Patent Application
20150088092
The present invention generally relates to a drug delivery device adapted to receive a drug filled cartridge and expel a dose therefrom. More specifically, the invention relates to the issue of informing a user of user-relevant events after detection of an end-of-dose condition.
In the disclosure of the present invention reference is mostly made to the treatment of diabetes, however, this is only an exemplary use of the present invention.
The most common type of durable drug delivery devices adapted to receive a drug filled cartridge and expel a set dose therefrom are driven by manual means or by a spring energized during dose setting, the cartridge being of the type comprising an axially displaceable piston having an initial proximal position. The device may be pen-formed or in the form of a more box-shaped so-called doser. In order to improve convenience, user-friendliness and provide additional features, e.g. detection and storing of expelling data, drug delivery devices have been provided with electrically driven means, typically in the form of an electronically controlled motor driving a piston rod through a gear arrangement, e.g. as shown in U.S. Pat. No. 6,514,230 and US 2011/306927. The same arrangement is also used in infusion pumps, e.g. as shown in U.S. Pat. No. 7,193,521. When a new cartridge is loaded into a motor-driven drug delivery device the piston is first moved proximally allowing a full cartridge to be inserted after which the piston rod is moved into contact with the cartridge piston to bring the drug delivery device in an operational state. The loading of a new cartridge may be performed manually, i.e. the user actuates buttons moving the piston rod back and forth, or it may be partly or fully automated, e.g. the device detects that a cartridge cover is opened and moves back the piston rod, this allowing the user to remove the used cartridge, insert a new and close the cover. When the device detects that the cover has been closed and a cartridge is inserted the piston rod is automatically advanced into engagement with the piston where after the device is ready for use or further initial operations, e.g. a user operated air shot to drive out air in the cartridge or an attached needle.
As indicated above, after a cartridge has been loaded proper operation of the system can be checked by performing an air shot until visible drug appears at the tip of the needle. Such a check can be performed both initially when a new cartridge has been loaded as well as each time a new needle is mounted to check that the needle is not defect or blocked, this also being the recommend when mounting a new needle. Although it is not recommend using a needle more than once, proper operation of a used needle should also be checked prior to each drug delivery. However, just as all users do not follow these recommendations, a needle may also be blocked during use, e.g. either by external matter during skin insertion or internal matter contained in the cartridge, e.g. crystals formed in the drug or dried-up drug from previous injections.
Correspondingly, for a motorized drug delivery device detection systems have been proposed adapted to detect a blocked needle condition or, for a similar type of device, a blocked infusion needle or infusion catheter in a drug delivery pump for continuous drug administration. Such systems have been based on the fact that when the infusion conduit, e.g. needle or catheter, downstream of the cartridge is blocked, then a blockage can be detected directly or indirectly by detecting pressure-build up in the system. For example, when resistance to piston movement increases the electric current to the motor in many control systems will increase which can then be detected and used to determine pressure rise and thus assumed needle or catheter blockage. Alternatively, US 2003/0073954 discloses the use of electronic switches and strain gauge sensors to detect pressure build up in an occluded system. US 2011/0172594 discloses that an occlusion detection sensor can be configured to detect alteration of a shape of the occlusion detection portion, e.g. by means a pressure sensor, a capacitance sensor, an optical sensor, or other type of sensor. However, in some systems and under some conditions, an occlusion may not result in a change of parameters which are sufficient to detect an actual occlusion. For example, in cartridge based system in which a set dose is small, e.g. less than 5 IU for a traditional 3 ml 100 Um/ml insulin cartridge, then the corresponding axial displacement of the piston drive member, e.g. the piston rod, will in most cases be absorbed by the cartridge piston which typically is manufactured from a polymeric rubber material. In this way the piston driver may be fully forwarded to an end-of-dose position merely deforming the piston and thus without a corresponding pressure or tension build-up in the drive system. Indeed, if a further elastic system such as a catheter infusion line is arranged between the cartridge and infusion needle then further piston driver movement may be absorbed without a corresponding pressure or tension build-up in the drive system.
Further, injection systems using an elastic rubber piston is characterised in that the piston will be more or less compressed when the piston drive is advanced. When the piston drive stops moving when it has reached its end-of-dose position, the piston will expand to its original form. The selected dose is not fully delivered until the piston has reached its form just before starting the injection. How much the piston is compressed depends mainly on the friction between the piston and the glass cartridge plus the counter pressure that builds up when the liquid has to pass through the very thin needle. This is the main reason why the user is recommended to keep the needle inserted for some period—typically six seconds. Removing the needle before six seconds has elapsed might lead to an under dose of up to 1 IU which could be substantial for small doses. Waiting six seconds is cumbersome and some users might ignore it with the risk of an under dose as a consequence. In most cases more than 95% of the dosage is delivered within 1-2 seconds after stopping the piston drive.
Having regard to the above, it is an object of the present invention to provide a method and a motorized drug delivery device adapted to receive a drug-filled cartridge, and which are adapted to detect one or more user-relevant end-of-dose conditions (events), i.e. conditions following the formal end of out-dosing. The conditions should be detected in a simple and effective way, the arrangement being sensitive, cost-effective and reliable. A specific object of the invention is to provide a system which will detect that a given dose has been (almost) fully delivered which in most cases will be before six seconds has elapsed. A further specific object of the invention is to provide a system which will detect an outlet blockage, e.g. a blocked needle.
In the disclosure of the present invention, embodiments and aspects will be described which will address one or more of the above objects or which will address objects apparent from the below disclosure as well as from the description of exemplary embodiments.
Thus, in accordance with a first aspect of the invention a method of detecting an end-of-dose condition in a pressurized system is provided, the method comprising the step of providing a system comprising a fluid-filled variable volume reservoir comprising an elastically deformable portion and an outlet, the elastically deformable portion having an initial configuration, means for pressurizing the interior of the reservoir to thereby expel fluid through the outlet, and means for measuring a property of the elastically deformable portion which varies with the internal pressure in the reservoir. The method comprises the further steps of actuating the pressurizing means to pressurize the reservoir to expel a desired amount of fluid by applying a force, thereby deforming the elastically deformable portion, measuring, after the actuating step, a property related to the elastically deformable portion as it regains its initial configuration, comparing a value for the measured property with one or more threshold values, and providing a user with an indication when a given threshold value has been reached, and/or when a given threshold value has not been reached within a given period of time.
In this way a method is provided adapted to detect user-relevant “end-of-dose” conditions taking place after actuation of the pressurizing means has stopped, e.g. an indication is provided that expelling of the desired amount of fluid has (almost) ended when the given threshold value has been reached, and/or an indication is provided that an occlusion state applies to the reservoir outlet when a given threshold value has not been reached within a given period of time.
In the context of the present invention the threshold value to be reached may not only be a specific value but may also be in the form of a rate of change of the measured property.
Values for the measured property after the actuating step may be determined based on a number of discrete measurements or continuous measurement of the property. Indeed, also continuous measurement normally takes place at a given sampling rate.
The one or more threshold values may be determined based on a reference value such as a value determined prior to pressurizing the reservoir, or a value determined at the end of the action pressurizing the reservoir. For example, a reference value may have been determined just prior to pressurizing the reservoir. Based on this value a difference to the end-of-dose value can be calculated which again can be used to calculate a threshold value. For example, the threshold value may correspond to when 90% of the difference between the two values has been regained, this indicating when the set dose has been almost fully expelled, typically after 1-2 seconds. Correspondingly, when a given threshold value, e.g. the same as above, has not been reached within a given period, e.g. 6 seconds, an occlusion state may be detected. Other values may be used.
The provided system may further comprise a reflecting surface adapted to reflect light, a light source directing light against the reflecting surface, and a light sensor adapted to measure light from the light source reflected from the reflecting surface, a measured light value varying with the deformation of the elastically deformable portion, wherein the measured property is light reflected from the reflecting surface.
The reservoir of the provided system may comprise a main portion having a general cylindrical configuration, and an axially displaceable piston arranged in the main portion, the piston comprising at least a part of the elastically deformable portion, and the reflecting surface. Alternatively to reflected light, the measured property may be pressure in the reservoir or tension in a part of the pressurizing means.
In accordance with a second aspect of the invention a drug delivery device is provided comprising a drug-filled cartridge in a loaded position or a compartment adapted to receive a drug-filled cartridge in a loaded position, the cartridge comprising a generally cylindrical body portion, an axially displaceable elastically deformable piston with a proximal portion comprising a surface adapted to reflect light, and a distal outlet portion adapted to be arranged in fluid communication with a flow conduit. The device further comprises an expelling assembly comprising an axially displaceable piston drive member adapted to engage the proximal piston portion of a loaded cartridge, the piston drive member being moveable in a distal direction to thereby expel drug from a loaded cartridge, the piston thereby being elastically deformed by the piston drive member from its initial configuration, a light source providing a light directed at least in part against the proximal piston portion of a loaded cartridge, a light sensor adapted to measure light from the light source reflected from the proximal piston portion, the light sensor being arranged to provide a measured value varying with the deformation of the piston, and a controller coupled to the light sensor. The controller is configured to detect (with a cartridge in a loaded position) an end-of-stroke state when the piston drive member has just been moved to a position corresponding to expelling of a set dose, the end-of-stroke state being characterized by the piston being elastically deformed by the piston drive member corresponding to a build-up of pressure in the cartridge, measure, after detection of the end-of-stroke state, light from the light source reflected from the proximal piston portion as the piston regains its initial configuration, and compare a measured light value with one or more threshold values. The controller is further configured to provide a user with an indication (e.g. that expelling of the desired amount of fluid has ended) when a given threshold value has been reached, and/or when a given threshold value has not been reached within a given period of time, e.g. an indication that an occlusion state applies to the reservoir outlet.
The threshold may be determined based on a reference value being one of a value determined prior to pressurizing the reservoir, and a value determined at the end of the action pressurizing the reservoir. The light source and the light sensor provide at least in part a proximity sensor system adapted to provide an output indicative of the distance between the proximal piston portion and the piston drive member.
In exemplary embodiments the expelling assembly is electronically controlled, the controller being coupled to the expelling assembly and adapted to control the expelling assembly in order to expel a set dose. The light source and/or the light sensor may be coupled to and move with the piston drive member.
In accordance with a further aspect of the invention an exemplary drug delivery device is provided comprising a drug-filled cartridge in a loaded position or a compartment adapted to receive a drug-filled cartridge in a loaded position, the cartridge comprising a body portion, an axially displaceable elastically deformable piston with a proximal portion comprising a surface adapted to reflect light, and a distal outlet portion adapted to be arranged in fluid communication with a flow conduit, an expelling assembly comprising an axially displaceable piston drive member adapted to engage the proximal piston portion of a loaded cartridge, the piston drive member being moveable in a distal direction to thereby expel drug from a loaded cartridge, the piston thereby being elastically deformed by the piston drive member. A light source provides a light directed at least in part against the proximal piston portion of a loaded cartridge, a light sensor is adapted to measure light from the light source reflected from the proximal piston portion, the light sensor being arranged to provide a measured value varying with the deformation of the piston. A controller is coupled to the light sensor. With a cartridge in a loaded position the controller is configured to: Detect a first “end-of-stroke” state when the piston drive member has just been moved to a position corresponding to expelling of a set dose, the first state being characterized by the piston being elastically deformed by the piston drive member corresponding to a build-up of pressure in the cartridge. Then after a given amount of time determine an end-of-dose sensor value based on light reflected from the proximal piston portion, and compare the end-of-dose sensor value with a reference value. Based on the difference between the end-of-dose sensor value and the reference value, the controller is configured to determine (i) a non-occlusion state when the elastically deformed piston has relaxed to such a degree that it is indicative of a reduction in the pressure build-up in the cartridge due to drug being expelled from the cartridge via a connected flow conduit by energy stored in the deformed piston, or (ii) an occlusion state when the elastically deformed piston has failed to relax thereby being indicative of a connected flow conduit being occluded. By this arrangement it is possible to detect an occlusion state for the delivery of relatively small dose amounts of drug from a drug delivery device. Alternatively a sound generator and an acoustic sensor could be used instead of the light source and light sensor.
The expelling assembly may be mechanical or electronically controlled, the controller being coupled to the expelling assembly and adapted to control the expelling assembly in order to expel a set dose. The light source and/or the light sensor may be coupled to and move with the piston drive member.
The reference sensor value may be determined in different ways, e.g. it may be determined prior to the piston drive being moved to expel a set dose or when the piston drive has just been moved to the position corresponding to expelling of a set dose. The reference sensor value may also be a pre-set value or it may be calculated from one or more determined values. Alternatively, instead of determining an end-of-dose sensor value the sensor output may be analysed over a period of time and used to determine an occlusion or non-occlusion state, e.g. by determining the rate of sensor value change.
The light source and the light sensor may also provide at least in part a proximity sensor system adapted to provide an output indicative of the distance between the proximal piston portion and the piston drive member. Such an output may be used to control movement of the piston drive member during initial cartridge loading.
The controller may be in the form of a CPU or a microcontroller as well as their supporting components or any other configuration of electronic components suitable for the described functionality.
The drug delivery device as described above may be provided in combination with a drug-filled cartridge comprising an axially displaceable piston having a proximal portion, the proximal portion comprising a surface adapted to reflect light as well as an engagement portion adapted to engage the piston drive member.
In a yet further aspect of the invention a method of detecting an obstruction of an outlet from a pressurized system is provided, comprising the steps of (a) providing a system comprising a fluid-filled variable volume reservoir comprising an elastically deformable portion and an outlet, means for pressurizing the interior of the reservoir to thereby expel fluid through the outlet, and means for detecting a property of the elastically deformable portion which varies with the internal pressure in the reservoir, (b) actuating the pressurizing means to pressurize the reservoir to expel a desired amount of fluid by applying a force, thereby deforming the elastically deformable portion, (c) after or over a given time after the actuating step measuring a property related to the elastically deformable portion, (d) comparing the measured property with a reference value, and (e) based on the result of the comparing step decide whether (i) a non-occlusion state or (ii) an occlusion state applies to the reservoir outlet.
More than one reference value may be used to improve accuracy of the system. By the described method it may be possible to detect an occlusion based on a pressure build-up which is normally associated with normal operation of a system.
A given reference value may be one of a rate of change of the measured property, a sensor value determined prior to pressurizing the reservoir, a sensor value determined at the end of the action pressurizing the reservoir, and a pre-set value.
In exemplary embodiments the provided system further comprises a reflecting surface adapted to reflect light, a light source directing light against the reflecting surface, and a light sensor adapted to measure light from the light source reflected from the reflecting surface, a measured value varying with the deformation of the elastically deformable portion, wherein the measured property is light reflected from the reflecting surface. Alternatively a sound generator and an acoustic sensor could be used instead of the light source and light sensor.
The reservoir of the provided system may further comprise a main portion having a general cylindrical configuration, and an axially displaceable piston arranged in the main portion, the piston comprising at least a part of the elastically deformable portion, and the reflecting surface.
Alternatively, other properties could be measured. For example, if an elastically deformable piston is made at least in part by a material having a dielectric constant different from air then a sensor system could be adapted to measure changes in deformation using capacitance. If an elastically deformable piston is made at least in part by a material having magnetic properties which changes with deformation a sensor system could be adapted to measure changes in deformation using such properties. As a further alternative an elastically deformable piston may be provided with a strain gauge allowing deformation to be measured.
In a further aspect of the invention a drug delivery device is provided comprising a housing, means for receiving and holding a drug-filled cartridge in a loaded position, the cartridge having a cylindrical configuration comprising an axially displaceable piston, the cartridge being adapted to be fitted with a hollow needle in fluid communication with the drug, a needle fitted on a loaded cartridge projecting from a distal end of the device, motor driven drug expelling means comprising a piston drive adapted to engage the piston of a loaded cartridge, the piston drive being axially moveable in a distal direction and along a general axis to thereby expel drug from a loaded cartridge, position detecting means adapted to measure the inclination of the general axis relative to a vertical position, a flow check state being determined when the position detecting means measures that the general axis is oriented within a pre-defined range relative to the vertical position, and a controller coupled to the position detecting means and adapted to control the expelling means. In such a device the controller is adapted to move the piston drive in the distal direction when a flow check state is determined, whereby, when the piston drive is engagement with the piston of a loaded cartridge fitted with a hollow needle, drug is expelled from the cartridge. In this way a user can perform an air-shot in an easy and convenient way without having to operate any buttons.
The drug delivery device may further comprise a cap releasably mountable on the drug delivery device and adapted to cover a fitted needle, as well as cap sensing means coupled to the controller and adapted to detect either a cap-off state or a cap-on state, wherein, when a cap-on state is detected, the controller will not move the piston drive based on input from the position detecting means. The controller may, when the conditions are met, start moving the piston drive after a pre-determined time delay. To avoid a jet of expelled drug, the controller may forward the piston drive in smaller steps, this allowing a droplet to neatly form at the distal tip of an attached needle. Proximity sensing means may be coupled to the controller and adapted to measure the distance of the distal end of the device from a skin surface, a proximity state being determined when a distance within a pre-defined range is measured, such that, when a flow check state and a proximity state are detected, the controller will not move the piston drive, this preventing misuse of the automated expelling. Further restraints to automated expelling may be implemented, e.g. maximum size and number of expelled air-shot doses.
In a yet further aspect of the invention a drug delivery device is provided comprising a housing, means for receiving and holding a drug-filled cartridge in a loaded position, the cartridge being adapted to be fitted with a hollow needle in fluid communication with the drug, a needle fitted on a loaded cartridge projecting or being adapted to project from a distal end of the device, and expelling means adapted to engage a loaded cartridge. The device further comprises detecting means adapted to measure and determine a delivery condition, and a controller coupled to the detecting means and adapted to control the expelling means, wherein the controller is adapted to actuate the expelling means when a delivery condition is determined, whereby, when a hollow needle is connected to the cartridge, drug is expelled from the cartridge. By this arrangement use of the drug delivery is simplified as the user no longer has to release or actuate the expelling mechanism.
The needle may be mounted in a fixed position projecting from the housing and thus adapted to be inserted manually, or it may be arranged in an initially retracted position and then inserted automatically prior to expelling of drug, e.g. initiated by detection of a delivery condition. The detecting means may be adapted to measure e.g. proximity of the device to a surface (e.g. light reflection as described above or sound reflection), actuation of a mechanical member (e.g. a mechanical switch), skin contact (e.g. based on properties unique to a skin surface), and needle insertion when performed manually (e.g. based on the needle having or providing a property that changes when it is inserted). The cartridge may comprise an axially displaceable piston and the expelling means may comprise a corresponding piston drive member.
As used herein, the term “drug” is meant to encompass any flowable medicine formulation capable of being passed through a delivery means such as a cannula or hollow needle in a controlled manner, such as a liquid, solution, gel or fine suspension, and containing one or more drug agents. Representative drugs include pharmaceuticals such as peptides (e.g. insulins, insulin containing drugs, GLP-1 containing drugs as well as derivates thereof), proteins, and hormones, biologically derived or active agents, hormonal and gene based agents, nutritional formulas and other substances in both solid (dispensed) or liquid form. In the description of exemplary embodiments reference will be made to the use of insulin containing drugs, this including analogues thereof as well as combinations with one or more other drugs.
In the following exemplary embodiments of the invention will be further described with reference to the drawings, wherein
In the figures like structures are mainly identified by like reference numerals.
When in the following terms such as “upper” and “lower”, “right” and “left”, “horizontal” and “vertical” or similar relative expressions are used, these only refer to the appended figures and not to an actual situation of use. The shown figures are schematic representations for which reason the configuration of the different structures as well as their relative dimensions are intended to serve illustrative purposes only.
An exemplary embodiment of the invention is implemented in an electronically controlled motorized drug delivery device adapted to receive a drug-filled cartridge comprising an outlet and an axially displaceable piston, the device comprising a housing, a compartment adapted to receive and hold a cartridge, an electronically controlled expelling assembly comprising an axially displaceable piston drive member adapted to engage the piston of a loaded cartridge, a controller coupled to the expelling assembly and configured to control the expelling assembly to move the piston in a distal direction to thereby expel drug from a loaded cartridge, an electrical energy source for the controller and the expelling assembly, as well as user-operated input means for setting a desired dose of drug to be expelled. Such a drug delivery device is known per se, e.g. in the form of a compact doser incorporating a flexible piston rod as disclosed in U.S. Pat. No. 6,514,230, a pen-formed device incorporating a rigid piston rod as disclosed in US 2011/306927 or an infusion pump as disclosed in U.S. Pat. No. 7,193,521 which are all hereby incorporated by reference.
As also described initially, a motorized drug delivery device is adapted to have an empty cartridge replaced with a new cartridge in which course the piston rod is normally moved proximally to a loading position by the motorized expelling assembly, which action may be activated by e.g. a cover being opened or a button being pressed. Correspondingly, when a new cartridge has been inserted the piston rod is normally moved automatically distally to a loaded position in contact with the piston by the motorized expelling assembly, which action may be activated by a cover being closed or a button being pressed. The device may further be provided with means for detecting that a cartridge has been loaded to prevent an initialization procedure when no cartridge is mounted.
Referring to
In
In
Correspondingly, the controller 30 is configured to detect an end-of-stroke (or end-of-dose) state when the piston drive member has just been moved to the end-of-stroke position corresponding to the fully expelling of a set dose, the end-of-stroke state being characterized by the piston being elastically deformed by the piston drive member corresponding to a build-up of pressure in the cartridge. After a given amount of time (e.g. 3 seconds) an end-of-dose sensor value is determined based on light reflected from the proximal piston portion which is then compared with a reference value. Based on the difference between the end-of-dose sensor value and the reference value the controller determines whether the system is in (i) a non-occlusion state in which the elastically deformed piston has relaxed to such a degree that it is indicative of a reduction in the pressure build-up in the cartridge due to drug being expelled from the cartridge via a connected flow conduit, e.g. a needle, by energy stored in the elastically deformed piston, or (ii) an occlusion state in which the elastically deformed piston has failed to relax to such a degree that is can be determined as being indicative of a connected flow conduit being occluded. If an occlusion state is detected the controller may indicate this to the user by appropriate signal means like an acoustic, visual and/or vibrational alarm.
In the
In the shown example a blocking condition is determined if L-ref2>k (ref1-ref2), in which k is a constant indicating the expected level of reproduction of the initial reflexion level. In the shown example k=50% although ideally k=100%. The following conditions must also be met: L>ref2 and ref1>ref2. Otherwise an error condition is detected. In the shown embodiment 1.6−0.5=1.1>0.5 (2.2−0.5)=0.85 indicating the expected finding of a non-occlusion state. All sensor values mentioned refers to measurements by the same sensor.
The determination of reference values is used to compensate for variations in e.g. sensors, materials and mounting. The determination of further reference values could be used to compensate e.g. non-linear output from a sensor system.
The algorithm used in the experiment according to
Correspondingly,
In the above description of the preferred embodiments, the different structures and means providing the described functionality for the different components have been described to a degree to which the concept of the present invention will be apparent to the skilled reader. The detailed construction and specification for the different components are considered the object of a normal design procedure performed by the skilled person along the lines set out in the present specification.
| Number | Date | Country | Kind |
|---|---|---|---|
| 12165249.9 | Apr 2012 | EP | regional |
| Filing Document | Filing Date | Country | Kind |
|---|---|---|---|
| PCT/EP2013/058456 | 4/24/2013 | WO | 00 |
| Number | Date | Country | |
|---|---|---|---|
| 61639393 | Apr 2012 | US |
