WO2007101772A1

WO2007101772A1 - A drug mixing device

Info

Publication number: WO2007101772A1
Application number: PCT/EP2007/051439
Authority: WO
Inventors: Bo Radmer; Claus MØLLER; Louise Charlotte Klok; Kristian GLEJBØL; Poul Larsen; Ulrik Nøsted
Original assignee: Novo Nordisk A/S
Priority date: 2006-03-07
Filing date: 2007-02-14
Publication date: 2007-09-13

Abstract

A drug mixing device (1) for mixing a dry drug, such as a lyophilized drug, with a liquid, thereby forming a liquid drug. The device (1) comprises a reservoir (2) containing a liquid, a vial holder (3) for receiving a vial (4) containing a dry drug, means (5, 7) for establishing a 5 fluid connection between the reservoir (2) and a vial (4) positioned in the vial holder (3) , means (8, 18) for forcing the liquid from the reservoir (2) to a vial (4) positioned in the vial holder (3) , and means (24, 9) for equalizing a pressure in the vial (4) . Transferring liquid from the reservoir (2) to the vial (4) causes the dry drug to become reconstituted. At least the reservoir (2) , the vial holder (3) , the means (5, 7) for establishing a fluid connection and (10) the forcing means (8, 18) form an at least substantially integral device.

Description

A DRUG MIXING DEVICE

FIELD OFTHE INVENTION

The present invention relates to a device for mixing a drug, in particular for mixing a dry drug, such as a powdered or lyophilized drug, with a liquid, such as a solvent liquid, i.e. for reconstitution of the drug. More particularly, the present invention relates to a drug mixing device which is suitable for use when a desired dose of reconstituted drug is larger than what corresponds to the drug contained in a single vial. Furthermore, the present invention relates to a drug mixing device which is suitable for being operated using one hand only.

BACKGROUND OF THE I NVENTI ON

It is sometimes necessary or desirable 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. In this case it is, however, necessary to reconstitute the drug before it is delivered to a person, i.e. it is necessary to mix the dry drug with a liquid, thereby forming a liquid drug. This is normally done by means of an ordinary syringe with an ordinary needle. Liquid is sucked into the syringe, the needle is then inserted in a vial containing the dry drug to be reconstituted, and the liquid is forced from the syringe into the vial by means of a movable piston of the syringe. When the dry drug has been properly reconstituted, the movable piston is pulled out, and the reconstituted drug is thereby retrieved to the syringe. The reconstituted drug may subsequently be delivered from the syringe to a person. There is a relatively high risk of contamination of the drug or the syringe during the described procedure due to the exposure of the surfaces and the needle to free air and dirt.

Various devices for reconstituting dry drug are known. WO 02/24259 discloses a reconstitution and injection system, including 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 it is desired to inject a dose, a syringe containing a liquid is positioned in the first port, and a vial containing a drug is positioned in the second port. Fluid communication is established between the first and second ports, and the liquid is forced from the syringe to the vial by means of a plunger in the syringe. When the drug has been properly reconstituted, the plunger is pulled out, thereby retrieving the reconstituted drug to the syringe. The fluid communication between the first and second ports is then inhibited, and a fluid communication between the first port and an injection needle is established. The reconstituted drug is then forced from the syringe to the injection needle by means of the plunger. In the system disclosed in WO 02/24259 it is not possible to remove the vial containing the reconstituted drug. This is partly because the design of the system does not allow this, and partly because a pressure is build-up in the vial when the liquid is forced into the vial. Removing the vial containing the dry drug may therefore result in reconstituted drug being expelled from the vial. In some situations, e.g. in case a desired dose of medication is larger than what corresponds to the contents of a single vial, or in case the reconstituted drug is not to be injected immediately, it is, however, desirable to be able to remove the vial containing the reconstituted drug from the system before the drug is injected.

EP 1 329210 discloses a fluid transfer device for use in the aseptic interm ixing of a powder component with a fluid component. The device includes a first adapter that can be connected to a container containing the powder component and a second adapter that can be removably interconnected with the first adapter and can also be connected to a container containing a fluid. When the containers are positioned in the adapters, a fluid connection is established between the containers, thereby allowing fluid from the fluid container to enter the powder container in order to mix the powder and the fluid. When the powder has been reconstituted, the adapters may be separated, and the mixed drug can be delivered from the powder container. In order to allow fluid from the fluid container to enter the powder container while at the same time being able to remove the powder container after reconstitution, the powder container must be under vacuum. This is a disadvantage.

US 2002/0022804 discloses a syringe device comprising a barrel having inner walls defining a compartment in the barrel, a closable nozzle at the base of the barrel and a plunger movable longitudinally within the barrel compartment. The plunger has inner walls defining a chamber suitable to receive a vial. A hollow needle extends through the plunger to enable fluid communication between the plunger chamber and barrel compartment. A compressible and puncturable sealing element within the plunger chamber provides a sterile seal for the needle and barrel compartment.

US 3,330,280 discloses a syringe in which liquid and powder can be stored and mixed immediately before use. It comprises a hollow vial adapted to contain a medicament in liquid or powder form, a syringe barrel which may also contain liquid, a stopper separating the two and means for communicating the vial and the barrel when desired.

SUMMARY OF THE I NVENTI ON

It is, thus, an object of the invention to provide a device for reconstituting a dry drug in which it is possible to remove a vial containing reconstituted drug prior to delivery of the reconstituted drug. It is a further object of the invention to provide a device for reconstituting a dry drug which allows construction of a dose of liquid drug using dry drug from two or more vials.

It is an even further object of the invention to provide a device for reconstituting a dry drug, where it is possible to remove a vial containing reconstituted drug without having to keep the vial under vacuum prior to reconstitution.

It is an even further object of the invention to provide a device for reconstituting a dry drug, the device being operable using one hand.

It is an even further object of the invention to provide a device for reconstituting a dry drug, where the device can be delivered as an 'all-in-one' package.

It is an even further object of the invention to provide a device for reconstituting a dry drug, wherein the risk of contamination of the reconstituted drug is reduced as compared to prior art devices.

According to a first aspect of the invention the above and other objects are fulfilled by providing a drug mixing device comprising:

- a reservoir containing a liquid,

- a vial holder for receiving a vial containing a dry drug,

- means for establishing a fluid connection between the reservoir and a vial positioned in the vial holder,

- means for forcing the liquid from the reservoir to a vial positioned in the vial holder, via an established fluid connection, and

- means for equalizing a pressure in a vial positioned in the vial holder,

wherein least the reservoir, the vial holder, the means for establishing a fluid connection and the forcing means form an at least substantially integral device.

The reservoir may be any suitable kind of reservoir, such as a container, a vial, a syringe, a flexible reservoir, e.g. a bag, or simply a chamber forming part of the device. The liquid contained in the reservoir is preferably a solvent liquid being suitable for reconstitution of a dry drug, such as a lyoph ilized drug, contained in the vial. The amount and kind of liquid in the reservoir is preferably chosen in such a manner that it matches a specific dry drug. Thereby it is ensured, that when a vial containing that specific dry drug is positioned in the vial holder, the dry drug is reconstituted correctly and in a suitable manner.

The vial holder is a part of the device which is shaped in such a manner that a vial may be positioned there in a manner which substantially fixes the vial relatively to the device, and in such a manner that access may be gained to the interior of the vial. Thus, the vial holder may comprise means for gripping a vial, e.g. a neck or shoulder part of a vial. The vial holder could also simply be a hollow spike adapted to penetrate a stopper of a vial, the spike thereby substantially fixing the vial relatively to the device. As an alternative, the vial holder could be a vial adapter.

The forcing means may comprise a movable piston or plunger positioned in the reservoir in such a manner that the liquid is forced out of the reservoir when the piston or plunger is moved in a specified direction. Alternatively, the forcing means may comprise suction means, e.g. a pump, for retrieving the liquid from the reservoir by means of suction, or means for pressurizing the liquid in the reservoir, e.g. by pumping air into the reservoir, etc.

The forcing means forces liquid from the reservoir into a vial positioned in the vial holder via a fluid connection which has been established between the reservoir and the vial. Thereby the dry drug contained in the vial will be reconstituted.

The drug mixing device comprises means for equalizing a pressure in a vial positioned in the vial holder. Thereby no additional pressure will be present in the vial when the liquid has been transferred to the vial and the dry drug has been reconstituted. It is therefore possible to remove the vial containing the reconstituted drug from the device, or it is possible to retrieve the reconstituted drug in another suitable manner, in a controlled way and without risking spilling of the drug. This is obtained without having to initially applying a low pressure in the vial. Thereby it is possible to reconstitute a dry drug without delivering the reconstituted drug immediately upon reconstitution. Furthermore, it is possible to constitute a dose of medication using reconstituted drug from two or more vials, i.e. it is possible to 'pool' the contents of two or more vials. This may be done by removing the vial from the device and subsequently retrieve the reconstituted drug to a common reservoir where the contents of other vials is also collected. Thereby the total dose which is eventually contained in the common reservoir will correspond to the combined dose of all the vials used. The total dose may then be delivered directly from the common reservoir. Thus, by making it possible to remove the vial from the device, pooling of the contents of two or more vials is made easier. This is an advantage. At least the reservoir, the vial holder, the means for establishing a fluid connection and the forcing means form an at least substantially integral device. In the present context the term 'integral device' should be interpreted to mean a device which is manufactured and operated as one device. The parts may, e.g., be at least substantially surrounded by a housing.

Thus, these parts may be delivered as an 'all-in-one' and/or a 'ready-to-use' package which is easy to operate. Thus, it is only necessary to position an appropriate vial in the vial holder, and to operate the means for establishing a fluid connection and the forcing means to cause the liquid from the reservoir to enter the vial. Preferably, the fluid connection is established as the vial is positioned in the vial holder, and in this case it will only be necessary for the user to operate the forcing means once the vial has been positioned in order to cause reconstitution of the dry drug. Most preferably, positioning the vial, establishing the fluid connection and forcing the liquid into the vial may be performed by the user in a single motion. This may even allow the user to operate the device using only one hand. Furthermore, it is ensured that the amount and kind of liquid in the reservoir matches the dry drug of a specific kind of vial. Thereby the risk of incorrect reconstitution of the drug is reduced.

The means for establishing a fluid connection may comprise a first spike positioned at or near the vial holder and being adapted to penetrate a stopper of a vial positioned in the vial holder. The first spike is preferably a hollow spike, the hollow part thereby giving access to the interior of the vial once the first spike has penetrated the stopper.

The means for establishing a fluid connection may further comprise a second spike adapted to penetrate the reservoir. The second spike is also preferably a hollow spike, the hollow part thereby giving access to the interior of the reservoir once the second spike has penetrated the reservoir. The first and second spikes may advantageously form part of a double pointed hollow needle. In this case the first spike will penetrate the stopper of the vial and the second spike will penetrate the reservoir, and the hollow portion of the double pointed hollow needle will thereby establish a fluid connection between the reservoir and the vial.

The first spike may be longer than the second spike. Thereby it can be ensured that the vial is penetrated before the reservoir is penetrated, thereby ensuring that all of the liquid enters the vial, and nothing is spilled.

The pressure equalizing means may comprise a channel formed in the first spike. The channel should provide a connection to the interior of the vial through which air from the vial may escape as liquid is forced from the reservoir into the vial. Thereby the pressure in the vial is equalized as the liquid enters the vial. Accordingly, when all of the liquid has been transferred to the vial and the dry drug has been properly reconstituted, the vial may be removed from the device as described above. Alternatively, the pressure equalizing means may be or comprise a filter, e.g. in the form of a membrane, which allows passage of atmospheric air and possibly liquid, but prevents passage of bacteria and viruses. Alternatively, the pressure equalizing means may be or comprise a unidirectional valve allowing passage of, e.g., air or liquid in a direction out of the vial, but preventing such passage in a direction into the vial. As another alternative, the pressure equalizing means may be or comprise a separate channel, e.g. a separate hollow spike.

The drug mixing device may further comprise a vial containing a dry drug, the vial being positioned in or forming part of the vial holder. According to this embodiment the vial also forms part of the device. Thus, the device may be delivered as an 'all-in-one' package, and it is only necessary for the user to cause the fluid connection to be established and to operate the forcing means to cause transfer of the liquid from the reservoir to the vial, in order to cause reconstitution of the dry drug. It may even be possible to do this in a single step, and/or using only one hand. In this embodiment the risk of incorrect reconstitution of the dry drug is eliminated because the package is delivered with matching vial containing dry drug and reservoir containing liquid. The vial may be a separate part which has been positioned in the vial holder by the manufacturer. Alternatively, the vial may form an integrated part of the vial holder, i.e. it may be formed directly as an integrated part of the device.

The drug mixing device may further comprise:

a first housing part containing the vial,

a second housing part containing the reservoir, said first and second housing parts being movably connected to each other, and

an intermediate part containing the means for establishing a fluid connection.

The first and second housing parts are preferably positioned one inside the other, so as to allow one part to slide telescopically into the other part. The first part is preferably closed in the end opposite to the second housing part, the vial being positioned in that end of the first part. Alternatively, the first part may be openable in this end in order to allow the vial to be replaced by a new vial when it has been used.

The second housing part is preferably openable in the end opposite to the first part in order to allow a user to gain access to the internal of the device. This end may advantageously be closed by a removable cover which, together with a seal, defines a sealed closure of the device. The cover may, in this case, stay attached to the device after having been removed in order to leave the user with as few pieces of waste material as possible.

The drug mixing device may further comprise locking means for locking the first housing part relatively to the second housing part when the means for forcing the liquid from the reservoir to a vial has reached an end position in which the liquid has been forced into the vial. The first and second housing parts are preferably guided relatively to each other by means of slots, and the locking means may be provided by a 'snap-lock' arranged in said slots. The 'snap-lock' may, e.g., be a loaded tap which enters a groove or hole in the slot when the second part reaches an end position relatively to the first part.

The means for establishing a fluid connection may comprise means for penetrating the reservoir and means for penetrating a septum of a vial, and the means for establishing a fluid connection may be adapted to penetrate the septum of a vial before penetrating the reservoir. This may, e.g., be obtained by selecting hollow needles having different lengths as described above. Alternatively, it may be obtained by selecting material of varying flexibility for the part of the device positioned at or near the vial holder, and for the part of the device positioned at or near the reservoir. Thereby it can be ensured that the material positioned at or near the vial holder flexes before the material positioned at or near the reservoir, and if the means for penetrating are arranged at these parts of the device, the septum of the vial will be penetrated before the reservoir. As mentioned above, this is an advantage because it can thereby be ensured that all of the liquid from the reservoir actually enters the vial, and nothing is spilled.

At least part of the vial holder may be removable from the device along with a vial positioned in the vial holder. In this case the vial holder, or at least the removable part of the vial holder, can be removed from the device along with the vial containing the reconstituted drug. This may, e.g., be advantageous in case the vial forms an integrated part of the device as described above. In this case it may be difficult, or even impossible, to remove just the vial from the device, and the vial may instead be removed along with at least part of the vial holder. Alternatively, in case the vial does not form an integrated part of the device, but must be positioned in the vial holder when it is desired to reconstitute the dry drug, the vial may be attached to the vial holder in such a manner that it is not possible to separate the vial and the vial holder at a later time, e.g. in order to ensure that the vial is kept firmly in place during reconstitution of the dry drug. In this case it will also be necessary to remove at least part of the vial holder from the device along with the vial if it is desired to remove the vial from the device. As an alternative, the drug mixing device may further comprise a liquid outlet being flu id Iy connectable to a vial positioned in the vial holder, a reconstituted drug thereby being deliverable from the device via said liquid outlet. According to this embodiment the vial does not need to be removed from the device in order to deliver the reconstituted drug. This makes it easier to operate the device.

The liquid outlet may be adapted to be connected to an infusion device, thereby allowing the reconstituted drug to be delivered directly from the device. Alternatively, a syringe may be attached to the liquid outlet for retrieving the reconstituted drug and subsequently deliver it.

The drug mixing device may further comprise means for establishing a fluid connection between a vial positioned in the vial holder and the liquid outlet. Such means may, e.g., comprise one or more spikes adapted to penetrate one or more membranes in order to establish said fluid connection once the drug has been properly reconstituted and is therefore ready to be delivered. According to this embodiment it is ensured that the drug is contained in the device until it is ready to be delivered, because the fluid connection between the vial and the liquid outlet is not established until the means for establishing said fluid connection is operated.

According to a second aspect of the invention the above and other objects are fulfilled by providing a mixing unit for mixing dry drug with liquid, the unit comprising;

a first and second housing part movable connected to each other and containing a vial with dry drug and a reservoir with liquid,

an intermediate part provided inside the housing parts for establishing a fluid connection between the reservoir and the vial upon moving the first and second housing part towards each other, said intermediate part comprising a first spike for penetrating a septum of the vial and a second spike for penetrating the reservoir, the first and second spike together defining a common fluid connection, and

a piston provided in said reservoir for forcing the liquid from the reservoir to the vial, via an established fluid connection, thereby causing the dry drug to become reconstituted, the piston comprising a liquid channel for connecting a liquid outlet of the unit with the internal of the vial via the established fluid connection.

It should be noted that a person skilled in the art would readily recognise that any feature described in combination with the first aspect of the invention could equally be combined with the second aspect of the invention, and vice versa. The first and second housing parts are preferably positioned inside each other so that one part can slide telescopically into the other part. The first part is preferably closed in the end opposite to the second housing part, the vial being positioned in that end of the first part. Alternatively, the first part may be openable in this end so that the vial may be replaced by a new vial, when it has been used.

The second housing part is openable in the end opposite the first part, so that the user can gain access to the internal of the unit and in particular to the liquid outlet. This end is preferably closed by a removable cover, which together with a seal defines a sealed closure of the unit. The cover may stay attached to the unit after having been removed in order to leave the user with as few pieces of waste material as possible.

The reservoir may be any suitable kind of reservoir, such as a cartridge, a syringe, a flexible reservoir, e.g. a bag, forming part of the unit. The liquid contained in the reservoir is preferably a solvent liquid being suitable for reconstitution of a dry drug contained in the vial. The amount and kind of liquid in the reservoir is preferably chosen in such a manner that it matches a specific dry drug. Thereby it is ensured, that when a vial containing that specific dry drug is positioned in the vial holder, the dry drug is reconstituted correctly and in a suitable manner.

The intermediate part provided inside the housing parts comprises a first spike being adapted to penetrate a septum of the vial, and a second spike adapted to penetrate a septum of the reservoir. Thus, the vial is positioned adjacent the first spike and the reservoir is positioned on the opposite side of the intermediate part adjacent the second spike.

The intermediate part preferably comprises a vial holder for receiving and retaining the vial in a fixed position relatively to the first spike, and a reservoir holder for receiving and retaining the reservoir in a fixed position in relation to the second spike when the first and second housing parts are moved towards each other. The holders are preferably shaped in such a manner that a vial and a reservoir are positioned there in a manner which substantially fixes them relatively to each other in the intermediate part. Thus, the holders may comprise means for gripping a part of the vial and reservoir, e.g. a neck or shoulder part thereof. The flexibility of the gripping means of the vial holder is preferably greater than the flexibility of the gripping means of the reservoir holder resulting in the vial holder receiving and retaining the vial before the reservoir holder receives and retains the reservoir when moving the first and second housing parts towards each other. This is to ensure that the first spike penetrates the vial before the second spike penetrates the reservoir. The first and second spikes are hollow spikes, the hollow part thereby giving access to the interior of the vial and reservoir, respectively, once the spikes have penetrated the septum, respectively. The first and second spikes may advantageously form part of a double pointed hollow needle establishing a fluid connection between the reservoir and the vial. The fluid connection is established between the reservoir and the vial by moving the first and second housing parts towards each other. The first spike is preferably longer than the second spike, so that the first spike is adapted to penetrate the septum of the vial before the second spike penetrates the septum of the reservoir, when moving the first and second housing parts towards each other.

The piston (or plunger) is positioned in the reservoir in such a manner that the liquid is forced out of the reservoir, via the established fluid connection provided by the spikes, when the piston is moved in a specified direction. The piston is preferably in connection with a part of the second housing part, or a part of the above mentioned cover, and by pressing the second housing part towards the first housing part, the piston is forced in said specified direction forcing liquid from the reservoir into the vial. Thereby the dry drug contained in the vial will be reconstituted. When the drug has been reconstituted, the drug is ready for infusion. In order to easily gain access to the reconstituted drug inside the vial, the piston comprises a liquid channel for connecting a liquid outlet of the unit with the internal of the vial via the established fluid connection. Thus, by removing the cover of the second housing part, the user can gain access to the internal of the vial via this channel and suck out the drug directly from the vial and does not need to disassemble the unit first. The liquid outlet preferably forms an end of the channel, and the outlet may be adapted for connection to an infusion device, such as a syringe. The outlet may e.g. be a Luer-lock connection.

The channel is preferably sealed by a membrane to make sure that drug or liquid does not enter the channel, while the piston is moved. The membrane is preferably adapted to be penetrated by the second spike, when the piston reaches its end position in the reservoir.

The unit preferably comprises locking means for locking the first housing part relatively to the second housing part, when the piston has reached an end position in which the liquid has been forced into the vial. The first and second housing parts are preferably guided in relation to each other by slots, and the locking means may be provided by a 'snap-lock' provided in said slots. The 'snap-lock' may, e.g., be a loaded tap that enters a groove or hole in the slot, when the second part reaches an end position in relation to the first part.

The first spike may comprise two separate channels; a first channel defining said fluid connection in combination with the second spike, and a second channel defining a fluid connection between the internal of the vial and an air outlet for equalising pressure provided in the vial. The second channel preferably comprises a filter being air permeable, but not liquid permeable. Thus, air from the vial may escape as liquid is forced from the reservoir into the vial. Thereby the pressure in the vial is equalized as the liquid enters the vial. Alternatively, the pressure equalization may be obtained by use of a unidirectional valve allowing passage of, e.g., air or liquid in a direction out of the vial, but preventing such passage in a direction into the vial. As another alternative, pressure equalization may be obtained by means of a separate hollow spike being adapted to penetrate the septum of the vial.

According to a preferred embodiment of the invention at least the first and second housing part, the intermediate part, the reservoir, the piston and the vial forms a substantially integral unit. In the present context the term 'integral unit' should be interpreted to mean a unit which is manufactured and operated as one unit.

According to this embodiment these parts may be delivered as an 'all-in-one' and/or a 'ready- to-use' package which is easy to operate. Thus, it is only necessary to operate the first and second housing parts in relation to each other which results in establishment of a fluid connection and forcing of the liquid from the reservoir to the vial. Furthermore, in this embodiment of the invention, it is ensured that the amount and kind of liquid in the reservoir matches the dry drug of a specific kind of vial. Thereby the risk of incorrect reconstitution of the drug is reduced. As the drug is reconstituted, the user can easily gain access to the drug via the channel provided in the piston, which is very convenient. The number of pieces of waste material is reduced to a minimum, as the user only needs to remove the cover in order to gain access to the drug and does not need to disassemble the unit and/or remove the vial or reservoir from the unit before gaining access to the reconstituted drug.

As an alternative, the first housing part may be openable or disassembled from the second housing part in order to allow positioning of a vial and/or replacing of a used vial with a new vial in the vial holder. In this case the user can position or replace a vial in the device.

The mixing unit according to the invention provides i.a. the following advantages; the number of steps needed to be performed by the user is reduced, the risk of contamination is reduced, the risk of incorrect reconstitution and dosage is reduced, and the unit is easy to operate, e.g. using just one hand.

BRI EF DESCRI PTI ON OF THE DRAWI NGS

The invention will now be described in further details with reference to the accompanying drawings in which Figs. 1 a-1 c are perspective views of a drug mixing device according to a first embodiment of the invention,

Figs.2a-2e illustrate operation of the drug m ixing device of Fig. 1 ,

Fig. 3 is a cross sectional view of a drug mixing device according to a second embodiment of the invention,

Fig. 4 is a cross sectional view of a drug mixing device according to a third embodiment of the invention, and

Fig. 5 is a cross sectional view of a drug mixing device according to a fourth embodiment of the invention.

DETAILED DESCRIPTION OFTHE DRAWINGS

Fig. 1 a is an exploded view of a drug delivery device 1 according to an embodiment of the invention. The device 1 comprises a reservoir 2 containing a liquid and a vial holder 3 for receiving a vial 4 containing a dry drug. At the vial holder 3 there is positioned a first hollow spike (5, not visible in Fig. 1a) adapted to penetrate a stopper 6 of the vial 4, and a second hollow spike 7 adapted to penetrate a movable plunger 8 positioned in the reservoir 2. When the first hollow spike 5 has penetrated the stopper 6 and the second hollow spike 7 has penetrated the movable plunger 8, a fluid connection is established between the reservoir 2 and the vial 4 via the hollow parts of the spikes 5, 7.

The plunger 8 is movable inside the reservoir 2 in an upwards direction. Thereby the plunger 8 may force liquid from the reservoir 2 through the hollow parts of the spikes 5, 7, and into the vial 4. Thereby the dry drug in the vial 4 is reconstituted.

Fig. 1 b is a perspective view of the device 1 of Fig. 1a, where the plunger 8 and the second spike 7 have been positioned in the part of the device 1 containing the reservoir 2, and the vial 4 has been positioned in the vial holder 3.

Fig. 1c is a perspective view of the device 1 of Figs. 1 a and 1b. In Fig. 1 c the vial holder 4 with the vial 3 has been positioned in the part of the device 1 containing the reservoir 2.

Figs.2a-2e illustrate operation of the drug delivery device 1 of Fig. 1. In Fig.2a the device 1 is ready for use. Thus the vial 4 has been positioned in the vial holder 3, but neither the stopper 6, nor the movable plunger 8 has been penetrated by the spikes 5, 7. Thus there is no fluid connection between the reservoir 2 and the vial 4. I n order to operate the device 1 , the user pushes the part of the device 1 containing the reservoir 2 in the direction indicated by arrow 10. Thereby the device 1 is compressed, thereby causing the first hollow spike 5 to penetrate the stopper 6 and the second hollow spike 7 to penetrate the movable plunger 8. Thereby a fluid connection between the reservoir 2 and the vial 4 is established. By pushing the device 1 further in the direction of the arrow 10, the movable plunger 8 is pushed into the reservoir 2. Thereby the liquid in the reservoir 2 is forced into the vial 4 via the established fluid connection, and the dry drug in the vial 4 is reconstituted.

The first hollow spike 5 is provided with a channel 9, through which air may pass from the interior of the vial 4 to the exterior. Thus, as liquid is transferred from the reservoir 2 to the vial 4 via the hollow parts of the spikes 5, 7, air is allowed to leave the vial 4 via the channel 9, thereby providing equalization of the pressure in the vial 4.

In Fig. 2b the part of the device 1 containing the reservoir 2 has been pushed sufficiently to cause the first spike 5 to penetrate the stopper 6 of the vial 4. However, the second spike 7 has not yet penetrated the movable plunger 8.

In Fig. 2c the part of the device 1 containing the reservoir 2 has been pushed further, and the second spike 7 has therefore penetrated the movable plunger 8. A fluid connection has therefore been established between the reservoir 2 and the vial 4. However, since the movable plunger 8 has not yet been moved, liquid from the reservoir 2 has not yet entered the vial 4.

In Fig. 2d the device 1 is shown in a fully compressed position, i.e. the part of the device 1 containing the reservoir 2 has been pushed in the direction of arrow 10 as far as possible. The vial 4 is locked by the vial holder 3 in such a manner that the vial 4 and the vial holder 3 can not be separated. Thereby the vial 4 is kept firmly in position during reconstitution of the dry drug. Accordingly, the first spike 5 has penetrated the stopper 6 and the second spike 7 has penetrated the movable plunger 8, as described above, and the movable plunger 8 has further been pushed to the bottom of the reservoir 2. Thereby all of the liquid has been transferred from the reservoir 2 to the vial 4, and the dry drug has therefore been reconstituted, or is in the process of being reconstituted. Due to the channel 9, the pressure in the vial 4 has been continuously equalized during the transfer of the liquid, and it is therefore possible to remove the vial 4 containing the reconstituted drug from the device 1.

Fig. 2e shows the vial 4 and the vial holder 3 detached from the remaining parts of the device 1. Since it is not possible to separate the vial 4 and the vial holder 3 as described above, the vial holder 3 must be removed along with the vial 4. Furthermore, the vial holder 3 is shaped in such a manner that aspiration of the reconstituted drug can be performed in an easier manner, and it is therefore desirable to remove it along with the vial 4.

Fig. 3 is a cross-sectional view of a drug mixing device 1 according to a second embodiment of the invention. The unit 1 comprises a first housing part 11 and a second housing part 12 which are connected to each other so that they can move telescopically into each other. The first housing part 11 has a closed end in which a vial 4 containing dry drug 13 is positioned. A reservoir 2 in the form of a cartridge is positioned opposite to the vial 4 and contains liquid 14 to be mixed with the drug 13.

An intermediate part 15 is provided between the vial 4 and reservoir 2 for establishing fluid connection there between. The intermediate part 15 comprises a vial holder 3 for receiving and retaining the neck of the vial 4, when the first and second housing parts 11, 12 are moved towards each other. The vial holder 3 comprises a first spike 5 adapted to penetrate a septum 6 of the vial 4. The intermediate part 15 further comprises a reservoir holder 16 for receiving and retaining the neck of the cartridge 2. A second spike 7 with one channel 7a at the reservoir holder 16 is adapted to penetrate the septum 17 of the cartridge 2.

When the first spike 5 has penetrated the septum 6 and the second spike 7 has penetrated the septum 17, a fluid connection is established between the cartridge 2 and the vial 4 via the hollow parts of the spikes 5, 7.

A piston 18 is movable inside the cartridge 2 in a downwards direction and is forced downwards by means of the part 19 of the second housing part 12 abutting the piston 18, when the two housing parts 11, 12 are moved towards each other. Thereby the piston 18 forces liquid 14 from the cartridge 2 through the hollow parts of the spikes 5, 7 and into the vial 4. Thereby the dry drug in the vial 4 is reconstituted.

As the neck of the vial 4 and cartridge 2 enter their respective holders 3, 16, the holders 3, 16 flex outwards in order to grip around the respective neck. In order to make sure that the septum 6 is penetrated by the first spike 5 before the septum 17 is penetrated by the second spike 7, the vial holder 3 is made more flexible than the reservoir holder 16 and the first spike 5 is made longer than the second spike 7.

The first housing part 11 has guide slots 20 provided inside, which guides the two housing parts 11 , 12 relatively to each other, and the slots 20 further comprise a hole or groove 21 in which a 'snap-lock' 22 enters when the second part 12 has reached an end position. Thereby, the two housing parts 11, 12 are interlocked. The first spike 5 has two channels 23, 24; one channel 23 forming part of the fluid connection between the cartridge 2 and the vial 4, and one channel 24 acting as a pressure equalizing outlet, and being flu id Iy connected to channel 9. Thereby, the air in the vial 4 can escape through channels 24 and 9 when liquid enters the vial 4. The channel 24 comprises a filter 25 which is permeable to air but not to liquid. The channel 24 extends further into the vial 4 than the channel 23, which ensures that the air, which is sucked back into the vial 4 as the vial 4 is being emptied, is not sucked around and into the spike 5.

The piston 18 comprises a liquid channel 26 for connecting a liquid outlet 27 with the internal of the vial 4 via the established fluid connection 5, 7. A membrane 28 ensures that liquid is not entering the channel 26 during pressing the piston 18 downwards. When the piston 18 reaches an end position, the membrane 28 is penetrated by the second spike 7, and an open liquid channel 26 is provided between the vial 4 and the outlet 27.

The second housing part 12 is closed by a removable cover 29 having a seal 30. After having removed the cover 29, the outlet 27 can be connected to a syringe, and the reconstituted drug can be sucked out from the vial 4 via the channel 27 and the fluid connection 5, 7.

The device 1 functions as follows;

In Fig. 3 no fluid connection between the cartridge 2 and the vial 4 has been established yet. In order to operate the device 1 , the user pushes the housing part 12 in the direction indicated by arrow 31. Thereby the device 1 is compressed, and the cartridge 2 is pressed towards the intermediate part 15. As the vial holder 3 is made more flexible than the reservoir holder 16 (as mentioned above), the vial 4 will enter the vial holder 3 and the first spike 5 will penetrate the septum 6 before the cartridge 2 enters the reservoir holder 16, and the second spike 7 penetrates the septum 17. As the spikes 5, 7 have penetrated each septum 6, 17, respectively, the fluid connection is established. By pushing the device 1 further in the direction of the arrow 31 , the movable piston 18 is pushed further into the cartridge 2. As liquid is transferred from the cartridge 2 to the vial 4 via the hollow parts of the spikes 5, 7, air is allowed to leave the vial 4 via the channels 24, 9, thereby providing equalization of the pressure in the vial 4. The liquid 14 in the cartridge 2 is forced into the vial 4 via the established fluid connection, and the dry drug in the vial 4 is reconstituted.

When the piston 18 reaches an end position, in which all liquid is forced into the vial 4, the second spike 7 will penetrate the membrane 28. The housing parts 11, 12 are now locked to each other as the 'snap-lock' 22 enters the groove or hole 21. Now, the cover 29 can be removed and a syringe can be connected to the outlet 27, and the reconstituted drug can be sucked out from the vial 4. The membrane 28 could be substituted by a valve system that opens when a syringe or any other infusion device is connected to the outlet.

Fig. 4 is a cross sectional view of a drug mixing device 1 according to a third embodiment of the invention. A housing part 11 contains a vial 4 with dry drug 13, and an intermediate part 15 having a vial holder 3 with a spike 5 to penetrate the septum 6.

A piston 18 closes a reservoir 2 containing liquid 14, and the piston 18 comprises a liquid channel 26 through which the liquid is forced into the vial 4. As the vial 4 is pressed downwards, the spike 5 first penetrates a rubber stopper 32 placed over the spike 5 and then the septum 6 of the vial 4. The fluid connection is now established, and the liquid is forced into the vial 4 by pressing the vial 4, and thus the piston 18, further downwards, and the dry drug 13 will be reconstituted. The piston 18 is now in an end position (not shown) and a sealing 33 provided in the bottom of the reservoir 2 is penetrated by a spike 34 on a syringe connector 35, and a liquid channel is provided between the vial 4 and a syringe 36 which is positioned in the syringe connector 35.

This device 1 of Fig.4 is not closed in one end, and this allows for pooling of vials, as the vial can be replaced with a new one when it is empty.

Fig. 5 is a cross sectional view of a drug mixing device 1 according to a fourth embodiment of the invention. The device 1 of Fig. 5 functions essentially as the embodiments of Figs.3 and 4, and parts and functions which have been described previously will therefore not be described in detail here.

The device 1 of Fig. 5 is operated as follows.

When it is desired to reconstitute and deliver the drug contained in the device 1 the first and second housing parts 11, 12 are moved towards each other as described above. Thereby the first spike 5 and spike 24 penetrate the septum 6 of the vial 4, and subsequently the second spike 7 penetrates the septum 17 of the reservoir 2. Piston 18 is then moved downwards, thereby pressing liquid 14 from the reservoir 2 into the vial 4 via the established fluid connection, and air inside the vial 4 will escape through the separate spike 24, thereby equalising the pressure inside the vial 4. During this the second spike 7 is positioned in recess 37 of stopper element 38. When the piston 18 abuts the stopper element 38 all of the liquid 14 has been transferred to the vial 4 and reconstitution of the dry drug 13 takes place.

The spike 24 preferably comprises a filter which is permeable to air but not to liquid. The spike 24, being separate from the spike 5, extends further into the vial 4 than the spike 5. Thereby it is ensured that the air which is sucked back into the vial 4 as the reconstituted drug is subsequently transferred out of the vial 4, is not sucked around and into the spike 5.

When the dry drug 13 has been properly reconstituted and it is desired to deliver the drug, removable cover 29 is removed, thereby exposing the liquid outlet 27. A Luer-lock is connected to the liquid outlet 27, and thereby syringe connector 35 is forced downwards. As a consequence spike 34 penetrates sealing 33, and a fluid connection is thereby established between the vial 4 and the liquid outlet 27. The reconstituted drug is then delivered via this fluid connection.

Claims

CLAI MS

1. A drug mixing device comprising:

- a reservoir containing a liquid,

- a vial holder for receiving a vial containing a dry drug,

- means for equalizing a pressure in a vial positioned in the vial holder,

wherein at least the reservoir, the vial holder, the means for establishing a fluid connection and the forcing means form an at least substantially integral device.

2. A drug mixing device according to claim 1, wherein the means for establishing a fluid connection comprises a first spike positioned at or near the vial holder and being adapted to penetrate a stopper of a vial positioned in the vial holder.

3. A drug mixing device according to claim 2, wherein the means for establishing a fluid connection further comprises a second spike adapted to penetrate the reservoir.

4. A drug mixing device according to claim 3, wherein the first spike is longer than the second spike.

5. A drug mixing device according to any of claims 2-4, wherein the pressure equalizing means comprises a channel formed in the first spike.

6. A drug mixing device according to any of the preceding claims, further comprising a vial containing a dry drug, the vial being positioned in or forming part of the vial holder.

7. A drug mixing device according to claim 6, further comprising:

a first housing part containing the vial, a second housing part containing the reservoir, said first and second housing parts being movably connected to each other, and

an intermediate part containing the means for establishing a fluid connection.

8. A drug mixing device according to claim 7, further comprising locking means for locking the first housing part relatively to the second housing part when the means for forcing the liquid from the reservoir to a vial has reached an end position in which the liquid has been forced into the vial.

9. A drug mixing device according to any of the preceding claims, wherein the means for establishing a fluid connection comprises means for penetrating the reservoir and means for penetrating a septum of a vial, and wherein the means for establishing a fluid connection is adapted to penetrate the septum of a vial before penetrating the reservoir.

10. A drug mixing device according to any of the preceding claims, wherein at least part of the vial holder is removable from the device along with a vial positioned in the vial holder.

11. A drug mixing device according to any of claims 1-9, further comprising a liquid outlet being flu id Iy connectable to a vial positioned in the vial holder, a reconstituted drug thereby being deliverable from the device via said liquid outlet.

12. A drug mixing device according to claim 11, wherein the liquid outlet is adapted to be connected to an infusion device.

13. A drug mixing device according to claim 11 or 12, further comprising means for establishing a fluid connection between a vial positioned in the vial holder and the liquid outlet.

14. A mixing unit for mixing dry drug with liquid, the unit comprising;

- an intermediate part provided inside the housing parts for establishing a fluid connection between the reservoir and the vial upon moving the first and second housing part towards each other, said intermediate part comprising a first spike for penetrating a septum of the vial and a second spike for penetrating the reservoir, the first and second spike together defining a common fluid connection, and

15. A mixing unit according to claim 14, further comprising locking means for locking the first housing part in relation to the second housing part, when the piston has reached an end position in which the liquid has been forced into the vial.

16. A mixing unit according to claim 14 or 15, wherein the first spike comprises two separate channels;

a first channel defining said fluid connection in combination with the second spike, and

a second channel defining a fluid connection between the internal of the vial and an air outlet for equalising pressure provided in the vial, said outlet comprising a filter being air permeable but not liquid permeable.

17. A mixing unit according to any of claims 15-16, wherein the first spike is longer than the second spike, the first spike being adapted to penetrate the septum of the vial before the second spike penetrates the septum of the reservoir, when moving the first and second housing parts towards each other.