The present invention relates to systems and methods providing auto disable (AD) features to a microneedle device and, in particular, systems and methods for performing such using microneedle-syringe mating arrangements. The invention also provides various other auto-disable or safety features not necessarily limited to microneedle applications.
Microneedles, defined herein as sharp projections with a total exposed length of no more than 1 millimeter, may be used for intradermal (ID) injections of fluids. Such injections may facilitate dose sparing. For example it has been previously demonstrated that reduced doses of a vaccine delivered intradermally can produce equivalent immune responses (or immunogenicity) with the full dose (and volume) of intra-muscular (IM) injection (Van Damme P, et al. Safety and efficacy of a novel microneedle device for dose sparing intradermal influenza vaccination in healthy adults. Vaccine (2008), oi:10.1016/j.vaccine.2008.10.077), as well as sometimes improve the immune response despite the use of lesser doses (Holland D, Booy R, De Looze F, Eizenberg P, McDonald J, Karrasch J, et al. Intradermal influenza vaccine administered using a new microinjection system produces superior immunogenicity in elderly adults: a randomized controlled trial. J Infect Dis 2008; 198:6508 and Hung I F N, Levin Y, To K W W, Chan K H, Zhang A J, Li P, Li C, Xu T, Wong T Y and Yuen K Y. Dose sparing intradermal trivalent influenza (2010/2011) vaccination overcomes reduced immunogenicity of the 2009 H1N1 strain. Vaccine. In Press. Available online 17 Aug. 2012. http://dx.doi.org/10.1016/j.vaccine.2012.08.014).
For some immunization (as well as therapeutic or diagnostic) applications, and for some markets (e.g. the developing countries markets, or globally for drug users) there is a need to “auto disable” the device, i.e., to prevent reuse of the drug delivery device, which might lead to cross infection and contamination.
Implementation of an auto-disable syringe with a microneedle injection interface presents particular challenges. Specifically, the short length of the microneedles prevents the injection interface from being used to withdraw a drug from a storage vial. Instead, a dedicated filling adapter (either a filling needle or a vial adapter) must first be used, and a microneedle adapter is then substituted for the filling adapter. The interchangeability of the adapters tends to facilitate improper repeat usage.
There is therefore a need for a microneedle intradermal drug delivery device which would provide auto-disable functionality.
An aspect of the present invention is a microneedle intradermal drug delivery device providing auto-disable functionality.
According to the teachings of an embodiment of the present invention there is provided, an intradermal drug delivery device comprising: (a) a syringe having a plunger displaceable along a barrel for drawing a quantity of a liquid drug through an outlet and expelling the liquid drug through the outlet; and (b) a microneedle adapter including at least one hollow microneedle, the microneedle adapter being configured to mate with the syringe so as to provide a leak-free flow path from the outlet through the at least one hollow microneedle for delivering the liquid drug intradermally, wherein the microneedle adapter and the syringe are configured for irreversible engagement such that, after attachment of the microneedle adapter to the syringe, the microneedle adapter is resistant to non-destructive manual removal from the syringe.
According to a further feature of an embodiment of the present invention, the outlet runs through a male conical fitting having a conical angle of less than 5.5%, and wherein the microneedle adapter is formed with a female conical fitting configured to mate with the male conical fitting.
According to a further feature of an embodiment of the present invention, the outlet runs through a male conical fitting formed with a circumferential groove, and wherein the microneedle adapter is formed with a female conical fitting having at least one ridge, the female conical fitting being configured to mate with the male conical fitting with the at least one ridge engaging the groove.
According to a further feature of an embodiment of the present invention, the outlet runs through a male conical fitting fowled with at least one projecting ridge, and wherein the microneedle adapter is formed with a female conical fitting having a circumferential groove, the female conical fitting being configured to mate with the male conical fitting with the at least one ridge engaging the groove.
According to a further feature of an embodiment of the present invention, the syringe is formed with at least one resilient engagement portion deployed to provide snap-engagement with a corresponding feature of the microneedle adapter.
According to a further feature of an embodiment of the present invention, the microneedle adapter is formed with at least one resilient engagement portion deployed to provide snap-engagement with a corresponding feature of the syringe.
According to a further feature of an embodiment of the present invention, the at least one hollow microneedle is integrally formed with a substrate from a single crystal material.
According to a further feature of an embodiment of the present invention, the at least one hollow microneedle is formed with at least one upright surface, an inclined surface intersecting with the at least one upright surface, and a fluid flow bore extending through the substrate and intersecting with the inclined surface.
According to a further feature of an embodiment of the present invention, there is also provided a vial adapter configured for releasable engagement with the outlet for filling of the syringe.
According to a further feature of an embodiment of the present invention, the plunger is formed with a plunger extension extending from a seal of the plunger and configured to advance within the outlet as the plunger is advanced, thereby reducing a dead-space of the syringe.
According to a further feature of an embodiment of the present invention, the plunger extension further comprises a resilient tip configured to extend beyond the outlet in a fully advanced position of the plunger, the resilient tip being configured to expand laterally so as to engage a region of the syringe around the outlet, thereby inhibiting withdrawal of the plunger extension.
According to a further feature of an embodiment of the present invention, the plunger further comprises a reduced-strength region configured to break under traction applied to withdraw the plunger after engagement of the resilient tip.
According to a further feature of an embodiment of the present invention, the syringe is an auto-disable syringe preventing refilling.
According to a further feature of an embodiment of the present invention, there is also provided a sheath circumscribing the barrel, the sheath being selectively displaceable to an advanced position in which the sheath covers the microneedle adapter, the sheath and the syringe having interlocking features configured to prevent retraction of the sheath from the advanced position.
According to a further feature of an embodiment of the present invention, the at least one hollow microneedle is implemented as a plurality of microneedles.
According to a further feature of an embodiment of the present invention, the at least one hollow microneedle is implemented as a linear array of at least three microneedles.
There is also provided according to an embodiment of the present invention, an auto-disable syringe comprising: (a) a syringe body comprising a barrel and terminating at an outlet; and (b) a plunger having a shaft for driving a seal along the barrel so as to deliver a quantity of liquid through the outlet, wherein the plunger is formed with a plunger extension extending from the seal of the plunger and configured to advance within the outlet as the plunger is advanced, and wherein the plunger extension further comprises a resilient tip configured to extend beyond the outlet in a fully advanced position of the plunger, the resilient tip being configured to expand laterally so as to engage a region of the syringe around the outlet, thereby inhibiting withdrawal of the plunger extension.
According to a further feature of an embodiment of the present invention, the shaft, the plunger extension and the resilient tip are integrally formed as a single element.
According to a further feature of an embodiment of the present invention, the plunger further comprises a reduced-strength region configured to break when force is applied to withdraw the plunger after engagement of the resilient tip.
The invention is herein described, by way of example only, with reference to the accompanying drawings, wherein:
An aspect of the present invention is a microneedle intradermal drug delivery device providing auto-disable functionality.
The principles and operation of drug delivery devices according to the present invention may be better understood with reference to the drawings and the accompanying description.
By way of introduction, an aspect of the present invention takes advantage of the inherent difficulty of refilling a drug delivery device via a microneedle adapter to provide auto-disable functionality. Specifically, according to certain preferred implementations of the present invention, by rendering attachment of a microneedle adapter to a syringe irreversible, this inherently limits the user's ability to refill the device for repeat usage.
Referring now to the drawings,
It is a particular feature of this aspect of the present invention that microneedle adapter 20 and syringe 12 are configured for irreversible engagement such that, after attachment of microneedle adapter 20 to syringe 12, microneedle adapter 20 is resistant to non-destructive manual removal from syringe 12. Since the microneedles are too short to penetrate the septum of a drug vial, irreversible engagement of the microneedle adapter with the syringe inherently prevents refilling of the syringe from a drug vial.
Turning now to
The sealed interconnection between the syringe 12 and microneedle adapter 20 is preferably provided (here and in all other embodiments) by male/female Luer connector surfaces, which may be standard taper surfaces or the modified taper angle surfaces described with reference to
Turning now to
In all of the above cases, microneedle adapter 20 has been described as having at least one hollow microneedle 22. Most preferably, the microneedle is integrally formed with a substrate from a single crystal material, typically silicon. A particularly preferred choice of microneedle structure is the hollow micropyramid commercially available from Nanopass Technologies Ltd. under the trade name MICRONJET 600. These microneedles are formed with at least one surface which is upright relative to the plane of the substrate surface and an inclined surface intersecting with the upright surface(s) to form an asymmetric pyramid structure. A fluid flow bore extends through the substrate and intersects with the inclined surface. Additional details about the manufacturing process for such needles may be found in U.S. Pat. No. 7,648,484. Most preferably, at least two microneedles are used, and typically a linear array of at least three microneedles.
Filling of syringe 12 must be performed prior to attachment of microneedle adapter 20, typically by attachment of a dedicated filling adapter, which may be a filling needle or a vial adapter. The filling adapter must be releasably engaged with syringe 12 so that it can be disconnected after filling. By way of one non-limiting example,
In certain cases, microneedle drug delivery devices are valuable for delivering particularly small doses of drugs intradermally. The term “drug” is used herein in the broadest possible sense to include all compositions which are delivered into the body for therapeutic or other medically relevant effect. In such cases, and particularly for expensive drugs, reduction of dead space within the drug delivery device is of great importance. A range of possible dead-space-reducing inserts are disclosed in co-pending PCT Publication No. WO2010/067319, and may be used to advantage in the context of the present invention.
In use, the assembly is provided with the plunger in a forward position but just short of its locked state. Filling is performed using a suitable filling adapter by drawing the plunger back, the microneedle adapter (or in other applications, a regular needle) is connected to the outlet, and bubbles are purged from the syringe in the normal manner. The syringe is then ready for drug delivery.
As the plunger advances, plunger extension 56 advances within outlet channel 18 with its resilient tip 58 compressed, progressively contributing to reduction of the dead space within the drug delivery device. As the plunger reaches the end of its stroke, resilient tip 58 clears the end of outlet 18 and expands laterally/radially, thereby preventing withdrawal of the plunger. If significant force is applied in an attempt to draw back the plunger (e.g., for refilling), shaft 54 breaks away from plunger extension 56 at reduced-strength region 60, leaving the plunger seal 14a inaccessibly lodged at the end of the barrel and preventing re-use of the syringe.
Although described herein in the context of the implementation of
Turning now to
The interlocking features are best seen in
The embodiment of
It should be noted that the various embodiments of the invention described above can be implemented using a wide range of materials. For example, possible syringe materials include but are not limited to glass and polymer (including PC, PP and others); possible hub materials include but are not limited to polymer (including PC, PP and others). Sealing elements are typically made from various elastomers, such as those commonly used in the industry. Silicone derivatives or rubbers could be employed for any such component. The drugs to be delivered may be anything that could be used in medicine, aesthetics and cosmetics. These could include liquid, and in some cases non-liquid, formulations or substances.
Additional elements such as safety syringe concepts, safety shields, safety needles, safety vial withdrawing systems and the like could be employed in combination with some of the embodiments.
The actuation of the different parts in some of the embodiments could be performed manually, but in various cases also mechanically (through spring or pressure mechanisms and others) and even electronically.
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.
Number | Date | Country | |
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61551448 | Oct 2011 | US |