WO2007101786A1

WO2007101786A1 - A drug delivery device with a valve

Info

Publication number: WO2007101786A1
Application number: PCT/EP2007/051623
Authority: WO
Inventors: Bo Radmer
Original assignee: Novo Nordisk A/S
Priority date: 2006-03-06
Filing date: 2007-02-20
Publication date: 2007-09-13

Abstract

A drug delivery device (1) comprising a reservoir (2) for holding a liquid, means for receiving a vial (3) containing a dry drug, e.g. a lyophilized drug, and a valve (8) being movable between at least two positions. In a first position the valve (8) establishes a continuous fluid connection between the reservoir (2) and a vial (3) positioned in the receiving means. Thereby the dry drug is reconstituted. In a second position the valve (8) establishes a continuous fluid connection between the vial (3) and an outlet opening (7). Thereby the reconstituted drug may be delivered. The reservoir (2) is connectable to a suction device (5, 13), e.g. a pump, adapted to draw liquid from the reservoir (2) by means of suction. This is an advantage because the reservoir (2) needs not to be designed to hold a movable piston, and it needs not to be designed to be able to withstand a pressure build-up in the reservoir (2). The reservoir (2) may then be designed to meet other needs, such as reduced size of the device (1) or low manufacturing costs.

Description

A DRUG DELIVERY DEVICE WITH A VALVE

FIELD OF THE INVENTION

The present invention relates to a drug delivery device for reconstituting a dry drug contained in a vial, and for delivering the reconstituted drug.

BACKGROUND OF THE INVENTION

For various reasons it may be desirable or necessary to store a drug in dry form, e.g. in lyophilized form. This may, e.g., be in order to reduce degradation of the drug during storage. Before the drug is delivered it must be reconstituted, i.e. it must be mixed with a solvent liquid to form a liquid drug ready to be delivered.

Various devices for reconstituting dry drugs are known. Thus, WO 02/24259 discloses a reconstitution and injection system which delivers a drug in solution under pressure, and injects powdered or lyophilized drugs that require reconstitution, rehydration or dilution. The system includes a first port receiving a syringe, a second port receiving a drug vial, a channel providing communication between the first and second ports, and a controller permitting or inhibiting fluid communication between the first and second ports. When a drug is to be mixed, a control valve is adjusted to establish a fluid connection between the first and second ports. Then the liquid from the syringe is pushed into the vial by means of a movable plunger. When the liquid and the drug have been properly mixed, the reconstituted drug is transferred back to the syringe. The control valve is then adjusted to terminate the fluid connection between the first and second ports, and the reconstituted drug is delivered using the movable plunger.

US 6,689,108 discloses a drug delivery system with a first port for receiving a first container that contains a solid substance, such as a powdered lyophilized drug, and a second port for receiving a second container that contains a fluid to be mixed with material in the first container. The fluid in the second container is pressurized, and thereby it is forced into the first container where the dry drug is reconstituted. The reconstituted drug is subsequently delivered from the first container.

In WO 02/24259 as well as in US 6,689,108 a pressure is applied to the liquid in order to force it into the vial containing the dry drug. In WO 02/24259 the liquid container needs to be formed in manner which allows a plunger to be positioned therein. In US 6,689,108 the second container must be sufficiently strong to withstand the pressure which it is necessary to build up therein. Thus, the fact that the liquid is supplied to the vial containing the dry drug by pushing the liquid out of the liquid container puts restrictions on the design of the liquid container, in terms of choice and thickness of material as well as in terms of shape.

It is desirable to be able to design the liquid container in a manner which is optimal for other purposes, e.g. in such a manner that the outer dimensions of the device may be reduced, or in such a manner that available space is used more efficiently, or in such a manner that requirements to the strength of the liquid container are less strict.

US 4,509,861 discloses a method of mixing a drug. A vial containing a drug and a vial containing water are positioned by press fit in depressions provided in a plate. The vials are then connected by means of syringes and tubing, and via a multi-way valve. The valve is provided with a number of ports, and by switching the valve, fluid connections can be obtained between various ports. Accordingly, the valve is first switched into a position in which liquid is sucked out of the liquid vial and into a syringe. Then the valve is switched to provide a fluid connection between the syringe and the drug vial, and the liquid is transferred to the drug vial. When the drug has been properly mixed, it is sucked back into the syringe. Afterwards, the valve is once again switched to establish a fluid connection between the syringe and an outlet opening, thereby allowing the mixed drug to be delivered.

It is a disadvantage of the method and device disclosed in US 4,509,861 that it is necessary to switch the valve several times during the operation described above. In particular, it is a disadvantage that it is not possible to deliver the mixed drug directly from the drug vial, and that it is not possible to deliver the water directly from the water vial to the drug vial.

SUMMARY OF THE INVENTION

It is, thus, an object of the invention to provide a drug delivery device for reconstituting a dry drug in which the total size of the device is reduced as compared to prior art devices.

It is a further object of the invention to provide a drug delivery device for reconstituting a dry drug in which available space is utilised to the maximum extent possible.

It is an even further object of the invention to provide a drug delivery device for reconstituting a dry drug in which the requirements to the liquid container in terms of withstanding a pressure are reduced as compared to prior art devices.

It is an even further object of the invention to provide a drug delivery device for reconstituting a dry drug, the device being operable using fewer steps than similar prior art devices. According to the invention the above and other objects are fulfilled by providing a drug delivery device comprising:

- a reservoir for holding a liquid, the reservoir being connectable to a suction device adapted to draw liquid from the reservoir by means of suction,

- receiving means for receiving a vial containing a dry drug, and

- a valve being movable between at least two positions, a first position establishing a continuous fluid connection between the reservoir and a vial positioned in the receiving means, via a connected suction device, thereby causing a dry drug contained in said vial to become reconstituted, and a second position establishing a continuous fluid connection between a vial positioned in the receiving means and an outlet opening, thereby allowing a reconstituted drug to be delivered.

The reservoir may be any suitable kind of reservoir. It may, e.g., be or form part of a bag, a container, a vial, etc. The liquid contained in the reservoir is preferably a solvent liquid being suitable for reconstituting a dry drug contained in a vial positioned in the receiving means.

The means for receiving a vial is preferably adapted to hold a vial in a substantially fixed position relatively to the drug delivery device, in such a manner that it is possible to gain access to the interior of the vial. This may, e.g., be achieved using a snap fit lock or the like adapted to hold a shoulder of a standard vial, and by means of a hollow needle adapted to penetrate a septum of a vial when positioned in the receiving means. Alternatively, the vial may form an integrated part of the device, i.e. it may be fixedly connected to the receiving means. This will be further described below.

The valve is movable between at least two positions. In the present context the term 'movable' should be interpreted broadly, i.e. it should be interpreted include that the complete valve or one or more parts of the valve is/are adapted to be moved rotationally, linearly, by flipping, etc.

When the valve is in the first position, it establishes a continuous fluid connection between the reservoir and a vial positioned in the receiving means. By means of the suction device, liquid is sucked from the reservoir and applied, directly and via the continuous fluid connection, to the vial. Thereby the dry drug in the vial is reconstituted. When the drug has been properly reconstituted, the valve is moved to the second position, thereby establishing a continuous fluid connection between the vial containing the reconstituted drug and an outlet opening. Thereby the reconstituted drug can leave the drug delivery device via the outlet opening, and directly from the vial. The outlet opening may comprise or be connectable to suitable delivery means, such as a syringe, a tube, an injection needle, an infusion apparatus, etc. This will be further described below.

It is an advantage that the established fluid connections are continuous, since it allows for the liquid to be transferred directly from the reservoir to the vial, and the reconstituted drug to be delivered directly from the vial to the outlet opening, without having to operate the valve during these operations. Thereby fewer operational steps are required as compared to prior art devices, and the device is easier for the user to operate.

The valve may be manually movable between the at least two positions by means of a selector.

It is an advantage of the drug delivery device of the invention that the reservoir is connectable to a suction device adapted to draw liquid from the reservoir by means of suction. Thereby a pressure build-up in the reservoir is not necessary in order to cause the liquid to be moved from the reservoir to the vial. Furthermore, it is not necessary to shape the reservoir in a manner which allows a piston to be positioned in the reservoir. Accordingly, restrictions to the design of the reservoir are minimised, and the reservoir may therefore be designed in manner which is optimal for other reasons. For instance, the reservoir may be designed in a manner which utilises available space in an optimal manner, e.g. 'wrapping' the reservoir around a neck or shoulder of a vial. Furthermore, the material and material thickness of the reservoir may be chosen in a manner which optimises manufacturing costs, and without consideration to durability or strength of the material. Accordingly, the drug delivery device can be manufactured in a less space consuming and/or in a cost effective manner.

The valve may be movable between at least three positions, the third position establishing a continuous fluid connection between the reservoir and the outlet opening. According to this embodiment the valve may further be moved to a third position, fluidly connecting the reservoir and the outlet opening. When the valve is in the third position and the outlet opening is fluidly connected to an injection site of a person, it is possible to draw a body fluid from the injection site towards the reservoir. This may be used for aspiration. When a drug is to be injected into a specific site, e.g. a blood vessel, a subcutaneous layer, or another suitable site, it is often necessary to ensure that the drug is delivered at a correct site. This may be achieved by means of aspiration where some body fluid is pulled into the device or a tube connecting the injection site and the device. By inspecting the aspirated body fluid, it is possible to determine the nature of the injection site. Thus, if the aspirated body fluid contains blood, then the injection site must be a blood vessel. In case the drug is to be injected into a blood vessel, then the site is correct, and the reconstituted drug can be safely delivered. If, on the other hand, the drug should be delivered to, e.g., a subcutaneous layer, then the injection site is incorrect, and another, suitable site should be found before the drug is delivered.

Aspiration will normally be performed after reconstitution and before delivery of the drug. Thus, during normal operation the valve will first be moved to the first position for reconstitution of the drug, then to the third position for aspiration, and finally to the second position for delivery of the drug.

The drug delivery device may further comprise a suction device connected to the reservoir. According to this embodiment the suction device forms an integrated part of the drug delivery device. Alternatively, the suction device may be a separate part which is merely connected to the reservoir when the drug delivery device is to be used. In this case the drug delivery device may be a disposable device while the suction device may be reusable.

The suction device may comprise a pump, such as a rotational pump or a piston pump known per se. Alternatively, the pump may be of a kind in which liquid is forced through a tube by pressing the tube against a rotating wheel comprising teeth or rollers which compress the tube from the exterior, thereby forcing the liquid in the moving direction of the teeth or rollers. Alternatively, the pump may be of a kind comprising a rubber ball with a unidirectional valve provided at opposite ends, in such a manner that liquid is sucked into the rubber ball when the ball expands, and expelled from the rubber ball in another direction when the ball is compressed. Alternatively, the pump may be of any other suitable kind.

Alternatively, the suction device may comprise a syringe provided with a movable piston. In this case the drug delivery device may be operated in the following manner. A syringe is positioned in fluid communication with the reservoir. The movable piston is then moved outwards, and thereby liquid is drawn from the reservoir to the syringe, via the valve which in this case advantageously may comprise a pair of unidirectional valves connected to the syringe. Then the movable piston is pushed in, and the liquid is thereby pushed from the syringe into the vial via another unidirectional valve. When the dry drug in the vial has been reconstituted, the valve is moved to the second position in which the unidirectional valves allow liquid to be transferred from the vial to the syringe. Then the movable piston is once again moved outwards, thereby drawing the reconstituted drug from the vial to the syringe. Subsequently, the reconstituted drug can be delivered from the syringe to a person. This embodiment is particularly useful in case the desired dose is larger than corresponding to the dry drug contained in a single vial. In this case a syringe having a volume which is sufficiently large to contain reconstituted drug corresponding to the desired dose can be chosen. The syringe may then successively be connected to several drug delivery devices, the number of devices corresponding to the desired dose. Thereby the syringe will contain the desired dose when the operation has been finished, i.e. the drug from a number of vials has been 'pooled' to form the desired dose.

The reservoir may be provided with at least one flexible wall. In this case the reservoir may be at least partly collapsible. When the liquid is drawn out of the reservoir by the suction device the flexible wall(s) will collapse or be drawn towards the interior of the reservoir. The volume occupied by the reservoir will thereby decrease as the liquid is drawn out by the suction device. The reservoir may be completely flexible, i.e. it may be in the form of a bag. In this case the reservoir collapses completely as the liquid is drawn out. By designing the reservoir with at least one flexible wall, it is possible to position the reservoir in the drug delivery device in a flexible manner. It may, e.g., be positioned in such a manner that it fills out space which would otherwise be unoccupied, e.g. around a neck or shoulder part of a vial positioned in the receiving means. Thereby the overall size of the drug delivery device can be reduced.

Alternatively or additionally, the reservoir may have a shape which is geometrically fitted to a shape of a vial to be received at the receiving means. In this case the reservoir may be arranged in the drug delivery device in such a manner that the available space is utilised to the greatest extent possible.

The drug delivery device may further comprise means for delivering a reconstituted drug to a patient. The delivery means should be fluidly connected to the outlet opening. Such delivery means may be or comprise a syringe, an injection needle, a butterfly needle, one or more tubes, an infusion device, an intravenous (IV) delivery device, etc. Alternatively, the drug delivery device may be adapted to be connected to any of the delivery means mentioned above.

The drug delivery device may further comprise a vial substantially fixedly connected to the receiving means. In this case the vial containing a dry drug forms part of the drug delivery device. According to this embodiment the drug delivery device may advantageously be a ready-to-use and disposable unit containing the vial with the dry drug, the reservoir containing the liquid, the valve and the necessary fluid connections. The amount and type of liquid is selected to match the amount and type of dry drug. This unit may be connectable to a suction device and to delivery means. After use the unit may be disconnected from the suction device and the delivery means, and the unit may be disposed of, while at least the suction device may be used again at a later time. Such a unit will be easy to use. It should be noted that the suction device and/or the delivery means may also form part of the unit. BRIEF DESCRIPTION OF THE DRAWINGS

The invention will now be described in further details with reference to the accompanying drawing, in which

Fig. 1 is a perspective view of a drug delivery device according to a first embodiment of the invention,

Fig. 2 is a cross sectional view of a valve for use in a drug delivery device according to the invention,

Fig. 3 is a perspective view of a drug delivery device according to a second embodiment of the invention,

Fig. 4 is an exploded view of a pump and a valve for use in a drug delivery device according to the invention, and

Figs. 5-8 illustrate a drug delivery device according to a third embodiment of the invention.

DETAILED DESCRIPTION OF THE DRAWINGS

Fig. 1 is a perspective view of a drug delivery device 1 according to a first embodiment of the invention. The drug delivery device 1 comprises a flexible reservoir 2 containing a liquid, and a vial 3 containing a dry drug. The flexible reservoir 2 is positioned around a neck portion 4 of the vial 3. Thereby space which would otherwise be unoccupied is utilised, and thereby the overall size of the drug delivery device 1 is reduced.

The drug delivery device 1 also comprises a pump 5. Connected to the pump 5 is a valve (not visible). The valve is manually operable by means of selector 6 to be moved between three positions. In a first position the valve establishes a continuous fluid connection between the reservoir 2 and the vial 3. When the valve is in this position, the pump 5 draws liquid from the reservoir 2 and delivers it to the vial 3. Thereby the dry drug in the vial 3 is reconstituted.

In a second position the valve establishes a continuous fluid connection between the vial 3 and an outlet opening 7. The outlet opening 7 may be connected to drug delivery means, e.g. a tube with a needle, e.g. a butterfly needle, and reconstituted drug may thereby be delivered from the vial 3 to a person, via the outlet opening 7, when the valve is in the second position. To this end, the pump 5 is used for drawing the reconstituted drug out of the vial 3.

In a third position the valve establishes a continuous fluid connection between the outlet opening 7 and the reservoir 2. When the valve is in this position the pump 5 is capable of drawing a body fluid from a person towards the reservoir 2, via the outlet opening. Thus, when the valve is in this position aspiration may be performed as described above.

The drug delivery device 1 of Fig. 1 is preferably operated in the following manner. Initially the outlet opening 7 of the drug delivery device 1 is connected to drug delivery means which is connected to a person. The valve is moved to the first position. The pump 5 then draws liquid from the reservoir 2 and delivers it to the vial 3. Thereby the dry drug in the vial 3 is reconstituted. Then the valve is moved to the third position, and the pump 5 draws some body fluid from the person, i.e. aspiration is performed. Afterwards, the valve is moved to the second position, and the pump 5 pumps the reconstituted drug from the vial 3 to the person, via the outlet opening 7. When the drug has been delivered, the delivery means is removed from the person and from the outlet opening 7, and the drug delivery device 1 is disposed of.

Fig. 2 is a cross sectional view of a valve 8 which is movable between three positions. The valve 5 may suitably be used in the drug delivery device 1 shown in Fig. 1 or in the drug delivery device 1 shown in Fig. 3.

The valve 8 comprises a first opening 9 connectable to a reservoir, a second opening 10 connectable to a vial, and a third opening 11 connectable to an outlet opening. The valve 8 further comprises a rotatable member 12 which is adapted to selectively interconnecting two of the openings 9, 10, 11. In Fig. 2 the valve 8 is shown in a position in which the rotatable member 12 establishes a fluid connection between the first opening 9 and the second opening 10. When the valve 8 is in this position liquid from the reservoir may enter the vial as described above. Rotating the rotatable member 12 120° about a central axis in a counter-clockwise direction, a fluid connection between the second opening 10 and the third opening 11 is established, thereby allowing a reconstituted drug to flow from the vial to the outlet opening as described above. Similarly, if the rotatable member 12 is rotated 120° about a central axis in a clockwise direction, a fluid connection between the first opening 9 and the third opening 11 is established, thereby allowing aspiration.

Fig. 3 is a perspective view of a drug delivery device 1 according to a second embodiment of the invention. Similarly to the drug delivery device of Fig. 1, the drug delivery device 1 of Fig. 3 comprises a flexible reservoir 2, a vial 3, a valve (not visible), a selector 6 and an outlet opening 7. These parts are positioned in the drug delivery device 1 as described in connection with Fig. 1. Instead of a pump the drug delivery device 1 of Fig. 3 is provided with a syringe 13 with a movable piston 14 positioned therein.

The drug delivery device 1 of Fig. 3 is preferably operated in the following manner. Initially the outlet opening 7 is connected to delivery means as described above. The valve is then moved to a position in which a fluid connection is established between the flexible reservoir 3 and the syringe 13, and between the syringe 13 and the vial 3, by means of unidirectional valves. The movable piston 14 is then pulled in an upwards direction, thereby drawing liquid from the reservoir 3 into the syringe 13. Then the movable piston 14 is moved back in a downwards direction. Thereby the liquid is forced into the vial 3. When the dry drug in the vial 3 has been reconstituted, the valve is moved to a position in which a fluid connection is established between the vial 3 and the syringe 13, and between the syringe and the outlet opening 7, by means of unidirectional valves. Then the movable piston 14 is once again pulled in an upwards direction, and the reconstituted drug is thereby drawn from the vial 3 into the syringe 13. The movable piston 14 is once again moved in a downwards direction, and the reconstituted drug is thereby delivered from the syringe 13 to a person, via the outlet opening 7.

Fig. 4 is an exploded view of a pump 5 and a valve 8 for use in a drug delivery device according to the invention. Rotatable member 12 is rotatably inserted into valve 8, and it may thereby establish fluid connection as described above with reference to Fig. 2. The rotatable member 12 is provided with unidirectional valves 15, which allow a flow of liquid in one direction, but prevents such a flow in the opposite direction, and these are positioned corresponding to openings 9 and 10 by rotating the rotatable member 12 appropriately. When pump piston 16 is pulled outwards, a low pressure is created in pump chamber 17. The unidirectional valve 15a positioned at opening 9 allows a flow of liquid into the pump chamber, and the unidirectional valve 15b positioned at opening 10 allows a flow of liquid out of the pump chamber 17. Accordingly, the low pressure in the pump chamber 17 will cause liquid to enter the pump chamber 17 via opening 9. When the pump piston 16 is subsequently pushed in, a high pressure is created in the pump chamber 17. Due to the directions of the unidirectional valves, this will cause liquid to leave the pump chamber 17 via opening 10. Thereby the pump 5 has caused a flow of liquid from a reservoir connected to opening 9 to a vial connected to opening 10. By rotating the rotatable member 12 as described above with reference to Fig. 2, unidirectional fluid connections may be established between other openings. Fig. 5 is a perspective view of a drug delivery device 1 according to a third embodiment of the invention. The drug delivery device 1 is operated essentially as the drug delivery device 1 of Fig. 1, so the operation will not be described in detail here.

The drug delivery device 1 of Fig. 5 comprises a first housing part 18 covering part of the vial 3, and a second housing part 19 substantially covering the remaining parts of the drug delivery device 1. The drug delivery device 1 further comprises a frame part 20 adapted to receive and retain the vial 3 the reservoir (not visible) and the pump (not visible). This will be explained further below.

Furthermore, the drug delivery device 1 comprises a selector 6. The selector 6 of the drug delivery device 1 of Fig. 5 is adapted to be rotated about a substantially vertical axis. Apart from that it operates as described above.

Fig. 6 is a perspective view of a frame part 20 for a drug delivery device 1 according to the third embodiment of the invention. The frame part 20 comprises a first compartment 21 adapted to receive a vial and a reservoir, and a second compartment 22 adapted to receive a pump. A first flow path 23 is adapted to establish a fluid connection between a vial and a pump, and a second flow path 24 is adapted to establish a fluid connection between a reservoir and the pump. At the ends of the flow paths 23, 24, spikes 25, 26 are formed for penetrating a vial and a reservoir, respectively.

Fig. 7 is a perspective view of the drug delivery device 1 of Fig. 5, but with the second housing part removed. A reservoir 2 and a vial 3 are arranged in the first compartment 21 of the frame part 20. The reservoir 2 is of a flexible type, and it is arranged around a neck portion 4 of the vial 3. There is no pump in the drug delivery device 1.

Fig. 8 is a perspective view of the drug delivery device of Figs. 5 and 7 with the frame part removed. The relative positions of the reservoir 2, the vial 3 and the pump 5 can be seen. Connected to the pump 5 via the selector 6 is a valve 8. The valve 8 is operated by means of the selector 6, essentially as described above with reference to Fig. 4.

Claims

1. A drug delivery device comprising :

- receiving means for receiving a vial containing a dry drug, and

2. A drug delivery device according to claim 1, wherein the valve is movable between at least three positions, the third position establishing a continuous fluid connection between the reservoir and the outlet opening.

3. A drug delivery device according to claim 1 or 2, further comprising a suction device connected to the reservoir.

4. A drug delivery device according to claim 3, wherein the suction device comprises a pump.

5. A drug delivery device according to claim 3, wherein the suction device comprises a syringe provided with a movable piston.

6. A drug delivery device according to any of the preceding claims, wherein the reservoir is provided with at least one flexible wall.

7. A drug delivery device according to claim 6, wherein the reservoir has a shape which is geometrically fitted to a shape of a vial to be received at the receiving means.

8. A drug delivery device according to any of the preceding claims, further comprising means for delivering a reconstituted drug to a patient.

9. A drug delivery device according to any of the preceding claims, further comprising a vial substantially fixedly connected to the receiving means.