Drug delivery device having an improved mechanism for controlling delivery rate

Abstract

A drug delivery device comprising a reservoir containing a fluid to be delivered from the device by advancing a piston in the reservoir at an advancement speed that defines a delivery rate for a medicament. An electric motor drives a delivery mechanism of the drug delivery device by rotating so as to advance the piston at the advancement speed. A control unit is configured to control the rotational speed and on / off state of the electric motor. The rotational speed of the electric motor is measured by operating the electric motor in a monitoring mode for detecting a back electromagnetic force signal, and the signal is sent to the control unit. The control unit controls the rotational speed of the electric motor so that the back electromotive force signal can be detected in the monitoring mode. In addition, the control unit adjusts the on / off state of the electric motor to control the delivery rate of the medicament through the outlet.

Description

Technical Field

[0001] The present invention relates to a drug delivery device, which includes a reservoir containing a fluid medicament to be delivered through an outlet in the reservoir by advancement of a piston using a delivery mechanism. The speed of advancement of the piston and the subsequent delivery rate through the outlet are controlled by a control unit, which controls the rotation speed of an electric motor driving the delivery mechanism. The back electromagnetic force (back electromotive force) signal of the electric motor is monitored by the control unit to measure the rotation speed of the electric motor or whether the electric motor is prevented from rotating due to an adverse event. Background Art

[0002] Injection and infusion devices are used for subcutaneous or IV delivery of liquid medications to patients to treat a wide variety of conditions, such as autoimmune diseases, chronic diseases such as diabetes, cancer, or hormone deficiencies.

[0003] The infusion device delivers the drug from the reservoir using a drive mechanism and a control mechanism that controls the advancement of a piston rod that abuts a movable plunger present in a cartridge containing the drug. The drug is delivered to the patient via a fluid path and an external infusion set including a needle for subcutaneous delivery. With such an infusion device, both continuous and intermittent drug delivery profiles can be programmed.

[0004] An injection device delivers a drug from a reservoir or prefilled syringe (PFS) using a drive mechanism for advancing a piston in the reservoir or PFS to expel the drug via a needle attached or attachable to the injection device. An injection device is preferably used to deliver a single dose, which may be a fixed dose or a variable dose. An injection device may be designed to deliver multiple single doses.

[0005] A patch device is an example of an infusion or injection device that can be attached to the patient's skin. Such a patch device does not require an external infusion set for delivery, because the needle is directly housed in the patch device and can be inserted into the patient from the patch device.

[0006] Depending on the treatment, the delivery rate for the medicament may change. For example, in the treatment of diabetes, the basal rate is delivered by the infusion device throughout the day and night, and a bolus injection is given for each meal. Even for the injection device (bolus syringe) that delivers a group of medicaments alone, the delivery rate and volume may also change based on age or disease severity. During the treatment for the patient, it may be required to modify the delivery rate of the medicament, because modern medicaments may require specific and time-dependent dosage regimens (dosage regimes). In addition, treatment based on high-viscosity medicaments (for example, based on macromolecules recovered from recombinant DNA sources) may require delivery at a low rate, because, otherwise, injection may be accompanied by pain, or the patient's body may not be able to absorb viscous medicaments. Treatment may be interrupted due to adverse events, and, therefore, the medicine of the expected amount cannot be delivered.

[0007] The drive mechanism for driving the piston in the injection or infusion device can be purely mechanically driven, for example using a coil or leaf spring, or the piston is driven by hydraulic (osmotic) pressure or by a pneumatic source or by a power source, which can be a volume change of a primary cell or an electric motor. The advantage of using an electric motor is that the rotational speed can be easily changed, and thus allows better control of the delivery rate compared to, for example, a purely mechanical or osmotic power source. The advantage of using an electric motor is that a transmission can be positioned between the motor and the delivery mechanism to increase or decrease the rotational speed (or torque). In particular, in combination with a device platform suitable for treating diseases with a variety of delivery rates and viscosities of a medicament, the use of an electric motor (with or without a transmission) is an attractive solution because, for a single design of the device, different delivery rates can be selected. The selection of the delivery rate is performed at the factory (pharmaceutical company) or by the patient. In addition, during treatment, interruptions in the delivery rate may occur, for example, occlusions in the fluid delivery path or mechanical obstructions of the delivery mechanism may occur. Thus, for safe treatment, it is important to monitor the drive mechanism and detect adverse events that may interrupt the delivery of the medicament.

[0008] In EP3539592A1, an example of a patch device is presented, which discloses a patch delivery device having: a bottom housing portion; a capacitive sensor; an adhesive patch having a first adhesive layer contacting the bottom housing portion and a second adhesive layer for contacting the patient's skin; and a release liner made of a coated paper or plastic sheet, which covers the second adhesive layer before the device is used. Exemplary subassemblies and components of the patch delivery device include: a cartridge holder; a needle insertion mechanism for inserting the cannula into the patient's skin; a fluid path for connecting the cannula to the cartridge; and a drive mechanism for dispensing liquid and including an electric motor and a battery. These patch injection devices are suitable for having at least 1, preferably at least 15 and most preferably at least 50 cP (0.050 kg / m -1 s -1 ) of a highly viscous injectable liquid. The rotational speed of the electric motor can be monitored using a sensor (e.g. using an encoder). In a sensorless configuration, no additional rotor position sensor is provided, and the rotation of the rotor is monitored based on a measurement of the back electromagnetic force (back electromotive force) at the terminals of the stator coils. In application EP 19176233.5, an arrangement of a driver circuit for monitoring the rotational speed of an electric motor using a back electromotive force signal is proposed.

[0009] The problem of using a back EMF signal to monitor the rotational speed of an electric motor is described in US4896085. The back EMF signal that is usually generated at high rotational speeds is not yet present at low rotational speeds. This is particularly important when the volume delivery rate for the medicament is low, because this also requires a low rotational speed for the electric motor. In addition, the transition from a rotating electric motor to a non-rotating motor caused by an adverse event requires reliable detection of the presence or absence of a back EMF signal before the adverse event.

[0010] The object of the present invention is to overcome the aforementioned disadvantages and to provide a drug delivery device driven by an electric motor with sensorless detection and control of rotational speed. As a specific object, the drug delivery device accurately delivers medicament at a low delivery rate while using back EMF to monitor the rotational speed to obtain reliable, low-cost control of the delivery rate.

[0011] This object is solved by the independent claim 1. Further advantageous embodiments are disclosed in the dependent claims and in claim 15 a method for operating a drug delivery device is proposed.

[0012] definition

[0013] The term "medicament" or "drug" includes any flowable pharmaceutical formulation suitable for controlled administration by a device such as, for example, a cannula or a hollow needle, and includes liquids, solutions, gels or fine suspensions containing one or more pharmaceutically active ingredients. A medicament can be a composition comprising a single active ingredient or a premixed or co-formulated composition having more than one active ingredient present in a single container. Drugs include drugs such as peptides (e.g., insulin, drugs containing insulin, drugs containing GLP-1 or derived preparations or similar preparations), proteins and hormones, active ingredients derived from or harvested from biological sources, hormone- or gene-based active ingredients, nutritional formulas, enzymes, and other substances in both solid (suspended) form or liquid form, as well as polysaccharides, vaccines, DNA, RNA, oligonucleotides, antibodies or portions of antibodies, and appropriate alkaline substances, auxiliary substances, and carrier substances.

[0014] The distal end or distal direction is defined by the direction of the needle configured to penetrate the patient's skin. For an injection pen, this may be the injection needle, and the end of the pen that holds the needle or is configured to hold the needle is the distal end. For an infusion device, the distal end and the distal direction are toward the needle configured to penetrate the patient's skin, which needle may be along the axis of the device or inclined or perpendicular to the axis of the device. The distal direction in an infusion device means the direction along which the medicament flows toward the insertion needle. The proximal direction or proximal end is opposite to the distal direction or distal end.

[0015] In the claims, the word "comprising" does not exclude other elements or steps and the indefinite article "a" or "an" does not exclude a plurality. For example "a control unit" does not exclude the fact that there may be two control units that functionally or structurally achieve the purpose of the "control unit". Summary of the invention

[0016] The drug delivery device may include one or more of the following units. The housing includes a wall that separates the internal part or unit from the surrounding environment and provides mechanical support. The wall may be part of a sterile barrier. The housing may have a pen shape or an elongated flat shape configured to be attached or worn on the patient's body. The housing with an elongated or flat shape may have a bottom housing portion for attaching to the body using an adhesive layer. The adhesive layer may include at least two adhesive layers, one for contacting the housing, and the other for contacting the skin. The adhesive layer may extend across the lateral dimensions of the housing. The skin adhesive layer is covered by a protective release liner before use. The housing includes a top housing portion, which may include an actuation button and an optical indicator, which is preferably located behind the wall. The bottom or top housing portion may have a viewing window for viewing an optical indicator and / or a reservoir comprising a medicament. The housing may have a removable cover, which is configured to close an opening in the housing intended to receive the reservoir. The cover closes the reservoir holder, which is suitable for holding and fixing the reservoir in the delivery device, and the cover may have a viewing window. The delivery device can be ready for use, for example, a reservoir with a medicament is present in the closure device, or the reservoir is inserted through an opening in the housing before use. In the latter case, it is beneficial to provide the medicament to the delivery device and the reservoir in a kit. The delivery device preferably has a fluid path unit, which includes a pipeline for connecting a skin insertion needle to the medicament present in the reservoir. Optionally, the fluid path unit includes a reservoir needle, which is suitable for penetrating into the reservoir, for example via a septum, to establish a fluid connection to the skin insertion needle via a pipeline. The reservoir may have a fluid outlet, or the outlet is established via the reservoir needle. The fluid path unit may be in a sterile state during the shelf life before operating the device. The fluid path unit may have an insertion mechanism, which is used to insert the skin needle into the injection site through the aperture in the housing. The insertion mechanism may have a needle retraction mechanism for retracting the skin needle once the medicament has been delivered. In addition, the insertion mechanism may also provide for insertion of the reservoir needle into the reservoir. The delivery of the drug from the reservoir is preferably driven by an electric motor, which optionally operates the delivery mechanism via a transmission mechanism located between the electric motor and the delivery mechanism. The delivery mechanism preferably includes a piston rod, which is used to drive a piston in the reservoir to deliver the drug through the outlet of the reservoir. The delivery device is preferably powered by a battery and controlled by a control unit. Optionally, the sensor system may be part of a circuit system for detecting skin attachment or skin separation of the device. The control unit, battery, delivery mechanism, reservoir, and fluid path unit including the insertion mechanism are located inside the housing of the device. The sensor may be located inside the housing, or may be part of an adhesive layer for attaching the device to the patient.

[0017] The drug delivery device comprises a reservoir containing a fluid medicament to be delivered from the device by advancing a piston in the reservoir at a forward speed, the forward speed defining a delivery rate for the medicament through an outlet of the reservoir. The electric motor drives a delivery mechanism of the drug delivery device by rotating so as to advance the piston at a forward speed (preferably at a target forward speed), and a control unit is configured to control the rotational speed and on / off state of the electric motor. The rotational speed of the electric motor or preferably the rotor in the electric motor is measured by operating the electric motor in a monitoring mode for detecting a back electromagnetic force (back electromotive force) signal of the electric motor, and the signal is sent to the control unit or monitored by the control unit. The control unit controls the rotational speed of the electric motor so that the back electromotive force signal, preferably a reliable back electromotive force signal, can be detected in the monitoring mode. In addition, the control unit adjusts the on / off state of the electric motor to control the delivery rate of the medicament through the outlet, preferably the target delivery rate. The forward speed is typically expressed in millimeters per minute (mm / min) and is preferably used to advance the piston linearly in the reservoir along the delivery direction or along the axis defined by the reservoir. The delivery rate for the medicament is preferably a volume delivery rate expressed in milliliters per minute (ml / min). The medicament is delivered by the linear advancement of the piston to reduce the volume of the medicament contained in the reservoir so that the fluid medicament is discharged through the outlet. The delivery mechanism includes a transmission system that transmits the rotation of the electric motor to the advancement of the piston in the reservoir. The delivery mechanism may include a piston rod that is directly or indirectly engaged with the piston in the reservoir. The delivery mechanism may include a transmission mechanism to drive the rotation of the electric motor upward or downward so that the piston is advanced in the reservoir. The piston rod may advance linearly without rotation, or advance by a combination of rotation and linear advancement (e.g., by spiral movement). The piston rod may be a threaded piston rod that includes an external thread that engages the internal thread of a nut component, which is a part of the delivery mechanism or a part of the transmission mechanism. The nut component may be a sleeve-shaped, wherein the thread or threaded segment on the inside engages the external thread of the piston rod. The piston rod may further include a longitudinally oriented groove oriented parallel to the longitudinal axis of the piston rod so as to be splined with the housing or housing portion of the drug delivery device so that when the nut component is rotated, the piston rod is linearly advanced, in which case the piston rod is linearly advanced without rotation. Optionally, the groove of the piston rod is spirally shaped, wherein the pitch is different from the pitch of the threaded engagement with the nut component. The groove is again splined to the housing so that rotation of the nut component advances the piston rod, which also rotates according to the pitch of the spiral groove. Alternatively, the piston rod can be a hollow piston rod comprising an internal thread that engages the external thread of the drive component. The drive component can be part of the drive mechanism or connected to the drive mechanism or to the transmission mechanism.If the hollow piston rod is prevented from rotating relative to the housing, rotation of the drive member drives the hollow piston rod without rotating.

[0018] Optionally, the threaded piston rod is threadedly engaged with the housing, and the nut part is splined to the longitudinal groove so that rotation of the nut part rotates the piston rod, which then advances by threaded engagement with the housing. The conveying mechanism is driven by the rotation of the electric motor, and the rotation is used to advance the piston rod at a forward speed. The transmission system of the electric motor, the conveying mechanism with or without a transmission mechanism, and the nut driving the piston rod are multi-part systems with a certain elasticity and clearance, for example, not rigid systems. For example, the parts can be made of plastic materials or metals each having a different elasticity, and the transmission wheel or worm gear can be designed to have a certain clearance between the two engaged parts.

[0019] Preferably, the piston rod is a single piece piston rod, alternatively, the piston rod may include a plurality of coaxially arranged sleeves forming a telescopic piston rod arrangement extending to advance the piston at a forward speed. As another alternative, the piston rod may be segmented, including segments connected to each, for example by a film link, and the segmented piston rod may be reversibly transformed from a linear configuration to a curved configuration.

[0020] The control unit is preferably located on a printed circuit board (PCB) comprising an integrated circuit for controlling the drug delivery device (in particular, the rotational speed of the electric motor and / or the on / off state of the electric motor). An advantage of a control unit adapted to control the rotational speed is that a wide range of delivery rates can be selected. Other units of the device that can be controlled by the control unit may be a visual signaler unit and / or an acoustic signaler unit and / or a tactile signaler unit of the device. The visual signaler may be based on an LED indicator, the acoustic signaler may use a load speaker, and the tactile feedback may be based on a vibration unit. The control unit is battery powered and may include a memory storing: a) parameters for operating the device, such as a target delivery rate, a target delivery speed, a delivery time, a correlation between a target rotational speed and a target delivery rate; and b) device indicators, such as a model or batch number, a production date, an expiration date, calibration data, the size and type of cartridge or the medicament used. The control unit may also include a transmitter / receiver unit, for example using Bluetooth low energy or direct to cloud technology, for example using 5G technology for wireless communication with external devices (such as a cell phone or smartphone) and / or to a cloud service or the like.

[0021] The rotation speed of the electric motor is defined by the number of steps per second of a rotor or drive shaft which is or can be coupled to a drive mechanism. For example, a stepper motor has a defined number of steps per revolution. The rotation speed is controlled by a control unit by varying the frequency of pulses directed to the electric motor, more preferably to the stator coils of the electric motor.

[0022] The switched-on state for the electric motor is defined by the fact that the drive shaft of the electric motor is rotating. This rotation preferably takes place at a continuous rotational speed. In the switched-on state, the drive shaft or rotor rotates while an electrical torque is applied to the shaft or drive shaft, or the rotor rotates due to its moment of inertia while no electrical torque is applied.

[0023] The cut-off state for the electric motor is defined by the fact that the drive shaft or rotor of the electric motor is not rotating positively.

[0024] In a monitoring mode for a drug delivery device (more preferably, for an electric motor as part of a drug delivery device), the rotation speed of the electric motor is monitored, or the number of steps per second is measured when the electric motor is rotating (e.g., in an on state). In the on state, the drive voltage can be interrupted or paused for a short time (preferably, less than milliseconds). The rotation speed is measured using a back electromagnetic force signal (back electromotive force) induced by the rotation of the electric motor during the interruption or pause. The advantage of using the back electromotive force signal is that it uses the components of the electric motor to detect the rotation speed, and does not require additional parts such as encoders or optical measurement units. The back electromotive force signal can be generated by the rotation of a conductive coil in a magnetic field (which can be established by a static magnet), or vice versa, by the rotation of a static magnet in a conductive coil (which is static). Such a back electromotive force signal is mainly generated when the conductive coil and the static magnet rotate relative to each other. At a rotation speed of zero revolutions (or steps) per second, no back electromotive force signal is generated. However, as mentioned in the prior art US4896085, the back-EMF signal is generated at higher rotational speeds and is not yet present at low rotational speeds, or at least the back-EMF signal cannot be reliably detected at low rotational speeds. The detection limit depends on the sensitivity of the sensor unit, which is part of the control unit, which may include filters such as bandpass filters to reduce the signal-to-noise ratio. Thus, once a minimum rotational speed for the electric motor has been reached, a reliable back-EMF signal can be sent to the control unit and measured by the sensor.

[0025] The control unit controls the rotation speed and regulates the on / off state of the electric motor. The on / off regulation is established by switching the electric motor between a rotating on state and a non-rotating off state. The electric motor is regulated according to time, for example, the motor is in the on state for a certain time (on time) and in the off state for a certain time (off time). The on / off periods can be equal, but can also be different from each other. Preferably, the off time is higher than the on time in order to operate the conveying device at a low target conveying rate. The rotation speed and the on / off regulation are controlled to meet the following requirements:

[0026] i) preferably, during the switched-on state, the rotational speed is controlled by the control unit at any time to be higher than the minimum rotational speed required for reliable generation and detection of the back-EMF signal, and

[0027] ii) On / off regulation is used to control the linear advancement speed of the piston in the cartridge (mm / min), and thereby the volumetric delivery rate (ml / min), and ultimately the delivery time.On / off regulation is preferably used to control the delivery rate to be at or close to a target delivery rate.

[0028] At low delivery rates (ml / min), if the electric motor would be permanently running in the on-state, and the first requirement (always rotating at a speed that is too low for back-EMF detection) would not be met, the rotation speed of the electric motor would be lower than the minimum rotation speed required for generating and detecting a reliable back-EMF signal. Thus, by regulating the electric motor between the on-state and the off-state, the electric motor can be operated at least at the minimum rotation speed for back-EMF detection (requirement i) and still operate the device at a low delivery rate (requirement ii). By operating the delivery device at the minimum rotation speed for detecting the back-EMF signal and on / off regulation, the delivery device can be operated at a low delivery rate without compromising the reliability and accuracy of the device.

[0029] If the required delivery rate is such that the continuous rotational speed is above the minimum rotational speed, no on / off regulation is required and the electric motor is constantly rotating when the medicament is delivered through the outlet of the cartridge. If the required delivery rate or target delivery rate is such that the rotational speed of the electric motor will be below the detection limit of a reliable back EMF signal, the rotational speed is set to at least the minimum rotational speed and the delivery rate is controlled by on / off regulation. Preferably, the device is calibrated and / or configured at the factory to establish a relationship between the delivery rate (ml / min) and the minimum rotational speed required for the electric motor. The device can be calibrated and / or configured to operate with different types of reservoirs having different volumes.

[0030] Furthermore, reliable detection of the back-EMF signal also ensures that deviations in the rotation of the electric motor, for example due to occlusions, mechanical blockages or when the piston has reached the end of the reservoir, can be detected.

[0031] The drug delivery device may comprise a piston rod which abuts a piston in the reservoir and whereby the piston rod is advanced at an advancing speed by the delivery mechanism.

[0032] The reservoir of the drug delivery device is preferably a cartridge comprising a piston that advances linearly in the cartridge toward the outlet of the cartridge by a delivery mechanism. The cartridge can be tubular in shape, comprising a barrel that is closed by a piston at one end and by a pierceable septum covering the outlet of the reservoir at the opposite end. The septum can be curled onto the shoulder section of the cartridge. The septum can be pierced by a needle that is connected to or can be connected to the patient to deliver the medicament. Alternatively, the reservoir is a syringe that is closed by a piston at one end and has a stacked needle at the opposite end that forms the outlet. The needle tip is preferably enclosed by a needle shield to maintain the sterility of the contents of the prefilled syringe. Alternatively, the cartridge can be non-linear in shape, such as curved to form an arcuate reservoir. The cartridge is preferably made of a rigid material such as glass or a rigid plastic material such as polypropylene or cyclic olefin copolymer (COC), and the piston is made of rubber which is at least partially elastically compressed to fit into the barrel of the cartridge to provide a tight seal for the medicament. The advantage of using a linear glass cartridge comprising a barrel and a pierceable septum is that this is a primary package established and well accepted by the pharmaceutical industry and can be filled on a standard filling finishing line. The rigid cartridge may have a circular or oval cross-section. Alternatively, a flexible or semi-rigid material may be used for the reservoir to form a compressible or collapsible reservoir.

[0033] The electric motor is preferably a brushless DC motor (BLDC), and the on state is defined by the control unit directing a drive voltage to at least one of a plurality of stator coils, thereby applying a drive torque to a rotor of the BLDC motor so as to set the rotor rotationally. The brushless DC motor (BLDC) comprises a rotor having a plurality of static magnets, the plurality of static magnets being surrounded by a plurality of stator coils, the plurality of stator coils being coupled to a DC source via a control unit. The control unit drives a drive voltage to at least one of the plurality of stator coils, thereby inducing a magnetic field, which is used to generate a drive torque on the rotor. The rotor may comprise a drive shaft, and the plurality of static magnets may be attached to the drive shaft. The BLDC motor has the advantage of being brushless, and the use of brushes may have the disadvantage of forming an oxide layer on the brushes, thereby affecting the start-up after the shelf life. An additional advantage of using a BLDC electric motor is that when a constant voltage is applied (e.g., requiring commutation), there is no rotation, and thus reliability is improved, and furthermore, the positioning of the rotor and the change in the rotation speed can be better controlled.

[0034] A drug delivery device, wherein the rotational speed is controlled by a pulse frequency (f puls ) intermittently directs a drive voltage to a plurality of stator coils. A drive voltage in the form of pulses (specifically, a sinusoidal waveform, or alternatively, a block waveform) is directed to at least one of the plurality of stator coils so that the rotor is rotationally set due to a drive torque applied with each pulse. Preferably, each pulse corresponds to one rotation step for the electric motor, and the rotor is rotationally set by applying a voltage pulse to a subsequent stator coil of the plurality of stator coils, or in other words, applying commutation. By varying the frequency of the pulses directed to the stator coils, the rotational speed of the rotor can be varied and controlled.

[0035] The cut-off state is defined by a control unit that does not direct a drive voltage to a plurality of stator coils, thereby not applying a drive torque, and thereby stopping the rotation of the rotor. The stop is defined as a gradual but rapid deceleration to zero rotation, without active interruption, and not caused by an adverse event. When a drive voltage is not applied to the stator coils, a drive torque is not applied to the magnets forming part of the rotor, and, therefore, the rotor will stop rotating. Optionally, due to the moment of inertia of the rotor, the rotor may rotate for several milliseconds during deceleration, preferably within a period of less than 10 milliseconds, more preferably less than 5 milliseconds, before deceleration to zero rotation. When no drive voltage is applied for a longer period (e.g., more than five milliseconds, preferably more than ten milliseconds), the rotor will completely stop rotating.

[0036] In the switched-on state, the rotation speed of the electric motor is equal to or higher than the minimum level for detecting the back EMF signal in the monitoring mode. In order to meet the first requirement (i) mentioned above, the rotation speed of the rotor in the electric motor must be equal to or higher than the minimum level for measuring or detecting the back EMF signal, preferably for detecting a reliable back EMF signal.

[0037] In the monitoring mode, no drive voltage is applied, thereby allowing a voltage measurement unit in the control unit to detect a back-EMF signal induced by the rotating rotor in the stator coils of the electric motor.

[0038] Thus, in the monitoring mode, the drive voltage is not applied by interrupting or pausing the drive voltage in the on state, thereby allowing the back electromotive force signal to be detected. The interruption (or pause) is short, preferably in the order of milliseconds, so that the rotor rotates at the same rotation speed as when the drive voltage is applied due to its moment of inertia.

[0039] In the monitoring mode, the drive voltage may be interrupted or paused for a period varying between 0.05 milliseconds and 2.0 milliseconds, preferably between 0.1 milliseconds and 1.0 milliseconds. The monitoring of the back electromotive force signal may be part of a cycle, and each cycle includes a monitoring mode in which the drive voltage is paused for a period varying between 0.05 milliseconds and 2.0 milliseconds, followed by the voltage being applied in the on state. The subsequent cycle begins when the voltage is paused for the next back electromotive force measurement. The electric motor for the conveying device is regulated in the on / off state to control the conveying rate by periodically switching the electric motor between an on state in which the rotational speed of the electric motor is equal to or above a minimum level and a cut-off state in which the rotor of the electric motor is not rotated.

[0040] The ratio between the off state and the on state is at least 1 to 5, preferably 1 to 2, more preferably 1 to 1, more preferably at least 2 to 1. The ratio is calculated as the quotient of one period in the on state and one period in the off state.

[0041] The delivery rate or target delivery rate for the medicament typically varies between 0.1 ml / min and 10 ml / min, preferably between 0.2 ml / min and 5 ml / min, most preferably between 0.3 ml / min and 1 ml / min.

[0042] The drug delivery device can be an infusion device, a bolus injector, a patch injector or an automatic injector. The drug delivery device can be removably carried on the body, for example, using an adhesive to attach to the body. Alternatively, the drug delivery device is carried by the patient in a retainer or belt that can be fixed to the patient's body. Alternatively, the drug delivery device can be used by health care professionals in a hospital, and is not carried or attached to the body, but is used as a separate device away from (but still close to) the patient. The medicament can be delivered to the patient by the drug delivery device via an infusion set outside the drug delivery device, the infusion set includes a pipeline that can be connected to the drug delivery device, and the pipeline terminates in a needle for subcutaneous or IV delivery. As an alternative, the medicament can be delivered by an infusion set or a fluid path located inside the drug delivery device. Such a fluid path includes a skin insertion needle for insertion into the injection site, and the skin insertion needle can be driven by a needle insertion mechanism from a retracted position inside the drug delivery device (or inside the housing or housing portion of the drug delivery device) to an extended position outside the drug delivery device. The needle insertion (and retraction) mechanism may be driven by a separate spring or may be driven by an electric motor. After delivery of the medicament has been completed, the skin insertion needle may be retracted into the interior of the drug delivery device by the needle insertion mechanism. Alternatively, after delivery of the medicament has been completed, the needle shield protects the extended needle, for example, a covering sleeve surrounding the needle tip extends from the drug delivery device after the medicament has been delivered and preferably when the drug delivery device is removed from the skin.

[0043] Bolus syringes typically deliver volumes between 1 ml and 20 ml at a time within the delivery range mentioned above.

[0044] The present invention further relates to a method for operating a drug delivery device, the method comprising at least the following steps:

[0045] i) determining a target rotational speed for the electric motor expressed as a pulse frequency based on the target delivery rate. Preferably, the target delivery rate is preset for the device or selected by a user or health care professional. The target rotational speed may be determined using a memory of the control unit, the memory comprising a correlation between the target rotational speed and the target delivery rate. The correlation may be based on a general factory calibration or individually based on a device specific calibration for each device. The minimum rotational speed for reliably detecting the back EMF signal may also be stored in the memory of the device.

[0046] ii) comparing the target rotational speed with the minimum rotational speed for detecting the back EMF signal, and

[0047] (iii) If the target rotational speed is lower than the minimum rotational speed: a ratio between the on-state and the off-state is defined, wherein the electric motor is operated at the minimum rotational speed in the on-state and at zero speed in the off-state. The ratio may be selected from a list of ratios in the memory of the device, or obtained by connecting the drug delivery device to an external database that may be stored in an external device (such as a cell phone), or obtained from the cloud.

[0048] If condition (iii) applies: operating the device in an alternating on / off mode according to the ratio to deliver the fluid medicament through the outlet of the reservoir at a target delivery rate.

[0049] However, if (iv) the target rotational speed is above the minimum rotational speed for measuring the back EMF signal, the device is operated in a continuous mode whereby the electric motor rotates at the target rotational speed to deliver the fluid medicament through the outlet of the reservoir at the target delivery rate.

[0050] Additionally, and optionally, step (v) may be part of the method: (v) selecting an (absolute) switch-on period comprising a minimum number of rotor revolutions to allow tracking deviations. A minimum number of revolutions or step size is required to reliably detect rotation of the electric motor, thereby also enabling reliable detection of non-rotation of the electric motor due to a) a blockage of the drive mechanism when the piston reaches the end of the reservoir, or b) due to an adverse event, such as an occlusion in the fluid delivery path.

[0051] In this method, the correlation between the target delivery rate (output) and the target rotational speed (input) of the electric motor driving the delivery mechanism depends on a number of parameters, such as the elasticity of the drive train, the reservoir size, the outlet size of the reservoir, the viscosity of the fluid medicament, the shelf life of the device including the medicament, and for reusable devices, the number of injections or infusions performed by the device to account for internal wear. The correlation can be a fixed correlation throughout the life of the device, or it can change or adapt itself to the situation, for example if a new reservoir is inserted into the device or wear in the device is to be taken into account. The device can be "self-learning" in that the correlation stored in the memory is able to adjust itself (updated correlation) based on previously stored correlations. BRIEF DESCRIPTION OF THE DRAWINGS

[0052] The subject matter of the invention will be explained in more detail in the following text with reference to preferred exemplary embodiments illustrated in the drawings, which show:

[0053] Figure 1 : Example of a drug delivery device according to the present invention: top view of a patch injector.

[0054] Figure 2: Example of a drug delivery device according to the present invention: longitudinal section of a patch injector.

[0055] Figure 3 : Regulation of the on / off state of the electric motor; a rotation speed above the minimum level for detecting the back electromotive force signal (continuous rotation). Alternatively, a rotation speed at the minimum level for detecting the back electromotive force signal with regulation of the on / off state.

[0056] Figure 4 : An embodiment of the relationship between on / off regulation and time.

[0057] Figure 5 : An embodiment of the relationship between on / off regulation and time. DETAILED DESCRIPTION

[0058] Figure 1 An example of a drug delivery device 1 according to the invention is shown. The drug delivery device is a patch injector comprising a housing 2 providing a wall to separate at least the fluid path unit 3, the delivery unit 6 and the reservoir 15 from the surrounding environment. The housing 2 has an elongated shape, wherein the bottom housing 2a is intended for positioning on or attaching to the patient's skin ( Figure 2). The fluid path unit 3 includes a fluid path 5 having a skin insertion needle (not shown) that is intended to move from the inside of the housing 2 through an aperture 23 in the fluid path unit into the patient's skin. The fluid path 5 includes a conduit that connects the skin insertion needle to the outlet 18 of the reservoir 15. The connection between the fluid path 5 and the reservoir 15 can be a permanent connection, or the fluid path 5 has a reservoir needle, not shown, that can be connected to the outlet 18 of the reservoir 15 or penetrate the outlet 18 of the reservoir 15. The delivery unit 6 includes: an electric motor 7; a transmission 8, which is coupled to or connectable to the electric motor 7; a control unit 9; and a battery 26 for powering the device. The battery 26 can be part of the delivery unit 6, or can form a separate unit within the housing 2. The battery 26 powers the control unit 9 and the electric motor 7 in order to control the device and control the delivery of the medicament 17 through the outlet 18 of the reservoir 15. The control unit 9 controls the rotation speed of the electric motor 7 in order to deliver the medicament 17 at a desired delivery rate. The rotational speed of the electric motor 7 is monitored using a sensorless system, preferably using a back electromotive force signal generated at the stator coil of the electric motor 7 during the rotation of the rotor. The control unit 9 controls the rotational speed so that a reliable back electromotive force signal can be detected, preferably by operating the electric motor 7 at a minimum rotational speed. The electric motor 7 is operated in a monitoring mode for monitoring the rotational speed, wherein the drive voltage is interrupted or suspended for a short period of time so that the back electromotive force signal can be detected and sent to the control unit. The rotation of the electric motor or the drive shaft connected to the electric motor is transmitted to the transmission device 8, which advances the piston rod 14 toward the piston 16 in the reservoir 15. The reservoir is preferably a glass cartridge, which is closed on one side by a movable piston 16 and on the opposite side by a pierceable septum forming part of the outlet 18. The piston rod 14 abuts the piston 16 in the cartridge to reduce the volume of the medicament 17 that can be discharged into the patient through the fluid path 5 via the outlet 18. In addition, the delivery unit includes a transmitter / receiver 10 for wireless communication with an external device (such as a smart phone). The transmitter / receiver can be based on Bluetooth, low-power Bluetooth, NFC, 5G or zigBee technology. The acoustic signaler system 11 and / or the visual signaler system 13 can be part of the delivery unit 6 or form a separate unit in the housing. The visual signaler 13 can have an LED light located behind the housing 2 or a translucent section in the housing, and multiple LED lights can use different colors to signal. Multiple LED lights can be arranged along a straight line or a curve, or individual LED lights can form a pattern. The push button 12 can be part of the housing, and the user can start the drug delivery or start the device by pressing the push button 12.

[0059] The drug delivery device 1 is suitable for use with an adhesive unit 19 ( Figure 1) to attach to the patient's skin. The surface area of ​​the adhesive unit 19 is at least equal to the area of ​​the bottom shell 2a. Preferably, the adhesive unit 19 has a larger area, and the edge of the adhesive unit 19 wraps around the shell 2 of the drug delivery device 1. The adhesive unit 19 is a multilayer system, which includes a base layer 20 that provides support to the adhesive layer 21. The base layer can be a woven textile or a non-woven textile. The adhesive layer 20 is covered by a release liner 22 covering the adhesive. The user removes the release liner 22 by pulling a pull tab or aperture not shown in the release liner, and then attaches the drug delivery device to the skin.

[0060] The fluid path unit 3 can form a sterile enclosure surrounding the fluid path unit 5. The sterile enclosure can be formed by a separate housing portion located within the housing 2. The fluid path unit 5 includes an aperture 23 for a skin needle. Optionally, the fluid path unit 5 includes a second aperture for a reservoir needle. The two needles can be moved by an insertion mechanism 4. The skin needle is configured to move from a retracted position within the fluid path unit 3 through the aperture 23 outside the housing 2 to an inserted or extended position, and the reservoir needle is configured to move from a retracted position within the fluid path unit 3 to the reservoir 15, for example by piercing a septum. The apertures for the skin needles and / or reservoir needles are covered by a seal 24, which forms a sterile barrier to protect the fluid path 5 from contamination during the shelf life. The seal 24 can be formed by a porous membrane (such as a Tyvek membrane). Before use, the seal 24 is preferably removed, or alternatively, the skin needle penetrates through the seal 24. The seal 24 can be removed separately from the release liner 22, or preferably, the seal 24 is removed simultaneously with the release liner 22. The release liner 22 can be attached to the seal 24, or a coupling (e.g., an adhesive) can connect the release liner to the seal 24. Optionally, the release liner 22 forms the seal 24, for example, a portion of the release liner 22 can be heat sealed to the fluid path unit 3. Preferably, the seal 24 is separate from the release liner 22, and the base layer 20 and the adhesive layer 21 include an aperture 25 forming a passage for the reservoir needle.

[0061] The insertion mechanism 4 can be triggered by the user, for example by pressing the push button 12 to mechanically release the latch mechanism, thereby starting the insertion of the skin needle into the skin and / or the insertion of the reservoir needle into the reservoir 15. Alternatively, the insertion mechanism 4 is activated by the electric motor 7, for example by rotating in a direction opposite to the direction of rotation for medicament delivery. The electric motor 7 can directly activate the insertion mechanism 4 or via the transmission 8. The insertion mechanism 4 can be powered by a biasing member (e.g., a mechanical spring, such as a compression spring or a leaf spring), or the inserter itself is powered by the electric motor 7. Optionally, the insertion mechanism 4 includes a skin needle retraction mechanism so that the skin needle can be retracted into the housing 2 after the medicament has been delivered. The drug delivery device 2 can have a skin sensing system, such as a capacitive sensor that senses the proximity of the skin. The skin sensing system can be integrated with the adhesive unit 19, or can be located within the housing 2, or can be part of the bottom housing 2a. The skin sensing system can detect the proximity of the skin (skin attachment), or can detect the separation of the device from the skin. Both skin attachment as well as skin detachment may be signaled to the control unit 9 via the visual signaler system 13 and / or the acoustic signaler system 11 in order to activate the device or to signal a malfunction to the user.

[0062] The operation and control of the electric motor 7 for the drug delivery device 1 proposed above is described in detail in Figures 3 to 5 . Preferably, a brushless DC motor is used and a pulsed drive voltage is directed by a control unit 9 to at least one of the plurality of stator coils so that the rotor is rotationally set due to the drive torque applied with each pulse. Preferably, each pulse corresponds to a rotation step and the rotor is rotationally set by applying a voltage pulse to a subsequent stator coil of the plurality of stator coils, or in other words, applying commutation. By varying the frequency of the pulses directed to the stator coils, the rotational speed of the rotor can be controlled. Thus, the rotational speed of the rotor (rev / sec) is linearly related to the pulse frequency in pulses per second (pps).

[0063] exist Figure 3 In FIG. 1 , the rotational speed is shown as a function of time. If the rotational speed required for the desired delivery rate is above the minimum level for detecting a reliable back-EMF signal, the control unit ensures that the electric motor is continuously running in the switched-on state ( Figure 3 During the on-state, the rotor rotates and the drive voltage is interrupted for 0.5 milliseconds in monitoring mode in order to measure the back EMF signal.

[0064] If the delivery rate or target delivery rate is low and this would require operation at a target rotational speed (shown as a dashed line) below the minimum level for back EMF detection, the control unit switches the electric motor between an on state, in which the rotational speed is sufficient to detect the back EMF signal in the monitoring mode, and an off state, in which the drive voltage is interrupted for a longer period of time so that the rotor stops rotating. By adjusting the on time and the off time, it is possible to deliver medicament at a desired or target (low) volumetric delivery rate without compromising sensorless detection of rotational speed. Figure 4 An example for an on / off regulation is presented in , where the electric motor is controlled such that the electric motor is in the on state for 2 / 3 of the time and in the off state for 1 / 3 of the time.

[0065] A more detailed calculation for the adjustment is presented below. The target rotation speed is expressed in pulses per second (pps), and for detecting the back EMF signal, V min =33 pps. This thus corresponds to a minimum rotational speed for back EMF detection. There is also a minimum number of steps (one step per pulse) required to detect a change in rotation. Such a change in rotation may be due to a mechanical blockage in the transmission or an occlusion in the fluid path. Such a blockage requires a certain number of steps to be recorded before the blockage to ensure reliable detection of the rotating rotor. The minimum step size depends on the sensitivity of the system. For this example, the minimum number of steps is S min =100 steps.

[0066] Switch-on time (t on ) is evaluated as:

[0067] T on =S min / V min

[0068] In this example, the on time is 3 seconds.

[0069] The percentage of time the device is operated in the on state (on % ) is calculated as the target delivery rate (V target ) and minimum detection speed (V min ) between:

[0070] on % =V target / V min

[0071] If the desired or target delivery rate V target(volume) corresponds to a target rotational speed expressed at a pulse frequency of 11 pps, the device is operated for 11 / 33 of the time in the on state (up to 3 seconds, t on 33%(on % ).

[0072] The percentage of time the device is operated in the off state (off % ) is calculated as

[0073] off % =l-on %

[0074] And, the ratio (R on / off ) is evaluated as:

[0075] R on / off =V target / V min / (1-V target / V min )

[0076] For this example, the on / off ratio is thus 1:2. And the off time can be calculated as:

[0077] t off =t on / R on / off

[0078] In this example, the device is thus operated for 3 seconds in the on state and for 6 seconds in the off state, and the example is Figure 5 Presented in.

[0079] If the target delivery rate corresponds to a pulse frequency of 40 pps (eg above the minimum level of 33 pps for back EMF detection), the device is continuously operated in the "on" state, see Figure 5 .

[0080] Changes in voltage regulation can be easily accounted for. For example, for a more sensitive system, reliable rotation detection may cost S min = 66 steps, and, in this case, at a minimum speed level V for back EMF detection min = 33 pps, a rotation of 66 / 33 = 2 seconds may be required at 33 pps. If the required delivery rate corresponds to 22 pps, the control unit operates the device for 2 seconds in the switched-on state and for 1 second in the switched-off state. Figure 4 As shown in , there is an interval operation where 2 / 3 of the time the device is in the on state.

[0081] Reference Symbols List

[0082] 1 Drug delivery devices

[0083] 2 Housing

[0084] 2a Bottom housing

[0085] 3 Fluid Path Unit

[0086] 4 Insertion mechanism

[0087] 5 Fluid Path

[0088] 6 Conveying unit

[0089] 7 Electric Motor

[0090] 8 Transmission

[0091] 9 Control unit

[0092] 10 Transmitter / Receiver

[0093] 11 Acoustic signaler

[0094] 12 Push button

[0095] 13 Optical annunciator (LED)

[0096] 14 Piston rod

[0097] 15 Storage

[0098] 16 Piston

[0099] 17 Pharmacy

[0100] 18 Exit

[0101] 19 Adhesion Units

[0102] 20 Grassroots

[0103] 21 Adhesion layer

[0104] 22 Release liner

[0105] 23 Pore fluid path unit

[0106] 24 Seals

[0107] 25 Porous base / adhesive layer

[0108] 26 Batteries.

Claims

1. A drug delivery device, comprising: a reservoir containing a fluid medicament to be delivered from the drug delivery device by advancing a piston in the reservoir at an advancement speed, the advancement speed defining a delivery rate of the medicament through an outlet of the reservoir, an electric motor comprising a drive shaft that drives a delivery mechanism by rotation so as to advance the piston, the delivery mechanism comprising a transmission system that transmits the rotation of the drive shaft of the electric motor into the advancement of the piston rod, a control unit configured to control a rotation speed and an on / off state of the electric motor, wherein the on-state is defined by the fact that the drive shaft is rotating positively, and the off-state is defined by the fact that the drive shaft is not rotating positively, wherein the rotational speed is measured by operating the electric motor in a monitoring mode for detecting a back electromotive force signal of the electric motor sent to the control unit, The invention is characterized in that, when in the on state, the control unit controls the rotation speed of the electric motor to be higher than a minimum speed so that a back electromotive force signal can be detected in the monitoring mode, and wherein the control unit adjusts the on / off state to control the delivery rate to be at a target delivery rate.

2. The drug delivery device according to claim 1, wherein: The delivery mechanism comprises a piston rod which abuts the piston in the reservoir and whereby the piston rod is advanced by the delivery mechanism at the advancement speed.

3. The drug delivery device according to claim 2, wherein: The reservoir is a cartridge comprising the piston which is linearly advanced in the cartridge towards the outlet of the cartridge by the delivery mechanism.

4. The drug delivery device according to claim 3, wherein: The electric motor is a brushless DC motor, and wherein the switched-on state is defined by the control unit directing a drive voltage to one or more of a plurality of stator coils, thereby applying a drive torque to the drive shaft, thereby rotationally setting the drive shaft.

5. The drug delivery device according to claim 4, wherein: The rotational speed is controlled by intermittently directing the drive voltage to the plurality of stator coils at a pulse frequency.

6. The drug delivery device according to claim 5, wherein: The cut-off state is defined by the control unit not directing a drive voltage to the plurality of stator coils, thereby not applying a drive torque, thereby stopping the rotation of the drive shaft.

7. A drug delivery device according to any one of the preceding claims, wherein: The rotation speed of the electric motor in the on-state is equal to or higher than a minimum speed for detecting the back electromotive force signal in the monitoring mode.

8. The drug delivery device according to claim 7, wherein: In the monitoring mode, no drive voltage is applied, thereby allowing a voltage measurement unit in the control unit to detect the back electromotive force signal induced by the rotating drive shaft in the stator coils of the electric motor.

9. The drug delivery device according to claim 8, wherein: In the monitoring mode, the drive voltage is not applied by interrupting the drive voltage in the on state, thereby allowing the back electromotive force signal to be detected.

10. The drug delivery device according to claim 9, wherein: The drive voltage is interrupted for a period varying between 0.05 milliseconds and 2.0 milliseconds.

11. The drug delivery device according to claim 9, wherein: The drive voltage is interrupted for a period varying between 0.1 milliseconds and 1.0 milliseconds.

12. The drug delivery device according to claim 10, wherein: The electric motor is regulated in the on / off state to control the delivery rate by periodically switching the electric motor between the on state in which the rotation speed of the electric motor is equal to or higher than the minimum speed and the off state in which the drive shaft of the electric motor is not rotated.

13. The drug delivery device according to claim 12, wherein: The ratio between the on state and the off state is 1 to 5.

14. The drug delivery device according to claim 12, wherein: The ratio between the on state and the off state is 1 to 2.

15. The drug delivery device of claim 12, wherein: The ratio between the on state and the off state is 1 to 1.

16. The drug delivery device of claim 12, wherein: The ratio between the on state and the off state is at least 2 to 1.

17. The drug delivery device of claim 13, wherein: The delivery rate varied between 0.1 ml / min and 10 ml / min.

18. The drug delivery device of claim 13, wherein: The delivery rate varied between 0.2 ml / min and 5 ml / min.

19. The drug delivery device of claim 13, wherein: The delivery rate varied between 0.3 ml / min and 1 ml / min.

20. The drug delivery device of claim 17, wherein: The device is an infusion device, a bolus injector, a patch injector, an on-body delivery system, or an autoinjector.

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