WO2009112513A1

WO2009112513A1 - Drug delivery system with two communicating devices providing continuous drug delivery

Info

Publication number: WO2009112513A1
Application number: PCT/EP2009/052843
Authority: WO
Inventors: Ole Christian Nielsen
Original assignee: Novo Nordisk AS
Current assignee: Novo Nordisk AS
Priority date: 2008-03-11
Filing date: 2009-03-11
Publication date: 2009-09-17
Anticipated expiration: 2010-09-11

Abstract

The invention provides a drug delivery system comprising a first drug delivery device (50) adapted to deliver a drug from a first reservoir and having, a transmitter, and a second drug delivery device (60) adapted to deliver a drug from a second reservoir and having a receiver, wherein the first drug delivery device is adapted to transmit a start signal to the second drug delivery device when a given remaining amount of drug has been detected in the first reservoir, and wherein the second drug delivery device starts to expel drug from the second reservoir when the start signal has been received.

Description

DRUG DELIVERY SYSTEM WITH TWO COMMUNICATING DEVICES PROVIDING CONTINUOUS DRUG DELIVERY

The present invention generally relates to drug delivery devices intended for continuous delivery of a drug from a reservoir. In a specific aspect such devices may be disposable and comprise a pre-filled reservoir containing a fluid drug and expelling means for expelling fluid drug out of the reservoir and through the skin of the subject via the transcutaneous device.

BACKGROUND OF THE INVENTION

A general problem with a continuous drug delivering device (e.g. an insulin pump) where the user gets drug on a continuous base is that the finishing of the drug now and then happens at an inconvenient time. Either because the user is asleep or because he would prefer not to have to change the drug reservoir at that specific time or if the device can't be refilled (reloaded) with drug he would prefer not to have to change the device itself with a new one at that specific time. It has been proposed to provide a drug delivery system with two reservoirs whereby the system can switch between an empty and a full reservoir.

DISCLOSURE OF THE INVENTION

Having regard to the above-identified problems, it is an object of the present invention to provide a drug delivery device and system which is compact in size yet allows continuous delivery of drug when a drug reservoir has been emptied. The configuration of the system and the components therefore should contribute in providing a medical delivery means which allows for easy and swift operation yet being reliable in use.

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.

If the continuous drug delivering device is a disposable device where the use of the device finishes when the drug reservoir is recognized as emptied by the device a solution is to attach at least one device more to the user and to let the 2 or more devices intercommunicate (directly or through another type of device, e.g. a remote control) letting the first device tell the second device that it is empty and that it can now take over the delivery of the drug to the user. This communication could be wired or wireless. Thus, in a first aspect of the invention a drug delivery system is provided comprising (a) a first drug delivery device adapted to deliver a drug, comprising: a first reservoir containing a fluid drug, expelling means adapted for cooperation with the first reservoir to expel fluid drug out of the reservoir, means for determining a remaining amount of drug in the first reservoir, and transmitting means, (b) a second drug delivery device adapted to deliver a drug, comprising: a second reservoir containing a fluid drug, expelling means adapted for cooperation with the second reservoir to expel fluid drug out of the reservoir, and receiving means, wherein the first drug delivery device is adapted to transmit a start signal to the second drug delivery device when a given remaining amount of drug is left in the first reservoir, and wherein the second drug delivery device is adapted to start expelling drug from the second reservoir when the start signal is received by the receiving means.

The given amount of drug in the first reservoir may be more than zero, and expelling of drug from the first reservoir stops when the start signal has been transmitted to the second drug delivery device. The given amount of drug may be fixed or it may be dynamic, e.g. calculated on the basis of the estimated remaining time for the drug in the reservoir and/or influenced by other properties such as time of the day. The first and second drug delivery device may be adapted to communicate bi-directional, such that expelling of drug from the first reservoir stops when a signal has been received from the second drug delivery device indicating that expelling of drug from the second reservoir has started. The system may alternatively comprise a remote controller with the first and second drug delivery device being adapted to communicate with each other via the remote controller. The first and second drug delivery device of the system may be substantially identical, e.g. varying only by different serial numbers.

The remaining amount of drug may be detected by directly detecting the remaining amount of drug in the first reservoir (e.g. by detecting the position of a piston drive member), or indirectly detecting the remaining amount of drug in the first reservoir by detecting the amount of drug expelled from the first reservoir (e.g. by detecting electronic impulses driving the expel- ling means). Each of the drug delivery devices may comprise a mounting surface adapted for application to the skin of the subject, just as reservoirs may be prefilled.

In the above a system in accordance with the invention has been described, however, the invention also provide an individual drug delivery device adapted to operate as part of the system. Thus, in a second aspect of the invention a drug delivery device is provided comprising a reservoir containing a fluid drug, expelling means adapted for cooperation with the reservoir to expel fluid drug out of the reservoir, means for determining a remaining amount of drug in the reservoir, and transmitting and receiving means. The drug delivery device is further adapted to receive a start signal from a first further drug delivery device, start expelling drug from the reservoir when the start signal is received by the receiving means, transmit a signal to the first further drug delivery device indicating that expelling of drug from the reservoir has started, and transmit a start signal to a second further drug delivery device when a given remaining amount of drug is left in the first reservoir. The expelling of drug from the reservoir stops when a signal has been received from the second further drug delivery device, this indicating that expelling of drug from the second further drug delivery device has started. The device may comprise the above-described further features for a drug delivery device.

The expelling means may be of any convenient type, e.g. a piston drive for expelling drug from a cylinder-piston cartridge, or a membrane pump for expelling drug from a flexible or ventilated reservoir.

If the continuous drug delivering device can be reloaded with a drug reservoir the pump should be adapted to keep a buffer amount of drug taken from the drug reservoir. This buffer should be large enough to keep drug for a suitable period (e.g. a sleeping period) making it possible to remove the now empty reservoir and reload the device with a fresh drug reservoir. When the buffer is emptied delivery will continue from the new reservoir. The other solution is to reload the device with a fresh drug reservoir before the already in-use reservoir is emptied hereby having both reservoirs connected to or included in the delivering device at the same time and letting the device switch to the new reservoir automatically when the already in-use reservoir gets emptied.

Thus, in a further aspect of the invention a drug delivery system is provided comprising a first reservoir containing a fluid drug, a second replaceable reservoir containing a fluid drug, and expelling means for expelling fluid drug out of the reservoirs, wherein the first reservoir can be filled from the second reservoir, this allowing drug to be expelled from the first reservoir during replacement of the second reservoir. In such a device replacement of an old second reservoir with a new second reservoir may result in the first reservoir being substantially emptied from drug before the first reservoir is filled with drug from the new second reservoir. By the above arrangements the user don't have to change the drug reservoir or (disposable) device at the specific time when it's empty but can wait until the time is convenient for him. This will improve convenience for the user or reduce loss of drug because the user alternatively changes the drug reservoir or (disposable) device before the drug reservoir is empty. These major advantages are even greater when a user is depending on another person to change drug reservoir or device.

As used herein, the term "drug" is meant to encompass any drug-containing flowable medicine capable of being passed through a delivery means such as a hollow needle in a con- trolled manner, such as a liquid, solution, gel or fine suspension. Representative drugs include pharmaceuticals such as peptides, 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 the exemplary embodiments reference will be made to the use of insulin. Correspondingly, the term "subcutaneous" infusion is meant to encompass any method of transcutaneous delivery to a subject. Further, the term needle (when not otherwise specified) defines a piercing member adapted to penetrate the skin of a subject.

BRIEF DESCRIPTION OF THE DRAWINGS

In the following the invention will be further described with references to the drawings, wherein

fig. 1 shows a user input device in the form of a remote control (RC), fig. 2 shows a patch unit useful with the present invention, fig. 3 shows the patch unit of fig. 24 in an actuated state, fig. 4 shows a patch unit with a pump unit partly attached, fig. 5 shows the pump unit of fig. 4 fully attached to the patch unit, fig. 6 shows in an exploded view a pump unit, fig. 7 shows a schematic representation of a process unit and a control unit, fig. 8 shows a first embodiment of a drug delivery system, and fig. 9 shows a second embodiment of a drug delivery system.

In the figures like structures are mainly identified by like reference numerals.

DESCRIPTION OF EXEMPLARY EMBODIMENTS 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 present invention comprises two skin-mountable drug delivery devices and a remote control adapted to be in wireless communication with the two devices. Each drug delivery device comprises a patch unit and a pump unit.

Fig. 1 shows a user input device 1 in the form of a remote control (RC) comprising an LCD display 30 arranged at the upper portion of the unit and buttons arranged beneath the display. The placement close to the centre line is chosen for ergonomic reasons. The remote comprises a rocker switch 10 and a left ACCEPT key 21 as well as a right ESCAPE key 22. The rocker switch is the fundamental navigation button and is a four-way switch having four areas 11 , 12, 13, 14 supporting respectively the directions: UP-DOWN and LEFT-RIGHT. Indeed, the four areas of the rocker switch may be replaced with a number of keys arranged in any desired configuration. The vertical axis functions to e.g. (i) scroll up/down in a menu, and (ii) increase or decrease a number. The horizontal axis LEFT RIGHT is used for e.g. (i) scrolling in time, and (ii) changing time related or secondary parameters. The accept button is the fundamental "Yes" button and functions as (i) go forth, enter, select, accept or confirm, and (ii) zoom-in in views. The Escape button is the fundamental "No" button and has the functions (i) no, escape, step back, exit or undo, and (ii) zoom-out in views. Additional func- tions may be added to the ones described. The display is a dot matrix display and may be a monochrome, greyscale or colour display. The display shows the main screen (MS) which normally is displayed when the RC is turned on. The MS serves to indicate to the user the status of the system controlled by the RC.

Fig. 2 shows a skin-mountable device in the form of a patch (or cannula) unit 400. The patch unit comprises a relatively rigid body portion 414 arranged on a flexible sheet member 430 with a lower mounting surface 431 provided with an adhesive allowing the sheet to be adhered to a skin surface of a subject. The sheet member comprises a central opening 432 through which a cannula can be inserted. The body portion comprises a housing portion 412 in which a cannula inserting mechanism is arranged, see below. The body portion further comprises two slider leg members 413 extending from the housing, the legs adding stiffness to the patch and further serves as guiding means when a pump/reservoir unit is attached the patch unit, see below. The housing is provided with a set of opposed grooves 420 serving as attachment means for a packaging and subsequently for a pump unit. The housing further comprises a fluid inlet 415 adapted to be mounted in fluid communication with a correspond- ing fluid outlet from an attached pump unit 450, an actuator 416 for actuating an electrical contact on the attached pump, and a release member 417 adapted to release a cannula inserting mechanism when the pump unit is attached for the first time, the cannula being inserted through the opening 432. The housing portion 412 also comprises a catch 419 adapted to engage a corresponding coupling structure on the pump unit. As appears, when the cannula 951 is inserted (see fig. 3), it is protected by the pump unit, however, the pump unit can be removed for subsequent inspection of the insertion site as shown in fig. 4.

Fig. 4 shows an alternative embodiment of a patch unit 1010 with a pump unit 1050 by its side, and fig. 27 shows the pump unit fully but releasably attached. More specifically, fig. 4 shows an embodiment of a medical device 1000, comprising a cannula unit 1010 of the type shown in fig. 2 and a thereto mountable pump (or reservoir) unit 1050. In the shown embodiment the cannula unit comprises a housing 1015 with a shaft into which a portion 1051 of the pump unit is inserted. The shaft has a lid portion 101 1 with an opening 1012, the free end of the lid forming a flexible latch member 1013 with a lower protrusion (not shown) adapted to engage a corresponding depression 1052 in the pump unit, whereby a snap- action coupling is provided when the pump unit is inserted into the shaft of the cannula unit. Also a vent opening 1054 can be seen. The housing 1015 is provided with a pair of opposed legs 1018 and is mounted on top of a flexible sheet member 1019 with a lower adhesive surface 1020 serving as a mounting surface, the sheet member comprising an opening 1016 for the cannula 1017.

As appears, from the housing of the cannula unit extends a cannula at an inclined angle, the cannula being arranged in such a way that its insertion site through a skin surface can be inspected (in the figure the full cannula can be seen), e.g. just after insertion. In the shown embodiment the opening in the lid provides improved inspectability of the insertion site. When the pump unit is connected to the cannula unit it fully covers and protects the cannula and the insertion site from influences from the outside, e.g. water, dirt and mechanical forces (see fig. 5), however, as the pump unit is detachable connected to the cannula unit, it can be released (by lifting the latch member) and withdrawn fully or partly from the cannula unit, this allowing the insertion site to be inspected at any desired point of time. By this arrangement a drug delivery device is provided which has a transcutaneous device, e.g. a soft cannula as shown, which is very well protected during normal use, however, which by fully or partly detachment of the pump unit can be inspected as desired. Indeed, a given device may be formed in such a way that the insertion site can also be inspected, at least to a certain degree, during attachment of the pump, e.g. by corresponding openings or transparent areas, however, the attached pump provides a high degree of protection during use irrespective of the insertion site being fully or partly occluded for inspection during attachment of the pump. In the shown embodiment an inclined cannula is used, however, in alternative embodiments a needle or cannula may be inserted perpendicularly relative to the mounting surface.

Fig. 6 shows in an exploded view a pump unit 300 of the same type as in fig. 4. The pump unit comprises an upper housing portion 310 and a lower housing portion 320 which in an assembled state provides a water-protected enclosure for the additional components of the reservoir unit: A pump assembly 330, an actuator 340, a reservoir 350, and electronic control means 360. In an initial state as supplied to the user, a protective cap assembly 370 is at- tached to the unit.

The lower housing portion is made from a transparent material allowing a reservoir (see below) to be inspected by a user from the outside, and comprises an opening 321 in which a water repelling vent 322 is arranged. A sheet member 325 with a window opening 326 is at- tached to the lower surface of the lower housing portion, this masking the transparent portion except for a window over the reservoir. The sheet member may be used to display user information, e.g. type and amount of drug.

The pump assembly 330 is in the form of a membrane pump comprising a piston-actuated pump membrane with flow-controlled inlet- and outlet-valves. The pump has a general layered construction comprising a number of body members between which are interposed flexible membrane layers, whereby a pump chamber, inlet and outlet valves, and one or more safety valves can be formed, the layers being hold together with clamps 338. The pump further comprises a fluid connector 335 in the form of hollow connection needle slidably positioned within the pump (for illustrative purposes shown outside of the pump), this allowing the pump to be connected with reservoir when the protective cap assembly 370 is activated. For a more detailed description of such a membrane pump reference is made to applicants co-pending application PCT/EP2006/060277, which is hereby incorporated by reference. The pump actuator is in the form of a coil actuator to which the pump assembly is attached by a clamp. For a more detailed description of such a coil actuator reference is made to applicants co-pending application WO 2005/094919, which is hereby incorporated by reference.

The drug reservoir is in the form of a flexible, pre-filled collapsible pouch 350 comprising a needle-penetratable septum 354 allowing the fluid connector to be pushed into the reservoir without leakage, thereby providing a fluid communication with the pump. A clip holder 352 is attached to the reservoir, this allowing the reservoir to be attached to the housing without influencing the reservoir per se. Under the reservoir (as seen from the lower surface of the unit) is arranged a sheet (not shown) comprising a contrast-enhancing pattern, e.g. a black line on a white background, allowing for easier visual identification of impurities in the drug, e.g. fibrillation in insulin.

The electronic control means 360 comprises a PCB or flex-print 362 with a processor 361 for controlling the pump assembly, a battery 366, an acoustic transducer 365 providing an alarm and communication interface with the user, as well as a contact mounted on the actuator allowing the control means to be activated by the user when taken into use for the first time (via the actuator 216). The control means may comprise a receiver and/or a transmitter allowing the reservoir to communicate wirelessly with a remote controller.

The protective cap assembly 370 comprises an attachment member 371 initially locked to the reservoir unit and an activation "push button" member 372 slidingly attached to the attachment member. When the reservoir unit is removed from its primary packaging (not shown) the user depresses the activation member towards the reservoir unit. This actuation results in three actions taking place: A first protrusion on the activation member will actuate a contact on the reservoir unit, this activating the electronics, and a second protrusion will engage the pump assembly and push the fluid connector 335 out from the pump assembly and into the reservoir, thereby establishing a fluid communication between the reservoir and the pump. Thirdly, depression of the activation member will "unlock" the attachment member and allow it, and thereby the activation member, to be removed from the reservoir unit. Thereafter the reservoir unit can be connected to the patch unit.

Fig. 7 shows a schematic representation of a process unit 200 (here corresponding to the pump unit 1050 of fig. 26) and a controller unit 100 (here in the form of a wireless "remote controller" or "external communication device" for the pump unit). It is considered that the general design of such units is well known to the skilled person, however, for a more detailed description of the circuitry necessary to provide the desired functionality of the present invention reference is made to US 2003/0065308 which is hereby incorporated by reference.

More specifically, fig. 7 depicts a simplified block diagram of various functional components or modules (i.e. single components or groups of components) included in the pump unit 200 and remote controller 100. The remote controller unit includes a housing 101 , a remote processor 110 including a CPU, memory elements for storing control programs and operation data and a clock, an LCD display 120 for providing operation for information to the user, a keypad 130 for taking input from the user, an audio alarm 140 for providing information to the user, a vibrator 150 for providing information to the user, a main battery 160 for supplying power to the controller, a backup battery 161 to provide memory maintenance for the controller, a remote radio frequency (RF) telemetry transmitter 170 for sending signals to the pump unit, a remote radio frequency (RF) telemetry receiver 180 for receiving signals from the pump unit, and a second transmitter 190. The controller further comprises a port 185, e.g. an infrared (IR) or RF input/output system, or a USB port for communicating with a further device, e.g. a blood glucose meter (BGM), a continuous blood glucose meter (CGM), a PC or a PDA.

As also depicted in fig. 7, the pump unit 200 includes a housing 201 , local processor elec- tronics 210 including a CPU and memory elements for storing control programs and operation data, battery 260 for providing power to the system, a process unit RF telemetry transmitter 270 for sending communication signals to the remote unit, a process unit radio frequency (RF) telemetry receiver 280 for receiving signals from the remote unit, a second process unit receiver 240 (which may be in the form of a coil of an acoustic transducer used in an audio alarm for providing feedback to the user), a reservoir 230 for storing a drug, and a pump assembly 220 for expelling drug from the reservoir through a transcutaneous device to the body of a patient. In alternative embodiments the pump unit may also comprise an LCD display for providing information to the user, a keypad for taking input from the user, and a vibrator or other tactile actuator for providing information to the user. RF transmission may be in accordance with a standard protocol such as Bluetooth ®.

As appears, the system of fig. 7 comprises first and second means of communication allowing a first and second group of data types to be transmitted between the two units. In this way different properties of the two means of communication can be used to secure that cer- tain data, e.g. during pairing of the two devices using near-field communication, can be transmitted in a more controlled way whereas other data can be transmitted in a less controlled way using longer-distance communication.

Fig. 8 shows a first embodiment of a system comprising two skin-mountable drug delivery devices 50, 60 adapted to communicate bi-directionally with each other, and wherein expelling of drug from the first drug delivery device stops when a signal has been received from the second drug delivery device indicating that expelling of drug from the latter has started. Fig. 9 shows a second embodiment of a system comprising two skin-mountable drug delivery devices 50, 60 in combination with a remote controller (RC) 70, the first and second drug de- livery device being adapted to communicate with each other via the remote controller.

In a situation of use a system comprising two patch/pump units and an RC could be used in the following way.

At bedtime the user checks the remaining amount of drug in an attached pump by looking at the RC. If the user expects the pump to run empty during the night at the current basal rate for the pump he may either switch to a new pump unit or attach a new patch/pump unit. Before or after doing so he will mate the second pump with the RC and indicate that the new pump is a back-up pump for the first pump. In the process the new pump will be provided with the programming of the old pump, e.g. about the basal rate. The RC may then transmit information about the new pump to the old pump which would allow the two pumps to communicate directly. However, the two pumps may also communicate via the RC. Correspondingly, when the first pump is about to run empty it will send a signal to the RC which will then start the new pump. When the new pump has started pumping it will confirm operation to the RC which will then stop operation of the old pump. If the old pump does not receive such a stop instruction it may sound an alarm indicating that the switching between the two pumps may not have taken place.

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. *****

Claims

1. A drug delivery system comprising: a) a first drug delivery device (50) adapted to deliver a drug, comprising: a first reservoir (230, 350) containing a fluid drug, - expelling means (220, 340) adapted for cooperation with the first reservoir to expel fluid drug out of the reservoir, means (210, 360) for determining a remaining amount of drug in the first reservoir, and transmitting means (270), b) a second drug delivery device (60) adapted to deliver a drug, comprising: a second reservoir containing a fluid drug, expelling means adapted for cooperation with the second reservoir to expel fluid drug out of the reservoir, and receiving means (280), - wherein the first drug delivery device is adapted to transmit a start signal to the second drug delivery device when a given remaining amount of drug is left in the first reservoir, and wherein the second drug delivery device is adapted to start expelling drug from the second reservoir when the start signal is received by the receiving means.

2. A drug delivery system as in claim 1 , wherein the given amount of drug in the first reservoir is more than zero, and wherein expelling of drug from the first reservoir stops when the start signal has been transmitted to the second drug delivery device.

3. A drug delivery system as in claim 1 , wherein the first and second drug delivery device are adapted to communicate bi-directionally, each drug delivery device comprising transmitting and receiving means (270, 280), and wherein expelling of drug from the first reservoir stops when a signal has been received from the second drug delivery device indicating that expelling of drug from the second reservoir has started.

4. A drug delivery system as in any of the previous claims, wherein the system comprises a remote controller (70, 100) having transmitting and receiving means (170, 180), and the first and second drug delivery device are adapted to communicate with each other via the remote controller.

5. A drug delivery system as in any of the previous claims, wherein the remaining amount of drug is detected by: directly detecting the remaining amount of drug in the first reservoir, or indirectly detecting the remaining amount of drug in the first reservoir by detecting the amount of drug expelled from the first reservoir.

6. A drug delivery system as in any of the previous claims, wherein each of the drug delivery devices comprises a mounting surface (1020) adapted for application to the skin of the subject.

7. A drug delivery system as in any of the previous claims, wherein the reservoirs are prefilled.

8. A drug delivery system as in any of the previous claims, wherein the transmitting and receiving means (170, 180, 270, 280) are wireless.

9. A drug delivery device (50) comprising: a reservoir (230, 350) containing a fluid drug, expelling means (220, 340) adapted for cooperation with the reservoir to expel fluid drug out of the reservoir, means (210, 360) for determining a remaining amount of drug in the reservoir, and transmitting and receiving means (270, 280), wherein the drug delivery device is adapted to: receive a start signal from a first further drug delivery device, - start expelling drug from the reservoir when the start signal is received by the receiving means, transmit a signal to the first further drug delivery device indicating that expelling of drug from the reservoir has started, and transmit a start signal to a second further drug delivery device when a given remain- ing amount of drug is left in the first reservoir, wherein expelling of drug from the reservoir stops when a signal has been received from the second further drug delivery device indicating that expelling of drug from the second further drug delivery device has started.