Electronics for dose sensing

Abstract

To provide a drug injector that includes a sensing system for determining a dosage of a medicament in a cartridge in the delivery device.SOLUTION: An injection device includes a cartridge 102 configured to hold a volume of fluid, the cartridge having a proximal end and a distal end through which the fluid is dispensed; a stopper 108 disposed in the cartridge and configured to move from the proximal end toward the distal end to cause the fluid to be dispensed through the distal end of the cartridge; and an electronic device 120 disposed at the distal end of the cartridge, the electronic device including an emitter 202 configured to transmit a signal toward the stopper, a receiver 204 configured to receive reflections of the signal from the stopper, and a microcontroller 210 configured to wirelessly transmit data related to a position of the stopper in the cartridge.SELECTED DRAWING: Figure 2

Description

[Technical field]

[0001] The present disclosure relates to injection devices, and more particularly to electronic components of injection devices for detecting the dosage of a medication to be administered. [Background technology]

[0002] There are various diseases that require treatment by injection of medication. Such injections can be performed using an injection device applied by a medical professional or by the patient himself. As an example, diabetes type 1 and type 2 can be treated by the patient himself, for example, by injecting insulin doses once or several times a day. For example, a pre-filled, disposable insulin pen or auto-injector can be used as the injection device. Alternatively, a reusable pen or auto-injector can be used. A reusable pen or auto-injector allows for replacement of an empty medication cartridge with a new medication cartridge. Either type of pen or auto-injector can be equipped with a set of single-use needles that are replaced before each use.

[0003] In particular, a drug injector is described that includes a sensing system for determining a dose of drug within a cartridge of a delivery device. Summary of the Invention [Means for solving the problem]

[0004] In one aspect, the injection device includes a cartridge configured to hold a volume of fluid. The cartridge has a proximal end and a distal end through which fluid is dispensed. The injection device also includes a stopper disposed within the cartridge and configured to move from the proximal end to the distal end such that fluid is dispensed through the distal end of the cartridge. The injection device also includes an electronic device disposed on the cartridge, or on the distal end of the cartridge housing. The electronic device includes an emitter configured to transmit a signal toward the stopper and a receiver configured to receive a reflection of the signal from the stopper. The electronic device also includes a controller configured to wirelessly transmit data related to the position of the stopper within the cartridge.

[0005] One or more embodiments are set forth in detail in the accompanying drawings and the description below. Other features, objects, and advantages will become apparent from the description and drawings, and from the claims. [Brief description of the drawings]

[0006] [Figure 1] FIG. 1 is an exploded view of an example of an injection device including an electronic measurement device. [Diagram 2] FIG. 1 is a cross-sectional view of an example of an injection device including an electronic measurement device. [Diagram 3] FIG. 1 is a cross-sectional view of an example of a stopper disposed within a cartridge and including an embedded electronic device. [Figure 4A] FIG. 1 is a cross-sectional view of an example of an injection device including an electronic measuring device with a battery located within the housing of the syringe. [Figure 4B] FIG. 1 is a cross-sectional view of an example of an injection device assembly with a removable electronic measurement device. [Diagram 5] FIG. 2 is a schematic diagram showing the relative positions of an emitter, a receiver, and a stopper. [Figure 6] FIG. 1 is a block diagram of an exemplary computer system. DETAILED DESCRIPTION OF THE PREFERRED EMBODIMENTS

[0007] In the various drawings, like reference symbols indicate like elements.

[0008] The drug delivery device may include an electronic device that may include a sensing system for determining a dose of a drug in a cartridge of the delivery device. The sensing system may include an emitter and a receiver, the emitter configured to bounce a signal off a stopper in the cartridge and the receiver configured to receive a reflection of the signal. Based on parameters of the reflected signal, a processor may determine a position of the stopper in the cartridge. Based on the geometry of the cartridge, the processor may calculate a dose of the drug dispensed as a function of the position of the stopper.

[0009] The subject matter described herein is described primarily with reference to drug delivery devices such as injection devices (e.g., insulin injection devices). However, the systems and techniques described herein are not limited to such applications and may be equally suitable for implementation in injection devices that release other medications, or in other types of medical devices (e.g., pumps).

[0010] The term "drug delivery device" is intended to encompass any type of device or system configured to administer a volume of a drug into the human or animal body. The volume can typically range from about 0.5 ml to about 10 ml. Without being limited thereto, drug delivery devices can include syringes, needle-safe systems, pen injectors, auto-injectors, large-volume devices (LVDs), pumps, perfusion systems, or other devices configured for subcutaneous, intramuscular, or intravascular delivery of drugs. Such devices often include a needle, which can include a small gauge needle (e.g., greater than about 24 gauge, including 27, 29, or 31 gauge).

[0011] In combination with a particular drug, the devices described herein can also be customized to operate within required parameters, for example, within a certain time period (e.g., about 3 to about 20 seconds for a syringe, about 5 to about 60 minutes for an LVD), with low or minimal levels of discomfort, or within specific conditions related to human factors, shelf life, expiration date, biocompatibility, environmental considerations, etc. Such differences can arise due to a variety of factors, such as, for example, the viscosity of the drug ranging from about 3 cP to about 50 cP.

[0012] The drug or agent can be contained within 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 container configured to provide a chamber suitable for storage (e.g., short-term or long-term storage) of one or more pharma- ceutical active compounds. For example, in some cases, the chamber can be designed to store the drug for at least one day (e.g., from 1 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 18-20°C) or at refrigerated temperatures (e.g., up to about 4-8°C). In some cases, the drug container can be or include a dual-chamber cartridge configured to store two or more components of a drug formulation (e.g., a drug and a diluent, or two different types of drugs) separately, 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 of the drug or agent prior to and / or during administration into the human or animal body. For example, the two chambers may be configured such that they are in fluid communication with one another (e.g., by a conduit between the two chambers) to allow mixing of the two components by a user prior to administration, if desired. Alternatively, or in addition, the two chambers may be configured to allow the components to mix as they are being administered into the human or animal body.

[0013] FIG. 1 is an exploded view of an example of an injection device 100. The injection device 100 can be a prefilled, disposable, or reusable injection pen. The injection device 100 includes a housing 110 that houses a cartridge 102. The cartridge 102 is configured to hold a volume of fluid. In some embodiments, the cartridge 102 is a medication container, such as an insulin container. The cartridge 102 includes a distal end 105 and a proximal end 106. In some embodiments, the proximal end 106 of the cartridge 102 may be inside the housing 110 of the injection device 100 and therefore may not be easily visible.

[0014] The injection device 100 includes a stopper 108 disposed within the cartridge 102. The stopper 108 is configured to move from the proximal end 106 of the cartridge 102 toward the distal end 105 of the cartridge 102 such that fluid is dispensed through the distal end 105 of the cartridge 102. The injection device 100 also includes a needle hub 115 disposed at the distal end 105 of the cartridge 102. A needle 114 can be attached to the needle hub 115 proximate the aperture 119 such that the fluid moves through the aperture 119 and the needle 114 when dispensed. In some embodiments, the needle hub 115 and the needle 114 can be threaded such that the needle 114 is screwed to the needle hub 115 or the needle hub 115 can be screwed to the needle 114. The needle 114 is protected by an inner needle cap 116 and an outer needle cap 117, which can then be covered by a cap 118.

[0015] A dose of drug (e.g., a dose of insulin) to be released from the injection device 100 can be selected by turning the dose knob 112, and the selected dose can then be displayed by the dose window 113. In some examples, the dose window 113 is a display, such as an electronic display. In some examples, the selected dose can be displayed as a multiple of international units (IU), where 1 IU is bioequivalent to approximately 45.5 micrograms of a drug such as pure crystalline insulin (e.g., 1 / 22 mg). An example of a selected dose displayed in the dose window 113 can be, for example, 30 IU, as shown in FIG. 1A. In some examples, the selected dose can be displayed in a different manner, such as, for example, by an electronic display. In some examples, the dose window 113 refers to a section of the injection device through or on which the selected dose can be viewed.

[0016] Turning the dose knob 112 can produce a mechanical click sound to provide auditory feedback to the user. The numbers displayed in the dose window 113 are printed on a sleeve contained within the housing 110 and which mechanically interacts with a piston in the cartridge 102. Medication is expelled from the injection device 100 when the needle 114 is inserted into an area of ​​the patient's skin and the injection button 111 is then pressed. The expulsion of a dose can also produce a mechanical click sound. Such a mechanical click sound can be different from the sound made when turning the dose knob 112.

[0017] The injection device 100 can be used for multiple injection procedures until the cartridge 102 is empty or until the expiration date of the injection device 100. In some examples, before using the injection device 100 for the first time, a "prime shot" is performed to empty the cartridge 102 and needle 114, for example by selecting two units of medication and pressing the injection button 111 while holding the injection device 100 with the needle 114 facing up. You may need to vent your mind.

[0018] The injection device 100 is configured to determine a volume of medicinal fluid (e.g., insulin) in the cartridge 102, which may represent a dose of the medicinal drug to be administered to the patient. For example, the injection device includes an electronic device 120 configured to measure the position of the stopper 108. The electronic device 120 includes an emitter 202 and a receiver 204 (shown in FIG. 2 ). In some embodiments, one or both of the emitter 202 and the receiver 204 may be disposed in the cartridge housing 104. The cartridge 102 and / or cartridge housing 104 may be made from and / or include a material that is transparent (or, for example, substantially transparent) to one or more waves emitted by the emitter and reflections of one or more waves.

[0019] 2, the emitter 202 is configured to transmit one or more signals 206 toward the proximal end 106 of the cartridge 102, where one or more waves are reflected from the proximal end 106 of the cartridge 102 (e.g., by bouncing off a surface of the stopper 108, as described in more detail below) and return to a receiver 204 located at the distal end. The receiver 204 is configured to receive a reflection 208 of the signal. Information related to the transmitted signal 206 and the reflection 208 of the one or more transmitted signals can be used to determine a volume of fluid within the cartridge 102. For example, information related to the one or more transmitted signals 206 and the reflection 208 of the one or more waves can be used to determine a distance traveled by the transmitted signal 206. The distance traveled by the transmitted signal 206 can be used to determine a volume of fluid within the cartridge 102, which can be used to determine a dose of a drug administered to a patient. In some embodiments, both the emitter 202 and the receiver 204 are included as components of a single transceiver package. The one or more signals may include acoustic waves, ultrasound waves, light waves, or any combination thereof.

[0020] In some embodiments, information related to one or more transmitted signals 206 (e.g., time of transmission, intensity at transmission) and information related to one or more reflections 208 of the transmitted signals (e.g., time of reception, intensity at reception) are provided to and / or received by a computing device (e.g., computer system 600 of FIG. 6 ), which uses such information to determine the volume of fluid within the cartridge 102. In some examples, the emitter 202 is an acoustic (e.g., ultrasound) transmitter configured to transmit one or more acoustic waves (e.g., ultrasound) toward the proximal end 106 of the cartridge 102, and the receiver 204 is an acoustic receiver configured to receive reflections of the one or more acoustic waves. The computing device can determine the time each of the acoustic waves was transmitted and, for each transmitted acoustic wave, the time the receiver 204 received the corresponding reflection. If the speed of the acoustic wave (e.g., the speed of sound in this case) is known, the elapsed time between transmission and reception of the wave, sometimes referred to as the time of flight (TOF), can be used to determine the distance traveled by the wave.

[0021] The distance traveled by the wave represents the distance from the emitter 202, toward the reflective surface (e.g., the surface of the stopper 108), and to the receiver 204. This distance can be divided by two to determine the distance between the stopper 108 and the receiver 204. Because the stopper 108 defines a fluid boundary near the proximal end 106 of the cartridge 102, the determined distance represents the length of the cartridge 102 within which fluid resides. The determined distance can be used in conjunction with the known dimensions of the cartridge 102 to determine the volume of fluid within the cartridge 102. For example, for a cylindrical cartridge, the volume (V) of fluid within the cartridge 102 can be calculated as: is the following formula: V=π*r^2*D_1 where r is the inner radius of the cartridge and D1 is the distance from the surface of the stopper 108 to the distal end 105 of the cartridge 102.

[0022] In one example, the emitter 202 transmits an acoustic wave at a first time t1. The first time t1 (e.g., the transmission time of the acoustic wave) is provided to a computing device. The acoustic wave travels from the emitter 202 toward the proximal end 106 of the cartridge 102 and is reflected (e.g., bounced off) the stopper 108. A reflection 208 (e.g., the reflected wave) of the acoustic wave travels from the stopper 108 toward the receiver 204. The reflected wave is received at a second time t2. The speed of the acoustic wave is the speed of sound in liquid. The elapsed time between the transmission and reception of the acoustic wave is t2-t1. Multiplying the elapsed time by the speed of sound determines the distance the wave traveled from the emitter 202 to the distal end 105 of the cartridge 102 and back to the receiver 204. Dividing the travel distance by two determines the distance between the emitter 202 / receiver 204 and the stopper 108. Multiplying the determined distance by the cross-sectional area of ​​the cartridge 102 determines the volume of fluid within the cartridge 102 (e.g., the volume of fluid contained within the cartridge 102 between the stopper 108 and the distal end 105). The determined volume of fluid within the cartridge 102 is the dose that is to be administered to the patient.

[0023] In some embodiments, the stopper 108 includes a reflective material 109 disposed at an end of the stopper 108 facing the emitter 202. The reflective material 109 is configured to improve the signal quality of the reflected signal (e.g., by minimizing signal loss upon reflection, reducing noise in the signal, improving the signal-to-noise ratio, etc.), thereby improving the calculated TOF.

[0024] 1-2 and 4A-4B, in some embodiments, the emitter 202 is a light source configured to transmit light toward the stopper 108, and the receiver 204 is a light receiver configured to receive the reflection or re-emission of light waves. In some examples, the cartridge housing 104 can be made of and / or include a material that is transparent (or, e.g., substantially transparent) to light waves and reflections of light waves. In some embodiments, the cartridge 102 includes a transparent material, such as one or both of glass and plastic.

[0025] Although the injection device 100 has been described primarily as configured to determine the volume of fluid in the cartridge 102 using information related to one or more transmitted signals and reflections of one or more signals, in some embodiments the injection device 100 may include one or more components other than or in addition to the emitter 202 and receiver 204 to determine the volume of fluid.

[0026] In some embodiments, the volume of fluid in the cartridge 102 can be determined continuously as the fluid is dispensed from the injection device 100. For example, while the injection button 111 is pressed and medication is expelled from the cartridge 102, the injection device 100 can continuously determine the volume of fluid in the cartridge 102, allowing the user to receive continuous feedback regarding the current volume of fluid in the cartridge 102.

[0027] In particular, in a manner substantially similar to that described above with respect to FIG. 2, information related to one or more transmitted signals (e.g., time of transmission) and information related to reflections of one or more transmitted signals (e.g., time of reception) may be provided to and / or received by a computing device. The time (e.g., TOF) can be multiplied by the speed of the signal (e.g., the speed of sound) to determine the distance traveled by the wave. The distance traveled by the wave represents the distance from the emitter 202 to the stopper 108 and back to the receiver 204. Dividing the traveled distance by two determines the distance between the emitter 202 / receiver 204 and the stopper 108. The determined distance is multiplied by the cross-sectional area of ​​the cartridge 102 to determine the volume of fluid in the cartridge 102 (e.g., the volume of the remaining fluid contained in the cartridge 102 between the stopper 108 and the distal end 105). The determined volume of fluid in the cartridge is the dose remaining in the cartridge 102 to be administered to the patient. The volume of fluid in the cartridge 102 can be determined continuously throughout the administration so that the remaining dose is known. The calculation of the dose can be performed by the microcontroller 210 on board the injection device 100 or by an external computer system 600. In some implementations, the microcontroller 210 on board the injection device 100 can be replaced by another type of processor.

[0028] FIG. 3 is a cross-sectional view of a stopper 300 disposed within a cartridge 350. The stopper includes embedded electronic components 306a, 306b, and 306c. The stopper 300 has a shell 302 and a core 304, in which the electronic devices 306a, 306b, and 306c are embedded. Optionally, an integrated sealing element 308 can be configured to provide a sealing interface with the cartridge 350 when the stopper is introduced into the cartridge. In some examples, the shell 302 provides a hard surface for interfacing with the head of a plunger. Thus, the shell 302 prevents the electronic devices 306a, 306b, and 306c from being deformed by the plunger pushing against the stopper 300 as the stopper 300 is moved along the length of the cartridge 350. In some examples, the shell 302 is heat resistant, which can protect the electronics 306a, 306b, and 306c from the heat generated during the heat sterilization process that sterilizes the stopper 300 and cartridge 350. It is contemplated that the shell and core can be made of various combinations of hard or soft materials to withstand the high temperatures used during the sterilization process, while also providing structure and support for the electronics and plunger. Alternatively, the shell / core can be made of a single piece with the electronics molded inside.

[0029] It is contemplated that the waves emitted by the emitter can be optical, acoustic, or ultrasonic in nature. In one example, the transmitter 306c transmits an acoustic wave at a first time t1. The first time t1 (e.g., the time of transmission of the acoustic wave) can be provided to an external device (e.g., a controller) via wireless transmission by the wireless transceiver 306b. The transmitter 306c and the wireless transceiver 306b can be powered by the power source 306a. The acoustic wave travels from the transmitter in the stopper 300 toward the distal end of the cartridge 350 (the end closest to the cap 354) and is reflected (e.g., bounced off) a surface or reflector (not shown) of the cartridge 350. A reflection of the acoustic wave (e.g., the reflected wave) travels from the distal end of the cartridge 350 toward a sensor in the stopper 300. The reflected wave is received at a second time t2. The speed of the acoustic wave is the speed of sound in the drug in the cartridge (e.g., 1484 meters / second in water). The time elapsed between transmission and reception of the acoustic wave is t2-t1. Multiplying the elapsed time by the speed of sound determines the distance the wave traveled from the transmitter to the distal end of the cartridge 350 and back to the sensor. Dividing the distance traveled by two determines the distance between the stopper 300 and the distal end of the cartridge 350. Multiplying the determined distance by the cross-sectional area of ​​the cartridge 350 determines the volume of drug in the cartridge 350 (e.g., the volume of drug contained within the cartridge 350 between the stopper 300 and the distal end). The determined volume of drug in the cartridge 350 is the dose to be administered to the patient.

[0030] 1-2 and 4A-4B generally, when a signal is emitted by the emitter 202 and a reflection of the signal is received by the receiver 204, the transmission of the signal is in the opposite direction (e.g., from the distal end 105 towards the proximal end 106 and back). This is advantageous because the stopper 108 provides a flat surface that is substantially equal to the cross section of the cartridge against which the signal can strike and be reflected (e.g., bounced back) towards the receiver. In an alternative configuration in which the emitter and receiver are located at the proximal end and the wave strikes and bounces off the distal end, it has been found that the shape and configuration of the cartridge does not provide a substantially flat surface against which the wave strikes and bounces off. Thus, locating the emitter and receiver at the distal end near the neck of the cartridge, allowing the wave to strike and bounce off a substantially flat surface of the stopper, increases the accuracy of the measurement. Including the electronics external to the stopper is also advantageous because the cartridge can be heat sterilized without concern that high heat will damage the electronics embedded in the stopper. Having the electronic components located external to the stopper simplifies the design and manufacture of the stopper.

[0031] 4A is an embodiment of an electronic device 120 including an emitter 202, a receiver 204, and an energy source 412. In this embodiment, the energy source 412 is disposed within the housing 110 of the injection device. The energy source 412 is electrically connected to the emitter 202 and the receiver 204 by electronic leads 414a and 414b. The energy source may include a battery. The electronic leads 414a and 414b extend through the cartridge housing 104. The electronic leads 414a and 414b enable the energy source 412 to provide energy to the emitter 202, the receiver 204, and the microcontroller 210.

[0032] The microcontroller 210 includes a wireless transceiver capable of communicating using any known wireless communication technology, including, for example, Bluetooth, NFC, or radio frequency. The microcontroller 210 can communicate data relating to the status of the cartridge or signals received at the receiver 204 to an external database. The status of the cartridge can correspond, for example, to the fill level of medication in the cartridge, or the position of a stopper. The status of the cartridge may enable the measurement of the dose of medication injected.

[0033] Communication with the microcontroller 210 can be one-way or two-way. In some examples, data communicated from the sensor device to the external database includes information related to device identification, such as a unique number, calibration data, production lot information, device material information, data related to storage time and production time, and information related to sensor measurements (e.g., time of measurement, sensor measurements such as temperature, distance, optical signal, acoustic signal). In some examples, data arriving from the external database device to the microcontroller 210 includes information related to a "wake up" signal, a measurement trigger, time information, or calibration data.

[0034] FIG. 5 is a schematic diagram showing the relative positions of the stopper 108, the emitter 202, and the receiver 204 with respect to the longitudinal axis 500. The emitter 202 is configured to be able to emit a signal at an angle between 0° and α. Correspondingly, the receiver 204 is configured to be able to receive the reflection of the signal after bouncing off the stopper 108 at an angle between 0° and α. When the stopper 108 moves a distance D1 from the proximal end 106 toward the distal end 105, the emitter 202 and the receiver 204 each have a range within which they can emit a signal and capture a reflection. In some embodiments, α is between 0° and 90°. In other embodiments, it is between 20° and 70°. In yet other embodiments, it is between 55° and 65°.

[0035] 4B is an embodiment of an electronic device 420 that is removable from the cartridge 400 or cartridge housing 440. The emitter 402 and receiver 404 are located within the removable electronic device 420 and are capable of emitting signals and receiving reflected signals, respectively, through a portion of the cartridge housing 440. The cartridge housing 440 is generally transparent to the signals 206 emitted from the emitter 402 and the reflections 208 of the signals received by the receiver 404. In some embodiments, the cartridge housing 440 is transparent to optical, ultrasonic, and / or acoustic signals.

[0036] The cartridge housing 440 includes ridges 442 with which clasps or snap portions of the electronic device 420 can interface to secure the electronic device 420 to the cartridge housing 440. The electronic device 420 can be installed and removed from the cartridge housing 440 so that it can be calibrated when installed in the cartridge housing 440. The calibration process typically allows the emitter and receiver to accurately determine the position of the stopper 108 within the cartridge 400. The microcontroller 450 can include memory to store drug related and dosing information useful for calibration.

[0037] The emitter 402 and receiver 404 are located within the removable electronic device 420 such that when the removable electronic device 420 is attached to the cartridge housing 440, the emitter 402 and receiver 404 are positioned such that the emitter can emit a signal at an angle between 0° and α relative to the longitudinal axis of the cartridge. Accordingly, the receiver 404 can receive a reflection of the signal after bouncing off the stopper 108 at an angle between 0° and α. In some embodiments, α is between 0° and 90°. In other embodiments, it is between 20° and 70°. In yet other embodiments, it is between 55° and 65°. Calibration may be required to ensure proper positioning of the emitter 402 and receiver 404 when the removable electronic device 420 is attached to the cartridge housing 440.

[0038] FIG. 6 is a block diagram of an exemplary computer system 600. For example, the computer system 600 can be incorporated into the injection device 100 of FIGS. 1-4 and / or the injection device 100 can be configured to interact with a separate computer system 600 (e.g., via the microcontroller 210 shown in FIG. 2). The system 600 includes a processor 610, a memory 620, a storage device 630, and an input / output device 640. Each of the components 610, 620, 630, and 640 can be interconnected, for example, using a system bus 650. The processor 610 can process instructions for execution within the system 600. The processor 610 can be a single-threaded processor, a multi-threaded processor, or a quantum computer. The processor 610 can process instructions stored in the memory 620 or the storage device 630. The processor 610 can perform operations such as causing the injection device 100 to perform one or more of the above-mentioned operations of determining the volume of fluid in the cartridge 102.

[0039] A portable computing device, such as a smartphone or tablet computer, can be an example of a computer system 600. In some implementations, the portable computing device runs applications for interfacing with the electronic device 120 of the injection device 100. For example, the portable computing device can communicate with the electronic device 120 using one or more computer networks (e.g., wireless or wired communication networks, or a combination of the two), and such applications running on the portable computing device can display information based on data received from the electronic device 120. In some implementations, other types of computer systems can operate the electronic device 120. The electronic device 120 may display information based on data received from the portable computing device. In some implementations, "cloud" computing technology is used to communicate information between the portable computing device and the electronic device 120. For example, both the portable computing device and the electronic device 120 may communicate with one or more cloud servers (which may be other examples of computer system 600) that act as facilities for intermediate data processing and storage. A cloud computing system may also provide access via the portable computing device to externally stored patient, dosage, or other data.

[0040] The memory 620 stores information within the system 600. In some embodiments, the memory 620 is a computer-readable medium. The memory 620 can be, for example, a volatile or non-volatile memory unit. In some embodiments, the memory 620 stores information related to one or more of the following: the speed of one or more waves transmitted by the emitter 202, the dimensions of the cartridge 102, and data usable to relate the applied voltage between the electrodes 202, 204 to the distance between the electrodes 202, 204.

[0041] The storage device 630 can provide mass storage for the system 600. In some embodiments, the storage device 630 is a non-transitory computer-readable medium. The storage device 630 can include, for example, a hard disk device, an optical disk device, a solid state drive, a flash drive, a magnetic tape, or some other mass storage device. Alternatively, the storage device 630 can be a cloud storage device, such as, for example, a logical storage device including multiple physical storage devices distributed over and accessed using a network. In some embodiments, information stored in the memory 620 can be stored in the storage device 630 in addition to or instead of the information stored in the memory 620.

[0042] The input / output device 640 provides input / output operations to the system 600. In some embodiments, the input / output device 640 includes one or more of a network interface device (e.g., an Ethernet card), a serial communication device (e.g., an RS-232 port), and / or a wireless interface device (e.g., a near field communication device, an 802.11 card, a 3G wireless modem, or a 4G wireless modem). In some embodiments, the input / output device 640 includes a driver device configured to receive input data and send output data to other input / output devices, such as keyboards, printers, and display devices (e.g., dosage window 113, etc.). In some embodiments, mobile computing devices, mobile communication devices, and other devices are used.

[0043] In some embodiments, system 600 is a microcontroller. A microcontroller is a device that includes multiple elements of a computer system within a single electronics package. For example, a single electronics package can include a processor 610, a memory 620, a storage device 630, and an input / output device 640.

[0044] Although an exemplary processing system has been described in FIG. 6, embodiments of the subject matter and functional operations described above may be embodied in other types of digital electronic circuitry, or in the form of computer software, firmware, or hardware, including the structures disclosed herein and structural equivalents thereof, or in one or more combinations thereof. Embodiments of the subject matter described herein may be implemented as one or more computer program products, e.g., for execution by a processing system or as part of a The present invention may be implemented as one or more modules of computer program instructions encoded on a tangible program carrier, such as a computer-readable medium, that controls the operation of the computer-readable medium. The computer-readable medium may be a machine-readable storage device, a machine-readable storage substrate, a memory device, a composition of matter carrying a machine-readable propagated signal, or a combination of one or more of these.

[0045] The term "computer system" can encompass all apparatus, devices, and machines for processing data, including, by way of example, a programmable processor, a computer, or multiple processors or computers. In addition to hardware, a processing system can include code that creates an execution environment for a given computer program, such as code that constitutes processor firmware, a protocol stack, a database management system, an operating system, or any combination of one or more of these.

[0046] A computer program (also known as a program, software, software application, script, executable logic, or code) can be written in any form of programming language, including compiled or interpreted languages, or declarative or procedural languages, and can be implemented in any form, including as a stand-alone program or as a module, component, subroutine, or other unit suitable for use in a computing environment. A computer program does not necessarily correspond to a file in a file system. A program can be stored as part of a file that holds other programs or data (e.g., one or more scripts stored in a markup language document), in a single file dedicated to the program, or in multiple associated files (e.g., files that store one or more modules, subprograms, or portions of code). A computer program can be implemented to be executed on one computer or on multiple computers at one site or distributed across multiple sites and interconnected by a communications network.

[0047] Computer-readable media suitable for storing computer program instructions and data include all forms of non-volatile or volatile memory, media, and memory devices, including, by way of example, semiconductor memory devices, such as EPROM, EEPROM, and flash memory devices; magnetic disks, such as internal hard disks or removable disks, or magnetic tapes; magneto-optical disks; and CD-ROM and DVD-ROM disks. The processor and memory may be supplemented by, or incorporated in, special purpose logic circuitry. The components of the system may be interconnected by any form or medium of digital data communication, e.g., a communications network. Examples of communications networks include local area networks ("LANs") and wide area networks ("WANs") such as the Internet.

[0048] The term "drug" or "medication" as used herein is used herein to describe one or more pharmacologic active compounds. As described below, a drug or medicament can include at least one small molecule or macromolecule, or a combination thereof, in various types of formulations for treating one or more diseases. Exemplary pharmacologic active compounds can include small molecules; polypeptides, peptides, and proteins (e.g., hormones, growth factors, antibodies, antibody fragments, and enzymes); carbohydrates and polysaccharides; and 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 vectors, plasmids, or molecular delivery systems such as liposomes. Mixtures of one or more of these drugs are also contemplated.

[0049] The drug delivery devices and drugs described herein can be used to treat and / or prevent many different types of disorders.Exemplary disorders include, for example, diabetes or complications associated with diabetes, such as diabetic retinopathy, thromboembolism, such as deep vein thromboembolism or pulmonary thromboembolism.Further exemplary disorders are acute coronary syndrome (ACS), angina pectoris, myocardial infarction, cancer, macular degeneration, inflammation, hay fever, atherosclerosis and / or rheumatoid arthritis.

[0050] Exemplary drugs for the treatment and / or prevention of diabetes or complications associated with 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 pharma- ceutically acceptable salt or solvate thereof, or any mixture thereof. As used herein, the term "derivative" refers to any substance that is sufficiently structurally similar to the original substance so that it can have a similar function or activity (e.g., therapeutic efficacy).

[0051] Exemplary insulin analogs are Gly(A21),Arg(B31),Arg(B32) human insulin (insulin glargine); Lys(B3),Glu(B29) human insulin; Lys(B28),Pro(B29) human insulin; Asp(B28) human insulin; human insulin in which the proline at position B28 is replaced by Asp, Lys, Leu, Val, or Ala, and in position B29, Lys may be replaced by Pro; Ala(B26) human insulin; Des(B28-B30) human insulin; Des(B27) human insulin and Des(B30) human insulin.

[0052] Exemplary insulin derivatives include, for example, B29-N-myristoyl-des(B30) human insulin; B29-N-palmitoyl-des(B30) human insulin; B29-N-myristoyl human insulin; B29-N-palmitoyl human insulin; B28-N-myristoyl-LysB28ProB29 human insulin; B28-N-palmitoyl-LysB28ProB29 human insulin; B30-N-myristoyl-ThrB29Ly sB30 human insulin; B30-N-palmitoyl-ThrB29LysB30 human insulin; B29-N-(N-palmitoyl-γ-glutamyl)-des(B30) human insulin; B29-N-(N-lithocholyl-γ-glutamyl)-des(B30) human insulin; B29-N-(ω-carboxyheptadecanoyl)-des(B30) human insulin, and B29-N-(ω-carboxyheptadecanoyl) human insulin. Exemplary GLP-1, GLP-1 analogs and GLP-1 receptor agonists include, for example: lixisenatide / AVE0010 / ZP10 / Lyxumia, exenatide / Exendin-4 / Byetta / Bydureon / ITCA650 / AC-2993 (a 39 amino acid peptide produced by the salivary glands of the Gila monster), liraglutide / Victoza, semaglutide, taspoglutide, synclear / albiglutide, dulaglutide, rExendin-4, CJC-1134-PC, PB-1023, TTP-054, Langrestine, These are Natide / HM-11260C, CM-3, GLP-1 Erigen, ORMD-0901, 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, TT-401, BHM-034, MOD-6030, CAM-2036, DA-15864, ARI-2651, ARI-2255, Exenatide-XTEN and Glucagon-Xten.

[0053] An exemplary oligonucleotide is, for example: mipomersen / quinamro, a cholesterol-lowering antisense therapeutic for the treatment of familial hypercholesterolemia.

[0054] Exemplary DPP4 inhibitors are vildagliptin, sitagliptin, denagliptin, saxagliptin, berberine.

[0055] Exemplary hormones include pituitary or hypothalamic hormones or regulatory active peptides and their antagonists, such as gonadotropins (follitropin, lutropin, chorion gonadotropins, menotropins), somatropins (somatropins), desmopressin, terlipressin, gonadorelin, triptorelin, leuprorelin, buserelin, nafarelin, and goserelin.

[0056] Exemplary polysaccharides include glycosaminoglycans, hyaluronic acid, heparin, low molecular weight heparin, or very low molecular weight heparin, or derivatives thereof, or sulfated forms of the above polysaccharides, such as polysulfated forms, 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 HylanG-F20 / Synvisc, sodium hyaluronate.

[0057] The term "antibody" as used herein 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 the ability to bind antigen. The antibody can be polyclonal, monoclonal, recombinant, chimeric, non-immunoglobulin or humanized, fully human, non-human (e.g., murine), or single chain antibody. In some embodiments, the antibody has effector function and can fix complement. In some embodiments, the antibody has reduced ability to bind or cannot bind Fc receptors. For example, the antibody can be an isotype or subtype, an antibody fragment, or a variant that does not support binding to Fc receptors, e.g., it has a mutated or deleted Fc receptor binding region.

[0058] The term "fragment" or "antibody fragment" refers to a polypeptide derived from an antibody polypeptide molecule (e.g., antibody heavy and / or light chain polypeptides) that does not include the full-length antibody polypeptide, but still includes at least a portion of the full-length antibody polypeptide that is capable of binding to an antigen. An antibody fragment can include a truncated portion of a full-length antibody polypeptide, but the term is not limited to such truncated fragments. Antibody fragments that are 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, and multispecific antibodies (e.g., diabodies, triabodies, tetrabodies), minibodies, chelating recombinant antibodies, tri- or bibodies, intrabodies, nanobodies, small modular immunopharmaceuticals (SMIPs), binding domain immunoglobulin fusion proteins, camelized antibodies, and VHH-containing antibodies. Further examples of antigen-binding antibody fragments are known in the art.

[0059] 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 but are primarily responsible for maintaining correct positioning of the CDR sequences to enable antigen binding. The framework regions themselves are generally defined as known in the art. Thus, while not directly involved in antigen binding, certain residues within the framework regions of a particular antibody may be directly involved in antigen binding or may influence the ability of one or more amino acids within the CDRs to interact with the antigen.

[0060] Exemplary antibodies are anti-PCSK-9 mAb (e.g., alirocumab), anti-IL-6 mAb (e.g., sarilumab), and anti-IL-4 mAb (e.g., dupilumab).

[0061] The compounds described herein can be used in pharmaceutical preparations that include (a) the compound or its pharmaceutically acceptable salt, and (b) a pharmaceutically acceptable carrier.The compounds can also be used in pharmaceutical preparations that include one or more other active pharmaceutical ingredients, or in pharmaceutical preparations in which the compound or its pharmaceutically acceptable salt is the only active ingredient present.Thus, the pharmaceutical preparations of the present disclosure encompass any preparation that is made by mixing the compounds described herein and a pharmaceutically acceptable carrier.

[0062] Pharmaceutically acceptable salts of any of the drugs described herein are also contemplated for use in the drug delivery device. Pharmaceutically acceptable salts are, for example, acid addition salts and base salts. Acid addition salts are, for example, HCl or HBr salts. Base salts are, for example, salts with a cation selected from an alkali or alkaline earth metal, for example Na+, or K+, or Ca2+, or an ammonium ion N+(R1)(R2)(R3)(R4), where R1 to R4 are each independently: hydrogen, an optionally substituted C1-C6-alkyl group, an optionally substituted C2-C6-alkenyl group, an optionally substituted C6-C10-aryl group, or an optionally substituted C6-C10-heteroaryl group. Further examples of pharma-ceutically acceptable salts are known to those skilled in the art.

[0063] Pharmaceutically acceptable solvates are, for example, hydrates or alkanolates, such as methanolates or ethanolates.

[0064] It will be understood by those skilled in the art that modifications (e.g., adjustments, additions, or deletions, etc.) of the various components of the substances, formulations, apparatus, methods, systems, devices, and embodiments described herein may be made without departing from the full scope and spirit of the inventive concept, which encompasses such modifications and any equivalents thereof.

[0065] Several embodiments of the systems and techniques described herein have been shown. However, it will be understood that various modifications can be made without departing from the spirit and scope of such systems and techniques. Accordingly, other embodiments are within the scope of the following claims. [Explanation of symbols]

[0066] 100 injection device 102 Cartridge 104 Cartridge housing 105 Cartridge Distal End 106 Cartridge proximal end 108 Stopper 109 Reflective materials 110 Housing 111 Injection button 112 Dosage knob 113 Dosage Window 114 needles 115 Needle Hub 116 Inner needle cap 117 Outer needle cap 118 Cap 119 Aperture 120 Electronic Devices 202 Emitter 204 Receiver 206 Signal 208 Reflection 210 Microcontroller 300 Stopper 302 Shell 304 Cores 306a power supply 306b Radio Transceiver 306c Transmitter 308 Integrated sealing elements 350 Cartridge 400 Cartridges 402 Emitter 404 Receiver 412 Energy Sources 414a Electronic Lead Wire 414b Electronic Lead Wire 420 Electronic Devices 440 Cartridge Housing 442 Ridge 450 Microcontroller 500 Longitudinal axis 600 Computer Systems 610 Processor 620 Memory 630 Storage Devices 640 Input / Output Devices 650 System Bus

Claims

1. An injection device (100) comprising: A housing (110); a medicament container (400) coupled to the housing (110) and configured to contain a medicament, the medicament container having a proximal end (106) and a distal end (105); a stopper (108) disposed within the medication container (400) and configured to move distally to dispense a medication from the medication container (400); and a removable electronic device (420) configured to be attached to the distal end (105) of the medication container (400), the removable electronic device (420) comprising: an emitter (402) positioned at a first angle within the removable electronic device (420) such that, when the removable electronic device (420) is attached to the medicament container (400), (i) the emitter (402) is positioned at a first angle relative to a longitudinal axis (500) of the medicament container (400), and (ii) the emitter (402) is configured to emit one or more signals (206) within the medicament container (400) to a stopper (108); a receiver (404) located within the removable electronic device (420) and configured to receive one or more reflections (208) of one or more signals (206) reflected off a distal surface of a stopper (108) when the removable electronic device (420) is attached to the medication container (400); The injection device, wherein the distal end of the drug container (400) has an angled portion configured to contact the emitter (402) and the receiver (404) when the removable electronic device (420) is attached to the distal end of the drug container (400).

2. The injection device (100) of claim 1, further comprising a controller (450) configured to determine a volume of the medicament based on one or more reflections (208).

3. 3. The injection device (100) of claim 2, wherein the controller (450) is configured to determine a dispensed volume of the medicament based on one or more reflections (208).

4. An injection device (100) as described in any one of claims 1 to 3, wherein the receiver (404) is configured to be positioned at a first angle with respect to a longitudinal axis (500) of the drug container (400) so as to receive one or more reflections (208) of one or more signals (206) reflected off a distal surface of the stopper (108) when the removable electronic device (420) is disposed at the distal end (105) of the drug container (400).

5. An injection device (100) as described in any one of claims 1 to 4, wherein the drug container (400) comprises a material that allows one or more signals (206) and one or more reflections (208) to substantially pass through the drug container (400).

6. An injection device (100) according to any one of claims 1 to 5, wherein the angled portion is located at a corner of the drug container (400), the corner being defined by (i) a first surface of the drug container (400) extending in a direction parallel to a longitudinal axis (500) of the drug container (400) and (ii) a second surface of the drug container (400) extending in a direction substantially perpendicular to the longitudinal axis (500) of the drug container (400).

7. An injection device (100) according to any one of claims 1 to 6, wherein the angled portion is angled with respect to a longitudinal axis (500) of the drug container (400) at a second angle substantially equal to the first angle.

8. An injection device (100) according to any one of the preceding claims, wherein the first angle is between 20 degrees and 70 degrees.

9. 9. The injection device (100) of claim 8, wherein the first angle is between 55 degrees and 65 degrees.

10. An injection device (100) according to any one of the preceding claims, wherein a proximal portion (106) of the medicament container (400) is disposed within the housing (110) and is not visible from outside the housing (110).

11. The injection device (100) of any one of claims 1 to 10, wherein the injection device (100) is configured for subcutaneous, intramuscular or intravascular delivery of a medicament.

12. The injection device (100) of any one of claims 1 to 11, wherein the medicament container (400) contains a medicament.

13. An injection device (100) according to any one of the preceding claims, wherein the drug container (400) comprises two chambers, each of the two chambers adapted to contain a respective component of the drug formulation.

14. 14. The injection device (100) of claim 13, wherein the drug container (400) contains each component of the drug formulation.

15. 15. The injection device (100) of claim 14, wherein the injection device (100) is configured to mix the respective components of the formulation before the drug is dispensed from the drug container (400) or while the drug is being dispensed from the drug container (400).

16. The injection device (100) according to any one of the preceding claims, wherein the injection device (100) is an auto-injector or a pen-injector.

17. An injection device (100) comprising: A medicament container (400) configured to contain a volume of medicament; a stopper (108) disposed within the drug container (400) and configured to move distally to dispense a drug from the drug container (400); and and a removable electronic device (420) configured to be attached to a distal end of the medication container (400), the removable electronic device (420) comprising: an emitter (402) located within the removable electronic device (420) and configured to emit one or more signals (206) through the angled portion of the drug container (400) when the removable electronic device (420) is attached to the distal end of the drug container (400); and a receiver (404) located within the removable electronic device (420) and configured to receive one or more reflections (208) of the one or more signals (206) reflected off the distal surface of the stopper (108); The injection device, wherein the angled portion of the drug container (400) is configured to contact the emitter (402) and the receiver (404) when the removable electronic device (420) is attached to the distal end of the drug container (400).

18. 18. The injection device (100) of claim 17, wherein the one or more reflections (208) are configured to pass through an angled portion of the drug container (400) after reflecting from a distal surface of the stopper (108) and before being received by the receiver (404).

19. An injection device (100) as claimed in claim 17 or 18, wherein the angled portion of the drug container (400) is located at a corner of the drug container (400), the corner being defined by (i) a first surface of the drug container (400) extending in a direction parallel to a longitudinal axis (500) of the drug container (400) and (ii) a second surface of the drug container (400) extending in a direction substantially perpendicular to the longitudinal axis (500) of the drug container (400).

20. An injection device (100) as described in claim 17 or 18, wherein the emitter (402) and the receiver (404) are angled with respect to the longitudinal axis (500) of the drug container (400) when the removable electronic device (420) is attached to the distal end of the drug container (400).

21. 21. The injection device (100) of claim 20, wherein the angled portion of the drug container (400) is angled relative to the longitudinal axis (500) of the drug container (400) at substantially the same angle as the angle at which the emitter (402) and receiver (404) are angled relative to the longitudinal axis (500) of the drug container (400) when the removable electronic device (420) is attached to the distal end of the drug container (400).

22. 1. A method for determining a volume of a drug in an injection device, comprising: an emitter (402) located within a removable electronic device (420) located at a distal end (105) of a drug container (400) of the injection device (100) and oriented at a first angle relative to a longitudinal axis (500) of the drug container (400), emitting one or more signals (206) from the emitter (402), the signals passing through an angled portion of the drug container (400) and toward a stopper (108) within the drug container (400); and a receiver (404) located in the removable electronic device (420) receiving one or more reflections (208) of the one or more signals (206) reflected from a distal surface of the stopper (108) of the injection device (100); The angled portion of the drug container (400) contacts the surface of the emitter (402) and the receiver (40 4).

23. 23. The method of claim 22, comprising determining, by the controller (450), a volume of the drug in the drug container (400) based on the one or more reflections (208).

24. 24. The method of claim 23, comprising determining, by the controller (450), a dispensed volume of the medication based on the one or more reflections (208).

25. 25. The method of claim 24, wherein the one or more reflections (208) are reflected from the stopper (108), pass through an angled portion of the drug container (400), and are received by a receiver (404).

26. 26. The method of any one of claims 22 to 25, wherein the angled portion is located at a corner of the medicament container (400), the corner being defined by (i) a first surface of the medicament container (400) extending in a direction parallel to a longitudinal axis (500) of the medicament container (400) and (ii) a second surface of the medicament container (400) extending in a direction substantially perpendicular to the longitudinal axis (500) of the medicament container (400).

27. 27. The method of any one of claims 22 to 26, wherein the angled portion of the medicament container (400) is angled at a second angle, relative to a longitudinal axis (500) of the medicament container (400), the second angle being substantially equal to the first angle.

28. The method of any one of claims 22 to 27, wherein the first angle is between 20 degrees and 70 degrees.

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