Drug delivery device

Abstract

To provide a drug delivery device that prevents false handling of a device and measures information on an injected dose and information on use of an injection device.SOLUTION: A drug delivery device includes: a housing; a drug delivery mechanism displaceable between pre-delivery and mechanical stop positions when a user presses down on a proximal end of the drug delivery mechanism; and an end-of-dose switch configured to be triggered prior to the drug delivery mechanism reaching the mechanical stop position, the end-of-dose switch comprising first and second sensor elements disposed at the drug delivery mechanism and the housing. The drug delivery mechanism is biased such that, when a user ceases to press on the proximal end of the drug delivery mechanism, the first and second sensor elements move out of the switch position. The drug delivery device further comprises a controller configured to, when a duration of time between the end-of-dose switch being triggered and the first and second sensor elements moving out of the switch position is less than a prescribed period, generate an error code indicative of a deviation between manipulations and a predetermined handling scheme.SELECTED DRAWING: Figure 13

Description

[Technical Field]

[0001] The present disclosure relates to drug delivery devices. [Background technology]

[0002] Pen-type drug delivery devices are used where injections by individuals without formal medical training are routine, and are becoming increasingly popular among diabetics, where self-medication allows patients to effectively manage their diabetes.

[0003] For good or perfect glycemic control, the dose of insulin or insulin glargine should be tailored to each individual according to the blood glucose level to be achieved. The present disclosure relates to syringes, for example handheld syringes, in particular pen-type syringes; i.e., the present disclosure relates to syringes of the type that administer by injecting a pharmaceutical product from a multi-dose cartridge. In particular, the present disclosure relates to such user-settable dose syringes. The dose to be injected can be manually selected on the syringe, for example, by turning a dose knob and observing the actual dose in a dose window or display of the injection device.

[0004] Users who self-administer insulin typically need to administer between 1 and 80 International Units. In order to be able to monitor the dose, it is desirable to measure information about the status and / or use of the injection device, e.g., information about the dose injected, e.g., to prevent mishandling of the device or to keep track of doses already taken. Summary of the Invention [Means for solving the problem]

[0005] In accordance with principles of the present disclosure, there is provided a drug delivery device comprising: a housing having a proximal end and a distal end; a drug delivery mechanism disposed at least partially within the housing, the drug delivery mechanism being displaceable between a pre-delivery position and a mechanical stop position to dispense a medication from the drug delivery device when a user depresses the proximal end of the drug delivery mechanism; and an end-of-dose switch configured to be triggered before the drug delivery mechanism reaches the mechanical stop position, the end-of-dose switch including a first sensor element disposed on the drug delivery mechanism and a second sensor element disposed within the housing; the end-of-dose switch is configured to be triggered by relative movement between the first sensor element and the second sensor element when the first and second sensor elements move to the switch position, and the drug delivery mechanism is biased in a proximal direction opposite the mechanical stop position such that the first and second sensor elements move away from the switch position when a user stops pressing the proximal end of the drug delivery mechanism; The drug delivery device further comprises: Recording when the end-of-dose switch is triggered; measuring a time period between the time the end-of-dose switch is triggered and the time the first and second sensor elements move away from the switch position; and generating an error code indicating incorrect use of the device when the measured time period is less than a predetermined time period. A drug delivery device is provided that includes a controller configured to:

[0006] The drug delivery mechanism may be displaceable relative to the housing between a pre-delivery position and a mechanical stop position to dispense medicament from the drug delivery device.

[0007] The error code further indicates that the dose of drug delivered during use of the device is greater than the predetermined dose of drug. It can be shown that the dose is less than .

[0008] Thus, if a user misuses the device, said misuse is recorded by the generation of an error code.

[0009] The error code may alert the user that the dose of drug delivered during use of the device may be less than the predetermined dose of the drug.

[0010] The switch position may be any position of the first and second sensor elements that causes the end-of-dose switch to be triggered.

[0011] The first and second sensor elements are movable to a switch position when the second sensor element moves past a distal edge of the first sensor element.

[0012] Thus, the switch position can be determined by simple sensor placement.

[0013] The end dose switch is configured to be triggered when the first sensor element moves distally past switch position 340 .

[0014] Thus, in embodiments of the present disclosure, the relative movement of a first sensor element relative to a second sensor element can be used to generate a signal.

[0015] The first sensor element may include a conductive strip on the drug delivery mechanism that is electrically connected to the controller.

[0016] Thus, a signal can be generated when the first sensor element comes into contact with the second sensor element.

[0017] The second sensor element may include a bridging contact configured to connect the conductive strip to a live strip on the drug delivery mechanism for transmitting an electrical signal to the controller.

[0018] The bridge contact is formed as a metal stamping and includes contacts disposed at the ends of cantilevered members of the metal stamping, the contacts being configured to contact the live strip and the first sensor element, respectively, to electrically connect the live strip to the sensor element.

[0019] The second sensor element may include two or more bridging contacts spaced apart on the inner surface of the housing.

[0020] Thus, regardless of the rotational position of the drug delivery mechanism relative to the housing, at least one live strip is connected to at least one conductive strip.

[0021] Two or more bridging contacts may be provided at the proximal end of the housing.

[0022] The drug delivery mechanism may include a dose setting component that is rotatable relative to the housing to set the drug dose to be administered; and the first sensor element includes a series of conductive strips spaced apart on an outer surface of the dose setting component.

[0023] The first sensor element may therefore be used as part of a rotary encoder that encodes the drug dose set by the dose setting component.

[0024] The dose setting component may further include conductive dose-coding strips and live strips spaced alternately on an outer surface of the dose setting component, the dose-coding strips each being electrically connected to the controller, and the bridging contacts connecting and disconnecting the dose-coding strips to the live strips as the dose setting component rotates relative to the housing to transmit an electrical signal to the controller and encode the set drug dose.

[0025] The first sensor element may include a plurality of conductive strips spaced around the proximal end of the dose setting component.

[0026] Thus, the end-of-dose switch is triggered just before the drug delivery mechanism moves to the mechanical stop position.

[0027] The plurality of conductive strips of the first sensor element may be spaced apart to allow the dose-coding strip to extend between them and make electrical connection with the controller.

[0028] The conductive strip and / or dose-coding strip are printed, plated or etched onto the outer surface of the dose setting component.

[0029] The controller can be configured to record a set drug dose that is encoded when the end dose switch is triggered.

[0030] The controller may be provided at the proximal end of the dose setting component, thereby providing a compact device.

[0031] The predetermined period of time may be based on human reaction times.

[0032] This ensures that in the overwhelming majority of cases, the dose is logged as being fully dispensed before the user stops pressing the drug delivery mechanism in response to reaching the mechanical stop.

[0033] The predetermined period of time may be between 0.2 and 0.4 seconds.

[0034] The predetermined period is preferably 0.25 seconds.

[0035] The drug delivery device may be configured to provide a visual and / or audio cue to a user of the drug delivery device to indicate that the set drug dose has been administered after the expiration of a predetermined period of time.

[0036] Thus, the user is informed that they may stop pressing the drug delivery mechanism.

[0037] The device can be configured to provide a visual and / or audio cue to a user of the device to alert the user that the set drug dose may not have been fully administered when the user stops pressing the proximal end of the drug delivery mechanism before the end of the predetermined period of time.

[0038] The following description refers to the following figure: [Brief explanation of the drawings]

[0039] [Figure 1] 1 shows an external view of a drug delivery device. [Figure 2] FIG. 2 shows a schematic diagram of the electronic components present in the drug delivery device of FIG. 1. [Figure 3] 3A and 3B show partial perspective views of a drug delivery mechanism of a drug delivery device. [Figure 4] 4A and 4B show partial plan views of a drug delivery mechanism of a drug delivery device. [Figure 5] 1 illustrates an exemplary conductive strip arrangement. [Figure 6] 1 illustrates an exemplary conductive strip arrangement. [Figure 7] FIG. 10 is a schematic diagram of an end dose switch. [Figure 8] Bridging contacts are shown. [Figure 9] 9A and 9B show the dose delivery button in the out and in positions, respectively. [Figure 10] 3 is a schematic diagram showing switch position 340 relative to mechanical stop position. [Figure 11] FIG. 1 is a schematic diagram showing the sequence of events for a user to operate a drug delivery device. [Figure 12] 1 is a flowchart illustrating three outcomes of the first use case scenario. [Figure 13] 10 is a flowchart illustrating two outcomes of the second use case scenario. [Figure 14] FIG. 10 is a schematic diagram showing an end-of-dose switch. [Figure 15]FIG. 10 is a schematic diagram showing an end-of-dose switch. DETAILED DESCRIPTION OF THE INVENTION

[0040] Referring first to FIG. 1 , an external view of a drug delivery device 100 according to an embodiment of the present invention is shown. The device 100 shown in FIG. 1 is a pen-type injection device having an elongated cylindrical shape for injecting and delivering medications such as insulin. The device 100 includes a housing 102 having a first housing member 104 and a second housing member 106. A rotatable dial 108 is located at a first end (or proximal end) of the first housing member 104. The rotatable dial 108 has substantially the same outer diameter as the first housing member 104. The second housing member 106 is removably connectable to a second end of the first housing member 104. The second housing member 106 is configured to have a needle (not shown) or similar drug delivery device attached thereto. To achieve this, the second end (or distal end) of the second housing member 106 can have a threaded portion 110. The threaded portion 110 can have a smaller diameter than the remainder of the second housing member 106.

[0041] A display mount 112 is located on the first housing member 104. A display 210 may be supported on the display mount 112. The display 210 may be an LCD display, a segmented display, or any other suitable type of display. The display mount 112 may cover a recess (not shown) in the first housing portion 104. Several electronic components, which will be described in more detail with reference to FIG. 2, may be disposed below the display mount 112.

[0042] The first housing member 104 houses a drug dose setting delivery mechanism. The second housing member 106 houses a drug cartridge (not shown). The drug contained in the drug cartridge may be any type of medication and is preferably in liquid form. The drug delivery mechanism of the first housing member 104 may be configured to engage with the drug cartridge of the second housing member 106 to facilitate drug ejection. The second housing member 106 may be detachable from the first housing member 104 to insert a drug cartridge or to remove a used cartridge. The first and second housing members 104, 106 may be coupled to each other in any suitable manner, for example, with a threaded or bayonet-type connection. The first and second housing members 104, 106 may be irreversibly coupled to each other such that the drug cartridge is permanently housed within the drug delivery device 100. Furthermore, the first and second housing members 104, 106 may form part of a single housing member.

[0043] The rotatable dial 108 is configured to be rotated by hand by a user of the drug delivery device 100 to set the drug dose to be delivered. The dial 108 can be coupled to a movable dose programming component (302, FIG. 3) of a dose setting mechanism (300, FIG. 3) that includes an internal thread system. When rotated in a first direction, the internal thread system axially displaces the dial 108 from the housing 102. The dial 108 can be rotatable in both directions or only in the first direction. Once the drug dose is set by rotating the rotatable dial 108, the device 100 is configured to deliver the set drug dose when the user applies axial force at the proximal end of the device. The rotatable dial 108 can support a dose delivery button (308, FIG. 3) that must be depressed to deliver the set drug dose. The display 210 can be configured to display information regarding the set and / or delivered drug dose. The display 210 may also show additional information, such as the current time, the time of last use / injection, the remaining battery charge, and one or more warning signs indicating that the dialed dose was not fully dispensed.

[0044] 2, there is shown a schematic diagram of an electrical circuit 200 forming part of the drug delivery device 100. The circuit 200 includes a controller 202 (herein processor 202), non-volatile memory such as ROM 204, writable non-volatile memory such as flash memory 205, volatile memory such as RAM 206, a display 210, conductive strips 212, and a bus 208 connecting each of these components. The circuit 200 also includes a battery 214 or some other suitable power source and a switch 216 for powering each of the components, which will be described in more detail below.

[0045] Circuit 200 may be integral to device 100. Alternatively, circuit 200 may be housed in an electronic module that may be attached to device 100. Additionally, circuit 200 may include additional sensors, such as optical or acoustic sensors. Circuit 200 may include an audible alarm (not shown), which processor 202 may control to sound an alarm when the dialed dose is not fully dispensed.

[0046] The ROM 204 can be configured to store software and / or firmware. The software / firmware can control the operation of the processor 202. The processor 202 utilizes the RAM 206 to execute the software / firmware stored in the ROM to control the operation of the display 210. Thus, the processor 202 may include a display driver. The processor 202 utilizes the flash memory 205 to store the determined dialed dose amount and / or the determined dispensed dose amount, as described in more detail below. The processor 202 can be a microcontroller or microcontroller unit.

[0047] A battery 214 can provide power to each of the components, including the conductive strip 212. The power supply to the conductive strip 212 can be controlled by the processor 202. The processor 202 can receive signals from the conductive strip 212, and therefore can also determine when the conductive strip 212 has been energized, and is configured to interpret those signals. Operation of the software / firmware and the processor 202 can cause information to be presented on the display 210 at the appropriate times. The information can include measurements determined from signals received by the processor 202 from the conductive strip 212.

[0048] A more complete description of the operation of the dose setting mechanism 300 will now be provided with reference to Figures 3 to 6. Figures 3A and 3B show partial perspective views of a dose setting mechanism 300 of a drug delivery device 100 suitable for use with the present invention, and Figures 4A and 4B show partial perspective views of a dose setting mechanism 300 of a drug delivery device 100 suitable for use with the present invention. 1 shows a partial plan view of a dose setting mechanism 300 of the drug delivery device 100 suitable for

[0049] The movable dose programming component 302 in this embodiment is cylindrical and arranged to rotate relative to the housing first member 104 during programming of a dose (but not rotate relative to the housing member 104 during delivery of said dose). Rotation of this component is encoded by selectively connecting and disconnecting conductive strips 212 on the dose programming component, which in turn causes alternating electrical signals to be received by the processor 202. The processor 202 may be implemented in any suitable electronic module that houses the electrical circuitry 200.

[0050] The electronic module housing the circuit 200 can be built into the button 308, which can eliminate the requirement to detach and reuse the electronic module when used in conjunction with a disposable pen injector or other disposable drug delivery device. The built-in electronic module can enable recording of the dialed dose and the dose delivered from the pen. This feature can be useful as a memory aid for a wide range of device users or to assist in detailed logging of dose history. It is also envisioned that the electronic module can be configured to connect to a mobile device or the like to enable periodic dose history downloads from the module.

[0051] As described with reference to Figures 3A and 3B, the dose programming component 302 may include several conductive strips 212. The conductive strips are printed, plated, or etched on the exterior surface of the movable dose programming component 302 (which exterior surface may be housed within the housing member 104 when no dose is set, as in the arrangement shown in Figure 1). For example, the conductive strips 212 may be formed from conductive ink. Some of the conductive strips 212 are live "source" strips 310 that are electrically connected to a voltage source to provide an electrical potential. Others of the conductive strips are "sensor" strips 306 that are electrically connected to input terminals of the processor 202. In this embodiment, the conductive strips 212 are electrically connected to the electrical circuit 200 contained within the button 308 by metal contacts 312, although any other suitable electrical contacts may be provided.

[0052] A bridging contact 304 electrically connects two of the conductive strips 212. The bridging contact 304 is mounted within the housing first member 104 but is not electrically connected to the processor 202. Rather, the bridging contact 304 serves to provide a conductive path between two of the conductive strips 212. In one embodiment of the bridging contact 304, the bridging contact 304 is formed using a metal stamping (e.g., using stainless steel) with three contacts 304a-304c formed as ridges, as shown in FIG. 8 . This manufacturing approach can facilitate the provision of a low-cost bridging contact. The contacts 304a-304c are formed at the end of a cantilevered member to provide preloading and ensure good radial contact pressure with the conductive strips 212, even in the worst-case tolerance conditions. The bridging contact is here non-rotatably and axially aligned within the cylindrical housing member 104.

[0053] In this embodiment, the bridging contacts 304 alternately connect and disconnect the source strip 310 to the adjacent sensor strip 306 as the dose programming component 302 rotates (shown in FIG. 4B). If the sensor strip 306 is connected to the live source strip 310 via the bridging contacts 304, the voltage state of the sensor strip 306 is considered to be "1," otherwise the voltage state is "0." By using the voltage states of the sensor strips 306 as inputs to the processor 202, a Gray code can be generated that represents the rotational position increment and direction of rotation.

[0054] 3 and 4 show an embodiment including four perpendicular conductive strips 212 (two alternating live source strips 310 and two sensor strips 306) suitable for encoding a 24-unit dose. Rather than using a detector to read a code printed on the dose programming component, such an arrangement uses the electrical state of the conductive strips 212 themselves to form input to the processor 202. In such an arrangement, the rotation of the dose programming component 302 can be electronically encoded to identify the selected dose value before the dose is delivered. The simplest Gray code that can be used to count doses and detect rotation direction is a 2-bit Gray code. The embodiment shown above uses three bridging contacts, equally spaced around the circumference of the dose programming component 302, each bridging between two points on the cylinder 60° apart. The following conductive pattern (shown in 2D in FIG. 5 below) has variable strip widths and gap ratios, and in conjunction with the three equally spaced bridging contacts described above, forms a 2-bit quadrature signal during rotation. The black areas represent regions of conductive material and the white areas represent regions where no conductive material is deposited. However, there are several configurations of conductive strips 212 (number of strips, strip width, etc.) and bridging contacts 304 that can be used to generate a cyclic Gray code during rotation and thus encode the desired dose setting.

[0055] Once the dose has been encoded as described above, the user can deliver the set drug dose by applying an axial force to the dose delivery button 308 to displace the drug delivery button 308 toward the proximal end of the first housing member 104. The drug delivery mechanism, along with the dose delivery button 308, is thus displaced relative to the housing 102, expelling the medication from the drug cartridge. When the full dose has been dispensed, a mechanical stop (320 in FIG. 10 ) physically prevents further displacement of the drug delivery button 308. The mechanical stop 320 may include a portion of the drug delivery mechanism or a portion of the housing 102 configured to abut the dial 108.

[0056] An end-of-dose switch is provided to record that a dose has been dispensed. When the switch is triggered, the encoded dose is electronically committed to memory. The switch is referred to herein as the "zero units" or "0U" switch.

[0057] In one embodiment, the switch includes first and second sensor elements 313, 314. The sensor elements 313, 314 are disposed on the 0U sensor strip 307 and within the housing member 104, respectively. The end-of-dose switch is triggered when relative movement between the first and second sensor elements 313, 314 moves the first and second sensor elements 313, 314 to a switch position 340. Thus, the switch position 340 is defined as any position of the first and second sensor elements 313, 314 that causes the end-of-dose switch to be triggered. In one embodiment, the first and second sensor elements 313, 314 move to the switch position 340 when the second sensor element 314 moves past the distal edge 330 of the first sensor element 313. Thus, as described further below, the switch is triggered when the second sensor element 314 moves past the distal edge 330 of the first sensor element 313.

[0058] In the embodiment illustrated by Figures 3a, 3b, 9a and 9b, the first sensor element 313 includes an additional sensor strip 307 at the proximal end of the programming component 302. The second sensor element 314 is comprised of the bridging contact 304 described above.

[0059] The additional sensor strip is referred to herein as the zero unit sensor strip 307 (0U sensor strip 307). The 0U sensor strip 307 is divided into separate regions 307a-307c, which have no interconnections between them to the other live strips 31. The metal contacts 312 are spaced circumferentially about the programming unit 302 to allow the sensor strips 306 to pass through to make electrical connection with the metal contacts 312. The conductive pattern including the sensor strips 307a-307c is shown in FIG.

[0060] The 0U sensor strip regions 307a-307c are connected to each other and do not change state during dialing. When the dose delivery button 308 is depressed to the mechanical stop 320 (0U state), the bridging contact 304 electrically connects at least one of the 0U sensor strip regions 307a-307c to the live strip 310, as shown by FIG.

[0061] 8, each bridging contact 304 has a third contact 304c axially proximal to the two contacts 304a, 304b, required for rotational encoding, which is designed to contact the 0U sensor strip 307 when the dose delivery button 308 is pressed to the 0U state.

[0062] During medication dispensing, the programming component 302 is displaced distally along the axis. The 0U sensor strips 307a-307c advance toward the bridging contacts 304 mounted adjacent the proximal end of the first member 104 of the housing 102. When the dose delivery button is pressed to the 0U state, at least one of the bridging contacts 304 provides a conductive path between the live strip 310 and the 0U sensor strips 307a-307c, thereby triggering the 0U sensor strip 307. In other words, the 0U sensor strip 307 is triggered when the third contact 304c of the corresponding bridging contact 304 passes through the distal edge 330 of the 0U sensor strip 307. The distal edge 330 defines a switch position 340.

[0063] By providing three bridging contacts 304 spaced 120° apart, at least one bridging contact 304 is in contact with the live strip 310. Thus, when the dose delivery button 308 is pressed to the 0U state, it is guaranteed that one of the three 0U sensor strips 307a-307c will be triggered.

[0064] The three 0U sensor strips 307a-307c are electrically connected to and form a single input to the processor 202. The electrical status of the 0U sensor strips 307a-307c is input to the processor 202, enabling the processor 202 to detect whether the dose delivery button has been pressed to its 0U position. The processor 202 can further be configured to provide a visual or audio indication to the user that the 0U state has been reached.

[0065] Variations in the tolerance of the 0U sensor strip 307 relative to the mechanical stop 320 mean that it cannot be guaranteed that the 0U sensor strip 307 will reach the mechanical stop 320 at the same time that it is triggered, which can lead to inaccuracies in the recorded dose. For example, if the 0U sensor strip 307 is triggered before reaching the mechanical stop 320, a smaller dose will be delivered than is recorded. Conversely, if the 0U sensor strip 307 reaches the mechanical stop 320 before being triggered, no dose will be recorded.

[0066] To prevent the device 100 from failing to register a dose, the 0U sensor strip 307 is nominally triggered before reaching the mechanical stop 320. This is shown schematically in Figure 10. The bridging contact 304 is configured to trigger the 0U sensor strip 307 before reaching the mechanical stop 320 under any tolerance conditions. In other words, the bridging contact 304 is positioned at a distance greater than the manufacturing tolerance relative to the 0U sensor strip 307. The distance is located just closer to the proximal end of the device 100 than the mechanical stop 320 .

[0067] Configuring the device 100 in this manner creates the possibility that the user will release pressure from the dose delivery button 308 before reaching the mechanical stop 320, resulting in a lower dose being delivered than recorded. It is therefore important that the user continue to apply pressure to the dose delivery button 308 after the 0U sensor strip 307 is triggered. One object of the present invention is to overcome this challenge by providing a delay before an audio or visual cue is given to the user that the dose has been complied with. The device 100 of the present invention is required to detect whether the dose delivery button 308 has been released before the end of the delay, herein the end of the delay period.

[0068] The dose delivery button 308 has an in state and an out state. Figures 9a and 9b show the dose delivery button in the out state and in state, respectively, relative to the bridging contact 304. The dose delivery button 308 is resiliently biased toward the out state by a spring (not shown) in the drug delivery mechanism. When a user presses down on the dose delivery button 308 during an injection, the spring compresses and the dose delivery button 308 assumes the in state. Further displacement of the dose delivery button 308 serves to displace the drug delivery mechanism and dispense the medication. Whenever the user releases pressure from the dose delivery button 308, the dose delivery button 308 returns to the out state. Because the dose programming unit 302 displaces with the dose delivery button 308, the dose programming unit 302 also moves between the in state and the out state depending on whether user pressure is applied to the dose delivery button 308.

[0069] As shown in FIG. 9a, in the out state, the bridging contact 304 is not able to make connection with the 0U sensor strip 307, even in the 0U state. Therefore, when a user presses the dose delivery button 308 to the 0U state, they must maintain pressure on the dose delivery button 308 to maintain the connection between the 0U sensor strip 307 and the live strip 310. Releasing pressure from the dose delivery button 308 releases the connection between the live strip 310 and the 0U sensor strip 307. In the in state, the third contact 304c overlaps the 0U sensor strip 307 to make connection with the live strip 310. However, in the out state, that connection is not made, and the 0U sensor strip 307 is not triggered.

[0070] Premature release of the dose delivery button 308 is detected as follows: When the user presses the dose delivery button 308 to the 0U state, the 0U sensor strip 307 is triggered. The electrical state of the 0U sensor strip 307 is input to the processor 202, which starts timing a delay period. If the user releases pressure from the dose delivery button 308, the dose delivery button 308 moves to the "out state," which is detected by the processor 202 as a change in the electrical state of the 0U sensor strip 307. If such a change in state occurs before the end of the delay period, a premature release occurs, and the device can signal an error, for example, by generating an error code. Alternatively, if the user maintains pressure on the dose delivery button 308, the device will provide an audio or visual cue that dose delivery is complete at the end of the delay period.

[0071] The error code indicates a deviation between the user's operation on the device and a predetermined handling scheme. The user's operation may be pressing and releasing the drug delivery mechanism. The predetermined handling scheme may be pre-programmed into the drug delivery device during manufacture and may include one or more thresholds that specify the time that the end-of-dose switch should remain triggered for the associated drug delivery to be considered complete. In this particular example, the error code indicates incorrect use of the device. More particularly, the error code indicates that the dose of drug delivered during use of the device is less than the predetermined dose of drug. Shows.

[0072] This error notification may prompt the user to check the dose record or change the dose behavior.

[0073] It is possible that a user could trigger the 0U sensor strip 307, reach the mechanical stop 320, and then immediately release the dose delivery button 308 before the end of the delay period. In that case, the device described thus far would report an error even though the mechanical stop 320 was reached and the entire dose was delivered. To mitigate this, it is desirable to set the delay period to the human reaction time or slightly lower. This ensures that in the vast majority of cases, the dose is logged as fully dispensed before the user reacts to reaching the mechanical stop 320 and releases the dose delivery button 308. This is shown schematically in FIG. 11. FIG. 11 shows that even if the 0U sensor strip 307 reaches the mechanical stop 320 at the same time it is triggered, the delay period is short enough that the dose is recorded without the device reporting an error.

[0074] Whenever the 0U sensor strip 307 is triggered, the coded dose is recorded and stored in the flash memory 205 of the device 100. The coded dose may be recorded against details of the injection event, such as the time and date the medication was administered and / or whether an error was reported.

[0075] Various outcomes during operation of the device 100 according to the invention will now be explained with reference to the flow diagrams of Figures 12 and 13, which illustrate a first and a second scenario respectively.

[0076] Scenario 1 12 illustrates the possible outcomes of the user releasing pressure from the dose delivery button 308 before reaching the mechanical stop 320 but after the 0U sensor strip 307 has been triggered. There are three possible outcomes:

[0077] Result 1: If the 0U sensor strip 307 is triggered for a period shorter than the delay period, i.e., if the user releases pressure from the dose delivery button 308 before the end of the delay period, the dose will be recorded, but an error flag will be communicated via the device's display 210 to indicate to the user that the encoded dose was recorded with low accuracy.

[0078] Result 2: If the 0U sensor strip 307 is triggered for a period longer than the delay period, but the delivered drug dose is less than the set and encoded drug dose, the drug dose will be recorded without an error flag. It should be understood that although there will still be an error in the recorded dose, the error will be significantly smaller than if the delay period were not used and the user were prompted to release pressure from the dose delivery button 308 earlier.

[0079] Result 2 indicates that the delay period may be set too short considering the cumulative tolerance between the 0U sensor strip 307 and the mechanical stop 320. This illustrates the importance of selecting the correct delay period so that the audio or visual cue to release the dose delivery button is given only after the mechanical stop 320 is reached.

[0080] Result 3: The OU sensor strip 307 is triggered for longer than the delay period and the full encoded dose is delivered. As a result, the drug dose is accurately recorded. No lag is presented and the delivered drug dose expected by the user matches the dispensed drug dose.

[0081] Scenario 2: 13 illustrates the possible outcomes of the user releasing pressure from the dose delivery button 308 after the mechanical stop 320 has been reached and the full encoded dose has been delivered. There are two possible outcomes:

[0082] Result 1: The 0U sensor strip 307 is triggered for a period longer than the delay period. As a result, the drug dose is accurately recorded. No error flag is presented to the user, and the user's expected delivered drug dose matches the dispensed drug dose.

[0083] Result 2: The user reacts to reaching the mechanical stop 320 and releases pressure from the dose delivery button 308 before the audio or visual cue to release pressure is given by the device 100 and before the end of the delay period. Although the full dose is delivered, the dose is recorded with an error flag and the user is prompted to check the dose even though the correct dose was delivered, further illustrating the importance of selecting the correct delay period.

[0084] To avoid the second outcome of both scenarios, a statistical model was employed that enabled a delay period of 0.25 seconds, slightly shorter than human reaction time. Two studies were performed. Each study consisted of a Monte Carlo simulation of 10 million individual events. Each event represented a single administration of medication by a different user and device.

[0085] In the first study, it was assumed that the user continued to apply pressure to the dose delivery button 308 for a randomly distributed length of time at the end of each dose, with the distribution being normal with a median of 5 seconds. A statistical model predicts that during the 0.25 second delay period, nearly all doses would be recorded without an error flag.

[0086] In a second study, it is assumed that the user releases pressure from the dose delivery button 308 at points uniformly distributed between the point at which the 0U sensor strip 307 is triggered and the point at which the mechanical stop 320 is reached. For such an unlikely event, the study predicts that 99.9% of doses will be recorded during the 0.25 second delay period, an error of less than 1 unit, compared to 17.66% when no delay period is implemented.

[0087] In the embodiment described above, the first and second sensor elements 313, 314 of the dose end switch include a conductive strip 307 and a bridging contact 304 respectively, however it is understood that other sensor elements may be used without departing from the scope of the present invention, as regardless of the type of sensor used the same problem may arise where the user releases pressure from the dose delivery button 308 before reaching the mechanical stop 320, resulting in a smaller dose being delivered than recorded.

[0088] In another embodiment, shown by FIG. 14 , which keeps the same reference numbers for similar components, the end-of-dose switch may include a Hall effect sensor. In this embodiment, the first sensor element 313 includes a semiconductor element 3131 (or alternatively a metal element) and the second sensor element 314 includes a magnet 3141. The magnet 3141 may be a permanent magnet or an electromagnet. Thus, when a user presses the dose delivery button 308 down towards the mechanical stop 320, the magnet moves towards the semiconductor element 3131, generating a Hall voltage. The semiconductor element 3131 is electrically connected to the processor 202, which detects when a threshold voltage is met and the magnet 3141 41 moves to switch position 340. When the user releases dose delivery button 308 to the out state, a second Hall voltage is generated as magnet 3141 and semiconductor 3131 move away from switch position 340. Processor 202 is configured to measure the time period between the time the end dose switch is triggered and the time the magnet 3141 and semiconductor 3131 move away from switch position 340, and processor 202 is further configured to generate an error code indicating an underdose when the measured time period is less than the delay period.

[0089] In another embodiment, shown by FIG. 15 , which maintains the same reference numbers for similar features, the end-of-dose switch may include an inductive sensor. In this embodiment, the first sensor element 313 includes an inductive element 3132, and the second sensor element 314 includes a magnet 3142. The magnet 31421 may be a permanent magnet or an electromagnet. Thus, when a user presses the dose delivery button 308 toward the mechanical stop 320, the magnet moves toward the inductive element 3132, inducing a current in the inductive element 3132. The inductive element 3132 is electrically connected to the processor 202, which detects that the magnet 3142 has moved to the switch position 340 when a threshold current is met. When the user releases the dose delivery button 308 to the out state, the magnet 3142 and the inductive element 3132 move away from the switch position 340, inducing a second current. The processor 202 is configured to measure the period between the time the end dose switch is triggered and the time the magnet 3141 and inductive element 3132 move away from the switch position 340, and the processor 202 is further configured to generate an error code indicating a low dose when the measured period is less than the delay period.

[0090] The terms "drug" or "medicament" are used interchangeably herein to describe a pharmaceutical formulation containing one or more active pharmaceutical ingredients or pharmaceutically acceptable salts or solvates thereof, and optionally a pharmaceutically acceptable carrier. An active pharmaceutical ingredient ("API"), in its broadest sense, is a chemical structure that has a biological effect on humans or animals. In pharmacology, drugs or medications are used to treat, cure, prevent, or diagnose disease or otherwise improve physical or mental well-being. Drugs or medications can be used for a limited duration or periodically for chronic disorders.

[0091] As described below, drugs or pharmaceutical agents may contain at least one API or a combination thereof in various types of formulations for the treatment of one or more diseases. Examples of APIs include small molecules with a molecular weight of 500 Da or less, polypeptides, peptides, and proteins (e.g., hormones, growth factors, antibodies, antibody fragments, and enzymes), carbohydrates and polysaccharides, as well as nucleic acids, double-stranded or single-stranded DNA (including naked and cDNA), RNA, antisense nucleic acids, such as antisense DNA and RNA, small interfering RNA (siRNA), ribozymes, genes, and oligonucleotides. Nucleic acids can be incorporated into molecular delivery systems such as vectors, plasmids, or liposomes. Mixtures of one or more drugs are also contemplated.

[0092] The drug or agent can be contained in a primary package or "drug container" adapted for use in a drug delivery device. The drug container can be, for example, a cartridge, syringe, reservoir, or other rigid or flexible vessel configured to provide a chamber suitable for storage (e.g., short-term or long-term storage) of one or more drugs. For example, in some cases, the chamber can be designed to store the drug for at least one day (e.g., from one day to at least 30 days). In some cases, the chamber can be designed to store the drug for about one month to about two years. Storage can occur at room temperature (e.g., about 20°C) or refrigerated temperatures (e.g., from about -4°C to about 4°C). In some cases, the drug container may be or include a dual-chamber cartridge configured to separately house two or more components of a pharmaceutical formulation to be administered (e.g., an API and a diluent, or two different drugs), one in each chamber. In such cases, the two chambers of the dual-chamber cartridge can be configured to allow mixing between the two or more components prior to and / or during administration to the human or animal body. For example, the two chambers can be configured to be in fluid communication with each other (e.g., via a conduit between the two chambers) and to allow mixing of the two components by a user, if desired, prior to administration. Alternatively or additionally, the two chambers can be configured to allow mixing upon administration of the components to the human or animal body.

[0093] The drugs or agents contained in the drug delivery devices described herein can be used to treat and / or prevent many different types of medical disorders. Examples of disorders include, for example, diabetes or complications associated with diabetes, such as diabetic retinopathy, and thromboembolic disorders, such as deep vein thromboembolism or pulmonary embolism. Further examples of disorders include acute coronary syndrome (ACS), angina, myocardial infarction, cancer, macular degeneration, inflammation, hay fever, atherosclerosis, and / or rheumatoid arthritis. Examples of APIs and drugs are those listed in handbooks such as Rote Liste 2014 (e.g., but not limited to, Main Group 12 (antidiabetic agents) or 86 (oncology agents)) and the Merck Index, 15th edition.

[0094] Examples of APIs for the treatment and / or prevention of type 1 or type 2 diabetes or complications associated with type 1 or type 2 diabetes include insulin, e.g., human insulin, or a human insulin analog or derivative; glucagon-like peptide (GLP-1), a GLP-1 analog or GLP-1 receptor agonist, or an analog or derivative thereof; a dipeptidyl peptidase-4 (DPP4) inhibitor; or a pharmaceutically acceptable salt or solvate thereof, or any mixture thereof. As used herein, the terms "analog" and "derivative" refer to a polypeptide having a molecular structure that is formally derivable from the structure of a naturally occurring peptide, e.g., the structure of human insulin, by deletion and / or replacement of at least one amino acid residue present in the naturally occurring peptide and / or by addition of at least one amino acid residue. The added and / or replaced amino acid residue can be either a codable amino acid residue, another naturally occurring residue, or a purely synthetic amino acid residue. Insulin analogs are also referred to as "insulin receptor ligands." In particular, the term "derivative" refers to a polypeptide having a molecular structure formally derivable from the structure of a naturally occurring peptide, for example, the molecular structure of human insulin in which one or more organic substituents (e.g., fatty acids) are attached to one or more of the amino acids. Optionally, one or more amino acids present in the naturally occurring peptide are deleted and / or replaced by other amino acids, including non-codable amino acids, or amino acids, including non-codable ones, are added to the naturally occurring peptide.

[0095] Examples of insulin analogues are Gly(A21), Arg(B31), Arg(B32) human insulin (insulin glargine); Lys(B3), Glu(B29) human insulin (insulin glulisine); Lys(B28), Pro(B29) human insulin (insulin lispro); Asp(B28) human insulin (insulin aspart); human insulin in which the proline at position B28 is replaced by Asp, Lys, Leu, Val or Ala and the Lys at position B29 may be replaced by Pro; Ala(B26) human insulin; Des(B28-B30) human insulin; Des(B27) human insulin and Des(B30) human insulin.

[0096] Examples of insulin derivatives are, for example, B29-N-myristoyl-des(B30) human insulin, Lys(B29)(N-tetradecanoyl)-des(B30) human insulin (insulin detemir, Levemir®); B29-N-palmitoyl-des(B30) human insulin; B29-N-myristoyl human insulin; B29-N-palmitoyl human insulin; B28-N-myristoylLysB28ProB29 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-omega-carboxypentadecanoyl-gamma-L-glutamyl-des(B30) human insulin (insulin degludec, Tresiba®); B29-N-(N-lithocholyl-gamma-glutamyl)-des(B30) human insulin; B29-N-(ω-carboxyheptadecanoyl)-des(B30) human insulin and B29-N-(ω-carboxyheptadecanoyl) human insulin.

[0097] Examples of GLP-1, GLP-1 analogs and GLP-1 receptor agonists are, for example, lixisenatide (Lyxumia®), exenatide (exendin-4, Byetta®, Bydureon®, a 39 amino acid peptide produced by the salivary glands of the flathead monster), liraglutide (Victoza®), semaglutide, taspoglutide, albiglutide (Syncria®), dulaglutide (Trulicity®), rexendin -4, CJC-1134-PC, PB-1023, TTP-054, langrenatide / HM-11260C, CM-3, GLP-1 Erigen, ORMD-0901, NN-9924, NN-9926, NN-9927, nodexene, Viadol-GLP-1, CVX-096, ZYOG-1, ZYD-1, GSK-2374697, DA-3091, MAR-701, MAR709, ZP-2929, ZP-3022, TT-401, BHM-034, MOD-6030, CAM-2036, DA-15864, ARI-2651, ARI-2255, exenatide-XTEN, and glucagon-Xten.

[0098] An example of an oligonucleotide is, for example, mipomersen sodium (Kynamro®), a cholesterol-lowering antisense therapeutic for the treatment of familial hypercholesterolemia.

[0099] Examples of DPP4 inhibitors are vidagliptin, sitagliptin, denagliptin, saxagliptin, and berberine.

[0100] Examples of hormones include pituitary or hypothalamic hormones or regulatory active peptides and their antagonists, such as gonadotropins (follitropin, lutropin, chorion gonadotropin, menotropin), somatropine (somatropin), desmopressin, terlipressin, gonadorelin, triptorelin, leuprorelin, buserelin, nafarelin, and goserelin.

[0101] Examples of polysaccharides include glycosaminoglycans, hyaluronic acid, heparin, low molecular weight heparin or very low molecular weight heparin or derivatives thereof, or sulfated polysaccharides, such as the polysulfated forms of the above polysaccharides, and / or pharmaceutically acceptable salts thereof. An example of a pharmaceutically acceptable salt of polysulfated low molecular weight heparin is enoxaparin sodium. An example of a hyaluronic acid derivative is Hylan G-F20 (Synvisc). c)®), sodium hyaluronate.

[0102] As used herein, the term "antibody" refers to an immunoglobulin molecule or an antigen-binding portion thereof. Examples of antigen-binding portions of immunoglobulin molecules include F(ab) and F(ab')2 fragments that retain antigen-binding ability. An antibody can be a polyclonal antibody, a monoclonal antibody, a recombinant antibody, a chimeric antibody, a deimmunized or humanized antibody, a fully human antibody, a non-human (e.g., murine) antibody, or a single-chain antibody. In some embodiments, an antibody has effector function and is capable of fixing complement. In some embodiments, an antibody has reduced or no binding ability to Fc receptors. For example, an antibody can be an isotype or subtype, antibody fragment, or mutant that does not support Fc receptor binding, e.g., has a mutation or deletion of the Fc receptor binding region. The term antibody also includes antigen-binding molecules based on tetravalent bispecific tandem immunoglobulins (TBTIs) and / or dual variable region antibody-like binding proteins (CODVs) with a crossover binding region orientation.

[0103] The term "fragment" or "antibody fragment" refers to a polypeptide (e.g., an antibody heavy and / or light chain polypeptide) derived from an antibody polypeptide molecule that does not include the full-length antibody polypeptide but comprises at least a portion of the full-length antibody polypeptide that is still capable of binding to antigen. Antibody fragments can include truncated portions of a full-length antibody polypeptide, but the term is not limited to such truncated fragments. Antibody fragments useful in the present invention include, for example, Fab fragments, F(ab')2 fragments, scFv (single-chain Fv) fragments, linear antibodies, monospecific or multispecific antibody fragments, e.g., bispecific, trispecific, tetraspecific, and multispecific antibodies (e.g., diabodies, triabodies, tetrabodies), monovalent or multivalent antibody fragments, e.g., bivalent, trivalent, tetravalent, and multivalent antibodies, minibodies, chelating recombinant antibodies, tribodies or bibodies, intrabodies, nanobodies, small modular immunopharmaceuticals (SMIPs), binding domain immunoglobulin fusion proteins, camelized antibodies, and VHH-containing antibodies. Additional examples of antigen-binding antibody fragments are known in the art.

[0104] The term "complementarity determining region" or "CDR" refers to short polypeptide sequences within the variable regions of both heavy and light chain polypeptides that are primarily responsible for mediating specific antigen recognition. The term "framework region" refers to amino acid sequences within the variable regions of both heavy and light chain polypeptides that are not CDR sequences and that are primarily responsible for maintaining the proper orientation of the CDR sequences to enable antigen binding. Although the framework regions themselves typically do not directly participate in antigen binding, as is known in the art, certain residues within the framework regions of a particular antibody may be directly involved in antigen binding or may affect the ability of one or more amino acids within the CDRs to interact with the antigen.

[0105] Examples of antibodies are anti-PCSK-9 mAb (e.g., alirocumab), anti-IL-6 mAb (e.g., sarilumab), and anti-IL-4 mAb (e.g., dupilumab).

[0106] Pharmaceutically acceptable salts of any of the APIs described herein are contemplated for use as drugs or medicaments in drug delivery devices. Pharmaceutically acceptable salts include, for example, acid addition salts and base salts.

[0107] Modifications (additions and / or omissions) to the various components, formulations, devices, methods, systems, and embodiments of the API described herein may be made without departing from the full scope and spirit of the invention, and it is intended that the invention encompass such modifications and all equivalents thereof. Those skilled in the art will understand.

Claims

1. 1. A drug delivery device comprising: a housing having a proximal end and a distal end; a drug delivery mechanism at least partially disposed within the housing and displaceable between a pre-delivery position and a mechanical stop position to dispense a medication from the drug delivery device when a user depresses a proximal end of the drug delivery mechanism; an end-of-dose switch configured to be triggered before the drug delivery mechanism reaches a mechanical stop position, the end-of-dose switch including a first sensor element disposed on the drug delivery mechanism and a second sensor element disposed within the housing; Including, the end-of-dose switch is configured to be triggered by relative movement between the first sensor element and the second sensor element when the first and second sensor elements move to a switch position, and the drug delivery mechanism is biased in a proximal direction opposite the mechanical stop position such that the first and second sensor elements move away from the switch position when a user stops pressing on the proximal end of the drug delivery mechanism; The drug delivery device further comprises: Record when the end-of-dose switch is triggered; measuring the time period between the time the end dose switch is triggered and the time the first and second sensor elements move away from the switch position 340; Generate an error code indicating incorrect use of the device when the measured duration is less than a predetermined duration The drug delivery device comprising a controller configured to:

2. 10. The drug delivery device of claim 1, wherein the first and second sensor elements move to the switch position when the second sensor element moves beyond the distal edge of the first sensor element.

3. 3. The drug delivery device of claim 2, wherein the end-of-dose switch is configured to be triggered when the first sensor element moves distally beyond a switch position.

4. 4. A drug delivery device according to claim 1, wherein the first sensor element comprises a conductive strip on the drug delivery mechanism that is electrically connected to the controller.

5. 5. The drug delivery device of claim 4, wherein the second sensor element includes a bridging contact configured to connect the conductive strip to a live strip on the drug delivery mechanism for transmitting an electrical signal to the controller.

6. The drug delivery device of claim 5, wherein the bridge contact is formed as a metal pressing and includes contacts disposed at the ends of cantilevered members of the metal pressing, the contacts being configured to contact the live strip and the first sensor element, respectively, to electrically connect the live strip to the sensor element.

7. The drug delivery device of claim 6 , wherein the second sensor element includes two or more bridging contacts spaced apart on the inner surface of the housing.

8. The drug delivery device of claim 7 , wherein the two or more bridging contacts are provided at the proximal end of the housing.

9. The drug delivery mechanism includes a dose setting component, the dose setting component rotatable relative to the housing to set a drug dose to be administered; and the first sensor element is coupled to the dose setting component.

9. The drug delivery device of claim 1, further comprising a series of spaced apart conductive strips on the outer surface of the component.

10. 10. The drug delivery device of claim 9, wherein the dose setting component further includes conductive dose-coding strips and live strips alternately spaced apart on an outer surface of the dose setting component, the dose-coding strips each being electrically connected to the controller, and the bridging contacts connect and disconnect the dose-coding strips to the live strips as the dose setting component rotates relative to the housing to transmit an electrical signal to the controller and encode the set drug dose.

11. The drug delivery device of claim 10 , wherein the first sensor element comprises a plurality of conductive strips spaced around the proximal end of the dose setting component.

12. 12. The drug delivery device of claim 11, wherein the plurality of conductive strips of the first sensor element are spaced apart to allow the dose-coding strip to extend therebetween and make electrical connection with the controller.

13. 13. A drug delivery device according to claim 11 or claim 12, wherein the conductive strip and / or the dose-coding strip are printed, plated or etched on the outer surface of the dose setting component.

14. 14. A drug delivery device according to any one of claims 10 to 13, wherein the controller is configured to record the encoded set drug dose when the end-of-dose switch is triggered.

15. 15. A drug delivery device according to any one of claims 9 to 14, wherein the controller is provided at the proximal end of the dose setting component.

16. The drug delivery device of any one of claims 1 to 15, wherein the predetermined period is based on a human reaction time.

17. A drug delivery device according to any preceding claim, wherein the predetermined period is between 0.2 and 0.4 seconds.

18. 18. The drug delivery device of claim 17, wherein the predetermined period is 0.25 seconds.

19. 19. A drug delivery device according to any one of claims 1 to 18, configured to provide a visual and / or audio cue to a user of the drug delivery device to indicate that a set drug dose has been administered after expiration of a predetermined period of time.

20. 20. A drug delivery device as claimed in any one of claims 1 to 19, configured to provide a visual and / or audio cue to a user of the device to alert the user that the set drug dose may not have been fully administered when the user stops pressing the proximal end of the drug delivery mechanism before the end of the predetermined period of time.

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