Patent Application
20150038911
The present invention relates to drug deliver devices and, in particular, it concerns a microneedle adapter for use with dosed drug delivery devices.
Dosed drug delivery devices, often referred to as “pen injectors,” are commonly used by diabetics for routine injection of insulin. Similar devices are also used for the delivery of hormones. Dosed drug delivery devices are a preferred means of delivery wherever the volume of drug delivered needs to be variable but accurate, small and frequently administered. Use of the term “pen injector” probably stems from the elongated pen-like form of many of the commercially available devices. However, unless otherwise specified, the term “pen injector” will be used herein interchangeably with the term “dosed drug delivery device” to refer generically to any and all free-standing portable device containing a plurality of doses of a therapeutic liquid which can be operated by a patient for self-injection to deliver metered doses of the liquid to the patient's body on a plurality of occasions. There are various kinds of pen injectors which may be variously classified according to different structural or functional features, such as: devices employing replaceable cartridges and devices which are disposed of when the contents are finished; devices with fixed dosage units or with various dialing and dosing features; devices with different flow activation mechanisms, ergonomics and design, reservoir systems and volume requirements etc.
Pen injectors are used with dedicated replaceable needle assemblies, referred to herein for convenience as “pen needles”. Commercially available pen needles known to the inventors all target the subcutaneous (SC) fatty layer and make use of tubular metal components (hypodermic stainless steel needles). Commercially available pen needles typically have lengths ranging from 1 mm to 25 mm.
Pen needles are configured to satisfy several requirements unique to pen injectors. On one side, they feature a connector for reversibly connecting to a liquid reservoir within the pen injector. The connector typically includes a hollow needle deployed for piercing a septum (resilient self-sealing membrane) integrated with the liquid cartridge, and an attachment configuration such as a threaded collar for attachment to the pen injector. On the other side, the pen needle features the skin-penetrating needle. The septum-piercing needle and the skin-penetrating needle are typically implemented as opposite ends of a single double-ended needle. The two ends typically have different point shapes, with the rear end configured to avoid coring of a hole in the septum and the front end shaped to minimize pain on penetration through the skin. This renders the double ended needle complex to manufacture. On the other hand, since a single continuous needle is used, there is typically no requirement of sealing between the needle and the surrounding connector body, often allowing the structure to be assembled without the sealing glue required for other hypodermic applications, and the “dead volume” of the needle is very small. For all of the above reasons, design considerations for pen needles are significantly different from those of other hypodermic needles, and such needles have attained a distinct status in the art, often being produced by Specialist companies which deal exclusively with pen needles and other pen injector related accessories.
Miniature needles used for pen injectors typically project a minimum of 1 millimeter. In the case of a miniature needle of conventional hypodermic type (i.e., a metal tube formed with a beveled end), the bevel of the needle tip itself typically has a length of at least 0.8 mm, making it impossible to achieve sealed fluid delivery to penetration depths less than 1 mm.
In some published documents, it has been proposed to use “microneedles” as a delivery interface for pen injectors. For the purpose of the present description and claims, the term “microneedle” in its broadest sense is used to refer to a projecting structure with a projecting length of less than 1 millimeter. Examples of such documents include US patent application publication nos. US 2003/0050602 to Pettis and US 2003/0181863 to Ackley et al. Theoretically, application of microneedles to pen injectors promises various advantages attributed to intradermal delivery including, but not limited to, altered kinetics (depending on the formulation and the exact injection site, either accelerated absorption, such as may be beneficial for insulin delivery or delayed absorption, for example if a slow release formulation is used), improved response (for example intradermal delivery of vaccines may enhance immune response, allow for smaller doses, potentially lesser booster shots, better vaccination, etc), reduced trauma (since microneedles are smaller than conventional hypodermic needles), and minimally painful or painless injections. The last feature, in particular, is considered highly significant, possibly increasing patient compliance, improving quality of life, improving disease control and reducing expenses on treatment of disease complications. This is particularly relevant in the case of insulin injections for treatment of diabetes due to the direct relation between long term control of blood glucose levels and the prevalence of long term complications.
In practice, implementations of microneedles for pen injectors are not straightforward due to a number of practical problems. A first major problem of many microneedle designs relates to mechanical weakness of the microneedles which tend to fracture on contact with the skin, particularly when exposed to shear forces due to lateral movement A further problem is that the highly elastic skin barrier tends to deform around the microneedles without the microneedles penetrating through the stratum corneum (SC). An additional problem is that of leakage around the microneedles' point of insertion and/or ejection of the needles by back-pressure generated during injection. Many designs are also prone to blockage of the bores of hollow microneedles due to punching-out of a plug of tissue during insertion through the skin.
Solutions to the aforementioned problems have been suggested in the context of applications such as infusion sets and syringes. Particularly, reference is made to a particularly advantageous robust microneedle structure as taught by U.S. Pat. No. 6,533,949, and to various microneedle insertion techniques as taught by PCT Patent Application Publication Nos. WO 03/074102 A2 and WO 2005/049107 A2, and in US Patent Application Publication No. US 2005/0209566 A1, these four publications mentioned in this paragraph all being hereby incorporated by reference in their entirety. However, these solutions have not previously been adapted to address the particular requirements of pen injectors. Furthermore, given the unique design considerations for pen needles, and the distinct status of pen needles as established in the art, such adaptations are not readily apparent to a person having ordinary skill in the art.
There is therefore a need for an adapter for achieving intradermal dosed delivery of a liquid by use of a dosed drug delivery device.
The present invention is an adapter for achieving intradermal dosed delivery of a liquid by use of a dosed drug delivery device.
According to the teachings of the present invention there is provided a first adapter for achieving intradermal dosed delivery of a liquid by use of a dosed drug delivery device, the dosed drug delivery device including a reservoir having a pierceable septum, the adapter comprising: (a) a connector including an attachment configuration for attachment to the dosed drug delivery device and a hollow needle deployed for piercing the septum; (b) a liquid delivery interface mechanically linked to the connector, the liquid delivery interface including a substantially straight skin contact edge and a linear array of hollow microneedles deployed substantially adjacent to, and arrayed substantially parallel to, the skin contact edge, the microneedles projecting away from the skin contact edge; and (c) a flow path arrangement interconnecting the needle and the array of hollow microneedles.
According to a further feature of the present invention, each of the microneedles has a height, and wherein a distance between the skin contact edge and each of the microneedles is no greater than the height of the microneedles.
According to a further feature of the present invention, the substantially straight skin contact edge is formed as an edge of a block of material, the block of material being integrally formed with at least part of the attachment configuration.
According to a further feature of the present invention, an extensional direction of the hollow needle of the connector defines a primary flow axis, and wherein each of the hollow microneedles includes a flow channel defining an injection direction, the injection direction being inclined relative to the primary flow axis by an angle of at least 20 degrees.
According to a further feature of the present invention, the injection direction is inclined relative to the primary flow axis by an angle of between 30 degrees and 150 degrees.
According to a further feature of the present invention, the injection direction is inclined relative to the primary flow axis by an angle of about 90 degrees.
According to a further feature of the present invention, the hollow microneedles are integrally formed with a substrate.
According to a further feature of the present invention, the substrate has a substantially planar surface, and wherein each of the microneedles is fainted by at least one wall standing substantially upright from the substantially planar surface and an inclined surface intersecting with the at least one wall.
According to a further feature of the present invention, each of the microneedles has a flow channel passing through the substrate and intersecting with the inclined surface.
According to a further feature of the present invention, the microneedles are formed from silicon.
There is also provided according to the teachings of the present invention, a combination of the aforementioned adapter with a dosed drug delivery device, the combination further including a dosed drug delivery device having a liquid reservoir including a pierceable septum, the adapter being connected to the dosed drug delivery device so that the hollow needle pierces the septum thereby bringing the microneedles into flow connection with contents of the reservoir.
According to a further feature of the present invention, the reservoir contains a quantity of insulin. Alternatively, the reservoir contains a quantity of a fertility hormone. In a further alternative, the reservoir contains a quantity of a growth hormone. In yet a further alternative, the reservoir contains a quantity of a vaccine.
There is also provided according to the teachings of the present invention, a second adapter for achieving intradermal dosed delivery of a liquid by use of a dosed drug delivery device, the dosed drug delivery device including a reservoir having a pierceable septum, the adapter comprising: (a) a connector including an attachment configuration for attachment to the dosed drug delivery device and a hollow needle deployed for piercing the septum; (b) liquid delivery interface mechanically linked to the connector, the liquid delivery interface including a substantially straight skin contact edge and at least one hollow microneedle deployed substantially adjacent to the skin contact edge, the at least one microneedle projecting away from the skin contact edge; and (c) a flow path arrangement interconnecting the needle and the at least one hollow microneedle.
Furthermore, according to the present invention there is provided a third adapter for achieving intradermal dosed delivery of a liquid by use of a dosed drug delivery device, the dosed drug delivery device including a reservoir having a pierceable septum, the adapter including: (a) a connector including: (i) an attachment configuration for attachment to the dosed drug delivery device by sliding the adapter onto the dosed drug delivery device so that a recess of the adapter mates with a matching projection of the dosed drug delivery device, and (ii) a hollow needle deployed for piercing the septum; (b) at least one hollow microneedle projecting from the connector; and (c) a flow path arrangement interconnecting the needle and the at least one hollow microneedle; wherein the recess is shaped to restrict the at least one microneedle to one of a finite number of rotational orientations relative to an axis of the dosed drug delivery device when the adapter is attached to the dosed drug delivery device.
Furthermore, according to the present invention there is provided a fourth adapter for achieving intradermal dosed delivery of a liquid by use of a dosed drug delivery device, the dosed drug delivery device including a reservoir having a pierceable septum, the adapter including: (a) a connector including an attachment configuration for attachment to the dosed drug delivery device and a hollow needle deployed for piercing the septum; (b) at least one hollow microneedle projecting from the connector; and (c) a flow path arrangement interconnecting the needle and the at least one hollow microneedle; wherein at least one of the connector and the needle is adapted for application of a sealant to cover the flow path arrangement and at least a portion of the needle so as to prevent leakage of the liquid from the flow path arrangement.
Furthermore, according to the present invention there is provided a fifth adapter for achieving intradermal dosed delivery of a liquid by use of a dosed drug delivery device, the dosed drug delivery device including a reservoir having a pierceable septum, the adapter including: (a) a connector including an attachment configuration for attachment to the dosed drug delivery device and a hollow needle deployed for piercing the septum; (b) a linear array of hollow microneedles projecting from the connector; and (c) a flow path arrangement, interconnecting the needle and the at least one hollow microneedle, that is wider, in a direction transverse to a direction of a flow of the liquid from the needle to the array of microneedles, than both the needle and the array of microneedles.
Furthermore, according to the present invention there is provided a sixth adapter, for achieving intradermal dosed delivery of a liquid, including: (a) a connector including an attachment configuration for attachment to a dosed drug delivery device; (b) a linear array of hollow microneedles projecting from the connector; wherein at least a portion of the connector adjacent the linear array of microneedles is wider in a direction parallel to the linear array of microneedles than in a direction perpendicular to the linear array of microneedles, the adapter further including: (c) a cap, shaped to conform to the connector and to slide onto the connector to cover the microneedles and at least a portion of the portion of the connector that is adjacent to the microneedles, an edge of the cap that receives the connector, when the cap is slided onto the connector, being recessed on a portion thereof that is parallel to the linear array of microneedles relative to a remainder thereof.
Furthermore, according to the present invention there is provided a cap, for a dosed drug delivery device from which at least one microneedle projects, the cap including: (a) a cap body, shaped to conform to at least a portion of the dosed drug delivery device when the cap is placed onto the dosed drug delivery device to cover the at least one microneedle; (b) a cap cover, at a distal end of the cap body, that substantially seals the distal end of the cap body; and (c) a mechanism, in the cap body, for reversibly urging the dosed drug delivery device away from the cap cover; wherein the cap cover includes an aperture from which the at least one microneedle protrudes when the dosed drug delivery device is urged towards the cap cover.
Furthermore, according to the present invention there is provided a fluid delivery device including: (a) a hollow needle; (b) a fitting for operationally connecting the needle to a syringe; (c) a cap that conceals the needle and that includes an aperture; and (d) a mechanism that reversibly urges the aperture away from the needle, thereby preventing the needle from emerging from the aperture unless an opposing force is applied to the fluid delivery device via the fitting.
The third adapter of the present invention is similar to the second adapter, with the attachment configuration being attached to the dosed drug delivery device by sliding the adapter onto the dosed drug delivery, device so that a recess of the adapter mates with a matching projection of the dosed drug delivery device. The recess is shaped to restrict the microneedle(s) to one of a finite number of rotational orientations, and preferably to a single such rotational orientation, relative to the axis of the dosed drug delivery device when the adapter is attached to the dosed drug delivery device.
Preferably, the liquid delivery interface includes a linear array of the microneedles.
A combination of the third adapter with a dosed drug delivery device also is provided, the combination further including a dosed drug delivery device having a liquid reservoir including a pierceable septum, the adapter having been connected to the dosed drug delivery device by sliding the adapter onto the dosed drug delivery device so that the recess mates with the projection and so that the hollow needle pierces the septum thereby bringing the microneedle(s) into flow connection with contents of the reservoir.
Preferably, the attachment configuration includes a mechanical arrangement for inhibiting removal of the ad pier from the dosed drug delivery device after the adapter has been attached to the dosed drug delivery device.
The fourth adapter of the present invention also is similar to the second adapter, with either or both of the connector or the hollow needle is/are adapted for application of a sealant to cover the flow path arrangement and at least part of the needle to prevent leakage of the liquid from the flow path arrangement. For example, the connector could include a port for introducing the sealant into the interior of the connector, or the outer surface of the needle could be formed in a manner that promotes bonding thereto of the sealant.
The fifth adapter of the present invention also is similar to the second adapter, with the flow path arrangement being wider in a direction transverse to the direction of the flow of the liquid from the needle to the array of microneedles, than both the needle and the array of microneedle(s).
The sixth adapter of the present invention includes the connector and. the liquid delivery interface of the second adapter. At least the portion of the connector that is adjacent to the array of microneedles is wider in the direction parallel to the array of microneedles than. in the direction perpendicular to the array of microneedles. The adapter also is provided with a cap that is shaped to conform to the connector and to slide onto the connector to cover the microneedles and the adjacent portion of the connector. The edge of the cap that receives the connector when the cap is slided onto the connector is recessed, relative to the rest of the edge, on the portion of the edge that is parallel to the array of microneedles.
The scope of the present invention also includes a cap for a dosed drug delivery device equipped with an adapter, such as the adapters of the present invention, from which one or more microneedles project. The cap includes a cap body and a cap cover. The cap body is shaped to conform to at least a portion of the dosed drug delivery device when the cap is placed on the dosed drug delivery device to cover the microneedle(s). The cap cover, at the distal end of the cap, substantially seals the cap body. The cap also includes a mechanism, in the cap body for reversibly urging the dosed drug delivery device away from the cap cover. The cap cover includes an aperture from which the microneedle(s) protrude(s) when the dosed drug delivery device is urged towards the cap cover.
Preferably, at least part of the outer surface of the cap cover is roughened to apply tension to skin into which liquid is being delivered via the microneedle(s) as the microneedle(s) protrude(s) from the aperture. Most preferably, the cap cover is substantially planar and is tilted so that the roughened portion of the cap cover contacts the skin before the microneedle(s) when the dosed drug delivery device, with the cap covering the liquid delivery interface, is applied to the skin to deliver the liquid into the skin via the microneedle(s) as the microneedle(s) protrude(s) from the aperture.
The scope of the present invention also includes a fluid delivery device that includes a hollow needle such as a microneedle, a fitting for operationally connecting the needle to a syringe, a cap that conceals the needle and that includes an aperture, and a mechanism that reversibly urges the aperture away from the needle, so that the needle is prevented from emerging from the aperture unless an opposing force is applied to the fluid delivery device via the fitting.
The invention is herein described, by way of example only, with. reference to the accompanying drawings, wherein:
The present invention is an adapter for use with a dosed drug delivery device to achieve intradermal dosed delivery of a liquid.
The principles and operation of adapters according to the present invention may be better understood with reference to the drawings and the accompanying description.
By way of introduction, the present invention relates to an adaptation of a microneedle drug delivery interface and corresponding technique described in US Patent Application Publication No US 2005/0209566 A1 to render it suitable for use as a disposable drug delivery interface for pen injectors. The adapter most preferably employs microneedles produced by MEMS techniques from a single-crystal block of material such as silicon according to the teachings of U.S. Pat. No. 6,533,949. Alternatively, various other forms of microneedles and/or other materials may be used, such as are taught in U.S. Pat. No. 6,503,231 to Prausnitz et al. These documents are hereby incorporated by reference herein and provide helpful background to the present invention.
Referring now to the drawings,
Turning now to
Prior to use, adapter 50 is preferably protected by a front cover 30, as shown in
Gamma irradiation or exposure to Ethylene Oxide.
The mode of use of adapter 50 will be understood with reference to
At this stage, it will already be apparent that the adapter of the present invention provides profound advantages over the prior art. Specifically, all pen injector art known to the inventors maintains the conventional approach of perpendicular insertion of the needle(s) into the skin, thereby suffering from the aforementioned limitations of penetration depths in excess of 1 millimeter for conventional needles, or problems of incomplete penetration and ejection by back pressure for microneedles. In contrast, by providing the unique geometry of the present invention in which an array of microneedles are adjacent to a skin contact edge, the present invention facilitates insertion of microneedles so that the microneedle flow channels are directed sideways, i.e., at an angle in the range of ±30° from the initial plane of the skin surface, into tissue not squashed under the device. As a result, the adapter of the present invention allows a pen injector to be used to achieve shallower intradermal liquid delivery than is possible using conventional devices, and is believed to encounter reduced flow impedance and achieve better intradermal distribution than would otherwise be achieved. These and other advantages of the present invention will be better understood with reference to the following description.
Turning now to the features of the present invention in more detail, skin contact edge 26 is preferably formed as an edge of a block of material which supports the microneedle array 10. Most preferably, this block is integrally formed with at least part of the attachment configuration. Thus, in the example of
Body 20 also preferably defines any flow paths 28 required to interconnect needle 25 with the flow channels of the microneedles. In the preferred implementation shown, this includes a transverse open channel formed under the point of attachment of microneedles array 10 so that, when the substrate is attached by use of adhesive, welding or other known methods, the channel together with the rear surface of the substrate forms a closed channel for distributing liquid from needle 25 to all of the microneedles. The positioning of this channel is chosen to intersect a central axis of the adapter 50 along which needle 25 is aligned, thereby simplifying manufacture of body 20, as will be clear to one familiar with plastic injection molding technology.
The form of body 20 is chosen to facilitate bringing the microneedles into contact with the skin in the correct orientation. In the preferred example shown here, body 20 is formed with a forward projecting portion which is roughly rectangular in cross-section, having a major dimension parallel to the extensional direction of microneedle array 10 and a minor dimension perpendicular thereto. The microneedles are preferably deployed with the inclined surface having flow channel 2 facing downwards, i.e., inwards towards the depth of the tissue.
In order to optimize the sideways insertion geometry, the microneedles are preferably close to edge 26. Preferably, a distance between skin contact edge 26 and each of the microneedles, defined as the distance between edge 26 and the closest part of the base of the microneedles, is no greater than the height of the microneedles themselves as measured perpendicular to the surface of the substrate. Most preferably, the microneedles are juxtaposed with their base starting substantially at edge 26. Parenthetically, it should be noted that edge 26 itself may be provided by either the edge of the substrate of microneedle array 10 or by an edge of body 20 adjacent to the array 10.
It will be noted that adapter 50 causes a significant deflection of the flow direction between the axial direction of the dosed drug delivery device (corresponding to the direction of needle 25) and the injection direction as defined by the flow channels of the microneedles.
This deflection is preferably at least about 20 degrees and, more preferably, between about 30 and about 150 degrees. In the case shown here, the deflection is roughly 40 degrees. Nevertheless, in order to achieve an injection direction near parallel to the initial plane of the skin, this embodiment requires deployment of the pen injector at an inclination as shown in
Parenthetically, although the device is illustrated here in a preferred embodiment in which a linear array of microneedles is used, it should be noted that a minimal embodiment in which a single microneedle is used in proximity to skin contact edge 26 also falls within the broad scope of the present invention.
In other respects, the structural features and function of adapter 55 will be understood by analogy to the corresponding features and function of adapter 50 described above, with like elements being labeled similarly.
The embodiments described above did not specify a rotational orientation of adapter 50 or 55 relative to pen injector 100. It often is advantageous to specify such an orientation. For example, as pen injector 100 is being used with adapter 50 as illustrated in
In
Adapter 102 is mounted on pen injector 108 by sliding adaptor 102 axially, i.e. in the direction defined by axis 105, towards pen injector 108 so that recess 104 mates with projection 106, and similarly for how adapters 112, 122, 132, 142 and 152 are mounted on pen. injectors 118, 128, 138, 148 and 158. Other mechanical arrangements for sliding an adapter onto a pen injector so as to be mounted only in one of a small number of preferred orientations also are possible. One such arrangement is illustrated in
Unlike adapters 50 and 55, adapters 102, 112, 122, 132, 142 and 152 can slide off of their respective pen injectors 108, 118, 128, 138, 148 and 158 as easily as they can slide on.
As described above, the septum-piercing needle and the skin-penetrating needle of a prior art pen needle typically are implemented as opposite ends of a single double-ended needle. As such, there is no danger of liquid leaking from a gap between the septum-piercing needle and the skin-penetrating needle. This is not the case for the adapters of the present invention, in which hollow needle 25 and microneedle array 10 are separate components that are connected via flow path arrangement 28. It is especially important to prevent leakage around flow path arrangement 28 in the typical case that the dose of liquid to be delivered via microneedle array 10 is very small. For this purpose, a sealant is introduced to the adapter to seal the interfaces between microneedle array 10, flow path arrangement 28 and needle 25. The sealant is introduced as a liquid that hardens in place to seal the interfaces between microneedle array 10, flow path arrangement 28 and needle 25.
Even a well-sealed flow path arrangement 28 could be breached by high pressure and turbulence in the liquid as the liquid is injected.
Returning temporarily to
The principles of cap 214 may be applied more widely than to just pen injectors.
It will be appreciated that the present invention may be used to advantage in a large number of drug delivery applications, including both applications for which pen injectors are conventionally used and new applications for which the shallow intradermal delivery achieved by the present invention may be advantageous. Examples of applications include, but are not limited to, administering: insulin, fertility hormones, growth hormone and vaccines. Other applications include, but are not limited to, the substances and modes of treatment mentioned in US Patent Application Publication No. 2005/0163711 A1, which is hereby incorporated by reference herein.
It will be appreciated that the above descriptions are intended only to serve as examples, and that many other embodiments are possible within the scope of the present invention as defined in the appended claims.
| Filing Document | Filing Date | Country | Kind |
|---|---|---|---|
| PCT/IB2013/050617 | 1/24/2013 | WO | 00 |
| Number | Date | Country | |
|---|---|---|---|
| 61589882 | Jan 2012 | US | |
| 61598364 | Feb 2012 | US |
