Patent Description:
Injection devices, such as auto-injectors, typically have a syringe into which a plunger is pushed to dispense medicament from the syringe into the patient via a needle. The injection process is completed when the plunger has been pushed the appropriate distance into the syringe. It is known to provide a feedback mechanism for indicating to the user when the appropriate volume of medicament has been injected.

<CIT> discloses a drug infusion device to permit the delivery of medication over an extended period of time. In an example, a plunger moves into a cartridge to dispense medicament, and a protrusion on the plunger interacts with a leaf spring to create a sound when the cartridge is empty.

<CIT> discloses an injection device for injecting a medicament from a cartridge through a needle cannula. The injection device includes an actuator for driving a piston driver and includes an end of stroke limiter. When the piston driver is arrested by the end of stroke limiter a shielding driver is automatically triggered to actively shift the needle cannula into a shielded state. The injection device may include a fluid dispensing interruption mechanism that automatically interrupts fluid flow when the piston driver has moved a predetermined stroke length. The injection device may also include a single pre-stressed spring acting exclusively in a linear compression mode or exclusively in a torsion mode and adapted to sequentially drive the device to enable fully automatic operation.

<CIT> discloses a device for delivering a medicament into a patient's body by injection into or through the patient's skin. The device includes a body having a reservoir disposed therein for containing the medicament. The device comprises an injection needle for penetrating the skin of the patient, the needle having a lumen and communicating with the reservoir, and a pressurizing system for pressurizing the reservoir. The device also includes indicator means visible outside the device for indicating that delivery of the medicament is substantially complete.

It is an object of the present invention to provide a feedback mechanism for an injection device that provides delayed feedback to a user, at a time after the medicament has been injected.

According to a first aspect of the invention, there is provided an injection device comprising a medicament delivery mechanism comprising a reservoir, a plunger that moves to displace medicament from the reservoir for delivery to a user during use of the injection device; and a feedback mechanism for an injection device, said injection device being configured to deliver a medicament to a user, the feedback mechanism comprising an actuator and a fluid chamber having a restricted outlet, wherein the actuator is adapted to urge fluid from the fluid chamber through the restricted outlet; and, an indicator adapted to provide feedback to said user after a predetermined volume of fluid has passed from the fluid chamber through the restricted outlet during use of the injection device, wherein the indicator comprises a membrane adapted to be inflated by fluid passing through the restricted outlet.

In some examples, the indicator comprises a shaped passage adapted to create an audible sound as fluid passes through the shaped passage.

The membrane may be adapted to be burst by fluid passing through the restricted outlet.

The actuator may be adapted to move into the fluid chamber after the plunger has reached a pre-determined position. Alternatively, the actuator may be adapted to move into the fluid chamber after a pre-determined amount of medicament has been displaced from the reservoir.

The injection device may further comprise a locking mechanism having a first position in which the locking mechanism holds the actuator, and a second position in which the locking mechanism releases the actuator such that the actuator urges fluid from the fluid chamber.

The locking mechanism may comprise a locking arm that engages the actuator during delivery of said medicament, and the locking arm may be arranged to disengage the actuator after said medicament has been delivered.

The locking arm may comprise a pivot that permits the locking arm to rotate out of engagement with the actuator, and a stop arranged to prevent rotation of the locking arm until said medicament has been delivered.

The locking mechanism may be configured to release the actuator when the plunger has moved to a pre-determined position during delivery of said medicament.

In some examples, the indicator is adapted to provide feedback to said user at a predetermined time after medicament has been delivered to the user. For example, the feedback may be provided more than <NUM> seconds after the medicament has been delivered to the user, or feedback may be provided more than <NUM> seconds after the medicament has been delivered to the user, or feedback may be provided more than <NUM> seconds after the medicament has been delivered to the user.

In some examples, the injection device is an auto-injector. In other examples, the injection device is a pen-injector. In other examples, the injection device is a large-volume device.

A drug delivery device, as described herein, may be configured to inject a medicament into a patient. For example, delivery could be sub-cutaneous, intra-muscular, or intravenous. The user of such a device could be a patient or care-giver, such as a nurse or physician, and can include various types of safety syringe, pen-injector, or auto-injector. The device can include a cartridge-based system that requires piercing a sealed ampule before use. Volumes of medicament delivered with these various devices can range from about <NUM> to about <NUM>. Yet another device can include a large volume device ("LVD") or patch pump, configured to adhere to a patient's skin for a period of time (e.g., about <NUM>, <NUM>, <NUM>, <NUM>, or <NUM> minutes) to deliver a "large" volume of medicament (typically about <NUM> to about <NUM>).

For example, the device may be customized to inject a medicament within a certain time period (e.g., up to about <NUM> seconds for auto-injectors, and about <NUM> minutes to about <NUM> minutes for an LVD). Common sizes are <NUM>, <NUM> and <NUM> Gauge.

The delivery devices described herein can also include one or more automated functions. For example, one or more of needle insertion, medicament injection, and needle retraction can be automated. Energy for one or more automation steps can be provided by one or more energy sources. Energy sources can include, for example, mechanical, pneumatic, chemical, or electrical energy. For example, mechanical energy sources can include springs, levers, elastomers, or other mechanical mechanisms to store or release energy. One or more energy sources can be combined into a single device. Devices can further include gears, valves, or other mechanisms to convert energy into movement of one or more components of a device.

The one or more automated functions of an auto-injector may each be activated via an activation mechanism. Such an activation mechanism can include an actuator, for example, one or more of a button, a lever, a needle sleeve, or other activation component. Activation of an automated function may be a one-step or multi-step process. That is, a user may need to activate one or more activation components in order to cause the automated function. For example, in a one-step process, a user may depress a needle sleeve against their body in order to cause injection of a medicament. Other devices may require a multi-step activation of an automated function. For example, a user may be required to depress a button and retract a needle shield in order to cause injection.

According to some embodiments of the present disclosure, an exemplary drug delivery device <NUM> is shown in <FIG>. Device <NUM>, as described above, is configured to inject a medicament into a patient's body. Device <NUM> includes a housing <NUM> which typically contains a syringe <NUM> containing the medicament to be injected and the components required to facilitate one or more steps of the delivery process. A cap <NUM> is also provided that can be detachably mounted to the housing <NUM>. Typically, a user must remove cap <NUM> from housing <NUM> before device <NUM> can be operated.

As shown, housing <NUM> is substantially cylindrical and has a substantially constant diameter along the longitudinal axis A-A. The housing <NUM> has a distal region D and a proximal region P. The term "distal" refers to a location that is relatively closer to a site of injection, and the term "proximal" refers to a location that is relatively further away from the injection site.

Device <NUM> can also include a needle sleeve <NUM> coupled to housing <NUM> to permit movement of sleeve <NUM> relative to housing <NUM>. For example, sleeve <NUM> can move in a longitudinal direction parallel to longitudinal axis A-A. Specifically, movement of sleeve <NUM> in a proximal direction can permit a needle <NUM> to extend from distal region D of housing <NUM>.

Insertion of needle <NUM> can occur via several mechanisms. For example, needle <NUM> may be fixedly located relative to housing <NUM> and initially be located within an extended needle sleeve <NUM>. Proximal movement of sleeve <NUM> by placing a distal end of sleeve <NUM> against a patient's body and moving housing <NUM> in a distal direction will uncover the distal end of needle <NUM>. Such relative movement allows the distal end of needle <NUM> to extend into the patient's body. Such insertion is termed "manual" insertion as needle <NUM> is manually inserted via the patient's manual movement of housing <NUM> relative to sleeve <NUM>.

Another form of insertion is "automated", whereby needle <NUM> moves relative to housing <NUM>. Such insertion can be triggered by movement of sleeve <NUM> or by another form of activation, such as, for example, a button <NUM>. As shown in <FIG>, button <NUM> is located at a proximal end of housing <NUM>. However, in other embodiments, button <NUM> could be located on a side of housing <NUM>.

Other manual or automated features can include drug injection or needle retraction, or both. Injection is the process by which a bung or piston <NUM> is moved from a proximal location within a syringe <NUM> to a more distal location within the syringe <NUM> in order to force a medicament from the syringe <NUM> through needle <NUM>. In some embodiments, a drive spring (not shown) is under compression before device <NUM> is activated. A proximal end of the drive spring can be fixed within proximal region P of housing <NUM>, and a distal end of the drive spring can be configured to apply a compressive force to a proximal surface of piston <NUM>. Following activation, at least part of the energy stored in the drive spring can be applied to the proximal surface of piston <NUM>. This compressive force can act on piston <NUM> to move it in a distal direction. Such distal movement acts to compress the liquid medicament within the syringe <NUM>, forcing it out of needle <NUM>.

Following injection, needle <NUM> can be retracted within sleeve <NUM> or housing <NUM>. Retraction can occur when sleeve <NUM> moves distally as a user removes device <NUM> from a patient's body. This can occur as needle <NUM> remains fixedly located relative to housing <NUM>. Once a distal end of sleeve <NUM> has moved past a distal end of needle <NUM>, and needle <NUM> is covered, sleeve <NUM> can be locked. Such locking can include locking any proximal movement of sleeve <NUM> relative to housing <NUM>.

Another form of needle retraction can occur if needle <NUM> is moved relative to housing <NUM>. Such movement can occur if the syringe <NUM> within housing <NUM> is moved in a proximal direction relative to housing <NUM>. This proximal movement can be achieved by using a retraction spring (not shown), located in distal region D. A compressed retraction spring, when activated, can supply sufficient force to the syringe <NUM> to move it in a proximal direction. Following sufficient retraction, any relative movement between needle <NUM> and housing <NUM> can be locked with a locking mechanism. In addition, button <NUM> or other components of device <NUM> can be locked as required.

<FIG> and <FIG> show an example injection device <NUM> that includes a syringe <NUM>, similar to as described above with reference to <FIG>. The injection device <NUM> of <FIG> also includes a housing <NUM>, partially shown in <FIG>.

As illustrated, the injection device <NUM> also includes a plunger <NUM> that acts on the piston <NUM> to move the piston <NUM> into the syringe <NUM> and dispense medicament through the needle (not shown). A drive spring <NUM> is provided to push the plunger <NUM> against the piston <NUM> and into the syringe <NUM> during use of the injection device <NUM>. The drive spring <NUM> may be pre-loaded, and a release mechanism may be provided to release the plunger <NUM> such that the drive spring <NUM> can push the plunger <NUM> and piston <NUM> to dispense medicament, as described previously. It will be appreciated that the piston <NUM> may be omitted and the end <NUM> of the plunger <NUM> may be adapted to act as a piston within the syringe <NUM>.

The injection device <NUM> of <FIG> also includes a delay mechanism that provides delayed user feedback at a time after the plunger <NUM> has moved into the syringe <NUM> and medicament has been dispensed. This delayed feedback informs the user that the medicament has been dispensed, and the further delay provides time for the medicament to have dispersed from the injection site.

As illustrated, the injection device <NUM> of this example includes an actuator, in this example a pusher <NUM> that is located within the plunger <NUM>. The plunger <NUM> is elongate and has a cylindrical bore <NUM> with an opening <NUM> at the distal end of the plunger <NUM>, in which the pusher <NUM> is located. The pusher <NUM> also has a cylindrical bore <NUM> with an opening <NUM> at the distal end, and the drive spring <NUM> is located within the cylindrical bore <NUM> of the pusher <NUM>. The drive spring <NUM> acts between a part of the housing <NUM> and the pusher <NUM>, and urges them apart.

A locking mechanism is provided to hold the plunger <NUM> and pusher <NUM> together during initial movement of the plunger <NUM> into the syringe <NUM>. The locking mechanism has locking arms <NUM> that fix the pusher <NUM> relative to the plunger <NUM>, so that the drive spring <NUM> urges the pusher <NUM> and plunger <NUM> into the syringe <NUM> together.

As illustrated in <FIG>, each locking arm <NUM> is pivotally attached to the plunger <NUM> via pivots <NUM>, and a first end <NUM> of each locking arm <NUM> is located in a groove <NUM> formed in the pusher <NUM>. Arm extensions <NUM> of the locking arms <NUM> extend radially of the plunger <NUM>. Stops <NUM> are arranged on the plunger <NUM> to prevent rotation of the locking arms <NUM> as the drive spring <NUM> urges the pusher <NUM> and the plunger <NUM> into the syringe <NUM>. In this way, when the drive spring <NUM> acts on the pusher <NUM>, the locking arms <NUM> are trapped between the stops <NUM> and the grooves <NUM>, and so the pusher <NUM> and plunger <NUM> are pushed together into the syringe <NUM>.

As illustrated in <FIG>, once the plunger <NUM> has completed its movement into the syringe <NUM>, i.e. when the medicament has been dispensed, the arm extensions <NUM> of the locking arms <NUM> contact the annular end <NUM> of the syringe <NUM> and the locking arms <NUM> are rotated so that the pusher <NUM> is released from the plunger <NUM>. In particular, the leverage applied to the arm extensions <NUM> of the locking arms <NUM> as they are pushed against the annular end <NUM> of the syringe <NUM> provides a force adequate to deform or brake the stops <NUM>, allowing the locking arms <NUM> to rotate and disengage from the grooves <NUM> in the pusher <NUM>. In alternative examples, the locking arms <NUM> may abut against another part of the housing <NUM> instead of the end <NUM> of the syringe <NUM>.

Therefore, once the plunger <NUM> has been pushed into the syringe <NUM> the locking arms <NUM> rotate and the pusher <NUM> is free to move independently of the plunger <NUM> under the force of the drive spring <NUM>.

The locking mechanism may be arranged to release the pusher <NUM> from the plunger <NUM> after the plunger <NUM> has been completely pushed into the syringe <NUM>, i.e. when the piston <NUM> reaches the end of the syringe <NUM>. Alternatively, the locking mechanism may be arranged to release the pusher <NUM> from the plunger <NUM> at a point before the plunger <NUM> and piston <NUM> have been completely pushed into the syringe <NUM>, but after an amount of medicament has been dispensed.

As shown in <FIG>, prior to using the injection device <NUM> a fluid chamber <NUM> is defined between the pusher <NUM> and the plunger <NUM>, at a distal end of the plunger <NUM>. In particular, the fluid chamber <NUM> is located in the distal end of cylindrical bore <NUM> of the plunger <NUM>, and is sealed by the distal end of the pusher <NUM>. The pusher <NUM> is provided with a sealing ring <NUM>, for example an 'O'-ring, to seal the fluid chamber <NUM>.

Once the locking arms <NUM> have rotated, as illustrated in <FIG>, the pusher <NUM> is urged further into the cylindrical bore <NUM> of the plunger, <NUM> and the fluid chamber <NUM> is compressed.

The fluid chamber <NUM> includes an outlet <NUM> and a passage <NUM> through the wall of the plunger <NUM>, through which fluid is urged as the pusher <NUM> compresses the fluid chamber <NUM>. A seal (not shown), for example a thin membrane, may be provided over the outlet <NUM>, and the seal may be broken the pressure of the fluid passing through the outlet <NUM> as the fluid chamber <NUM> is compressed. The seal will prevent fluid moving through the outlet <NUM> until the plunger <NUM> has completed its movement.

A membrane <NUM> is located in the passage <NUM> to the fluid chamber <NUM> and blocks the fluid passing through the outlet <NUM> as the pusher <NUM> compresses the fluid chamber <NUM>. As shown in <FIG>, the membrane <NUM> is inflated by fluid passing through the outlet <NUM>.

In an alternative embodiment, the membrane <NUM> is located on the opposite side of the passage <NUM> to the fluid chamber <NUM>, on the outside of the plunger <NUM>.

The inflated membrane <NUM> may be visible from the exterior of the injection device <NUM> and thereby provide a visual indication to the user. The membrane <NUM> may be coloured, or the membrane <NUM> may be transparent or translucent and the fluid may be coloured. Alternatively, the inflated membrane <NUM> may burst after receiving an amount of the fluid via the outlet <NUM>, and thereby provide an audible indication to the user. The fluid in the fluid chamber <NUM>, that passes through the outlet <NUM> and into the membrane, <NUM> may be a liquid or a gas. For example, the fluid may be water. The fluid may be coloured or transparent.

The outlet <NUM> comprises a restriction that slows fluid passage through the outlet <NUM>. This restriction ensures that it takes time for the membrane <NUM> to be inflated and optionally burst, and so the indication is provided to the user at a time after the locking mechanism has released the pusher <NUM>. This delay allows the medicament to disperse from the injection site.

The length of this delay is defined by various factors, such as the size of the outlet <NUM>, the pressure applied to the pusher <NUM> and fluid chamber <NUM>, the type of fluid used, the viscosity of the fluid used, the bursting strength of the membrane <NUM>, and other such factors. This provides a delayed feedback mechanism, which is started when the pusher <NUM> is released by the locking arms <NUM>, and completed when the visual and/or audible indication is provided to the user.

The duration of the delay may be, for example, more than <NUM> seconds, or more than <NUM> seconds, or more than <NUM> seconds, or between <NUM> and <NUM> seconds, or between <NUM> and <NUM> seconds.

In an alternative embodiment similar to that of <FIG>, the locking arms <NUM> may be replaced with locking protrusions that protrude from the plunger <NUM> into the pusher <NUM>, or vice versa, and are configured to be deformed or broken by the force provided by the drive spring <NUM> once the plunger <NUM> has been adequately pushed into the syringe <NUM>. In this way, the plunger <NUM> and pusher <NUM> move together until the plunger <NUM> reaches the end of the syringe <NUM>, then the locking protrusions deform or break to permit the pusher <NUM> to compress the fluid chamber <NUM> and thereafter provide delayed feedback.

<FIG> shows an alternative example, with the same plunger <NUM>, pusher <NUM>, locking arms <NUM> and fluid chamber <NUM> as described with reference to <FIG>. However, in this example the outlet <NUM> of the fluid chamber <NUM> and/or the passage <NUM> through the wall of the plunger <NUM>, is shaped to generated an audible sound, for example a whistling sound. No inflatable membrane is provided.

In this example as the locking arms <NUM> rotate and release the pusher <NUM> as previously described, the pusher <NUM> compresses the fluid chamber <NUM> and fluid is urged through the outlet <NUM> and the shaped passage <NUM> and a whistling sound is generated. The outlet <NUM> has a restriction to slow fluid flow through the outlet <NUM> and ensure that the indication is provided at a time after the medicament has been delivered, to allow medicament to disperse from the injection site. In this example, the fluid is preferably a gas.

The feedback mechanism may be configured such that the start of the whistling sound informs the user that the plunger <NUM> has moved to the end of the syringe <NUM> and the medicament has been injected, and the end of the whistling sound informs the user that an appropriate amount of time has elapsed to account for dispersion of the medicament from the injection site. The duration of the whistling sound can be determined by various factors, including the size of the fluid chamber <NUM>, the size of the outlet <NUM>, and the force provided by the drive spring <NUM>.

The whistling sound may last for a duration of, for example, more than <NUM> seconds, or more than <NUM> seconds, or more than <NUM> seconds, or between <NUM> and <NUM> seconds, or between <NUM> and <NUM> seconds.

<FIG> show an alternative example injection device <NUM> that includes a syringe <NUM>, similar to as described above with reference to <FIG>. The injection device <NUM> of <FIG> also includes a housing <NUM>, partially shown in <FIG>.

As illustrated, the injection device <NUM> also includes a plunger <NUM> that acts on the piston <NUM> to move the piston <NUM> into the syringe <NUM> and dispense medicament from the needle (not shown). A drive spring <NUM> is provided to push the plunger <NUM> against the piston <NUM> and into the syringe <NUM> during use of the injection device <NUM>. The drive spring <NUM> may be pre-loaded, and a release mechanism may be provided to release the plunger <NUM> such that the drive spring <NUM> can push the plunger <NUM> and piston <NUM> to dispense medicament, as described previously. It will be appreciated that the piston <NUM> may be omitted and the end <NUM> of the plunger <NUM> may act as a piston within the syringe <NUM>.

In this example, the plunger <NUM> has a cylindrical bore <NUM> that is open at the proximal end, and the drive spring <NUM> is located in the cylindrical bore2 <NUM>. An actuator, in this example a carrier <NUM>, is provided near the proximal end of the injection device <NUM> and the drive spring <NUM> acts between the plunger <NUM> and the carrier <NUM> to urge the plunger <NUM> distally into the syringe <NUM> to dispense medicament.

The carrier <NUM> is initially held in position by a locking mechanism. In particular, locking arms <NUM> hold the carrier <NUM> in position. The locking arms <NUM> have inward deflections <NUM> at their proximal ends that prevent the carrier <NUM> moving in a proximal direction. The locking arms <NUM> are pivotally mounted to the housing <NUM> about pivots <NUM>, but in the position of <FIG> the locking arms <NUM> are prevented from rotation about the pivots <NUM> by the presence of the plunger <NUM>. Therefore, in the position shown in <FIG>, the drive spring <NUM> can push on the carrier <NUM>, which is held in place by the locking arms <NUM>.

<FIG> illustrates the injection device <NUM> prior to use, and <FIG> illustrates the injection device <NUM> during use. As shown in <FIG>, the drive spring <NUM> has moved the plunger <NUM> distally into the syringe <NUM> and medicament has been dispensed. In this position, with the medicament having been dispensed from the syringe <NUM>, the proximal end <NUM> of the plunger <NUM> has moved past the locking arms <NUM> which are now free to rotate and release the carrier <NUM>, as illustrated in <FIG>. The drive spring <NUM> pushes the carrier <NUM> against the inward deflections <NUM>, which urges the locking arms <NUM> to rotate apart to release the carrier <NUM>. The carrier <NUM> then moves in a proximal direction under the force of the drive spring <NUM>.

The locking mechanism may be arranged to release the carrier <NUM> after the plunger <NUM> has been completely pushed into the syringe <NUM>, i.e. when the piston <NUM> reaches the end of the syringe <NUM>. Alternatively, the locking mechanism may be arranged to release the carrier <NUM> at a point before the plunger <NUM> and piston <NUM> have been completely pushed into the syringe <NUM>, but after an amount of medicament has been dispensed.

A fluid chamber <NUM> is formed at the distal end <NUM> of the plunger <NUM>. As illustrated in <FIG>, the distal end <NUM> of the plunger <NUM> includes a recess <NUM> in which the fluid chamber <NUM> is located. A pusher <NUM> is also located in the recess <NUM> and is connected to the carrier <NUM> via a tether <NUM> that extends through the plunger <NUM>. The pusher <NUM> seals against the recess <NUM> to define the fluid chamber <NUM>. As shown, the pusher <NUM> includes a sealing ring <NUM>, for example an 'O'-ring.

As illustrated in <FIG> and <FIG>, as the locking arms <NUM> rotate to release the carrier <NUM>, the carrier <NUM> is moved proximally by the drive spring <NUM> and pulls the tether <NUM>, which in turns pulls the pusher <NUM> proximally and compresses the fluid chamber <NUM>.

The fluid chamber <NUM> includes an outlet <NUM> through the wall of the recess <NUM> of the plunger <NUM>, through which the fluid is urged as the pusher <NUM> compresses the fluid chamber <NUM>. A seal (not shown), for example a thin membrane, may be provided over the outlet <NUM>, and the seal may be broken by the pressure of the fluid passing through the outlet <NUM> as the fluid chamber <NUM> is compressed. The seal will prevent fluid moving through the outlet <NUM> until the plunger <NUM> has completed its movement.

A membrane <NUM> is located at the outlet <NUM> and blocks the fluid passing out of the fluid chamber <NUM> as the pusher <NUM> compresses the fluid chamber <NUM>. As shown in <FIG>, the membrane <NUM> is inflated by fluid passing through the outlet <NUM>.

The inflated membrane <NUM> may be visible from the exterior of the injection device <NUM> and thereby provide a visual indication to the user. The membrane <NUM> may be coloured, or the membrane <NUM> may be transparent or translucent and the fluid may be coloured. Alternatively, as shown in <FIG>, the inflated membrane <NUM> may burst after receiving an amount of the fluid via the outlet <NUM>, and thereby provide an audible indication to the user. The fluid in the fluid chamber <NUM>, that passes through the outlet <NUM> and into the membrane <NUM>, may be a liquid or a gas. For example, the fluid may be water. The fluid may be coloured or transparent.

<FIG> shows an alternative example injection device <NUM>, with the same plunger <NUM>, pusher <NUM> and locking arms <NUM> as described with reference to <FIG>. However, in this example the outlet <NUM> of the fluid chamber <NUM> has a shaped passage <NUM> that generates an audible sound, for example a whistling sound, as fluid passes through it. No inflatable membrane is provided.

In this example as the locking arms <NUM> rotate and release the carrier <NUM>, the carrier <NUM> pulls the pusher <NUM> via the tether <NUM> to compress the fluid chamber <NUM> and fluid is urged through the outlet <NUM> and the shaped passage <NUM> and a whistling sound is generated. In this example, the fluid is preferably a gas, for example air or an inert gas.

The delay mechanism may be arranged such that the start of the whistling sound informs the user that the plunger <NUM> has moved to the end of the syringe <NUM> and the medicament has been injected, and the end of the whistling sound informs the user that an appropriate amount of time has elapsed to account for dispersion of the medicament from the injection site. The duration of the whistling sound can be determined by various factors, including the size of the fluid chamber <NUM>, the size of the outlet <NUM>, and the force provided by the drive spring <NUM>.

The duration of the whistling sound may be, for example, more than <NUM> seconds, or more than <NUM> seconds, or more than <NUM> seconds, or between <NUM> and <NUM> seconds, or between <NUM> and <NUM> seconds.

<FIG> show an alternative example injection device <NUM> that includes a syringe (not shown), plunger <NUM> and actuator (carrier <NUM>), similar to as described above with reference to <FIG>. The injection device <NUM> of <FIG> also includes a housing <NUM>.

As with other examples, the plunger <NUM> acts on a piston (e.g. <NUM>, see <FIG>) to move the piston into the syringe (e.g. <NUM>, see <FIG>) and dispense medicament from a needle (e.g. <NUM>, see <FIG>). A drive spring <NUM> is provided to push the plunger <NUM> against the piston and into the syringe during use of the injection device <NUM>. The drive spring <NUM> may be pre-loaded, and a release mechanism may be provided to release the plunger <NUM> and cause the medicament to be dispensed, as described previously.

The injection device <NUM> of <FIG> also includes a delay mechanism that provides delayed user feedback at a time after the plunger <NUM> has moved into the syringe (e.g. <NUM>, see <FIG>). This delayed feedback informs the user that the medicament has been dispensed, and the delay provides time for the medicament to have dispersed from the injection site.

In this example, the plunger <NUM> has a cylindrical bore <NUM> that is open at the proximal end <NUM>, and the drive spring <NUM> is located in the cylindrical bore <NUM>. An actuator, in this example a carrier <NUM>, is provided near the proximal end of the injection device <NUM> and the drive spring <NUM> acts between the plunger <NUM> and the carrier <NUM> to urge the plunger <NUM> distally into the syringe (e.g. <NUM>, see <FIG>) to dispense medicament.

The carrier <NUM> is initially held in position by a locking mechanism. In particular, locking arms <NUM> hold the carrier <NUM> in position. The locking arms <NUM> have inward deflections <NUM> at their proximal ends that prevent the carrier <NUM> moving in a proximal direction. The locking arms <NUM> also include pivots <NUM>, but in the position of <FIG> the locking arms <NUM> are prevented from rotation about the pivots <NUM> by the presence of the plunger <NUM>. Therefore, in the position shown in <FIG>, the drive spring <NUM> can push on the carrier <NUM>, which is held in place by the locking arms <NUM>.

<FIG> illustrates the injection device <NUM> prior to use, and <FIG> illustrates the injection device <NUM> during use. As shown in <FIG>, the drive spring <NUM> has moved the plunger <NUM> distally and medicament has been dispensed. In this position, with the medicament having been dispensed, the proximal end <NUM> of the plunger <NUM> has moved past the locking arms <NUM> which are now free to rotate and release the carrier <NUM>. In this position, the drive spring <NUM> pushes the locking arms <NUM> apart and the inward deflections <NUM> release the carrier <NUM>. The carrier <NUM> can therefore move in a proximal direction under the force of the drive spring <NUM>.

The locking mechanism may be arranged to release the carrier <NUM> after the plunger <NUM> has been completely pushed into the syringe (e.g. <NUM>, see <FIG>). Alternatively, the locking mechanism may be arranged to release the carrier <NUM> at a point before the plunger <NUM> has been completely pushed into the syringe (e.g. <NUM>, see <FIG>), but after a volume of medicament has been delivered.

As shown, a fluid chamber <NUM> is located at a proximal end of the housing <NUM>. The fluid chamber <NUM> is defined by a membrane <NUM> that holds a fluid on the inside the fluid chamber <NUM>. The proximal end of the housing <NUM> includes an outlet <NUM> that is aligned with the fluid chamber <NUM>. A second chamber <NUM> is located on the outside of the housing <NUM>, aligned with the outlet <NUM>.

Therefore, as illustrated in <FIG>, when the carrier <NUM> is released by the locking arms <NUM> the carrier <NUM> is urged proximally and engages and compresses the membrane <NUM> on the inside of the housing <NUM>. This urges fluid through the outlet <NUM> and into the second chamber <NUM>.

The second chamber <NUM> may be transparent, so that the user can see the fluid entering the second chamber <NUM> as an indication that the plunger <NUM> has completed its movement into the syringe and an appropriate additional delay has elapsed for medicament to disperse from the injection site. The fluid may be coloured. The fluid may be a liquid, for example water.

The outlet <NUM> comprises a restriction that slows fluid passage through the outlet <NUM> and into the second chamber <NUM>. This restriction ensures that it takes time for fluid to reach the second chamber <NUM>, providing a delay between the time the locking mechanism releases the carrier <NUM> and the time that the indication is provided to the user. This delay allows the medicament to disperse from the injection site.

The length of this delay is defined by various factors, such as the size of the outlet <NUM>, the pressure applied to the pusher <NUM> and fluid chamber <NUM>, the type of fluid used, the viscosity of the fluid used, and other such factors. This provides a delayed feedback mechanism, which is started when the carrier <NUM> is released by the locking arms <NUM>, and completed when the visual and/or audible indication is provided to the user.

<FIG> show a similar example to that of <FIG>, with a plunger <NUM>, actuator (carrier <NUM>) and a membrane <NUM> that defines a fluid chamber <NUM>. In this example, the second chamber <NUM> on the outside of the proximal end of the housing <NUM> comprises a deflectable wall <NUM>.

In particular, as shown in <FIG>, prior to use a deflectable wall <NUM> of the second chamber <NUM> is deflected inwards, indicating that the injection device <NUM> has not been used and/or that it is not ready to be removed from the user. After use, when fluid has been urged through the outlet <NUM> and into the second chamber <NUM> by the carrier <NUM>, as illustrated in <FIG>, the deflectable wall <NUM> of the second chamber <NUM> has been deflected outwards by the increased fluid pressure within the second chamber <NUM>.

The outlet <NUM> includes a restriction that slows fluid flow through the outlet <NUM> and therefore delays the time at which the deflectable wall <NUM> is deflected outwards by the fluid.

This outwardly deflected wall <NUM> therefore provides an indication that the plunger <NUM> has completed its movement into the syringe (e.g. <NUM>, see <FIG>) and the medicament has been dispensed, and that an appropriate amount of time has elapsed for the medicament to have dispersed from the injection site.

The second chamber <NUM> may additionally be transparent, so that the user can see the fluid entering the second chamber <NUM> as an indication that the plunger <NUM> has completed its movement into the syringe (e.g. <NUM>, see <FIG>). The fluid may be coloured. The fluid may be a liquid, for example water.

<FIG> show a similar example injection device <NUM> to those of <FIG>, <FIG>. The injection device <NUM> includes a plunger <NUM>, an actuator (carrier <NUM>), and rotatable locking arms <NUM> that hold the carrier <NUM> until the plunger <NUM> has been moved a distance into the syringe (e.g. <NUM>, see <FIG>). Once the carrier <NUM> is released, the drive spring <NUM> urges the carrier <NUM> in a proximal direction.

In this example, the proximal end of the housing <NUM> has a cylindrical protrusion <NUM> and a piston <NUM> is provided within the cylindrical protrusion <NUM> to define a fluid chamber <NUM>. A seal <NUM> is provided between the piston <NUM> and the cylindrical protrusion <NUM>. The proximal wall <NUM> of the housing <NUM>, within the cylindrical protrusion <NUM>, includes an outlet <NUM>. A second chamber <NUM> is provided on the opposite side of the outlet <NUM> to the fluid chamber <NUM>. The second chamber <NUM> is optionally provided with an air outlet <NUM>.

As shown in <FIG>, when the carrier <NUM> is released by the locking arms <NUM>, after the plunger <NUM> has moved distally, the drive spring <NUM> urges the carrier <NUM> against the piston <NUM>, which is pushed into the fluid chamber <NUM> and urges fluid through the outlet <NUM> and into the second chamber <NUM>. Air may be displaced from the second chamber <NUM> through the air outlet <NUM>.

A seal <NUM> may initially be provided over the outlet <NUM> to prevent movement of the fluid into the second chamber <NUM> before the carrier <NUM> has been released.

The outlet <NUM> includes a restriction that slows fluid flow through the outlet <NUM>, thereby delaying the movement of the piston <NUM>, and delaying the indication to the user. This provides a delay for the medicament to disperse from the injection site.

Alternatively or additionally, as illustrated in <FIG>, the piston <NUM> may trigger an audible indication to the user. In this example, the piston <NUM> comprises an arm <NUM> that protrudes from the piston <NUM> and engages a sound generator <NUM>. The sound generator <NUM> is a pre-stressed element that is held in a deflected position by the arm <NUM> until the piston <NUM> moves into the fluid chamber <NUM>, at which point the arm <NUM> disengages the sound generator <NUM> and the pre-stressed element returns to its natural shape. This changing of shape of the sound generator <NUM> generates an audible sound, which provides the user with an indication that enough time has elapsed for the medicament to have dispersed from the injection site. In particular the arm <NUM> does not disengage the sound generator <NUM> until a volume of fluid has passed into the second chamber <NUM>, which is delayed by the restricted outlet <NUM>, thereby providing a delay in the feedback.

In any of the examples of <FIG>, a seal may be provided over the outlet <NUM>, <NUM> that is broken by the pressure provided by the carrier <NUM> compressing the fluid chamber <NUM>, <NUM>. The seal prevents fluid moving through the outlet <NUM>, <NUM> prior to use of the injection device <NUM>, <NUM>, <NUM>.

In each of the examples of <FIG>, the carrier <NUM> is released at or near the end of the movement of the plunger <NUM> into the syringe (e.g. <NUM>, see <FIG>), when all or nearly all of the medicament has been injected into the user. The arrangement of the fluid chamber <NUM>, <NUM> and outlet <NUM>, <NUM> then provides a delay before the user is provided with the indication. This delay allows the medicament to disperse from the injection site before the indication is provided to the user. It is intended that the indication informs the user that they may remove the injection device from the injection site.

<FIG> show an alternative example injection device <NUM>, similar to the examples of <FIG>. In this example the plunger <NUM>, actuator (carrier <NUM>) and locking arms <NUM> are similar to as described with reference to <FIG>. However, in this example the fluid chamber <NUM> is not defined by a membrane but by a cylindrical protrusion <NUM> located on the inside of the proximal end <NUM> of the housing <NUM>. An outlet <NUM> passes through the proximal end <NUM> of the housing <NUM> to atmosphere - no second chamber is provided as per the examples of <FIG>.

In this example, once the carrier <NUM> is released by the locking arms <NUM> the carrier <NUM> is pushed into the cylindrical protrusion <NUM> by the drive spring <NUM>, and the carrier <NUM> sealably closes a fluid chamber <NUM>, as illustrated in <FIG>. The carrier <NUM> may include a sealing ring <NUM>, for example an 'O'-ring.

The fluid chamber <NUM> is subsequently compressed by the carrier <NUM> and fluid, in this example air, is urged through the outlet <NUM>.

The outlet <NUM> has a shaped passage <NUM> that generates an audible sound, for example a whistling sound, as fluid passes through it. The outlet <NUM> also has a restriction that slows fluid flow through the outlet <NUM>, therefore delaying the indication to the user.

The feedback mechanism may be arranged such that the start of the whistling sound informs the user that the medicament has been injected, and the end of the whistling sound informs the user that an appropriate amount of time has elapsed to account for dispersion of the medicament from the injection site. The duration of the whistling sound can be determined by the size of the cylindrical protrusion <NUM> (and fluid chamber <NUM>), the size of the outlet <NUM>, and the force provided by the drive spring <NUM>.

<FIG> show examples of the configuration of an outlet <NUM> for generating an audible sound, e.g. whistling. These may be used for the examples of <FIG>, <FIG>, or <FIG>.

In the example of <FIG>, the outlet <NUM> is shaped to generate a hissing or whistling sound as fluid is urged through the outlet <NUM> from the fluid chamber <NUM>. The outlet <NUM> has a tapered entry <NUM> to accelerate fluid flow through the outlet <NUM> and thereby increase the volume of the sound. In the example of <FIG> an amplifier <NUM> is provided with a funnel shaped passage <NUM> located in line with the outlet <NUM> to further amplify the volume of the sound as fluid is urged through the outlet <NUM>.

It will be appreciated that the drive spring of each of the examples described herein may be omitted if the injection device is adapted to be manually operated. For example, the injection device may be provided with a lever or button that the user manually operates to push the plunger into the syringe. In this case, the force provided by the user may be used to subsequently compress the fluid chamber.

In any of the above-described examples, the delay between the beginning of compression of the fluid chamber and the indication being provided to the user may be increased by using a highly viscous, or non-Newtonian fluid. This reduces the rate at which the fluid can pass through the outlet during compression of the fluid chamber and thereby delays the indication to the user.

Without limitation, a drug delivery device may be an injection device (e.g., syringe, pen-injector, auto-injector, large-volume device, pump, perfusion system, or other device configured for intraocular, subcutaneous, intramuscular, or intravascular delivery), skin patch (e.g., osmotic, chemical, micro-needle), inhaler (e.g., nasal or pulmonary), implantable (e.g., coated stent, capsule), or feeding systems for the gastrointestinal tract.

The drug container may be, e.g., a cartridge, syringe, chamber, or other vessel configured to provide a suitable chamber for storage (e.g., short- or long-term storage) of one or more pharmaceutically active compounds.

Exemplary insulin derivatives are, for example, B29-N-myristoyl-des(B30) human insulin; B29-N-palmitoyl-des(B30) human insulin; B29-N-myristoyl human insulin; B29-N-palmitoyl human insulin; B28-N-myristoyl LysB28ProB29 human insulin; B28-N-palmitoyl-LysB28ProB29 human insulin; B30-N-myristoyl-ThrB29LysB30 human insulin; B30-N-palmitoyl- ThrB29LysB30 human insulin; B29-N-(N-palmitoyl-gamma-glutamyl)-des(B30) human insulin; B29-N-(N-lithocholyl-gamma-glutamyl)-des(B30) human insulin; B29-N-(ω-carboxyheptadecanoyl)-des(B30) human insulin and B29-N-(ω-carboxyhepta¬decanoyl) human insulin. Exemplary GLP-<NUM>, GLP-<NUM> analogues and GLP-<NUM> receptor agonists are, for example: Lixisenatide / AVE0010 / ZP10 / Lyxumia, Exenatide / Exendin-<NUM> / Byetta / Bydureon / ITCA <NUM> / AC-<NUM> (a <NUM> amino acid peptide which is produced by the salivary glands of the Gila monster), Liraglutide / Victoza, Semaglutide, Taspoglutide, Syncria / Albiglutide, Dulaglutide, rExendin-<NUM>, CJC-<NUM>-PC, PB-<NUM>, TTP-<NUM>, Langlenatide / HM-11260C, CM-<NUM>, GLP-<NUM> Eligen, ORMD-<NUM>, NN-<NUM>, NN-<NUM>, NN-<NUM>, Nodexen, Viador-GLP-<NUM>, CVX-<NUM>, ZYOG-<NUM>, ZYD-<NUM>, GSK-<NUM>, DA-<NUM>, MAR-<NUM>, MAR709, ZP-<NUM>, ZP-<NUM>, TT-<NUM>, BHM-<NUM>. MOD-<NUM>, CAM-<NUM>, DA-<NUM>, ARI-<NUM>, ARI-<NUM>, Exenatide-XTEN and Glucagon-Xten.

Claim 1:
An injection device (<NUM>, <NUM>) comprising a medicament delivery mechanism comprising a reservoir, a plunger (<NUM>, <NUM>) that moves to displace medicament from the reservoir (<NUM>) for delivery to a user during use of the injection device; and a feedback mechanism for an injection device (<NUM>, <NUM>), said injection device (<NUM>, <NUM>) being configured to deliver a medicament to a user, the feedback mechanism comprising an actuator (<NUM>, <NUM>) and a fluid chamber (<NUM>, <NUM>) having a restricted outlet (<NUM>, <NUM>), wherein the actuator (<NUM>, <NUM>) is adapted to urge fluid from the fluid chamber (<NUM>, <NUM>) through the restricted outlet (<NUM>, <NUM>); and, an indicator (<NUM>, <NUM>) adapted to provide feedback to said user after a predetermined volume of fluid has passed from the fluid chamber (<NUM>, <NUM>) through the restricted outlet (<NUM>, <NUM>) during use of the injection device (<NUM>, <NUM>), wherein the indicator (<NUM>, <NUM>) comprises a membrane (<NUM>, <NUM>) adapted to be inflated by fluid passing through the restricted outlet (<NUM>, <NUM>).