Patent Publication Number: US-2012041387-A1

Title: Medicament Delivery Devices

Description:
This invention relates to medicament delivery devices for delivering medicine to the human or animal body and in particular, but not exclusively, to devices having a replaceable medicament cartridge. Such devices are commonly used by those with diabetes for the administration of insulin. 
     Medicament delivery devices are routinely used by persons without formal medical training, i.e. patients where self-management of their condition is increasingly common. These circumstances set a number of requirements for medicament delivery devices of this kind. The injector should be robust in construction, yet easy to use in terms of its operation by a user and the manipulation of the parts. In the case of those with diabetes, many users will be of impaired vision and may also be physically infirm. Devices that are too large of cumbersome may therefore prove difficult to use, particularly someone with reduced dexterity. 
     Patent Specification WO 03/061736 describes a medicament injection device with an axially displaceable lead screw. In this device, the lead screw is in threaded piston engagement with a drive mechanism that comprises a gear and electric motor. The rotational drive of the motor is translated into an axial force by the gear and threaded piston, the axial force being applied to a bung or elastomeric piston of the medicament cartridge. This driving action is operative to expel an amount of the medicine from the cartridge. In order to fully empty the cartridge, the length of the lead screw has to be at least equal to the length of the cartridge, making the total length of the device at least twice the length of the cartridge. A problem with this type of injection device is that the total length is too long to fit unobtrusively within into a jacket pocket or handbag. 
     In order to produce a device that is shorter than twice the length of the cartridge, a telescopic piston rod has been developed. Such a telescopic piston rod is shown, utilized in an infusion device, in WO 97/00091. This patent specification describes a linear-transmission syringe plunger that has a piston rod comprising a plurality of pieces or parts connected to one another by mating threads. The distal part of the telescopic piston rod is connected to the elastomeric piston of the syringe, and is prevented from rotating by a number of bushings surrounding the telescopic piston rod. The bushing of the largest diameter needs to fit within the diameter of the syringe with the consequence that the telescopic piston is only suitable for a syringe of considerable size. 
     It is an aim of the present invention to provide a medication delivery device that has a telescopic piston rod assembly that is more compact. 
     According to the present invention, there is provided a medicament delivery device comprising: a housing; a telescopic piston rod assembly for driving a bung of a medicament container; and a drive mechanism for the telescopic piston rod assembly, wherein the telescopic piston rod assembly has an input drive telescopically coupled to a plunger for driving the bung via an intermediate coupling; characterised in that: 
     the intermediate coupling comprises: first and second members telescopically coupled to one another, the plunger being telescopically coupled to one of the first and second members and the input drive being telescopically coupled to the other one of the first and second members; and a key for restraining rotation of the plunger relative to the housing; 
     wherein the input drive, the first and the second members, and the plunger, cooperate to expand or retract with respect to one another when the input drive is driven by the drive mechanism. 
     The key may comprise first and second sleeves that are telescopically coupled and keyed to one another, the plunger and the housing so that they are axially but not rotationally moveable relative to the housing. In other words, the plunger and intermediate coupling are not rotatable relative to the housing. The key may be effected by way of splines and corresponding grooves or recesses provided in the plunger, the first and second sleeves. The first and second members may be generally cylindrical to form first and second cylinders. The first and second sleeves preferably have lengths that substantially correspond to the respective lengths of the first and second cylinders. The plunger and the input drive preferably also have lengths that correspond to the lengths of the first and second cylinders so as to minimise the length of the telescopic piston rod assembly when in a retracted state. The telescopic relationship between the plunger, the first and second cylinders, and the input drive are such that their respective diameters progressively decrease from the plunger to the input drive. Conversely, the telescopic relationship between the plunger, the first and second sleeves is such that their respective diameters progressively increase from the plunger to the input drive. 
     The plunger may have an internal screw thread that cooperates with an outer screw thread of the second cylinder. The second cylinder is provided with an inner screw thread at its end remote from the plunger that cooperates with an outer screw thread of the first cylinder. Similarly, the first cylinder is provided with an inner screw thread at its end remote from the second cylinder that cooperates with an outer screw thread provided on the input drive. An input gear is fixed to the end of the input drive remote from the first cylinder for engagement with a gear train of the drive mechanism. This provides for transmission of drive from a battery powered motor of the drive mechanism to the telescopic piston rod assembly via the gear train. 
     Embodiments of the present invention are not limited to telescopic piston rod assemblies that extend and contract in any particular phased or staged manner. Extension/contraction of the telescopic piston rod assembly from/to a retracted state where the plunger, the first and second cylinders and the sleeves lie within one another may, in some embodiments, be performed progressively. This may be in three phases or stages or, in other embodiments, the extension/contraction of the components of the telescopic piston rod may be sequential. In yet further embodiments, the extension or contraction of the telescopic piston rod assembly 
     components may be in no definite predictable order. The order in which the plunger, the first and second members and the input drive extend or contract may differ according to the design of internal and external threads, as well as the relative diameters and frictional characteristics, at interfaces of these components. 
     In phase 1, the input drive is rotated by the gear train of the drive mechanism engaging with the input gear but is constrained in an axial direction by the housing. The input drive therefore transfers axial forces into the housing while transferring the torque input from the drive mechanism into the first cylinder. During phase 1, the first cylinder, the second cylinder, the first and second sleeves and the plunger move bodily and axially (but without rotation) along the length of the input drive. This occurs on account of: the first cylinder transferring the torque input from the input drive and provides an axial force into the second cylinder; the second cylinder transferring the axial input force from the first cylinder and transferring the axial input force into the plunger; the first sleeve reacts the torque from the second sleeve and transfers it into the housing; the second sleeve reacts the torque from the plunger and transfers it into the first sleeve; and the plunger transfers the axial force into the bung of the medicament cartridge in order to dispense the medicament. 
     Phase 2 begins when the first cylinder has fully extended, that is, has moved down the length of the input drive until relative rotation between them is arrested by an extension stop. At this point, the first cylinder no longer moves axially but rotates with the input drive. The first cylinder then transfers the input torque from the input drive into the second cylinder, thus causing the second cylinder to progress axially along the first cylinder without rotation. The second cylinder transfers the torque input from the first cylinder and provides an axial force into the plunger. The plunger moves axially without rotation. The plunger transfers the torque input from the second cylinder and provides an axial force into the bung of the medicament cartridge in order to dispense the medicament. During phase 2, the first sleeve does not move but reacts the torque from the second sleeve and transfers it into the drive mechanism housing. The second sleeve does not move and reacts the torque from 
     the plunger and transfers it into the first sleeve so that it does not rotate. The keying of the sleeves may be facilitated by way of light fit between axially running splines and corresponding grooves. The order of movement of the sleeves is not essential or predictable. It will depend on the relative friction between the sleeves and the plunger. The grooves would be blind at one end (not shown) to prevent the sleeves and the plunger decoupling. 
     Phase 3 begins when the second cylinder has fully extended, that is, has moved down the length of the first cylinder until relative rotation is arrested by a second extension stop, it no longer moves axially but rotates with the input drive and the first cylinder. The second cylinder then transfers the torque from the first cylinder into the plunger so that the plunger moves axially along the length of the second cylinder without rotating. The plunger is keyed to the second sleeve so that it is prevented from rotating with the input drive, thereby achieving relative rotation with the second cylinder. A third extension stop is provided to arrest relative rotation between the plunger and the second cylinder when the plunger is fully extended relative thereto. The first, second and third extension stops, which may be provided by closed end threads, also serve to prevent the telescopic piston rod assembly from de-coupling. Clip-on stop rings may be provided for preventing the screw components from decoupling. The clip-on stop rings have been specifically developed to provide sufficient stop strength without requiring a bonding process or constraining the material selection of the screw components. 
     The order of operation of the first and second sleeves is governed by the frictional efficiency of the drive screws. The first cylinder will tend to move first in preference to the second cylinder and plunger during the first phase of the sequential extension of the telescopic piston rod assembly due to the relatively low friction between the smallest diameter screw interface between the input drive and the first cylinder. In other words, the successive extension of the first cylinder, then second cylinder, and finally the plunger is enabled by the increasing friction arising as their respective screw interfaces. 
     The term “medicament delivery device” according to instant invention shall mean a single-dose or multi-dose or pre-set dose or pre-defined, disposable or re-useable device designed to dispense a user selectable or pre-defined dose of a medicinal product, preferably multiple doses, e.g. insulin, growth hormones, low molecular weight heparins, and their analogues and/or derivatives etc. Said device may be of any shape, e.g. compact or pen-type. Dose delivery may be provided through a mechanical (optionally manual) or electrical drive mechanism or stored energy drive mechanism, such as a spring, etc. Dose selection may be provided through a manual mechanism or electronic mechanism. Additionally, said device may contain components designed to monitor physiological properties such as blood glucose levels, etc. Furthermore, the said device may comprise a needle or may be needle-free. In particular, the term “medicament delivery device” may refer to a needle-based device providing multiple doses having an electrical drive mechanism, which is designed for use by persons without formal medical training such as patients. Preferably, the drug delivery device is of the automated-type, i.e. an auto-injector. 
     The term “housing” according to instant invention shall preferably mean any exterior housing (“main housing”, “body”, “shell”) or interior housing (“insert”, “inner body”) having a unidirectional axial coupling to prevent proximal movement of specific components. The housing may be designed to enable the safe, correct, and comfortable handling of the drug delivery device or any of its mechanism. Usually, it is designed to house, fix, protect, guide, and/or engage with any of the inner components of the drug delivery device (e.g., the drive mechanism, cartridge, plunger, piston rod) by limiting the exposure to contaminants, such as liquid, dust, dirt etc. In general, the housing may be unitary or a multipart component of tubular or non-tubular shape. Usually, the exterior housing serves to house a cartridge from which a number of doses of a medicinal product may by dispensed. 
     The term “motor” according to the instant invention shall preferably mean any motorised means for driving the gearing system and ultimately the input drive means. In the instant invention a stepper motor is preferably utilised although any means for driving the gearing system or the drive means, including a mechanical or manual actuation means, may also be incorporated into the device. 
     The “proximal end” of the device or a component of the device shall mean the end, which is furthest away from the dispensing end of the device. 
     The “distal end” of the device or a component of the device shall mean the end, which is closest to the dispensing end of the device. 
     Embodiments of the present invention provide a four-stage telescopic piston rod assembly for more compact medicament delivery devices, both in terms of the axial length of the device as well as the diameter of the medicament container. Telescopic piston rod assemblies embodying the invention may be made from extremely thin walled injection mounded parts, using sophisticated technical plastics materials. Specifically, the input drive has a diameter that has been reduced to provide space for the surrounding components. Consequently, devices embodying the invention may be usefully deployed in re-useable medicament delivery devices that comprise replaceable medicament cartridges and may also be deployed within an auto-injector device. 
    
    
     
       The invention will now be further described by way of example with reference to the accompanying drawings, in which like reference numerals designate like elements: 
         FIG. 1  is a front view of a medicament delivery device that may include an embodiment of the present invention; 
         FIG. 2  is a front view of the medicament delivery device of  FIG. 1  with a medicament cartridge door shown in an open position for receiving a medicament cartridge; 
         FIG. 3  is a perspective view of a telescopic piston rod assembly embodying the present invention, showing a motor, gear and drive mechanism housing; 
         FIG. 4  is a sectional perspective view of the motor, the gear train and drive mechanism of  FIG. 3 ; 
         FIG. 5  is a sectional view of the telescopic piston rod assembly in an extended position within a medicament cartridge; 
         FIG. 6  is a sectional view of a modified embodiment of the door locking member and the telescopic piston rod assembly in an extended position; 
         FIG. 7  is a sectional view of a modified embodiment of the telescopic piston rod assembly of  FIG. 3  in a retracted state, and a door locking member in a forward position; and 
         FIG. 8  is a sectional view of a modified embodiment of  FIG. 7  with the door locking member in a rearward position. 
     
    
    
     In  FIG. 1 , a medicament delivery device  1  comprises a case  2  having a display  3  for displaying functional information relating to the operation of the medicament delivery device, including the set dose, number of doses remaining in the medicament cartridge. User interface buttons  4 ,  5  and  6  are provided to allow the user to operate the injector including priming, setting a dose, opening a medicament cartridge holder and door  7 , and activating the dispensing of the set dose. A threaded needle attachment  8  is provided to which a needle can be attached for dose delivery and subsequently removed and discarded. A cover (not shown) may be provided to fit over the lower portion of the case  2  to assist in protect the device from the ingress of particles and fluid.  FIG. 2  shows the medicament delivery device  1  with the cartridge holder and door  7  in an open position for receiving a replacement medicament cartridge  9 . 
       FIG. 3  is a perspective view of a telescopic piston rod assembly  12 , described in more detail below with reference to  FIGS. 5-8 , together with a motor  13 , and a housing  15  which houses a drive mechanism for transferring drive to the telescopic piston rod assembly  12 . The telescopic piston rod assembly  12  is provided with keys  14  which will be described below with reference to  FIG. 5 . This assembly may be housed in a chassis  16  of the medicament delivery device  1 . The chassis of the medicament delivery device  1  comprises space for a battery (not shown) and space for the medicament cartridge holder and door  7 . 
       FIG. 4  is a sectional perspective view of the assembly of  FIG. 3  with the housing removed  15 . This view shows a drive mechanism  17  which includes a gear train  19 , input gear  21  and input drive  23  of the telescopic piston rod assembly  12 . The gear train  19  comprises a motor pinion  25  and three compound gear stages  27 ,  29  and  31 . The motor pinion  25  is retained on a shaft of the motor  13  with an interference fit and has a pair of moulded flags  33  disposed at 180 degrees about the motor pinion  25 . The flags  33  interrupt a motion detect optical sensor (not shown) in the chassis, the sensor being operative to provide an output corresponding to and indicative of the speed of rotation of the motor  13 . The motor pinion  25 , each compound gear stages  27  to  31  and the input gear  21  together serve to reduce the rotational speed of the drive between the motor  13  and input drive  23  in any suitable ratio which may be, for example, 62.8:1 so that for every revolution of the input drive  23 , the motor rotates 62.8 times. A transfer gear  35 , located between the compound gear  31  and the input gear  21  is non-reducing and so serves to provide a mechanical link. The compound reduction gear stages  27  to  31  are mounted on two parallel stainless steel pins  37  and  39 . The input gear  21  is supported within the housing  15  so as to be rotatably engaged with the transfer gear  35  such as to drivingly rotate the input drive  23 . The input gear  21  and input drive  23  are non-movable in an axial direction. 
       FIG. 5  is a sectional view of the telescopic piston rod assembly  12  in an extended position within the medicament cartridge  9 . The telescopic piston rod assembly  12  comprises an input drive  23  at the proximal end which is non-rotatably fixed the input gear  21 . The input drive  23  has a threaded outer surface  41  which co-operates with an internally threaded portion  43  of a first cylinder  45  of an intermediate coupling, which also has a threaded outer surface  47 . The threaded outer surface  47  of the first cylinder  45  co-operates with an internally threaded portion  48  at the proximal end of a second cylinder  49  of the intermediate coupling, the second cylinder also having a threaded outer surface  51 . The distal end  63  of the threaded outer surface  51  co-operates with an internally threaded portion  53  at the proximal end of a plunger  55 . The plunger  55  is provided with an outwardly extending flange  57  at its distal end for spreading a load exerted by the plunger  55  on a bung  59  of the medicament cartridge  9 . The load exerted on the bung  59  arises when the motor  13  drives the telescopic piston rod assembly  12  such that it extends to drive the bung  55  along the medicament cartridge  9  in order to expel medicament therefrom during use. An inwardly extending annular insert  61  is provided at the distal end of the plunger  55  and serves to stop the plunger retracting beyond a distal end  63  of the second cylinder  49 . A corresponding end stop  62  is mounted on the proximal end of the first cylinder  45  and serves to stop the second cylinder  49  from retracting beyond a proximal end of the first cylinder  45 . The distal ends of the input drive  23 , first cylinder  45  and the second cylinder  49  are provided with closed threads to prevent them from becoming de-coupled from one another. 
     The plunger  55  is keyed to the housing by means of a first sleeve  65  and a second sleeve  67 . A key  14  (see  FIG. 3 ) is provided so as to render the plunger  55  and the first and second sleeves  65 ,  67  non-rotatable relative to one another and the housing. Key  14  is provided by a longitudinal (i.e. axially extending) groove or recess running along the outer surface of each of the plunger  55  and the first and second sleeves  65 ,  67 . The groove or recess cooperates with a corresponding peg or spline  69  provided in the inner surface of the housing (not shown) as well as the inner surface of the first sleeve  65  and the second sleeve  67 . 
       FIGS. 6 to 8  show a modified embodiment of the device according to the current invention.  FIG. 6  shows the telescopic piston rod assembly  12  in an extended position together with the detail of a locking member  71  which sits rotatably and axially movably within the housing  15 . The locking member  71 , which will be described in more detail below with reference to  FIGS. 7 and 8 , has an outwardly extending tab  73  which is operative for engaging/disengaging with a door catch release mechanism (not shown) depending on its axial position relative to the input gear  21  and input drive  23 . Clip-on stop rings  75  are additionally provided on the proximal ends of each one of the first and second threaded cylinders  45 ,  49  for preventing the components from decoupling. The clip-on stop rings  75  are provided with sufficient stop strength on the one hand but without requiring a bonding process on the other. 
       FIGS. 7 and 8  are sectional views of the telescopic piston rod assembly  12  shown in a retracted state and with a door locking member in a forward ‘door closed’ position and rearward ‘door release’ position respectively. As the drive mechanism drives the input gear  21  and the input drive  23  to retract the telescopic piston rod assembly  12 , the plunger  55 , the first and second cylinders  47  and  49  eventually move into a retracted state as illustrated in  FIG. 7 . In this position, there remains a gap d between the proximal end of the locking member  71  and the input gear  21 . In this position, the tab  73  has not progressed or retracted far enough to disengage a medicament cartridge door opening latch (not shown). When it is desired to replace the medicament cartridge  9 , a motor controller (not shown) drives the motor  13  so that the drive mechanism  17  drives the input drive  23  to retract the telescopic piston rod assembly  12  until the gap d is closed, hence disengaging the tab  73  and releasing the door opening latch. 
     The operation of the medicament delivery device  1  described above will now be described. 
     Extension of the telescopic piston rod assembly  12  from an initial retracted state (as shown in  FIGS. 7 and 8 ) where the plunger  55 , the first and second cylinders  45 ,  49  and the sleeves  65 ,  67  lie within one another is performed in three phases or stages. 
     In phase 1, the input drive  23  is rotated by the gear train  19  of the drive mechanism  17  engaging with the input gear  21 . The input drive  23  therefore transfers axial forces into the housing  15  while transferring the torque input from the drive mechanism  17  into the first cylinder  45 . During phase 1, the first cylinder  45 , the second cylinder  49 , the first and second sleeves  65 ,  67  and the plunger  55  move bodily and axially (but without rotation) along the length of the input drive  23 . This occurs on account of: the first cylinder  45  transferring the torque input from the input drive  23  and providing an axial force into the second cylinder  49 ; the second cylinder  49  transferring the axial input force from the first cylinder  45  and transferring the axial input force into the plunger  55 ; the first sleeve  65  reacts the torque from the second sleeve  67  and transfers it into the housing  15 ; the second sleeve  67  reacts the torque from the plunger  55  and transfers it into the first sleeve  65 ; and the plunger  55  transfers the axial force from the plunger and transfers it into the medicament cartridge  9 . 
     Phase 2 begins when the first cylinder  45  has fully extended, that is, has moved down the length of the input drive  23  until relative rotation between them is arrested by an extension stop  75  or closed thread. At this point, the first cylinder  45  has reached its axial limit and no longer moves axially but rotates with the input drive  23 . The first cylinder  45  then transfers the input torque from the input drive  23  into the second cylinder  49 , thus causing the second cylinder to progress axially along the first cylinder without rotation. The second cylinder  49  transfers the torque input from the first cylinder  45  and provides an axial force into the plunger  55 . The plunger moves axially without rotation. The plunger  55  transfers the torque input from the second cylinder  67  and provides an axial force into the medicament cartridge  9 . 
     During phase 2, the first sleeve  65  does not move but reacts the torque from the second sleeve  67  and transfers it into the drive mechanism housing  15 . The second sleeve  67  does not move and reacts the torque from the plunger  55  and transfers it into the first sleeve  65  so that it does not rotate. 
     Phase 3 begins when the second cylinder  49  has fully extended, that is, has moved down the length of the first cylinder  45  until relative rotation is arrested by a second extension stop  75  or closed thread, it no longer moves axially, as it has reached its axial limit, but rotates with the input drive  23  and the first cylinder  45 . The second cylinder  49  then transfers the torque from the first cylinder  45  into the plunger  55  so that the plunger moves axially along the length of the second cylinder without rotating. The plunger  55  is keyed to the second sleeve  67  so that it is prevented from rotating with the input drive  23 , thereby achieving relative rotation with the second cylinder  49 . A third extension stop in the form of a closed thread is provided to arrest relative rotation between the plunger  55  and the second cylinder  67  when the plunger is fully extended relative thereto. 
     The medicament delivery device  1  includes an electronic control system (not shown) for controlling the operation of the device. The control system is operative for controlling the motor  13  to drive the input drive  23  via the drive mechanism  17 . Sensors (not shown) are provided for sensing the state of the telescopic piston rod assembly  12  and providing the user with operational information.