DRUG DELIVERY DEVICE WITH AN IMPROVED MECHANISM FOR CONTROLLING THE DELIVERY RATE

Abstract

A drug delivery device including a reservoir configured to contain a fluid to be delivered by advancing a piston in the reservoir at an advancement speed defining a delivery rate for the medicament. The device further includes an electric motor configured to drive the delivery mechanism by rotation to advance the piston at the advancement speed. The device further includes a control unit that controls a rotational speed and an on state/off state of the electric motor. The control unit determines rotational speed of the electric motor based on a back-electromagnetic force signal provided from the electric motor while operating in a monitoring mode. The control unit controls the rotational speed of the electric motor such that a back-emf signal can be detected in the monitoring mode. The control unit modulates the on state/off state of the electric motor to adjust the delivery rate of the medicament.

Claims

1. A drug delivery device including a reservoir configured to contain a fluid medicament to be delivered by advancing a piston in the reservoir at an advancement speed defining a delivery rate for the medicament through an outlet of the reservoir, an electric motor configured to drive a delivery mechanism by rotation to advance the piston, a control unit configured to control a rotational speed and an on state and an off state of the electric motor, wherein the control unit is configured to determine the rotational speed based on a back-electromagnetic force (back-emf) signal provided from the electric motor while the electric motor is operating in a monitoring mode, wherein the control unit is configured to control the rotational speed of the electric motor to be, while in the on state, above a minimum speed such that a back-emf signal can be detected in the monitoring mode, and wherein the control unit is configured to modulate the on state and the off state of the electric motor to adjust the delivery rate to a target delivery rate.

2. The drug delivery device of claim 1, wherein the delivery mechanism comprises a piston rod that abuts the piston in the reservoir, and wherein the piston rod is advanced at the advancement speed by the delivery mechanism.

3. The drug delivery device of claim 2, wherein the reservoir includes a cartridge comprising the piston that is configured to be linearly advanced in the cartridge by the delivery mechanism towards an outlet of the cartridge.

4. The drug delivery device of claim 3, wherein the electric motor includes a brushless direct-current (DC) motor, and wherein the control unit is configured to control the on state by providing a driving voltage to a stator coil of the DC motor, wherein provision of the driving voltage to the stator coil of the DC motor is configured to cause application of a driving torque to a rotor of the DC motor to cause rotation of the rotor.

5. The drug delivery device of claim 4, wherein the control unit is configured to control the rotational speed by intermittently providing the driving voltage to the stator coil based on a pulse frequency.

6. The drug delivery device according to claim 5, wherein the control unit is configured to control the off state by stopping provision of the driving voltage to the stator coil, wherein, in response to the control unit stopping provision of the driving voltage to the stator coil, rotation of the rotor of the DC motor is stopped.

7. The drug delivery device of claim 1, wherein the rotational speed of the electric motor in the on state is equal to or above a minimum level for detecting the back-emf signal in the monitoring mode.

8. The drug delivery device of claim 4, wherein, while in the monitoring mode, the control unit is configured to stop provision of the driving voltage to the stator coil of the DC motor and a voltage measurement unit of the control unit is configured to detect the back-emf signal induced in the stator coil caused by rotation of the rotor of the DC motor while the control unit has stopped provision of the driving voltage.

9. The drug delivery device of claim 8, wherein, while in the monitoring mode, the control unit is configured to stop provision of the driving voltage by interrupting the driving voltage in the on state to allow detection of the back-emf signal.

10. The drug delivery device of claim 9, wherein the control unit is configured to interrupt the driving voltage for a time period selected from times including and between 0.05 to 2.0 milliseconds.

11. The drug delivery device of claim 9, wherein the control unit is configured to modulate the on state and the off state of the electric motor to control the delivery rate by periodically switching the electric motor between the on state where the rotational speed of the electric motor is equal to or greater than the minimum level, and the off state where the rotor of the electric motor stops rotation.

12. The drug delivery device of claim 11, wherein a ratio between the on state and the off state is 1 to 5.

13. The drug delivery device of claim 1 wherein the delivery rate varies between 0.1 ml/min and 10 ml/min.

14. The drug delivery device of claim 1, wherein the device includes an infusion device, a bolus injector, a patch injector, an on body delivering system, or an autoinjector.

15. A method, comprising: determining a target rotational speed for an electric motor of a drug delivery device in terms of pulse frequency based on a target delivery rate for delivery of a fluid medicament through an outlet of a reservoir of the drug delivery device; comparing the target rotational speed with a minimum rotational speed for detecting a back-emf signal of the electric motor; in response to the target rotational speed being less than a minimum rotational speed: defining a ratio between an on state and an off state such that the electric motor is operated in the on state at the minimum rotational speed and at zero speed in the off state; operating the electric motor in an alternating fashion between the on state and the off state based on the ratio in order to drive a delivery mechanism and cause advancement of a piston of the drug delivery device, wherein advancement of the piston is configured to cause the fluid medicament to be delivered at the outlet of the reservoir at a delivery rate that is based on the target delivery rate; and in response to the target rotational speed being equal to or greater than the minimum rotational speed: operating the electric motor continuously in the on state at the target rotational speed in order to drive the delivery mechanism and cause advancement of the piston of the drug delivery device, wherein advancement of the piston is configured to cause the fluid medicament to be delivered at the outlet of the reservoir at a delivery rate that is based on the target delivery rate.

16. A drug delivery device, comprising: a reservoir configured to contain a fluid medicament to be delivered by advancing a piston in the reservoir at an advancement speed defining a delivery rate for the medicament through an outlet of the reservoir; an electric motor configured to drive a delivery mechanism by rotation to advance the piston, the electric motor including a rotor and a stator coil, wherein the rotor is configured to rotate in the stator coil; a control unit configured to control a rotational speed and an on state and an off state of the electric motor, wherein the control unit is configured to determine the rotational speed of the electric motor based on a back-electromagnetic force (back-emf) signal provided from the electric motor while the electric motor is operating in a monitoring mode and measuring a back-electromagnetic force (back-emf) signal from the electric motor, wherein the control unit is configured to control the rotational speed of the electric motor while in the on state to be above a minimum speed such that a back-emf signal can be detected in the monitoring mode, and wherein the control unit is configured to modulate the on state and the off state to adjust the delivery rate to a target delivery rate, wherein, while in the monitoring mode: the control unit is configured to stop provision of a driving voltage to the electric motor by interrupting the driving voltage while in the on state, and while the control unit has stopped provision of the driving voltage to the electric motor, a voltage measurement unit of the control unit is configured to detect the back-emf signal induced by rotation of the rotor in the stator coil.

17. The drug delivery device of claim 16, wherein the control unit is configured to modulate the electric motor in the on state and the off state to control the delivery rate by periodically switching the electric motor between the on state where the rotational speed of the electric motor is equal to or greater than the minimum level, and the off state where the rotor of the electric motor stops rotation.

18. The drug delivery device of claim 17, wherein the electric motor includes a brushless direct-current (DC) motor, and wherein the control unit is configured to control the on state by providing a driving voltage to the stator coil, wherein provision of the driving voltage to the stator coil of the DC motor is configured to cause application of a driving torque to the rotor to cause rotation of the rotor.

19. The drug delivery device of claim 18, wherein the control unit is configured to control the rotational speed by intermittently providing the driving voltage to the stator coil based on a pulse frequency.

20. The drug delivery device of claim 19, wherein the control unit is configured to control the off state by stopping provision of the driving voltage to the stator coil, wherein, in response to the control unit stopping provision of the driving voltage to the stator coil, the rotation of the rotor is stopped.

Description

BRIEF DESCRIPTION OF THE DRAWINGS

[0049] FIG. 1 depicts a top view of an example of a drug delivery device according to the present disclosure.

[0050] FIG. 2 depicts a longitudinal section of the example of a drug delivery device according to the present disclosure.

[0051] FIG. 3 is a timing diagram depicting changes in rotational speed of an electric motor over time according to the present disclosure.

[0052] FIG. 4 is a timing diagram depicting modulation of an on/off state of an electric motor according to the present disclosure.

[0053] FIG. 5 is a timing diagram depicting changes in rotational speed of an electric motor over time according to the present disclosure.

DETAILED DESCRIPTION

Definitions

[0054] The term “medicament” or “medication” may include any flowable medical formulation suitable for controlled administration through a means such as, for example, a cannula or a hollow needle and includes a liquid, a solution, a gel or a fine suspension containing one or more medical active ingredients. A medicament can be a composition including a single active ingredient or a pre-mixed or co-formulated composition with more than one active ingredient present in a single container. Medication includes drugs such as peptides (e.g., insulin, insulin-containing drugs, GLP-1 containing drugs or derived or analogous preparations), proteins and hormones, active ingredients derived from—or harvested by—biological sources, active ingredients based on hormones or genes, nutritional formulations, enzymes and other substances in both solid (suspended) or liquid form but also polysaccharides, vaccines, DNA, RNA, oligonucleotides, antibodies or parts of antibodies but also appropriate basic, auxiliary and carrier substances.

[0055] The distal end or distal direction is defined by the direction of the needle configured to penetrate the skin of the patient. For an injection pen, this may be the injection needle and the end of the pen holding the needle or being configured to hold the needle is the distal end. For an infusion device the distal end and the distal direction is towards the needle configured to penetrate the skin of the patient, which may be along the axis of the device or tilted or perpendicular to the axis of the device. The distal direction in an infusion device represents the direction in which the medicament flows towards the insertion needle. The proximal direction or end is opposite to the distal direction or end.

[0056] FIG. 1 depicts an example of a drug delivery device 1 according to the present disclosure. FIG. 2 depicts a longitudinal section of the example of a drug delivery device according to the present disclosure. The drug delivery device may include a patch injector including a housing 2 providing a wall to separate at least a fluid path unit 3, a delivery unit 6 and a reservoir 15 from the ambient. The housing 2 may have an elongated shape with a bottom housing 2a intended for positioning on, or attachment to, the skin of a patient (FIG. 2). The fluid path unit 3 may include a fluid path 5 having a skin insertion needle (not shown) that is intended to move from inside the housing 2 through an aperture 23 in the fluid path unit into the skin of the patient. The fluid path 5 may include a tubing connecting the skin insertion needle to an outlet 18 of the reservoir 15. The connection between the fluid path 5 and the reservoir 15 may be a permanent connection or the fluid path 5 has a not shown reservoir needle capable of connecting to, or penetrating, the outlet 18 of the reservoir 15. The delivery unit 6 may include an electric motor 7, a gearing 8 that is coupled or connectable to the electric motor 7, a control unit 9 and a battery 26 for powering the device. The battery 26 may be part of the delivery unit 6 or may form a separate unit within the housing 2. The battery 26 powers the control unit 9 and the electric motor 7 for controlling the device and delivery of a medicament 17 though the outlet 18 of the reservoir 15. The control unit 9 controls the rotational speed and on/off state of the electric motor 7 to deliver the medicament 17 at the desired delivery rate. The rotational speed of the electric motor 7 is monitored using a sensor-less system, using the back-emf signal generated at the stator coils of the electric motor 7 during rotation of a rotor. The control unit 9 controls the rotational speed such that a reliable back-emf-signal can be detected, 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, where the driving voltage is interrupted or paused for a short period of time such that the back-emf signal can be detected and sent to the control unit. The rotation of the electric motor or a drive shaft connected to the electric motor is transmitted to the gearing 8 which advances a piston rod 14 towards a piston 16 in the reservoir 15. The reservoir includes a glass cartridge closed on one side by the moveable 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 available for the medicament 17 that is expelled via the outlet 18 through the fluid path 5 into the patient. The delivery unit may furthermore include a transmitter/receiver 10 for wireless communication with an external device such as a smart phone. The transmitter/receiver may be based on Bluetooth®, a low energy Bluetooth®, a NFC, 5G, or a ZigBee® technology. An acoustic signaling system 11 and/or a visual signaling system 13 may be part of the delivery unit 6 or form a separate unit within the housing. The visual signaling 13 may have LED lights located behind the housing 2 or a translucent section within the housing and a plurality of LED lights may signal using different colors. The plurality of LED lights may be arranged along a straight line or a curved line or individual LED lights may form a pattern. A push button 12 may be part of the housing and the user may activate the drug delivery or activate the device by pushing the push button 12.

[0057] The drug delivery device 1 may be adapted to be attached to the skin of the patient using an adhesive unit 19 (FIG. 1). The surface area of the adhesive unit 19 may be at least equal to the area of the bottom housing 2a. The adhesive unit 19 may have a larger area and a rim of the adhesive unit 19 surrounds the housing 2 of the drug delivery device 1. The adhesive unit 19 is a multilayered system including a base layer 20 providing support to an adhesive layer 21. The base layer may be a woven or 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 not shown pull tab or an aperture in the release liner and subsequently attaches the drug delivery device to the skin.

[0058] The fluid path unit 3 may form a sterile enclosure surrounding the fluid path unit 5. The sterile enclosure may be formed by a separate housing part located within the housing 2. The fluid path unit 5 includes an aperture 23 for the skin needle. Optionally, the fluid path unit 5 includes a second aperture for the reservoir needle. Both needles may be moved by an insertion mechanism 4. The skin needle may be configured to move from a retracted position, which is within the fluid path unit 3, to an inserted or extended position through the aperture 23 outside of the housing 2, and the reservoir needle may be configured to move from a retracted position within the fluid path unit 3 into the reservoir 15, for example by piercing the septum. The apertures for the skin needle and/or the reservoir needle may be covered by a sealing 24 forming a sterile barrier to protect the fluid path 5 from contamination during storage. The sealing 24 may be formed by a porous membrane such as a Tyvek membrane. Prior to use, the sealing 24 may be removed, or alternatively, the skin needle penetrates through the sealing 24. Removal of the sealing 24 may be separate from removing the release liner 22, or the sealing 24 is removed simultaneously with the release liner 22. The release liner 22 may be attached to the sealing 24 or a coupler, for example, a sticker, may connect the release liner to the sealing 24. Optionally, the release liner 22 forms the sealing 24, for example, a part of the release liner 22 may be heat sealed to the fluid path unit 3. In some examples, the sealing 24 may be separate from the release liner 22 and the base layer 20 and adhesive layer 21 may include an aperture 25 forming a passage for the reservoir needle.

[0059] The insertion mechanism 4 may be triggered by the user, for example, by pressing the push button 12 to mechanically release a mechanism (e.g., a latching mechanism), activating the insertion of the skin needle into the skin and/or the reservoir needle into the reservoir 15. Alternatively, the insertion mechanism 4 may be activated by the electric motor 7, for example by rotation in a direction that is opposite to the rotation direction for medicament delivery. The electric motor 7 may directly activate the insertion mechanism 4 or via the gearing 8. The insertion mechanism 4 may be powered by a biasing member, such as a mechanical spring (e.g., a compression or leaf spring), or the insertion itself is powered by the electric motor 7. Optionally, the insertion mechanism 4 includes a skin needle retraction mechanism such that the skin needle may be retracted into the housing 2 after the medicament has been delivered. The drug delivery device 2 may have a skin sensing system, such as a capacitive sensor sensing the proximity of the skin. The skin sensing system may be integrated with the adhesive unit 19 or may be located within the housing 2 or may be part of the bottom housing 2a. The skin sensing system may detect the proximity of the skin (skin attachment) or may detect detachment of the device from the skin. Both skin attachment as well as skin detachment may be signaled to the control unit 9 for activating the device or signaling malfunctioning to the user via the visual and/or acoustic signaling system 13, 11.

[0060] Example operation and control of the electric motor 7 for the drug delivery device 1 presented above with reference to FIGS. 1 and 2 is presented in FIGS. 3 to 5. In some examples, a brushless DC motor may be used and the pulsed driving voltage may be directed by the control unit 9 to at least one of the plurality of stator coils such that the rotor is set in rotation due to the driving torque applied with each pulse. In some examples, each pulse may correspond to one step of rotation and the rotor is set in rotation by applying voltage pulses to subsequent stator coils of the plurality of stator coils, or in other words, applying commutation. By changing the frequency of the pulses directed to the stator coils, the rotational speed of the rotor may be controlled. The rotational speed of the rotor (e.g., revolutions/s) may linearly correlate with the pulse frequency in pulses per second (pps).

[0061] FIG. 3 is a timing diagram depicting changes in rotational speed of an electric motor over time according to the present disclosure. In FIG. 3, the rotational speed is shown as a function of time. If the rotational speed that is required for a desired delivery rate is above the minimum level for detecting a reliable back-emf signal, then the control unit ensures that the electric motor is running continuously in the on-state (e.g., represented by a solid horizontal line in FIG. 3). In the example depicted in FIG. 3, during the on-state the rotor rotates and the driving voltage is interrupted in the monitoring mode for a time period (e.g., 0.5 milliseconds) to allow for measuring the back-emf signal.

[0062] If the delivery rate or the targeted delivery rate is lower, and this may result in operation of the electric motor at a target rotational speed below the minimum level for reliable back-emf detection (shown as the dotted line), then the control unit may switch the electric motor between the on-state, where the rotational speed is sufficient for detecting a reliable back-emf signal in the monitoring mode, and the off-state where the driving voltage is interrupted for a longer period of time such that the rotor stops rotating. By modulation of the on and off-time, the medicament can be delivered at the desired or targeted (low) volumetric delivery rate without compromising the sensorless detection of the rotational speed for rotor in the electric motor. FIG. 4 is a timing diagram depicting modulation of an on/off state of an electric motor according to the present disclosure. In the example depicted in FIG. 4, the electric motor is controlled such that it is for ⅔ of the time in the on-state and for ⅓ of the time in the off-state. It is appreciated that the on-off duty cycle depicted in FIG. 4 is exemplary, and other on/off duty cycles may be implemented without departing from the scope of the disclosure.

[0063] A more detailed calculation for the modulation is presented in the following. The targeted rotational speed is expressed in pulses per seconds (pps) and, in this example, a minimum level of V.sub.min=33 pps is required for detection of reliable back-emf signal. This may correspond to the minimum rotational speed for back-emf detection. There may also be a minimum number of steps required (each pulse corresponds to one step) for detecting changes in rotation. Such a change in rotation can be due to mechanical blockage in the gearing mechanism or an occlusion within the fluid path. Such blocking may need a certain number of steps to be recorded prior to blockage to ensure a reliable detection of a rotating rotor. The minimum steps may depend on the sensitivity of the system. For this specific, non-limiting example, the minimum number of steps is S.sub.min=100 steps.

[0064] The on-time (t.sub.on) may be calculated as:

t.sub.on=S.sub.min/V.sub.min

[0065] In this example, the on-time is 3 seconds.

[0066] The percentage of the time where the device is operated in the on-state (on %) may be calculated as the ratio between the target delivery rate (V.sub.target) and the minimum detection speed (V.sub.min):

On %=V.sub.target/V.sub.min

[0067] If the desired or targeted delivery rate V.sub.target (volumetric) corresponds to a target rotational speed in terms of a pulse frequency of 11 pps, then the device is operated for 11/33 is 33% (on %) of the time in the on-state (for 3 seconds, t.sub.on).

[0068] The percentage of the time where the device is operated in the off-state (off %) is calculated as:

off %=1−on %

[0069] And the ratio between the on-state and the off-state (R.sub.on/off) where the device is operated in the on-state is calculated as:

R.sub.on/off=V.sub.target/V.sub.min/(1−V.sub.target/V.sub.min)

[0070] For the current example, the on/off ratio is thus 1:2. And the off time can be calculated as:

t.sub.off=t.sub.on/R.sub.on/off

[0071] FIG. 5 is a timing diagram depicting changes in rotational speed of an electric motor over time according to the present disclosure. In this example, the device is thus operated for 3 seconds in the on-state and for 6 seconds in the off-state, which is presented in FIG. 5.

[0072] If the targeted delivery rate corresponds to a pulse frequency of 40 pps (e.g. above the minimum level of 33 pps for back-emf detection) then the device is continuously operated in the “on” state. See FIG. 5. It is appreciated that the specific pps and time values and the on-off duty cycle depicted in FIG. 5 are exemplary, and other pps and time values and on/off duty cycles may be implemented without departing from the scope of the disclosure.

[0073] Variations on the voltage modulation can easily be calculated. For example for a more sensitive system, it may take S.sub.min=66 steps for a reliable detecting of rotation and in that case, with a minimum speed level V.sub.min=33 pps for back-emf detection, it may take 66/33=2 seconds rotation at 33 pps. If the required delivery rate corresponds to 22 pps, then the control unit operates the device for 2 seconds in the on-state and for 1 second in the off-state. Thus, an interval operation where ⅔ of the time the device is in the on-state, as shown in FIG. 4.

[0074] 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 fulfill the purpose of “a control unit”.

LIST OF REFERENCE SIGNS

[0075] 1 Drug delivery device [0076] 2 Housing [0077] 2a Bottom housing [0078] 3 Fluid path unit [0079] 4 Insertion mechanism 17 Medicament [0080] 5 Fluid path [0081] 6 Delivery unit [0082] 7 Electric motor [0083] 8 Gearing [0084] 9 Control unit [0085] 10 Transmitter/receiver [0086] 11 Acoustic signaling [0087] 12 Push button [0088] 13 Optical signaling (LED) [0089] 14 Piston rod [0090] 15 Reservoir [0091] 16 Piston [0092] 18 Outlet [0093] 19 Adhesive unit [0094] 20 Base layer [0095] 21 Adhesive layer [0096] 22 Release liner [0097] 23 Aperture fluid path unit [0098] 24 Sealing [0099] 25 Aperture base layer/adhesive layer [0100] 26 Battery