Prefilled syringe plunger simulation training device

In an embodiment, an injection simulation device is provided including a housing defining a channel, the housing comprising a proximal end and a distal end, a plunger comprising a plunger rod body having a proximal end and a distal end and a stopper disposed at the distal end of the plunger rod, the plunger movable proximally and distally within the channel; and a friction feature associated with the housing, the friction feature for interfacing with the plunger rod, wherein the plunger moves in a distal direction relative to the housing to simulate medicament delivery and in a proximal direction to reset the injection simulation device, wherein the friction feature optionally causes differential resistance on the plunger rod, when the plunger rod moves in either the distal or proximal direction.

BACKGROUND

Injectable medications are required for a number of varying illnesses and diseases. Many injectable medications require self-injection by a patient. Self-injection of a medicament using a device having a needle carries with it a certain stigma. Oftentimes users are weary of administering an injection for fear or anxiety related to handling an injection device, failing to deliver a complete dose of the medication, anticipated pain associated with injecting oneself, fear of accidentally sticking oneself with the needle during manipulation of the injection device, and difficulties in adequately grasping the dosing mechanism or injection device to inject oneself, among other concerns. An additional concern exists in instances in which users with little or no medical knowledge or experience are required to inject themselves or another subject using these devices. Moreover, the viscosities of medications vary from one medication to another. The viscosity of the medication being dispensed with an injection device has an effect on the amount of pressure needed to deliver the medication through the needle and into the subject. For those who are inexperienced in providing injections, or persons who are not familiar with the sensation related to the amount of pressure on a plunger of a prefilled syringe device needed to disperse medicament from a vial, through a needle, and into a patient would benefit from a training device designed to familiarize a user with this process. Moreover, familiarization with the sensations experienced during an injection with a medication having a particular viscosity. and requiring a certain amount of force and time to deliver the medication to the user would be beneficial in reducing the anxiety associated with delivering the medicament via injection, as well as ensuring an effective dose is delivered with the medicament delivery device.

SUMMARY

In an embodiment, an injection simulation device is provided including a housing defining a channel, the housing comprising a proximal end and a distal end, a plunger comprising a plunger rod body having a proximal end and a distal end and a stopper disposed at the distal end of the plunger rod, the plunger movable proximally and distally within the channel; and a friction feature associated with the housing, the friction feature for interfacing with the plunger rod, wherein the plunger moves in a distal direction relative to the housing to simulate medicament delivery and in a proximal direction to reset the injection simulation device, wherein the friction feature optionally causes differential resistance on the plunger rod, when the plunger rod moves in either the distal or proximal direction.

In other embodiments, an injection simulation device is provided including a housing defining a channel, the housing comprising a proximal end and a distal end, a plunger comprising a plunger rod having a proximal end and a distal end and movable proximally and distally within the channel, and a stopper at the distal end of the plunger rod, and a stopper protrusion member for creating a resistance on the stopper relative to the housing, wherein the stopper protrusion member optionally causes differential resistance on the stopper during movement of the stopper in either the distal or proximal direction.

In yet other embodiments, an injection simulation device is provided including a housing defining a channel, the housing comprising a proximal end and a distal end, an inner surface and an outer surface, a plunger comprising a plunger rod having a proximal end and a distal end and a stopper disposed at the distal end of the plunger rod, the plunger movable proximally and distally within the channel such that the stopper interfaces with the inner surface of the housing, and a surface texture region on the inner surface of the housing, the stopper, or the plunger rod, or a combination thereof, wherein the interface between the stopper or the plunger rod and the inner surface of the housing increases a coefficient of friction during movement of the plunger relative to the housing.

DETAILED DESCRIPTION

The inventors have identified herein that it would be advantageous to simulate the tactility of a plunger during an injection with a prefilled syringe to set the expectations of a patient, and familiarize the patient with the forces that are sensed by a user during the delivery of medicament with a medicament-containing prefilled syringe used in an injection.

The inventors have discovered herein, embodiments of an injection training device used to simulate an injection device, wherein the device simulates an injection using drugs of varying viscosities, for example. The injection simulation device embodiments provided herein simulate an injection experience for a user, such that a user senses the resistance(s) felt during injection with an injection device and a drug having a certain viscosity. The injection simulation device embodiments described provide for resistance applied to a plunger of the device, in some non-limiting embodiments, and ease of reset of the device for subsequent use in non-limiting embodiments.

FIG.1Ais a perspective view of an embodiment100of an injection simulation device including a housing110having a proximal end110aand a distal end110b, and defining a channel112there within. The device100further includes a plunger114having a proximal end114aand a distal end114b, and a plunger rod116extending therebetween. The embodiment100shows a stopper126attached to the distal end of the plunger114b. Disposed on the plunger rod116is a flange portion118. The flange portion118is further shown in the perspective view ofFIG.1B. The flange portion118includes a flange outer portion120, an opening122, and a friction feature124. In some non-limiting embodiments, the friction feature124may be positioned at or near the opening of the flange portion.

The flange portion118may define an opening122of various shapes. Shown here is a cross-shaped opening; however, the opening is not limited to a cross shape. The opening122may be circular, square, triangular, or any other shape. The shape of the opening122may compliment the profile of the plunger rod116, as shown herein, to allow the plunger rod116to slide relative to the opening118during movement of the plunger114within the channel112of the housing110. During movement of the plunger114toward the distal end of the housing110b, the interface between the friction feature124and the plunger rod116increases a resistance on the plunger rod116movement, in one non-limiting embodiment. The friction feature124may include a number of friction flaps125as shown inFIG.1B. The friction flaps125may be formed with any material; however, in one non-limiting embodiments the friction flaps125may be formed, at least in part, of a flexible material to allow the flaps125to flex or bend during movement of the plunger114, and in a further, non-limiting embodiment, during movement of the plunger114in the proximal direction (i.e. during reset of the plunger114). In non-limiting embodiments, the plunger rod116may be cross-shaped as shown in a non-limiting example inFIG.1A, cylindrical as shown in another non-limiting example inFIG.10A, or any other shape. The plunger rod119may include a generally continuous width from proximal end117ato distal end117bas shown in an alternative, non-limiting plunger embodiment example117inFIG.2

FIG.1Cshows the proximal end of the plunger114aand a contact member115at the proximal end. The contact member115is the point at which a user presses the plunger114to move the plunger114toward the distal end of the housing110b, in one non-limiting embodiment.FIG.1Dshows the distal end of the plunger rod116and the stopper126, which may be removably or permanently associated therewith.

In some non-limiting embodiments provided herein, the force profile simulated by the injection simulation device may include a breakaway force characterized by an initial greater resistance followed by a glide force with a lower resistance relative to the breakaway force. The differences in resistance may be possible due to the friction feature, in one non-limiting embodiment, which may simulate, at least in part, the breakaway force in one example.

FIG.2shows a plunger117embodiment including a plunger rod119having a cross-shape, wherein the proximal end117ais substantially the same width as the distal end117b. A stopper126is shown at the distal end of the plunger117b, and a contact member115is disposed at the proximal end of the plunger rod117a.

FIG.3A-3Bdemonstrates an interface between a plunger rod119of a plunger117and a friction feature124′ during distal (FIG.3A) and proximal (FIG.3B) movement, in a non-limiting embodiment. During distal movement of the plunger rod119, the contact between the rigid material124bof the friction feature124′ and the flexible material124aof the friction feature124′ and the plunger rod119resistance on the plunger119is increased. During proximal movement of the plunger117(FIG.3B), the flexible material124aflexes to provide a relief, such that resistance on the movement of the plunger117decreases, due to the decrease in contact between the friction feature124′ and the plunger rod119. In some non-limiting embodiments, as shown inFIGS.3A-3B, a space127between the rigid material124band the plunger rod119may be provided to assist in relieving the resistance during proximal plunger117movement. A close-up of the friction feature124′ shown inFIGS.3A-3Bdemonstrates there may be a small overlap of the flexible material124a(or flexible flaps), over the rigid material124bto provide for increase resistance on the distal movement of the plunger117and decrease resistance on the proximal movement of the plunger117, in some non-limiting embodiments.

FIGS.5A-CandFIGS.6A-Cshow different embodiments of the plunger rod114,114′. InFIG.5, a side view of a plunger rod116having a cross shaped profile is shown. The width B of each cross member154of the plunger rod116is substantially equivalent as seen inFIGS.5B,5C.FIG.5Bincludes a cross-section taken at X-X ofFIG.5Aadjacent to the proximal plunger end114a, andFIG.5Cincludes a cross section taken at Y-Y ofFIG.5Aadjacent to the distal plunger end114b. A first width F of the plunger rod116is substantially equivalent from the proximal end114ato the distal end114b, however, a second width D, E, of the plunger rod is greater (D) adjacent to the proximal plunger end114a, and smaller (E) adjacent to the distal plunger end114b, in one non-limiting embodiment. In the embodiment shown, the second width of the plunger rod116decreases from the proximal end114ato the distal end of the plunger114b. The varying dimensions of the components of the plunger rod can be used to control the force required to move the plunger relative to the housing and to simulate an injection, or to reset the device. A resistance nodule or breakaway feature113may be provided on a portion of the plunger rod116to simulate a breakaway force of an injection device. The breakaway feature113interfaces with an inner surface of the housing110of the injection simulation device provides a resistance on the movement of the plunger114to simulate the breakaway force sensed during an injection with an injection device containing medicament.

FIG.6A-Cshows an embodiment of a plunger rod116′ wherein a first width F of the plunger rod116′ is substantially equivalent at the proximal plunger end114aand the distal plunger end114b, and a second width C of the plunger rod116′ is substantially equivalent at the proximal plunger end114aand the distal plunger end114b. In the embodiment shown inFIGS.6A-B(FIG.6Bis a cross section taken at A-A ofFIG.6AandFIG.6Cis a cross section taken at B-B ofFIG.6A). One or more of the cross members157of the plunger rod116′ may include a width A that is larger near the proximal plunger end114a′ than a width B of the cross member157near the distal plunger end114b′ as shown inFIG.6A. The variation in the width of the cross members157may affect the directionally-controlled resistance on the plunger114during movement of the plunger relative to the housing110of the injection simulation device, in a non-limiting embodiment. The resistance may be caused by the interface between a portion of the plunger and an inner surface of the housing via increased and decreased surface contact, or by interaction with a friction feature as described herein.

In yet another embodiment shown inFIG.7, the plunger rod145may include a taper wherein the width of the plunger rod145allows simulation of the force profile of an injection device including breakaway force (section3), glide force (section2) and delivery of medicament force (section1). Once past the breakaway section (section1) and the glide section (section2), the resistance on the plunger rod145increases during distal movement of the plunger relative to the housing as shown in section1of the tapered plunger rod profile inFIG.7, to simulate various viscosities of medicament encountered in an injection device.

FIGS.8A-Dprovides an embodiment200in which a clip424is provided including, having one or more protrusions426on an inner surface thereof for interfacing with a plunger218of a device200. An interface between the protrusions426and the plunger rod218may cause a resistance on the movement of the plunger rod218. The resistance may be directionally controlled by altering the profile of the plunger rod218. For example, as described in other embodiments herein, wherein the width of the plunger rod218itself increases from distal end to proximal end, the resistance during distal movement of the plunger rod will increase, and during proximal movement will decrease. In other embodiments, the profile of each cross member may be altered as shown inFIG.6to control the resistance on plunger movement. The one or more protrusions426may traverse apertures422in the housing410of the device shown inFIG.8B, in one non-limiting embodiment. The housing410may include a housing flange411at or near its proximal end. The clip body428, then surrounds a portion of the device housing410surface. Upon proximal movement of the plunger214, the protrusions426contact the plunger rod218, and may cause resistance during plunger214movement in some embodiments. The plunger214may also include a stopper216at its distal end. In some embodiments, the proximal movement of the plunger214may be limited by the interface between the stopper216and the clip424, preventing removal of the plunger214from the device housing410. In some non-limiting embodiments, the interface between the protrusions426and the plunger rod218limits or prevents axial rotation of the plunger214.

FIGS.9A-Cprovide views of yet another embodiment300of an injection simulation device including a clip524with a clip body528and a protrusion526having a pinching feature. The protrusion526may extend through an aperture522(not shown) in the device housing510to contact the plunger rod218, wherein upon movement of the plunger214, resistance may be caused by the interface between the protrusion and the plunger rod218as seen inFIGS.9B-9C. Furthermore, proximal movement of the plunger214may be limited by the interaction between the clip524and the stopper216. Plunger214removal from the device housing510may be prevented in this manner. Axial rotation of the plunger214may limited or prevented by the interface between the protrusion526and the plunger rod218. Interface between the protrusion526and the plunger rod cross member154may increase resistance on the movement of the plunger. In some non-limiting embodiments, for example when the plunger rod cross member width varies from proximal end to distal end as shown inFIGS.6A-C, the resistance on the movement of the plunger may vary between distal plunger movement and proximal plunger movement.

FIGS.10A-Dincludes yet another embodiment in which a device600includes a plunger614, movable within a chamber612of a device housing610. The device housing610includes a proximal end610aand a distal end610b, and a flange at or near its proximal end611. The plunger614may include a cylindrical shaped plunger rod618, in a non-limiting embodiment, and a stopper616at or near its distal end. The plunger614may include an at least partially hollow or solid plunger rod (solid plunger rod shown inFIG.10B). In some embodiments the diameter of the plunger rod614may differ at the proximal end and at the distal end of the plunger. In one example, the plunger rod may include a greater diameter near its proximal end and a smaller diameter near its distal end. The plunger may taper from the proximal end to the distal end in some embodiments. In other embodiments, the plunger may include a rod having a larger diameter at its distal end, and a smaller diameter at its proximal end. The plunger may taper from the distal end to the proximal end in, some embodiments. In other embodiments, the diameter of the plunger rod may be substantially consistent from the proximal end to the distal end. The flange611may include or be associated with an annular member609, which in some examples may include a toroidal or cannulated spring, an o-ring, or other annular device. The annular member609may be formed as part of the flange611or may be associated therewith in some embodiments. Upon assembly of the device, the annular member609and flange611may be placed on the plunger rod618or at the proximal end of the device housing610, such that during movement of the plunger614in the proximal direction the stopper616abuts a portion of the flange611, for example, a lower surface of the flange607within the chamber612, preventing removal of the plunger614from the device housing610, for example. In some embodiments, a pocket613may be provided either on the plunger rod618(not shown inFIG.10B) or in the device housing610as shown inFIG.10B, or even in the flange body611for resting and/or containing of at least a portion of the annular member609. The annular member also provides a resistance mechanism to confer resistance to the plunger614during movement of the plunger relative to the housing610. This feature may be used to simulate an injection device for training purposes. In some non-limiting embodiments, resistance may be greater during distal movement of the plunger (movement toward the distal end of the device housing610b), and lesser during plunger reset (i.e., during proximal plunger movement). The proximal plunger movement may also be restricted or limited at different points along the device, for example, at a predetermined fill line, in order to mimic or simulate the fill line reset of an injection device. In other non-limiting embodiments, the plunger rod may decrease in diameter from the proximal plunger rod end to the distal plunger rod end, such that resistance on the distal movement of the plunger relative to the housing may be greater than the resistance during proximal movement of the plunger, to provide a simulated injection, and allow for ease during reset of the device.

In the embodiment shown inFIG.10A-D, the resistance may be caused by the interface between the annular member609and the plunger rod618as the rod618moves relative to the housing610. The pocket613may be shaped such that the annular member is maintained within the pocket613during distal movement of the plunger614, but that the annular member is released from the pocket613during proximal movement of the plunger to decrease resistance on the proximal plunger movement during reset of the device, in some embodiments.

In some non-limiting embodiments herein a friction feature is described. The friction feature may be one component or a combination of components. The friction feature may relate to the movement of one component relative to another, or movement of two or more components relative to one another.

In one non-limiting example, the friction feature may include one or more protrusions as shown inFIG.8AandFIG.8C, for example, wherein the interface between the protrusions426and a portion of the plunger rod118as they move relative to one another causes a resistance on the plunger rod during movement of the plunger114. In some embodiments, the resistance may be greater in one direction of movement of the plunger than in the opposing direction. This differential resistance may be caused by a particular shape of the protrusion causing more resistance in one direction and less resistance in the opposing direction, in a non-limiting embodiment. In other embodiments, this resistance differential may be caused by the profile of the plunger ord. In non-limiting examples, the plunger rod may include embodiments as shown inFIGS.5A,6A,12A,14B, therefore the interface between the friction component during movement of the plunger relative to the housing may cause a differential resistance on the plunger rod during movement. Moreover, a combination of a variation of the shape of the protrusion(s) and a variable profile of the plunger rod as shown in the non-limiting examples ofFIGS.5A,6A,12A,14B, may cause a differential resistance on the plunger rod during movement.

In another example, shown inFIG.1A-1Dthe friction feature may include one or more flap members disposed in an opening of a flange, such that movement of the plunger relative to the friction feature causes a resistance on the movement of the plunger as described herein. However, in other non-limiting embodiments, the friction feature may not cause a differential resistance on the plunger rod during movement in either the proximal or distal direction. In some instances, the resistance on the plunger rod may be substantially equal regardless of the direction of movement.

FIG.11is an exploded view of an injection simulation device embodiment800, including a housing810, and a plunger814for being received there within, the plunger814comprising a plunger rod818comprising a core813and a number of cross members815. Each of the cross members815comprising a profile for allowing the simulation of forces of an injection device as the plunger814is moved relative to the housing810, due to the friction feature816. The friction feature816includes a friction component824and an annular member826. When assembled, the annular member826, which may be an o-ring or other annular member as described in other embodiments herein, or known to those skilled in the art, is held within the friction component824, and the plunger rod812slides within the opening of the friction feature816, such that the cross members816interface with the annular member826as the plunger rod812slides therethrough, creating a resistance on the plunger814. As a plunger rod protrusion817, shown inFIG.11, interfaces with the annular member826, an increased friction on the plunger814movement occurs as the plunger is moved distally, to simulate a break out glide force sensed during operation of an injection device. Following the initial break out glide force resistance during movement of the plunger protrusion817relative to the annular member826, the resistance on the plunger814decreases slightly as the plunger rod812is further moved distally relative to the housing810. Continued movement of the plunger814distally within the housing810causes an increase in resistance on the plunger814as the profile of the cross members815changes toward the proximal end of the plunger rod812.

FIG.12Ais a perspective view of the plunger814having a plunger rod818and a stopper812, the plunger rod818comprising a proximal end818a, a distal end818b, a core813and a number of cross members815extending between the proximal and distal end818a,818b. Shown inFIG.12Ais a plunger rod protrusion817configured to simulate a break out glide force when the plunger rod protrusion traverses the friction feature816upon distal movement of the plunger815relative to the housing810.FIG.12Bis a side view of the plunger814having a plunger rod having a proximal end818aand a distal end818b. The plunger rod818comprising a plurality of cross members815, each cross member comprising a profile to cause a resistance on the plunger movement relative to the housing (housing not shown inFIG.12B). Plunger rod section850simulates a puncture and/or breakaway force, wherein section852simulates a glide force, and section854simulates a delivery of medicament force as these portions of the plunger rod contact the friction feature816(not shown inFIG.12B).FIG.12Cincludes a cross sectional view of the plunger rod814taken at B-B ofFIG.12B, wherein cross members857are shown, along with core813, and stopper812, and inFIG.12Da cross section of the plunger rod814, taken at A-A ofFIG.12Bcan be seen, showing cross members857, the stopper812, and the core813. As can be seen from the cross-sectional views inFIGS.12C-12D, a height G of the cross members857is larger near the proximal end818aof the plunger rod, than at the distal end818bof the plunger rod, such that resistance increases as the plunger rod814moves distally relative to the friction feature816.

FIG.13Ais an exploded view of a friction feature816embodiment, comprising an annular member826and a friction component824for maintaining the annular member826there within. The friction component824includes a friction component opening as shown, configured to receive a plunger rod.FIG.13Bis a perspective view of an annular member826embodiment.FIG.13Cis a top side view of the frictional component824embodiment showing the opening for receiving the plunger rod.FIG.13Dis a cross sectional view of the friction component824embodiment showing an inset portion825for receiving the annular member826, (shown inFIG.13B). The cross-sectional view of the friction component824ofFIG.13Dis taken at L-L ofFIG.13C.

FIG.14Ais an exploded view of an embodiment of an injection simulation device800′.FIG.14Bis a perspective view of a plunger814embodiment, including a plunger rod818′ and a stopper812, wherein the plunger rod818′ includes a proximal end818a′ and a distal end818b′, and a number of cross members815′ and a core813′. The cross members815′ may include a profile to simulate forces sensed during an injection with an injection device, including, but not limited to puncture force(s), break out glide force(s) (BOGF), insertion force(s), and/or removal force(s) as shown inFIG.14B-14C.FIG.14Cis a side view of the plunger814′ showing an embodiment of the profile of the cross member815′, which extends from the proximal end818a′ to the distal end818b′ of the plunger rod818. The plunger protrusion817′ disposed near the distal end may simulate a BOGF during a simulation with the device. Similar toFIG.12B, various sections of the plunger rod818simulate various resistances as the rod is moved distally toward the housing810, wherein generally a resistance on the rod increases with distal movement.FIG.14D-14Eare cross-sectional views of the plunger rod embodiment818′ taken at sections N-N and R-R ofFIG.14C, respectively. In both FIGS., the stopper812can be seen, and the core803and cross members857′ of the plunger rod818′ embodiment are shown. Near the proximal end, the cross members857′ include a height E, which is larger than the height E at near the distal end (shown inFIG.14E). This allows for an increase in resistance on the plunger rod818′ as the plunger814is moved distally relative to the housing810, due to the interaction between the cross members857′ and the friction feature816. The cross members in the plunger embodiment814′ shown inFIG.14A-E, as compared to the cross members of the plunger embodiment814shown inFIGS.12A-Ddiffer in width. The cross members857are narrower than the cross members857′. The non-limiting embodiments shown provide examples of varying heights and widths for the cross members to affect an overall difference in the resistance applied to the plunger during use of the device. As the cross members widen, as in embodiment814′, a greater force is required to move the plunger distally relative to the housing, and therefore, by virtue of movement of the plunger distally relative to the housing, a greater resistance is placed on the plunger rod, due to an increase in surface area contact between the plunger rod and the friction feature (i.e., the annular member in embodiments800,800′). A comparison of plunger force versus plunger travel distance for two different plunger profiles is shown in the illustrative graph ofFIG.12E. InFIG.12E, for example, the plunger rod of Profile 2 may include one or more wider cross members, requiring a greater plunger force for movement, whereas a plunger rod of Profile 1 may include one or more narrower cross members as compared to the plunger of Profile 2, requiring a lesser relative force for plunger movement.

FIGS.15A-Dinclude various views of a friction feature816′ having a friction component824′ and an annular member826. The exploded view ofFIG.15Aprovides the annular member826and the friction component824′ for receiving the annular member. An opening for receiving a plunger rod818′ is shown inFIG.15A.FIG.15Bis a perspective view of the annular member826.FIG.15Cis a top view of the friction component824′ showing the opening for receiving the plunger rod818′.FIG.15Dis a cross-sectional view of the friction component824′ taken at section V-V ofFIG.15C, wherein the inset portion825′ for receiving annular member826is shown.

FIG.16Ais a side view of an injection simulation device embodiment800including a housing810and a plunger814.FIG.16Bis a cross sectional view of the embodiment800taken at section C-C ofFIG.16A, wherein the friction feature816is shown. Friction feature816includes friction component824and annular member826. In some embodiments, the friction feature816may be removable from the housing810, in other embodiments the friction feature816may be affixed onto the housing810, in yet other embodiments, the friction feature816may be formed as part of the housing810. The plunger814is shown inFIG.16Bas partially within the friction feature, such that the plunger protrusion817is adjacent to the annular member826, further distal movement of the plunger814would increase resistance on the plunger rod due to the interface between the plunger protrusion817and the annular member826.FIG.16Cis a partial cross-sectional view of the device800, showing the position of the annular member826relative to the plunge protrusion817.

FIGS.17A-Cprovide side, cross-sectional and partial cross-sectional views of the embodiment800shown inFIGS.16A-C, wherein the plunger814is further moved distally relative to the housing810, such that the plunger protrusion817has traversed the annular ring826as shown in the cross-sectional view ofFIG.17B, taken at section E-E ofFIG.17A. The profile of the plunger814including sections854,852, and850for simulating breakout glide force and insertion force are shown inFIG.17B.FIG.17Cis a partial cross-sectional view ofFIG.17B.

FIGS.18A-Cprovide side, cross-sectional and partial cross-sectional views of the embodiment800shown inFIGS.16A-Cand17A-C, wherein the plunger814is yet further inserted into the housing810and the plunger814is entering the “delivery of medicament force” simulation section, section854, wherein a resistance on the plunger movement will increase as the annular member826moves from section852to section854of the plunger rod to simulate the forces sensed during the delivery of medicament. As the diameter of the plunger rod increases, as shown inFIGS.16A-18C, the resistance created during movement of the plunger in the distal direction can increase. In some non-limiting embodiments discussed herein, upon applied pressure on the annular member826, the annular member may deform, or become compressed as different pressures are applied thereto.

FIG.19Aprovides a perspective view of an injection simulation device embodiment having a housing1109and a plunger1110having a proximal end1120B and a distal end1120A. The housing1109forming a channel1121, wherein the plunger1110may slide relative to the housing1109, within the channel1121, in some, non-limiting embodiment. The housing may include a proximal end1119aand a distal end1119b. The plunger1110may be inserted into the channel1121at the proximal end1119aof the housing1109and may be slidable in a distal direction toward the distal end of the housing1119b, in a non-limiting embodiment.FIG.19Bshows an exploded view of the injection simulation device embodiment provided inFIG.19A, with the plunger1110removed from the channel1121of the housing1109.FIG.19Cis a side view of the injection simulation device embodiment shown inFIGS.19A-19B, andFIG.19Dis a cross-sectional view of the embodiment of the injection simulation device shown inFIG.19Ctaken at section x-x ofFIG.19C. The distal end1120of the plunger1110is the portion shown in various embodiments inFIGS.20-25. In the embodiment shown inFIGS.19A-D, at least one protrusion1114is provided at the distal end of the plunger1110.

In a first embodiment1100shown inFIG.20A-Fa plunger embodiment1110ais provided having a proximal end (not shown inFIG.20) and a distal end112a, and at least one protrusion1122A disposed near the distal end1120A. During movement of the plunger110ain a distal direction, as shown by the arrow inFIG.20A, the at least one protrusion1122A expands laterally as shown inFIG.20B, increasing a contact between the protrusions1122A and a housing1109as shown inFIG.20C, of an injection simulation device1100. Consequently, a friction is increased on the movement of the plunger1110aduring movement in the distal direction. The housing1109has an inner surface1109aand an outer surface1109b, and the plunger1110amay slide relative to the housing1109, such that the at least one protrusion1122A interfaces with the inner surface1109aof the housing.

Movement of the plunger1110ain a proximal direction as shown by the arrow inFIG.20, causes the protrusions1122A to move inward (i.e., to retract), as shown inFIG.20D, such that the friction between the protrusions1122A and an inner surface1109aof the housing within which the plunger1110amay slide is decreased. Movement of the plunger1110ain the proximal direction as shown inFIG.20C-Dresets the plunger1110afor a subsequent use. The protrusions1122A may be provided on a distal portion of the plunger1110ain one embodiment. In another embodiment, the protrusions1122A may be provided on a stopper associated with the plunger distal end1120A.FIGS.20E-Finclude cross sectional views of the plunger embodiment1110ashown inFIGS.20A-B, demonstrating movement of the plunger110ain the distal direction. A portion of the plunger1110a, the plunger rod portion1113is viewable inFIGS.20E-F.

An alternative embodiment1150of a plunger embodiment110a′ is provided inFIG.20G-20H, wherein the at least one protrusion1122A is movable relative to the plunger1110a′. In one non-limiting embodiment, the at least one protrusion1122A may be slidable relative to the plunger1110a′ between a first position as shown inFIG.20Gand a second position as shown inFIG.20F. The at least one protrusion1122A may not be further slidable once the protrusion1122A interfaces with the protrusion interfacing surface1111. In non-limiting embodiments, the plunger embodiments described herein may include different shapes, sizes, and/or surface textures. In one non-limiting embodiment, the plunger1110a′ may include a plunger rod portion1113′ having a variable cross sectional surface area from proximal end1120B to distal end1120A. In one non-limiting embodiment, the cross-sectional surface area of the plunger rod portion1113′ or any portion of the plunger1110a′ for example, may decrease between the protrusion interfacing surface1111and the distal end of the plunger1120A, for example. In the embodiment shown inFIG.20G-20H, the plunger rod portion1113′ decreases in cross sectional surface area between the protrusion interfacing surface1111and an area adjacent to the distal end of the plunger1120A. This variable plunger rod portion1113′ allows the at least one protrusion1122A to slide relative to the plunger rod portion1113′, and to create a greater resistance when the plunger1110a′ is moved distally, than when the plunger1110a′ is moved proximally. As the plunger1110a′ is moved distally as shown inFIG.20G, the at least one protrusion1122A slides toward the proximal end of the plunger increasing resistance on the plunger as it moves toward the proximal end, due in part to the change in cross-sectional surface area of the plunger rod portion1113′, which serves to increase contact between the at least one protrusion1122A and the inner surface of the housing1109a(seeFIG.20H). Additionally, when the at least one protrusion1122A interfaces with the protrusion interfacing surface1111, movement of the plunger1110a′ in the distal direction may cause additional friction between the at least one protrusion1122A and the inner surface of the housing1109to provide further resistance on the plunger1110a′. In one non-limiting embodiment, a combination of distal movement of the plunger1110a′, sliding of the at least one protrusion1122A and interfacing with the protrusion interfacing surface1111may increase friction to increase resistance on the distal movement of the plunger1110a′. The friction may increase as the plunger1110a′ is moved in the distal direction due to the interaction between the components described herein.

In another embodiment1200shown inFIG.21A-C, a plunger1110bhaving a proximal end (not shown inFIG.21A-C), a distal end1120A, and a plunger rod1113is provided. The plunger1110bmay include one or more apertures1118at or near its distal end1120A. The plunger1110bcomprises one or more vents1120and at least one one-way valve1116, in one non-limiting embodiment. In a non-limiting embodiment, as shown inFIGS.21A-C, the one-way valve may include at least one protrusion1122B, which may include a stopper in one non-limiting embodiment, which is slidable on the plunger rod1113. The at least one protrusion1122B may serve to further increase the friction between the plunger1110band the housing during movement of the plunger1110bin the distal direction. The plunger1110bmay include one or more vents1120in a portion thereof, for providing fluid flow there through. In one non-limiting embodiment, the at least one protrusion member1122B (i.e., stopper) may serve as a valve. In a further non-limiting embodiment, the protrusion member1122B may serve as a one-way valve as shown inFIGS.21A-C.

Upon movement of the plunger in a distal direction as shown inFIG.21A, the one-way valve1116blocks the one or more vents1120and prevents fluid flow therethrough, increasing the friction and pressure inside the chamber1121of the housing1109. The increased pressure and friction creates a resistance on the plunger1110bduring movement of the plunger1110bin the distal direction to simulate movement of a plunger of a medicament delivery device.

The plunger1110bmay include one or more apertures1118, in one non-limiting embodiment. These apertures1118may be provided in the plunger distal end1120A as shown inFIGS.21A-C. In a non-limiting embodiment, the one or more apertures1118may provide a pathway for fluid flow there through. In a non-limiting embodiment, the fluid may include air. The housing1109may further include one or more fluid flow ports1123in a portion thereof, providing fluid flow there through. The one or more fluid flow ports1123provides fluid flow out of the housing1109when the plunger is moved in the distal direction in one non-limiting embodiment. The size and/or shape of the ports1123, and/or the number of ports1123may be used to control the resistance on the plunger by increasing or decreasing the pressure within the chamber1121.

FIG.21Cprovides a cross-sectional view ofFIG.21B, wherein the plunger1110bis moved in the proximal direction, revealing the vents1120in the plunger1110b, and allowing fluid flow therethrough, as the at least one protrusion1122B is shifted toward the distal end1120A of the plunger so as to decrease a resistance on the movement of the plunger1110btoward the proximal end. InFIG.21B-Cfluid flow may escape the plunger via the one or more apertures1118, and fluid may enter the air ports1123of the housing1109during reset of the plunger1110btoward the proximal end of the housing1109. A differential force may be required to move the plunger1110bin the distal direction versus the proximal direction. Movement of the plunger1110bin the proximal direction as shown inFIG.21Ballows the plunger1110bto be reset for a subsequent use (i.e., a subsequent training), for example. In one non-limiting embodiment, movement of the plunger1110bin the proximal direction causes less resistance on the plunger1110bthan movement of the plunger1110bin the distal direction.

A resistance on the plunger1110bduring movement in the distal direction simulates the movement of a plunger in a medicament-containing injection device. Injectable medicaments often vary in viscosity; consequently, the injection simulation device embodiments provided herein are configured to simulate delivery of medicaments with different viscosities to accurately simulate the injection experience for a user of the simulation device.

FIGS.22A-Dillustrate an embodiment1300of a plunger1110dhaving a proximal end (not shown inFIGS.22A-D) and a distal end1120D. At least one protrusion member1122D is associated with the plunger110d. In the embodiment1300shown inFIGS.22A-D, at least one protrusion member1122D may include a shell1124for housing one or more annular members1126. The term “annular member” as used herein, includes but is not limited to a ring-shaped member, including, for example, a garter/toroidal spring, an o-ring, or other seal, or any member having an annular-shape.

Movement of the plunger1110din a distal direction as shown by the arrow inFIG.22Amay cause the one or more annular members1126to contact an inner surface of the housing1109a(housing not shown inFIGS.22A-D), directly or indirectly via a shell1124, such that a friction between the annular member(s)1126and/or the shell1124and the housing1109causes a resistance on the movement of the plunger1110dtoward the distal end movement of the plunger1110din the distal direction as shown in the embodiment ofFIG.22Aincreases a resistance on the plunger1110d. The shell1124serves to limit movement of the annular member1126as the plunger is moved. The at least one protrusion1122D may further include a groove1128. Movement of the plunger1110din a proximal direction as shown inFIG.22Callows the annular member1126to move toward the groove1128, decreasing pressure of the shell1124and/or the annular member1126on the housing1109, to reduce the friction between the protrusion member1122D and the housing. In one non-limiting embodiment, the annular member1126may include a garter/toroidal spring, wherein movement of the plunger1110din a proximal direction may reduce an outer diameter of the garter/toroidal spring1126and decrease the friction caused thereby.FIGS.22B and22Ddemonstrate the directional movement of the annular member1126inFIGS.22A and22B, respectively.

In an alternative, non-limiting embodiment1400, the at least one protrusion member1122E, or alternatively, a distal portion of the plunger1110eitself, may include a groove1128and may not include a shell1124as shown in the embodiment ofFIG.23A-C, for example. In this case, the annular member1126may move relative to the groove1128to increase and/or decrease the resistance on the plunger1110eas the plunger1110emoves in a distal direction and/or proximal direction relative to the housing1109as described above. In a non-limiting embodiment, an annular member interfacing surface1129may be provided adjacent to the groove1128, such that proximal movement of the annular member1126is restricted by the annular member interfacing surface1129when the plunger1110eis moved in a distal direction as shown inFIG.23B. This movement increases friction by increased contact between the annular member1126and an inner surface1109aof the housing. The friction on movement of the plunger1110ein the distal direction may further be increased by contact between the at least one protrusion1122E and the inner surface1109aof the housing in another non-limiting embodiment. Movement of the plunger1110ein the proximal direction as shown inFIG.23Callows the annular member1126to move toward and/or into the groove1128, decreasing the contact between the annular member1126and the inner surface1109aof the housing, so as to reduce friction there between during movement of the plunger1110ein the proximal direction. In a non-limiting embodiment, movement of the annular member1126away from or toward the groove includes expanding or reducing in the diameter of the annular member1126.

In a further non-limiting embodiment, the device may be provided wherein the plunger comprises one or more grooves, and the annular member1126may move relative thereto as the plunger is moved in distal and proximal directions relative to the housing.

FIGS.24A-Fprovide a further embodiment1500of a plunger1110ccomprising a proximal end (not shown inFIG.24) and a distal end1112c. At least one protrusion1122C are associated with the plunger1110cas shown inFIGS.24A-F. In one non-limiting embodiment, a stopper may be associated with the plunger110c, and the protrusions1122C may be a component of the stopper. In other non-limiting embodiments, the protrusions1122C may be a component of the plunger1110c. In the embodiment1500provided inFIGS.24A-F, the protrusions1122C may further include or be associated with a flexible member1122. In one non-limiting embodiment, the protrusion member1122C may form the flexible member1122, in another embodiment the flexible member1122may be associated with the protrusion member1122C of the plunger1110cor the stopper. In embodiments described herein, the plunger1110cmay be housed within a chamber1121of an injection simulation device housing1109, consequently the plunger1110cmay be movable relative to the housing1109. A resistance on the plunger1110cmay occur by interaction between at least a portion of a plunger (i.e., a protrusion1122C or stopper) and the housing1109of the device in certain embodiments.

As shown inFIG.24B, a flexible member1122is associated with the protrusion1122C, and movement of the plunger1110cin a distal direction may cause one or more flexible members1122to be displaced. In one non-limiting embodiment, displacement may include movement of the flexible member1122by bending or folding of the flexible member1122as shown inFIGS.24B-C. This displacement causes an increase in friction between the protrusion member1122C and the housing1109when the plunger1110cis moved in the distal direction so as to increase a resistance on the plunger1110cduring movement. Further resistance may occur during distal movement of the plunger1110conce the flexible member is folded over the protrusion member1122C as shown inFIG.24Cdue to the increase in contact and friction between the protrusion1122C and the housing1109via the flexible member1122, for example.

Movement of the plunger1110cin the proximal direction as shown by the arrows inFIGS.24D-Fallows for a reset of the plunger1110c. The movement of the plunger1110cin the proximal direction, may cause the flexible member(s)1122to return to its original position as shown inFIG.24E-F, decreasing the friction between the plunger1110cand the housing of the injection device as the plunger is moved in the proximal direction, such that a differential force is required to move the plunger in the proximal direction than that which is required to move the plunger in the distal direction.

FIG.25Bis a cross-sectional view of the side view ofFIG.25A, andFIG.25Dis a cross sectional view of the side view ofFIG.25Cof a further embodiment of an injection simulation device. In the non-limiting injection simulation device embodiment1600shown inFIGS.25A-D, a housing1109defining a channel1121is provided, wherein a plunger1110having a proximal end1120B and a distal end1120A is movable relative to the channel1121. The plunger comprises a plunger rod and at least one protrusion1114that interfaces with the housing1109. The housing1109may include a simulated needle1140associated with a distal end of the housing, in one non-limiting embodiment. In a further non-limiting embodiment, the simulated needle1140may be retractable relative to the housing as shown inFIG.25. The retractable simulated needle1140may be used to simulate the needle of an injection device, and may be used to train a user to deliver an injection. The simulated needle1140may be associated with a biasing member1142, such that it may be retracted and extended relative to the housing1109. The simulated needle1140has a proximal end and a distal end, the distal end for associating with a target surface of a user. The distal end comprising a profile such that use of the device1600will not puncture the target surface of a user. The proximal end of the simulated needle1140may include or be associated with a valve closing member1138, configured to associate with a valve1136. In one non-limiting embodiment, upon full retraction of the simulated needle1140, the valve closing member1138prevents fluid flow through the valve1136. In the embodiment1600, retraction of the simulated needle as shown inFIG.25Cresulting in an interface between valve1136and valve closing member1138increases the pressure within the chamber1121, consequently, blocking of the valve1136with the valve closing member1138causes an increase in resistance on the movement of the plunger1110in the distal direction (i.e., toward the distal end of the housing1109) as shown inFIGS.25C-25D. A fluid flow port1123may be provided in the housing1109as shown inFIG.25, providing for fluid flow there through in some non-limiting embodiments, so as to allow for movement of the plunger1110within the housing1109.

As illustrated in the embodiments ofFIG.25A-25D, a surface treatment or surface texture region1195may be applied to an inner surface of the housing1109. the surface texture region1195may be provided on an inner surface of the housing, or on a portion of the plunger and/or the stopper or protrusion member in some embodiments, or a combination thereof. The surface texture region1195may increase the coefficient of friction during movement of the plunger relative to the housing. The surface texture region may be included in any of the embodiments provided herein. In some embodiments, the surface texture region(s) may include a higher average roughness (Ra) relative to other non-surface texture regions.

Non-limiting examples of surface texture regions described herein may include a surface texture profile comprising a number of peaks and valleys, wherein the peak to valley distance (Rz) is the largest distance between the highest and lowest points of the profile for a given evaluation length. The average roughness (Ra) may be calculated as the average distance of the profile from the centerline and the root-mean-square (rms) roughness Rq is taken as the root-mean-square of the profile distance from the centerline. See, for example, the sample graph showing the relationship between the Rz, Rq and Ra values provided inFIG.27.

Controlling the surface finish of selected regions of a core pin used in the injection molding process to manufacture the device according to one embodiment, can be used to vary the surface roughness along the length of the inner diameter of the produced part. Varying the surface finish of portions of the core pin can be accomplished through selective masking and secondary finishing processes. There is a strong correlation between increased surface roughness and an increased coefficient of friction in dry sliding wear. Varying the surface roughness of selected regions along the length of the vial can therefore be used to vary the force required to move the plunger along its length. The level of achievable surface finish variation along the length of the vial will vary depending on the degree of draft angle of the inner diameter. The surface finish of portions of the vial can be varied from approximately 0.001 Ra (μm) to 25.0 Ra (μm), in other embodiments, the Ra value may range from 0.012 μm to 18.0 μm, and in some embodiments, from approximately 0.012 Ra (μm) to 6.35 Ra (μm). These varying Ra values may occur through the selective application of finishing methods, for example.

In some examples, ranges for Rq may include between 0.001 μm and 0.1 μm, in some embodiments Rq value may range between 0.012 μm and 0.025 μm. In other embodiments, Rq may range between 0.013 μm and 0.027 μm.

FIGS.26A-26Dillustrate a further non-limiting embodiment of an injection simulation device1700for simulating plunger resistance of an injection device. The embodiment7100includes a housing1109defining a channel1121, and a plunger1110for movement relative to the channel1121. The plunger1110includes a proximal end1120B and a distal end1120A and a protrusion1114at the distal end for interfacing with the housing1109.FIG.26Bis a cross sectional view of the device as shown inFIG.26A, andFIG.26Dprovides a cross sectional view of the device as shown inFIG.26C. A retractable simulated needle1144is shown, the simulated needle1144is retractable relative to the housing1109. The simulated needle1144having a proximal end and a distal end, and a distal end component1145associated with its distal end of the simulated needle in one non-limiting embodiment. The distal end of the simulated needle1144for contacting a target surface of a user during use of the device1700. The proximal end of the simulated needle1144may include a distal end component receiving notch1146for receiving the distal end component1145. The distal end component receiving notch1146may be complimentary to the distal end component, such that when the distal end component1145interfaces with the distal end component receiving notch1146, fluid flow through the distal end aperture1143is restricted. The interface between the distal end component receiving notch1146and the distal end component1145as shown inFIGS.26C-Dincreases pressure in the chamber1121, to increase a resistance on the plunger110during movement in the distal direction. This allows simulation of the resistance sensed during movement of a plunger in a medicament-containing injection device. The interface between the distal end component1145and the distal end component receiving notch1146serves to block the valve1149of the housing1109, preventing fluid flow from passing therethrough. A biasing member1142is associated with the simulated needle1144, the biasing member1142configured to extend the simulated needle1144, in one non-limiting embodiment, when the force on the distal end of the simulated needle1144is removed or reduced.

Consequently, the embodiment1700of the injection simulation device provides a multi-step approach to training a user for using an injection device, wherein the simulated needle1144must be retracted before the plunger is actuated (i.e., moved toward the distal end), to simulate an injection delivery device. An injection delivery device as mentioned herein includes a medicament containing injection device, and more specifically, in non-limiting embodiments, a needle-containing medicament-containing injection device such as a prefilled syringe, for example.

It should be borne in mind that all patents, patent applications, patent publications, technical publications, scientific publications, and other references referenced herein are hereby incorporated by reference in this application in order to more fully describe the state of the art to which the present invention pertains.

Reference to particular buffers, media, reagents, cells, culture conditions and the like, or to some subclass of same, is not intended to be limiting, but should be read to include all such related materials that one of ordinary skill in the art would recognize as being of interest or value in the particular context in which that discussion is presented. For example, it is often possible to substitute one buffer system or culture medium for another, such that a different but known way is used to achieve the same goals as those to which the use of a suggested method, material or composition is directed.

It is important to an understanding of the present invention to note that all technical and scientific terms used herein, unless defined herein, are intended to have the same meaning as commonly understood by one of ordinary skill in the art. The techniques employed herein are also those that are known to one of ordinary skill in the art, unless stated otherwise. For purposes of more clearly facilitating an understanding the invention as disclosed and claimed herein, the following definitions are provided.

While one or more embodiments of the present invention have been shown and described herein, such embodiments are provided by way of example only. Variations, changes and substitutions may be made without departing from the invention herein. Accordingly, it is intended that the invention be limited only by the spirit and scope of the appended claims. The teachings of all references cited herein are incorporated in their entirety to the extent not inconsistent with the teachings herein.