Patent ID: 12246154

DETAILED DESCRIPTION

Throughout this disclosure, singular forms such as “a,” “an,” and “the” are often used for convenience; however, it should be understood that the singular forms are meant to include the plural unless the singular alone is explicitly specified or is clearly indicated by the context.

Positional terms such as “top” and “bottom” or “left” and “right” are not used herein in reference to position with respect to the ground, the user, the floor, the earth, or the direction of a gravitational pull. Instead, these terms are used as relative terms to refer to opposing or approximately opposing sides or portions of an object. For example, while the “top” of an object is understood to be opposing or approximately opposing the “bottom,” it is not necessary that the “bottom” be disposed closer to the ground that the “top.”

A microneedle array applicator can include a housing and a plunger. The housing and the plunger can be made of any suitable material, but are most typically plastic. Common plastics that can be used include polyethylene, such as high density polyethylene, polypropylene, nylon, such as nylon 6,6, and the like. The housing and the plunger need not be made of the same material, although this is most common.

The housing can have a first major surface that is configured to be positioned towards the skin and defining a bottom of the housing. The first major surface is configured to releaseably engage with a microneedle device, particularly a microarray carrier portion of a microarray applicator.

The housing can also have a second major surface opposite the first major surface and defining a top of the housing.

The housing can have a cavity that extends through the first and second major surfaces. An interior surface can define the cavity. The interior surface can have one or more ridges. The one or more ridges typically have a ridge height, which is defined by the distance between the one or more ridges and the first major surface. In most cases, the cavity will have an annular shape, not including the one or more ridges, and there will be only one ridge that forms a circle around the entire interior surface. The entire ridge in this case has the same ridge height. In the cases where the cavity has another shape, for example when the cavity has a square, triangular, or other cross-section, then there will be more than one ridge, one ridge per side of the cavity, and each of the ridges will have the same ridge height.

The housing can also include a holder located between the first and second major surfaces for holding at least part of a microarray device within the housing. The holder can have any suitable configuration, which will depend in part on the configuration of the microarray device that it is designed to hold. Some exemplary configurations are depicted in U.S. Patent Application Publication No. US2016/0235958, particularly inFIGS.8,9,10,11,12,13,14, and15, and in PCT Publication No. WO0230300, particularly inFIG.16. One particular configuration for the holder is shown in the Figures of this disclosure, although it should be understood that other configurations are possible. In the configuration depicted in the Figures of this disclosure, the holder is in the form of a slot in the housing, the bottom of the slot being defined by the first major surface, and the top of the slot being defined by an additional surface. The microneedle array device can fit within the slot and slideably engage with the holder. Groves can be present in the slot to engage with the microneedle array device.

In many cases, depending on the configuration of the holder, the first major surface does not extend all the way across the housing. In such cases, the first major surface can, for example, extend only part of the way across the housing, extend only along parts of one or more sides or edges of the housing, and the like. Nonetheless, even in cases where the first major surface is part of the holder, the first major surface will typically be below the portion of the housing that is configured to receive the microneedle array device.

The plunger can have a top and a bottom, as well as one or more sides. The plunger is configured to slideably engage with the cavity in the housing. In particular, the bottom of the plunger can be placed within the cavity in the housing. Thus, the shape of the plunger will depend on the shape of the cavity of the housing. In most cases the interior cavity of the housing has a circular cross-section, and thus the plunger also has a circular cross-section, and is cylindrical in shape, excluding the ridges.

The plunger can have a first set of one or more notches located proximate to the bottom of the plunger, all of which are located substantially the same distance from the top of the plunger. The first set of one or more notches have a first depth into the one or more sides of the plunger. The first width is equal to or less than the ridge width. The first set of one or more notches is configured such that, when fully engaged with the ridge in the housing, a first force can release the first notch in a direction towards the bottom of the housing and a second force can release the first notch in a direction towards the top of the housing, the first force being substantially the same as the second force. The first and the second forces are substantially the same, such that they preferably differ by no more than 10%. This is typically accomplished by providing a first and second notch with a profile that is substantially rotationally symmetric about an axis substantially normal to the side of the plunger adjacent to the notch. “Substantially rotationally symmetric” refers to rotational symmetry that is within manufacturing tolerances, particularly to a rotational symmetry that is greater than 90% symmetrical, and even more particularly to rotational symmetry that is greater than 95%. “Substantially normal,” it is meant that the angle between axis and the side of the plunger is approximately 90°, and in particular cases the angle is from 80° to 100°.

The plunger can also have a second set of one or more notches located proximate to the top of the plunger. The second set of one or more notches is configured such that, when fully engaged with the notch in the housing, a third force can release the ridge in a direction towards the bottom of the housing and a fourth force can release the ridge in a direction towards the top of the housing, the third force being substantially the same as the fourth force. The third and fourth forces are substantially the same, and particularly differ by no more than 10%. This is typically accomplished by providing a second notch with a profile that is substantially rotationally symmetric about an axis substantially normal to the side of the plunger adjacent to the ridge. “Substantially rotationally symmetric” refers to rotational symmetry that is within manufacturing tolerances, particularly to a rotational symmetry that is greater than 90% symmetrical, and even more particularly to rotational symmetry that is greater than 95%. “Substantially normal,” it is meant that the angle between axis and the plunger is approximately 90°, and in particular the angle is from 80° to 100°. The second width is equal to or less than the ridge width.

The first and second set of one or more notches are separated by a distance. The distance between the first and second sets of one or more notches is greater than the ridge height.

The shape of the plunger can vary depending on the shape of the cavity in the housing such that the plunger can slideably engage with the cavity. Typically, when the cavity has a circular cross-section, the plunger also has a circular cross-section. In this case the plunger can be cylindrical. When the plunger is referred to as being cylindrical, this does not include the first and second sets of one or more notches or the optional head (discussed below), which can extend from the plunger making the overall plunger not a perfect cylinder. When the plunger is cylindrical, there is typically only one notch in the first set of one or more notches and only one ridge in the second set of one or more notches.

The plunger can slideably engage with the cavity in the housing. The plunger is moveable within the cavity between a first position and a second position within the cavity. In the first position, the first set of one or more notches is engaged with the one or more ridges in the interior of the cavity of the housing, for example, to releasably interlock the plunger with the housing. In the first position, the bottom of the plunger does not extend below the first major surface of the housing.

In the second position, the second set of one or more notches engages with the one or more ridges on the interior surface of the cavity, for example to releseably interlock the plunger with the housing. In this position, the bottom of the plunger extends below the first major surface of the housing. The bottom of the plunger extends far enough below the first major surface of the housing that it is capable of ejecting a microneedle patch from a microarray device, when a microarray device, such as a microarray device as described herein, is in the holder of the housing.

The top of the plunger can, in some cases, comprise a head. When present, the head typically extends beyond the sides of the plunger farther than the cavity in the housing. Thus, the head can serve to block the top of the plunger from entering the housing. The head can be configured in any suitable shape, but most commonly has a mushroom-cap shape. The head of the plunger, if present, can also make it easier for a user to push the plunger into the housing and from the first position to the second position by providing an increased surface area on which to push. The head of the plunger can also prevent the plunger from moving through the bottom of the housing by abutting the second major surface of the housing when the plunger is in the second position. The head of the plunger is not required, and in some cases it is not present.

Typically, the applicator does not include an energy storage device, such as a spring, for moving the plunger from the first position to the second position or from the second position back to the first position. Instead, the force of a user pushing on the top of the plunger, such as the head of the plunger when present, can move the plunger from the first position to the second position.

A microarray device can engage with the holder of the housing such that at least a portion of the microarray device is releaseably restrained within the housing. The microarray device will typically have a microarray carrier, which is typically plastic but can be any suitable material including metal or others, that carries a microneedle patch. The microneedle patch is typically in the form of a flexible sheet with microneedles protruding therefrom. The term “microneedles” refers to needles or similar projections having a size on the microscale; other disclosures have used the term “microprotrusions” in the same sense, in which case the term microneedles is intended to include such microprotrusions. Microneedles can be hollow or solid, and can even be dissolvable within the body. When hollow, the microneedles will often contain one or more active agents, often along with optional excipients, within the microneedles. When solid, the microneedles will often contain a coating of one or more active agents, often along with optional excipients. When dissolvable, the microneedles will often be made out of a dissolvable matrix having one or more active agents, often along with optional excipients, in the matrix. The microneedle patch is supported by the microneedle array carrier, but it can be ejected from the carrier in use.

In use, the bottom of the plunger can be inserted into the cavity. Pushing on the top of the plunger can move the plunger to the first position wherein the first set of one or more notches is engaged with the ridge in the interior of the cavity. A microneedle device can be placed within the holder (either before or after inserting the plunger into the first position). The second first major surface of the actuator can be placed against the object that is to receive the microneedles, which is usually skin, such as the skin of a subject, but can also be other things such as testing device (e.g., for testing the velocity of the plunger or pressure applied by the plunger), an eye, and the like. The plunger can be inserted and moved to the first position either before or after the second major surface is placed against the skin.

A force sufficient to move the plunger from the first position to the second position is applied to the top of the plunger. Typically, this force is sufficient to eject the microneedle patch from the microneedle device, such as to detach the microneedle patch from the microarray carrier, and also sufficient such that the microneedles can pierce the skin of a subject. The required force will vary depending on the particular application, but it can be controlled by varying the depth of the notch and the width of the ridge, as well as the dimensions of the ridge and notch. When the first depth of the first set of one or more notches, and the corresponding depth of the ridge, is larger, then more force is required to disengage the first set of one or more notches from the ridge and move the plunger to the second position increases. When the first depth of the first set of one or more notches, and the corresponding width of the ridge, is smaller, then less force is required to disengage the first set of one or more notches from the ridge and move the plunger to the second position. An increased force requirement to move the plunger from the first to the second position can provide a greater velocity of the plunger, which in turn increases the force applied by the microneedles on the skin. Thus, the velocity, for example, of the plunger and the microneedles when the microneedle patch ejects from the applicator and contacts the skin, can be controlled by varying the first width.

Once the plunger has moved to the second position, that is, the second set of notches is engaged with the ridge, continued downward pressure on the plunger provides a pressure on the microneedle patch. The pressure provided can be controlled by way of increasing or decreasing the second width of the second set of one or more ridges.

After ejecting the microneedle patch, the plunger can be re-set for another use. To reset the plunger the remaining portion of the microneedle device (that is, the portion that was not ejected) can be removed from the holder in the housing. The bottom of the plunger can then be pushed back up towards the top of the housing until the plunger returns to the first position. A new microneedle device can be placed in the holder, and the microneedle applicator can be used again. However, because the microneedle applicator is a simple design that is inexpensive to manufacture and requires no expensive materials, the microneedle applicator can be designed for a single-use only, and can be discarded after use.

Typically, no stored energy devices are used during the process. For example, in most cases no springs or chemical systems are needed to move the plunger between the first and second positions. In the case where a stored energy device is used, it is typically not an integrated component of the actuator. Instead, it is usually a separate device that is used to help push the plunger, for example, in cases where the user does not have sufficient strength to push the plunger hard enough to move it from the first to the second position. In most cases, no stored energy device of any type is used.

In some cases, when sufficient force is applied to the plunger, the second set of notches can disengage with the ridge and the plunger can move downwards past the second position. When this is a concern, the head of the plunger can be useful. For example, the head of the plunger, which typically extends beyond the sides of the plunger and the cavity of the housing, can stop the plunger from proceeding too far into the housing, for example, it can stop the top of the plunger from entering the housing.

Turning now to the figures,FIG.1is a top-down view of housing1000wherein second major surface1100and cavity1200are visible. In this Figure, cavity1200has a circular cross-section. Other shapes are also possible.

FIG.2Ais a cut-away side view of housing2000, featuring first major surface2100and opposing second major surface2200. Cavity2300extends through the entire housing2000, including featuring first major surface2100and second major surface2200. Note that in this Figure, first major surface2100does not extend all the way across housing2000. Holder2400is, in this Figure, present in the form of groves in housing2000for receiving and retaining a microneedle array device (not shown). Cavity2300features interior surface2310and ridge2320. Ridge2320is characterized by ridge height2322, which is the distance between the ridge and first major surface2100.

FIG.2Bis a blow-up of a portion ofFIG.2, wherein ridge2320is featured in more detail. Ridge depth2321, the depth that ridge2320extends from interior surface2310, is visible in this Figure.

FIG.3is a cut-away side view of housing3000, featuring first major surface3100, second major surface3200and cavity3300extending through the entire housing3000including featuring first major surface3100and second major surface3200. In this Figure, first major surface3100extends further across housing3000than the corresponding first major surface2100inFIG.2. Holder3400is, in this Figure, present in the form of groves in housing3000for receiving and retaining a microneedle array device (not shown). Cavity3300features interior surface3310and ridge3320.

FIG.4is a bottom view of housing4000, featuring first major surface4100, second major surface4200, and cavity4300. A holder (not shown) may be present in the form of slots for holding the microneedle array device within the housing.

FIG.5is a three-quarter view of housing5000, wherein the first major surface is not visible, but second major surface5200and cavity5300are visible. A portion of notch5320is visible within cavity5300. A portion of holder5400for holding a microneedle array device within housing5000is also visible.

FIG.6is a side view of plunger6000, featuring top6100, bottom6200and side6300. InFIG.6the plunger6000is approximately cylindrical, so there is only one side6300, but if the plunger were shaped differently it could have more than one side. On the side6300is a first notch6310located proximate to the bottom6200of the plunger6000and a second notch6320located proximate to the top6100of the plunger6000. InFIG.6, first notch6310and second notch6320are continuous around the entire side6300of plunger6000, however other configurations are possible. For example, first notch6310could be first set of multiple notches the same distance from bottom6200. Likewise, second notch6320could be a second set of multiple notches the same distance from the top, which is in the form of head7110.

FIG.7ais a side view of plunger7000, featuring a top in the form of head7110that extends outward past the side7300, as well as bottom7200. In this Figure, the plunger7000is approximately cylindrical, so there is only one side7300, but if the plunger were shaped differently it could have more than one side. On the side7300is a first notch7310located proximate to the bottom7200of the plunger7000and a second notch7320located proximate to the top, which is in the form of head7110, of the plunger7000. In this Figure, first notch7310and second notch7320are continuous around the entire side7300of plunger7000, however other configurations are possible. For example, first notch7310could be first set of multiple ridges the same distance from bottom7200. In the same way, second notch7320could be a second set of multiple notches the same distance from the top, which is in the form of head7110.

FIG.7bis a detail of second notch7320and side7300shown from a cross-section cut-away perspective. Second notch7320extends second width W2from side7300and has a profile that is substantially rotationally symmetric about axis X2. Axis X2is substantially normal to side7300, and forms angle A2with side7300. Angle A2is 90° in this Figure, though other substantially normal angles are possible. Second width W2is equal to or less than the ridge depth of the housing with which plunger7000is to be used.

FIG.7cdetail of first notch7310and side7300shown from a cross-section cut-away perspective. First notch7310extends first width W1from side7300and is has a profile that is substantially rotationally symmetric about axis X1. Axis X1is substantially normal to side7300, and forms angle A1with side7300. Angle A1is 90° in this Figure, though other substantially normal angles are possible. Second width W1is equal to or less than the notch depth of the housing with which plunger7000is to be used.

FIG.8Ais a three-quarter bottom view of microarray carrier8000, including microarray holder8100as shown inFIG.8Aas well as microneedle patch8200. Microneedle patch8200includes a central portion8210featuring a plurality of microneedles8211disposed on flexible backing8220. While the plurality of central portion8210is shown as being roughly circular, other shapes are possible. Further, whereas the plurality of microneedles8211are shown as being arranged in a particular manner, other arrangements are possible. Any suitable number of microneedles can be used, and the microneedles may be solid, hollow, or a mixture of solid and hollow. When the microneedles are solid microneedles, such as those described in U.S. Patent Application Publication No. US2015/0246214, then the microneedle patch8200typically has 90 to 1,200 microneedles, such as greater than 200 microneedles, greater than 300 microneedles, greater than 400 microneedles, less than 500 microneedles, or less than 400 microneedles on the patch, although any desired number of microneedles can be used. When the microneedles are hollow, such as those described in US20160151616, then the microneedle patch8200typically has 3 to 30 microneedles, most often 12 microneedles, although any desired number of microneedles can be used.

FIG.8Bis a three-quarter bottom view of microarray holder8100featuring tabs8101,8102,8103, and8104, which can serve to retain a microneedle patch, though no microneedle patch is shown in this Figure. Other elements for restraining a microneedle patch, such as one or more ridges or notches, could be used in a related configuration. Handle8110is a convenient feature for manipulating microarray holder8100, for example, for placing it within a housing as described herein.

FIG.9Ais a cut-away side view of assembled microarray applicator9000featuring housing2000(shown separately inFIG.2) and plunger7000(shown separately inFIG.7A). Plunger7000is in a first position, wherein first notch7310of plunger7000is engaged with ridge2320of housing2000. Second notch7320of plunger7000is outside housing2000.FIG.9Bis a blow-up showing the interaction of first notch7310and ridge2320in more detail. Bottom7200of plunger7000does not extend below first major surface2100of housing2000.

In use, pressing plunger7000in the direction of first major surface2100of housing2000with sufficient force to disengage first notch7310of plunger7000from ridge2320of housing2000can move plunger7000to a second position.

FIG.9Cis a cut-away side view of assembled microarray applicator9000featuring housing2000(shown separately inFIG.2) and plunger7000(shown separately inFIG.7A). Plunger7000is in a second position, wherein second notch7320of plunger7000is engaged with ridge2320of housing2000. Bottom7200of plunger7000extends below first major surface2100of housing2000.

FIG.10Ais a cut-away side view of assembled microarray applicator10000, which is similar to microarray applicator9000as shown inFIG.9Abut also includes microarray carrier8000, which is retained within housing2000by virtue of microarray carrier8000being engaged with holder2400. Microneedle patch8200and flexible backing8220are positioned such that the central portion8210has microneedles8211protrude in the direction opposite from the bottom7200of plunger7000. Bottom7200of plunger7000sits on or, more commonly, slightly above microneedle patch8200. In this Figure, plunger7000is in a first position, having first notch7310engaged with ridge2320. Handle8110(not shown inFIG.10A; seeFIGS.8A and8B) is preferably present as a component of microarray holder8100for ease of use.

FIG.10Bis a cut-away side view of assembled microarray applicator10000after activation, wherein plunger7000is in a second position such that second notch7320is engaged with ridge2320. Here, bottom7200of plunger7000extends below first major surface2100of housing2000, and has ejected microneedle patch8200, thereby applying microneedles8211to substrate10100, which is typically the skin of a subject. In practice, a user can maintain contact between microneedles8211and substrate10100by continuing to apply pressure on plunger7000.

Once microneedle patch8200has been ejected from housing2000, the microarray applicator can be reused. To do so, microarray holder8100can be removed from holder2400, for example by using handle8110(not shown inFIGS.10A and10B). Plunger7000can then be moved from the second position to the first position by pushing on bottom7200of plunger7000until first notch7310engages with ridge2320.

The applicator as described herein is inexpensively manufactured, for example, all of the components can be made with simple dies by extruding inexpensive plastics such as polypropylene. Thus, the applicator is economical to be used as a single-use device. It can also be re-used, in which case there is little chance of requiring expensive maintenance or repair because it does not contain any complex parts. Further, because it can be easily used by an operator without the need for complex priming steps, it can be viable for an operator who is not a medical professional to use the disclosed applicator, allowing easy application of a microneedle patch without the need for a medical professional to administer it.