An auto-injector operable in a single activation step. The auto-injector is automatically armed when removed from its carrying receptacle. The auto-injector may be prefilled with more than one constituent of a beneficial agent, stored in separated compartments, in such an arrangement that the compartments will automatically merge when the auto-injector is removed from its carrying receptacle.

FIELD

The present disclosure pertains to the field of parenteral drug delivery, and more particularly to prefilled injection devices.

BACKGROUND

Auto-injectors are used for clinical parenteral administration of a fixed dose of a beneficial agent to a subject. They are particularly advantageous, and hence more commonly practiced, in emergency applications in which proper administration, potentially by an untrained or minimally trained user, under extreme duress, in less than optimal conditions, is needed to be perform in a timely manner. Auto-injectors are more proper for these applications than regular syringes as they require fewer and simpler to implement operative steps. It is hence an important aspect of auto-injector design to minimize the number and complexity of the operation steps of an auto-injector. Many auto-injector technologies require two hand preparation of the device for injection, such as arming of the device, release of a safety catch, and removal of an aseptic barrier that ensure the sterility of the device until the time of use. According to one usability aspect of auto-injectors, the need to perform two hand operations introduces a level of complexity and confusion to the user, as eventually the device has to be properly repositioned, in the proper orientation, in the hand that is used for administration.

One example of an commonly used auto-injector is the EpiPen® manufactured by Meridain Medical Technologies (Columbia, Md.). The EpiPen® applies a spring force to automatically deliver a dose of epinephrine from a glass syringe. The EpiPen® requires two hand operation to remove a cap and arm the device, at the end of which the device needs to be reoriented and properly grasped by the hand that delivers the injection. Several publications describe user error in handling the EpiPen® where the user applies the wrong side of the EpiPen® auto-injector to the subject, and wasting the medication dose toward the opposite side (away from the target injection site).

U.S. Pat. No. 8,425,462 teaches an auto-injector propelled by a CO2cartridge. The auto-injector has an actuation guard that is removable to allow activation of the device. Two hand operation is required to remove the actuation guard and prepare the device for injection. As a result, it is likely that reorientation of the device and change in hand grasp would be performed during preparation for injection.

U.S. Pat. No. 6,979,316 teaches an auto-injector operated by a spring. A molded safety cover is fitted onto the forward end of the housing and maintains the sterility of the internal components and also prevents inadvertent actuation of the device. The safety cover must be removed from the device before it can be used.

In similar fashion, other auto-injector technologies, in commercial embodiments and in published documentation, require two hand operation to prepare for injection and bare the risk of mishandling for administration.

SUMMARY

According to some embodiments described herein, an auto-injector is described that is activatable to administer a beneficial agent to a subject. The auto-injector is configured to be operable single-handedly, without changing the hand grasp of the auto-injector body, from a pre-used configuration in its storage or carrying package or receptacle, to administration. According to some embodiments described herein, the auto-injector automatically mixes components of the beneficial agent without altering the operation simplicity. According to some embodiments described herein, the auto-injector further comprises an ornamental feature to facilitate tactile and visual recognition of the device. According to some embodiments described herein, a first auto-injector can be stored or carried with a second auto-injector, and the first auto-injector comprises at least one of ornamental, graphical, and color recognition feature allowing a user to at least one of tactile and visually differentiate the first auto-injector from the second auto-injector. According to some embodiments described herein, the auto-injector provides tactile, visual, and audible feedback when it is moved from the pre-use configuration to the armed configuration, from the armed configuration to administration, and/or when administration is completed. Embodiments of the auto-injector described herein is designed to minimize user errors.

According to some embodiments described herein, the auto-injector arrangement comprises (a) an auto-injector comprising an injector body housing a beneficial agent, and (b) an actuator moveably connected to the auto-injector, the actuator comprising an anchoring link adapted to be connected to an anchoring body, wherein when in a first auto-injector arrangement state, the auto-injector is rendered incapable of expelling the beneficial agent, and when in a second auto-injector arrangement state, corresponding to the auto-injector having being moved relative to the anchoring body from the first auto-injector arrangement state, the auto-injector is rendered capable of expelling the beneficial agent.

According to some embodiments described herein, the auto-injector, comprises (a) an injector housing having an injection end, (b) an administration assembly disposed within the injector housing, the administration assembly having a delivery end proximate to the injection end through which a beneficial agent housed within the administration assembly is capable of being expelled, and (c) an actuator moveably connected to the administration assembly, wherein when in a first auto-injector state, the actuator is coupled to the administration assembly such that the delivery end is rendered incapable of being applied to a subject and the administration assembly is rendered incapable of expelling the beneficial agent, and when in a second auto-injector state, corresponding to the actuator having been manipulated from the first auto-injector state, the administration assembly is rendered capable of expelling the beneficial agent, the auto-injector thereafter movable into a third auto-injector state in which the actuator is separated from the auto-injection.

In some embodiments described herein, the auto-injector can be carried in a receptacle in a safe configuration, and is armed when removed from the receptacle. In the safe mode the auto-injector will not activate under any carrying conditions including when it is exposed to external force, shock, vibration, or other environmental condition. When removed from the receptacle the auto-injector changes from the safe configuration to armed configuration. In some arrangements, in the armed configuration the auto-injector is automatically activated by depressing the injection side of the auto-injector against an injection site of a subject. In some arrangements activation of the auto-injector triggers an injection sequence comprising deploying a needle from a concealed position in the auto-injector body, delivering the beneficial agent, and retracting the needle. In some arrangements the auto-injector stores at least two constituents of a beneficial agent, in separated compartments, and the compartments are automatically merged when the auto-injector is removed from the carrying receptacle. The carrying receptacle may by, but not limited to, a carrying case, a pouch, a pocket, a cradle, a hanger, a bracket, a box, a kit, a belt, or any combination thereof, or other carrying receptacles know in the art.

In some embodiments, the auto-injector comprises a removable link having a first end attached to the auto-injector and a second end attached to an attachment point at or in proximity to the carrying receptacle, and the arrangement is such that when the auto-injector is removed from the carrying receptacle the removable link is pulled and causes the auto-injector to arm. After the auto-injector is armed, the removable link is detached either from the attachment point and/or the auto-injector. The removable link may be one of, but not limited to, a strap, a string, a chain a rope, a cable, a combination of the above, or any other linking mechanism known in the art. In some arrangements the auto-injector comprises a removable cap that is attached to the removable link, and the arrangement is such that when the removable link pulls on the removable cap, the removable cap manipulates the auto-injector to an armed configuration, before the cap is removed from the auto-injector. In some arrangements the auto-injector comprises a removable link and at least two constituents of a beneficial agent, separately stored in individual compartments, and the arrangement is such that when the removable link is pulled, the auto-injector is manipulated to merge these compartments. In some arrangements the auto-injector comprises a removable link joined to a removable cap, and at least two constituents of a beneficial agent, separately stored in individual compartments, and the arrangement is such that when the removable link pulls the removable cap, the auto-injector is manipulated to merge these compartments.

In some embodiments described herein, the auto-injector is movable from a safe, pre-use configuration to an armed configuration, and while in the carrying receptacle the auto-injector is maintained in the safe configuration. A spring biases the auto-injector toward the armed configuration such that when the auto-injector is removed from the carrying receptacle the spring moves the auto-injector from a safe configuration to the armed configuration.

In some embodiments described herein, the carrying receptacle is configured in such a way that the hand grasp necessary for removal of the auto-injector from the receptacle is substantially similar to the hand grasp for injection such that the auto-injector can be single-handedly operated without substantially changing the hand grasp, from the removal from the carrying receptacle, all the way to completion of the injection procedure. In some arrangements the carrying receptacle and the removable link are configured in such a way that the hand grasp necessary for removal of the auto-injector from the receptacle is substantially similar to the hand grasp for injection such that the auto-injector can be single-handedly operated without substantially changing the hand grasp, from the removal from the carrying receptacle all the way to completion of the injection procedure. In some arrangements the carrying receptacle, the removable link, and the removable cap are configured in such a way that the hand grasp necessary for removal of the auto-injector from the receptacle is substantially similar to the hand grasp for injection such that the auto-injector can be single-handedly operated without substantially changing the hand grasp, from the removal from the carrying receptacle to completion of the injection procedure.

DETAILED DESCRIPTION

FIGS. 1a-1fillustrate a simplified arrangement of an auto-injector100of the present disclosure teaching the basic principles of its construction and operation.FIGS. 1aand 1billustrate an arrangement of the auto-injector100comprising a shell102(hereafter, by itself or in combination with other auto-injector elements, sometimes referred to as the auto-injector housing or auto-injector body), and a needle housing101, together defining the external shell of the auto-injector100. The auto-injector100has a generally elongated cylindrical form comprising a proximal end (hereafter sometimes referred to as the injection end)101comprising a needle port103, and distal end102, where the auto-injector100may be hand grasped during the injection procedure. A movable piston assembly (also referred to as the administration assembly)120separates the interior volume of the auto-injector into a pressure chamber104and a sterile needle housing105. The administration assembly120comprises a piston121, a beneficial agent package assembly130joined to its distal end, within the pressure chamber104, and a movable needle assembly140joined at its proximal end, within the needle housing105. The needle assembly140comprises a needle141comprising a proximal sharp end and a distal sharp end, and a needle hub142, and is movable between a first pre-use position and a second injection position, as will be detailed in the following Figures. The package assembly130comprises a first flexible wall131and a second wall132joined along their peripheral edges in a permanent seal fashion. The first package wall131and the second package wall132are further joined across the package to form a first frangible seal136defining a first compartment134adjacent to a second compartment135. A second frangible seal137separates between the compartments134-135and a fitment138that is joined to the piston121. The first compartment134and the second compartment135may be filled with at least one beneficial agent or constituents thereof. The fitment138comprises a membrane section139confronting the distal sharp end of the needle141. A spring114biases the piston assembly toward the pressure chamber104. An adhesive label115seals over the needle port103to maintain the needle141sterile until the time of use.FIG. 1cillustrates a configuration of the auto-injector100where the first compartment134and the second compartment135have been merged, by breaking the first frangible seal136, allowing the at least first beneficial agent constituent in the first compartment134and at least a second constituent in the second compartment134to mix and or interact. The package130may comprise more than two mergeable compartments.FIG. 1dis showing a configuration of the auto-injector100where the second frangible seal (137inFIG. 1a) of the package assembly130has been ruptured establishing fluid communication between the beneficial agent(s) and the fitment138.FIG. 1dillustrates an injection configuration of the auto-injector100, wherein pressure is introduced into the pressure chamber104in the auto-injector body. The pressure is introduced from a pressure source that when opened creates pressure in the auto-injector body. When the pressure surpasses a first threshold value, the pressure causes the piston to overcome the spring113force displacing the needle assembly120toward the proximal end101. The needle assembly140moves along with the piston until the needle hub142stops against the bottom of the needle housing112. During usage of the auto-injector100, in this configuration it is held at the distal end102while the proximal end101is depressed against an injection site of a subject, such that the proximal end of the needle141is inserted into the subject. An arrangement of the pressurizing mechanism of the pressure chamber104is shown in following Figures. InFIG. 1ethe piston assembly120continues its displacement toward the proximal end101, while the needle assembly140is stationary, causing the back end of the needle142to pierce the membrane (139inFIG. 1b) of the fitment138, thereby establishing fluid communication between the package assembly130and the needle141. The pressure in the pressure chamber104causes the first wall131to collapse and deliver the beneficial agent(s) through the needle141. The pressure in the pressure chamber104is gradually reduced by releasing the gas within through a bleeding arrangement (not shown).FIG. 1fillustrates a configuration of the auto-injector100after the pressure in the pressure chamber104has dropped to such a degree that the spring113can displace the needle assembly120toward the distal end102of the auto-injector100until the needle is concealed again in the needle housing112.

FIG. 2aillustrates an arrangement of an auto-injector200comprising an auto-injector body comprising a shell102and a needle housing112which together form the exterior of the auto-injector200. A piston assembly120is disposed in the auto-injector body (hereafter can be referred to as the auto-injector housing) and comprises a piston121, accommodating a package assembly130at its distal side, and a needle assembly140at its proximal side. An actuation assembly210is disposed in the pressure chamber104, comprising a support structure213which hold in alignment a pressurized cartridge211in a confronting position to a piercing pin212. The support structure213further accommodates a compression panel214for manipulating the compartment of the package assembly130to merge.FIG. 2billustrates a cross section of auto-injector200in the first auto-injector state (hereafter can be referred to as the pre-use configuration). The compression panel214confronts the first compartment134on its first side and leans against a cam221at its second side. The cam221is fixed to the shell102. A latch feature222is also fixed to the shell102. The pin's212sharp end is facing the pierceable region of the pressurized cartridge211, and is free to move along its axis. However in this configuration nothing can apply an axial force to the pin212and hence an accidental piercing of the cartridge211is not possible.FIG. 2cillustrates a second auto-injector state and an mixing auto-injector state wherein the shell102is extended away from the needle housing112, causing the cam221to push the compression panel214which in return depresses the package130causing its compartments to merge, and establish fluid communication with the fitment138. The support structure213holds the pin212from moving upward while the latch feature222moves along with the shell102, slides over the pin's212shaft, and engages with a detent ridge215of the pin212. At this point the pin212is retained to the shell102. A slot231in the shell102allows connecting an anchoring link (here after sometimes referred to as the anchoring link) such as a strap or other devices to facilitate pulling the shell102to the extended position. InFIG. 2dthe shell102is moved down, carrying along the pin212which pierces the pierceable region of the pressurized cartridge211, thereby pressurizing the pressure chamber104. The pressurized canister211may contain carbon dioxide, nitrogen, argon, or other gasses or supercritical fluids. When the pressure in the pressure chamber104exceeds a first threshold value, the force it exerts on the piston112overcomes the spring113force, moving the piston112toward the proximal injection end101. The needle assembly140moves with the piston121until it is stopped by the needle housing101floor, at which point the needle141is fully extend. With the needle assembly140now stationary, the pressure in the pressure chamber104continues to move the piston121down, resulting in a relative movement between the needle assembly140and the piston121, causing the distal end of the needle141to pierce the package assembly130and establish fluid communication with the beneficial agent. With the pressure chamber104still pressurized, the beneficial agent is squeezed out of the package130and administered via the needle141to a subject. In one arrangement the position of the cam221relative to the compression panel214, and the position of the latch222relative to the detent ridge215are such, that a first move of the needle housing112changes the device200to the mixing auto-injector200state, where the compartments of the package130are merged, and a subsequent second move moves the device200to the third auto-injector state (here after sometimes referred to as the armed configuration). This arrangement is particularly beneficial where the beneficial agent is ready for injection only after a certain time from mixing, such that the device can be kept at a safe, unarmed state during mixing.FIG. 2eillustrates the auto-injector200in a manufacturing configuration. The needle housing101assembly is sterile and ready to fill at the filling site. Special access regions233in the package assembly130allows the filling machine to fill the package and subsequently seal the channels232connecting the access regions233and the compartments134,135. When filling is completed the access regions233may be removed and the shell102is installed on the needle housing assembly250. An According to one aspect of the arrangement ofFIG. 2a-d, the auto-injector200comprises: (a) an injector housing102having an injection end101, (b) an administration assembly230, comprising the piston assembly120, the actuation assembly210, and the needle housing112, disposed within the injector housing102, the administration assembly230having a delivery end231proximate to the injection end101through which a beneficial agent housed within the administration assembly230is capable of being expelled; when in the auto-injector200state illustrated inFIGS. 2a-2b, the administration assembly230is rendered incapable of expelling the beneficial agent; and when in the auto-injector200state illustrated inFIG. 2c, the administration assembly230is rendered capable of expelling the beneficial agent. The administration assembly230comprises a first compartment134for storing at least a first constituent of the beneficial agent, and at least a second compartment135for storing at least a second constituent of the beneficial agent separate from the first constituent; and wherein at the auto-injector state illustrated inFIG. 2c, the first compartment134and the at least second compartment135are merged.

FIG. 3aillustrates an auto-injector arrangement330and an auto-injector300in the first auto-injector state (hereafter can be referred to as the pre-use configuration of an auto-injector300) comprising an auto-injector housing comprising a shell302. An actuator in the form of a removable cap311is joined with the proximal end of the administration assembly310, providing a sterile seal to the needle housing310. The cap311is joined to an anchoring link comprising a strap312that terminates with a buckle313. The cap311comprises detent arms (not shown inFIG. 3a), that reach into a gap between the outer diameter of the administration assembly310and the inner diameter of the shell302, and fit in a circumferential recess on the outer diameter of the administration assembly310(not shown inFIG. 3a), such that when the strap312is pulled, as shown inFIG. 3b, it extends the administration assembly310away from the shell302, thereby moving the auto-injector300to a second auto-injector state (hereafter can be referred to as the auto-injector300armed configuration). The detent teeth314can then be dislodged from the recess315in the administration assembly310, as shown inFIG. 3c, until the cap311is completely removed as shown inFIG. 3d.FIG. 3dillustrate the device when it's ready for activation by depressing the administration assembly310against a subject. In one arrangement, the auto-injector300comprises at least two beneficial agent constituents, housed in the auto-injector body302, that need to be mixed prior to injection, and a mixing action is initiated when the cap311is moved to the mixing auto-injector arrangement state shown inFIG. 3b, and subsequently the device is armed upon a second move when the cap311is removed as shown inFIG. 3c. The buckle313can be attached to any anchoring body including the auto-injector's carrying receptacle (not shown), or in its vicinity such as a garment of the user.

According to one aspect of the arrangement ofFIGS. 3ato 3d, the auto-injector330arrangement, comprises: (a) an auto-injector300comprising an injector body302housing a beneficial agent; and (b) an actuator311moveably connected to the auto-injector300, the actuator comprising an anchoring link320adapted to be connected to an anchoring body, wherein: when in a first auto-injector arrangement330state, the auto-injector300is rendered incapable of expelling the beneficial agent; and when in a second auto-injector arrangement330state, corresponding to the auto-injector300having being moved relative to the anchoring body from the first auto-injector arrangement330state, the auto-injector300is rendered capable of expelling the beneficial agent. Moving the actuator from the first auto-injector arrangement300state, illustrated inFIG. 3a, to the second auto-injector arrangement300state, illustrated inFIG. 3b, comprises moving the actuator311relative to the injector housing302. In one arrangement, the sequence steps illustrated inFIGS. 3bto 3dare combined, such that in the second auto-injector arrangement300state the actuator311is separated from the auto-injector300. In one arrangement the anchoring link320comprises at least one of a strap, a clip, a chain, a cable, a lanyard, a hook or a combination thereof. In one arrangement, the actuator311comprises a cap. In one arrangement, at the first auto-injector arrangement300state, illustrated inFIG. 3a, the cap isolates at least a portion of the auto-injector300from the surrounding environment. In one arrangement the anchoring body comprises an auto-injector receptacle inside of which, in the first auto-injector arrangement state, at least a portion of the auto-injector is accommodated, and wherein the receptacle comprises at least one of an enclosure, a package, a bag, a pouch, a pocket, a belt, a container, a holster, a cradle, a kit, a garment, or any combination thereof. The relative movement of the actuator311relative to the anchoring body, to move the auto-injector arrangement from300from the first auto-injector arrangement state to the second auto-injector arrangement state, comprises linear motion. In one arrangement the injector body302comprises a first compartment for storing at least a first constituent of the beneficial agent, and at least a second compartment for storing at least a second constituent of the beneficial agent separate from the first constituent; and when in a mixing auto-injector arrangement state, corresponding to the auto-injector300having been moved relative to the anchoring body from the first auto-injector arrangement330state, the first compartment and the at least second compartment are merged and the auto-injector300is rendered incapable of expelling beneficial agent. In one arrangement transitioning the auto-injector arrangement330from the first auto-injector arrangement330state to the mixing auto-injector arrangement330state comprises a first movement of the auto-injector300relative to the anchoring body and transitioning the auto-injector arrangement330from the mixing auto-injector arrangement330state to the second auto-injector arrangement330state comprises a second movement of the auto-injector300relative to the anchoring body. In one arrangement the mixing auto-injector arrangement300state and the second auto-injector arrangement state330are the same. In one arrangement the actuator311is separated from the auto-injector300in the second auto-injector arrangement330state. In one arrangement the auto-injector300is removed from the receptacle in the second auto-injector arrangement330state. In one arrangement the auto-injector further comprises a compressed gas source that when opened provides gas pressure within the injector body302to expel the beneficial agent, and wherein the compressed gas source is incapable of opening in the first auto-injector arrangement330state, and the compressed gas source is capable of being opened in the second auto-injector arrangement330state. According to one aspect of the auto-injector arrangement330, the injector body302comprises an activation member317, extending therefrom, which is the delivery end of the administration assembly310, that when moved toward the injector body302, activates the auto-injector300to expel the beneficial agent, and wherein the actuator311impedes the activation member317from moving toward the injector body302in the first auto-injector arrangement330state, illustrated inFIG. 3a. The activation member317comprises a delivery end318from where the beneficial agent is expelled.

According to one aspect of the auto-injector arrangement330, the auto-injector300, comprises: (a) an injector housing302having an injection end301; (b) an administration assembly310disposed within the injector housing302, the administration assembly310having a delivery end318proximate to the injection end301through which a beneficial agent housed within the administration assembly310is capable of being expelled; and (c) an actuator311moveably connected to the administration assembly310, wherein: when in a first auto-injector300state, illustrated inFIG. 3athe actuator311is coupled to the administration assembly310such that the delivery end318is rendered incapable of being applied to a subject and the administration assembly310is rendered incapable of expelling the beneficial agent; and when in a second auto-injector300state, illustrated inFIG. 3b, corresponding to the actuator311having been manipulated from the first auto-injector300state, the administration assembly310is rendered capable of expelling the beneficial agent, the auto-injector300thereafter movable into a third auto-injector300state, illustrated inFIG. 3d, in which the actuator311is separated from the auto-injector. Manipulating the actuator311from the first auto-injector300state to the second auto-injector300state comprises moving the actuator relative to the injector housing302. The actuator311is moveably connected to the delivery end318of the administration assembly311, but it would be obvious to one skilled in the art that the actuator311can be connected to the administration assembly in other locations, such as the opposite end of the injection end301. In one arrangement the administration assembly310comprises a first compartment for storing at least a first constituent of the beneficial agent, and at least a second compartment for storing at least a second constituent of the beneficial agent separate from the first constituent; wherein at the second auto-injector state, the first compartment and the at least second compartment are merged.

FIGS. 4aand 4billustrate the auto-injector300nested in a carrying receptacle in a form of a cradle or holster411. The cradle comprises a protective cover412and it can be strapped down to a person's arm, belt, leg, or a package, bag etc. The cradle411is configures such that the auto-injector300can be single handedly removed from the cradle411. The auto-injector may be removed by holding the shell (also referred to as the auto-injector housing)302in substantially the same hand grasp that the auto-injector300should be held for activation, hence the auto-injector300can be removed from the carrying receptacle311, pulled off from the strap312for arming, and be depressed onto the injection site in a single action, single handedly, at a substantially similar hand grasp of the shell302.

According to one aspect of the auto-injector arrangement400, the auto-injector arrangement400, comprises: (a) an auto-injector300comprising an injector body302housing a beneficial agent; and (b) an actuator311moveably connected to the auto-injector300, the actuator311comprising an anchoring link320connected to an anchoring body410comprising a holster411; wherein: when in a first auto-injector arrangement400state, illustrated inFIGS. 4aand 4b, the auto-injector is rendered incapable of expelling the beneficial agent; and when in a second auto-injector arrangement400state, corresponding to the auto-injector300having being moved relative to the anchoring body410, as illustrated inFIG. 4c, from the first auto-injector arrangement400state, the auto-injector300is rendered capable of expelling the beneficial agent. Moving the actuator311from the first auto-injector arrangement400state to the second auto-injector arrangement400state comprises moving the actuator311relative to the injector body302. In one arrangement, in the second auto-injector arrangement400state, the actuator311is separated from the auto-injector300. In one arrangement the anchoring link320comprises at least one of a strap, a clip, a chain, a cable, a lanyard, a hook or a combination thereof. The actuator311comprises a cap, and in one arrangement, at the first auto-injector arrangement400state, the cap isolates at least a portion of the auto-injector300from the surrounding environment. The anchoring body410comprises an auto-injector receptacle inside of which, in the first auto-injector arrangement400state, at least a portion of the auto-injector300is accommodated. In some arrangements the receptacle comprises at least one of an enclosure, a package, a bag, a pouch, a pocket, a belt, a container, a holster, a cradle, a kit, a garment, or any combination thereof. The relative movement of the auto-injector300relative to the anchoring body410, from the first auto-injector arrangement400state to the second auto-injector arrangement400state, comprises linear motion. In one arrangement the injector body302comprises a first compartment for storing at least a first constituent of the beneficial agent, and at least a second compartment for storing at least a second constituent of the beneficial agent separate from the first constituent; and when in a mixing auto-injector arrangement400state, corresponding to the auto-injector300having been moved relative to the anchoring body410from the first auto-injector arrangement400state, the first compartment and the at least second compartment are merged and the auto-injector300is rendered incapable of expelling beneficial agent. In one arrangement transitioning the auto-injector arrangement400from the first auto-injector arrangement400state to the mixing auto-injector arrangement400state comprises a first movement of the auto-injector300relative to the anchoring body410, and transitioning the auto-injector arrangement from the mixing auto-injector arrangement400state to the second auto-injector arrangement400state comprises a second movement of the auto-injector300relative to the anchoring body410. In one arrangement the mixing auto-injector arrangement400state and the second auto-injector arrangement400state are the same. In one arrangement the actuator311is separated from the auto-injector300in the second auto-injector arrangement400state. In one arrangement the auto-injector300is separated from the receptacle400in the second auto-injector arrangement400state. In one arrangement the auto-injector300further comprises a compressed gas source that when opened provides gas pressure within the injector body302to expel the beneficial agent, and wherein the compressed gas source is incapable of opening in the first auto-injector arrangement400state, and the compressed gas source is capable of being opened in the second auto-injector arrangement400state. In one arrangement the injector body302further comprises an activation member extending there from that, when moved toward the injector body302, activates the auto-injector to expel the beneficial agent, and wherein the actuator311impedes the activation member from moving toward the injector body302in the first auto-injector arrangement400state. In one arrangement the activation member comprises an injection end from where the beneficial agent is expelled.

According to one aspect of the auto-injector arrangement400, the auto-injector300comprises: (a) an injector housing302having an injection end301; (b) an administration assembly disposed within the injector housing, the administration assembly having a delivery end proximate to the injection end through which a beneficial agent housed within the administration assembly is capable of being expelled; and (c) an actuator311moveably connected to the administration assembly, wherein: when in a first auto-injector300state, the actuator311is coupled to the administration assembly310such that the delivery end is rendered incapable of being applied to a subject and the administration assembly is rendered incapable of expelling the beneficial agent; and when in a second auto-injector300state, corresponding to the actuator311having been manipulated from the first auto-injector300state, the administration assembly is rendered capable of expelling the beneficial agent, the auto-injector300thereafter movable into a third auto-injector300state in which the actuator311is separated from the auto-injector. Manipulating the actuator311from the first auto-injector300state to the second auto-injector300state comprises moving the actuator311relative to the injector housing. The actuator311is moveably connected to the delivery end of the administration assembly. In one arrangement the administration assembly comprises a first compartment for storing at least a first constituent of the beneficial agent, and at least a second compartment for storing at least a second constituent of the beneficial agent separate from the first constituent; and wherein at the second auto-injector300state, the first compartment and the at least second compartment are merged.

FIGS. 5aand 5billustrate another arrangement of an auto-injector500where the piston513accommodates a first beneficial agent package assembly130a, confronting a first needle141a, and a second beneficial agent package assembly130bconfronting a second needle141b. Each beneficial agent package assembly and needle assembly set is operable in the same manner as the auto-injector arrangements100,200,300described in earlier Figures, such that two injections can be given simultaneously from the auto-injector500without changing the operation mode or the product500complexity.FIG. 5aillustrates the auto-injector500in an armed configuration andFIG. 5billustrates the auto injector500when it is activated. In one arrangement at least one of beneficial agent package assemblies130aand130bcomprises more than one compartment that are merge at or prior to the arming step.

According to one aspect ofFIGS. 5a-5b, the auto-injector500is adapted for delivering to a patient at least a first beneficial agent and a second beneficial agent, comprising: (a) an auto-injector body511comprising an injection end512, (b) a piston513disposed in the auto-injector body511to form a pressure chamber514, the piston513is moveable from a pre-use position to a deployed position (c) a first beneficial agent communicable with a first administration device141ais connected to the piston153, (d) a second beneficial agent communicable with a second administration device141bis connected to the piston153, wherein when pressure is applied in the pressure chamber514the piston513moves to deploy the first and second administration devices141aand141bthrough the injection end512, and the first and second beneficial agents are administered through their respective administration devices.

FIGS. 6a-6cillustrate another arrangement of the auto-injector600, activatable to administer a beneficial agent to a subject.FIG. 6aillustrates the auto-injector600at a first auto-injector state (here after sometimes referred to as the pre-use configuration). An administration assembly620(also referred to as the carriage assembly) comprises the package assembly630, piston621, and a needle assembly640. The package assembly630comprises a collapsible tube. The piston621comprises a piston core component626and a piston skirt component627, that are latched together via a lateral ridge and groove joint. This joint is substantially fluid tight seal but for a bleeding passageway628formed there between to deplete the pressure from the pressure chamber605after the device600has been activated. The bleeding passageway628is formed as a torturous path (such as a labyrinth) that prevents bacteria and contamination from reaching into sterile needle chamber604before use. The spring613biases the piston core626toward the pressure chamber605. In another arrangement the bleeding passageway is configured such that it only opens when the piston is moved, for example by providing an inward protrusion (such as a rib) that comes off the needle housing601wall and interrupts the seal of the piston skirt627against that wall, when the piston621reaches that protrusion as it travels down.FIG. 1billustrates the device600when activated where the cartridge691has been ruptured, and, after exceeding a first pressure threshold value, the pressure in the pressure chamber605has driven down the piston assembly621toward the proximal end of the device600. The pressured gas in the pressure chamber605is depleting through the bleeding passageway628. The base of the piston skirt627is latched with a detent ridge619inwardly facing from the needle housing601wall.FIG. 6cillustrates the auto-injector600after the pressure in the pressure chamber has dropped to below a second threshold value where the spring613was able to release the piston core626from the piston skirt627, and retract the piston core626back toward the pressure chamber605, carrying along the administration assembly620(except for the skirt627). The piston skirt627remains latched at the bottom position. By separating the piston core626from the skirt627the pressure in the pressure chamber605is instantly vented through opening618in the needle housing601, allowing abrupt retraction of the administration assembly620. The opening618allows inspection that the auto-injector600has been operated by viewing the piston skirt627through this opening618.

FIG. 7illustrates an auto-injector70for delivering a first beneficial agent to a subject, comprising an auto-injector body having an elongated shape, comprising an injection end73and a distal end71opposite to the injection end71. The distal end has a tactilely distinguishable triangular shape. The auto-injector70may be intended to be stored, or carried adjacent to at least a second auto-injector and the distal end71shape allows for the user to tactilely distinguish the auto-injector70from the at least a second auto-injector, for delivering a second beneficial agent, with a different distal end shape. The auto-injector70further comprises graphics72of triangular shape which allow a visual recognition of the auto-injector that corresponds to the tactile recognition of the auto-injector70. The end piece71may also be distinguished from other auto-injectors by the color of the distal end71. The auto-injector70. In one arrangement the injection end73comprises a tactilely, graphical or color features that allows distinguishing the auto-injector70from other auto-injectors. In one embodiment at least one of the distinguishing features of the injection end correlate to a distinguishing feature of the distal end. In one arrangement the injection73comprises a cap that bares the distinguishing feature. The distal end71may be a cap mounted over the auto-injector70body.

FIGS. 8, 9, and 10illustrates auto-injectors with distal ends of different shapes.FIG. 7illustrates an auto-injector70comprising an ornamental end piece71comprising a triangular shape. The end piece71further comprises printed, stacked-on, or embossed triangular graphics72that resemble the triangular shape of the end piece72. Resembling.FIG. 8illustrates an auto-injector80comprising an ornamental end piece81comprising a pointed shape.FIG. 9illustrates an auto-injector90comprising an ornamental end piece91comprising a rounded shape. The distal end ofFIG. 9comprises graphic92of a circular shape that correlates to the spherical shape of the distal end91.FIG. 10illustrates an auto-injector1000comprising an ornamental end piece1001comprising a flat screwdriver head shape. It would be obvious to one skilled in the art that corresponding ornamental shapes and graphics can be applied to the opposite ends73,83,93, and1003of auto-injectors70,80,90, and1000respectively. According to one aspect of the auto-injectors70,80,90, and1000, a first auto-injector for delivering at least a first beneficial agent intended to be carried or stored adjacent to at least a second auto-injector for delivering at least a second beneficial agent, comprising a generally elongated body comprising an injection end73,83,93, and1003, and a distal end71,81,91, and1001opposite to the injection end, where at least one of said ends comprises a tactile distinguishable shape from the at least one end of the second auto-injector. According to another aspect ofFIGS. 7,8,9, and 10, a set of at least a first and a second auto-injectors, each comprising a generally elongated body comprising an injection end73,83,93, and1003, and a distal end71,81,91, and1001opposite to the injection end, at least one of said ends comprises a shape, where said shape of the first auto-injector is tactilely distinguishable from the shape of the at least second auto-injector. The end of the first auto-injector can be distinguished from the at least second auto-injector by at least one of a color, color pattern, and graphics. In one arrangement the auto-injector at least one of the injection end and the distal end comprises a cap and the shape is in the cap. The ornamental shapes can be at least one of a dome, a circle, a triangle, a square, a flat screwdriver head, a Philips screwdriver head, a star, a chess rook, a cone, or a combination or a blend of the formers. The shape and the graphics substantially represent the same shape. In some arrangements the ornamental shape comprises at least one of an indentations, a neck, a recess, through hole, or a blend or a combination of the formers. In some arrangements the shape comprises at least one of indentations, recesses, grooves, notches, or a combination or blend of the formers, arranged in a circumferential, longitudinal, or radial pattern, or a combination or a blend of the above.

FIG. 11atoFIG. 11fillustrate an auto-injector arrangement1110activatable to deliver a beneficial agent to a subject by an operator, comprising an auto-injector1115comprising an auto-injector body1111(hereafter can be referred to as auto-injector housing1111) comprising an injection end1114, and an anchoring body comprising a receptacle1112, in a form of a holster, for accommodating therein at least a portion of the auto-injector body1111before use. The receptacle1112can be mounted or otherwise joined to a belt, a garment, a gear, a bag, a package.FIGS. 11aand 11billustrate the auto-injector arrangement1110at a first configuration wherein the auto-injector body1111seats close to the holster1112and, when worn on a belt or other garment or gear, it is substantially protected from accidental impact or interference.FIGS. 11cand 11dillustrate the auto-injector arrangement1110at a second configuration where the auto-injector body1111is tilted away from the holster1112to allow accessing the auto-injector body1111by the operator allowing accessibility for a firm hand grip. The arrangement is such that the auto-injector body1111is manipulable relative to the receptacle1112from a first configuration, shown inFIGS. 11aand 11b, where the auto-injector body1111is substantially protected from physical interferences (such as accidental and unintentional manipulation), to a second position where the auto-injector body1111is partially removed, and substantially extended from the receptacle1112to facilitate the operator hand grasp of the auto-injector body1111. According to one aspect of the present disclosure, the auto-injector is single handedly operable from a pre-use configuration to activation avoiding hand repositioning, thereby reducing the risk of accidentally dropping the device or disorienting it for activation. In the second configuration the device can be confidently hand grasped in the position for activation. In one arrangement the auto-injector1115in manipulable from a first auto-injector state (may be referred to as the pre-use configuration), where activation is disabled, to second auto-injector state (may also be referred to as an armed configuration), where activation is enabled, by a relative movement between the auto-injector body1111and the receptacle1112. The arrangement is such that the second configuration facilitates the operator manipulation of the device from the first auto-injector state to the second auto-injector state. In one arrangement the first and second configuration the activation of the device1110is disabled. The anchoring body1112is not limited to a holster fashion and can be fitted for a particular application, carrying or storing consideration, and may be of different forms and fashions including a package, a bag, a pouch, a pocket, a container, a cradle, a closure, and a cap, or any combination of the above. In one embodiment the movement of the auto-injector1115from the anchoring body1112comprises axial movement.FIGS. 11a-ffurther illustrate an actuator1116comprising an anchoring link1113communicating between the anchoring body1112and the auto-injector1115, to facilitate manipulation of the auto-injector1115. The actuator1116is in a form of a cap that extends from the auto-injector body1111, and covers the injection end of the auto-injector. InFIGS. 11eand 11fthe device1111is armed by pulling the auto-injector1115away from the actuator1116which remains connected to the anchoring body1112via anchoring link1113. The anchoring link1113form is not limited to that shown in this figure and can comprise at least a closure, a strap, a clip, a chain, a cable, lanyard, or a combination of the formers. In one embodiment, at the first configuration the auto-injector1115is in the first auto-injector state and cannot be moved to the second auto-injector state (armed configuration) without first moving to the second configuration.

According to one aspect ofFIGS. 11a-f, the auto-injector arrangement1110is activatable to deliver a beneficial agent to a subject by an operator. The auto-injector arrangement1110comprises: (a) an auto-injector1115comprising an auto-injector body1111comprising an injection end1114, and (b) an anchoring body1112comprising a receptacle for accommodating at least a portion of the auto-injector body therein before use, the arrangement is such that the auto-injector1115is manipulable relative to the anchoring body1112, from a first position where the auto-injector body is substantially protected from physical interferences (such as accidental and unintentional manipulation), and a second position where the auto-injector1115is substantially extended from the anchoring body1112to facilitate the operator hand grasp of the auto-injector body1111. The auto-injector arrangement1115is further manipulable from a first auto-injector1115state (pre-use configuration), where activation is disabled, to a second auto-injector1115state (an armed configuration), where activation is enabled, and where the arrangement is such that the second configuration facilitates the operator manipulation of the auto-injector1115from the first auto-injector state to the second auto-injector state. In one arrangement at the first and the second configurations, the auto-injector1115activation is disabled. In one arrangement the auto-injector1115is moved from the first auto-injector state (the pre-use configuration) to the second auto-injector state (armed configuration) when it is separated from the anchoring body1112.

According to one aspect ofFIGS. 11eand 11f, the auto-injector arrangement1110, comprises: (a) an auto-injector1115comprising an injector body1111housing a beneficial agent; and (b) an actuator1116moveably connected to the auto-injector1115, the actuator comprising an anchoring link1113adapted to be connected to an anchoring body1112, wherein: when in a first auto-injector arrangement1110state, the auto-injector1115is rendered incapable of expelling the beneficial agent; and when in a second auto-injector arrangement1110state, corresponding to the auto-injector1115having being moved relative to the anchoring body1112from the first auto-injector arrangement1110state, the auto-injector1115is rendered capable of expelling the beneficial agent. Moving the auto-injector1115from the first auto-injector arrangement state1110to the second auto-injector arrangement1110state further comprises moving the actuator1116relative to the injector housing1112. In one arrangement, in the second auto-injector arrangement1110state the actuator1116is separated from the auto-injector1115. In one arrangement the anchoring link1113comprises at least one of a strap, a clip, a chain, a cable, a lanyard, a hook or a combination thereof. The actuator1113comprises a cap, and in one arrangement, at the first auto-injector arrangement1110state, the cap1113isolates at least a portion of the auto-injector1115from the surrounding environment. The anchoring body112comprises an auto-injector receptacle in a form of a holster, inside of which, in the first auto-injector arrangement1110state, at least a portion of the auto-injector1115is accommodated. In some arrangement the receptacle1112comprises at least one of an enclosure, a package, a bag, a pouch, a pocket, a belt, a container, a holster, a cradle, a kit, a garment, or any combination thereof. In one arrangement the injector body1111comprises a first compartment for storing at least a first constituent of the beneficial agent, and at least a second compartment for storing at least a second constituent of the beneficial agent separate from the first constituent; and when in a mixing auto-injector arrangement state, corresponding to the auto-injector1115having been moved relative to the anchoring body1112from the first auto-injector arrangement1110state, the first compartment and the at least second compartment are merged and the auto-injector1115is rendered incapable of expelling beneficial agent. In one arrangement transitioning the auto-injector arrangement1110from the first auto-injector arrangement state to the mixing auto-injector arrangement state comprises a first movement of the auto-injector1115relative to the anchoring body1112and transitioning the auto-injector arrangement1110from the mixing auto-injector arrangement to the second auto-injector arrangement state comprises a second movement of the auto-injector1115relative to the anchoring body1112. In one arrangement the mixing auto-injector arrangement1110state and the second auto-injector arrangement1110state are the same. In one arrangement the actuator1116is separated from the auto-injector1115in the second auto-injector arrangement1110state. In one arrangement the auto-injector1115is removed from the receptacle in the second auto-injector arrangement1110state. In one arrangement the auto-injector1115further comprises a compressed gas source that when opened provides gas pressure within the injector body1111to expel the beneficial agent, and wherein the compressed gas source is incapable of opening in the first auto-injector arrangement1110state, and the compressed gas source is capable of being opened in the second auto-injector arrangement1110state. The injector body1111comprises an activation member1117extending therefrom that, when moved toward the injector body1111, activates the auto-injector1115to expel the beneficial agent, and wherein the actuator1116impedes the activation member1117from moving toward the injector body1111in the first auto-injector arrangement1110state. The activation member comprises an injection end1119from where the beneficial agent is expelled.

According to one aspect of the auto-injector arrangement1110, the auto-injector1115, comprises: (a) an injector housing1111having an injection end1114; (b) an administration assembly1121disposed within the injector housing, the administration assembly1121having a delivery end1119proximate to the injection end1114through which a beneficial agent housed within the administration assembly1121is capable of being expelled; and (c) an actuator1116moveably connected to the administration assembly1121, wherein: when in a first auto-injector1115state, the actuator1116is coupled to the administration assembly11211121such that the delivery end1119is rendered incapable of being applied to a subject and the administration assembly1121is rendered incapable of expelling the beneficial agent; and when in a second auto-injector1115state, corresponding to the actuator1116having been manipulated from the first auto-injector1115state, the administration assembly1121is rendered capable of expelling the beneficial agent, the auto-injector1115thereafter movable into a third auto-injector1115state in which the actuator1116is separated from the auto-injection1115. Manipulating the actuator1116from the first auto-injector1115state to the second auto-injector1115state comprises moving the actuator1116relative to the injector housing. In one arrangement the administration assembly1121comprises a first compartment for storing at least a first constituent of the beneficial agent, and at least a second compartment for storing at least a second constituent of the beneficial agent separate from the first constituent; and wherein at the second auto-injector1115state, the first compartment and the at least second compartment are merged.

FIGS. 12aand 12billustrate an auto-injector arrangement1220activatable to administer a beneficial agent to a subject comprising an auto-injector1210comprising: (a) an auto-injector body1221, comprising an injection end1226, and (b) an actuator1222, wherein, at the first auto-injector state (peruse configuration) shown inFIG. 12a, is mounted on the injection end1226. The auto-injector arrangement1220is moveable from a first auto injector state (pre-use configuration) where activation is disabled, to a second auto-injector state (an armed configuration) where activation is enabled. The auto-injector body1221comprises helical ramps1225, and the actuator1222comprises reciprocal helical ramps1223such that at the first auto-injector1210state, when the cap is rotated counter clock wise the auto-injector1210is moved from the first auto-injector1210state to the second auto-injector1210state, thereafter the auto-injector1210is separated from the actuator1222as shown inFIG. 12b. The actuator1222can be joined to an anchoring body for instance by threading a strap, or a band (i.e. anchoring link) in through hole1229such that rotating the auto-injector1210relative to the anchoring body will move the auto-injector1210from the first auto-injector state to the second auto-injector state. The anchoring body may be a garment, a package, a bag a pouch, a kit, a container, an enclosure, a combination thereof, or other objects that the auto-injector may need to connect to. According to one aspect of the auto-injector arrangement1220, the auto-injector1210, comprises: (a) an injector housing1221having an injection end1211; (b) an administration assembly1212disposed within the injector housing1221, the administration assembly1212having a delivery end1213proximate to the injection end1211through which a beneficial agent housed within the administration assembly1212is capable of being expelled; and (c) an actuator1222moveably connected to the administration assembly1212, wherein: when in a first auto-injector1210state, the actuator1222is coupled to the administration assembly1212such that the delivery end1119is rendered incapable of being applied to a subject and the administration assembly1212is rendered incapable of expelling the beneficial agent; and when in a second auto-injector1210state, corresponding to the actuator1116having been manipulated from the first auto-injector1210state, the administration assembly1212is rendered capable of expelling the beneficial agent, the auto-injector1210thereafter movable into a third auto-injector1210state in which the actuator1222is separated from the auto-injection1210. Manipulating the actuator1222from the first auto-injector1210state to the second auto-injector1210state comprises moving the actuator1222relative to the injector housing1221. In one arrangement the administration assembly1212comprises a first compartment for storing at least a first constituent of the beneficial agent, and at least a second compartment for storing at least a second constituent of the beneficial agent separate from the first constituent; and wherein at the second auto-injector1210state, the first compartment and the at least second compartment are merged.

FIGS. 13ato 13nillustrate an auto-injector1300of the present disclosure in several operation sequence configurations. The auto-injector1300is activatable to administer a beneficial agent to a subject. The auto-injector1310, comprises: (a) an injector housing1301(also referred to as auto-injector body1301) having an injection end1307; (b) an administration assembly1310disposed within the injector housing1301, the administration assembly1310having a delivery end1316proximate to the injection end1307through which a beneficial agent housed within the administration assembly1310is capable of being expelled; and (c) an actuator1302(also referred to as cap1302or sterile cap1302) moveably connected to the administration assembly1310, wherein: when in a first auto-injector1300state, the actuator1302is coupled to the administration assembly1310such that the delivery end1316is rendered incapable of being applied to a subject and the administration assembly1310is rendered incapable of expelling the beneficial agent; and when in a second auto-injector1300state, corresponding to the actuator1302having been manipulated from the first auto-injector1300state, the administration assembly1310is rendered capable of expelling the beneficial agent, the auto-injector1300thereafter movable into a third auto-injector1300state in which the actuator1302is separated from the auto-injection1300. Manipulating the actuator1302from the first auto-injector1300state to the second auto-injector1300state comprises moving the actuator1302relative to the injector housing1301. In one arrangement the administration assembly1310comprises a first compartment for storing at least a first constituent of the beneficial agent, and at least a second compartment for storing at least a second constituent of the beneficial agent separate from the first constituent; and wherein at the second auto-injector1300state, the first compartment and the at least second compartment are merged.

FIGS. 13aand 13billustrate longitudinal cross-sections of the auto-injector1300in a first auto-injector state (also referred to as the pre-use configuration). The auto-injector1300comprises an injector housing1301(also referred to as the auto-injector housing1301or the auto-injector body1301) comprising an injection end1307, aseptically protected by a sterile cap1302, and an ornamental end piece1303joined to the distal end1304opposite to the injection end1307. An administration assembly1310is axially moveable in the auto-injector body1301between a pre-use position, an armed position, and an activated position, corresponding to the first auto-injector state, the second auto-injector state, and the third auto-injector state respectively, as will be described hereunder. The administration assembly1310comprises a carriage1311, a piston assembly1330, a needle assembly1360and a beneficial agent package1333. The administration assembly1310is air tight sealed against the auto-injector body via an O-ring seal1313and a wiper seal1312. The wiper seal provides for a lower friction force as the administration assembly1310moves relative to the body1301, and avoid sticking that sometimes occur when an O-ring is compressed against a sealing surface for an elongated time. A piston assembly1330is moveably disposed in the carriage1311and divides the internal volume of the auto-injector body1310into a pressure chamber1305and a sterile needle housing1306. The piston assembly1330comprises a piston core1331and a piston wiper seal1332moveably joined in a fluid tight fashion. The piston wiper seal1332is moveably sealed in a fluid tight fashion with the needle housing walls1306. A beneficial agent package1333in a form of a tube is disposed in the pressure chamber1305and is joined to the distal end of the piston core1331, such that the spout of the tube is confronting a membrane1334. The beneficial agent package1333comprises a compartment for storing at least one constituent of a beneficial agent, and a connector for joining the package1333to the piston core1331. In one arrangement the package1333comprises a membrane1335for aseptically sealing the beneficial agent. The piston core1331is axially biased by a biasing mechanism1350comprising a spring1351, to seat against stopper1314—an inner circumferential ridge protruding from the carriage1311. A needle assembly1360is disposed in the needle housing1306and is moveably joined to the proximal end of the piston core1331. The needle assembly1360comprises a hypodermic needle1361, having a proximal hypodermic bevel tip1363, and a distal sharp tip1364configured to pierce into the beneficial agent package1333; and a needle hub1362. The needle hub1362is moveably disposed in a bore in the piston core1331in such a manner that substantial force is required to axially move the needle assembly1360relative to the piston core1331. The force required to move the needle assembly1360relative to the piston core1331can be calibrated by several means including interference features, and friction. The proximal needle tip1363is received at the needle abutment1315, confronting an opening in the delivery end1316in the administration assembly1310. At this pre-use configuration the needle is concealed in the auto-injector body and is maintained sterile in the aseptically sealed needle housing1306by the aseptic cap1302. The aseptic cap inner circumferential ridge1308seals against the cap detent ridge1317of the carriage1311. The edge of the cap1302is confined in the auto-injector body, preventing the cap circumferential ridge1308from expanding and dislodging from the cap detent ridge1317of the carriage1311. A compressed gas source in a form of metal cartridge1321is supported at the distal end of the auto-injector body1301in the pressure chamber1305, and comprises a rupturable membrane,1322oriented toward the injection end1307. An arming mechanism1370is moveably joined at the distal end of the carriage1311. The arming mechanism1370comprises a piercing arm1371and a piercing element1372biased by torsion spring1373from a pre-use position, where the piercing element is not aligned with the cartridge membrane1322(as is clearly illustrated inFIG. 13band later inFIG. 14a), to the armed position, which is illustrated in subsequent Figures. The piercing arm protrusion1374leans against the cartridge1321and prevent the piercing element1371from aligning with the cartridge membrane1322. This arrangement of the arming mechanism is advantageous for its inherent safety as the piercing element1372cannot pierce the cartridge1321regardless of the force applied to the auto-injector body. Actuator1302comprises a through pass1318for hooking the auto-injector body1301to an anchoring link such as a lanyard, a chain, a ring, a strap or other form of attachments known in the art. In one arrangement the actuator1302is configured to connect to a receptacle wherein at least a portion of the auto-injector body1301is accommodated for storage or carrying. Forms of receptacles for auto-injector1300can be, but not limited to, a holster, a bracket, a cradle, a closure, a package, a bag, a pocket, a purse, a tube and a combination of the above.

In one arrangement the compressed gas source is at least partially external to the auto-injector body. In one such example the gas is supplied by a hose to the pressure chamber1305. A valve, or a pierceable membrane can be accommodated in the auto-injector body1301to control the introduction of pressure to the pressure chamber1305.

The carriage can be formed from an assembly of parts that are joined by threads, screws, welding, gluing or other means known in the art such as in the arrangement illustrated inFIG. 14c.

FIGS. 13cand 13dillustrate cross section views of the auto-injector1300in the second auto-injector state (also referred to as the armed configuration). The administration assembly1310is axially moved relative to the auto-injector body1301toward the injection end1307, from its pre-use position to the armed position, at which point the piercing arm protrusion1374(not shown) disengages from the side of the gas cartridge1321, allowing the torsion spring1373to move the piercing arm1371to the armed position where the piercing element1372is in a confronting position with the cartridge membrane1322. A similar arrangement of the arming mechanism is illustrated inFIG. 15aandFIG. 15band can provide further clarity to the principle of operation of this arming mechanism. The cap1302edge is dislodged from behind the auto-injector body1301allowing it to radially expand and to be removed from the cap detent ridge1317of the carriage1311. The administration assembly1310can be manipulated from the pre-use position to the armed position by pulling the cap1302away from the auto-injector body1301. In some arrangements the cap1302is attached to an anchoring link or an anchoring body such that the movement from the pre-use configuration to the armed configuration can be accomplished by merely grasping the auto-injector body in the palm and single-handedly moving it relative to the anchoring link or the anchoring body.

FIGS. 13eand 13fillustrate cross section views of the auto-injector1300in the third auto-injector state when the cap1302is removed and the auto-injector1300is ready for injection. The use indication windows1319are exposed when the cap1302is removed. In some arrangements the cap1302is connected to an anchoring link or a receptacle and is removed by merely grasping the auto-injector body1301in the palm and moving it relative to the anchoring link or the receptacle. In one arrangement the auto-injector1300is moved from the first auto-injector state (pre-use configuration) illustrated inFIG. 13a-b, to the third auto-injector state (armed configuration with the cap1302removed) as shown inFIG. 13e-fin a single continuous action. Accordingly, in an arrangement where the cap302is connected to an anchoring link or an anchoring body, the auto-injector1300is moved from the first auto-injector state to the third auto-injector state where it is ready for injection by separating it from the anchoring link or the anchoring body, in a single hand operation, which is a unique feature of the present disclosure.

FIGS. 13gand 13hprovide longitudinal cross-sections of the auto-injector1300, showing a snapshot of the device as it is activated to expel the beneficial agent. The administration assembly1310is moved relative to the auto-injector body1301toward its distal end, causing the piercing element to pierce through the cartridge membrane1322, thereby opening the pressure source1321, allowing the compressed gas to fill the pressure chamber1305. Several type of gas can be loaded in the cartridge1321in a gaseous or two-phase form including nitrogen, argon and carbon-dioxide. The administration assembly1310can be moved from the armed position to the activated position by grasping the auto-injector body1301in the palm in substantially the same hand grasped used to move the auto injector1300from the first auto-injector state to the second and third auto-injector state, and pressing the injection end1307against the subject's target injection site. In one arrangement the palm grasp of the auto-injector body1301for activating the auto-injector1300is substantially the same as the palm grasp used to move the auto-injector body from the pre-use configuration to the armed configuration, hence, combined with the arrangement described in the discussion ofFIGS. 13e-f, in this arrangement the auto-injector1300can be operated from a pre-use configuration to an activation in a single hand operation without changing the palm grasp, which is a unique feature of the present disclosure that simplify the device1300operation and reduces the room for user errors.

FIGS. 13iand 13jprovide longitudinal cross-sections of the auto-injector1300, showing a snapshot of the device in the activation position shortly after the cartridge1321is pierced and the pressure chamber1305is pressurized. When the pressure at the pressure chamber1305surpasses a first threshold value, it exerts a force on the piston assembly1330that overcomes the preloaded biasing spring1351force, causing the piston assembly1330to move, together with the package1333and the needle assembly1360, toward the injection end1307, while extending the needle1361through the opening in the delivery end1316. The needle1306reaches its extended position when the needle hub1362is stopped by the needle abutment1315. The package1333is still not in communication with the needle, preventing injection of the beneficial agent before the needle1361has reached its fully extended position. As the pressure in the pressure chamber1305continues to force the piston assembly toward the injection end1307, a relative movement between the needle assembly1360and the piston assembly1303is initiated as illustrated inFIGS. 13k-l.

FIGS. 13kand 13lprovide longitudinal cross-sections of the auto-injector1300during injection. The pressure in the pressure chamber1305continued to move the piston assembly1330toward the injection end1307. With the needle assembly1360now stationary, the piston assembly1330moves relative to the needle assembly1360causing the back end of the needle1364to pierce the piston core membrane1334and the tube membrane1335, and establish fluid communication between the package1333and the needle1361, allowing the beneficial agent to be administered. The pressure in the pressure chamber1305compresses the package1333to deliver the beneficial agent. As would be obvious to those skilled in the art, several packages are practically applicable for this auto-injector1300beside a tube, so long as they provide the adequate connection to the piston core1331and that their volume can be depleted by applying pressure to at least one of their walls. Such packages include, but are not limited to, metal tubes, laminated tubes, plastic tubes, molded tubes, tubes made from extruded material, blow molded packages, Blow-Fill-Seal packages, blister packages, pouch, sachet, bags, injection molded packages, and piston-barrel arrangements, and combination of the formers. In some arrangement of the auto-injector, one of the package membrane1335and piston core membrane1334is eliminated. The purpose of these membranes1335,1334is to maintain the needle housing1306and the package1333aseptically sealed, however, as will be demonstrated in the description ofFIG. 14, in certain manufacturing procedures of the auto-injector1300the piston core1331and the package1333are joined prior to filling of the beneficial agent, and prior to sterilization of the needle housing1306, thus one membrane can provide the aseptic seal of the needle housing1306and the package1333. In one arrangement the piercing element is other than the distal tip of the needle1364. In one arrangement the needle1361terminates in the needle hub1362and the piercing element extends from the distal end of the needle hub1362either as a protruded extension of the needle hub1362or a separate part that is joined to the needle hub1362and extends from its distal end. When the piston assembly1330reaches the final activation position, the piston wiper is located under bleeding holes1309allowing the compressed gas to vent from the pressure chamber1305. The pressure bleeding is used to control the dwelling time of the needle1361in the extended position, to allow enough time for the beneficial agent administration. This arrangement is particularly beneficial as the pressure bleeding cannot occur until the needle1361is fully extended, ensuring that: a) maximum pressure is available to force the needle insertion, and b) accurate timing of the needle dwelling in the extended position. As more clearly noticed inFIGS. 13a-b, bleeding holes1309of several sizes are embedded in the needle housing1306wall. These bleeding holes1309can be sealed, leaving the desired bleeding holes1309open, to achieve a desired bleeding rate, i.e. a desired dwell time. Other controllable bleeding passageway can be implemented to vent the pressure chamber including a valve, a labyrinth, etc. The bleeding holes1309are covered with a filter1381such as a Tyvek breathable laminate to prevent contamination of the needle housing1305prior to use of the device1300. Piston wiper seal1332is now showing in the use indication windows1319, indicating that the needle1361is fully extended and that the beneficial agent administration is taking place.

FIGS. 13mand 13nprovide longitudinal cross-sections of the auto-injector1300after the needle1361has retracted. When the pressure in the pressure chamber drops under a second threshold pressure value, the spring1351moves the piston core1331away from the injection end1307, separating from the piston wiper seal1332which is retained in its activated position due to a combination of friction with the needle housing1306wall and interference of the wiper seal lip1383with inward protrusions1382. As soon as the piston core starts its back travel, the seal between the piston core1331and the piston wiper seal is breached, causing a sudden drop of pressure in the pressure chamber1305to the surrounding pressure. With no pressure in the pressure chamber1305and no seal friction force to counter, the spring1351force causes the piston core1331, together with the needle assembly1360, to abruptly retract to the pre-use position. This is particularly advantageous as: a) slow needle retraction can cause discomfort to the subject, and b) the abrupt needle retraction provides a tactile confirmation to the user/operator that injection is completed, and c) it reduces the chance of needle1361exposure after the device1300has been removed from the subject.

According to one aspect of the arrangement ofFIGS. 13ato 13n, the auto-injector1300comprises an injector body1301housing a beneficial agent; and an actuator1302moveably connected to the auto-injector1300, the actuator1302is adapted to be connected to an anchoring link which is adapted to be connected to an anchoring body, wherein: when in a first auto-injector1300state, corresponding toFIGS. 13a-b, the auto-injector is rendered incapable of expelling the beneficial agent; and when in a second auto-injector1300state, corresponding toFIGS. 13c-dwhere the auto-injector1300having being moved relative to the anchoring body from the first auto-injector1300state, the auto-injector1300is rendered capable of expelling the beneficial agent. Moving the auto-injector1300from the first auto-injector state to the second auto-injector state further comprises moving the actuator1302relative to the injector housing1301. In one arrangement, in the second auto-injector1300state the actuator1302is separated from the auto-injector1301. In one arrangement the anchoring link comprises at least one of a strap, a clip, a chain, a cable, a lanyard, a hook or a combination thereof. In one arrangement the injector body1301comprises a first compartment for storing at least a first constituent of the beneficial agent, and at least a second compartment for storing at least a second constituent of the beneficial agent separate from the first constituent; and when in a mixing auto-injector state, corresponding to the auto-injector having been moved relative to the anchoring body from the first auto-injector state, the first compartment and the at least second compartment are merged and the auto-injector1300is rendered incapable of expelling beneficial agent. In one arrangement transitioning the auto-injector1300from the first auto-injector state to the mixing auto-injector state comprises a first movement of the auto-injector1300relative to the anchoring body and transitioning the auto-injector1300from the mixing auto-injector state to the second auto-injector state comprises a second movement of the auto-injector1300relative to the anchoring body. In one arrangement the mixing auto-injector state and the second auto-injector state are the same. In one arrangement the actuator1302is separated from the auto-injector1300in the second auto-injector state. In one arrangement the auto-injector1300is removed from the anchoring body in the second auto-injector state. According to one aspect of the arrangement ofFIGS. 13a-13n, the delivery end1316of the administration assembly1310acts as an activation member extending from the auto-injector body1301and, when moved toward the injector body1301, the activation member activates the auto-injector1300to expel the beneficial agent, and wherein the actuator1302impedes the activation member from moving toward the injector body1301in the first auto-injector state.

According to one aspect of the arrangement ofFIGS. 13a-13m, the auto-injector1300comprises: (a) an auto-injector body1311comprising an injection end1307, (b) a needle assembly1360moveable from a pre-use position, where the needle assembly is concealed in the auto-injector body1311, to a deployed position where the hypodermic tip of the needle1361extends from the auto-injector body1307, (c) a biasing mechanism1350configured to bias the needle assembly1360to the pre-use position, (d) a pressure chamber1305(also referred to as pressure capsule1305), and (e) a pressure release valve that, when opened, vents the pressure capsule; wherein when compressed gas pressure in the pressure chamber1305exceeds a first threshold pressure value, the needle assembly1360is moved to the deployed position, and when the pressure in the pressure chamber1305drops under a second threshold pressure value, the pressure release valve opens. The auto-injector1300further comprises a pressure bleeding passageway1309configured to gradually deplete the pressure in the pressure chamber1305. The pressure release valve is configured to instantly deplete the pressure in the pressure chamber1305. When the pressure release valve opens, at least a portion of the needle assembly abruptly retracts toward the auto-injector body1311. The needle assembly1360is joined to a moveable piston1330that manipulates the needle1361from the pre-use position to the deployed position, and the pressure release valve is incorporated in the piston1330. The biasing mechanism1350is configured to manipulate the release valve to open. The needle assembly1360is incorporated in the pressure release valve. The piston assembly1330comprises a first portion (i.e. piston core1331) and a second portion (i.e. piston seal1332), and the needle assembly1360is joined to the piston first portion1331, and the biasing mechanism1350is a spring1351disposed between the injection end1307and the piston first portion1331, such that the biasing mechanism1350manipulates the release valve to open by moving the piston first portion1331relative to the piston second portion1332. The piston first portion1331retracts the needle1361toward the pre-use position when the pressure release valve is opened. The piston second portion1332provides a visual indication that the piston1330has moved to the deployed position. The bleeding passageway controls the timing of the opening of the pressure release valve.

According to one aspect of the arrangement ofFIGS. 13a-13m, the auto-injector1300comprises: (a) an auto-injector body1311comprising an injection end1307, (b) a compressed gas source1321, (c) a needle assembly1360, (d) a needle biasing mechanism1350, (e) a calibrated pressure bleeding passageway1309, and a pressure release valve; wherein the pressure profile produced by the combination of the pressure source1321, the bleeding passageway1309, and the release valve produces a sequence of: (f) deploying the needle1361from a pre-use position where it is substantially concealed in the auto-injector body1311to extend through the injection end1307, (g) retain the needle1361in the deployed position for a defined time to deliver an injection, and (h) retract the needle1361toward the pre-use position.

According to one aspect of the arrangement ofFIGS. 13a-13m, the auto-injector1300comprises: (a) a body1311comprising an injection end1307, (b) a needle assembly1360moveable from a pre-use position to a deployed position, (c) an indicator1332moveable from a pre-use position to a deployed position; wherein when the needle assembly1360is moved from the pre-use position to the deployed position, the indicator1332is moved from the pre-use position to the deployed position, and when the needle assembly1360is removed from the deployed position the indicator1332remains in the deployed position. The needle assembly1360and the indicator1332are moved to the deployed position by a piston1330. The piston assembly1330comprises at least a first portion1331and a second portion1332, and the needle assembly1360is joined to the piston first portion1331, and the piston second portion1332comprises the indicator. The auto-injector body1311comprises at least one indication window1319, and the indicator1332shows in the indication window when in the deployed position. At its deployed position the indicator1332indicates that the needle1361has been deployed. In one arrangement at its deployed position the indicator1332indicates that the auto-injector1300has been used.

FIGS. 14ato 14fillustrate another arrangement of the auto-injector1400device of the present disclosure. The functionality of this arrangement is the same as that of the auto-injector1300illustrated inFIGS. 13a-n, but the construction of the administration assembly1411, and the auto-injector body1401is configured to allow for a certain manufacturing process that will be described here under.FIGS. 14aand 14eillustrate a sterile assembly, comprising the needle housing1421, the piston assembly1430to which the package1433is joined on its distal side, and the needle assembly1460is joined on its proximal side. The needle assembly1460is aseptically enclosed in the needle housing1421. The sterile assembly1420can be provided to the beneficial agent filling site and filling equipment when it is pre sterilized and properly packaged to maintain sterility. The package1433is open at its distal side1433to allow filling of the beneficial agent, which after the distal end of the package1434is sealed. This filling step is preferably done in aseptic conditions, however once the package1433is sealed the sterile assembly1420can be moved out of the controlled filling environment as all the components that require sterility (i.e. the needle1461, the beneficial agent, and the surfaces of the device that are to be in contact with the subject), are aseptically sealed.FIGS. 14band 14fillustrate another filling process approach of the device1400where the package1433is filled prior to it being joined to the piston assembly1430. The sterile assembly1420can be supplied sterile to the filing site in proper packaging. The piston core membrane1434provides an aseptic seal to the needle1461in the needle housing1421when the package1433is not joined to the sterile assembly1420.FIG. 14cillustrate the pressure chamber assembly1440, comprising the auto-injector body1401, the distal portion of the administration assembly1412, and arming mechanism1470. In some arrangements the pressure chamber assembly1440doesn't need to be sterile, and can be joined with the already filled sterile assembly1420after the last has been out of the controlled environment.FIG. 14dillustrates the assembled device1400where the pressure chamber1440is joined with the sterile assembly1420by coupling the female thread at the distal end of the needle housing1421with the male thread of the distal portion of the administration assembly1412to form the complete administration assembly1411.

FIG. 15aandFIG. 15billustrate an arming mechanism, similar to the one illustrated in device1300ofFIGS. 13a-n. A piercing arm1571comprises a cartridge piercing element1572, and is biased toward the cartridge1521by the torsion spring1573.FIG. 15aillustrates an arming mechanism in a safe state corresponding to the first auto-injector state (pre-use configuration) where protrusion1574leans against the cartridge1521side, preventing the piercing arm from moving toward the cartridge1521.FIG. 15billustrates the arming mechanism in an armed state corresponding to the second and third auto-injector states (armed configuration) in which the administration assembly1521has been axially moved relative to the cartridge1521, such that the protrusion1574no longer leans against the cartridge1521, allowing the piercing arm1571to move to the armed position where the cartridge piercing element1522is confronting the pierceable membrane1522of the cartridge1521. In a subsequent activation step the cartridge1521is axially moved toward the piercing arm1571causing the piercing element1522to penetrate the cartridge membrane1522.

The foregoing Figures and arrangements are provided by way of example and are not intended to limit the generality of this disclosure.