WO2011012849A1

WO2011012849A1 - Injector

Info

Publication number: WO2011012849A1
Application number: PCT/GB2010/001421
Authority: WO
Inventors: Martin Mcloughlin
Original assignee: Ucb Pharma S.A.
Priority date: 2009-07-28
Filing date: 2010-07-26
Publication date: 2011-02-03
Also published as: GB0913136D0

Abstract

There is provided a syringe that is suitable for use in the injected delivery of drug to a patient. The syringe comprises a barrel for containing a volume of a liquid drug formulation; a hollow needle at a front end of said barrel, the hollow needle defining a needle tip for dispensing of said liquid drug formulation; a syringe plunger that is axially movable within the barrel; and a drive transfer element for transferring axial drive. The drive transfer element defines a plunger end receivable within the barrel of the syringe and axially movable there within such that a cushion is definable between the syringe plunger and the plunger end such that drive is communicable from the plunger end of the drive transfer element to the syringe plunger by way of the cushion. The cushion may be an air cushion or a compressible cushioning element.

Description

Injector

The present invention relates to a syringe and an injector device for receipt of the syringe that is suitable for use in the injected delivery of a drug formulation to a patient.

It is well-known to use syringes for the delivery of injectable liquid drug formulation to a patient. Syringes rely on puncturing of the patient's skin by a hollow needle through which the injectable liquid drug (e.g. in solution or suspension form) is delivered to the muscle or tissue of the patient. Typically, such syringes comprise a barrel for containing a volume of the liquid drug; a hollow needle defining a needle tip for dispensing of the liquid; and a plunger that is axially movable within the barrel.

It is also well-known to provide injectors for use with syringes. Such injectors typically comprise a body for housing the syringe and an actuating mechanism, which is triggered in use, to allow for automatic delivery of the liquid drug formulation from the syringe. Actuating mechanisms typically comprise a source of automatic drive (e.g. a strong spring) for drivable movement of a drive transfer element (e.g. a plunger rod) that transfers drive to the syringe plunger for axial movement thereof within the syringe barrel. Such movement of the syringe plunger results in the plunged driving of the liquid drug from the syringe barrel to the hollow needle for dispensing to the patient via the needle tip thereof.

For safety and hygiene reasons, it is desirable that the hollow needle does not protrude from the housing of the injector other than when expelling the liquid drug formulation during an injection procedure. Thus, injectors have been developed in which, the housing is arranged such that a needle receiving part allows for the needle of the syringe to be axially moveable therein from a first (i.e. rest) position in which the hollow needle is shrouded by the needle receiving part to a second (i.e. use or ready to inject) position in which at least the tip of the needle protrudes from that needle receiving part of the housing. It is recognized to be beneficial that (1) this needle un -shrouding movement is readily enabled, but also (2) that such un-shrouding movement does not result in any premature delivery of the liquid drug. Thus, one ideal mode of operation comprises a triggering of the actuating mechanism, which first acts to transfer force to move the syringe from the 'rest' to the 'use' (needle -protruding) position, and which only then acts to transfer force to the syringe plunger for expelling of liquid drug contents from the syringe barrel.

It is known that the desired sequential operation of these functions may be achieved by use of an actuating mechanism including a coupling -decoupling arrangement, in which the various functions of operation are sequenti ally performed responsive to a series of coupling and/or decoupling actions powered by the source of drive.

In one exemplary aspect, a drive transfer element (e.g. plunger rod) reversibly couples to the syringe barrel. Initially, the coupling is in place and drive movement applied to the plunger rod results in drivable movement of the syringe as a whole from the 'rest' to the 'use' position. That coupling then decouples such that further drive movement applied to the plunger rod results in drivable movement of the syringe plunger within the syringe barrel, ultimately to the 'fully plunged' position when most, preferably all of the liquid drug contents of the syringe barrel have been drivably expelled therefrom.

A possible limitation of arrangements of this type is that the required coupling- decoupling actions are usually set to operate at one or more pre -determined positions set by the relative positions of fixed and driven members of the device. Correctly and accurately locating the pre-determined positions is thus critical to the successful operability of the device.

In one aspect, if the pre-determined position relating to the end of injection procedure is set too 'short' then an incomplete injection may result in which a patient does not receive a full dose of liquid medicament. In a contrary aspect, if that pre-determined position is set too 'long' then the syringe plunger within the liquid reservoir of the syringe barrel may be driven against the end of that barrel before the decouple mechanism can operate with the result that the mechanism may seize resulting in a failure to transition to the needle protection state. It is also usually important to drive the syringe plunger as far as possible within the liquid reservoir of the syringe barrel before decoupling to maximise the dose delivered whilst minimising wasted liquid medicament. This often means that high precision is required in the setting of the pre-determined decouple position and therefore that there is a narrowly defined 'acceptable zone' for the predetermined decouple position to ensure consistent and reliable operation.

It is known that imprecision in the manufacture of the components of the device, the syringe and the liquid reservoir of the syringe barrel itself, inevitably introduces variance into the manufactured dimensions thereof. In practice, each component is produced to a specified manufacturing tolerance. However, Applicant has now appreciated that when assembled into a complete device these individual tolerances'may 'stack-up' to produce a combined higher overall variability for the assembly. Indeed, it becomes possible that the stack -up of manufacturing tolerances may be greater than the precision required in the dimensions for the pre-determined couple and/or decouple position(s). In such circumstances it has been appreciated that correct functioning of the device may be aversely affected. In one particular aspect, there may be a sufficiently high 'zone of uncertainty' created to give rise to the possibility of incomplete dosing and/or device seizure and/or which may prevent reliable dosing or needle protection.

In another particular aspect, the possibility of device seizure is exacerbated by the comparative incompressibility of the device and liquid reservoir components, including that of the syringe plunger, particularly when confined in the barrel of the syringe. This may result in the syringe plunger reaching a 'hard stop' at the end of the syringe barrel with the result that any squeezing of the syringe plunger at the end of the barrel to maximise delivery (as is often done in manual injections) risks device seizure. This is because if all movement of the syringe plunger arrests prior to the pre-determined decouple point at which the end of injection is reached then the pre-determined decouple point will never be reached and the device will seize. Typically therefore the pre-determined decouple point in such devices is set just before the syringe plunger starts to be compressed. However, due to the aforementioned tolerance stack up this may risk incomplete dosing without eliminating the risk of device seizure. Indeed, decoupling typically occurs over a finite range of travel of the driven member rather than at any one point, which may add still further uncertainty to the actual, decouple point.

Applicant has now appreciated that some or all of the aforementioned problems may be ameliorated by the use of a drive transfer element that defines a plunger end receivable within the barrel of the syringe and is axially movable there within such that a cushion (e.g. an air cushion) is definable between the syringe plunger and the plunger end. The defining of such an air cushion is assisted by forming the syringe plunger and/or the plunger end of the drive transfer element from a material (e.g. rubber or a plastic polymer) that provides good sealing properties with the (typically glass) syringe barrel such that an airtight seal can be readily created. As a result of defining the air cushion, axial drive is communicable from the plunger end ('secondary plunger') of the drive transfer element to the syringe plunger within the syringe barrel by means of that cushion of compressible air.

Thus, in one aspect when the end of the syringe barrel is reached the syringe plunger can be driven hard against the end of the syringe barrel by further compression of the air that defines the cushion between the two plunger parts. However, as a result of the higher compressibility of air, it is now possible if required, to compress that air cushion and hence to drive the syringe plunger against the end of the syringe barrel to ensure complete dosing whilst enabling the drive transfer element or any element(s) coupled thereto to continue their forward motion to a pre-determined decouple point. Dependent on the size (e.g. axial length or volume) of the air cushion, the geometry and hardness of the syringe plunger and plunger end, the zone of acceptability for the predetermined decouple position can therefore be broadened such that it i s wider than the tolerance stack-up of the device assembly and therefore consistent and reliable operation can be assured. In effect, the definition of a compressible air cushion within the syringe barrel eliminates the abrupt transition between moving syringe plunger and arrested syringe plunger or 'hard stop', encountered when a comparatively incompressible syringe plunger is used. Greater flexibility in choice of plunger material is thus, also provided. In alternative aspects, the air cushion may be replaced by a compressible cushioning element, which in essence, performs the same function.

The use of a 'secondary plunger' to define the compressible air cushion has the further advantage that its position can be set independently without interfering with the sterile seal which the syringe plunger forms with the syringe barrel. This in turn, may enable more precise setting of volume of the liquid reservoir defined within the syringe barrel, which may further improve the consistency and reliability of operation of the device. A still further advantage is that the position of the 'secondary plunger' may be set independently of that of the syringe plunger, which allows for additional flexibility during manufacture and assembly of the device.

In another aspect, where the syringe is to be employed in an auto-injector device capable of providing axial drive of defined drive stroke length, the use of the 'secondary stopper' provides the still further advantage that variable dose volumes may be accommodated in the syringe barrel by correspondingly varying the volume of the cushion employed. So for example, a larger dose volume would be accommodated by means of a correspondingly reduced cushion volume and vice-versa. In this way the overall 'start' position of the plunger end, which is a function of the dose volume plus cushion volume, may be constantly defined to match the defined drive stroke of the auto -injector.

In embodiments, it is also desirable for the injector to be provided with a syringe needle tip shroud advance mechanism. This acts to advance a needle tip shroud over the needle tip following completion of the injection procedure, thereby shrouding off at least the used needle tip. Applicant has realized that operation of such a syringe needle tip shroud advance mechanism may in embodiments, be enabled if the source of drive (e.g. drive spring) couples to the needle tip shroud once the 'fully plunged' position has been reached. Such operation may be better enabled if in addition, the drive transfer e lement (e.g. plunger rod) decouples from the source of drive (e.g. drive spring) at that 'fully plunged' position such that further axial movement thereof is unhindered by any action of the drive source. The needle shroud advance mechanism may thus be advanced to shroud the needle tip of the syringe unhindered by any interaction with the now freely movable drive transfer element (e.g. plunger rod). Applicant has realized that use of a 'secondary plunger' type drive arrangement as described hereinbefore may also be employed to increase the consistency and reliability of operation of such a needle shroud advance mechanism. According to one aspect of the present invention there is provided a syringe comprising a barrel for containing a volume of a liquid drug formulation; a hollow needle at a front end of said barrel, said hollow needle defining a needle tip for dispensing of said liquid drug formulation; a syringe plunger that is axially movable within the barrel; and a drive transfer element for transferring axial drive, wherein the drive transfer element defines a plunger end receivable within the barrel of the syringe and axially movable there within such that a cushion is definable between said syringe plunger and said plunger end such that drive is communicable from the plunger end of the drive transfer element to the syringe plunger by way of said cushion.

The cushion acts such as to provide cushioning between the syringe plunger and plunger end. Preferably, the cushion is compressible, at least to a degree such as to provide a 'soft' cushioning type function. Preferably, the cushion is both compressible to a degree and resilient to a degree, and thus may be described as resiliently compressible. In embodiments, the cushion comprises an air cushion. Air is naturally compressible to a degree, but also naturally exhibits resilience to compression. As a result of the defining of the air cushion, drive is communicable from the plunger end of the drive transfer element to the syringe plunger indirectly by way of (i.e. via) the air cushion. In embodiments, the cushion comprises a compressible cushioning element, such as a resiliency compressible cushioning element, which provides essentially the same function as the definable air cushion. In embodiments, the compressible cushioning element is comprised of a foamed (e.g. sponge) material. In embodiments, the foamed material defines either an open cell or closed cell structure. Thus, the foamed material, in essence, defines a compressible 'air cushion' within the foam cell structure thereof.

In embodiments, the compressible cushioning element is comprised of a resilient (e.g. springy) material. In embodiments, the resilient material defines a sprung structure. Thus, in essence, the resilient material defines a compressible 'cushion' within the resilient structure thereof.

In embodiments, an airtight seal is defined between the syringe plunger and the plunger end. Thus, in essence the cushion is an airtight sealed cushion.

The syringe is suitable for use with an injector. In embodiments, the injector comprises a housing defining a housing cavity arranged for receipt of the syringe and a needle delivery aperture; and within the housing cavity, a syringe as herein defined, wherein the syringe is movable from a rest position, in which the needle tip is within the housing cavity to a use position, in which the needle tip protrudes from said needle delivery aperture.

In embodiments, the injector is configured as an auto -injector and thus typically includes an energy store, which provides a source of the axial drive. In other embodiments, the axial drive may be provided manually (manual injector) or manually in combination with release of energy from an energy store (auto- assisted manual injector). In embodiments, the injector additionally comprises a first coupling for coupling the drive transfer element to the syringe barrel of the syringe, wherein the first coupling is a reversible coupling arranged for decoupling when the syringe moves to the use position. Thus, in the initial rest position, the first coupling couples the drive transfer element to the syringe barrel. Application of axial drive force to the drive transfer element therefore results in movement of the syringe as a whole, but preferably not of the syringe plunger relative to the syringe barrel. It may be appreciated that this preferred initial absence of relative syringe plunger movement is favoured if the frictional forces to be overcome in moving the syringe barrel within the housing are arranged to be much less than for moving the syringe plunger within the syringe barrel. This is typically so since the syringe plunger is often a natural or synthetic polymer (e.g. rubber) element, which frictionally interacts with the side wall of the syringe barrel.

Once the syringe is in the use position (i.e. needle protruding) the first coupling decouples (e.g. demounts) such that no coupling then exists between the drive transfer element and the syringe barrel. All further axial drive force applied to the drive transfer element, therefore results in plunging axial drive applied to the syringe plunger via the plunger end and air cushion within the syringe barrel.

The resulting axial movement of the syringe plunger acts to drive the liquid drug formulation contents of the syringe barrel into the hollow needle for injected delivery from the needle tip. These and other embodiments of the present invention are set forth in the later description, which describes for illustrative purposes only various embodiments thereof.

There is provided a syringe and an injector device that is arranged for use with such a syringe that contains a liquid drug formulation. The syringe is arranged to be suitable for use in the injected delivery of the liquid drug formulation to a patient.

The injector comprises a housing that defines a housing cavity (e.g. chamber form) that is arranged for receipt of the syringe and is therefore typically sized and shaped for this purpose. The housing may be arranged as a single part or a multi-part (e.g. two part) housing assembly.

The syringe that is received within the housing cavity comprises a syringe barrel for holding a volume of the liquid drug formulation; a hollow needle at a front end of the barrel, the hollow needle defining a needle tip for dispensing of said liquid drug formulation; and a syringe plunger (e.g. in the form of a rubber stopper) that is axially movable within the syringe barrel. The syringe plunger is movable axially within the barrel so as to enable the liquid drug formulation to be expelled from the barrel and thence through the hollow needle via the dispensing tip for injection into the patient. The syringe barrel is typically comprised of glass but may also be comprised of a relatively hard plastic polymer such as hardened polyethylene, polycarbonate or cyclic olefin polymers. In embodiments, the syringe plunger is comprised of a natural or synthetic polymer friction material, which frictionally interacts with the side wall of the syringe barrel. Suitable plunger materials include natural or synthetic polymers such as rubbers or elastomeric materials. In more detail, the syringe barrel is selected such as to define a barrel chamber for containing a suitable volume of the liquid drug formulation. In embodiments, that suitable volume is selected to correspond to a single dose of the drug formulation to be delivered to the patient. In other words, delivery of that single dose involves expelling all of the liquid drug formulation contents of the barrel chamber through the hollow needle for injection into the patient. The hollow needle defines a needle bore, which is most typically of circular cross-section and of selected bore diameter. In embodiments, the bore diameter may affect the force required to expel the liquid drug formulation through the needle and also the velocity at which the liquid drug formulation is expelled.

The selected needle bore may also, in embodiments affect the degree of patient discomfort during injection. Smaller bore diameters typically provide more patient comfort, whereas larger bore diameters enable more rapid / lower force delivery of the liquid through the needle. A compromise is therefore needed in selecting needle bore to provide acceptable patient comfort and liquid delivery through the needle characteristics.

Examples of typical needles that are suitable for use therein include 12.5mm ("half inch") long thin wall needles of grade 23G, 25G or 27G. These have a needle bore of from about 0.2 to 0.4mm such as from 0.25 to 0.35mm. O ther examples include both regular and thin wall needles used in conventional syringes including those with bevels such as 3 and 5 bevels. The housing and any inner housing sub assembly of the injector is shaped to define a housing cavity within which the syringe is receivable, and a needle delivery aperture. The housing cavity is typically cylindrical in form, thereby matching the typically cylindrical outer profile of a syringe. The housing cavity may be further shaped with any manner of grooves, indentations or other shaping or surface details to define a 'lock and key' relationship between the housing and any inner housing sub assembly thereof and the syringe. Colour guides, arrows and any other surface markings may also be employed.

Typically, the housing and /or any inner housing sub assembly thereof is provided with a barrel receiving part for receiving the barrel of the syringe; a plunger receiving part for receiving the plunger of the syringe; and a needle receiving part for receiving the hollow needle of the syringe.

In embodiments, the plunger receiving part of the housing and /or any inner housing sub assembly thereof allows the syringe plunger within the syringe barrel to be received thereby and for the syringe plunger to be movable (e.g. axially) therein from a first position to a second position, in which it is moved somewhat into the barrel. During use the syringe plunger is in embodiments, movable to a fully plunged position in which most, preferably all of the liquid drug formulation contents of the barrel have been expelled.

The needle receiving part of the injector housing and /or any inner housing sub assembly thereof includes a needle delivery aperture through which the hollow needle may protrude from the housing, for example during expelling of the liquid drug formulation through the hollow needle and its needle tip for delivery to the patient.

The syringe is movable within the housing cavity from a rest position, in which the needle tip is within the housing to a use position, in which the needle tip protrudes from the needle delivery aperture.

In more detail, it is desirable for safety and hygiene reasons that the needle does not protrude from (i.e. outwith) the housing other than when expelling the liquid drug formulation during an injection procedure. Thus, the housing and /or any inner housing sub assembly thereof and housing cavity defined thereby is generally arranged such that the needle receiving part thereof allows for the needle of the syringe to be axially moveable therein from a first (i.e. rest) position in which the needle is wholly housed (or shrouded) by the needle receiving part to a second (i.e. use) position in which at least the tip of the needle protrudes from that needle receiving part of the housing. In certai n embodiments, the housing includes biasing means (e.g. a spring) arranged such that the needle is normally biased towards the first (i.e. rest) position, wherein such biasing means are overcome during the actuation of the syringe (e.g. by an actuating mechanism) to allow for movement of the needle to the second (i.e. use) position.

In terms of function, the injector is arranged to allow for actuation (i.e. firing) of the syringe. The injector thus, also includes a drive transfer element for transferring axial drive to the syringe. Preferably, that drive transfer element takes the form of a plunger rod, but other suitable forms are also envisaged. In embodiments, the source of axial drive is automatically applied. Thus, in embodiments the injector includes an actuating mechanism.

In preferred embodiments, the injector includes an energy store for storing energy that can then be released to provide the axial drive to the syringe via the drive transfer element. In embodiments, the injector includes a secon d coupling (e.g. in the form of a shuttle element) for coupling the energy store to the drive transfer element. In embodiments, the energy store comprises a mechanical energy store such as a spring (e.g. a compression or torsion spring). In other aspects, the energy store may be provided by a container of compressed liquid or gas propellant that on release provides a source of jet energy propulsion.

In embodiments, the energy store is able to exert an axial drive force of up to 6ON on the syringe. Where the energy store is a compression spring the force exerted typically varies over the actuation profile such as from a range of 60 to 40N at the start of actuation to from 40 to 2ON at the end of the actuation profile. Where the energy store is a compressed liquid or gas propellant a more constant force is typically exerted over the actuation profile. In preferred embodiments, release of axial drive force (e.g. actuation of the actuating mechanism) is responsive to a trigger (e.g. a user-actuable trigger). In embodiments, the trigger comprises a button, switch or lever arrangement. In other embodiments, a press actuation mechanism that is actuable in response to pressing of the housing of the device against the skin is also envisaged.

The drive transfer element defines (e.g. a front or leading) plunger end that is receivable within the barrel of the syringe and axially movable there within such that a cushion (e.g. an air cushion) is definable between the syringe plunger and the plunger end. Thus in embodiments, a volume (or gap) capable of

accommodating air that may act as an air cushion is definable between the syringe plunger, plunger end of the drive transfer element and inner wall of the syringe barrel. In embodiments, an airtight seal is defined between the syringe plunger and the plunger end.

In preferred embodiments, the drive transfer element is non -compressible or at least is non-compressible in the direction of the axial drive force. Thus in embodiments, the drive transfer element comprises a non -compressible material and/or has a three-dimensional structure that provides such preferred axial non- compressibility.

In embodiments, the plunger end defines a disc -shaped leading face, wherein in embodiments the diameter of that disc is slightly less than the inner diameter of the syringe barrel.

In embodiments, the plunger end is provided with one or more holes that serve as air vents during assembly when the plunger end is partly-inserted into syringe barrel to define an 'air cushion' volume between the plunger end, syringe plunger and inner wall of the syringe barrel. In embodiments, one or more holes for such air venting are radially disposed about the plunger end part. In embodiments, a central hole for venting is provided to the plunger end part.

The purpose of the one or more venting holes is so that the air in the defined air cushion volume is not compressed during assembly. In practice, once the plunger end ('secondary plunger') is in place in the syringe barrel any radial holes are sealed off and no longer provide a channel for air to escape. The central hole, if present, still provides a channel for air to escape however this may be sealed off after assembly, or the entire front end of the plunger rod assembly may be effectively airtight if sufficiently close fitting components are used, or if greases or resilient materials (e.g. O-rings) are additionally used to provide an air tight seal. In some embodiments it may be desirable to allow an escape path for compressed air to enable the syringe plunger and plunger end to meet. This may be necessary in some embodiments if the compression of air is sufficient to arrest travel to the predetermined decouple point, or if there is an uncertainty in the size of the air gap but a pre-determined point must be reached.

In embodiments, the plunger end part of the drive transfer element is partly or wholly comprised of a natural or synthetic polymer friction material, which frictionally interacts with the side wall of the syringe barrel. Suitable plunger end materials include natural or synthetic polymers or elastomeric materials.

In embodiments, the injector includes a first coupling for coupling the drive transfer element to the syringe barrel of the syringe. In embodiments, the drive transfer element is a plunger rod.

The first coupling is a reversible (e.g. demountable) coupling arranged for decoupling (e.g. demounting) when the syringe moves to the use position. In embodiments, the first coupling is at a forward position of the drive transfer element. Thus during a use operation, the first coupling is initially in place and axial drive force applied to the drive transfer element (e.g. plunger rod) results in drivable movement of the syringe from the rest to the use position. That first coupling then decouples such that further axial drive force applied to the drive transfer element (e.g. plunger rod) results in drivable movement of the syringe plunger within the syringe barrel, ultimately to a fully plunged position when most, preferably all of the liquid drug formulation contents of the syringe barrel have been drivably expelled therefrom. In embodiments, the first coupling is a friction clutch coupling arranged for decoupling by declutching thereof when the syringe moves to the use position. By 'friction clutch coupling' it is meant a coupling that is frictional in nature and capable of adopting both a 'clutched' (i.e. coupled) state corresponding to high frictional interaction and a 'declutched' (i.e. uncoupled) state corresponding to low frictional interaction. Suitable examples of friction clutch couplings are described in Applicant's co-pending UK patent application no. 0910681.6 having a filing date of 16^th June 2009, the contents of which are incorporated herein by reference. In embodiments, the drive transfer element is arranged to transfer axial drive to the syringe barrel and the friction clutch coupling acts to vary the frictional contact between the plunger end of the drive transfer element and the syringe barrel. Thus, the frictional contact is variable from (i) a high frictional contact state corresponding to coupling (i.e. clutched) interaction therebetween to (ii) a low frictional contact state corresponding to decoupling (i.e. declutched) interaction therebetween.

In embodiments, the friction clutch coupling comprises an element (or means) for distorting (e.g. compressing) the shape of the plunger end of the drive transfer element, thereby affecting its degree of frictional contact with the interior walls of the syringe barrel.

In embodiments, the drive transfer element and the means for distorting (e.g. compressing) the shape of the plunger end thereof is provided to the syringe plunger rod such as by means of a movable plunger rod sleeve thereof. Thus, distortion of the plunger end (and hence, variance of the frictional

coupling/clutching state) is by movement of the plunger rod sleeve relative to the plunger end. In such aspects, the plunger end is selected to have in

embodiments, a distortable (e.g. compressible) nature, for examp Ie comprising a natural or synthetic polymer material.

In embodiments, the plunger rod has the form of a multi-part assembly and comprises a plunger rod part; a plunger end part; and a coupler part locating there between. In embodiments, the coupler part latches onto the forward end of the plunger rod part by radial snaps. The radial snaps are preferably designed so that for ease of assembly this latching connection may be made when the two parts are confined within the plunger rod sleeve. In embodiments , the plunger end part defines a disc-shaped face of diameter slightly smaller than the inner diameter of the syringe barrel; a shank onto which the plunger rod sleeve is receivable; and a radial arrangement of inwardly deflecting snap fits which snap into the coupler part. Again, for ease of assembly these snap fits are designed so that the connection may be made when the two parts are confined within the plunger rod sleeve.

In embodiments, movement of the plunger rod sleeve relative to the plunger rod to thereby change the frictional coupling/clutching state is responsive to movement of a shuttle element, the axial movement of which, in turn is responsive to the axial drive force provided by the source of axial drive. Thus, the axial drive acts on both the plunger rod and the driven shuttle. In embodiments, the shuttle has an axially symmetric form such as cylindrical form, wherein the plunger rod and sleeve therefor are suitably received axially within the cylindrical form. Guides (e.g. a central aperture of an end wall) may be provided to the shuttle to assist that axial receipt.

In embodiments, the shuttle is provided with one or more followers (e.g. pegs or notches) arranged for track -follower receipt by one or more tracks (e.g. grooves or slots) of the plunger rod sleeve, thereby coupling the movement of the plunger rod sleeve to that of the driven shuttle.

In embodiments, in a first actuation step the track -follower relationship is arranged such that on initial driven movement of the shuttle (a nd plunger rod) forward axial drive force is transferred to the plunger rod sleeve. In

embodiments, initial movement of the plunger rod is damped (e.g. through use of a source of damping between plunger rod and inner housing sleeve. In embodiments, the source of damping comprises an O-ring that locates between plunger rod and a boss provided to the rear end of the inner housing sleeve. Opposing forces are thus, set up between freely moving plunger rod sleeve and damped moving plunger rod, which centre at the plunger causing distortion thereof and set up a 'friction clutch' type interaction thereat.

In embodiments, at a further actuation step the source of damping is overcome, removed or becomes exhausted such that the opposing frictional forces between plunger rod and plunger rod sleeve reduce or cease and the 'friction clutch' is therefore effectively de-clutched. At this point, the plunger rod however, continues to receive axial drive and is thus, propelled forward with the plunger rod sleeve to drive the plunger end thereof into the syringe barrel against the air cushion and thus driving the syringe plunger to eject the liquid contents of the syringe barrel. In embodiments, in a still further actuation step the track -follower relationship is arranged such that on subsequent driven movement of the shuttle (and plunger rod with sleeve) the driven shuttle and plunger rod with sleeve become decoupled such that forward axial drive force is no longer transferred to the plunger rod and sleeve. This corresponds to the fully plunged (or 'end of injection stroke') position of the device.

The track-follower relationship between driven shuttle and plunger rod with sleeve is in embodiments, set up to provide the decoupling therebetween by means of a discontinuity (e.g. sharp curve in the track) which allows the follower of the driven shuttle to decouple from the track of the plunger rod sleeve.

In embodiments, the driven shuttle also couples to the inner housing sleeve such as by means of a second track -follower relationship. Thus, the shuttle is provided with one or more second followers (e.g. pegs or notches) arranged for track-follower receipt by one or more tracks (e.g. grooves or slots) of the inner wall of the inner housing sleeve. In embodiments, the second track-follower relationship is arranged such that at a point corresponding to the fully plunged position a discontinuity (e.g. curve) is provided, which causes the shuttle to rotate. It will be appreciated that this rotation of the shuttle will also affect its track-follower relationship with the plunger rod sleeve such as to cause a corresponding discontinuity therein. In embodiments, the rotation of the shuttle enables its decoupling from the plunger rod and sleeve by fundamentally changing the relationship between the follower thereof and the track of the plunger rod sleeve. Once so-decoupled the shuttle will continue to be subject to any remaining axial drive, but the plunger rod and sleeve is no longer subject to that axial drive. Variations of the track -follower relationships described above are also envisaged including those in which the track-follower parts are substituted (e.g. track on shuttle, followers on plunger rod sleeve and/or inner housing sleeve). Further examples of track-follower relationships are described in Applicant's co-pending PCT patent application no. WO2009/081,132, the contents of which are incorporated herein by reference.

In other embodiments, the first coupling takes the form of a first collet arranged for demountable coupling (e.g. by peg elements thereof) to the drive transfer element (e.g. at notches thereof). One or more washer elements may also be provided to assist with coupling of the first collet to the drive transfer element. Suitable examples of demountable collet type couplings are described in

Applicant's co-pending PCT patent application no. WO2009/081.132, the contents of which are incorporated herein by reference.

In one embodiment, in the rest position, the first collet seats against a washer, which in turn seats against end barrel lip (e.g. circular or part-circular) of the syringe barrel. In embodiments, demounting of the first collet from the drive transfer element may be achieved by means of a track and follower demounting arrangement. Thus, in embodiments, the first collet is provided with one or more followers (e.g. lugs) for example, disposed arranged around its circumference. Each of the one or more followers is arranged to engage in a first track (e.g. slot or groove form) that is in embodiments provided to the inner wall of the housing cavity or of a sleeve housing provided thereto. In embodiments, each track defines a straight path running parallel to the axis of the syringe for the most of the length thereof, but at the forward part thereof define a curved (e.g. helical) path the following of which serves to rotate the first collet to disengage the peg elements from the drive transfer element such that the first collet demounts from the drive transfer element. The effect of this demounting is that application of further axial drive to the drive transfer element no longer results in forward movement of the syringe barrel and of any associated washers, but rather only moves the plunger end forward against the air cushion and thus, the syringe plunger for expelling the liquid drug formulation contents of the syringe barrel through the tip of the hollow needle. In embodiments, once the first collet demounts from the drive transfer element it may engage in a further straight track (e.g. slot or groove form) that is in embodiments, provided to the inner wall of the housing cavity or of a sleeve housing provided thereto.

In embodiments, the first track defines a curved path arranged to rotate the first coupling for decoupling thereof from the. drive transfer element. In embodiments, the first track defines both a straight path running parallel to the axis of the syringe and a curved path locating at a forward part thereof. In embodiments, a further straight track is provided to the inner wall of the housing cavity or to an inner housing sleeve housing provided thereto, and wherein subsequent to decoupling the first coupling engages in said further straight track.

In other embodiments, the first collet has the form of an expanding collet, which expands into a ring shaped recess that is in embodiments, provided to the inner wall of the housing cavity or of a sleeve housing provided thereto. Such an expanding collet is generally provided with movable lugs (e.g. arranged at spaced intervals around a circumference thereof). In other embodiments, the first coupling takes the form of a movable sleeve arranged for demountable coupling (e.g. by tag elements thereof) to the drive transfer element (e.g. at notches thereof). Suitable examples of demountable sleeve type couplings are described in pending PCT patent application nos. WO2005/070,481 and WO2007/083,115 both in the name of The Medical House PIc, the contents of which are incorporated herein by reference. In embodiments, it is desirable for the injector to allow for the needle of the syringe to be shrouded by a needle shroud element after use. Thus, in particular it is desirable to be able to provide a means of shrouding the needle of the syringe that is moved or otherwise brought into operation after completion of the injection procedure. Such means in embodiments comprise a movable shroud element that is adapted to be movable to a shrouding configuration at the end of the injection procedure. Where the axial drive is provided by an energy store that couples to the drive transfer element by means of a second coupling (e.g. provided by reversible coupling of the drive shuttle to the plunger rod and sleeve as described above) it has been appreciated that such movement of a needle shroud element ('needle shroud means') may be enabled if the movable needle shroud element couples (e.g. via a third coupling) to the source of axial drive, wherein said coupling is a reversible coupling arranged to be coupled when the plunger moves to a fully plunged position within the syringe barrel. Thus, at this fully plunged position, axial drive becomes transferable to the movable shroud element to move it into a shrouding position.

In another aspect, it is desirable for the injector to allow for the needle of the syringe to be retracted into the housing after use. Thus, it is desirable to be able to retract the needle back into the needle receiving part of the housing after the injection procedure, that is to say to retract the needle from the second (i.e. use) position to a retracted position that may in embodiments, correspond to the first (i.e. rest) position or in other embodiments, correspond to a third position, which in embodiments is further away from the needle delivery aperture. Where the axial drive is provided by an energy store that couples to the drive transfer element by means of a second coupling it has been appreciated that such syringe retraction is better enabled if the drive transfer element (e.g. plunger rod) reversibly couples to the energy store. Thus, in embodiments, the energy store communicates with the drive transfer element via a second coupling, wherein the second coupling is a reversible coupling arranged for decoupling when the plunger end of the drive transfer element moves to a position that results in full plunging of the syringe plunger within the syringe barrel (e.g. provided by reversible coupling of the drive shuttle to the plunger rod and sleeve as described above). Thus, the second coupling is a reversible (e.g. demountable) coupling arranged for decoupling (e.g.

demounting) when the syringe plunger has been moved to a fully plunged position. Ideally in use, once decoupled from the energy store (i.e. source of axial drive force) the drive transfer element is free to move such that reverse axial movement thereof is unhindered. A needle retract mechanism may then be arranged (e.g. responsive to a light return spring) to retract the syringe needle back into the housing unhindered by any interaction with the now free to move drive transfer element. Or alternatively, a needle shroud mechanism may be arranged to be activated at this point.

In embodiments, the injector additionally comprises a second coupling for coupling the drive transfer element to a source of axial drive, wherein said second coupling is a reversible coupling arranged for decoupling when the syringe plunger moves to a fully plunged position within the syringe barrel.

In embodiments, the injector additionally comprises a movable needle shroud element; and a third coupling for coupling the movable shroud element to said source of axial drive, wherein said third coupling is a reversible coupling arranged for coupling when the syringe plunger moves to a fully plunged position within the syringe barrel.

In embodiments, any or all of the first, second and third couplings are comprised within a common coupling element. In embodiments, a reset mechanism is provided for resetting the firing

mechanism after actuation thereof. The reset mechanism may for example, comprise a spring, motor, mechanical arrangement or a reset coupling. In embodiments, the injector housing is provided with a removable cap that fits over and thereby, acts such as to close off, the needle delivery aperture. It may therefore, be appreciated that when in the capped position, the removable cap acts such as to prevent ingress of contaminants into the needle receiving part of the housing.

In embodiments, the injector further comprises a needle cover defining a needle sheath arranged in a rest configuration for sealing of the needle tip.

In embodiments, the needle sheath is comprised of a (e.g. resiliently)

compressible material such as a natural or synthetic rubber material. In the rest configuration, the needle tip sticks into (e.g. is spiked or staked into) the needle sheath such that sealing of the needle tip is achieved. Usually, at least the first 3 to 4mm of the needle tip end is so sheathed. It will be appreciated that for clinical reasons, the sealing of the needle tip is preferably such as to prevent passage of contaminant, bacterial or otherwise, through the needle tip and thus into the needle bore and syringe barrel chamber. Sterile sealing is preferred.

In embodiments, the needle cover is provided with a needle sheath cover for covering the needle sheath thereof. In embodiments, the needle sheath cover is provided with one or more gripping elements (e.g. hooks) arranged for gripping of the needle sheath. In embodiments, the needle sheath is provided with one or more features arranged for receipt of the one or more g ripping elements such as one or more indents, grooves or cavities. In embodiments, the needle cover is provided to (e.g. fixed to or integral with) a removable cap for the housing. Thus, in embodiments, the needle cover projects within the cap such that when the removable cap is in the capped position the needle sheath cover and needle sheath therewithin projects towards the needle tip of the syringe. In such embodiments, when in the capped position, the needle tip is sheathed by the needle sheath, and when the cap is removed the needle sheath cover and needle sheath within are also removed such as to thereby, unsheathe the needle tip. In embodiments, the removable cap defines an essentially closed cylindrical cap chamber, optionally tapering, and the need le sheath cover is provided along the axis of that cylindrical chamber.

In embodiments, the housing is provided with one or more (e.g. resiliently) flexible elements that extend (e.g. protrude) into the housing cavity. In

embodiments, the one or more (e.g. resiliently) flexible elements are provided as one or more separate parts that attach or fix to an inner wall of the housing or are otherwise in embodiments held within the housing. In other embodiments, the one or more (e.g. resiliently) flexible elements are provided integrally with the housing (e.g. formed as an integral moulding therewith). The one or more flexible elements are typically provided to the needle receiving part of the injector housing

The one or more (e.g. resiliently) flexible elements are desirably arranged to perform two separate functions. Generally, in the rest configuration the needle sheath locates to seal off the needle tip, the one or more (e.g. resiliently) flexible elements contact the needle cover to restrict (e.g. prevent) movement thereof. Thus, movement of the needle cover is restricted by the action of the (e.g. resiliently) flexible elements, which in embodiments engage with the needle cover to hold it, and thereby restrict movement thereof. Such restriction of movement assists in maintaining the integrity of the seal relationship between the needle tip and the needle sheath.

In the use configuration, the needle cover is generally removed from the needle tip such as to unseal that tip. In this use configuration, the one or more (e.g. resiliently) flexible elements flex into the housing cavity to provide a barrier surface. This barrier surface acts such as to obstruct the exit of the syringe barrel from the housing cavity. Such obstructing function is particularly important in the instance of fracture (i.e. breakage) of the syringe, which is generally comprised of glass material. In this instance, the barrier surface acts such as to obstruct the exit of fractured parts (e.g. glass shards) of the syringe from the housing cavity. The patient is thereby, protected from coming into contact with such fractured parts, and thus potential injury in the event of such a syringe fracture event occurring.

In embodiments, the one or more (e.g. resiliently) flexible elements comprise a ring comprised of a (e.g. resiliently) flexible material such as a plastic polymer (e.g. an elastomer) or natural or synthetic rubber material. That ring (e.g. an O- ring) is generally provided to an inner wall of the (cylindrical) housing such that the outer ring circumference thereof attaches to the inner wall of the housing. In embodiments in the rest configuration, the inner ring circumference thereof contacts the needle cover (e.g. the needle sheath or a needle sheath cover provided thereto) and is somewhat compressed inwards as a result of that contact, the effect of which is to restrict movement of the needle cover. Thus in the use configuration, the needle cover is removed, and in the absence of compressive contact with the needle cover, the ring expands outwards into the housing cavity to provide a barrier surface, which acts such as to obstruct the exit of the syringe barrel from the housing cavity. In other embodiments in the rest configuration, the inner ring circumference thereof contacts an interior part of the cap. Preferably, the diameter of the uncompressed inner ring circumference of the ring is less than that of the syringe barrel such that when the ring is in its uncompressed state the syringe barrel may not pass through the ring. In embodiments, each of the one or more (e.g. resiliently) flexible elements comprises a flexible finger element comprised of a (e.g. resiliently) flexible material such as a plastic polymer. Each finger element is generally provided to an inner wall of the (cylindrical) housing such that the finger base thereof attaches to the inner wall of the housing. Typically, an arrangement (e.g. circular arrangement) of flexible finger elements is employed such as from three to eight finger elements. In the rest configuration, the finger tip of each finger element contacts the needle cover (e.g. the needle sheath or a needle sheath cover provided thereto) and is somewhat flexed inwards as a result of that contact, the effect of which is to restrict movement of the needle cover. In the use

configuration, the needle cover is removed, and in the absence of the

compressive contact with the needle cover, the flexible finger element(s) flex into the housing cavity to provide a barrier surface, which acts such as to obstruct the exit of the syringe barrel from the housing cavity. Where the flexible finger elements are provided as a circular arrangement, it is preferable that the diameter of the inner circumferential aperture defined by the extremes of the finger tips thereof is less than that of the syringe barrel such that when the finger elements of that circular arrangement flex outwards the syringe barrel may not pass through the inner circumferential aperture defined thereby. For ease of assembly, Applicant has realized that it is advantageous if the one or more (e.g. resiliently) flexible elements are arranged such that when the needle cover is inserted into the housing for sheathing of the needle tip, part thereof interacts with the one or more (e.g. resiliently) flexible elements such that these flex (or compress) towards the inner wall of the housing. On completion of that insertion step (i.e. in the rest configuration) the one or more (e.g. resiliently) flexible elements are thus, in a somewhat tensed state, which better acts such as to impact on thus, restrict movement of the needle cover. Conversely, on removal of the needle cover during a use operation the one or more (e.g. resiliently) flexible elements flex (or compress) away from the inner wall of the housing, and thus further into the housing cavity.

Representative injectors that may be modified in accord with the present invention include those described in United States Patent No.s US-A-4,553,962; US-A-4,378,015; US-A-5,304,128 and PCT Patent Application No.s

WO99/22790 (Elan Corporation); WO00/09186 (Mediject Corporation); and WO2005/070.481 and WO2007/083,115 (The Medical House PLC) and

Applicant's co-pending PCT patent applications nos. WO2009/081 , 103,

WO2009/081.130, WO2009/081.132, WO2009/081.133 and WO2010/007,395, all of which are incorporated herein by reference.

In embodiments, the injector is provided with child-resistant features to prevent undesirable actuation of the actuating mechanism by a young child.

In embodiments, the injector is provided with a visual indicator that is arranged to provide the user with a visual indication of the temperature state of the injector, and particularly of the syringe and its contents (i.e. the liquid drug formulation), which at least allows the user to differentiate between a 'too cold to use' state and a 'sufficiently warm to use' state. Such visual indicators are described in Applicant's co-pending PCT patent application no.

WO2008/146,021 , the contents of which are incorporated herein by reference.

In embodiments, the syringe of the injector herein contains a liquid drug formulation, which is designed for refrigerated rest (e.g. at from 2-8⁰C) and for injected delivery at room temperature (e.g. at or about 18-30°C). In

embodiments, the viscosity of the liquid drug formulation is less than 120 mPa.s (120 centipoise), preferably less than 100 mPa.s (100 centipoise) at a delivery temperature of 20⁰C.

Applicant has appreciated that the concept of using a ring comprised of a (e.g. resiliency) flexible material such as a plastic polymer or natural or synthetic rubber material as a barrier surface is more generally applicable.

Thus, the injector may comprise a needle cover defining a needle sheath arranged in a rest configuration for sealing of said needle tip; and a flexible ring element, wherein in a use configuration said ring provides a barrier surface for obstructing exit of the syringe barrel therefrom, with the proviso that the ring is not provided to the housing.

Unlike previously described embodiments, the ring is typically not provided (e.g. directly) to the housing. That is to say, the ring does not fix or attach to the housing or is not provided as an integral part thereof. The ring is comprised of a (e.g. resiliently) flexible material such as a plastic polymer or natural or synthetic rubber material, and is embodiments of O -ring form. In embodiments, the ring is provided to the injector such that in the rest configuration, the ring contacts the needle cover to restrict movement thereof, and wherein in a use configuration the needle cover is removed from the needle tip such that the ring extends into the housing cavity to provide a barrier surface for obstructing exit of the syringe barrel therefrom.

In embodiments, the needle barrel is provided with a barrel sleeve that is arranged to fit over part or all of the length of the needle barrel, and the ring is provided to that sleeve (e.g. by attaching or fixing thereto or as an integral part thereof). In these embodiments, the ring (e.g. an O -ring) is generally provided to an inner wall of the (cylindrical) barrel sleeve such that the outer ring circumference thereof attaches to the inner wall of the barrel sleeve. The barrel sleeve may also extend out beyond the syringe barrel to wholly or partly enclose a length of the end-shoulder of the syringe barrel and of the hollow needle that extends from (the end-shoulder) of the syringe barrel.

In embodiments, the ring is provided to a forward part of the barrel sleeve (e.g. corresponding to a part that extends out beyond the syringe barrel). In

embodiments thereof, in the rest configuration, the inner ring circumference contacts the needle cover (e.g. the needle sheath or a needle sheath cover provided thereto) and is somewhat compressed inwards as a result of that contact, the effect of which is to restrict movement of the needle cover. In the use configuration, the needle cover is removed, and in the absence of

compressive contact with the needle cover, the ring expands outwards into the housing cavity to provide a barrier surface, which acts such as to obstruct the exit of the syringe barrel from the barrel sleeve, and preferably hence also from the housing cavity. Preferably, the ring provides the only such barrier surface and the barrel sleeve is not provided with any other barrier surface-providing elements such as flexible fingers or flanges. Preferably, the diameter of the uncompressed inner ring circumference of the ring is less than that of the syringe barrel such that when the ring is in its uncompressed state the syringe barrel may not pass through the ring.

According to a further aspect of the present invention there is provided a kit of parts comprising an injector as described above but absent the syringe; and a syringe containing a liquid drug formulation.

According to a further aspect of the present invention there is provided a kit of parts comprising an injector as described above but absent the syringe; and packaging therefor; and optionally a syringe containing a liquid drug formulation. Suitable packaging typically comprises a container for the injector and syringe. In embodiments, the packaging comprises a compartment for the injector preloaded with the syringe. In embodiments, the packaging comprises a separate compartment for a 'kit' of the injector and the syringe.

The invention will now be described further with reference to the accompanying drawings in which:

Figure 1 is a perspective view of an injector herein in the 'at rest' position with removable cap thereof in docked receipt by the outer housing thereof;

Figure 2 is a sectional view of the injector of Figure 1 also in the 'at rest' position; Figure 3 is a perspective view of the injector of Figure 1 in the 'at rest' position with removable cap thereof now removed from the outer housing thereof;

Figure 4 is a sectional cut-away view in perspective of the removable cap of the injector of Figure 1 ;

Figure 5 is a perspective view of the cage-like needle cover gripping part of the removable cap of Figure 4;

Figure 6 shows a perspective view of the injector of Figure 1 with outer housing removed and showing an inner housing assembly of front cylinder and rear inner housing sleeve as shown in the 'end of use' position;

Figure 7 is a perspective view of the front cylinder of the inner housing assembly of Figure 6; Figure 8 is a perspective view of the rear inner housing sleeve of the inner housing assembly of Figure 6;

Figure 9 is a sectional cut-away view in perspective of the rear inner housing sleeve of Figure 8 shown rotated by about 150° from the configuration of Figure 8;

Figure 10 is a perspective view of the syringe barrel sleeve ('syringe carriage') of the injector of Figures 1 and 2;

Figure 11a is a sectional view and Figure 11b a perspective view of the plunger rod assembly of the injector of Figures 1 and 2;

Figure 12 is an exploded view of the plunger rod assembly of Figures 11a and 11b;

Figure 13 is a perspective view of the inner plunger rod part of the plunger rod assembly of Figures 11 a and 11 b; Figure 14a is a perspective view and Figure 14b a cut away perspective view of the coupler part of the plunger rod assembly of Figures 11a and 11b;

Figure 15a is a perspective view and Figure 15b a cut away perspective view of the plunger end part of the plunger rod assembly of Figures 11a and 11b;

Figure 16 is a sectional view of a step in the bringing together of parts of the plunger rod sub assembly of Figures 11a and 11b with the capped syringe during manufacturing assembly of the device of Figures 1 and 2; Figures 17a to 17d respectively show perspective; sectional cut-away in perspective; side; and end-on views of the follower shuttle part of the injector of Figures 1 and 2; Figures 18a to 18e show sectional views of the injector of Figures 1 and 2 during sequential use steps thereof;

Figures 19a to 19e show sectional views of the injector of Figures 1 and 2 during sequential use steps thereof, but shown rotated by about 120 ° from the views of Figures 18a to 18e;

Figure 20 is a perspective view of a second injector herein in the 'at rest' position with removable cap thereof in docked receipt by the outer housing thereof;

Figure 21 is a sectional view in of the injector of Figure 20 also in the 'at rest' position;

Figures 22a to 22c respectively show perspective, sectional and exploded views of the syringe and plunger rod assembly of the second injector of Figures 20 and 21 ;

Figure 23 is a perspective view of the plunger rod assembly of the second injector of Figures 20 and 21 ;

Figure 24 is a perspective view of the plunger rod part of the plunger rod assembly of Figure 23;

Figure 25 is a perspective view of the plunger end part of the plunger rod assembly of Figure 23; Figures 26a to 26d show perspective views of the second injector of Figures 20 and 21 during sequential use steps thereof; Figures 27a to 27d show sectional views of the second injector of Figures 20 and 21 during sequential use steps thereof;

Figure 28 shows an exploded view of an alternative syringe and plunger rod assembly for use with the second injector of Figures 20 and 21 ;

Figure 29 is a perspective view of the plunger rod part of the alternative syringe and plunger rod assembly of Figure 28;

Figure 30 is a perspective view of the plunger end part of the alternative syringe and plunger rod assembly of Figure 28;

Figures 31a and 31b show sectional views of the alternative syringe and plunger rod assembly of the injector of Figure 28 in the respective 'ready for use' and 'post-injection' positions;

Figure 32 is a perspective sectional view of the syringe barrel sleeve of the second injector of Figures 20 and 21 ; and

Figures 33a and 33b are perspective and perspective sectional views of the drive shuttle of the second injector of Figures 20 and 21.

Referring now to the drawings, Figures 1 and 2 show a first injector device 1 herein that is arranged for use with a syringe 10 that contains a liquid drug formulation 5. The injector device 1 comprises a generally cylindrical form outer housing 20 that is arranged for receipt of the syringe 10 and is sized and shaped for this purpose. Release trigger 48 may be seen to protrude from the rear of the outer housing 20. The outer housing 20 is provided with a viewing window 2 that allows for viewing of the contents of the syringe 10 to check for dispensing thereof. The device 1 is provided with a removable cap 60 that is shown in the capped position. Figure 3 shows the injector device 1 with the cap 60 removed, which cap 60 is shown separately and in more detail in Figure 4.

The syringe 10 comprises a barrel 12 for holding the liquid drug formulation 5; a hollow needle 14 at one end of the barrel 12; and a syringe plunger 18 in the form of a rubber stopper that is arranged for axial movement (e.g. in response to plunging motion of plunger rod assembly 70) within the barrel 12 such as to enable the liquid drug formulation 5 to be expelled through the hollow needle 14. The hollow needle 14 defines a needle bore, which is of circular cross -section (e.g. 23G, 25G or 27G bore diameter) and a needle tip 15.

The outer housing 20 of the injector device 1 is arranged to receive an inner housing assembly (shown at Figure 6) comprising front cylinder 30 (shown in more detail at Figure 7) and rear inner housing sleeve 40 (shown in more detail at Figures 8 and 9), which in combination define an inner housing cavity within which the syringe 10 and its syringe barrel sleeve are received. In more detail, the inner housing assembly of the injector defines a needle receiving cavity 22, barrel receiving cavity 23 and plunger receiving cavity 24. The needle receiving cavity 22 is provided with a needle delivery aperture 25 through which in use, the hollow needle 14 of the syringe 10 may protrude from the inner housing assembly. It may be seen that the inner wall 26 of needle receiving cavity 22 of the front cylinder 30 steps inwardly to define a needle delivery aperture 25 of reduced diameter compared to the diameter of the needle receiving cavity 22.

Referring now in particular to Figures 2 to 4, the removable cap 60 may be appreciated to function such as to close off, the needle delivery aperture 25 (i.e. as shown at Figures 1 and 2). Projecting into the cap 60 interior, from the top inner surface 61 thereof, there is provided central boss 63 and interio r thereto a cage-like needle sheath gripper 62 (shown in detail at Figure 5) that at its forward end projects away from the top inner surface 61 of the cap 60 and towards its rear end defines hooks 64 arranged for gripped receipt of the needle sheath 17. Other suitable cap arrangements are disclosed in Applicant's co- pending PCT publication no. WO2010/007395, the entire contents of which are incorporated herein by reference. In the 'at rest¹ position of Figure 2, the needle sheath 17, which typically comprises a natural or synthetic rubber, may be seen to sheathe the needle tip 15 of hollow needle 14 to provide a hygienic seal thereat. The hooks 64 (see Figures 4 and 5) of the needle sheath gripper 62 act such as to grip the outer part of the needle sheath 17, thereby maintaining the sheath 17 in close proximity with the needle 14 and its sheathed tip 15 when the cap 60 is in the capped position. The needle sheath 17 is also provided with a sheath shell (e.g. of polypropylene), one purpose of which is to add rigidity and to reduce the tendency of the needle sheath 17 to flex away from the axis defined by the needle 14, and /or a polypropylene end ring, which comprises an integral moulded part of needle sheath shell and which assists in maintaining rigidity of the rear end portion thereof. Other needle sheath 17 and needle sheath gripper 62 arrangements are disclosed in Applicant's co-pending PCT application no. WO2009/081 ,130 the entire contents of which are incorporated herein by reference.

It may also be seen that the needle receiving cavity part 22 of the front cylinder 30 is provided close to the stepped inner wall 26 thereof with a flexible element in the form of an O-ring 80 comprised of a plastic polymer or natural or synthetic rubber material. An outer ring circumference of that O-ring 80 attaches to the inner wall of the front cylinder 30. In the 'at rest' configuration of Figures 2 and 14a, the inner ring circumference 82 thereof contacts the rigid central boss 63 of the cap needle sheath gripper 62. The rigid central boss 63 acts such as to direct the hooks 64 of the gripper 62 into the needle sheath 17 to thereby restrict movement of the needle sheath 17. In the 'ready for use¹ configuration of Figures 18b and 19b, the cap 60 and gripped needle sheath 17 are removed to open up the needle delivery aperture 25. In the absence of compressive contact with the rigid central boss 63, the O-ring 80 expands outwards into the needle receiving cavity 22 to provide a barrier surface 83 at its syringe-facing wall. The barrier surface 83 may thus, act such as to obstruct the exit of the syringe barrel 12 from the front cylinder 30. This barrier function is assisted by the fact that the diameter of the uncompressed inner ring circumference 82 of the O -ring 80 is less than the diameter of the syringe barrel 12 such that the syringe barrel 12 is unable to pass through the uncompressed O-ring 80. In the event of fracture of the syringe 10, the O-ring 80 thus, acts to obstruct passage of any syringe 10 fragments through the needle delivery aperture 25, and thereby protects the patient from harm. Other O-ring barrier arrangements are disclosed in

Applicant's co-pending PCT application no. WO2009/081 ,133, the entire contents of which are incorporated herein by reference.

Further details of the inner housing assembly may be seen by reference to Figures 6 to 9. Front cylinder 30 may be seen to be provided with forward radially spaced tabs 32; radially spaced cut out latch slots 33; central radially spaced tabs 34; rear radially spaced tabs 36; and rear radially spaced notches 38. Rear inner housing sleeve 40 may be seen to be provided with first and second radially spaced axial slots 41 , 42; viewing window 43; central radially spaced latch arms 44 with inner facing latch ramps 45; and track arrangement comprising forward straight track 46, curved track 47 and rearward straight track 48.

As will be described in more detail hereinafter, in the 'at rest' position ramps 45 of the radially spaced latch arms 44 of the rear inner housing sleeve latchingly engage in radially spaced notches 38 of the front cylinder. In addition, rear radially spaced tabs 36 of the front cylinder are received within, and to the rearwards part of, the radially spaced axial slots 42 of the inner housing sleeve. In the 'end of use' position of Figure 6 (also corresponding to Figures 18e and 19e), ramps 45 of the radially spaced latch arms 44 of the rear inner housing sleeve have disengaged from the radially spaced notches 38 of the front cylinder. The outer cylinder 30 has then been displaced somewhat forwards relative to the rear inner housing sleeve 40. The rear radially spaced tabs 36 of the front cylinder are still received within, but now rest against the forwards part of, the radially spaced axial slots 42 of the inner housing sleeve 40, thereby restricting absolute detachment of the forwardly-displaced front cylinder 30 from the inner housing sleeve 40.

As may be seen in Figure 9, rear housing sleeve 40 is further provided with boss 50 at the rear end thereof, which inner boss walls 51 define a cylindrical passage arranged for receipt of the rear end of the plunger rod assembly 70, as described in more detail hereinafter.

Figure 10 shows details of the barrel sleeve 35, which has front 39 and rear flanges 37 provided thereto. The rear 37 flange is also provided with pair of diametrically oppositely located trailing latch arms 85, each with latch ramp 87 having end tip 88.

The inner housing sleeve 40 of Figures 8 and 9 is provided with an additiona I latch slot 41 , which is sized shaped and located for receipt of end latch ramp 87 of the barrel sleeve 35. The front cylinder 30 of Figures 6 and 7 is provided with a cut out latch slot 33, which is also sized, shaped and located for receipt of end latch ramp 87 of the barrel sleeve 35. It will be appreciated that in the assembly of Figure 6, the latch slots 33, 41 of the front cylinder 30 and inner housing sleeve 40 rest co-axially with each other, both receiving the end latch ramp 87 of the barrel sleeve 35, which thus couples these parts 30, 40 together and acts to restrict their axial motion relative to each other.

As may be seen in Figure 2, the barrel sleeve 35 is received within the front cylinder 30 at a position corresponding to the barrel receiving part 23 thereof. The barrel sleeve 35 is cylindrical and arranged for receipt of the syringe barrel 12, wherein an end circular barrel lip 13 of the syringe barrel 12 seats against the rear flange 37. In embodiments, the barrel lip 13 may be of truncated circular or other suitable form. As is described in more detail hereinafter, during actuation (e.g. see Figures 18c and 19c) the syringe barrel sleeve 35, syringe barrel 12 and needle 14 move axially forward such that the barrel sleeve 35 seats up against the O-ring 80 and the tip 15 of the needle 14 protrudes out through the delivery aperture 25 of the needle -receiving part 22 of the housing 20 to enable the liquid drug formulation 5 to be delivered by injection to a patient.

The syringe barrel 12 is provided with a rubber syringe plunger 18, which communicates with the plunger rod assembly 70 via defined air cushion 19. The plunger rod assembly 70, which is now described in more detail by reference to Figures 11a to 15b, is provided with plunger end 56. It may be appreciated that in general terms, actuation of the syringe 10 occurs in response to plunging of the plunger end 56 of the plunger rod assembly 70 against air cushion 19 to transfer force to the rubber plunger 18, thereby plunging this part 18 into the barrel 12 of the syringe 10, which causes the liquid drug formulation 5 to be expelled through the tip 15 of the hollow needle 14.

As may be seen at Figures 11a, 11b and 12 the plunger rod assembly 70 comprises an outer plunger rod 72; an inner plunger rod 75 (shown at Figure 13); a plunger end 56 (shown at Figures 15a and 15b); a coupler 65 (shown at Figures 14a and 14b); and rubber ring 76. The plunger end 56 comprises a natural or synthetic polymer material.

The outer plunger rod 72 is essentially an outer cylinder within which the inner plunger rod 75 locates. The outer plunger rod 72 is provided with a track arrangement comprising first 73a and second 73b parallel, but displaced track sections separated by perpendicular link section 74. The track arrangement 73a, 73b, 74 is arranged for receipt of inner follower pegs 94 of follower shuttle 90, which will be described in more detail hereinafter.

Inner plunger rod assembly comprises separable plunger end 56; coupler 65; and inner plunger rod 75 parts. The forward end of the inner plunger rod 75 is provided with radially spaced flexible tags 68 arranged for snap-fit engagement with radially spaced slots 66 of the coupler part 65. The rearward end of the plunger end part 56 is provided with boss 57, which is provided with radially spaced flexible tags 69 arranged for snap-fit engagement with circumferential ledge 67 of the coupler part 65. The plunger end 56 and inner plunger rod parts 75 are thus, in use coupled together via the coupler 65. This coupling

arrangement provides a rotational degree of freedom so that the inner plunger rod part 75 can be oriented and positioned with respect to the inner housing sleeve 40, plunger rod sleeve 72 and follower 94 of the drive shuttle 90 without the need to rotate the syringe plunger 18 in the syringe 10.

The mid-rift part of the inner plunger rod 75 defines a relatively narrow waist 77 section to allow for receipt of the inner follower pegs 92 of the follower shuttle 90 by the track arrangement 73a, 73b, 74 of the outer plunger rod 72. The rear part of the inner plunger rod 75 is provided with a slot 78 for the receipt of release trigger 48 and an embedded O-ring 79 (typically housed within a groove). The inner plunger rod 75 is further provided with an incomplete band of material 69 against which the inner follower pegs 94 of the follower can be braced to restrict the movement in use, and also to an extent during storage, of the outer plunger rod 72. In the full plunger rod assembly 70 the plunger end may be seen to seat against rubber ring 76, which itself seats against the forward end of the outer plunger rod 72.

Referring now in particular to Figures 15a and 15b the plunger end 56 may be seen to define a disc-shaped front (i.e. leading) face 58. Central 59a and radially spaced 59b air holes are provided to the face. The purpose of the venting holes 59a, 59b is so that the air in the air cushion 19 is not compressed by bringing together of the syringe 10 and plunger rod assembly 70 parts during

manufacturing assembly of the device as shown at Figure 16. In practice, once the plunger end 56 is in place in the syringe barrel 12 the radial holes 59b are sealed off and no longer provide a channel for air to escape. In embodiments, the central hole 59a may still provide a channel for air to escape, however in other embodiments this hole 59a is sealed off after assembly such that a fully airtight seal is defined between the syringe plunger 18 and the plunger end 56.

Figures 17a to 17d show details of the follower shuttle 90, which defines an essentially cylindrical form and is provided at its front with end wall 95 having central aperture 96 defined therein and arranged for receipt of the plunger rod assembly 70. The outer wall of the cylinder 90 is provided with a pair of outer follower pegs 92 locating diametrically opposite each other. The central aperture 96 is provided with a pair of inner follower pegs 94 also locating diametrically opposite each other.

Within the device of Figures 1 and 2, the follower shuttle 90 is received within the rearwards section of the inner housing sleeve 40. The outer follower pegs 92 (not visible) thereof locate within the rear straight part 48 of the track section of the inner housing sleeve 40. The inner follower pegs 94 (also not visible) thereof locate within the first, rearward part 73a of the track section of the outer plunger rod 72. Rear end of the plunger rod assembly 70 is received within the

cylindrical passage 51 defined by the boss 50 at rear end 49 of the rear housing sleeve 40. The slot 78 at the rear end of the inner plunger rod 75 protrudes from the boss 50 to allow for receipt of the release trigger 48. Embedded O -ring 79 also at the rear part of the inner plunger rod 75 seats up against inner wall 51 of the boss 50 and frictionally engages therewith.

Referring now also to Figures 18a to 18e and 19a to 19e, the actuating mechanism of the injector device 1 comprises a strong drive compression spring 55 that fits within follower shuttle 90 around the rear end of the plunger rod assembly 70 and boss 50 at end of the rear housing sleeve 40. The forward end of the spring 55 seats against the forward end wall 91 of the follower shuttle 90 and the rearward end of the spring 55 seats against rear end wall 49 of the inner sleeve housing 40. In the 'at rest' position of Figures 18a and 19a, the inner plunger rod 75 is firmly held by the trigger release 48, thereby preventing any forward movement of the plunger rod assembly 70 and follower shuttle 90 coupled thereto.

In an aspect of detail, it will be noted that although the inner plunger rod 75 is restrained firmly by the trigger release 48, the outer plunger rod 72 is

unrestrained except for the indirect restraint on it through the plunger end 56 itself. This inevitably means that the spring 55 is always pushing and squeezing the rubber plunger end 56, even prior to release of the trigger 48. This may help provide a tight seal and for a low strength spring 55 may well be advantageous. When the cap 60 is on, the detent tabs prevent the syringe advancing, however if the device 1 has a strong spring 55, after cap 60 removal there is a risk that the outer plunger rod 72 may push the plunger end 56 forward and thereby, start an uncontrolled premature injection. To prevent this eventuality the inner plunger rod 75 is also provided with band of material 69 at a point that lies in use one millimetre (mm) or so in front of the inner follower pegs 94. This prevents excessive movement of the outer plunger rod 72 with respect to the inner plunger rod 75. The band of material 69 is arranged to have a gap aligned with the outer plunger rod tracks 73a, 73b 74 for the inner follower pegs 94 to move through on the decouple stroke.

Further aspects of the first injector device 1 herein may now be appreciated by reference to Figures 18a to 18e; and Figures 19a to 19e, which show key parts of the device assembly; and to the following description of a typical use operation. For clarity, only the parts of Figures 18b to 18e; and 19b to 1 9e most relevant to the use operation being described are labelled.

In a first stage of a typical use operation, the device 1 'at rest' (e.g. as shown in Figures 2, 18a and 19a) is taken and the cap 60 is removed to uncover the needle delivery aperture 25 as shown at Figure 18b and 19b. Once uncapped, in the absence of the needle sheath gripper 62 and needle sheath 17, the O -ring 80 expands into the needle receiving cavity 22 to provide a barrier surface 83 as previously described. Prior to and during cap 60 removal, the forward radially spaced tabs 32 of the inner cylinder 30 are sprung inwards and interact with the front flange 39 of the syringe barrel sleeve 35 to thereby prevent forward movement of the syringe 10 during cap removal, which may otherwise cause the syringe plunger 18 to be dislodged from the syringe barrel 12 spilling its contents.

Referring now to Figures 18c and 19c, in a second use stage, the trigger 48 is released by decoupling from the rear notch 78 of the inner plunger rod 75.

Under the action of the drive spring 55 the forward part of outer plunger rod 72 pushes against rubber ring 76, which in turn pushes against the plunger end 56 in the syringe barrel 12, but is resisted by the inner plunger rod 75, the motion forward of which is retarded by the friction of the embedded O -ring 79 in the boss 50 in the inner housing sleeve 40. This results in squeezing of the plunger end 56 as it experiences shear forces due to conflict between the retarded motion of the inner plunger rod 75 and the unrestrained motion of the outer plunger rod 72 and rubber ring 76 pressing against the rear surface thereof. The disc face 58 of the plunger end 56 therefore distorts radially against the syringe barrel 12 and the resulting high friction 'clutching' between syringe barrel 12 and plunger end 56 prevents relative movement of the two with the result that the entire syringe 10 with needle 14 and its contents are advanced forward to the 'ready to inject' position of Figures 18c and 19c, in which the needle tip 15 of the syringe protrudes from the needle delivery aperture 25. Since the font plunger end 56 and hence syringe plunger 18 are prevented moving forward within the syringe barrel 12, no fluid 5 is expelled during this syringe

advancement step.

In the 'ready to inject' position, the end -shoulder 11 of the syringe 10 seats up against the syringe-facing wall 83 of the O-ring 80, thereby acting to somewhat compress (e.g. 'squash') the O-ring 80 which thus, tends to flex inwards e.g. to block/grip the syringe 10. In alternative embodiments, a forward end 39 of the syringe barrel sleeve 35 seats up against the syringe-facing wall 83 of the O-ring 80 in this position, which again acts such as to somewhat compress (e.g.

'squash') the O-ring 80 which thus, tends to flex inwards e.g. to block/grip the syringe 10. The syringe barrel sleeve 35 may thus, be provided with shaped end-features (e.g. lip or flange form), which facilitate this seating up against the O-ring 80 and compression thereof. In a third use stage, the embedded O-ring 79 of the inner plunger rod 75 emerges from the boss 50 of the inner-housing sleeve. As a result, the opposing forces on the plunger end 56 are relaxed and the frictional force between the plunger end 56 and syringe barrel 12 is reduced (i.e. 'friction un-clutching'), thus enabling the plunger end 56 to slide down the syringe barrel 12 to exert axial force via the air cushion 19 to the syringe plunger 18, the plunging movement of which results in expelling of the fluid contents 5 of the syringe. In effect, the syringe plunger 18 is therefore forced along the barrel on the cushion 19 of compressed air. When the end of the syringe barrel 12 is reached by the syringe plunger 18 the plunger end 56, driven by the inner plunger rod 75 which has not yet reached its predetermined decouple point, continues to move forward, further compressing the air in the air cushion 19 gap between the plungers 18, 56, thereby forcing the plunger end 56 closer to and possibly even nearly contacting the syringe plunger 18, which is forced hard against the end of the syringe barrel 12. The resistance due to the compressed air 19 slows the forward motion of the plunger rod assembly 70 under the action of the drive spring 55 but crucially does not let it come to a complete stop until the predetermined decouple point of the shuttle 90 from the plunger rod assembly 70 is reached. When this point is reached, the plunger rod assembly 70 may decouple from the shuttle 90, which can continue forward to activate the needle shrouding mechanism.

Thus, as shown in Figures 18d and 19d, as the end of the injection stroke is reached, the follower shuttle 90 begins to rotate due to the outer follower pegs 92 entering the curved section 47 of the track arrangement of the i nner housing sleeve 40. In turn, this causes the inner follower pegs 94 to rotate in their track 73a, 74 in the outer plunger rod 72, causing the follower shuttle 90 and outer - plunger rod 72 to decouple. As a result of this decoupling, the spring 55 can no longer exert drive force on the outer plunger rod 72. However, the spring 55 continues to exert drive force on the follower shuttle 90 which moves forward to engage with ramps 45 of radially spaced latch arms 44 of the rear inner housing sleeve. This results in unlatching of the latch arms 44 from the notches 38 of the front cylinder. Under the continuing influence of the spring 55, the follower 90 pushes the now unlatched front cylinder 30 forwards relative to the inner housing sleeve to the 'end of use' position of Figures 18e and 19e, in which the forward end 31 of the front cylinder 30 is advanced over the syringe 10 to shroud the needle tip 15 thereof.

In this 'end of use' position, the front cylinder 30 has been advanced to a stop point, in which the rear radially spaced tabs 36 of the front cylinder locate at the furthest forward extent within the axial slots 42 of the inner housing (as shown at Figure 6). Also at this stop point, central radially spaced tabs 34 on the front cylinder 30 spring out and lock the front cylinder 30 in its 'at rest' position. Also in this position, end latch ramps 87 of the latch arms 85 of the barrel sleeve 35 abut up against the forward wall of the latch slot 41 of the inner housing sleeve 40. Further, front wall 95 of shuttle 90 also abuts end tip 88 of each latch arm 87. Thus overall, the barrel sleeve 35, and hence the syringe 10 carried thereby, is held in restrained relationship with modified inner housing 40 and shuttle 90 such as to prevent any further forward movement thereof. The syringe 10 is thus, effectively prevented from advancing out from its shrouded position, thereby removing any danger of possible inadvertent contact of the used needle 14, 15 with a user.

Figures 20 and 21 show a second injector device 101 herein that is a variant of the injector described in pending PCT patent application no. WO2007/083,115 in the name of The Medical House PIc, the contents of which are incorporated herein by reference.

The second injector device 101 is arranged for use with a syringe 110 that contains a liquid drug formulation 105. The injector device 101 comprises a generally cylindrical form outer housing 120 that is arranged for receipt of the syringe 110 and is sized and shaped for this purpose. The outer housing 120 is provided with a viewing window 102 that allows for viewing of the contents of the syringe 110 to check for dispensing of syringe contents. The device 101 is provided with a removable cap 160 that is shown at Figures 20 and 21 in the capped position.

The syringe 110 comprises a barrel 112 for holding the liquid drug formulation 105; a hollow needle 114 at one end of the barrel 112; and a syringe plunger 118 in the form of a rubber stopper that is arranged for axial movement (e.g. in response to plunging motion of plunger rod assembly 170) within the barrel 112 such as to enable the liquid drug formulation 105 to be expelled through the hollow needle 114. The hollow needle 114 defines a needle bore, which is of circular cross-section (e.g. 23G, 25G or 27G bore diameter) and a needle tip 115.

In more detail, the inner housing assembly of the injector defines a needle receiving cavity 122, barrel receiving cavity 123 and plunger receiving cavity 124. The needle receiving cavity 122 is provided with a needle delivery aperture 125 through which in use, the hollow needle 114 of the syringe 110 may protrude from the inner housing assembly.

The barrel 112 of the syringe 110 is carried by cylindrical syringe barrel sleeve 135 shown in more detail at Figure 32, which has rear edge 137, sprung front latches 138 and circumferential front end lip 139. On receipt of the syringe barrel 112, front shoulder 111 of the syringe barrel 112 seats against the sprung front latches 138 of the barrel sleeve 135. The outer housing 120 of the injector device 101 is arranged to receive an inner housing comprising rear inner housing part 140 and front inner housing part 142, which in combination define an inner housing cavity within which the syringe 110 and the syringe barrel sleeve 135 are received. The rear inner housing 140 may be seen to be provided with rear ledge end 143, front ledge end 144; middle slot or recess145; and front slot or recess146. The outer housing 120 is further provided with retaining boss clip 150 at the rear end thereof to lock outer 120 and rear inner 140 housings together. The rear inner housing 140 is provided with drive spring-receiving cavity 151 arranged for receipt of drive spring 155. In the 'at rest' position, the forward end of the drive spring 155 seats up against the rear end of drive shuttle 190, as will be described in more detail hereinafter.

A light return spring 154, which forms part of a syringe return mechanism described in more detail hereinafter, is provided at the front end of th e device 101. As may be seen in Figure 21 , the light return spring 154 locates around the front part of the syringe 110 and barrel sleeve 135 and seats between a return spring-receiving cavity 141 of the front inner housing part 142 and the forward end lip 139 of the syringe barrel sleeve. The removable cap 160 may be appreciated to function such as to close off, the needle delivery aperture 125 (i.e. as shown at Figures 20 and 21). Projecting into the cap 160 interior from the top inner surface thereof, there is provided 'split mushroom' headed support 163 that engages with needle sheath shell 162 of needle sheath 117. In the 'at rest' position of Figure 21, the needle sheath 117, which typically comprises a natural or synthetic rubber, may be seen to sheathe the needle tip 115 of hollow needle 114 to provide a hygienic seal thereat. The hooks 164 of the needle sheath gripper 162 act such as to grip the outer part of the needle sheath 117, thereby maintaining the sheath 117 in close proximity with the needle 114 and its sheathed tip 115 when the cap 160 is in the capped position. In the 'ready for use' configuration of Figures 18b and 19b, the cap 160 and gripped needle sheath 117 are removed to open up the needle delivery aperture 125.

The syringe barrel 112 is provided with a rubber syringe plunger 118, which communicates with the plunger rod assembly 170 via defined air cushion 119. The plunger rod assembly 170, which is now described in more detail by reference to Figures 22a to 25, is provided with plunger end ring 156. It may be appreciated that in general terms, actuation of the syringe 110 occurs in response to plunging of the plunger end ring 156 of the plunger rod assembly 170 against air cushion 119 to transfer force to the rubber plunger 118, t hereby plunging this part 118 into the barrel 112 of the syringe 110, which causes the liquid drug formulation 105 to be expelled through the tip 115 of the hollow needle 114. A generally airtight seal is defined between the syringe plunger 18 and the plunger end 156.

Figures 22a to 22c shows the syringe 110 having syringe barrel 112 with front- shoulder 111 and end barrel lip 111 ; needle 114 and needle tip 115; and plunger rod assembly 170 (as shown in Figure 23) comprising plunger rod 172 (shown at Figure 24) and plunger end ring 156 (shown at Figure 25).

The plunger rod 172 includes tapered drive head 174 and circumferential groove 176 provided at its front end for receipt of plunger end ring 156 to form the plunger rod assembly 170. The plunger end ring 56 comprises a natural or synthetic rubber polymer material.

As shown in more detail at Figures 33a and 33b the second injector also includes drive shuttle 190, which defines an essentially cylindrical form. The drive shuttle 190 is provided at its rear end with a set of radially-spaced inwardly-facing flexible tags 192 having ramped forward walls 191. The drive shuttle 190 is also provided at its rear end with a set of radially-spaced outwardly-facing flexible tags 194 having ramped rearward walls 193 and square front edge 195. It may be appreciated that the tags 192,194 share a common flexible stem 197 and hence, that flexing movement of one tag 192, 194 results in reverse flexing movement of its neighbouring tag 194, 192. The drive shuttle 190 is provided at its front end with a second set of radially-spaced outwardly-facing flexible tags 196 having ramped rearward walls 195.

In the 'at rest¹ position of Figure 21 , the rear sets of tags 192, 194 are not tensed such that the outwardly-facing set of tags 194 engages the rear end ledge 143 of the rear inner housing 140. The effect of this engagement is to constrain any forward motion of the drive shuttle 190 relative to the rear inner housing 140, thereby preventing the drive spring 155, the forward end of which seats up against the rear end of drive shuttle 190 and the rear end seats up against end-bar 159, from providing forward drive. Also in the 'at rest position', the forward set of tags 196 flexes inwardly such as to engage with the end lip 113 of the syringe barrel 112, thereby coupling the drive shuttle 190 to the syringe barrel 112. Further aspects of the second injector device 101 herein may now be

appreciated by reference to Figures 26a to 26d; and Figures 27a to 27d and to the following description of a typical use operation. For clarity, only the parts of Figures 26a to 26d; and Figures 27a to 27d most relevant to the use operation being described are labelled.

In a first stage of a typical use operation, the device 101 'at rest' (e.g. as shown in Figures 20 and 21) is taken and the cap 160 is removed to uncover the needle delivery aperture 125 as shown at Figures 26a and 27a. The device 101 is now in its 'ready to use' state, in which it is noted that the tip 115 of the needle 114 remains sheathed by the front inner housing 142.

The user now grips the outer housing 120 and places the needle delivery aperture 125 against the skin at the desired injection point. Downward pressure is now applied to the front inner housing 142 by pressing this against the injection surface of the skin, which pressure results in rearward motion of the inner housing 140, 142 as a whole relative to the outer housing 120. The drive shuttle 190 is also initially moved slightly rearwards as a result of the

engagement of the outwardly-facing set of tags 194 thereof with the rear end ledge 143 of the rear inner housing 140. Another effect of this slight rearwards movement of the drive shuttle 190 is also to bring ramped forward walls 193 of the tags 194 into contact with tapered inner reaction surface 128 of the housing 120. As a result, the tags 194 are flexed inwards with the first effect that they disengage with the rear end ledge 143 of the rear inner housing 140 such as to now enable movement of the drive shuttle 190 relative to the inner housing 140 under the driving force of the drive spring 155. A second result of this inwards - flexing is to bring ramped forward walls 191 of opposing tags 192 into

engagement with the tapered drive head 174 of the plunger rod 172, thereby forming a 'hammer head' which later acts to couple the drive shuttle 190 and plunger rod 172. The drive shuttle 190 also remains coupled to the syringe barrel 112 as a result of the engagement of forward set of tags 196 thereof with the end lip 113 of the syringe barrel 112.

The drive shuttle 190 now moves forward under the action of the drive spring 155. Initially, this forward drive is transferred only to the syringe barrel 112 and syringe barrel sleeve 135 to advance the syringe 110 as a whole to the

'injection' position of Figures 26b and 27b, in which the syringe needle tip 115 protrudes from the needle delivery aperture 125. Since the front plunger end ring 156 and hence syringe plunger 118 do not move forward within the syringe barrel 112, no fluid 105 is expelled during this syringe advancement step. The advancement of the syringe 110 is only lightly resisted by the light return spring 154, which interacts with the forward end flange 139 of the syringe barrel sleeve 135. At the 'injection' position the circumferential lip 139 of syringe barrel sleeve 135 abuts end stop 152 of the front inner housing 140 and further forward movement of the syringe 110 is prevented. At or about this point, the forward set of tags 196 of the drive shuttle flex outwardly into the front slot 145 of the rear inner housing 142 such as to enable disengagement of those tags 196 from the end lip 113 of the syringe barrel 112, thereby decoupling the drive shuttle 190 from the syringe barrel 112. As a result of the decoupling of the drive shuttle 190 from the syringe barrel 112, all further forward drive experienced by the drive shuttle 190 is transferred to the plunger rod 172. The plunger end ring 156 is therefore pushed down the syringe barrel 112 to exert axial force via the air cushion 119 to the syringe plunger 118, the plunging movement of which results in expelling of the fluid contents 105 of the syringe. In effect, the syringe plunger 118 is therefore forced along the barrel on the cushion 119 of compressed air. Wh en the end of the syringe barrel 112 is reached by the syringe plunger 118 the plunger end ring 156, driven by the plunger rod 172 which has not yet reached its predetermined decouple point, continues to move forward, further compressing the air in the air cushion 119 gap between the plungers 118, 156, thereby forcing the plunger end ring 156 closer to and possibly even nearly contacting the syringe plunger 118, which is forced hard against the end of the syringe barrel 112. The resistance due to the compressed air 119 slows the forward motion of the plunger rod assembly 170 under the action of the drive spring 155 but crucially does not let it come to a complete stop until the pre -determined decouple point of the shuttle 190 from the plunger rod assembly 170 is reached. When this point is reached, the plunger rod assembly 170 may decouple from the shuttle 190.

In more detail, as shown in Figures 26c and 27c, as the end of the injection stroke is reached, tags 192, 194 flex outwards and the square front edges 195 of tags 194 are received within mid-slot 145 of the rear inner housing 140. The effect of this outwards -flexing is to bring ramped forward walls 191 of opposing tags 192 out of engagement with the tapered drive head 174 of the plunger rod 172, thereby removing the 'hammer head' and decoupling the drive shuttle 190 from the plunger rod 172. The plunger rod assembly 170 is then able to move axially within the inner housing 140 free from any influence of the drive spring 155. Also in this 'end of injection' position, forward tags 196 of drive shuttle 190 seat up against the front ledge end 144 of front slot 146 of the rear inner housing 140, thereby preventing any further forward movement of the drive shuttle 190.

The syringe barrel sleeve 135 and syringe 110 carried thereby, now experience the return force of the earlier-compressed light return spring 154, which acts such as to move the barrel sleeve 135 backwards to retract the syringe 110 to the 'end of use' position of Figures 26d and 27d, in which the tip 115 of the syringe needle 114 is again shrouded by the front inner housing 142. The plunger rod head 174 and syringe end lip 113 pass through the rear inward tags 192 of the shuttle 190 in this phase and the rear outward tags 194 deflect outwards into mid-slot 145 of the rear inner housing 140 to permit this. The syringe 110 is thus, effectively returned to its initial shrouded position, thereby removing any danger of possible inadvertent contact of the used needle 114, 115 with a user.

Figures 28 to 31 b show aspects of an alternative syringe and plunger rod assembly 270 arranged for use with the second injector 101 of Figures 20 and 21. This alternative syringe and plunger rod assembly 270 is thus substituted for the syringe and plunger rod assembly 170 of Figures 22a to 22c as hereinbefore described with all other aspects of the second injector device 101 remaining as previously described.

In functional terms the alternative syringe and plunger rod assembly 270 makes use of a compressible cushioning element in the form of a foam ring 219 rather than the compressible air cushion 119 of the syringe and plunger rod assembly of Figures 22a to 22c. The plunger rod 272 is also adapted slightly for receipt of this compressible foam ring 219. All other elements of the syringe and plunger rod assemblies 170, 270 correspond. In embodiments, an airtight seal is defined between the syringe plunger 118 and the plunger end 256.

Thus, Figures 28, 31a and 31b show the syringe 110 having syringe barrel 112 with front-shoulder 111 and end barrel lip 111; needle 114 and needle tip 115; and alternative plunger rod assembly 270 comprising plunger rod 272 (shown at Figure 29) having integral plunger end 256 and provided with compressible foam ring 219 (shown at Figure 30). The plunger rod 272 includes plunger end 256; tapered drive head 274 and shank 276 provided at its front end for receipt of compressible foam ring 256 to form the plunger rod assembly 270. The compressible foam ring 256 comprises an open or closed cell foam structure formed of a natural or synthetic polymer material.

Figures 31a and 31b respectively show the alternative syringe and plunger rod assembly 270 in the respective 'ready for use' and 'fully plunged' positions (i.e. corresponding to the positions of previous Figures 27a and 27c. It will be appreciated that during plunging of the syringe 110 the compressible foam ring 219 functions in corresponding fashion to the air cushion 119 of the previously described embodiment. Thus, on plunging the plunger end 256 is pushed down the syringe barrel 112 to exert axial force via the compressible foam ring 219 to the syringe plunger 118, the plunging movement of which results in expelling of the fluid contents 105 of the syringe. In effect, the syringe plunger 118 is therefore forced along the barrel by the cushion defined by the compressible foam ring 219. When the end of the syringe barrel 112 is reached by the syringe plunger 118 the plunger end 256, driven by the plunger rod 172 which has not yet reached its predetermined decouple point, continues to move forward, further compressing the structure of the foam ring 219 between the plungers 118, 256, thereby forcing the plunger end 256 closer to the syringe plunger 118, which is forced hard against the end of the syringe barrel 112. As may be seen in Figure 31a, at this stage, the shank 276 of the plunger rod 272 is also pushed somewhat into the interior of the syringe plunger 118. The resistance due to the now compressed foam ring 119 slows the forward motion of the plunger rod assembly 170 under the action of the drive spring 155 but crucially does not let it come to a complete stop until the pre -determined decouple point of the shuttle 190 from the plunger rod assembly 170 is reached. When this point is reached, the plunger rod assembly 170 may as before decouple from the shuttle 190.

In a further variation, the alternative plunger rod assembly 270 of Figures 28 to 31a is provided with a rubber seal ring locating between the compressible foam ring 219 and the plunger end 256 of the plunger rod 272. An airtight seal may therefore be established between the rubber seal ring, syringe plunger 118 and wall of the barrel 112 of the syringe 110.

The injector of the invention is suitable for the injected delivery of drug, particularly for the treatment and/or prophylaxis of a number of diseases, disorders or conditions, including infections (viral, e.g. HIV infection, bacterial, fungal and parasitic); endotoxic shock associated with infection; inflammatory diseases/autoimmunity such as osteoarthritis, rheumatoid arthritis, psoriatic arthritis, systemic lupus erythematosus (SLE), ankylosing spondilitis, COPD, asthma, Alzheimer's Disease, Crohn's disease, ulcerative colitis, irritable bowel syndrome and psoriasis; immune mediated inflammatory disorders of the central and peripheral nervous system such as multiple sclerosis and Guillain-Barr syndrome; graft-versus-host disease; organ transplant rejection; pain; cancer (including solid tumours such as melanomas, hepatoblastomas, sarcomas, squamous cell carcinomas, transitional cell cancers, ovarian cancers and hematologic malignancies, acute myelogenous leukaemia, chronic myelogenous leukemia, gastric cancer and colon cancer); congenital disorders, e.g. cystic fibrosis and sickle cell anaemia; growth disorders; epilepsy; treatment of infertility; heart disease including ischaemic diseases such as myocardial infarction as well as atherosclerosis and intravascular coagulation; bone disorders such as osteopenia and osteoporosis; and metabolic/idiopathic disease, e.g. diabetes.

Appropriate drugs may thus be selected from biologically active agents, including chemical entities, polysaccharides, steroids and, especially, naturally occurring and recombinant proteins, including glycoproteins, polypeptides and oligopeptides and polymeric derivatives thereof. Particular proteins, polypeptides and oligopeptides include hormones, such as insulin, epinephrine,

norepinephrine, adrenocorticotrophin, somatotropin, erythropoietin and oxytocin; cytokines, such as lymphokines, chemokines and interleukins and receptors therefor, e.g. interleukin (IL)-I α , IL-I p, IL-1R, IL-2, IL-3, IL-4, IL-5, IL-6, IL-13, IL17, interferon (IFN)-α, IFN-β, IFN-γ, granulocyte, monocyte colony stimulating factor, tumour necrosis factor-α; growth factors, such as nerve growth factor and platelet-derived growth factor; enzymes, such as tissue plasminogen activator; and, especially, immunoglobulins. Immunoglobulins include whole antibodies and functionally active fragments and/or derivatives thereof, for example polyclonal, monoclonal, recombinant, multi-valent, mono- or multi-specific, humanised or chimeric antibodies, single chain antibodies, Fab fragments, Fab' and F(ab')2 fragments. Polymeric derivatives of such proteins, polypeptides and oligopeptides include derivatives formed between the protein, polypeptide or oligopeptide and a naturally occurring or synthetic polymer, e.g. a

polysaccharide or a polyalylklene polymer such as a poly(ethyleneglycol) [PEG] or derivative thereof, e.g. methoxypoly(ethyleneglycol) [mPEG]. Particular agents include growth hormones and hormones for the treatment of infertility. Other particular agents are for the treatment of epilepsy such as brivaracetam and seletracetam. The injector device herein has been found to be of particular utility where the drug is an immunoglobulin or a fragment thereof, especially a PEGylated or mPEGylated antibody fragment.

The liquid drug formulations herein are typically aqueous formulations, which comprise the drug in solution and additionally other optional formulation components, which may include buffers (e.g. lactate, acetate), NaCI, and pH modifiers (e.g. NaOH).

The injector device herein has been found to be of particular utility wherein the concentration of the drug (e.g. a therapeutic biologic type drug) in the liquid drug formulation is quite high. In particular, where the drug is a pegylated antibody the injector device has been found to be of particular utility wherein the concentration of the drug is greater than 10Omg/ml, particularly greater than 150mg/ml such as 200mg/ml.

It will be understood that the present disclosure is for the purpose of illustration only and the invention extends to modifications, variations and improvements thereto.

The application of which this description and claims form part may be used as a basis for priority in respect of any subsequent application. The claims of such subsequent application may be directed to any feature or combination of features described therein. They may take the form of product, method or use claims and may include, by way of example and without limitation, one or more of the following claims:

Claims

1. A syringe comprising a barrel for containing a volume of a liquid drug formulation; a hollow needle at a front end of said barrel, said hollow needle defining a needle tip for dispensing of said liquid drug formulation; a syringe plunger that is axially movable within the barrel; and a drive transfer element for transferring axial drive, wherein the drive transfer element defines a plunger end receivable within the barrel of the syringe and axially movable there within such that a cushion is definable between said syringe plunger and said plunger end such that drive is communicable from the plunger end of the drive transfer element to the syringe plunger by way of said cushion.

2. A syringe according to claim 1 , wherein said cushion comprises an air cushion.

3. A syringe according to claim 2, wherein the plunger end is provided with one or more holes that serve as air vents during assembly on insertion of the plunger end into the syringe barrel to define the air cushion.

4. A syringe according to claim 3, wherein said one or more holes for air venting during assembly are radially disposed about the plunger end.

5. A syringe according to either of claims 3 or 4, wherein a central hole for air venting during assembly is provided to the leading face of the plunger end.

6. A syringe according to any of claims 3 to 5, wherein said one or more holes are subsequently sealed off such as to define an airtight seal between the syringe plunger and the plunger end.

7. A syringe according to claim 1, wherein said cushion comprises a compressible cushioning element.

8. A syringe according to claim 7, wherein the compressible cushioning element is comprised of a foamed material.

9. A syringe according to claim 8, wherein said foamed material defines either an open cell or closed cell structure.

10. A syringe according to claim 7, wherein the compressible cushioning element is comprised of a resilient material.

11. A syringe according to claim 10, wherein said resilient material defines a sprung structure.

12. A syringe according to any of claims 1 to 11 , wherein an airtight seal is defined between the syringe plunger and the plunger end.

13. A syringe according to claim 12, wherein the plunger end defines a disc-shaped leading face.

14. A syringe according to claim 13, wherein the diameter of said discshaped leading face is slightly less than the inner diameter of the syringe barrel.

15. A syringe according to any of claims 1 to 14, wherein the syringe plunger and/or the plunger end comprises a frictional material arranged for frictional interaction with the side wall of the syringe barrel.

16. A syringe according to claim 15, wherein said friction material is compressible in nature.

17. A syringe according to either of claims 15 or 16, wherein the syringe plunger and/or the plunger end comprises a natural or synthetic polymer material.

18. An injector comprising a housing defining a housing cavity and a needle delivery aperture; and within said housing cavity, a syringe according to any of claims 1 to 17, wherein said syringe is movable from a rest position, in which the needle tip is within the housing cavity to a use position, in which the needle tip protrudes from said needle delivery aperture.

19. An injector according to claim 18 additionally comprising an energy store for storing energy that is releasable to provide said axial drive to the drive transfer element.

20. An injector according to claim 19, wherein said energy store comprises a drive spring.

21. An injector according to claim 19, wherein the energy store comprises a container of compressed liquid or gas.

22. An injector according to any of claims 18 to 21 , additionally comprising a first coupling for coupling said drive transfer element to the syringe barrel of the syringe, wherein said first coupling is a reversible coupling arranged for decoupling when the syringe moves to the use position.

23. An injector according to claim 22, wherein the first coupling is a friction clutch coupling arranged for decoupling by declutching thereof when the syringe moves to the use position.

24. An injector according to claim 23, wherein the drive transfer element is arranged to transfer axial drive to the syringe barrel via the plunger end and the friction clutch coupling acts to vary the frictional coupling contact between the plunger end and the syringe barrel.

25. An injector according to either of claims 23 or 24, wherein the friction clutch coupling comprises a shape modifier element for modifying the shape of the plunger end, thereby affecting the degree of frictional contact thereof with the syringe barrel.

26. An injector according to claim 25, wherein the drive transfer element comprises a syringe plunger rod, which interacts with the plunger end, and the shape modifier element is provided to said syringe plunger rod.

27. An injector according to claim 26, wherein said shape modifier element comprises a movable plunger rod sleeve provided to the syringe plunger rod.

28. An injector according to either of claims 26 or 27, wherein the syringe plunger rod has a multi-part assembly form comprising a plunger rod part; a plunger end part; and a coupler part locating there between.

29. An injector according to either of claims 27 or 28, wherein a damping element is provided such that initial movement of the plunger rod is damped relative to movement of the plunger rod sleeve such that opposing frictional forces are initially established therebetween.

30. An injector according to claim 29, wherein said damping element is provided between the plunger rod and part of the housing.

31. An injector according to claim 30, wherein the damping element comprises an O-ring provided between the plunger rod and a boss provided to the housing, thereby providing a damping relationship therebetween.

32. An injector according to any of claims 18 to 31 additionally comprising a drive shuttle element arranged for receipt of axial drive and in reversible coupling relationship with the drive transfer element.

33. An injector according to claim 32, wherein the drive shuttle element has an axially symmetric form.

34. An injector according to claim 33, wherein the drive shuttle has a cylindrical form and the drive transfer element is received within said cylindrical form.

35. An injector according to any of claims 32 to 34, wherein the drive shuttle element is provided with one or more followers (e.g. pegs or notches) arranged for track-follower receipt by one or more tracks (e.g. grooves or slots) of the drive transfer element, thereby reversibly coupling the movement of the drive transfer element to that of the driven shuttle.

36. An injector according to claim 35, wherein the track -follower relationship is arranged such that when the plunger is in the fully plunged position within the syringe the drive shuttle decouples from the drive transfer element such that axial drive is no longer transferable

37. An injector according to claim 36, wherein the track -follower

relationship is arranged such that at said fully plunged position the drive shuttle rotates to enable decoupling thereof from the drive transfer element.

38. An injector according to claim 37, wherein said rotation is guided by a curve provided to a second track-follower relationship between the drive shuttle and the housing.

39. An injector according to any of claims 22 to 38, additionally comprising a second coupling for coupling the drive transfer element to a source of axial drive, wherein said second coupling is a reversible coupling arranged for decoupling when the syringe plunger moves to a fully plunged position within the syringe barrel.

40. An injector according to any of claims 19 to 39, additionally comprising a movable shroud element; and a third coupling for coupling the movable shroud element to a source of axial drive, wherein said third coupling is a reversible coupling arranged for coupling when the syringe plunger moves to a fully plunged position within the syringe barrel.

41. An injector according to claim 40, wherein any or all of the first, second and third couplings are comprised within a common coupling element.

42. An injector according to claim 39, additionally comprising a needle retract mechanism that is actuable on decoupling of the second coupling.

43. An injector according to any of claims 18 to 42, wherein the syringe contains a liquid drug formulation.

44. An injector according to claim 43, wherein the barrel of said syringe has a volume corresponding to a single dose of said liquid drug formulation.

45. An injector according to either of claims 43 or 44, wherein said liquid drug formulation is arranged for rest at from 2-8°C and for injected delivery at from 18-3O⁰C.

46. An injector according to claim 45, wherein the liquid drug formulation has a viscosity of less than 120 mPa.s at a delivery temperature of 2O⁰C.

47. An injector according to any of claims 43 to 46, wherein the liquid drug formulation comprises an aqueous formulation of a therapeutic biologic type drug.

48. An injector according to claim 47, wherein said biologic type drug comprises an immunoglobulin or a fragment thereof.

49. An injector according to claim 47, wherein said biologic type drug comprises a PEGylated or mPEGylated antibody fragment.

50. An injector according to any of claims 47 to 49, wherein said aqueous formulation comprise additional formulation component selected from the group consisting of buffers, NaCI, and pH modifiers.

51. An injector according to any of claims 47 to 50, wherein the

concentration of the drug in the liquid drug formulation is greater than 100mg/ml.