Determining injection status

Abstract

To provide a medication device determining a state of injection of medicine administered by an injection device.SOLUTION: An electronic device 104 includes: a housing 203 to be fitted to an injection device 102; a first sensor assembly including a first coil and two magnets of the opposite polarities in which the first coil is configured to provide first voltage pulse when a first Wiegand wire 224 of the injection device 102 moves from a first position close to one of the magnets of the first sensor assembly to a second position close to the other magnet of the first sensor assembly; and one or more processors configured to enter a usable state from a sleep state after receiving first voltage pulse from the first coil.SELECTED DRAWING: Figure 2

Description

[Technical field]

[0001] The present disclosure relates to determining the status of an injection, and more particularly, to determining the status of an injection of a medication administered by an injection device. [Background technology]

[0002] Various diseases can be treated by injection of medication. Such injections can be performed using an injection device, which is applied by a medical professional or by the patient himself. As an example, type I and type II diabetes can be treated by the patient himself injecting a dose of insulin, for example, by one or several injections per day. For example, a disposable pre-filled insulin pen or auto-injector can be used as the injection device. Alternatively, a reusable pen or auto-injector can be used. In a disposable or reusable pen or auto-injector, the empty medication cartridge can be replaced with a new medication cartridge. Both types of pens or auto-injectors come with a set of disposable needles that are replaced before each use. Summary of the Invention [Means for solving the problem]

[0003] In one embodiment, the electronic device includes a housing for mounting to the injection device and a first sensor assembly. The first sensor assembly includes a first coil and two magnets of opposite polarity. The first coil is configured to provide a first voltage pulse when a first Wiegand wire of the injection device moves from a first position close to one magnet of the first sensor assembly to a second position close to the other magnet of the first sensor assembly. The electronic device further includes one or more processors configured to enter an enabled state from a sleep state after receiving the first voltage pulse from the first coil.

[0004] Implementations may include one or more of the following features.

[0005] In some embodiments, the one or more processors consume no power when the one or more processors are in a sleep state.

[0006] In some embodiments, the one or more processors are configured to process data when the one or more processors are enabled.

[0007] In some embodiments, the one or more processors are configured to receive a first voltage pulse from the first coil, wherein a time of receipt of the first voltage pulse indicates a start time of injection of the medicament by the injection device.

[0008] In some embodiments, the electronic device includes a second sensor assembly including a second coil and two magnets of opposite polarity. The second coil is configured to provide a second voltage pulse when a second Wiegand wire of the injection device moves from a first position close to one magnet of the second sensor assembly to a second position toward the other magnet of the second sensor assembly. The one or more processors are configured to receive the second voltage pulse from the second coil. The time of receipt of the second voltage pulse indicates the end of the injection.

[0009] In some embodiments, the first Wiegand wire and the second Wiegand wire each comprise an outer shell and an inner core, the coercivity of the outer shell being greater than the coercivity of the inner core.

[0010] In some embodiments, the first voltage pulse and the second voltage pulse each have a magnitude that meets a predetermined threshold.

[0011] In some embodiments, the first Wiegand wire is secured to a needle shield of the injection device and the second Wiegand wire is secured to a drive mechanism of the injection device.

[0012] In some embodiments, the first sensor assembly is located near the needle shield and the second sensor assembly is located near the drive mechanism.

[0013] In some embodiments, a first voltage pulse is provided when the needle shield moves from the extended position to the retracted position, and a second voltage pulse is provided when the drive mechanism is substantially extended.

[0014] In some embodiments, the time of receipt of one or both of the time of receipt of the first voltage pulse and the time of receipt of the second voltage pulse are stored in one or more non-transitory computer readable media.

[0015] In some embodiments, the one or more non-transitory computer-readable media includes non-volatile memory configured to store data without a continuous power source.

[0016] In some embodiments, the memory is a ferroelectric random access memory (FRAM).

[0017] In some embodiments, the one or more processors are configured to transmit to the computing device one or both of the receipt time of the first voltage pulse and the receipt time of the second voltage pulse.

[0018] In some embodiments, one or both of the time of receipt of the first signal and the time of receipt of the second signal are transmitted wirelessly.

[0019] In some embodiments, the receipt time of one or both of the receipt time of the first signal and the receipt time of the second signal are transmitted via a Universal Serial Bus (USB) interface.

[0020] In some embodiments, the housing is sleeve-shaped and configured to surround and removably attach to an outer housing of the injection device.

[0021] In another embodiment, the system includes an injection device including a needle shield. A Wiegand wire is secured to the needle shield. The system further includes an electronic device for mounting to the injection device. The electronic device includes a sensor assembly including a coil and two magnets of opposite polarity. The coil is configured to provide a voltage pulse when the Wiegand wire moves from a first position near one magnet to a second position near the other magnet. The electronic device further includes one or more processors configured to enter an enabled state from a sleep state after receiving a voltage pulse from the coil.

[0022] In another embodiment, the system includes a variable dose injection device including a dosage knob and a plurality of Wiegand wires positioned around a periphery of the dosage knob. Each Wiegand wire corresponds to an increment in a dosage of a medication injected by the variable dose injection device. The system further includes an electronic device configured to attach to the variable dose injection device. The electronic device includes a sensor assembly including a coil and two magnets of opposite polarity. The coil is configured to provide a voltage pulse for each of the plurality of Wiegand wires moving from a first position near one magnet to a second position near the other magnet. The electronic device further includes one or more processors configured to receive the voltage pulses and increment a counter each time a voltage pulse is received. The value stored by the counter corresponds to a dosage of a medication injected by the variable dose injection device.

[0023] In another embodiment, the method includes receiving, by an electronic device configured to attach to the injection device, a voltage pulse from a coil of the sensor assembly when a Wiegand wire of the injection device moves from a first position to a second position. The first position is near one magnet corresponding to the sensor assembly, and the second position is near another magnet corresponding to the sensor assembly. The magnets have opposite polarities. The method further includes entering an enabled state from a sleep state by the electronic device after receiving the voltage pulse from the coil. [Brief description of the drawings]

[0024] [Figure 1] FIG. 1 illustrates an example of a system for activating an injection device and / or determining the status of an injection of a medication. [Diagram 2] FIG. 2 shows an example of the injection device of FIG. 1. [Diagram 3] FIG. 3 illustrates an example of an add-on device of FIGS. 1 and 2. [Figure 4] FIG. 2 illustrates an example of a block diagram of a first sensor assembly and a second sensor assembly of an add-on device. [Diagram 5] 5A-D show various positions of a first Wiegand wire of an injection device relative to a first sensor assembly. [Figure 6] 6A-C are diagrams illustrating various positions of a second Wiegand wire of an injection device relative to a second sensor assembly. [Figure 7] 1 is a flow diagram of an exemplary process for determining a status of an injection of a medication. [Figure 8] FIG. 1 is a block diagram of an exemplary computer system. DETAILED DESCRIPTION OF THE PREFERRED EMBODIMENTS

[0025] Like reference numbers in the various drawings indicate like elements.

[0026] Described herein is a drug delivery device configured to identify events related to a drug injection, such as, among others, a start time of an injection, an end time of an injection, and a hold time of an injection. The drug delivery device may include an add-on device including various components and electronic circuitry configured to identify such events based on an interaction with a Wiegand wire fixed to and / or incorporated into a component of the drug delivery device. A Wiegand wire is a wire including an outer shell and an inner core, where the coercive force of the outer shell is greater (e.g., significantly greater) than the coercive force of the inner core. The Wiegand wire exhibits a relatively large magnetic hysteresis that generates a voltage pulse / spike in the coil of the add-on device when a magnetic threshold is reached (e.g., when the Wiegand wire is located at a particular position relative to the magnet of the add-on device).

[0027] In some implementations, this voltage pulse can wake up the add-on device (e.g., "wake up" it from a sleep state and make it available). For example, initially, the add-on device may be placed in a sleep state in which the add-on device consumes little or no power. After receiving a voltage pulse, the add-on device may wake up such that the electronic circuitry of the add-on device enters a state in which the electronic circuitry can process data and / or signals from one or more electrical components (e.g., a sensor of the add-on device, a separate sensor, etc.).

[0028] In some embodiments, the needle shield of the drug delivery device can include a first Wiegand wire, and the add-on device can be configured to determine the position of the first Wiegand wire (and thus the position of the needle shield) at various times. The determined position of the needle shield at a first time can be used to determine the start time of the injection, and the determined position of the needle shield at a second time can be used to determine the hold time of the injection. Similarly, the drive mechanism of the drug delivery device can include a second Wiegand wire, and the add-on device can be configured to determine the position of the second Wiegand wire (and thus the position of the drive mechanism) at various times. The determined position of the drive mechanism at a third time can be used to determine the end time of the injection.

[0029] The subject matter described herein is primarily described with respect to drug delivery devices, such as injection devices (e.g., insulin injection devices), such as disposable or reusable injection devices. However, the systems and techniques described herein are not limited to such applications and can be equally advantageously deployed with injection devices that release other medications or other types of medical devices (e.g., pumps). In other words, the systems and techniques described herein can be used to enable electronic circuitry in other devices and / or to record information about injections by other devices.

[0030] The term "drug delivery device" encompasses any type of device or system configured to administer a volume of a drug to the human or animal body. This volume can typically range from about 0.5 ml to about 10 ml. Drug delivery devices can include, but are not limited to, 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).

[0031] In combination with a particular drug, the devices described herein can also be customized to operate within required parameters, for example, within a certain period of time (e.g., about 3 to about 20 seconds for a syringe, about 5 to about 60 minutes for an LVD), or with low or minimal levels of discomfort, or within certain conditions related to human factors, shelf life, expiration, biocompatibility, environmental considerations, etc. Such variations can result from a variety of factors, such as, for example, a drug having a viscosity ranging from about 3 cP to about 50 cP.

[0032] The drug or agent can be contained in a primary package or "drug container" adapted for use with a drug delivery device. The drug container can be, for example, a cartridge, syringe, reservoir, or other container configured to provide a suitable chamber for storing (e.g., short-term or long-term storage) one or more pharma- ceutically 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 chambers can be designed to store the drug for between one month and about two years. Storage can be at room temperature (e.g., about 20° C.) or at cold temperature (e.g., about −4° C. to about 4° C.). In some cases, the drug container can be or include a two-chamber cartridge configured to separately store two or more components of a drug formulation (e.g., a drug and a diluent or two different types of drugs), one in each chamber. In such cases, the two chambers of the two-chamber cartridge can be configured to allow mixing of two or more components of a drug or agent prior to and / or during administration to the human or animal body. For example, the two chambers can be configured such that the two chambers are in fluid communication with each other (e.g., by a conduit between the two chambers) and to allow mixing of the two components when desired by a user prior to administration. Alternatively or additionally, the two chambers can be configured to allow mixing when the components are being administered to the human or animal body.

[0033] FIG. 1 is an example of a system 100 for waking up an injection device and / or determining a status of an injection of a medication. The system 100 includes an injection device 102 and an add-on device 104 that can be removably attached to the injection device 102. The injection device 102 can be a disposable or reusable pre-filled injection pen configured to hold a medication and dispense the medication to a patient. The add-on device 104 can be an electronic device (e.g., a computing device). The system 100 can be used, for example, to determine a status of an insulin injection administered by the injection device 102 using the add-on device 104. The status information can include a start time of the injection, an end time of the injection, a hold time of the injection, etc. Based on the start time, end time and / or hold time, additional status information can be determined, such as a duration of the injection, among others. Such status information can be used to record a history of one or more injections provided by the injection device 102.

[0034] In general, the injection device 102 enables the selection and administration of a selected dosage of a medication to a patient. With the add-on device 104 attached to the injection device 102, the dosage of the medication can be administered. The add-on device 104 is configured to identify various events and / or conditions of the injection device 102 and the corresponding times at which those events / conditions occurred based on interactions between components of the add-on device 104 and the injection device 102. For example, the add-on device 104 may be configured to determine a start time of an injection by identifying a time when the needle shield (220 in FIG. 2) of the injection device 102 is retracted (retraction of the needle shield means, for example, that the injection device 102 has been or is being pressed against the patient's skin); the add-on device 104 may be configured to determine an end time of an injection by identifying a time when the drive mechanism (206 in FIG. 2) of the injection device 102 is substantially extended (substantial extension of the drive mechanism means, for example, that the medicament has been substantially released); the add-on device 104 may be configured to determine a hold time of an injection by identifying a time when the needle shield 220 of the injection device 102 is extended (extension of the needle shield means, for example, that the injection device 102 has been or is being removed from the patient's skin).

[0035] 2 is an exploded view of an example of the injection device 102 of FIG. 1. The injection device 102 can be a disposable or a reusable pre-filled injection pen. The injection device 102 includes a housing 203 and a cartridge 204. The cartridge 204 is configured to hold a volume of a medication (e.g., in a fluid form). In some embodiments, the cartridge 204 is a medication container, such as an insulin container. In some embodiments, the cartridge 204 is configured to hold a volume of a medication (e.g., in a fluid form). ... In such a manner, a portion of the cartridge 204 may be located within the housing 203 and / or within the cartridge housing 205 of the injection device 102 and therefore may not be directly visible.

[0036] The injection device 102 includes a drive mechanism 206 configured to expel the medicament from the cartridge 204. The drive mechanism 206 includes a stopper 207 movably disposed within the cartridge 204 and a piston 208 (e.g., a plunger arm). The piston 208 is configured to move the stopper 207 from a distal end of the cartridge 204 toward a proximal end of the cartridge 204, thereby causing fluid to be dispensed through the proximal end of the cartridge 204. The injection device 102 further includes a needle assembly 215 disposed at the proximal end of the cartridge 204. The needle assembly 215 includes an opening through which fluid is dispensed. A needle 209 can be fixed near the opening of the needle assembly 215 such that fluid moves through the opening and the needle 209 when dispensed. In some embodiments, the needle assembly 215 and / or the needle 209 are threaded so that the needle 209 can be screwed onto the needle assembly 215. In some embodiments, the cartridge 204 is threaded so that the needle assembly 215 can be threadedly attached to the cartridge 204 .

[0037] The needle 209 can be protected by a needle shield 220 that prevents inadvertent contact with the needle 209. The needle shield 220 is a tubular structure located within the housing 203 along the length of the injection device 102. The needle shield 220 can be configured to move between an extended position and a retracted position. In the example shown in FIG. 2, the needle shield 220 is in an extended position to minimize and / or prevent inadvertent contact with the needle 209. The needle shield 220 is typically configured to remain in the extended position by default (e.g., with no pressure applied to the needle shield 220). The needle shield 220 is configured to move from the extended position toward the retracted position when the injection device 102 (and, for example, the needle shield 220 in particular) is pressed against and pressure is applied toward the patient's skin, thereby causing the needle 209 to be inserted into the patient's skin. In some embodiments, the needle shield 220 can have a retractable configuration that allows the needle shield 220 to retract into the housing 203 of the injection device 102 when pressure is applied.

[0038] By turning the dosage knob 212, a dosage of the drug (e.g., a dose of insulin) to be released from the injection device 102 can be selected, and the dosage window 213 can display the selected dosage. In some examples, the dosage window 213 is a display device, such as an electronic display device. In some examples, the selected dosage can be displayed in multiples of international units (IU), with 1 IU being the biological equivalent of approximately 45.5 micrograms (e.g., 1 / 22 mg) of a drug, such as pure crystalline insulin. An example of a selected dosage displayed in the dosage window 213 can be, for example, 30 IU, as shown in FIG. 2. In some examples, the selected dosage can be displayed in a different manner, for example, by a non-electronic display device. In some examples, the dosage window 213 relates to a section of the injection device 102 through or on which the selected dosage can be viewed.

[0039] Turning the dosage knob 212 may produce a mechanical click sound providing audio feedback to the user. The numbers displayed in the dosage window 213 are printed on a sleeve contained in the housing 203, which mechanically interacts with the drive mechanism 206. Insertion of the needle 209 into an area of ​​the patient's skin and then pressing the injection button 211 expels medication from the injection device 102. Expulsion of a dose also produces a mechanical click sound. Such a mechanical clicking sound may be different from the sound produced when the dosage knob 212 is turned.

[0040] The injection device 102 can be used to perform multiple injection processes until the cartridge 204 is empty or until the expiration date of the injection device 102 is reached (e.g., 28 days after first use). In some examples, before using the injection device 102 for the first time, it may be necessary to perform a "prime shot" to remove air from the cartridge 204 and needle 209, for example, by selecting two units of medication and pressing the injection button 311 while holding the injection device 102 with the needle 209 pointing up.

[0041] The injection device 102 may include one or more components affixed to and / or integrated with respective corresponding components of the injection device 102 configured to interact with the add-on device 104. For example, the one or more components may be configured to wirelessly communicate with and / or provide a wireless signal to the add-on device 104, and the add-on device 104 may be configured to wake up from a sleep state to an enabled state and / or to determine the location of the respective corresponding component of the injection device 102 based on characteristics of the wireless signal.

[0042] In the example shown in FIG. 2, a first Wiegand wire 224 is provided on the needle shield 220 (e.g., fixed to the needle shield 220), and a second Wiegand wire 226 is provided on the drive mechanism 206, in particular the piston 208 of the drive mechanism (e.g., fixed to the drive mechanism 206, in particular the piston 208 of the drive mechanism). The Wiegand wires 224, 226 each include an outer shell and an inner core. The coercivity of the outer shell is greater (e.g., significantly greater) than the coercivity of the inner core. Thus, the Wiegand wires 224, 226 exhibit a relatively large magnetic hysteresis. When a magnet is brought close to the Wiegand wires 224, 226, the high coercivity outer shell largely rejects the magnetic field from the low coercivity inner core until a certain magnetic threshold is reached. When the magnetic threshold is reached, the overall magnetization polarity of the Wiegand wires 224, 226 rapidly switches. This phenomenon is sometimes referred to as the Wiegand effect.

[0043] When the magnetization polarity of the inner core switches while the magnetization polarity of the outer shell remains the same, a voltage spike (e.g., a relatively large voltage spike in some examples) is induced in a nearby coil (e.g., a sensor coil). The magnitude of the induced voltage is proportional to the switching speed. Because the switching speed of the Wiegand wires 224, 226 is relatively fast (e.g., a few microseconds) compared to the switching speed that would be obtained with a wire having a relatively small magnetic hysteresis, the induced voltage spike is relatively large and can be more easily detected electronically. Once the magnetization polarity of the entire Wiegand wires 224, 226 (e.g., both the inner core and the outer shell) switches, the Wiegand wires 224, 226 retain that polarity until they are switched in the opposite direction (e.g., by introducing a magnetic field of opposite polarity that meets a magnetic threshold). When the magnetization polarity of the inner core switches again, a second voltage spike is induced in the nearby coil. The second voltage spike may have a polarity opposite to that of the first voltage spike.

[0044] 2, each of the Wiegand wires 224, 226 is located on a movable component of the injection device 102. For each Wiegand wire 224, 226, a sensor coil and a magnet of opposite polarity are positioned in a fixed position relative to the corresponding respective Wiegand wire 224, 226 such that movement of the corresponding component of the injection device 102 causes the corresponding respective Wiegand wire 224, 226 to transition from a magnetic field of a first polarity to a magnetic field of a second polarity, thereby inducing a voltage spike in the corresponding coil. The sensor coil and magnet can be placed at a location on the injection device such that, based on the time at which the voltage spike occurs, the location of the corresponding component of the injection device can be inferred, as will be explained in more detail below. In some implementations, the sensor coil and magnet can be integrated into the add-on device 104.

[0045] Figure 3 shows an example of the add-on device 104 of Figures 1 and 2. The add-on device 104 includes a housing 302 configured to attach (e.g., removably attach) to the injection device 102. In some embodiments, the add-on device 104 has the shape of a sleeve (e.g., the shape of a cylinder) configured to slide along the length of the injection device 102 and surround the housing 203 of the injection device 102 to be fixed in place.

[0046] The add-on device 104 includes a first sensor assembly 304, a second sensor assembly 306, and a microcontroller 308, which may include one or more processors and one or more memory devices. In some embodiments, the one or more memory devices include one or more non-transitory computer-readable media having instructions stored thereon operable to cause the one or more processors to perform operations. The first sensor assembly 304 is positioned such that, when the add-on device 104 is attached to the injection device, the first sensor assembly 304 is located near the first Wiegand wire 224 of the needle shield 220 of the injection device 102, and the second sensor assembly 306 is positioned such that, when the add-on device 104 is attached to the injection device, the second sensor assembly 306 is located near the second Wiegand wire 226 of the drive mechanism 206 of the injection device 102. This will be described in more detail below. The one or more processors of the microcontroller 308 are configured to receive signals from the first sensor assembly 304 and the second sensor assembly 306 .

[0047] In some cases, the add-on device 104 includes a display device 310 configured to present information, such as date / time information, and / or instructions to assist the patient in operating the injection device 102. For example, the display device 310 can be configured to present the current date / time, the date / time the injection was administered, instructions to assist the patient in starting, maintaining, and / or completing the injection, etc.

[0048] The add-on device 104 may include a power source such as a battery 312, e.g., a coin cell type battery. To transfer data from the add-on device 104 to one or more other computing devices, the add-on device may further include a data communication interface 314, such as a universal serial bus (USB) interface. In some implementations, the add-on device may be configured to wirelessly communicate with one or more other computing devices by other means, such as a short-range wireless protocol (e.g., Bluetooth).

[0049] FIG. 4 illustrates an example block diagram of the first and second sensor assemblies 304, 306 of FIG. 3. Each of the sensor assemblies 304, 306 includes a first magnet 402a, 402b having a first polarity and a second magnet 404a, 404b having a second (e.g., opposite) polarity. In some implementations, the first magnet 402a, 402b has a North polarity and the second magnet 404a, 404b has a South polarity. Each of the sensor assemblies 304, 306 further includes a coil 406a, 406b (e.g., a sensor coil). In response to a change in the magnetic field, a coil 406a, 406b (e.g., a corresponding respective Wiegand wire 324, 326) is moved from a first position near one magnet to a second position near the other magnet. When moved to the second position, a voltage pulse / spike (caused by the transition of each corresponding Wiegand wire 324, 326 from a magnetic field of a first polarity to a magnetic field of a second polarity) can be induced.

[0050] 5A-D show various positions of the first Wiegand wire 224 of FIG. 2 relative to the first sensor assembly 304. These figures show a front view of the injection device 102. For clarity, these figures are not drawn to scale in order to focus on the portions of the system 100 that are relevant to this accompanying description. Additionally, these figures omit the housing 302 and other components of the add-on device 104.

[0051] In FIG. 5A, the needle shield 220 is in an extended position. To prevent inadvertent contact with the needle 209, the needle shield 220 may be in the extended position by default (e.g., with no pressure applied to the needle shield 220). The state of the injection device 102 shown in FIG. 5A may correspond to a time before the injection of the medication begins. When the needle shield 220 is in the extended position, the first Wiegand wire 224 of the needle shield 220 is substantially aligned with the first magnet 402a of the first sensor assembly 304. In the illustrated position, the first Wiegand wire 224 is saturated with a magnetic field having a first polarity (e.g., N polarity). That is, the magnetic field provided by the first magnet 402a when the first Wiegand wire 224 is in the illustrated position meets a magnetic threshold that orients the polarities of the outer shell and inner core of the first Wiegand wire 224 in the same direction. When the polarities of the outer shell and inner core remain oriented in the same direction (eg, when no switching of magnetization polarity occurs in the first Wiegand wire 224), no voltage spike is induced in the coil 406a.

[0052] In FIG. 5B, the needle shield 220 begins to move from the extended position to the retracted position. The state of the injection device 102 shown in FIG. 5B may correspond to the time when the patient begins to push the needle 209 into his / her skin. Such time may indicate the start time of the injection of the medication. As the needle shield 220 retracts, the first Wiegand wire 224 is introduced into a magnetic field having an opposite second polarity (e.g., S polarity) provided by the second magnet 404a. As the needle shield 220 continues to retract and the first Wiegand wire 224 moves closer to the second magnet 404a, the strength of the S polarity magnetic field increases until it reaches a magnetic threshold at which the magnetization polarity of the inner core switches. Such switching induces a voltage spike in the coil 406a. The coil 406a may provide a signal (e.g., including a voltage spike) to the microcontroller 308 of the add-on device 104. In some embodiments, this signal is provided to an analog-to-digital (A / D) converter, which provides a digital signal to the microcontroller 308. The time of receipt of this signal indicates the start of the injection, which can be recorded if the voltage spike meets a predetermined threshold.

[0053] In some implementations, the add-on device 104 may be placed in a sleep state before injection begins. For example, the add-on device 104 (including, e.g., the microcontroller 308) may be placed in a state in which the add-on device 104 consumes little or no power. As described above, the state of the injection device 102 (e.g., shown in FIG. 5B ) when the needle shield 220 begins to move from the extended position to the retracted position may correspond to the time when the patient begins to push the needle 209 into his or her skin. At such time, it may be desirable for the add-on device 104 to “wake up” (e.g., enter an available state from a sleep state). Upon waking up, the electronic circuitry of the add-on device 104 may enter a state in which the electronic circuitry can process data and / or signals from one or more electrical components.

[0054] The voltage spike induced in the coil 406a can cause the add-on device 104 to enter an enabled state. Specifically, the coil 406a can provide this voltage spike to the microcontroller 308, which can cause the microcontroller 308 to enter an enabled state. In some implementations, this voltage spike can be provided to a switching circuit (e.g., an interval switch circuit), which can cause the microcontroller 308 to enter an enabled state. In some implementations, this voltage spike can be provided to an interval switch via a voltage rectifier. The interval switch circuit can be an electronic relay. In some implementations, the interval switch circuit can be a transistor base emitter switch.

[0055] This voltage spike allows the microcontroller 308 (and, for example, the add-on device 104) to enter an enabled state for a predetermined period of time. For example, the microcontroller 308 may remain in the enabled state for 10-15 seconds to allow the injection to be completed and to allow information about the injection to be stored, as will be described in more detail below. While the microcontroller 308 is in the enabled state, data processing is supported by a power source (e.g., the battery 312). In some implementations, the microcontroller 308 may remain in the enabled state until a second voltage pulse (e.g., corresponding to the end of the injection) is received by the microcontroller 308, as will be described in more detail below.

[0056] In FIG. 5C, the needle shield 220 continues to move to a further retracted position. The state of the injection device 102 shown in FIG. 5C may correspond to a time during which the patient holds the injection device 102 against his / her skin (e.g., while completing an injection). As the needle shield 220 continues to retract, the first Wiegand wire 224 substantially aligns with the second magnet 404a. As the retraction continues, the strength of the south polarity magnetic field increases until it reaches a magnetic threshold at which the magnetization polarity of the outer shell switches to the same magnetization polarity as that of the inner core. Such switching induces a voltage spike in the coil 406a. Such a voltage spike may be significantly smaller than the voltage spike generated in the arrangement shown in FIG. 5B. The coil 406a may provide a signal (e.g., including a voltage spike) to the microcontroller 308 (e.g., via an A / D converter). However, in some implementations, the microcontroller 308 may be configured to ignore the signal if the magnitude of this voltage spike does not meet a predetermined threshold.

[0057] In FIG. 5D, the needle shield 220 begins to move from the retracted position toward the extended position. The state of the injection device 102 shown in FIG. 5D may correspond to the time when the patient begins to remove the injection device 102 from his / her skin. Such a time may indicate a holding time (e.g., end of holding). The holding time may represent a dwell time, such as the time the patient should continue to hold the injection device 102 at the injection site (e.g., against the skin) after the injection is completed and the medication is injected. Such a holding time may ensure that all the medication is injected. When the needle shield 220 is extended, the first Wiegand wire 224 is reintroduced into the magnetic field having a first polarity (e.g., north polarity) provided by the first magnet 402a. As the needle shield 220 continues to extend and the first Wiegand wire 224 moves closer to the first magnet 402a, the strength of the north polarity magnetic field increases until it reaches a magnetic threshold at which the magnetization polarity of the inner core switches. Such switching induces a voltage spike in the coil 406a. This voltage spike may have a similar magnitude and opposite polarity to the voltage spike generated in the arrangement shown in FIG. 5B. The coil 406a may provide a signal (e.g., including the voltage spike) to the microcontroller 308 (e.g., via an A / D converter). The time of receipt of this signal indicates the holding time. If the voltage spike meets a predetermined threshold, This time of receipt can be recorded.

[0058] 6A-C show various positions of the second Wiegand wire 226 of FIG. 2 relative to the second sensor assembly 306. These figures show a side view of the injection device 102. For clarity, these figures are not drawn to scale in order to focus on the portions of the system 100 that are relevant to this accompanying description. Additionally, these figures omit the housing 302 and other components of the add-on device 104.

[0059] In FIG. 6A, the drive mechanism 206 is in a substantially retracted position. The state of the injection device 102 shown in FIG. 6A may correspond to a time before the injection is initiated. For example, the stopper 207 of the drive mechanism 206 may be placed at the distal end of the cartridge 204 with the cartridge 204 containing a drug. When the drive mechanism 206 is in the retracted position, the second Wiegand wire 226 located on the piston 208 is substantially aligned with the second magnet 404b of the second sensor assembly 306. In the illustrated position, the second Wiegand wire 226 is saturated with a magnetic field having a second polarity (e.g., S polarity). That is, the magnetic field provided by the second magnet 404b when the second Wiegand wire 226 is in the illustrated position meets a magnetic threshold that orients the polarities of the outer shell and the inner core of the second Wiegand wire 226 in the same direction. When the polarities of the outer shell and inner core remain oriented in the same direction (eg, no switching of magnetization polarity occurs in the second Wiegand wire 226), no voltage spike is induced in the coil 406b.

[0060] In FIG. 6B, the drive mechanism 206 is in a substantially extended position. The state of the injection device 102 shown in FIG. 6B may correspond to a time when the injection is completed (e.g., the end of the injection). For example, after the needle 209 of the injection device 102 is inserted into the patient's skin (which corresponds, for example, to the position shown in FIG. 5C), the patient can press the injection button 211, which causes the piston 208 to push the stopper 207 toward the proximal end of the cartridge 204, thereby releasing the medicament. When the piston 208 is substantially extended, the second Wiegand wire 226 is introduced into the first magnetic field (e.g., having a north polarity) provided by the first magnet 402b. As the piston 208 extends, the strength of the north polarity magnetic field increases until it reaches a magnetic threshold at which the magnetization polarity of the inner core switches. Such switching induces a voltage spike in the coil 406b. The coil 406b can provide a signal (e.g., including a voltage spike) to the microcontroller 308 of the add-on device 104 (e.g., via an A / D converter). The time of receipt of this signal indicates the end of the injection. If the voltage spike meets a predetermined threshold, this time of receipt can be recorded.

[0061] The voltage spike induced in the coil 406b can cause the add-on device 104 to enter a sleep state. Specifically, the coil 406b can provide this voltage spike to the microcontroller 308, which causes the microcontroller 308 to enter the sleep state again from the enabled state. As described above, in some implementations, this voltage spike can be provided to a switching circuit. In some implementations, after receiving the voltage spike, the microcontroller 308 can remain in the enabled state for a certain amount of time (e.g., 5-10 seconds) before entering the sleep state again. Such a delay allows the injection to be completed and information about the injection to be stored.

[0062] In Figure 6C, the drive mechanism 206 has returned to a substantially retracted position. The state of the injection device 102 shown in Figure 6C may correspond to the injection device 102 being prepared to contain another dose of medication for a subsequent injection. For example, in some embodiments, the cartridge 204 may be refilled and the stopper 207 may be removed from the cartridge 204 in preparation for another injection. The second Wiegand wire 226 can be returned to the distal end of the ridge 204. In some embodiments, the cartridge 204 can be replaced with a new cartridge and the stopper 207 can be placed on the distal end of the new cartridge in preparation for another injection. When the drive mechanism 206 is returned to the retracted position, the second Wiegand wire 226 is substantially aligned with the second magnet 404b of the second sensor assembly 306. In the illustrated position, the second Wiegand wire 226 is again saturated with a south polarity magnetic field, so that the polarities of the outer shell and inner core of the second Wiegand wire 226 are again oriented in the same direction. In this way, the second Wiegand wire 226 is placed in a state where the magnetization polarity of the inner core can again be switched when the drive mechanism 206 is extended for a subsequent injection, thereby recording the end time of the subsequent injection.

[0063] The system 100 (e.g., the add-on device 104) is configured to determine a status of the injection of the medication based on the time of receipt of the signals described above with respect to FIGS. 5A-D and 6A-C. For example, the time of receipt of the signal described with respect to FIG. 5B can be identified and / or recorded as a start time of the injection; the time of receipt of the signal described with respect to FIG. 5D can be identified and / or recorded as a hold time (e.g., end of hold) of the injection; and the time of receipt of the signal described with respect to FIG. 6B can be identified and / or recorded as an end of the injection. Based on the start, end and / or hold times, additional status information, such as the duration of the injection, among others, can be determined. For example, the elapsed time between the start and end times can correspond to the duration of the injection. This status information can be used to record a history of one or more injections provided by the injection device 102. Such status information can be used to ensure patient compliance with a prescribed medication regimen and / or to correlate a patient's health status with the recorded injection times.

[0064] In some implementations, some or all of the state information can be stored by the microcontroller 308. For example, the state information can be stored in one or more memory devices of the microcontroller 308. In some implementations, the one or more memory devices include non-volatile memory, such as ferroelectric random access memory (FRAM), that does not require a continuous power source to store data. In other words, the non-volatile memory can be configured to store data without a continuous power source. Such memory can help the add-on device 104 conserve power, thereby facilitating long-term use. In addition to using a wake-up mechanism on the microcontroller 308 as described above, using FRAM can provide a low-power solution for the add-on device 104 that requires minimal battery capacity for long-term use.

[0065] In some implementations, some or all of the status information can be provided by the add-on device 104 to a separate device (e.g., a separate computing device). In some implementations, the status information can be transmitted to a connected computing device, such as a smartphone, laptop, etc., connected to the add-on device 104 via a data communication interface (e.g., a USB interface). In some implementations, the add-on device 104 can include a transceiver configured to transmit (e.g., wirelessly) the status information to a remote computing device, such as a server (e.g., a cloud server). In some implementations, the status information can be transmitted to a medical server and / or directly to a medical professional. In this manner, status information regarding the injection can be provided to a remote medical entity for analysis and / or further treatment recommendations.

[0066] FIG. 7 is a flow diagram of an example process 700 for determining a status of an injection of a medication from an injection device, such as the injection device 102 of FIGS. 1, 2, 5A-D, and 6A-C. 00 may be performed by components of an electronic device such as add-on device 104 of FIGS. 1, 3, 5A-D and 6A-C.

[0067] In step 702, a first signal is received when the first Wiegand wire 224 of the injection device 102 moves from a first position to a second position. For example, the first signal can be received by an electronic device configured to attach to the injection device 102. The first signal can be received from the coil 406a of the first sensor assembly 304 when the first Wiegand wire 224 moves from a first position near one magnet (e.g., the first magnet 402a) to a second position near another magnet (e.g., the second magnet 404a) having an opposite polarity to the first magnet 402a. The first Wiegand wire 224 can be fixed to the needle shield 220 of the injection device 102.

[0068] At step 704, a start time of injection of the medication is determined based on the time of receipt of the first signal. For example, this movement of the first Wiegand wire 224 may correspond to the needle shield 220 of the injection device 102 moving from an extended position to a retracted position. Such movement of the needle shield 220 may correspond to a time when the patient begins to push the needle 209 into their skin.

[0069] At step 706, a second signal is received when the second Wiegand wire 226 of the injection device 102 moves from a first position to a second position. For example, the second signal can be received by the electronic device from the coil 406b of the second sensor assembly 306 when the second Wiegand wire 226 moves from a first position near one magnet (e.g., the second magnet 404b) to a second position near another magnet (e.g., the first magnet 402b) having an opposite polarity to the magnet and the second magnet 404b. In some implementations, the second position is closer to the first magnet 402b than to the second magnet 404b. The second Wiegand wire 226 can be fixed to the drive mechanism 206 of the injection device 102.

[0070] At step 708, an end time of the injection is determined based on the time of receipt of the second signal. For example, movement of the second Wiegand wire 226 may correspond to the drive mechanism 206 of the injection device 102 being in a substantially extended position. Such movement of the drive mechanism 206 may correspond to the time that the medicament has been completely expelled from the cartridge 204.

[0071] In some implementations, a third signal is received when the first Wiegand wire 224 moves from the second position toward the first position. For example, the third signal can be received from the coil 406a of the first sensor assembly 304. The holding time of the injection is determined based on the time of receipt of the third signal.

[0072] In some embodiments, each of these signals includes a voltage spike whose magnitude meets a predetermined threshold, and in some embodiments, the sign of the voltage spike of the first signal is opposite to the sign of the voltage spike of the second signal.

[0073] Although certain implementations have been described herein, other implementations are possible.

[0074] Although the sensor assembly has been described as including two magnets, in some embodiments the magnets may be located in other parts of the system. For example, in some embodiments the magnets may be located on the injection device and / or in separate components of the system. The magnets may be coupled to corresponding Wiegand wires such that the Wiegand wires signal the corresponding coils of the sensor assembly as described with respect to FIGS. 5A-D and 6A-C. The magnets can be arranged to provide a signal (e.g., a voltage spike) to the coil of the injection device. In some embodiments, one or more of these magnets can be incorporated into the housing of the injection device. For example, a first magnet can be incorporated into the housing of the injection device at a position near the start position (e.g., default position) of one of the Wiegand wires, thereby saturating the Wiegand wire with a magnetic field of a first polarity. A second magnet can be incorporated into the housing of the injection device at a position near the target position (e.g., a position corresponding to the start time, end time and / or holding time of the injection) of one of the Wiegand wires. In this way, the Wiegand wire can generate a voltage spike in the corresponding coil when the Wiegand wire reaches the target position.

[0075] In some implementations, a Wiegand wire or magnet can be placed on the piston to record the time when the piston begins to move from the distal end of the cartridge towards the proximal end of the cartridge. Detection of such movement of the piston can be performed by the sensor assembly described above or by a separate sensor assembly.

[0076] Although the sensor assembly has been described as including a magnet and the injection device has been described as including a Wiegand wire, in some embodiments, a magnet can be disposed in the injection device and a Wiegand wire can be disposed in the sensor assembly (e.g., an add-on device). For example, one or more magnets can be incorporated into the needle shield and / or piston, with a corresponding Wiegand wire disposed adjacent to or within the coil of each corresponding sensor assembly. Such a configuration can generate a relatively large voltage spike (e.g., 3.5-5V) compared to a configuration in which a Wiegand wire is incorporated into the needle shield and piston (e.g., which can generate a voltage spike of less than 3.5V).

[0077] For implementations in which the voltage spike is primarily used to "wake up" the add-on device (e.g., to put it into an enabled state), a configuration that generates a relatively small voltage spike (e.g., less than 3.5V) may be sufficient. For example, when the voltage spike is used to put the add-on device into an enabled state (e.g., not to allow injection information to be stored), an implementation in which a Wiegand wire is incorporated into the needle shield and piston and a magnet is incorporated into the add-on device may be sufficient. Such a configuration may be desirable for such implementations because incorporating a Wiegand wire into an injection device may be easier (and, e.g., less expensive) than incorporating a magnet into an injection device. On the other hand, for implementations in which the voltage spike is used to allow injection information to be stored, a configuration that generates a relatively large voltage spike (e.g., 3.5-5V) may be desirable. This is because such a large voltage spike (e.g., a large output signal) may improve the detectability of the corresponding state of the injection device.

[0078] Although the sensor assembly or injection device has been described as including one or more magnets, in some embodiments, other magnetic materials may be used in addition to or instead of the magnets. For example, in some embodiments, rather than incorporating magnets in the needle shield and / or piston, the needle shield and / or piston itself may be partially magnetic. In some embodiments, the needle shield and / or piston may include a magnetized plastic material that exhibits a similar effect to that described above for the north and south pole magnets. In this way, a voltage spike may be induced in a corresponding coil when the magnetized plastic material is moved near that coil.

[0079] In some implementations, a variable dose injection device (e.g., the SoloSTAR® Pen manufactured by Sanofi®) can be configured to interact with a sensor assembly similar to the sensor assembly described above (e.g., sensor assembly 304). The variable dose injection device can be similar to the injection device 102 described above. For example, the sensor assembly can be used to detect and / or record a selected dose for injection by the variable dose injection device. In some implementations, the sensor assembly can be incorporated into a separate device (e.g., a separate add-on device) located near the dosage knob of the variable dose injection device. The separate add-on device can be substantially similar to the add-on device 104 described above with some modifications to the housing to facilitate attachment to an appropriate portion of the variable dose injection device. For example, the dosage knob can include multiple Wiegand wires each located around a perimeter of the dosage knob. The Wiegand wires can be positioned equidistant from each other such that each Wiegand wire corresponds to a dosage increment indicated on the dosage knob. Each Wiegand wire can be positioned on the dosage knob at a location that "clicks" when the dosage knob is rotated. In this way, each click can correspond to a dosage increment. In some examples, the dosage knob rotates in single increments of International Units (IU). Thus, for each click when the dosage knob is rotated, a separate Wiegand wire rotates closer to the sensor assembly. Each rotation of the Wiegand wire closer to the sensor assembly (e.g., when the Wiegand wire moves from a first position near one magnet to a second position near the other magnet) generates a voltage pulse in the coil. Each voltage pulse can increment a counter in the sensor assembly such that the value stored by the counter corresponds to the number of IUs of the dialed dosage. Such dosage information can be stored along with the start, end and holding times of the injection.

[0080] FIG. 8 is a block diagram of an exemplary computer system 800. For example, the add-on device 104 of FIGS. 1 and 3 can be an example of the computer system 800. In some implementations, the injection device 102 of FIGS. 1 and 2 can incorporate the computer system 800 and / or can be configured to interact with a separate computer system 800. The system 800 includes a processor 810, a memory 820, a storage device 830, and an input / output device 840. For example, a system bus 850 can be used to interconnect the respective components 810, 820, 830, and 840. The processor 810 can process instructions for execution within the system 800. The processor 810 can be a single-threaded processor, a multi-threaded processor, or a quantum computer. The processor 810 can process instructions stored in the memory 820 or the storage device 830. The processor 810 may perform operations to cause the add-on device 104 to determine the status of injection of the medication according to the process described above (eg, process 700 of FIG. 7).

[0081] The memory 820 stores information within the system 800. In some implementations, the memory 820 is a computer readable medium. The memory 820 can be, for example, a volatile or non-volatile memory unit. In some implementations, the memory 820 stores information regarding the status of an injection of a drug, such as time data indicating a start time of an injection, an end time of an injection, a holding time of an injection, a duration of an injection, etc.

[0082] The storage device 830 is capable of providing mass storage to the system 800. In some implementations, the storage device 830 is a non-transitory computer-readable medium. The storage device 830 may be, for example, a hard disk device, an optical disk device, a solid-state drive, or a The memory 820 may include a state drive, a flash drive, a magnetic tape, or some other mass storage device. Alternatively, the storage device 830 may be a cloud storage device, e.g., a logical storage device including multiple physical storage devices distributed over a network, accessed using a network. In some implementations, information stored on the memory 820 may also be stored on the storage device 830 or may be stored on the storage device 830 instead of the memory 820.

[0083] The input / output devices 840 provide input / output operations to the system 800. In some implementations, the input / output devices 840 include 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 short-range wireless communication device, an 802.11 card, a 3G wireless modem, or a 4G wireless modem). In some implementations, the input / output devices 840 include driver devices that receive input data and send output data to other input / output devices, such as keyboards, printers, and display devices. In some implementations, mobile computing devices, mobile communication devices, and other devices are used.

[0084] In some implementations, system 800 is a microcontroller. A microcontroller is a device that contains many elements of a computer system in a single electronic circuit package. For example, the single electronic circuit package can include a processor 810, a memory 820, a storage device 830, and an input / output device 840.

[0085] Although an exemplary processing system is illustrated in FIG. 8, embodiments of the subject matter and functional operations described above may be implemented in other types of digital electronic circuitry, or in computer software, firmware, or hardware, including the structures disclosed herein and their structural equivalents, or in a combination of one or more of these. Embodiments of the subject matter described herein may be implemented as one or more computer program products, e.g., as one or more modules of computer program instructions encoded on a tangible program carrier, e.g., a computer-readable medium, for execution by or control of the operation of a processing system. The computer-readable medium may be a machine-readable storage device, a machine-readable storage substrate, a memory device, a composition producing a machine-readable propagated signal, or a combination of one or more of these.

[0086] The term "computer system" may 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 may include code that creates an environment for the execution of the computer program, such as code that constitutes a processor firmware, a protocol stack, a database management system, an operating system, or a combination of one or more of these.

[0087] 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 deployed in any form, including a stand-alone program, or 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; it may contain other programs or data (e.g., one or more scripts stored in a markup language document). A program may be stored in part of a file, in a single file dedicated to that program, or in multiple files coordinated together (e.g., multiple files storing one or more modules, subprograms, or code portions). A computer program can be deployed to be executed on one computer or on multiple computers located at one site or distributed across multiple sites, interconnected by a communications network.

[0088] 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, e.g., EPROM, EEPROM and flash memory devices; magnetic disks, e.g., internal hard disks or removable disks or magnetic tapes; magneto-optical disks; and CD-ROM and DVD-ROM disks. The processor and memory can be supplemented by, or incorporated in, special purpose logic circuitry. The components of the system can 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"), e.g., the Internet.

[0089] The term "drug" or "medicament" is used herein to describe one or more pharma- ceutical active compounds. As described below, a drug or medicament may include at least one small molecule or macromolecule or combinations thereof in various types of formulations for the treatment of one or more diseases. Exemplary pharma- ceutical active compounds may include small molecules, polypeptides, peptides, and proteins (e.g., hormones, growth factors, antibodies, antibody fragments, and enzymes), carbohydrates and polysaccharides, as well as nucleic acids, double-stranded or single-stranded DNA (including naked and cDNA), RNA, antisense nucleic acids such as antisense DNA and RNA, small interfering RNA (siRNA), ribozymes, genes, and oligonucleotides. Nucleic acids may be incorporated into vectors, plasmids, or molecular delivery systems such as liposomes. Mixtures of one or more of these drugs are also contemplated.

[0090] The drug delivery devices and drugs according to the present invention can be used for the treatment and / or prevention of many different types of disorders. Exemplary disorders include, for example, diabetes or complications associated with diabetes, such as diabetic retinopathy, thromboembolic disorders, such as deep vein thromboembolism or pulmonary thromboembolism. Further exemplary disorders are acute coronary syndrome (ACS), angina, myocardial infarction, cancer, macular degeneration, inflammation, hay fever, atherosclerosis and / or rheumatoid arthritis.

[0091] 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 as to have substantially the same functionality or activity (e.g., therapeutic effect).

[0092] 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 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.

[0093] 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-ThrB29Lys B30 human insulin; B30-N-palmitoyl-ThrB29LysB30 human insulin; B29-N-(N-palmitoyl-gamma-glutamyl)-des(B30) human insulin; B29-N-(N-lithocholyl-gamma-glutamyl)-des(B30) human insulin; B29-N-(ω-carboxyheptadecanoyl)-des(B30) human insulin and B29-N-(ω-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 flathead monster), liraglutide / Victoza, semaglutide, taspoglutide, synclear / albiglutide, dulaglutide, rExendin-4, CJC-1134-PC, PB-1023, TTP-054, Langrena These include: cefotide / HM-11260C, CM-3, GLP-1 Erigen, ORMD-0901, NN-9924, NN-9926, NN-9927, nodexene, Viadol-GLP-1, CVX-096, ZYOG-1, ZYD-1, GSK-2374697, DA-3091, MAR-701, MAR709, ZP-2929, ZP-3022, TT-401, BHM-034, MOD-6030, CAM-2036, DA-15864, ARI-2651, ARI-2255, exenatide-XTEN and glucagon-Xten.

[0094] An exemplary oligonucleotide is, for example, the cholesterol-lowering antisense therapeutic mipomersen / quinamro for the treatment of familial hypercholesterolemia.

[0095] Exemplary DPP4 inhibitors are vidagliptin, sitagliptin, denagliptin, saxagliptin, berberine.

[0096] Exemplary hormones include pituitary or hypothalamic hormones or regulatory active peptides and their antagonists, such as gonadotropins (follitropin, lutropin, chorion gonadotropin, menotropin), somatropine (somatropin), desmopressin, terlipressin, gonadorelin, triptorelin, leuprorelin, buserelin, nafarelin, and goserelin.

[0097] Exemplary polysaccharides include glycosaminoglycans, hyaluronic acid, heparin, low molecular weight heparin or very low molecular weight heparin or derivatives thereof, or sulfated polysaccharides, such as the above-mentioned polysaccharides in polysulfated form, and / or their pharmaceutically acceptable salts.An example of a pharmaceutically acceptable salt of polysulfated low molecular weight heparin is enoxaparin sodium.An example of a hyaluronic acid derivative is Hylan G-F20 / Synvisc, sodium hyaluronate.

[0098] As used herein, the term "antibody" refers to an immunoglobulin molecule or an antigen-binding domain thereof. The term "antigen-binding portion" refers to a portion of an antibody that binds to an Fc receptor. Examples of antigen-binding portions of an immunoglobulin molecule include F(ab) and F(ab')2 fragments that retain the ability to bind to an antigen. The antibody can be a polyclonal antibody, a monoclonal antibody, a recombinant antibody, a chimeric antibody, a deimmunized or humanized antibody, a fully human antibody, a non-human (e.g., murine) antibody, or a single chain antibody. In some embodiments, the antibody has effector function and is capable of fixing complement. In some embodiments, the antibody has reduced or no ability to bind to an Fc receptor. For example, the antibody can be an isotype or subtype, antibody fragment, or mutant that does not support binding to an Fc receptor, e.g., has a mutation or deletion of the Fc receptor binding region.

[0099] The term "fragment" or "antibody fragment" refers to a polypeptide (e.g., antibody heavy and / or light chain polypeptide) derived from an antibody polypeptide molecule that does not include the full-length antibody polypeptide but comprises at least a portion of the full-length antibody polypeptide that is still capable of binding to an antigen. An antibody fragment can include truncated portions of a full-length antibody polypeptide, but the term is not limited to such truncated fragments. Antibody fragments useful in the present invention include, for example, Fab fragments, F(ab')2 fragments, scFv (single-chain Fv) fragments, linear antibodies, monospecific or multispecific antibody fragments, such as bispecific, trispecific, and multispecific antibodies (e.g., diabodies, triabodies, tetrabodies), minibodies, chelating recombinant antibodies, tribodies or bibodies, intrabodies, nanobodies, small modular immunopharmaceuticals (SMIPs), binding domain immunoglobulin fusion proteins, camelized antibodies, and VHH-containing antibodies. Additional examples of antigen-binding antibody fragments are known in the art.

[0100] The term "complementarity determining region" or "CDR" refers to short polypeptide sequences in the variable regions of both heavy and light chain polypeptides that are primarily responsible for mediating specific antigen recognition. The term "framework region" refers to amino acid sequences in the variable regions of both heavy and light chain polypeptides that are not CDR sequences and are primarily responsible for maintaining the proper arrangement of the CDR sequences to allow antigen binding. Although the framework region itself typically does not directly participate in antigen binding, as is known in the art, certain residues in the framework region of a particular antibody may be directly involved in antigen binding or may affect the ability of one or more amino acids in the CDR to interact with the antigen.

[0101] Exemplary antibodies are anti-PCSK-9 mAbs (e.g., alirocumab), anti-IL-6 mAbs (e.g., sarilumab), and anti-IL-4 mAbs (e.g., dupilumab).

[0102] The compounds described herein can be used in pharmaceutical preparations that include (a) the compounds or their pharmaceutically acceptable salts, and (b) pharmaceutically acceptable carriers.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 compounds or their pharmaceutically acceptable salts are the only active ingredient.Thus, the pharmaceutical preparations of the present disclosure encompass any preparation made by mixing the compounds described herein with a pharmaceutically acceptable carrier.

[0103] Pharmaceutically acceptable salts of any of the drugs described herein are 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 include, for example, salts of alkali or alkaline earth metals, such as Na+, or K+, or Ca2+, or ammonium ions N+(R1)(R2)(R3)(R4), where R1 to R4 are, independently of one another: hydrogen, an optionally substituted C1-C6-alkyl group, an optionally substituted aryl ... substituted C2-C6-alkenyl, optionally substituted C6-C10-aryl, or optionally substituted C6-C10-heteroaryl. Further examples of pharma- ceutically acceptable salts are known to those skilled in the art.

[0104] Pharmaceutically acceptable solvates are, for example, hydrates or alkanolates, such as methanolates or ethanolates.

[0105] Those skilled in the art will appreciate that modifications (e.g., adjustments, additions, or removals) of the various components of the materials, 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 includes such modifications and all equivalents thereof.

[0106] Although several implementations of the systems and techniques described herein have been presented, various modifications may be made without departing from the spirit and scope of such systems and techniques. Accordingly, other implementations are within the scope of the following claims.

Claims

1. A medical device (102) comprising: A housing (203); a rotatable component (212) configured to rotate relative to a housing (203) and including a plurality of Wiegand wires (224, 226), the plurality of Wiegand wires (224, 226) being equidistantly disposed around a periphery of the rotatable component (212); a Wiegand sensor (304, 306) including coils (406a, 406b) configured to generate a voltage pulse when a plurality of Wiegand wires (224, 226) of a rotatable component (212) rotates relative to a housing (203), the Wiegand sensor (304, 306) not moving relative to the housing when generating the voltage pulse, the voltage pulse indicating an incremental rotational position of the rotatable component (212) relative to the housing (203); The medical device comprising:

2. The medical device of claim 1 , wherein the medical device is a pump.

3. The medical device (102) of claim 1 or 2, wherein the rotatable component (212) is rotatably mounted to the housing (203).

4. The medical device (102) of any one of claims 1 to 3, wherein the Wiegand sensor (304, 306) is configured to detect a voltage pulse by sensing a change in voltage in a coil (406a, 406b) of the Wiegand sensor (304, 306).

5. 5. The medical device of claim 4, wherein the Wiegand sensor is configured to generate a voltage pulse while the coil is exposed to a magnetic field generated by one or more magnets of the Wiegand sensor.

6. The medical device (102) of any one of claims 1 to 4, wherein the Wiegand sensor (304, 306) is configured to generate a voltage pulse when the rotatable component (212) rotates from a first position proximate a first magnet of the Wiegand sensor (304, 306) to a second position proximate a second magnet of the Wiegand sensor (304, 306).

7. The medical device (102) of any one of claims 1 to 6, further comprising a processor (308) configured to determine a rotational position of the rotatable component (212) based on the voltage pulses.

8. The medical device of claim 7, wherein the processor is configured to determine a rotational position of the rotatable component based on a time at which the processor receives the voltage pulse signal.

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