Apparatus for detecting operation of an injection device - Patent application

Abstract

A device for detecting operation of an injection device, configured to be disposed within a housing of the injection device, includes: a cam member configured to be rotatable relative to a driven member; a resilient member arranged to bias the members into abutment with each other, wherein rotation of the cam member relative to the driven member causes reciprocating movement of the driven member, which is configured to reciprocate in the axial direction of the injection device; and a contact sensor disposed between the cam member and the driven member and configured to detect reciprocating movement of the driven member. The cam member includes a shaped section with an axially varying profile disposed in abutment with the driven member and configured to cause reciprocating movement of the driven member, and the contact sensor is disposed on the cam member and configured to move away from the driven member when the driven member reciprocates.

Description

[Technical field]

[0001] The present disclosure relates to an apparatus for detecting operation of an injection device, and in particular to an apparatus for detecting operation of a dose setting or dose dispensing mechanism of an injection device during injection of a medicament. [Background technology]

[0002] There are various diseases that require regular treatment with drug injections. Typically, a medical professional plans a dosing regimen that governs the timing and administration of injections for the patient to follow. Thus, the timing and / or administration of injections can vary from patient to patient and from injection to injection. Often, as part of the dosing regimen, the user needs to record parameters of the injection, for example to monitor the effectiveness of the treatment or as feedback while calculating parameters for a later injection. This can be achieved by keeping a handwritten data diary.

[0003] Injections can be performed by medical personnel or by the patient themselves using an injection device. An injection device (i.e. a device capable of delivering medication from a pharmaceutical container) typically has a syringe connected to a medication container and a dose dispensing mechanism that pushes the medication through a needle. The medication chamber can be reusable, with the dose dispensing mechanism designed to be reset so that an empty medication cartridge can be replaced with a new one. Alternatively, the injection device may be disposable, with the injection device being discarded when the contents of the filled medication container are emptied. Suitably, the injection device includes a dose setting mechanism that allows the user to set or "dial" the amount of medication to be administered.

[0004] As an example, type 1 and type 2 diabetes can be self-treated by patients by injecting insulin doses according to a regimen, for example one or several injections per day. Patent document 1 discloses a suitable injection device, typically referred to as a pen, and references to the pen herein can be substituted with the injection device. It is known that disposable pens are equipped with a set of unidirectional needles that are attached to the pen before each use. The insulin dose to be injected and prescribed by the regimen can then be manually selected via a dose setting mechanism, for example by turning a dose knob to the required volume. The dose is then injected by inserting the needle into the appropriate skin area and pressing the injection button of the dose dispensing mechanism. As part of the administration of the regimen, the user records the parameters of the injection. Such parameters can be, for example, one or more of the date and time of the injection, blood glucose level, medication and dose, and / or dietary and exercise information. [Prior art documents] [Patent documents]

[0005] [Patent Document 1] WO2004 / 078241 Summary of the Invention [Means for solving the problem]

[0006] According to various aspects herein, there is provided an apparatus for detecting operation of an injection device, the apparatus including: a cam member configured to be rotatable relative to a driven member; a resilient member arranged to urge the members into abutment with one another, where rotation of the cam member relative to the driven member causes reciprocating movement of the driven member; and a contact sensor disposed between the cam member and the driven member, the contact sensor configured to detect reciprocating movement of the driven member.

[0007] According to various aspects herein, there is provided an apparatus for detecting operation of an injection device configured to be disposed within a housing of the injection device, the apparatus comprising: A cam member configured to be rotatable relative to a driven member; a resilient member arranged to bias the members into abutment with one another, the resilient member being configured such that rotation of the cam member relative to the driven member causes reciprocating movement of the driven member such that the driven member reciprocates in an axial direction of the injection device; a contact sensor disposed between the cam member and the driven member and configured to detect reciprocating motion of the driven member; the cam member includes a shaped section including an axially varying profile disposed in abutment with the driven member and configured to induce reciprocating motion of the driven member; An apparatus is provided in which a contact sensor is disposed on the cam member and configured to move away from the driven member when the driven member reciprocates.

[0008] By providing a contact sensor between the cam member and the driven member, the contact sensor can provide a signal in response to reciprocating movement of the driven member that can be used to determine the dose delivered by or dialed into the injection device from the detected reciprocating movement of the driven member.

[0009] Thus, according to exemplary embodiments, there is provided an improved injection device as set forth in the accompanying claims. Other configurations of the present disclosure will become apparent from the description and other aspects of this application. By using sensors to monitor the movement of members of the injection device, dose measurements can be recorded electronically, thus providing improved dose management capabilities.

[0010] Exemplary embodiments are described with reference to the accompanying drawings. [Brief description of the drawings]

[0011] [Figure 1] FIG. 1 is a schematic diagram of an injection device. [Diagram 2] FIG. 2 is a view of exploded parts of the injection device of FIG. 1. [Diagram 3] FIG. 1 is a cross-sectional view of a dose counting mechanism. [Figure 4] FIG. 4 is a cross-sectional view of the dose counting mechanism of FIG. [Diagram 5] FIG. 4 is a cross-sectional view of the dose counting mechanism of FIG. [Figure 6] FIG. 4 is a cross-sectional view of the dose counting mechanism of FIG. [Figure 7] FIG. 13 is a diagram of an alternative dose counting mechanism. DETAILED DESCRIPTION OF THE PREFERRED EMBODIMENTS

[0012] Reference will now be made in detail to exemplary embodiments, examples of which are illustrated in the accompanying drawings, in which like reference numerals refer to like elements throughout.

[0013] 1 is an exploded view of an injection device 200 suitable for use in an exemplary embodiment. The illustrated injection device is often referred to as an injection pen or pen. Various designs of pens are known and a brief description is provided herein, although it will be understood that the specific configuration of the pen may be modified or varied from the following description.

[0014] The injection device 200 has a distal end and a proximal end, the term "distal" referring to a position relatively closer to the injection site and the term "proximal" referring to a position relatively farther from the injection site.

[0015] The injection device 200 includes a grip assembly 202, a cap 203 and a needle assembly 204. The grip assembly is formed from a housing 210 and a cartridge assembly 220. The cartridge assembly 220 includes a cartridge holder 222 for receiving a cartridge 224 containing a medicament. As shown, the housing 210 is substantially cylindrical and has a substantially constant diameter from the proximal end to the distal end along its longitudinal axis. The longitudinal axis has a proximal-distal direction extending from the proximal end to the distal end and an inverse distal-proximal direction.

[0016] The cartridge assembly 220 is assembled to the housing 210 to form the grip assembly 202. Suitably, the proximal end of the cartridge assembly 220 includes a coupling member (not shown) and the distal end of the housing 210 includes a corresponding coupling member (not shown) that cooperatively engage with one another to couple the two members. As shown, the cartridge holder 222 is substantially cylindrical and has a hollow receptacle for the cartridge 224. The cartridge includes a stopper 228 that can be advanced within the cartridge 224 during use to expel the medicament from the cartridge 224. It will now be appreciated that the needle assembly 204 cooperates with the grip assembly to act as a conduit for the medicament during injection.

[0017] The cartridge holder 222 has a porthole 226 on its side. The porthole 226 allows a user to view the cartridge 224 through the porthole 226 when the cartridge 224 is housed in the cartridge holder 222. FIG. 1 shows that the stopper 228 of the cartridge 224 is visible through the porthole 226. Although FIG. 1 shows the cartridge holder 222 with one porthole 226, the cartridge holder 222 can instead have two or more portholes 226. For example, the cartridge holder 222 can have a first porthole 226 located on one side of the cartridge holder 222 and a second porthole located on a second side, and in some cases on the opposite side, of the cartridge holder 222. In this manner, a first side of the cartridge 224 in the cartridge holder 222 can be visible through the first porthole 226 and a second, different side of the cartridge 224 can be visible through the second porthole. Other porthole configurations may be used.

[0018] Shown is a needle assembly including a needle 206, an inner needle cap 207, and an outer needle cap 208. The needle 206 of the needle assembly 204 can be mounted in a cartridge holder 222 such that the needle 206 is in fluid communication with a medicament in a cartridge 224. The needle 206 is protected by the inner needle cap 207 and the outer needle cap 208.

[0019] A removable cap 203 is attached to the cartridge assembly. When the cap 203 is attached to the grip assembly, it at least partially covers the cartridge holder 222 and therefore the cartridge 224. The cap 203 can also be attached to the grip assembly such that it at least partially covers the cartridge holder 222 with or without one or more of the needle 206, inner needle cap 207 or outer needle cap 208.

[0020] The cartridge holder 222 can have a cap retention feature 223 on an outer surface, for example, adjacent a proximal end of the cartridge holder 222 and adjacent the mounting portion of the housing 210. Thus, the cap 203 can substantially cover the cartridge assembly when fitted. The cap retention feature 223 engages with a corresponding interlocking feature on an inner surface of the cap 203 to hold the cap 203 in place when attached to the grip assembly. The cap retention feature 223 can include one or more of a ridge, groove, bump, lock, and / or pip. In some examples, the cap retention feature is located on the housing 210 of the injection device 200.

[0021] As shown in FIG. 2, the housing 210 houses a dose dispensing mechanism and a dose setting mechanism. The dose setting mechanism is used to select the dose to be injected, and the dose dispensing mechanism is activated to inject the dose. In this example, the dose dispensing mechanism is activated to push the stopper 228 towards the distal end of the cartridge 224. The injection device 200 can be used for multiple injection processes until the cartridge is empty or the expiration date of the injection device 200 is reached (e.g., 28 days from first use). The injection device 200 can be disposable or reusable.

[0022] To push the stopper 228 into the cartridge 224, the dose dispensing mechanism includes a piston rod 232, a drive sleeve 234, and a trigger button 236, which together act to push a pressure plate 237 into the cartridge 224 against the stopper 228. The drug dose or drug dose to be ejected from the drug delivery device 200 is selected by turning a dose knob 242. The dose knob 242 is connected to a dose dial sleeve 244 by a threaded insert 243, whereby the selected dose is displayed in a dose window 212 of the housing 210 when the dose dial sleeve 244 is rotated by the dose knob 242, and a clicker 250 interacts with the drive sleeve 234 via a spring clutch 252. The dose knob 242, the dose dial sleeve 244, and the clicker 250 together are the dose setting mechanism. The dose dial sleeve 244 is disposed around a clicker 250 which includes a feedback mechanism 251 that generates tactile or audible feedback with rotation of the dose dial sleeve 244. The clicker 250 is coupled to the drive sleeve 234 with a metal clutch spring 252.

[0023] The drive sleeve 234 is provided with a last dose nut 260 (LDN). The last dose nut 260 advances with each dose dispensing operation to track the total drug remaining in the cartridge 224. The trigger button 236 is pressed down to activate the dose dispensing operation of the drug delivery device 200. The drive sleeve 234 includes flanges 262 and 264 protruding from the drive sleeve. For example, the flanges may be radial flanges. The LDN 260 is a threaded member, suitably a half nut. The drive sleeve typically includes a threaded bolt section extending between the two flanges. When the drive sleeve is rotated by a corresponding rotation of the dose setting mechanism, the LDN 260 is moved along the drive sleeve by the cooperation of the respective threads. The LDN is suitably positioned to move from the flange 262, which is the smallest flange, which indicates the starting position of the LDN when the LDN abuts against the flange and the cartridge is full. The LDN moves repetitively along the drive sleeve each time a dose is injected. The LDN advances in response to rotation of the dose setting mechanism but does not translate relative to the drive sleeve when the drive sleeve is forced away during a dose dispensing operation. The LDN abuts the other flange, which is the largest flange, which prevents the LDN from moving and thus prevents the dose dialing mechanism from dialing a dose that exceeds the dose remaining in the cartridge.

[0024] As discussed above, although the dose setting mechanism is shown as a dose knob 242, a dose dial sleeve 244, and a clicker 250, those skilled in the art will understand that any number of different dose setting mechanisms are conventional in the art for setting a dose of a drug delivery device, and that aspects of the present disclosure may be substituted for other such dose setting mechanisms. Similarly, although the dose dispensing mechanism is shown as including a piston rod 232, a drive sleeve 234, and a trigger button 236, a number of different dose dispensing mechanisms (e.g., drive mechanisms) for delivering or dispensing a dose of a drug delivery device are known in the art, and that aspects of the present disclosure may be substituted for other such dose dispensing mechanisms.

[0025] Continuing with the operation of the drug delivery device 200, turning the dose knob 236 rotates the dose dial sleeve 244 relative to the clicker 250, causing a mechanical click sound to provide audio feedback to the user. The numbers displayed on the dose display 212 are printed on the dose dial sleeve 244, which is housed in the housing 210 and mechanically interacts with the drive sleeve 234 via a metal spring clutch 252. When the injection button 236 is pressed, the drug dose displayed on the display 212 is ejected from the drug delivery device 200. During a dose setting operation, the drive sleeve 234 is spirally rotated in a distal-proximal direction with the dose dial sleeve 244 spiraling outward. When the injection button 236 is pressed, the drive sleeve 234 is released and advances distally, which causes the piston rod 232 to rotate. Rotation of the piston rod 232 pushes a pressure plate 237 against the stopper 228 of the cartridge 224, which pushes the stopper 228 into the cartridge 224, expelling the drug from the cartridge 224. A more detailed description of an exemplary drug delivery device is provided in U.S. Patent No. 7,935,088 (B2), issued May 3, 2011.

[0026] When the drug delivery device 200 is at the end of a dose setting operation and before a dose dispensing operation, the dose dial sleeve 244 and the drive sleeve 234 are helically rotated relative to the housing 210 and the threaded end 233 of the piston rod 232 to set a dose. The final dose nut 260 advances along the drive sleeve 234 from an initial position to a position indicating the dose remaining in the drug delivery device 200. When the injection button 236 dispenses a dose, the drive sleeve 234 advances into the housing 210 and the bearing nut 280 induces the rotation of the piston rod 232. The bearing nut 280 is fixedly seated inside the housing 210 and is threadedly engaged with the piston rod 232. As the piston rod 232 rotates, the bearing nut 280 cannot move and therefore the piston rod 232 is threaded (relative to the housing 210). Rotation of the piston rod 232 urges the piston rod 232 and pressure plate 237 proximally in the proximal-distal direction, forcing the stopper 228 into the cartridge 224. When a dose is dispensed, the drive sleeve is in the non-dose dial setting position.

[0027] The drug dose to be delivered from the injection device 200 can be selected by turning the dosing knob 242, and the selected dose is then displayed via the dosing window 212, for example in multiples of international units (IU). An example of a selected dose displayed in the dosing window 12 may be "30" IU, as shown in Figure 1. It should be noted that the selected dose may equally well be displayed in different formats, for example by an electronic display.

[0028] By turning the dosing knob 242, a mechanical click sound provides audio feedback to the user. The numbers displayed in the dosing window 212 are printed on a sleeve 244 housed in the housing 210. When the needle 206 is inserted into the patient's skin area and the injection button 236 is then pressed, the drug dose displayed in the display window 212 is ejected from the injection device 200. If the needle 206 of the injection device 200 remains on the skin area for a period of time after the injection button 236 is pressed, then a portion of the dose is actually injected into the patient's body. Upon ejection of the drug dose, the dosing clicker also provides a mechanical click sound, which is different from the sound produced by the clicker 250 when using the dosing knob.

[0029] Although a pen injection device is briefly described, other injection devices are envisioned as are known in the art.

[0030] 3 shows a dosage clicker 300, which includes a cam member 301, a follower member 302 and a spring 303. The spring 303 is arranged to bias the follower member 302 against the cam member 301. The cam member 301 is attached to the housing 210.

[0031] In some examples, the follower member 302 can be coupled to a dose dispensing mechanism. For example, the follower member 302 can be attached to the piston rod 232. In such examples, the dose clicker 300 can be configured to detect a dispensed dose.

[0032] In some other examples, the follower member 302 can be coupled to a dose setting mechanism. In such examples, the dose clicker 300 can be configured to detect the set dose.

[0033] The cam member 301 is configured to be fixed relative to the driven member 302. The cam member 301 is prevented from axial movement. The driven member 302 is axially movable by compression and expansion of the spring 303. The driven member 302 is configured to rotate when the dose is being delivered during the delivery phase.

[0034] The cam member 301 includes a shaped section, shown in the figures as a sawtooth profile. The follower member 302 has a corresponding profile configured to engage with the shaped portion of the cam member 301. The shaped sections of the cam member 301 and follower member 302 are shown fully engaged. A spring 303 is positioned to bias the follower member 302 against the cam member 301. The spring 303 maintains the engagement between the shaped sections of the cam member 301 and follower member 302.

[0035] As the follower member 302 rotates, the shaped section of the cam member 301 disengages from the shaped section of the follower member 302. The cam member 301 is fixed relative to the follower member 302 and cannot rotate, so as the follower member 302 is rotated as shown in FIG. 4, it is pushed axially away from the cam member 301. The "uphill" section of the sawtooth profile pushes the two members apart. As the follower member 302 moves away from the cam member 301, the spring 303 is compressed. As the follower member 302 rotates further, the cam member 301 and follower member 302 can move back together. On the "downhill" section of the sawtooth profile, the two members can move together. The spring 303 expands and urges the follower member 302 axially towards the cam member 301.

[0036] Continued rotation of the follower member 302 relative to the cam member 301 results in axial reciprocation of the follower member 302. A sawtooth profile on the cam member 301 results in reciprocation of the follower member 302. Each "tooth" on the sawtooth profile may correspond to a minimum of the dose delivery movement. That is, each tooth may correspond to one click of the dosing clicker 300 associated with ejection of a drug dose. The follower member 302 may reciprocate once for each step reduction in dosage as the dose is delivered during the delivery phase.

[0037] The dose detection mechanism 300 further includes a piezoelectric sensor 310. A piezoelectric sensor is an example of a contact sensor. As shown in Figure 5, the dose detection mechanism 300 can include an outer section disposed radially outward of the inner section shown in Figures 3 and 4. The piezoelectric sensor 310 can be disposed on the outer section of the dose detection mechanism 300. The piezoelectric sensor 310 can be formed as a piezo ring extending around the periphery of the inner section.

[0038] In some other examples, the piezoelectric sensor 310 may be formed such that it does not form a complete ring. For example, the piezoelectric sensor 310 may be formed to be a different shape (e.g., square or rectangular) that extends only a portion of the circumference of the inner section of the cam member 301, for example as shown in FIG. 7. In such examples, at least one dome may be formed on the outer section of the dose detection mechanism 300 that is positioned to extend at least a portion of the circumference of the inner section of the cam member 301. In this manner, the dome can ensure that the driven member 302 makes proper contact with the piezoelectric sensor 310 and / or that the driven member 302 is prevented from tilting when it comes together with the cam member 301.

[0039] In one embodiment, the piezoelectric sensor 310 is attached to the cam member 301. The piezoelectric sensor 310 is positioned in contact with the driven member 302. The driven member 302 may be urged against the piezoelectric sensor 310 by a spring 303. Alternatively, the piezoelectric sensor 310 may be attached to the driven member 302. The piezoelectric sensor 310 may be positioned in contact with the cam member 301. The piezoelectric sensor 310 may be urged against the cam member 301 by a spring 303.

[0040] The piezoelectric sensor 310 is positioned such that when the shaped sections of the cam member 301 and the follower member 302 are fully engaged, the follower member 302 contacts the piezoelectric sensor 310. When the shaped section of the cam member 301 disengages from the shaped section of the follower member 302, the follower member 302 is moved away from the piezoelectric sensor 310. In this manner, the reciprocating motion of the follower member 302 repeatedly moves the follower member 302 into and out of contact with the piezoelectric sensor 310.

[0041] The piezoelectric sensor 310 is configured to generate a voltage in response to an applied pressure. The piezoelectric sensor 310 generates a voltage in response to physical contact with another element. For example, the piezoelectric sensor 310 generates a voltage in response to physical contact with the driven member 302. The piezoelectric sensor 310 provides a sensor signal having a voltage level indicative of physical contact between the piezoelectric sensor 310 and the driven member 302. The sensor signal has a high voltage level when the piezoelectric sensor 310 is in contact with the driven member 302. In this manner, the piezoelectric sensor 310 can produce a sensor signal having a voltage signal corresponding to the reciprocating motion of the driven member 302.

[0042] Each rotation of the follower member 302 as a dose is delivered corresponds to one tooth on the sawtooth profile and results in a corresponding voltage peak in the sensor signal. Hence, each step reduction in dosage as the dose is delivered during the delivery phase results in a corresponding voltage peak in the sensor signal.

[0043] The sensor signal output by the piezoelectric sensor 310 is provided to an electronic system. The electronic system includes a signal filter, an analog-to-digital converter (ADC), a processor, a battery, and a display. The signal filter is configured to filter the sensor signal for improved processing by the ADC and the processor. The signal filter may include a low pass filter configured to reduce high frequency noise in the sensor signal. The signal filter may include a threshold filter configured to reduce low level noise in the sensor signal.

[0044] The ADC is configured to convert the analog sensor signal to a digital signal for processing. The ADC can convert each voltage peak generated by contact between the piezoelectric sensor 310 and the driven member 302 to a logic high or digital "1." In other cases, portions of the sensor signal that do not include voltage peaks can be converted to logic low or digital "0."

[0045] In some examples, the battery may be co-located with the processor of the electronic system. In other examples, the battery may be co-located with the piezoelectric sensor 310.

[0046] The electronic system may further include an amplifier circuit that can amplify the voltage pulses generated by the piezoelectric sensor 310 as needed for further processing.

[0047] In some examples, the processor may include a microcontroller. The processor may include an input pin that receives the sensor signal from the piezoelectric sensor 310. The input pin of the processor may be configured to trigger an interrupt in the processor in response to receiving the sensor signal so that the processor can count voltage pulses associated with dosage delivery provided to the sensor signal. The processor may receive the sensor signal directly from the piezoelectric sensor 310 or may receive the sensor signal via a signal filter, an ADC, and / or an amplification circuit.

[0048] In some examples, the processor can distinguish between voltage pulses in the received sensor signal associated with dose delivery and voltage pulses in the received sensor signal associated with an external stimulus, e.g., dropping of the injection device. For example, the processor can implement a signal analysis algorithm to determine differences in signal characteristics.

[0049] In some other examples, the received sensor signal can be used to "wake up" the processor. The processor can be configured to be in a sleep mode to conserve energy consumption, and therefore battery life, until a transition to an active mode is triggered. The processor can be configured to transition from the sleep mode to the active mode in response to, for example, an initial "click" associated with a dose delivery detected in the sensor signal.

[0050] The processor is configured to count a number of voltage peaks in the sensor signal. Based on the number of voltage peaks, the processor can determine a corresponding value for the delivered dose. The processor can output the determined delivered dose for display on the display. Each voltage peak in the sensor signal can result in a corresponding increase in the determined delivered dose. The determined delivered dose can be increased by a predetermined amount based on a minimum dose delivery increment of the injection device. Each "click" of the dosing clicker 300 associated with a drug dose can result in a corresponding increase in the determined delivered dose.

[0051] The processor may be configured to store the currently displayed dosage in the memory. The processor may store the dosage together with the current time and / or date.

[0052] The injection device may further include a communication module to transmit the stored data to an external device. For example, the communication module may provide wireless communication capabilities (e.g., Bluetooth, Wi-Fi, NFC) or wired communication capabilities. The external device may be any external device suitable for receiving the transmitted data, such as a smartphone, a personal computer, a server, or another smart device.

[0053] FIG. 6 shows an arrangement for connecting the piezoelectric sensor 310 with an electronic system. The electronic system and its connections as shown in FIG. 6 can be arranged in the housing 210 of the injection device 200. The electronic system and its connections are thus arranged to be fixed relative to the piezoelectric sensor 310. The piezoelectric sensor 310 can be electrically connected to the electronic system via contacts, e.g., tracks or wires. In some other examples, the electronic system can be arranged between the housing 210 and the cartridge holder 222.

[0054] The contacts are provided by the inner sleeve 402 and the outer sleeve 400. For example, a first contact is provided by the inner sleeve 402 and a second contact is provided by the outer sleeve 400. The inner sleeve 402 is separated from the outer sleeve 400 by an insulating sleeve 401. The piezoelectric sensor 310 includes a first conductive surface 311 and a second conductive surface 312. The inner sleeve 402 is configured to make electrical contact with the second conductive surface 312 of the piezoelectric sensor 310, and the outer sleeve 400 is configured to make electrical contact with the first conductive surface 311. In this manner, the transmission of electronic signals between the electronic system and the piezoelectric sensor 310 can be performed via the electrical connection. Additionally or alternatively, the electronic system provides power to the piezoelectric sensor 310 via the electrical connection.

[0055] As described above, as the dose is delivered, the follower member 302 reciprocates for each step of the dose reduction, thereby repeatedly moving the follower member 302 into and out of contact with the piezoelectric sensor 310. The above described arrangement therefore allows electrical contact to be maintained between the electronic system and the piezoelectric sensor 310 during dose delivery.

[0056] Figure 7 shows a diagram of an alternative dose counting mechanism. In this example, the piezoelectric sensor 310 is formed to be rectangular, extending only a portion of the circumference of the inner portion of the cam member 301. In addition to the piezoelectric sensor 310, as shown in Figure 7, the cam member 301 may include at least one dome that extends around a portion of the circumference of the inner portion of the cam member 301, and the portion over which the dome extends may be different and / or spaced apart from the portion over which the piezoelectric sensor 310 extends.

[0057] Although claims have been formulated in this application to specific combinations of features, it is to be understood that the scope of the present disclosure also includes any novel features or any novel combinations of those features, or generalizations thereof, explicitly or implicitly disclosed herein, whether or not they relate to the same features as currently claimed in any claim, and whether or not they alleviate any or all of the same technical problems as the present disclosure. Applicants hereby give notice that new claims may be formulated to such features and / or combinations of features during prosecution of this application or of any further application derived therefrom.

[0058] While several embodiments have been shown and described, those skilled in the art will recognize that changes may be made to those embodiments without departing from the principles of the present disclosure as defined in the claims.

[0059] The terms "drug" or "medicament" are used interchangeably herein to describe a pharmaceutical formulation containing one or more active pharmaceutical ingredients or their pharma- ceutically acceptable salts or solvates, and optionally a pharma- ceutically 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 medicines are used to treat, cure, prevent, or diagnose diseases or otherwise improve physical or mental well-being. Drugs or medicines can be used for a limited duration or periodically for chronic disorders.

[0060] As described below, drugs or agents may include at least one API or combinations thereof in various types of formulations for the treatment of one or more diseases. Examples of APIs may include small molecules with molecular weights 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 may be incorporated into molecular delivery systems such as vectors, plasmids, or liposomes. Mixtures of one or more drugs are also contemplated.

[0061] 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 be at room temperature (e.g., about 20° C.) or at refrigerated temperatures (e.g., from about −4° C. to about 4° C.). In some cases, the drug container can be or include a dual-chamber cartridge configured to separately store 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 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.

[0062] The drugs or agents contained in the drug delivery devices described herein can be used for the treatment and / or prevention of many different types of medical disorders. Examples of disorders include, for example, diabetes or complications associated with diabetes, such as diabetic retinopathy, thromboembolic disorders, such as deep vein thromboembolism or pulmonary thromboembolism. Further examples of disorders are acute coronary syndromes (ACS), angina, myocardial infarction, cancer, macular degeneration, inflammation, hay fever, atherosclerosis and / or rheumatoid arthritis. Examples of APIs and drugs are those found in handbooks such as Rote Liste 2014 (e.g., but not limited to, main groups 12 (antidiabetic agents) or 86 (oncology agents)) and the Merck Index, 15th edition.

[0063] 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, analog or derivative thereof, a dipeptidyl peptidase-4 (DPP4) inhibitor, or a pharma-ceutically 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 or 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, e.g., 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-codeable amino acids, or amino acids, including non-codeable ones, are added to the naturally occurring peptide.

[0064] 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 in position B28 may be replaced by Asp, Lys, Leu, Val or Ala and in which the Lys in 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.

[0065] Examples of insulin derivatives are e.g. 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-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-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.

[0066] 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 (efpegrenatide). , HM-15211, CM-3, GLP-1 Erigen, ORMD-0901, NN-9423, NN-9709, NN-9924, NN-9926, NN-9927, Nodexene, Viador-GLP-1, CVX-096, ZYOG-1, ZYD-1, GSK-2374697, DA-3091, MAR-701, MAR709, ZP-2929, ZP-3022, ZP -DI-70, TT-401 (Pegapamodtide), BHM-034, MOD-6030, CAM-2036, DA-15864, ARI-2651, ARI-2255, Tirzepatide (LY3298176), Bamadutide (SAR425899), Exenatide-XTEN and Glucagon-Xten.

[0067] Examples of oligonucleotides are, for example, the cholesterol-lowering antisense therapeutic mipomersen sodium (Kynamro®) for the treatment of familial hypercholesterolemia, or RG012 for the treatment of Alport Syndrome.

[0068] Examples of DPP4 inhibitors are linagliptin, vidagliptin, sitagliptin, denagliptin, saxagliptin, berberine.

[0069] 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.

[0070] 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 above-mentioned polysaccharides in polysulfated form, and / or their pharma- ceutically acceptable salts. An example of a pharma-ceutically acceptable salt of polysulfated low molecular weight heparin is enoxaparin sodium. An example of a hyaluronic acid derivative is Hylan G-F20 (Synvisc®), sodium hyaluronate.

[0071] The term "antibody" as used herein refers to an immunoglobulin molecule or an antigen-binding portion thereof. Examples of antigen-binding portions of an immunoglobulin molecule include F(ab) and F(ab')2 fragments that retain the ability to bind to an antigen. 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, an antibody fragment, or a mutant that does not support binding to Fc receptors, e.g., with a mutation or deletion of the Fc receptor binding region. The term antibody also includes antigen-binding molecules based on tetravalent bispecific tandem immunoglobulins (TBTI) and / or dual variable region antibody-like binding proteins (CODV) with crossover binding region orientation.

[0072] The term "fragment" or "antibody fragment" refers to a polypeptide (e.g., 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 an antigen. An antibody fragment 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, such as bispecific, trispecific, tetraspecific and multispecific antibodies (e.g., diabodies, triabodies, tetrabodies), monovalent or multivalent antibody fragments, such as 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.

[0073] The term "complementarity determining region" or "CDR" refers to short polypeptide sequences in 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 in the variable regions of both heavy and light chain polypeptides that are not CDR sequences and are primarily responsible for maintaining the proper arrangement of the CDR sequences to allow antigen binding. Although the framework region itself typically does not directly participate in antigen binding, as is known in the art, certain residues in the framework region of a particular antibody may be directly involved in antigen binding or may affect the ability of one or more amino acids in the CDR to interact with the antigen.

[0074] Exemplary antibodies are anti-PCSK-9 mAb (eg, alirocumab), anti-IL-6 mAb (eg, sarilumab), and anti-IL-4 mAb (eg, dupilumab).

[0075] Pharmaceutically acceptable salts of any of the APIs described herein are contemplated for use in the drug or medicament in the drug delivery device. Pharmaceutically acceptable salts include, for example, acid addition salts and base salts.

[0076] Those skilled in the art will appreciate that modifications (addition and / or deletions) to the various components of the APIs, formulas, apparatus, methods, systems and embodiments described herein may be made without departing from the full scope and spirit of the invention, which encompasses such modifications and all equivalents thereof.

[0077] Exemplary drug delivery devices may include needle-based injection systems as described in Table 1 of Section 5.2 of ISO11608-1:2014(E). As described in ISO11608-1:2014(E), needle-based injection systems can be generally distinguished into multi-dose container systems and single-dose container systems (with partial or full discharge). The container may be a replaceable or non-replaceable one-piece container.

[0078] As further described in ISO11608-1:2014(E), a multi-dose container system may include a needle-based injection device with a replaceable container. In such a system, each container holds multiple doses and may be fixed or variable in size (pre-set by the user). Another multi-dose container system may include a needle-based injection device with a non-replaceable integral container. In such a system, each container holds multiple doses and may be fixed or variable in size (pre-set by the user).

[0079] As further described in ISO11608-1:2014(E), a single-dose container system may include a needle-based injection device with a replaceable container. In one example of such a system, each container holds a single dose, and in so doing, the entire deliverable volume is expelled (full expelled). In a further example, each container holds a single dose, and in so doing, a portion of the deliverable volume is expelled (partial expelled). Also as described in ISO11608-1:2014(E), a single-dose container system may include a needle-based injection device with a non-replaceable integral container. In one example of such a system, each container holds a single dose, and in so doing, the entire deliverable volume is expelled (full expelled). In a further example, each container holds a single dose, and in so doing, a portion of the deliverable volume is expelled (partial expelled).

Claims

1. An apparatus for detecting operation of an injection device, configured to be disposed within a housing of an injection device, the apparatus comprising: A cam member configured to be rotatable relative to a driven member; a resilient member arranged to bias the members into abutment with one another, such that rotation of the cam member relative to the driven member causes reciprocating movement of the driven member; and a contact sensor disposed between the cam member and the driven member and configured to detect reciprocating motion of the driven member; Including, the driven member is configured for axial reciprocation of the injection device; the cam member includes a shaped section including an axially varying profile disposed in abutment with the driven member and configured to induce reciprocating motion of the driven member; The contact sensor is disposed on the cam member and configured to move away from the driven member when the driven member reciprocates. The apparatus.

2. 2. The apparatus of claim 1, wherein the cam member is fixed non-rotatably and the driven member is rotatable.

3. The apparatus of claim 2 , wherein the driven member is configured to rotate in response to the injection device delivering a dose, the amount of rotation of the driven member corresponding to the dose.

4. The apparatus of claim 1 , wherein rotation of the cam member is configured to set a dose for the injection device.

5. and a dose setting mechanism configured to be rotatable to set a dose for the injection device, wherein: The driven member is fixed in position relative to the dose setting dial; An apparatus according to any one of claims 1 to 4.

6. The cam member is: a flat section that has a smaller axial change than the shaped section and is configured to move away from the driven member when the driven member reciprocates. The apparatus according to any one of claims 1 to 5, comprising:

7. The apparatus of claim 6 , wherein the flat section and the shaped section of the cam member are radially spaced apart.

8. 8. Apparatus according to claim 6 or 7, wherein the follower member includes a shaped section which corresponds to a shaped section of the cam member.

9. An apparatus according to any one of claims 6 to 8, wherein the shaped section comprises a sawtooth profile.

10. The apparatus of claim 6 , wherein the sawtooth profile includes a plurality of teeth, each tooth corresponding to a fixed dosage for the injection device.

11. An apparatus according to any one of claims 6 to 10, wherein the contact sensor is located on a flat section of the cam member.

12. An apparatus according to any preceding claim, wherein the contact sensor is located on a section of the driven member adjacent the cam member.

13. An apparatus according to any one of the preceding claims, wherein the contact sensor is a piezoelectric contact sensor configured to generate a current when in contact with another member of the injection device.

14. A device according to any preceding claim, wherein the device comprises a cartridge containing the medicament.

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