Electronics for dosage sensing

Abstract

To provide a drug injector that includes a sensing system for determining a dosage of a medicament in a cartridge in a delivery device.SOLUTION: An injection device includes a cartridge 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 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 disposed at the distal end of the cartridge, the electronic device including an emitter configured to transmit a signal toward the stopper, a receiver configured to receive reflections of the signal from the stopper, and a controller 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 an injection device, and more particularly to an electronic member of an injection device for detecting the dosage of a drug scheduled for administration.

Background Art

[0002] There are various diseases that require treatment by injection of a drug. Such injections can be performed using an injection device applied by a medical professional or the patient themselves. As an example, type 1 and type 2 diabetes can be treated by the patient themselves, for example, by injecting insulin doses once or several times a day. For example, as an injection device, a pre-filled disposable insulin pen or an autoinjector can be used. Alternatively, a reusable pen or autoinjector can also be used. With a reusable pen or autoinjector, it becomes possible to replace an empty drug cartridge with a new drug cartridge. Both types of pens or autoinjectors can be provided with a set of single-use needles that are replaced before each use.

[0003] In particular, a drug syringe including a detection system for determining the dosage of a drug in the cartridge of a delivery device will be described.

Summary of the Invention

Means for Solving the Problems

[0004] In one aspect, an injection device includes a cartridge configured to hold a volume of fluid. The cartridge has a proximal end and a distal end through which the 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 the fluid is dispensed through the distal end of the cartridge. The injection device also includes an electronic device disposed at the distal end of the cartridge or a cartridge housing. The electronic device includes a transmitter 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] In the accompanying drawings and the following description, one or more embodiments are described in detail. Other features, objects, and advantages will be apparent from the description and drawings, and from the claims.

Brief Description of the Drawings

[0006]

Figure 1

Figure 2

Figure 3

Figure 4A

Figure 4B

Figure 5

Figure 6

Best Mode for Carrying Out the Invention

[0007] In various figures, like reference numerals refer to like elements.

[0008] A drug delivery device can include an electronic device capable of including a sensing system for determining the dosage of a medicament within a cartridge of the delivery device. The sensing system can include an emitter and a receiver, the emitter being configured to bounce a signal off a stopper within the cartridge and the receiver being configured to receive the reflection of the signal. Based on the parameters of the reflected signal, a processor can determine the position of the stopper within the cartridge. Based on the geometry of the cartridge, the processor can calculate the dosage of the medicament dosed according to the position of the stopper.

[0009] The subject matter described herein is mainly described 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 can be equally suitably introduced in injection devices that release other medicaments or other types of medical devices (e.g., pumps).

[0010] The term "drug delivery device" shall be taken to encompass any type of device or system configured to administer a volume of drug into the body of a human or animal. The volume can typically range from about 0.5 ml to about 10 ml. By way of non-limiting example, drug delivery devices can include syringes, needle safety systems, pen-type injectors, auto-injectors, large-volume devices (LVDs), pumps, infusion systems, or other devices configured for subcutaneous, intramuscular, or intravascular delivery of drugs. Such devices often include a needle, which can include small-gauge needles (e.g., greater than about 24 gauge, including 27, 29, or 31 gauge).

[0011] In combination with a specific drug, the devices described herein can be customized to operate within a range of required parameters, e.g., within a certain time period (e.g., about 3 to about 20 seconds for a syringe, about 5 minutes to about 60 minutes for an LVD), at a low or minimal level of discomfort, or within a range of specific conditions related to human factors, shelf life, expiration date, biocompatibility, environmental considerations, etc. Such differences can be caused by various factors, e.g., 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 pharmaceutically 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 up to at least 30 days). In some cases, the chamber can be designed to store the drug for about 1 month to about 2 years. Storage can be carried out at room temperature (e.g., about 18 - 20 °C) or refrigerated temperature (e.g., down to about 4 - 8 °C). In some cases, the drug container can be a dual - chamber cartridge configured to store two or more components of a pharmaceutical formulation (e.g., a drug and a diluent, or two different types of drugs) separately, one in each chamber, or can include such a cartridge. In such cases, the two chambers of the dual - chamber cartridge can be configured to allow mixing between two or more components of the drug or agent before and / or during dosing into a human or animal body. For example, the two chambers can be configured to be in fluid communication with each other (e.g., by a conduit between the two chambers) and, if desired, allow the user to mix the two components before dosing. It can be done. Alternatively, or in addition to this, the two chambers can be configured to allow mixing when the components are being dosed in a 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 filled, 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 certain volume of fluid. In some embodiments, the cartridge 102 is a drug 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 thus 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 towards the distal end 105 of the cartridge 102 such that fluid is dosed 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 so as to be proximate to an aperture 119 and configured to move through the aperture 119 and the needle 114 when fluid is dosed. In some embodiments, the needle hub 115 and the needle 114 can be threaded and the needle 114 can be screwed onto the needle hub 115 or the needle hub 115 can be screwed onto the needle 114. The needle 114 is protected by an inner needle cap 116 and an outer needle cap 117 and as a result can be covered by a cap 118.

[0015] The dose of the drug (e.g., insulin dose, etc.) scheduled to be released from the injection device 100 can be selected by turning the dose knob 112, and then the selected dose can 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), and 1 IU is biologically equivalent to a drug (e.g., 1 / 22 mg) such as about 45.5 micrograms of pure crystalline insulin. An example of the 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 different forms, for example, by an electronic display. In some examples, the dose window 113 refers to a section of the injection device through which or on which the selected dose can be viewed.

[0016] By turning the dose knob 112, a mechanical clicking sound can be generated to provide the user with auditory feedback. The numbers displayed in the dose window 113 are contained within the housing 110 and printed on a sleeve that mechanically interacts with the piston within the cartridge 102. When the needle 114 is inserted into the patient's skin portion and then the injection button 111 is pressed, the drug is released from the injection device 100. The release of the dose can also generate a mechanical clicking sound. Such a mechanical clicking sound can be made different from the sound emitted 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, for example, select 2 units of the drug and press the injection button 111 while holding the injection device 100 with the needle 114 facing upward to perform a "prime shot" to remove air from the cartridge 102 and the needle 114. It may be necessary in some cases.

[0018] The injection device 100 is configured to determine the volume of the pharmaceutical fluid (e.g., insulin) within the cartridge 102, and this volume can represent the dosage of the pharmaceutical 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 can be disposed in the cartridge housing 104. The cartridge 102 and / or the cartridge housing 104 can be made of, and / or include, a material that passes (or, for example, substantially passes) one or more waves emitted by the emitter and the reflection of one or more waves.

[0019] Referring to FIG. 2, the emitter 202 is configured to transmit one or more signals 206 toward the proximal end 106 of the cartridge 102, and one or more waves are reflected from the proximal end 106 of the cartridge 102 (e.g., by hitting and bouncing off the surface of the stopper 108, as described in detail below) and return to the receiver 204 disposed at the distal end. The receiver 204 is configured to receive the reflection 208 of the signal. Using the transmitted signal 206 and the information related to the reflection 208 of one or more transmitted signals, the volume of the fluid within the cartridge 102 can be determined. For example, using the information related to the one or more transmitted signals 206 and the reflection 208 of one or more waves, the distance traveled by the transmitted signal 206 can be determined. Using the distance traveled by the transmitted signal 206, the volume of the fluid within the cartridge 102 can be determined, and using the volume of the fluid within the cartridge 102, the dosage of the pharmaceutical administered to the patient can be determined. 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 can include acoustic waves, ultrasonic 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 the time of transmission), and information related to reflections 208 of one or more transmitted signals (e.g., time of reception, intensity at the time of reception) are provided to and / or received by a computing device (e.g., computer system 600 of FIG. 6), and the computing device uses such information to determine the volume of fluid within cartridge 102. In some examples, emitter 202 is an acoustic (e.g., ultrasonic) transmitter configured to transmit one or more acoustic waves (e.g., ultrasonic waves) toward proximal end 106 of cartridge 102, and receiver 204 is an acoustic receiver configured to receive reflections of one or more acoustic waves. The computing device can identify the time at which each acoustic wave was transmitted and the time at which receiver 204 received the corresponding reflection for each transmitted acoustic wave. If the speed of the acoustic wave (e.g., the speed of sound in this case) is known, the distance the wave traveled can be determined using the elapsed time between transmission and reception of the wave, sometimes referred to as the time of flight (TOF).

[0021] The distance the wave traveled represents the distance from emitter 202, toward a reflective surface (e.g., the surface of stopper 108), and to receiver 204. Dividing this distance by two can determine the distance between stopper 108 and receiver 204. Since stopper 108 defines the boundary of the fluid near proximal end 106 of cartridge 102, the determined distance represents the length of cartridge 102 within which the fluid is present. Using the determined distance along with the known dimensions of cartridge 102, the volume of fluid within cartridge 102 can be determined. For example, in the case of a cylindrical cartridge, the volume (V) of fluid within cartridge 102 is given by the following equation: V = π * r^2 * D_1 It is determined by, 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 the computing device. The acoustic wave travels from the emitter 202 towards the proximal end 106 of the cartridge 102 and hits the stopper 108 and is reflected (e.g., bounced back). The reflection 208 of the acoustic wave (e.g., the reflected wave) travels from the stopper 108 towards 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 the 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 travels from the emitter 202 to the distal end 105 of the cartridge 102 and back to the receiver 204. Dividing the traveled distance by 2 determines the distance between the emitter 202 / receiver 204 and the stopper 108. By multiplying the determined distance by the cross-sectional area of the cartridge 102, the volume of fluid within the cartridge 102 (e.g., the volume of fluid that enters between the stopper 108 and the distal end 105 within the cartridge 102) is determined. The determined volume of fluid within the cartridge 102 is the dose scheduled 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 that faces 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 value of the TOF.

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

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

[0026] In some embodiments, the volume of fluid within cartridge 102 can be determined continuously while dispensing the fluid from injection device 100. For example, while injection button 111 is pressed and the drug is being dispensed from cartridge 102, injection device 100 can continuously determine the volume of fluid within cartridge 102 and enable the user to receive continuous feedback regarding the current volume of fluid within 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 the reflection of one or more transmitted signals (e.g., time of reception) can be provided to and / or received by a computing device. The elapsed time between signal transmission and reception The distance the wave has traveled can be determined by multiplying the speed of the signal (e.g., the speed of sound) by the time (e.g., TOF). The distance the wave has traveled represents the distance from the emitter 202 to the stopper 108 and back to the receiver 204. Dividing the travel distance by 2 determines the distance between the emitter 202 / receiver 204 and the stopper 108. By multiplying the determined distance by the cross-sectional area of the cartridge 102, the volume of fluid within the cartridge 102 (e.g., the volume of the remaining fluid that has entered between the stopper 108 and the distal end 105 within the cartridge 102) is determined. The determined volume of fluid within the cartridge is the dose remaining within the cartridge 102 that is scheduled to be administered to the patient next. The volume of fluid within the cartridge 102 can be continuously determined throughout the administration so that the remaining dose is known. The calculation of the dose can be performed by a microcontroller 210 mounted on the injection device 100 or by an external computer system 600. In some implementations, it is possible to use another type of processor instead of the microcontroller 210 mounted on the injection device 100.

[0028] FIG. 3 is a cross-sectional view of a stopper 300 disposed within a cartridge 350. The stopper includes embedded electronic members 306a, 306b, and 306c. The stopper 300 has a shell 302 and a core 304, and the electronic devices 306a, 306b, and 306c are embedded in the core 304. Optionally, an integrated sealing element 308 can be configured to provide a sealing interface with the cartridge when the stopper is introduced into the cartridge 350. In some examples, the shell 302 provides a rigid surface for engaging the head of the plunger. Thus, the shell 302 prevents the electronic devices 306a, 306b, 306c from being deformed when the plunger presses against the stopper 300 as the stopper 300 is moved along the length of the cartridge 350. In some examples, the shell 302 has heat resistance, thereby protecting the electronic members 306a, 306b, and 306c from the heat generated during a heat sterilization process for sterilizing the stopper 300 and the cartridge 350. The shell and the core are made of various combinations of rigid or soft materials so as to withstand the high temperatures used during the sterilization process, while also being intended to provide structure and support for the electronic device and the plunger. Alternatively, the shell / core can be made of a single-piece member with the electronic device molded therein.

[0029] The waves emitted by the emitter are intended to be essentially light waves, sound waves, or ultrasonic waves. In one example, the transmitter 306c transmits sound waves at a first time t1. The first time t1 (e.g., the transmission time of the sound waves) 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 energized by the power supply 306a. The sound waves travel from the transmitter in the stopper 300 towards the distal end of the cartridge 350 (the end closest to the cap 354) and are reflected (e.g., bounced back) when hitting the surface of the cartridge 350 or a reflector (not shown). The reflection of the sound waves (e.g., the reflected waves) travels from the distal end of the cartridge 350 towards the sensor in the stopper 300. The reflected waves are received at a second time t2. The speed of the sound waves is the speed of sound in the drug within the cartridge (e.g., 1484 meters per second in water). The elapsed time between the transmission and reception of the sound waves is t2 - t1. Multiplying the elapsed time by the speed of sound determines the distance the wave has traveled from the transmitter to the distal end of the cartridge 350 and back to the sensor. Dividing the traveled distance by 2 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 the drug within the cartridge 350 (e.g., the volume of the drug that has entered between the stopper 300 and the distal end within the cartridge 350). The determined volume of the drug within the cartridge 350 is the dose intended for administration to the patient.

[0030] Referring generally to FIGS. 1-2 and 4A-4B, when a signal is emitted by emitter 202 and the reflection of the signal is received by receiver 204, the signal transmission occurs in the opposite direction (e.g., from distal end 105 towards proximal end 106 and bouncing back). This is advantageous because stopper 108 provides a flat surface that is substantially equal to the cross-section of the cartridge, allowing the signal to hit and reflect (e.g., bounce back) towards the receiver. In another configuration where the emitter and receiver are placed at the proximal end and the wave hits the distal end and bounces back, it has been found that the shape and configuration of the cartridge cannot provide a substantially flat surface for the wave to hit and bounce back. Therefore, placing the emitter and receiver at the distal end close to the neck of the cartridge, such that the wave can hit and bounce back off the substantially flat surface of the stopper, increases the accuracy of the measurement. Also, including the electronic components outside the stopper is advantageous because the cartridge can be heat sterilized without considering that the electronic components embedded in the stopper may be damaged by high heat. When the electronic components are placed outside the stopper, the design and manufacture of the stopper are simplified.

[0031] FIG. 4A is an embodiment of an electronic device 120 that includes 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 electrical leads 414a and 414b. The energy source can include a battery. The electrical leads 414a and 414b extend through the cartridge housing 104. The electrical leads 414a and 414b enable the energy source 412 to supply 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 transmit data related to the state of the cartridge or signals received by the receiver 204 to an external database. The state of the cartridge can correspond to, for example, the filling level of the drug in the cartridge or the position of the stopper. Depending on the state of the cartridge, it may be possible to measure the dose of the injected drug.

[0033] Communication with the microcontroller 210 can be one-way or two-way. In some examples, the data transmitted from the sensor device to the external database includes information related to the identification of the device, such as a unique number, calibration data, production lot information, material information of the device, data related to the storage time and production time, and information related to the sensor measurements (for example, the time of measurement, the measurement results of the sensor such as temperature, distance, optical signal, acoustic signal). In some examples, the data received by the microcontroller 210 from the external database device includes a "startup" signal, a trigger for measurement, time information, or information related to 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. Accordingly, the receiver 204 is configured to be able to receive the reflection of the signal after hitting and 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 towards the distal end 105, the emitter 202 and the receiver 204 each have a range within which the emission and reflection of the signal can be captured. In some embodiments, α is between 0° and 90°. In other embodiments, it is between 20° and 70°. In still other embodiments, it is between 55° and 65°.

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

[0036] The cartridge housing 440 includes a protrusion 442 with which a fixture or snap portion of the electronic device 420 engages to enable the electronic device 420 to be secured to the cartridge housing 440. Since the electronic device 420 is attachable and removable with respect to the cartridge housing 440, it can be calibrated when attached to the cartridge housing 440. The calibration process typically enables the emitter and receiver to accurately determine the position of the stopper 108 within the cartridge 400. The microcontroller 450 can include a memory that stores information related to the agent useful for calibration and dosing information.

[0037] Emitter 402 and receiver 404 are located within a removable electronic device 420, and 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 radiate a signal at an angle between 0° and α with respect to the longitudinal axis of the cartridge. Accordingly, the receiver 404 is able to receive the reflection of the signal after hitting the stopper 108 and bouncing back 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 still other embodiments, it is between 55° and 65°. When the removable electronic device 420 is attached to the cartridge housing 440, calibration may be required to ensure proper positioning of the emitter 402 and receiver 404.

[0038] FIG. 6 is a block diagram of an exemplary computer system 600. For example, it is possible to incorporate the computer system 600 into the injection device 100 of FIGS. 1-4 and / or configure the injection device 100 to interact with an independent 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 one or more of the above-described operations for determining the volume of fluid within the cartridge 102 in the injection device 100.

[0039] Portable computing devices such as smartphones and tablet computers can be an example of the computer system 600. In some implementations, the portable computing device runs an application for associating 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 an application 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 display information based on data received from the ele ctronic device 120. In some implementations, "cloud" computing technology is used to transfer information between the portable computing device and the electronic device 120. For example, both the portable computing device and the electronic device 120 can communicate with one or more cloud servers (which can be another example of the computer system 600) that serve as intermediate data processing and storage facilities. The cloud computing system can also provide access to externally stored patient, dosage, or other data via the portable computing device.

[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 memory unit or a non-volatile memory unit. In some embodiments, the memory 620 stores information related to one or more of the data that can be used to associate the speed of one or more waves transmitted by the emitter 202, the dimensions of the cartridge 102, and the applied voltage between the electrodes 202, 204 with the distance between the electrodes 202, 204.

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

[0042] The input / output device 640 provides input / output operations for 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 wireless 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 a keyboard, a printer, and a display device (e.g., the dosage window 113, etc.). In some embodiments, mobile computing devices, mobile communication devices, and other devices are used.

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

[0044] Although an exemplary processing system has been described with reference to FIG. 6, embodiments of the above-described subject matter and functional operations may be implemented in the form of other types of digital electronic circuitry, or in the form of computer software, firmware, or hardware including the structures disclosed herein and their structural equivalents, or in the form of one or more combinations thereof. Embodiments of the subject matter described herein may be implemented as one or more computer program products, e.g., one or more modules consisting of computer program instructions encoded on a tangible program carrier, e.g., a computer-readable medium, for execution by, or to control the operation of, a processing system. The computer-readable medium can be a machine-readable storage device, a machine-readable storage substrate, a memory device, a composition that provides a machine-readable propagated signal, or one or more combinations thereof. The term "computer system" can include all apparatus, devices, and machines for processing data, e.g., programmable processors, computers, or multiple processors or computers. The processing system can include, in addition to hardware, code that creates an execution environment for the computer program in question, e.g., code constituting processor firmware, protocol stack, database management system, operating system, or one or more combinations thereof.

[0045]

[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 introduced in any form, such as as a stand-alone program or as a module, component, subroutine, or other unit of composition suitable for use in a computing environment. A computer program does not necessarily correspond to a file in a file system. The program can be stored as part of a file that holds other programs or data (such as one or more scripts stored in a markup language document), in a single file dedicated to the program, or in multiple coordinated files (such as files that store each part of one or more modules, subprograms, or code). A computer program can be introduced to be executed on one computer, or at one site, or distributed across multiple computers interconnected by a communication network and executed on those multiple computers.

[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, by way of example, semiconductor memory devices such as, for example, EPROM, EEPROM, and flash memory devices; magnetic disks such as internal hard disks or removable disks, or magnetic tape; magneto-optical disks; and CD-ROM and DVD-ROM disks. The processor and memory can be supplemented by, or incorporated in, specific purpose logic circuitry. The components of the system can be interconnected by any form or medium of digital data communication, such as, for example, any form of communication network. Examples of communication networks include local area networks ("LAN") and wide area networks ("WAN") such as the Internet.

[0048] As used herein, the term "drug" or "agent" is used herein to describe one or more pharmaceutically active compounds. As described below, a drug or agent can include at least one small molecule or macromolecule, or a combination thereof, of various types of formulations for treating one or more diseases. Exemplary pharmaceutically active compounds include small molecules; polypeptides, peptides, and proteins (such as 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 molecular delivery systems such as vectors, plasmids, or liposomes. One or more mixtures of these drugs are also contemplated.

[0049] The drug delivery devices and drugs described herein can be used for the treatment and / or prevention of numerous different types of disorders. Exemplary disorders include, for example, diabetes or complications associated with diabetes such as diabetic retinopathy, and thromboembolism such as deep vein thrombosis or pulmonary embolism. Further exemplary disorders are acute coronary syndrome (ACS), angina, 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, such as human insulin, or human insulin analogs or derivatives, glucagon-like peptide (GLP-1), GLP-1 analogs or GLP-1 receptor agonists, or analogs or derivatives thereof, dipeptidyl peptidase-4 (DPP4) inhibitors, or pharmaceutically acceptable salts or solvates thereof, or any mixture thereof. As used herein, the term "derivative" refers to any substance that is structurally similar enough to the original substance so as to be able to 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 which Lys at position B29 may be replaced by Pro; Ala(B26) human insulin; Des(B28-B30) human insulin; Des(B27) human insulin and Des(B30) human insulin.

[0052] Exemplary insulin derivatives are, for example, B29-N-myristoyl-des(B30) human insulin; B29-N-palmitoyl-des(B30) human insulin; B29-N-myristoyl human insulin; B29-N-palmitoyl human insulin; B28-N-myristoyl LysB28ProB29 human insulin; B28-N-palmitoyl-LysB28ProB29 human insulin; B30-N-myristoyl-ThrB29LysB30 human insulin; B30-N-palmitoyl-ThrB29LysB30 human insulin; B29-N-(N-palmitoyl-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 are, for example: lixisenatide / AVE0010 / ZP10 / lixumia, exenatide / exendin-4 / byetta / vidurian / ITCA650 / AC-2993 (a 39-amino acid peptide produced by the salivary glands of the Gila monster), liraglutide / victoza, semaglutide, taspoglutide, syncria / albiglutide, dulaglutide, r exendin-4, CJC-1134-PC, PB-1023, TTP-054, langlenatide / HM-11260C, CM-3, GLP-1 erigen, ORMD-0901, NN-9924, NN-9926, NN-9927, nodexen, viadorl-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] Exemplary oligonucleotides include, for example, mipomersen / kinamro, a cholesterol-lowering antisense therapeutic for the treatment of familial hypercholesterolemia.

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

[0055] Exemplary hormones include pituitary hormones or hypothalamic hormones or regulatory active peptides and their antagonists such as gonadotropins (folitropin, lutropin, chorionic gonadotropin, menotropin), somatropin (somatropin), desmopressin, terlipressin, gonadorelin, tryptorelin, leuprolide, buserelin, nafarelin, and goserelin.

[0056] Exemplary polysaccharides include glucosaminoglycans, hyaluronic acid, heparin, low molecular weight heparin, or ultra-low molecular weight heparin, or their derivatives, or sulfated forms of the above polysaccharides, for example, poly-sulfated forms, and / or pharmaceutically acceptable salts thereof. An example of a pharmaceutically acceptable salt of poly-sulfated low molecular weight heparin is enoxaparin sodium. Examples of hyaluronic acid derivatives include Hylan G-F20 / Synvisc and sodium hyaluronate.

[0057] As used herein, the term "antibody" refers to an immunoglobulin molecule or an antigen-binding portion thereof. Examples of antigen-binding portions of immunoglobulin molecules include F(ab) and F(ab’)2 fragments that retain the ability to bind antigen. Antibodies can be polyclonal, monoclonal, recombinant, chimeric, non-immune or humanized, fully human, non-human (e.g., murine), or single-chain antibodies. In some embodiments, the antibody has effector function and can fix complement. In some embodiments, the antibody has low or no ability to bind to Fc receptors. For example, the antibody can be an isotype or subtype, an antibody fragment or 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., an antibody heavy chain and / or light chain polypeptide) that does not include the full-length antibody polypeptide but still includes at least a portion of the full-length antibody polypeptide that can bind to an antigen. Antibody fragments can include cleaved portions of the full-length antibody polypeptide, but the term is not limited to such cleaved fragments. Antibody fragments useful in the present invention include, for example, single-specificity or multi-specificity antibody fragments such as Fab fragments, F(ab’)2 fragments, scFv (single-chain Fv) fragments, linear antibodies, bispecific, trispecific, and multi-specific antibodies (e.g., diabodies, triabodies, tetra-bodies), minibodies, chelate recombinant antibodies, tribodies 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 "complementary determining region" or "CDR" refers to short polypeptide sequences within the variable regions of both the heavy and light chain polypeptides that primarily play a role in mediating specific antigen recognition. The term "framework region" refers to the amino acid sequences within the variable regions of both the heavy and light chain polypeptides that primarily play a role in maintaining the correct positioning of the CDR sequences and enabling antigen binding, rather than being CDR sequences themselves. The framework region itself is not normally, as is known in the art, directly involved in antigen binding, although specific residues within the framework region of a particular antibody can be directly involved in antigen binding or one or more amino acids within the CDR can affect the ability to interact with the antigen. As such, although not directly involved in antigen binding, specific residues within the framework region of a particular antibody can be directly involved in antigen binding or one or more amino acids within the CDR can affect the ability 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 formulations comprising (a) a compound or a pharmaceutically acceptable salt thereof, and (b) a pharmaceutically acceptable carrier. The compounds can also be used in pharmaceutical formulations comprising one or more other pharmaceutical active ingredients, or in pharmaceutical formulations where the compound or its pharmaceutically acceptable salt present is the sole active ingredient. Accordingly, the pharmaceutical formulations of the present disclosure include any formulation 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 drug delivery devices. Pharmaceutically acceptable salts include, for example, acid addition salts and basic salts. Acid addition salts include, for example, HCl or HBr salts. Basic salts include, for example, alkali or alkaline earth metals such as Na+, or K+, or Ca2+, or ammonium ions N+(R1)(R2)(R3)(R4) (wherein R1 to R4 are each independently: hydrogen, optionally substituted C1-C6-alkyl group, optionally substituted C2-C6-alkenyl group, optionally substituted C6-C10-allyl group, or optionally substituted C6-C10-heteroaryl group). Further examples of pharmaceutically acceptable salts are known to those skilled in the art.

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

[0064] Those skilled in the art will understand that various modifications (such as adjustments, additions, or deletions) of the substances, formulations, devices, methods, systems, devices, and various components of the embodiments described herein can be made without departing from the full scope and spirit of the concepts of the invention that include such modifications and any equivalents thereof.

[0065] Some 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 also within the scope of the following claims.

Explanation of Signs

[0066] 100 Injection device 102 Cartridge 104 Cartridge housing 105 Distal end of the cartridge Proximal end of the cartridge 108 Stopper 109 Reflective material 110 Housing 111 Injection button 112 Dosage knob 113 Dosage window 114 Needle 115 Needle hub 116 Inner needle cap 117 Outer needle cap 118 Cap 119 Aperture 120 Electronic device 202 Emitter 204 Receiver 206 Signal 208 Reflection 210 Microcontroller 300 Stopper 302 Shell 304 Core 306a Power supply 306b Wireless transceiver 306c Transmitter 308 Integrated sealing element 350 Cartridge 400 Cartridge 402 Emitter 404 Receiver 412 Energy source 414a Electronic lead wire 414b Electronic lead wire 420 Electronic device 440 Cartridge housing 442 Protrusion 450 Microcontroller 500 Longitudinal axis 600 Computer system 610 Processor 620 Memory 630 Storage device 640 Input / output device 650 System bus

Claims

1. An injection device (100), comprising: a cartridge (102) configured to hold a volume of fluid and having a proximal end (106) and a distal end (105) through which the fluid is dispensed; a stopper (108) disposed within the cartridge (102) and configured to move from the proximal end (106) to the distal end (105) such that fluid is dispensed through the distal end (105) of the cartridge (102); an electronic device (120) disposed at the distal end (105) of the cartridge (102); wherein the electronic device includes an emitter (202) configured to transmit a signal (206) towards the stopper (108), a receiver (204) configured to receive a reflection (208) of the signal (206) from the stopper (108), and a controller (210) configured to wirelessly transmit data related to the position of the stopper (108) within the cartridge (102). The injection device as described above.

2. The injection device (100) according to claim 1, wherein the cartridge (102) includes a material that allows the signal (206) and the reflection (208) of the signal (206) to pass through.

3. The injection device (100) according to claim 2, wherein the material includes a transparent material.

4. The injection device (100) according to any one of claims 1 to 3, wherein the emitter (202) is an acoustic device and the signal (206) includes acoustic waves.

5. The injection device (100) according to any one of claims 1 to 4, wherein the emitter (202) is an ultrasonic emitter and the signal (206) includes ultrasonic waves.

6. The injection device (100) according to any one of claims 1 to 5, wherein the emitter (202) is an optical emitter and the signal (206) includes light waves.

7. The injection device (100) according to any one of claims 1 to 6, wherein the electronic device (120) is integrated with the cartridge housing (104) of the injection device (100).

8. The injection device (100) according to any one of claims 1 to 6, wherein the electronic device (120) is removable from the cartridge housing (104) of the injection device (100).

9. The injection device (100) according to claim 8, wherein the electronic device (120) is configured to be clipped to the cartridge housing (104) of the injection device.

10. The electronic device (120) includes a battery (412) electrically connectable to the electronic device (120), and is the injection device (100) according to any one of claims 1 to 9.

11. The injection device (100) according to claim 10, wherein the battery (412) is disposed in the housing (110) of the injection device.

12. The injection device (100) according to claim 11, wherein the battery (412) is electrically connected to the electronic device (120) by electronic lead wires (414a, 414b) disposed in the cartridge housing (104).

13. The injection device (100) according to any one of claims 1 to 12, wherein the electronic device (120) includes a memory configured to store data related to the position of the stopper (108).

14. The injection device (100) according to claim 13, wherein the controller (210) is configured to calculate the volume of the fluid dosed based on data related to the position of the stopper (108).

15. The injection device (100) according to any one of claims 1 to 14, containing a fluid, the fluid containing a drug.

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