52A-52D and they are positioned 90° from each other with respect toaxis42.
• Theslots52A-52D extend through thepatch50 to create openings or passageways, which permit air to pass through theside wall34. Openings defined by theslots52A-52D allow air to escape from the interior volume of thepatch50 as it collapses. This helps promote predictable movement of themicroneedle array40 during deployment, and helps reduce sound (e.g., a “popping” sound) generated during patch collapse. The sizes of each of theslots52A-52D can be selected according to the amount of airflow desired during collapse of thepatch50. In addition, theslots52A-52D can be pre-formed in thepatch50, or formed or cut into thepatch50 as part of a patch application process. In general, a vented system will have at least one air outlet defined in the collapsible patch element, so that it allows venting when the patch is placed against a continuous target surface and the patch volume is compressed.
• The embodiment of openings or passageways shown inFIGS. 4 and 5 are merely exemplary, and other means of providing openings are possible. For instance,FIG. 6 is a side view of a portion of another embodiment of amicroneedle patch60 having achannel62 defined therethrough. Thechannel62 is substantially an inverted U-shape and disposed in aperimeter lip36, along a bottom,skin contacting face64 of theperimeter lip36. Thechannel62 creates a generally radially extending opening or passageway that permits air to escape from the interior volume of thepatch60 as it collapses. The size of the channel can be selected according to the amount of airflow desired during collapse of thepatch60. One or more channels can be included, as desired.
• FIG. 7 is a side view of a portion of another embodiment of amicroneedle patch70 having arib72 disposed thereon. Therib72 can be a protrusion extending from a bottom, skin-contactingface64 of aperimeter lip36 of thepatch70. Therib72 is elongate, and extends generally radially along theperimeter lip36. In further embodiments, therib72 can have nearly any shape, and nearly any number of ribs can be included. When the skin-contactingface64 of theperimeter lip36 is positioned against a surface (e.g., against the skin of a patient or test subject), therib72 spaces at least a portion of the surface from the skin-contactingface64 of theperimeter lip36. This creates a passageway adjacent therib72 that permits air to escape from the interior volume of thepatch70 as it collapses. The height of therib72 can be selected according to the amount of airflow desired during collapse of thepatch70.
• FIG. 8 is a bottom view of amicroneedle patch80 showingpossible feature locations82A-82D. Airflow features such as those shown and described with respect toFIGS. 6 and 7 can be disposed at any or all of thelocations82A-82D. As shown inFIG. 8, the airflow features (atlocations82A-82D) can extend generally radially along theperimeter lip36, relative toaxis42. Other feature locations are possible, as those shown inFIG. 8 are merely exemplary.
• FIG. 19 is a cross-sectional view of another embodiment of a microneedle patch in an expanded state. Themicroneedle patch230 has a collapsible patch element comprising a generallycircular base portion232, at least oneside wall234 extending from thebase portion232, and aperimeter lip236 extending from theside wall234 opposite thebase portion232. Thebase portion232, theside wall234 and theperimeter lip236 can be formed integrally. An adhesive238 is disposed on thebase portion232, and amicroneedle array240 is supported by the base portion232 (individual microneedles of thearray240 are not visible in the figures). Theside wall234 is generally perpendicular to thebase232 and thelip236, such that the inner diameter of theperimeter lip236 is about the same size as the perimeter of thebase portion232. As seen inFIG. 19, theside wall234 is pleated, such that it can fold in a manner similar to an accordion.FIG. 20 is a cross-sectional view of themicroneedle patch230 in the collapsed state where the pleats have been pressed against one another.
• In order to store and transport microneedle arrays and microneedle patches, packages according to the present invention can be provided. These packages offer protection to microneedle arrays that are often fragile and contamination-sensitive. In addition, these packages permit storage of the collapsible microneedle patches while reducing the risk of undesired patch collapse, due to inadvertent contact or other factors.
• FIG. 9 is a cross-sectional view of a microneedle patch assembly90 that includes amicroneedle patch30 and acarrier92 that together form a closed package. Thecarrier92 includes abase portion94, a raisedportion96, and arecess98 disposed in the raisedportion96. Thepatch30 is positioned on thecarrier92, such that the raisedportion96 of thecarrier92 extends at least partially into the volume defined between the base32 and theside wall34 of thepatch30. Thus the raisedportion96 of thecarrier92 may be considered to mate with thepatch30. Therecess98 extends toward thebase portion94 of thecarrier92, creating a volume into which themicroneedle array40 can extend. This permits thebase portion94 of thecarrier92 to contact theperimeter lip36 of thepatch30 and the raisedportion96 to contact theside wall34 and the base32 (or adhesive38 disposed on the base32) of thepatch30 without thecarrier92 contacting themicroneedle array40. However, the carrier can be shaped in other ways. For instance, the raisedportion96 need not come into contact with the base32 (or adhesive38 disposed on the base32) of thepatch30.
• A number of discrete raisedportions96 can extend from asingle base portion94 of thecarrier92. This permits a plurality ofindividual patches30 to be carried on asingle carrier92. In addition, thecarrier92 can be optionally adhered to thepatch30, for example, by the adhesive38. In further embodiments, thecarrier92 can be adhered to thepatch30 with adhesive disposed on theperimeter lip36. Theportion94 of thecarrier92 that contacts theperimeter lip36 of thepatch30 may be a release or non-stick surface, such that the adhesive of the patch may be easily removed from it. This may be achieved by suitable selection of adhesive and carrier material or it may be desirable to provide a release coating, such as a low surface energy silicone, fluoropolymer, or fluoro-silicone release coating on thecarrier92.
• Thecarrier92 is separable from thepatch30. Thepatch30 can be positioned on thecarrier92 for storage and transportation. Thecarrier92 is then removed from thepatch30 prior to application of thepatch30 to a patient. Because thecarrier92 is only disposed relative to one side of thepatch30, an operator can pick up thepatch30 and separate it from thecarrier92 either manually or with a tool such as a patch applicator device. Thecarrier92 is typically formed so as to be relatively rigid. Suitable materials include polymers, such as polypropylene, polybutylene terephthalate, polystyrene, polyethylene, polythermide, polyethylene terephthalate, polystyrene, polyvinyl chloride, polymethylmethacrylate, acrylonitrile-butadiene styrene, polycarbonate, and blends thereof. The carrier may be formed from the same material as the collapsible patch element, but the carrier thickness will typically be greater than the thickness of part or all of the patch element. Rigidity of thecarrier92 offers protection to thepatch30 from undesired collapse, and from damage and contamination.
• FIG. 10 is a cross-sectional view of another embodiment of amicroneedle patch assembly100. Theassembly100 includes apatch30, a (first)carrier92, and asecond carrier102 that together form a package. Thepatch30 and thecarrier92 are similar to those shown and described with respect toFIG. 9. Thesecond carrier102 includes abase portion104 and a raisedportion106 extending from thebase portion104. Thepatch30 is disposed on the (first)carrier92, and thesecond carrier102 is disposed on or over thepatch30, opposite the (first)carrier92. The raisedportion106 of thesecond carrier102 defines a volume into which thepatch30 can extend. The raisedportion96 of the (first)carrier92 can also extend into the volume defined by the raisedportion106 of thesecond carrier102. The (first)carrier92 and thesecond carrier102 can be sealed or adhered together about their respective peripheries (such as atlocation105 inFIG. 10) in order to better protect thepatch30 for contamination and other damage, as well as to better preserve any substances (e.g., pharmaceuticals) carried by themicroneedle array40. Sealing may be by any suitable means, such as by use of an adhesive or a heat seal. In one embodiment a hermetic seal is provided to protect the patch from environmental influences so that the patch may be stored, for example, while maintaining sterility. Both carriers may be separable from the patch and one or both may be removed by hand or with the aid of an applicator device. They may be removed in any order or they may be removed simultaneously. The second carrier is generally formed so as to be relatively rigid and in one embodiment may be formed from the same material as the first carrier.
• FIG. 11 is a cross-sectional view of another embodiment of amicroneedle patch assembly110. Theassembly110 is similar to that shown and described with respect toFIG. 10. However, in this embodiment, anopening112 is defined through a center region of the raisedportion106 of thesecond carrier102. The opening112 permits access to thepatch30 near themicroneedle array40. Theopening112 can allow a portion of a patch applicator device to contact thebase32 of thepatch30 above themicroneedle array40 to apply a force, which can collapse thepatch30 and move themicroneedle array40 toward a target site (after the (first)carrier92 is removed). Prior to deployment of themicroneedle array40, for storage and transportation, theopening112 can be covered and sealed, for instance, with foil or other type of removable cover. In the embodiment shown inFIG. 11 the second carrier may be removed after collapse of the patch while allowing the patch to remain in contact with the target surface. Alternatively, the second carrier may stay in place on the target surface until removal of the patch.
• A number of patch assemblies can be arranged together as a package.FIG. 12 is a cross-sectional view of astack120 of a plurality of nestedmicroneedle patch assemblies100 that forms a package. The raisedportion106 of thesecond carrier102 of onepatch assembly100A extends into the volume defined by the raisedportion96 of the (first)carrier92 of anadjacent patch assembly100B. Almost any number ofpatch assemblies100 can be nested together. Moreover, different types of patch assemblies can be stacked together. Thestack120 facilitates storage and transportation of patch assemblies.
• In operation, apatch30 according to the present invention can be applied to a target location using an applicator device. Examples of suitable microneedle application devices are disclosed in International Patent Publication WO 05/123173 and U.S. Patent Application Publication No. 2002-0087182, which are hereby incorporated by reference in their entirety. However, a variety of patch applicators can be used to apply thepatch30.
• A first method of applying a patch includes adhering the patch to a surface and then bringing an applicator device to the patch for activation.FIG. 13 is a cross-sectional view of amicroneedle patch30 in an expanded state adhered to anapplication surface130, and amicroneedle patch applicator132 spaced from thepatch30. Thepatch30 can be adhered to theapplication surface130, for example, by adhesive disposed on theperimeter lip36 of thepatch30. Once themicroneedle patch30 is in place on theapplication surface130, themicroneedle patch applicator132 can be placed over thepatch30. Acollar portion134 can then engage thepatch30, and, in one embodiment, may include one or more vent cutters thereon for cutting through a portion or portions of thepatch30 to form vent openings therethrough. Thepatch applicator132 is activated, as explained below, to engage themicroneedle array40 with theapplication surface130. It should be understood that after the patch is adhered to the target surface it may simply be pressed manually to engage the microneedle array with the application surface. Manual application, however, may not be as reproducible as that obtained with an appropriately configured applicator device.
• Another method of applying a patch includes placing the patch on or in an applicator device before either is positioned near an application surface.FIG. 14 is a cross-sectional view of amicroneedle patch30 in an expanded state held on amicroneedle patch applicator132. Thepatch applicator132 has anouter collar portion134, which can be cylindrical in shape or have another shape that corresponds to a shape of thepatch30. Theperimeter lip36 of thepatch30 can rest against a bottom portion of thecollar134 of theapplicator device132, and theside wall34 andbase32 of thepatch30 can extend into an interior portion of thecollar134. In this position, themicroneedle array40 of thepatch30 is generally disposed in the interior portion of thecollar134 of theapplicator device132.
• Once thepatch30 is placed in or on theapplicator device132, according to the methods described with respect toFIGS. 13 and 14 or by other methods, thepatch30 andapplicator device132 are both positioned to deploy themicroneedle array40 of thepatch30.FIG. 15 is a cross-sectional view of amicroneedle patch30 in an expanded state held on amicroneedle patch applicator132, with both thepatch30 and theapplicator132 positioned relative to anapplication surface130 prior tomicroneedle array40 deployment to atarget site136. As shown inFIG. 15, apatch accelerator138 of theapplicator device132 is spaced from thepatch30 and has not yet contacted or moved thepatch30.
• After thepatch30 and theapplicator132 are positioned relative to thetarget site136, themicroneedle array40 can be deployed.FIG. 16 is a cross-sectional view of themicroneedle patch30 in a collapsed state after deployment of themicroneedle array40 to thetarget site136 on theapplication surface130 by themicroneedle patch applicator132. Themicroneedle array40 has been moved into contact with theapplication surface130 by thepatch accelerator138. Thepatch30 can be adhered to theapplication surface130 with an adhesive38 disposed on thebase32 of thepatch30, as desired.
• After themicroneedle array40 of thepatch30 is deployed, thepatch30 can remain in contact with theapplication surface130 while theapplicator device132 is moved away.FIG. 17 is a cross-sectional view of themicroneedle patch30 adhered to theapplication surface130 aftermicroneedle array40 deployment, with themicroneedle patch applicator132 spaced from the patch30 (i.e., thecollar134 of theapplicator device132 does not contact the patch30).
• In one embodiment, an applicator will accelerate themicroneedle array40 to a desired velocity that is effective to pierce the microneedles into the skin. The desired velocity is preferably controlled to limit or prevent stimulation of the underlying nerve tissue. The maximum velocity achieved by the microneedle array upon impact with the skin is often 20 meters per second (m/s) or less, potentially 15 m/s or less, and possibly 10 m/s or less. In some instances, the maximum velocity may be 8 m/s or less. In other instances, the minimum velocity achieved by the microneedle array upon impact with the skin is often 2 m/s or more, potentially 4 m/s or more, and possibly 6 m/s or more.
• FIG. 18 is a schematic representation of amanufacturing system180 for producing microneedle patches according to the present invention. Thesystem180 includes afilm heater182 and adie tool184 having at least onecavity186. Additional cavities can be provided in thedie tool184. In the embodiment shown inFIG. 18, thesystem180 further includes amovable plug188 having anengagement portion190 for cooperatively engaging thecavity186 of thedie tool184. In further embodiments, thedie tool184 can utilize a vacuum forming assembly either in addition to or in place of plug assist from theplug188.
• In operation, a web ofmaterial192 is provided. The web ofmaterial192 can be in the form of a film from aroll194 of film stock. First, the web ofmaterial192 is unrolled, and is heated by thefilm heater182. This heating helps prepare the web ofmaterial192 for being formed into a three-dimensional shape by making it more readily deformable. Next, a portion of the heated web ofmaterial192 is positioned at thecavity186 of thedie tool184, between thedie tool184 and theplug188. Theplug188 moves toward thedie tool184 such that theengagement portion190 of the plug and thecavity186 of thedie tool184 cooperatively deform the web ofmaterial192 to form at least one collapsible patch (e.g.,collapsible patch30 shown and described with respect toFIGS. 1-2B and3A-3B). Then theplug188 is moved away from thedie tool184. A formedpatch element196 of the web ofmaterial192, formed with thedie tool184 and plug188, is then moved away from thedie tool184.
• Additional patch elements can be formed on the web ofmaterial192 in a similar fashion as that described above. The individual patch elements can be separated from each other after they have been formed, or the patch elements can remain connected for transportation and further processing (e.g., for connecting microneedle arrays and or for affixing adhesive to a portion of the lower face of the web material).
• In one embodiment, a microneedle array may be formed directly on the web ofmaterial192 during a forming step that can take place before, after, or concurrent with the plug forming step. Additional details regarding molding processes suitable for forming a microneedle array as part of a web may be found in United States Patent Application Ser. No. 60/753,808, filed Dec. 23, 2005, the disclosure of which is herein incorporated by reference.
• The microneedle arrays useful in the various embodiments of the invention may comprise any of a variety of configurations, such as those described in the following patents and patent applications, the disclosures of which are herein incorporated by reference. One embodiment for the microneedle arrays comprises the structures disclosed in United States Patent Application Publication No. 2003/0045837. The disclosed microstructures in the aforementioned patent application are in the form of microneedles having tapered structures that include at least one channel formed in the outside surface of each microneedle. The microneedles may have bases that are elongated in one direction. The channels in microneedles with elongated bases may extend from one of the ends of the elongated bases towards the tips of the microneedles. The channels formed along the sides of the microneedles may optionally be terminated short of the tips of the microneedles. The microneedle arrays may also include conduit structures formed on the surface of the substrate on which the microneedle array is located. The channels in the microneedles may be in fluid communication with the conduit structures. Another embodiment for the microneedle arrays comprises the structures disclosed in U. S. Patent Application Publication No. 2005/0261631, which describes microneedles having a truncated tapered shape and a controlled aspect ratio. Still another embodiment for the microneedle arrays comprises the structures disclosed in U.S. Pat. No. 6,091,975 (Daddona, et al.) which describes blade-like microprotrusions for piercing the skin. Still another embodiment for the microneedle devices comprises the structures disclosed in U.S. Pat. No. 6,313,612 (Sherman, et al.) which describes tapered structures having a hollow central channel. Still another embodiment for the micro arrays comprises the structures disclosed in U.S. Pat. No. 6,379,324 (Gartstein, et al.) which describes hollow microneedles having at least one longitudinal blade at the top surface of tip of the microneedle.
• Microneedle patches of the present invention may be used to deliver drugs (including any pharmacological agent or agents) through the skin in a variation on transdermal delivery, or to the skin for intradermal or topical treatment, such as vaccination.
• In one aspect, drugs that are of a large molecular weight may be delivered transdermally. Increasing molecular weight of a drug typically causes a decrease in unassisted transdermal delivery. Microneedle patches of the present invention have utility for the delivery of large molecules that are ordinarily difficult to deliver by passive transdermal delivery. Examples of such large molecules include proteins, peptides, nucleotide sequences, monoclonal antibodies, DNA vaccines, polysaccharides, such as heparin, and antibiotics, such as ceftriaxone.
• In another aspect, microneedle patches of the present invention may have utility for enhancing or allowing transdermal delivery of small molecules that are otherwise difficult or impossible to deliver by passive transdermal delivery. Examples of such molecules include salt forms; ionic molecules, such as bisphosphonates, preferably sodium alendronate or pamedronate; and molecules with physicochemical properties that are not conducive to passive transdermal delivery.
• In another aspect, microneedle patches of the present invention may have utility for enhancing delivery of molecules to the skin, such as in dermatological treatments, vaccine delivery, or in enhancing immune response of vaccine adjuvants.
• Microneedle patches may be used for immediate delivery, that is where they are applied and immediately removed from the application site, or they may be left in place for an extended time, which may range from a few minutes to as long as 1 week. In one aspect, an extended time of delivery may be from 1 to 30 minutes to allow for more complete delivery of a drug than can be obtained upon application and immediate removal. In another aspect, an extended time of delivery may be from 4 hours to 1 week to provide for a sustained release of drug.
• Although the present invention has been described with reference to several alternative embodiments, workers skilled in the art will recognize that changes may be made in form and detail without departing from the spirit and scope of the invention. For instance, various types of microneedle arrays can be utilized according to the present invention.

Claims (26)

1. A microneedle patch comprising:

a base, at least one collapsible side wall extending from the base, and a lip disposed along the at least one collapsible sidewall and opposite the base;

an adhesive disposed along the base; and

a microneedle array affixed to the base.

2. The microneedle patch ofclaim 1, wherein the adhesive disposed on the base surrounds the microneedle array.

3. A microneedle patch assembly comprising:

a collapsible patch element having a base and at least one side wall extending from the base, wherein the base has an upper face and an opposite bottom face, and wherein the at least one side wall generally extends from the bottom face of the base;

a microneedle array affixed to the bottom face of the base of the collapsible patch element; and

a first carrier disposed adjacent to the collapsible patch element and relative to the bottom face of the base, wherein the first carrier covers the microneedle array, and wherein the first carrier is separable from the collapsible patch element.

4. The assembly ofclaim 3, and further comprising:

a second carrier disposed adjacent to the collapsible patch element and relative to the upper face of the base.

5. The assembly ofclaim 4, wherein the second carrier is separable from the collapsible patch element.

6. The assembly ofclaim 4, wherein the second carrier has an opening defined therein for permitting a portion of an application device to contact the collapsible patch element for microneedle array deployment while the second carrier remains positioned adjacent to the collapsible patch element.

7. The assembly ofclaim 4, wherein the second carrier is formed of a material that is generally more rigid than the at least one side wall of the collapsible patch element.

8. The assembly ofclaim 4, wherein the first and second carriers are sealed together to form a closed package that contains the collapsible patch element.

9. The assembly ofclaim 3, wherein the first carrier has a lower portion and a raised portion with a recess, wherein the raised portion is generally configured to mate with the collapsible patch element, and wherein the recess is configured such that the first carrier does not touch the microneedle array.

10. The assembly ofclaim 9, wherein the raised portion of the first carrier is releasably affixed to the base of the collapsible patch element.

11. The assembly ofclaim 3, and further comprising:

an adhesive disposed along the base of the collapsible patch element.

12. The assembly ofclaim 3, wherein collapse of the collapsible patch element causes deformation of the at least one side wall.

13. The assembly ofclaim 3, and further comprising:

at least one air outlet defined in the collapsible patch element.

14. The assembly ofclaim 13, wherein the at least one air outlet is an opening in the at least one side wall of the collapsible patch element.

15. The assembly ofclaim 3, wherein the collapsible patch element further comprises:

a lip disposed along the at least one sidewall and opposite the base.

16. The assembly ofclaim 15, wherein the at least one air outlet is a generally U-shaped channel disposed along the surface of the lip opposed to the base.

17. The assembly ofclaim 15, wherein the at least one air outlet is defined adjacent one or more ribs, each rib being disposed along the surface of the lip opposed to the base.

18. The assembly ofclaim 17, wherein the rib is elongate in shape and extends radially with respect to an axis defined at a center of the base.

19. The assembly ofclaim 15, and further comprising:

an adhesive disposed along the lip.

20. The assembly ofclaim 3, wherein the first carrier is formed of a material that is generally more rigid than the at least one side wall of the collapsible patch element.

21. A microneedle patch assembly comprising:

a web of material having an upper face and a lower face;

an adhesive disposed along the lower face of the web of material; and

a microneedle array affixed to the lower face of the web of material,

wherein the patch has a first state wherein the web of material defines a first volume relative to its lower face and the microneedle array is spaced from a target site, and wherein the patch has a second state wherein the web of material defines a second volume that is less than the first volume and the microneedle array contacts the target site.

22. (canceled)

23. (canceled)

24. (canceled)

25. (canceled)

26. (canceled)

Images