The present invention relates to an injection device, a syringe and a method of providing a dried medicament, such as a lyophilised medicament.

It is known to provide medicaments in the form of a freeze-dried or lyophilised "cake". The lyophilised medicament may be held within an impervious container, such as a glass vial or syringe. For injection purposes, the medicament is reconstituted with water, usually sterile water for injection (sWFI). Other drying processes, such as evaporation, spray drying, etc could be used and the medicament could be reconstituted with other liquids.

The reconstitution step may be carried out manually, for instance by injecting water into a sealed vial containing the medicament and then withdrawing the resulting solution back into the syringe. The medicament solution may then be injected directly from this syringe or transferred to an alternative injection device.

Such arrangements are awkward and involved for the operators and it would be desirable to provide a more straightforward arrangement.

Various arrangements have been proposed for automatically deploying the needle of a syringe and then dispensing its contents, for instance as described in WO 95/35126, EP-A-O 517 473, US 6,159,181 and WO 03/092771. The present application recognises for the first time the desirability of providing a lyophilised medicament in such injection devices.

According to the present invention, there is provided a method of providing a substantially dried, such as lyophilised, medicament for dispensing, the method including providing the dried medicament in a space within the bore of a syringe, providing liquid, such as water, in a reservoir, providing a permanent connection between the reservoir and the space

via a one-way valve, and driving liquid from the reservoir to the space through the one-way valve in response to movement of the syringe to deploy the needle of the syringe.

In this way, the user is not required to carry out multiple operations, for instance injecting liquid into a container of the medicament and then withdrawing the solution back into the syringe. The required solution can easily be produced by the user merely by driving the liquid from the reservoir through the one-way valve. Furthermore, since driving of the water occurs as a result of movement of the syringe, the user need not be aware of a separate step of mixing the liquid and medicament. As the body of the syringe is moved with the needle, transfer of the liquid from the reservoir to the space occurs automatically such that the required solution is available for dispensing by movement of the dispensing piston of the syringe.

Preferably, the reservoir is provided within the bore of the syringe.

The method may include locating a plunger in the bore of the syringe between the dispensing piston and the end wall of the syringe, the space being defined between the plunger and the end wall and the reservoir being defined between the plunger and the dispensing piston.

The one-way valve may be provided in the plunger.

The method preferably includes moving the syringe so as to deploy the needle of the syringe whilst holding the plunger still, thereby driving liquid from the reservoir to the space.

In this way, both the liquid and the medicament may be held within the syringe. By moving the syringe relative to the plunger during movement of the syringe to deploy its needle, the plunger reduces the volume defined with the dispensing piston for the reservoir whilst increasing the volume defined with the end wall for the space such that liquid passes

through the one-way valve of the plunger to mix with the medicament and form the required solution ready to be dispensed by movement of the dispensing piston.

This method can be used effectively within an injection device for automatically deploying ^• the needle of a syringe and dispensing the contents of the syringe.

According to the present invention, there is provided an injection device including:

a syringe having an end wall defining a throughhole, side walls defining a bore extending from the end wall, a needle communicating with the bore through the end wall and a dispensing piston movable in the bore towards the throughhole so as to expel contents of the syringe through the needle, the bore including a space for holding a substantially dried, such as lyophilised, medicament;

a housing containing the syringe and having an opening at one end through which the needle may extend;

a drive element movable towards said one end so as to move the needle of the syringe out of the opening and to move the dispensing piston of the syringe towards the end wall;

a reservoir for containing liquid, such as water; and

a one-way valve connecting the reservoir to the space; wherein

the reservoir is arranged such that as the drive element moves towards said one end so as to move the needle of the syringe out of the opening, the volume of the reservoir is reduced so as to drive liquid through the one-way valve to said space.

Thus, movement of the syringe by the drive element automatically causes liquid to be driven from the reservoir into the space so as to form the desired medicament solution.

The user is not faced with having to carry out separate operations for mixing the liquid and medicament.

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Like the prior-art arrangements discussed above, the injection device could then automatically dispense the contents of the syringe and then retract the needle back into the housing of the device.

Preferably, the reservoir is defined by walls fixed relative to the syringe and at least one wall fixed relative to the housing during movement of the needle of the syringe out of the opening.

In this way, as the syringe is moved relative to the housing so as to deploy its needle, the walls fixed relative to the syringe move relative to the housing. During this operation, the at least one wall remains fixed relative to the housing and the volume defined in the reservoir can thereby be reduced automatically causing liquid to be driven through the one-way valve to the space.

Preferably, the injection device further includes a plunger in the bore between the end wall and the dispensing piston, the space being defined between the end wall and the plunger and the reservoir being defined between the plunger and the dispensing piston.

This provides a particularly convenient and compact way of holding both the liquid and the medicament.

When the syringe is moved in the housing to deploy the needle, the bore and the dispensing piston will move with it. By maintaining the plunger in a position relative to the housing, the reservoir is thereby reduced in size forcing liquid out of the reservoir.

Preferably, the plunger includes the one-way valve. In this way, the plunger will itself allow liquid to transfer from the reservoir to the space.

The plunger may comprise a cone seal, though other seals are possible, such as an O-ring which, when moved towards the dispensing piston, unrolls and breaks its seal.

Preferably, the injection device includes a connection rod extending from the plunger through the dispensing piston for connection to the housing.

In this way, the plunger is held in a position fixed relative to the housing whilst the syringe with its dispensing piston are moved during deployment of the syringe needle.

Preferably, the connection rod is detachably connected to the housing such that, when the plunger reaches the dispensing piston, the connection rod detaches from the housing.

In this way, the injection device is able to continue its automatic operation of the syringe. The drive element can drive the dispensing piston along the bore of the syringe with the plunger being pushed ahead of it. Hence, once the needle of the syringe has been deployed and the bore and dispensing piston of the syringe have moved relative to the plunger so as to drive liquid into the space, the plunger can then move relative to the housing with the dispensing piston.

The connection rod can be positively detached from connection to the housing according to the position of the syringe within the housing or, alternatively, the connection with the housing may be broken merely by the force of the dispensing piston pushing the plunger away from its connection with the housing.

As part of an automatic deployment and retraction system, the injection device may further include a resilient member for biasing the syringe and needle inwardly of the housing and a mechanism operable to release the syringe such that the needle moves inwardly of the housing.

In this way, after the dispensing piston has been moved to dispense the contents of the syringe, the mechanism can release the needle.

The present invention is particularly advantageous in conjunction with the mechanism as described in WO 03/092771. In this regard, the injection device preferably includes

a drive coupling for extending from said drive element to the dispensing piston of the syringe so as to transfer movement of said drive element to the dispensing piston; wherein

the drive coupling is compressible in length such that, after the drive element has moved the dispensing piston to the end wall, the drive coupling gradually reduces in length whilst the dispensing piston is maintained at the end surface until said mechanism releases the syringe.

Preferably, the mechanism is operable when the drive element reaches a predetermined position in said housing and the drive coupling gradually reduces in length such that, after the dispensing piston reaches the end wall, the drive element continues to move in said housing to said predetermined position.

Preferably, the injection device further includes an engagement for transferring drive directly from the drive coupling to the syringe walls such that movement of the drive element towards said one end causes no relative movement of the dispensing piston in the syringe; wherein

the engagement is releasable once the needle of the syringe extends out of the opening such that movement of the drive element towards said one end causes relative movement of the dispensing piston in the syringe bore.

Alternatively, the injection device may include

a drive coupling for extending from the drive element to the dispensing piston of the syringe so as to transfer movement of said drive element to the dispensing piston; and

an engagement for transferring drive directly from the drive coupling to the syringe walls such that movement of the drive element towards said one end causes no relative movement of the dispensing piston in the syringe; wherein

the engagement is releasable once the needle of the syringe extends out of the opening such that movement of the drive element towards said one end causes relative movement of the dispensing piston in the syringe bore.

Preferably, the housing includes a release portion which interacts with the engagement to release drive to the syringe.

It will be appreciated that a syringe could be provided separately. Hence, according to the present invention, there is provided a syringe including:

an end wall defining a throughhole for connection to a needle;

side walls extending from the end wall defining a bore extending from the end wall;

a dispensing piston movable in said bore towards said end wall so as to expel contents of the syringe through the throughhole;

a plunger positioned between the dispensing piston and the end wall and moveable in said bore;

a one-way valve formed in the plunger allowing flow from a dispensing piston side of the plunger to an end wall side of the plunger; and

a connection rod extending from the plunger away from the end wall and through the dispensing piston so as to allow a user to hold the plunger whilst moving the syringe and dispensing piston.

Thus, in the same way as described above, the user is able to deploy the syringe whilst automatically causing flow from the dispensing-piston side of the plunger to the end-wall side of the plunger.

Preferably, liquid, such as water, is contained in a reservoir formed in the bore between the dispensing piston and the plunger.

Preferably, substantially dried, such as lyophilised, medicament is contained in a space formed in the bore between the plunger and the end wall.

As discussed above, the plunger could comprise a cone seal or any other seal providing the one-way valve functionality.

The present invention provides an injection device for automatically deploying the needle of a syringe such as defined above and dispensing the contents of that syringe.

The invention will be more clearly understood from the following description, given by way of example only, with reference to the accompanying drawings, in which:

Figure 1 illustrates a syringe including features according to the present invention;

Figure 2 illustrates an alternative one-way valve.

Figure 3 illustrates an injection device embodying the present invention; and

Figure 4 illustrates an alternative injection device embodying the present invention.

Various automatic injection devices are known for deploying the needle of a syringe, dispensing the contents of the syringe and then retracting the needle of the syringe. The present invention is particularly advantageous in conjunction with these arrangements, but

the principles of forming the required medicament solution will be described with reference merely to a syringe.

As illustrated in Figure 1, a syringe 2 is provided with an end wall 4 to which a needle 6 is attached. The syringe includes side walls 8 which extend away from the end wall 4 in an opposite direction to the needle 6 so as to define a bore 10. The needle 6 communicates with a throughhole in the end wall 4 and, hence, with the bore 10.

A dispensing piston 12 seals with the inner surfaces of the side walls 8 and is movable along the bore 10 of the syringe. The dispensing piston 12 includes a drive element 14 for driving the dispensing piston 12 along the bore 10 of the syringe 2.

These features of the syringe may take the form of any known syringe.

In contrast to a conventional syringe, the syringe of Figure 1 further includes a plunger 16 which is positioned within the bore 10 between the end wall 4 and dispensing piston 12. The plunger 16 seals with the inner surfaces of the side walls 8 so as to divide the bore 10 into a reservoir 18 on the dispensing-piston side and a space 20 on the end-wall side. Like the dispensing piston 12, the plunger 16 is slidable along the bore 10.

A connection rod 22 extends from the plunger 16 away from the end wall 4 and through the dispensing piston 12 and its drive element 14. As will be appreciated, the dispensing piston 12 also seals with the connection rod 22 so as to maintain the reservoir 18.

By holding the connection rod 22 and moving the rest of the syringe in the direction of the needle 6 (to the right as illustrated in Figure 1), the plunger 16 is drawn along the bore 10 away from the end wall 4.

The plunger 16 is provided with a one-way valve. As illustrated, this is a cone seal which increases in diameter towards the end wall 4 such that it will allow flow from the

dispensing-piston side to the end-wall side. However, it should be appreciated that the plunger 16 may be formed with any type of one-way valve allowing flow in that direction. As an alternative, the plunger 16 could be formed from an 0-ring as illustrated in Figure 2.

When the connection rod 22 moves to the left (in diagram) the O-ring 17 is rolled from the position shown on to the reduced diameter with the relief groove 19. The O-ring 17 is no longer stretched radially, so reduces in diameter and no longer seals in the syringe bore

Liquid in the reservoir 18 can therefore pass around the O-ring 17 and trough the relief groove 19 into space 10 to reconstitute the dried, such as lyophilised, substance (not shown)

When the connection rod 22 (which may be pushed by the dispensing piston) moves to the right, the 'O' ring rolls back to the position shown and seals off the bore, so that fluid is forced out of the syringe

Thus, with the connection rod 22 and plunger 16 held in place, movement of the syringe body, including its side walls and the dispensing piston 12, will cause the dispensing piston 12 to move towards the plunger 16. This will reduce the volume defined for the reservoir 18 and cause flow from the reservoir 18 into the space 20.

In practice, the syringe can be provided with water, such as sterile water for injection (sWFI) in the reservoir 18 and lyophilised medicament, for instance in the form of a cake 24 of medicament, in the space 20. In this situation, movement of the syringe body relative to the connection rod 22 and plunger 16 will cause the water to move from the reservoir 18 into the space 20 so as to form the desired medicament solution in the enlarged space 20.

Once a suitable solution has been formed, usually once the plunger 16 reaches or at least approaches the dispensing piston 12, the contents of the syringe may be dispensed. Of

course, this is achieved by using the drive element 14 to move the dispensing piston 12 towards the end wall 4, thereby expelling the solution through the throughhole of the end wall 4 and the needle 6.

The present invention proposes fitting a syringe similar to this into an automatic injection device such as described in WO 03/092771. Figure 3 illustrates schematically a similar and highly advantageous arrangement. Components in common with Figure 1 are given the same reference signs.

The drive element 30 associated with the dispensing piston 12 is very similar to that of Figure 1, but includes some additional features to be discussed below. Similarly, the connection rod 32 is very similar to that of Figure 1, but includes a detachable connection to be discussed below.

The injection device includes a housing 40 which extends from one end 42 having an opening 44. A resilient member such as a return spring 46 urges the syringe 2 away from the end 42 and opening 44 towards the opposite end 48 of the housing 40. At the opposite end 48 of the housing 40, another resilient member, such as drive spring 50, urges a drive mechanism towards the one end 42 and opening 44, the drive mechanism being used to move the syringe 2 against the bias of the return spring 46 and deploy the needle 6 through the opening 44. A trigger 52 is operable to hold a first drive component 54 against the bias of the drive spring 50 and is operable by the user to release the first drive component.

As illustrated, a first latch 56 connects the first drive component 54 to the drive element 30 of the dispensing piston 12. The return spring 46 is arranged to provide a relatively small bias on the syringe 2 compared to the resistence to movement of the dispensing piston 12 in the bore 10 of the syringe 2 (at least partly due to the resistance in dispensing the contents of the syringe through the needle 6). Hence, when the trigger 52 releases the first drive component 54, the main drive spring 50 moves the syringe 2 against the bias of the return spring 46 and deploys the needle 6 through the opening 44.

As illustrated, the connection rod 32 of the plunger 16 is connected to the housing 40 by means of an internal housing extension 60. The extension 60 extends along the axis of the housing 40 from the opposite end 48 and is attached to the connection rod 30 by means of a second latch 62. Thus, as the main drive spring 50 moves the syringe 2 towards the one end 42 so as to deploy the needle 6 through the opening 44, the connection rod 32 and plunger 16 are held in place relative to the housing 40. In this way, as was described with reference to Figure 1, water in the reservoir 18 transfers to the space 20 to mix with the lyophilised medicament 24. By means of the plunger 16 and connection rod 30, it is possible automatically to mix the water and lyophilised medicament as part of the same process of moving the syringe 2 and deploying the needle 6.

As mentioned above, the connection rod 32 is attached to the extension 60 of the housing 40 by means of latch 62. However, when the syringe 2 reaches its deployed position, a second drive component 64 to be described below will have moved beyond the latch 62, thereby releasing the latch 62 and detaching the connection rod 32 from the extension 60. This will enable the dispensing piston 12 to travel along the bore 10 pushing the plunger 16 in front of it and dispensing the contents of the syringe 2.

As mentioned above, the drive mechanism includes a second drive component 64 which is connected to the first drive component 54 by means of a third latch 66. As illustrated, the second drive component 64 extends along and inside the drive element 30 forming with it a damper chamber 68 to be discussed below. The connection rod 32 and extension 60 extend through the second drive component 64.

In use, as described above, the main drive spring 50 drives the syringe 2 towards the one end 42 so as to deploy the needle 6 through the opening 44. During this process, the first drive component 54 drives the drive element 30 of the syringe 2 by means of the latch 56 and, simultaneously, the second drive component 64 is driven via the third latch 66. When the syringe 2 is in its deployed position, the first latch 56 reaches a first latch release portion 70 in the housing 40. This releases the first latch such that the drive element 30 is

no longer driven by the first drive component 54 and relative movement becomes possible between the second drive component 64 and the drive element 30.

After this time, the first drive component 54 continues to act on the dispensing piston 12 through the drive element 30, but only via the second drive component 64. The dispensing piston 12 comes to the end of its travel in the bore 10 so as to fully expel the contents of the syringe 2. Fluid continues to leak from the damper chamber 68 such that, even though the drive element 30 is no longer moving relative to the housing, the second drive component 64 still does. Eventually, the third latch 66 reaches the third latch release portion 72 in the housing 40 and the connection between the first drive component 54 and the second drive component 64 is released. At this point, there is nothing to resist the bias of the return spring 46 and the needle 6 is retracted back into the housing 40.

It will be appreciated that the various latches and release arrangements are not essential to the invention. Indeed, the second latch 62 can be replaced by a detent latch which is released upon the application of sufficient force by the dispensing piston 12 on the plunger 16.

The invention provides an arrangement by which the movement of the syringe to deploy the needle 6 is used to cause relative movement with a plunger for driving water into the space housing the lyophilised medicament. This can be used in other arrangements, for instance where the injection device housing includes a separate reservoir which would not normally be considered as part of the syringe but which connects to the lyophilised medicament space and is reduced in volume with movement of the syringe so as to cause the required mixing of water and lyophilised medicament. By way of example, the water reservoir and lyophilised medicament space could be formed in two side-by-side chambers, rather than in the coaxial arrangement as described above.

A similar arrangement to Figure 3 is possible where an engagement is provided for transferring drive directly from the first drive component to the walls 8 of the syringe 2 so

that there is no relative movement of the dispensing piston 12 in. the bore 10 during deployment of the needle 6. The engagement is then releasable once the needle of the syringe is deployed such that further movement of the drive component moves the dispensing piston 12 to expel all of the contents of the syringe. A damping chamber can still be provided to allow the drive component to continue moving after the dispensing piston 12 has reached the end of its travel, thereby to ensure that all of the contents of the syringe is expelled before the release mechanism allows the return spring to retract the needle of the syringe.

It is also possible to embody the present invention in injection devices without the damper described above.

In the arrangement illustrated in Figure 4, a housing 140 encloses a syringe body 102 which may be moved to deploy a needle 106 through an opening 144. As with the embodiment of Figure 3, upon operation of a trigger 152, a drive component 154 is released and driven by a main spring 150 to move the syringe body 102 and needle 106 against the bias of a return spring 146 to the deployed position.

A plunger 116 is located in the bore 110 of the syringe body 102 between an end wall 104 and a dispensing piston 112. A connection rod 132 extends from the plunger 116 to an extension 160 of the housing 140. The connection rod 132 passes through the dispensing piston 112 and the drive element 130 of the dispensing piston 112. Preferably, in this embodiment, the connection rod 132 is released from the extension 160 merely by the dispensing piston 112 applying sufficient force on the plunger 116.

Unlike the embodiment of Figure 3, there is no second drive component. The drive component 154 acts directly on the drive element 130 by means of outwardly extending arms 180. The housing includes an internal release member 182 which is arranged to deflect the arms 180 inwardly and release their engagement with the drive component 154. The various components are dimensioned such that, at the point at which the dispensing

piston 112 (with the plunger 116) has expelled all of the contents (or at least a known proportion of the contents) from the syringe body 102, the release member 182 causes the arms 180 to become released from the drive member 154 such that the syringe body 102 and needle 106 are retracted under the force of the return spring 146.

As with the embodiments discussed above, transfer of water from the reservoir 118 to the space 120 happens automatically with movement of the syringe body 102 to its deployed position.