Abstract:
A metered droplet medicament delivery device for delivering metered doses of medicament includes a proximal part and a distal part having opposite distal and proximal ends; a medicament container with a movable stopper; and a dose delivery mechanism that includes a plunger rod, operably arranged to act on the stopper. The proximal and distal parts are releasably connectable to each other. The proximal part includes a medicament container holder accommodating the medicament container, and the distal part includes the dose delivery mechanism. A plunger rod positioning member is engageable with a proximal end of the plunger rod and with a proximal area of the distal part for positioning the plunger rod in a longitudinal direction in relation to the proximal area.

Description:
TECHNICAL AREA 
       [0001]    The present invention relates to a medicament delivery device and in particular a device capable of delivering a number of predetermined metered doses. 
       BACKGROUND OF INVENTION 
       [0002]    For a number of years, medicament delivery devices have been developed, which contain a medicament container provided with a stopper arranged movable inside the container for delivering doses of medicament. The stopper is usually moved by an elongated plunger rod, the plunger rod is in turn often drivably connected to a force mechanism, such as spring force members, capable of accumulating energy for driving the plunger rod when released. 
         [0003]    With many devices, a medicament container is placed inside one housing part of the device, while the drive mechanism, comprising the plunger rod, is arranged in another housing part. The device is then assembled in that the housing parts are connected to each other to make the device ready for delivery of a dose of medicament. Usually a proximal end of the plunger rod is, during the connection, brought in contact with a distally directed surface of the stopper. Before connection, the plunger rod is often brought manually to a position that theoretically will ensure a contact with the stopper after assembly. The same situation may also occur when a device has been used such that the medicament container has been emptied. When a new, full medicament container is to replace the empty container, the plunger rod is in its most proximal position and has to be brought to its initial position. 
         [0004]    However, medicament containers tend to have quite a large tolerance range in the longitudinal direction, i.e. the actual length of a certain type of medicament container may vary within a span of several millimetres. Also the actual position of the stopper in the longitudinal direction of a new and unused medicament container may vary within quite a large span. These tolerance ranges may in total lead to a gap between the plunger rod and the stopper when the device has been assembled. In turn, this gap will lead to a delivered first dose that is smaller than the preset, intended dose because the plunger rod moves a certain distance during its delivery stroke without moving the stopper. 
         [0005]    Because of the tolerance ranges, it is further difficult to provide a fixed stop for the plunger rod at the initial position, because either there will be a gap or the stopper will be pressed and deformed against the plunger rod, which may lead to difficulties in assembling the housing parts and/or that a large pressure is built up inside the medicament container or in the flexible stopper, which may lead to leakage or premature dose delivery. 
         [0006]    US 2011/0245780 discloses a medicament delivery device comprising an adjustment mechanism for handling or adjusting an end surface of a plunger rod in relation to a stopper inside a medicament container. The adjustment mechanism comprises an adjustment member threadedly engaging an end of the plunger rod such that rotation of the adjustment member will cause it to move in the longitudinal direction in relation to the plunger rod, whereby an end surface of the engagement member will contact the stopper. 
         [0007]    One drawback with the solution according to US 2011/0245780 is that it is difficult to know beforehand where to position the adjustment member in relation to the plunger rod for a certain medicament container. It would therefore be necessary to adjust and try the connection between the plunger rod and the medicament container a number times in order to eventually find the appropriate position with contact between the plunger rod and the stopper but without any force from the plunger rod on the stopper. 
         [0008]    There is thus still a need for devices where it is ascertained that there is an initial positive contact between a plunger rod and a stopper of a medicament container before an initial dose delivery. 
       BRIEF DESCRIPTION OF INVENTION 
       [0009]    As used herein, the term “liquid” encompasses all solutions, suspensions, emulsions, oils, gels and so forth, which generally behave as liquids at operating temperatures. 
         [0010]    The term explicitly includes solid compositions dissolved or dispersed in a liquid carrier. Materials behaving as highly viscous liquids are also included. 
         [0011]    In the present application, when the term “distal part/end” is used, this refers to the part/end of the medical delivery device, or the parts/ends of the members thereof, which during use of the device is located the furthest away from the delivery site of the patient. Correspondingly, when the term “proximal part/end” is used, this refers to the part/end of the device, or the parts/ends of the members thereof, which under use of the device is located closest to the delivery site of the patient. 
         [0012]    The aim of the present invention is to remedy the drawbacks of the state of the art devices. This is obtained by a medicament delivery device according to the features of the independent patent claim  1 . Preferable embodiments of the invention form the subject of the dependent patent claims. 
         [0013]    According to the present invention, a medicament delivery device for delivering metered doses of medicament is provided. The device comprises a generally elongated body comprising a proximal and a distal part having opposite distal and proximal ends and a compartment inside said body, capable of accommodating a medicament container. The medicament container is arranged with a movable stopper. The medicament delivery device may also comprise a dose delivery mechanism, which in turn comprises a plunger rod, operably arranged to act on said stopper. 
         [0014]    According to a preferable embodiment of the invention, the proximal part and the distal part are releasably connectable to each other. This facilitates insertion of a medicament container, whereby the proximal part comprises the compartment for accommodating the medicament container. Also, the distal part comprises said dose delivery mechanism with said plunger rod. 
         [0015]    According to the present invention, there is provided a plunger rod positioning member. It may be engageable with a proximal end of the plunger rod as well as engageable with a proximal area of the distal part. This enables the positioning of the plunger rod in a longitudinal direction of the device in relation to the proximal area by displacing the plunger rod distally using the positioning member until the positioning member connects with the proximal end of the distal part. 
         [0016]    Thereby, the plunger rod is positioned appropriately when the proximal part with the medicament container is to be connected to the distal part. When positioned, the plunger rod protrudes a predetermined distance from the proximal end of the distal part, which distance is chosen such that it is ascertained that all tolerance variations of the medicament container, and the variations in actual position of the stopper inside a full medicament container are handled such that the proximal end of the plunger rod is always in contact with the distal end surface of the stopper when the proximal part with the medicament container, is connected to the distal part. This eliminates the risk that the first delivered dose from a new medicament container is not a full dose due to that the plunger rod was not in initial contact with the stopper. 
         [0017]    According to a preferable embodiment, the plunger rod positioning member is arranged removable from said distal part after adjustment of said plunger rod such that the proximal part can be attached. The medicament delivery device may then be arranged with an attachment area where the plunger rod positioning member may be attached until a subsequent positioning procedure. The attachment area may for example be at a distal end of the device. 
         [0018]    Preferably, the plunger rod positioning member may comprise a seat for the proximal end of said plunger rod as well as a contact surface for contact with said distal part. In this manner, precisely defined reference surfaces are obtained, in turn providing a well-defined position of the plunger rod in relation to the distal part when the plunger rod positioning member has been utilized. 
         [0019]    The device may further be provided first holding members on said plunger rod positioning member cooperating with corresponding second holding members on said distal part for releasably holding said plunger rod positioning member. The plunger rod positioning member may thus also be used as a transport cover, which protects the plunger rod and the proximal end of the distal part. The holding members reduce the risk of the plunger rod positioning member falling off the distal part. Alternatively the holding members could be replaced by a push-fit connection between the plunger rod positioning member and the distal part. 
         [0020]    The dose delivery mechanism may further comprise a plunger rod guide member arranged in a rotationally locked relation with said plunger rod as well as a drive nut threadedly connected to said plunger rod, wherein said plunger rod guide member is rotatably arranged in said distal part such that said plunger rod may rotate, and thereby move in the distal direction when in engagement with said plunger rod positioning member, i.e. when the distal part is detached from the proximal part. 
         [0021]    Also, the distal part may preferably comprise a plunger rod guide member lock capable of rotationally locking said plunger rod guide member in relation to the distal part when said distal and said proximal parts are connected to each other. 
         [0022]    According to a further aspect of the invention the medicament delivery device is an inhalation device, an eye spray device or an injector. 
         [0023]    These and other aspects of, and advantages with, the present invention will become apparent from the following detailed description of the invention and from the accompanying drawings. 
     
    
     
       BRIEF DESCRIPTION OF DRAWINGS 
         [0024]    In the following detailed description of the invention, reference will be made to the accompanying drawings, of which 
           [0025]      FIG. 1  is a perspective view of a medicament delivery device comprising the present invention, 
           [0026]      FIG. 2  is an exploded view of a proximal part of the device of  FIG. 1 , 
           [0027]      FIG. 3  is a cross-sectional view of the proximal part of  FIG. 2   
           [0028]      FIG. 4  is a detailed view of a cross-sectional, distal area of the proximal part of  2 , 
           [0029]      FIG. 5  is a perspective view of a distal area of the proximal part of  FIG. 2 , 
           [0030]      FIG. 6  is a perspective view of a distal part of the device of  FIG. 1 , 
           [0031]      FIG. 7  is an exploded view of the distal part of  FIG. 6 , 
           [0032]      FIG. 8  is a cross-sectional view of the distal part of  FIG. 6 , 
           [0033]      FIGS. 9-18  are detailed views of components comprised in the distal part of  FIG. 6 , 
           [0034]      FIGS. 19-20  are detailed views showing different functional states, 
           [0035]      FIG. 19  is a perspective view of the distal part of the device of  FIG. 1  arranged with a plunger rod positioning member according to the invention, 
           [0036]      FIG. 20  is a detailed view of the plunger rod positioning member according to  FIG. 21 , and 
           [0037]      FIG. 21  is a cross-sectional detailed view of the plunger rod positioning member according to  FIG. 21 . 
       
    
    
     DETAILED DESCRIPTION OF THE INVENTION 
       [0038]    One embodiment of a device shown in the drawings comprises a generally elongated body  10 . The body  10  is in the embodiment shown divided into two parts; a proximal part  12  and a distal part  14 ,  FIG. 1 . 
         [0039]    The proximal part  12  comprises a generally tubular housing part  16 ,  FIG. 2 . A proximal end of the housing part  16  is arranged with an attachment area  18 ,  FIG. 2 , onto which a medicament delivery member  20  can be releasably attached. The attachment means between the medicament delivery member  20  and the housing  16  could for example be ledges  22  that snap into corresponding grooves  23  (not shown). It is however to be understood that other types of attachment means could be utilized. The medicament delivery member  20  is in the embodiment shown a mouthpiece through which a user inhales when a dose of medicament is to be delivered. It is however to be understood that other types of medicament delivery members could be used, such as nasal pieces, eye pieces and even injection needles and the like. 
         [0040]    The proximal part  12  is further arranged with a generally elongated tubular medicament container holder  24 ,  FIG. 2 , arranged to accommodate a medicament container  26 . The medicament container holder  24  is arranged with generally radially flexing legs  28 ,  FIG. 3 , with outwardly extending ledges  30  that fit into recesses  32  in the housing part  16 . 
         [0041]    The medicament container  26  is in the embodiment shown arranged with a proximal neck  34  and a movable stopper  36  inside the container. At the proximal end of the medicament container holder  24 , a nebulizing nozzle  38  is arranged,  FIGS. 2 and 3 . The nebulizing nozzle  38  contains a chip (not shown) with a plurality of micro channels capable of creating an aerosol of droplets of medicament. 
         [0042]    A medicament container guide member  40 ,  FIGS. 2 and 3 , is arranged with a central passage and is intended to be pushed onto the medicament container  26  from its proximal end and into contact with an annular ledge  42  at the distal end of the medicament container  26 ,  FIG. 4 . The medicament container guide member  40  is arranged with a number of proximally extending arms  44 ,  FIG. 3 , arranged generally radially flexible and having outwardly extending protrusions  46 . These protrusions  46  are arranged to grip around an annular ledge  48  of the housing for locking the medicament container guide member  40  and thus the medicament container  26  in the radial direction. 
         [0043]    A medicament holder locking member  50 ,  FIG. 4 , is arranged to be pushed into the distal end of the medicament container holder  24 , and moved in contact with a distally directed end surface of the medicament container  24 . The medicament holder locking member  50  is arranged with a central passage  52  and is provided with a number of generally radially flexible tongues  54  having outwardly extending protrusions  56 ,  FIG. 4 . These protrusions  56  are arranged to fit into recesses  58  on inner surfaces of the medicament container guide member  40  such that when the medicament holder locking member  50  is in place, the medicament container  26  is locked in the axial direction. 
         [0044]    The distal part  14  is arranged with a housing. In the embodiment shown the housing is designed as two housing halves  60 ,  62 ,  FIG. 6 . It is however to be understood that the housing may be arranged in other ways and in more parts without departing from the scope of the invention. 
         [0045]    Inside the distal part, a generally tubular chassis  64  is arranged,  FIGS. 7 ,  9 ,  10 . It is arranged with a transversal interior wall  66 ,  FIGS. 9 and 10 . The interior wall  66  is further provided with a central passage  68 . At a proximal end of the chassis, attachment means  70 ,  FIG. 6 , are arranged, in the embodiment shown as grooves for a bayonet connection. In this context it is to be understood that other types of attachment means may be employed, such as threads, snap-on fittings or the like, all within the imagination of the person skilled in the art. The attachment means  70  of the chassis  64  are intended to interact with corresponding attachment means  72  on the distal end of the generally tubular housing part  16 ,  FIG. 5 . 
         [0046]    Coaxially arranged inside the chassis  64  and extending in the longitudinal direction of the device is an elongated plunger rod  74 ,  FIGS. 6 and 7 . The plunger rod  74  is intended to be in contact with a stopper arranged in the medicament container. The plunger rod  74  is arranged inside a so called drive member extension  76 ,  FIGS. 11 and 12 , having a generally tubular shape. A proximal end of the drive member extension  76  is arranged with spline grooves  78  on its outer surface,  FIGS. 11 and 12 . The spline grooves  78  mate with corresponding spline ridges  80  on an inner surface of a generally tubularly shaped drive nut  82 ,  FIG. 11 . 
         [0047]    The inner surface of the drive nut  82 ,  FIG. 11 , is further provided with threads  84 , which cooperate with threads  86  on the outer surface of the plunger rod  74 . The drive nut  82  is further arranged with an annular ledge  88  with a distally directed end surface having a number of slanting wedge-shaped surfaces  90 . The proximally directed surface of the interior wall  66  of the chassis  64  is arranged with corresponding slanting wedge-shaped surfaces  92 ,  FIG. 9 . 
         [0048]    The plunger rod  74  is further arranged through a guide nut  94 ,  FIG. 11 . The guide nut  94  is arranged with guide ledges  96  which cooperate with longitudinal grooves  98  of the plunger rod  74 ,  FIG. 6 , providing a rotational lock but allowing a longitudinal movement of the plunger rod  74  in relation to the guide nut  94 . The guide nut  94  fits into a guide nut lock member  100 , which is attached to the chassis  64  via radially outwardly extending protrusions  102  fitting into recesses  104  in the interior surface of the chassis  64 ,  FIG. 9 . The nut lock member  100  is arranged with tongues  106  that are arranged flexible in the generally radial direction. The inner surfaces of the flexible tongues  106  are arranged with wedge-shaped teeth  108 ,  FIG. 11 , extending in the radial direction. The teeth  108  of the tongues  106  are intended to engage corresponding wedge-shaped teeth  110  arranged around the circumference of the guide nut  94 . A spring  111 ,  FIG. 8 , is arranged between the drive nut  82  and the guide nut  94  for urging the latter in the proximal direction. 
         [0049]    Further, the drive member extension  76  is arranged with a ring-shaped part  112 ,  FIG. 11 , with a hollow interior, where the inner surface of the interior is arranged with transversal stop ledges  114 . These stop ledges  114  cooperate with flexible arms  116  arranged at a proximal end of a generally elongated drive member  118 ,  FIG. 12 . 
         [0050]    However the stop ledges  114  and flexible arms  116  are arranged such that the drive member  118  may only be rotated in one direction in relation to the drive member extension, where the flexible arms  116  slide over the stop ledges  114 . In the other direction, the ends of the flexible arms  116  abut the stop ledges  114 , thereby blocking their relative rotation. The drive member  118  is further arranged with a disk-shaped member  120 ,  FIG. 12 . On the proximally directed side of the disk-shaped member  120 , two stop ledges  122  are arranged diametrically on opposite sides of a longitudinal axis  124 ,  FIG. 1 , of the device. The stop ledges  122  are arranged to co-act with corresponding stop ledges  126 ,  FIG. 10 , arranged in the interior of the chassis  64  for limiting the rotation of the drive member  118 . 
         [0051]    A spring force member, shown as a spiral drive spring  134 ,  FIG. 13 , is arranged around the drive member  118  and attached with an inner end in an elongated slit  136 ,  FIG. 12 , in the drive member  118  and with the other end in a slit  138  in a spring house  140 ,  FIG. 13 . The spring house  140  is in turn placed inside the distal part of the chassis  64 ,  FIG. 10 , and held fixed in relation to the chassis  64  by longitudinal grooves  142  in the outer surface of the spring house  140  fitting with corresponding ridges  144 . The spring house  140  is held in place in the chassis  64  by a spring house cover  146 ,  FIG. 14 , which is attached to the chassis  64  by proximally directed arms  148  with passages  150 , which accommodate ledges  152  on the outer surface of the chassis  64 . The spring house cover  146  is further arranged with a distally directed tubular member  154 . 
         [0052]    The distal end of the drive member  64  with the ledges  156  are further arranged to fit into a corresponding recess  164  on a dose knob  166 ,  FIG. 15 . The recess  164  is positioned on a central post  168  inside the dose knob  166 ,  FIG. 15 . The dose knob  166  is further arranged with a number of proximally directed arms  170 , which arms  170  are flexible in the generally radial direction. The free ends of the arms  170  are arranged with inwardly extending ledges  172 , which ledges  172  are designed to fit around an annular ledge  174 ,  FIG. 14 , arranged on the circumference of the tubular member  154 . A spring  176 ,  FIG. 18 , is further arranged between an end wall  160  of a guide member  158  (not shown) and an interior, proximally directed wall of the dose knob  166 , urging the latter in the distal direction. 
         [0053]    Further, an activation mechanism  178 ,  FIG. 16 , is arranged in the device. It comprises an activation button  180  extending through an opening of one of the housing halves  60 . The activation button  180  comprises two inwardly extending arms,  182 , one on each side of the longitudinal direction  124  of the device. Each arm  182  is arranged with a first surface  184  facing in the proximal direction. The first surface  184  transitions into a second surface  186 , inclined with respect to the first surface  184 . The second surface  186  thereafter transitions into a third surface  188  generally parallel with the first surface  184 . 
         [0054]    The arms  182  are in contact with a dose activator  190 , Fig,  11 , comprising a ring-shaped body  192 ,  FIG. 11 , surrounding a part of the drive member extension  76 . The ring-shaped body  192  is arranged with two elongated posts  194 , extending in the longitudinal direction of the device. Each post is arranged with a groove  196 , in which grooves the arms  182  of the activation button  180  fit,  FIG. 17 . 
         [0055]    A distally directed end surface of the ring-shaped body  192  is arranged with an engagement mechanism comprising a number of circumferentially directed stop ledges  198 ,  FIG. 11 , the function of which will be described below. The stop ledges  198  are to interact with stop ledges  200  on an outer surface of the drive member extension  76 . A compression spring  202 ,  FIG. 13 , is arranged between an interior surface of the activation button  180  and an outer side surface of the chassis  64  for urging the activation button  180  towards an extended position. Further a second compression spring  204 ,  FIG. 8 , is arranged between a proximally directed end surface of the ring-shaped body  192  of the dose activator  190  and a distally directed surface of the transversal wall  66  for urging the ring-shaped body  192  in the distal direction and in engagement between the stop ledges  198  of the ring-shaped body  192  and the stop ledges  200  of the drive member extension  76 . 
         [0056]    The present invention is further arranged with a plunger rod positioning member  210 , e.g. a cap,  FIGS. 19 to 21 . In the embodiment shown the plunger rod positioning member is arranged as a generally tubular body  212  that together with an end wall  214 , forms a cap,  FIG. 21 . On the inner surface of the tubular body adjacent an edge  220 , first holding members, in the form of inwardly directed ledge portions  216 ,  FIG. 20 , are arranged. The ledge portions  216  are arranged to cooperate with second holding members, in the form of an annular groove  218 , arranged at the proximal end of the distal part  14  when a distally directed end surface  220  of the cap is moved in contact with a proximally directed annular ledge  222  of the distal part. An interior surface of the end wall  214  of the cap may further be arranged with a centrally positioned seat  224 ,  FIG. 21 , in which the plunger rod  74  may fit. 
         [0057]    The device is intended to function as follows. When the device is delivered to a user for the first time, the proximal and the distal parts are delivered separate from each other. Also the medicament container may be delivered separate from the proximal part. The distal part  14 , when delivered, has the cap attached to its proximal end,  FIG. 19 . When the plunger rod positioning member  210  has been attached to the device during assembly before delivery to a user, the plunger rod positioning member  210  is used to position the plunger rod  74  at a certain predetermined distance d in relation to a proximal end surface  226  of the distal part  14 ,  FIG. 21 . Thus the proximal end of the plunger rod  74  is fitted into the seat  224  of the cap  210 ,  FIG. 23 . In this way the cap also protects the device, and especially the plunger rod during handling, i.e. before the proximal and the distal parts are assembled. When no proximal part is attached to the distal part, the teeth  108  of the tongues  106  of the guide nut lock member  100  are out of engagement with the teeth  110  of the guide nut  94 . The guide nut  94  is thus free to rotate, and when the plunger rod  74  is pushed in the distal direction by the plunger rod positioning member  210 , it may rotate together with the guide nut  94 , in relation to the chassis  64  and the drive nut  82 , thereby moving the plunger rod  74  in the distal direction of the device. 
         [0058]    The plunger rod  74  is moved in the distal direction until the edge  220  of the plunger rod positioning member  210  is moved in contact with the annular ledge  222  of the distal part, when the ledge portions  216 , fit into the annular groove  218  of the distal part  14 . The dimensions of the cap in relation to the annular ledge  222  and the distance to the proximal end  226  of the device are chosen such that the plunger rod protrudes a certain pre-determined distance d beyond the proximal end of the device. When the device made ready for use, the plunger rod positioning member  210  is removed. It may then be attached to a distal end of the device for later re-use as seen in  FIG. 6  and  FIG. 18 . When plunger rod positioning member cap is removed, the plunger rod protrudes that pre-determined distance d beyond the proximal end surface  226  of the distal part  14 . 
         [0059]    Now the proximal part  12  is connected to the proximal end of the distal part  14 . First, an appropriate medicament container  26  is placed in the medicament container holder  24  together with the medicament container guide member  40  such that its arms snap in engagement with the medicament holder. The medicament holder is subsequently inserted into the housing part  16 . Then the medicament holder locking member  50  is pushed in engagement with the medicament container guide member  40 . The proximal part  12  is thereafter connected to the distal part  14  and the chassis  64  via the attachment means  70 ,  72 . 
         [0060]    During connection, the proximal end of the plunger rod is moved into contact with the stopper of the medicament container. Thus, the pre-determined distance, d, of the protruding plunger rod has been chosen such that it is ascertained that there is a positive contact between the proximal end of the plunger rod and the stopper, regardless of any differences in tolerances of the medicament container and regardless of any differences in actual position of the stopper inside a full medicament container. Thereby it is ascertained that the initial dose from the device really is a full dose of medicament. Otherwise, if there is a gap between the plunger rod and the stopper at the initial dose delivery, the first delivered dose will not be a full dose. 
         [0061]    The distal end of the medicament container guide member  40  is designed such that it engages the outer surface of the guide nut lock member  100 , whereby the tongues  106  are pressed radially inwards such that the teeth  108  of the tongues  106  engage the teeth  110  of the guide nut  94 , whereby the guide nut  94  becomes rotationally locked. 
         [0062]    When a dose is to be set and delivered the dose knob  166  cooperates with the drive member  118  in spring force tensioning mechanism, when operated, e.g. rotated. In order to connect the dose knob  166  to the dose setting mechanism, the dose knob  166  is pushed in the proximal direction against the force of the spring  176 . The dose knob  166  and the drive member  118  are then connected in that the ledges  156  fit into the recess  164 . Thus, when the dose knob  166  is rotated, the drive member  118  is also rotated. The rotation of the drive member  118  causes the spiral drive spring  134  to be tensioned from an initial state where it was pre-tensioned during manufacture of the device. 
         [0063]    During rotation, the flexible arms  116  of the drive member  118  move out of contact with the stop ledges  114  of the ring-shaped member  112  of the drive member extension  64  until they are moved in contact with subsequent stop ledges  114 . The drive member  118  is prevented from being rotated back because the contact of the flexible arms  116  with the stop ledges  114 . 
         [0064]    Further, the drive member extension  64  is in turn prevented from rotating because the stop ledges  198  of the dose activator  192  are in contact with the stop ledges  200  on the drive member extension  64 . 
         [0065]    The dose knob  166  is rotated until the stop ledge  122  of the drive member  118  comes in contact with the corresponding stop ledge  126  of the chassis  64 . This ensures that the user cannot turn the dose knob  166  beyond a pre-set position. Therefore a too large dose cannot be set. 
         [0066]    The user may now position the medicament delivery device at the delivery site and may manually activate the medicament delivery device by pressing the activation button  180  into the device against the force of the return spring  202 . The movement of the activation button  180  causes the arms  182  to slide in the grooves  196  of the posts  194 . After a certain movement, the inclined second surface  186  is moved in contact with a distally directed surface of the groove  196  and thereafter the third surface  188 ,  FIG. 17 . This contact of the second and third surfaces forces the ring-shaped body  192  in the proximal direction. This in turn causes the stop ledges  198  of the dose activator  190  to move out of contact with the stop ledges  200  of the drive member extension  64 . The drive member extension  64  and thereby the drive member  118 , because of the connection between the flexible arms  116  and the stop ledges  114 , are now free to rotate by the force of the spring  134 , and due to the splines connection between the drive member extension  64  and the drive nut  82 , the latter is also rotated. 
         [0067]    Due to the rotation of the drive nut  82 , which is in threaded engagement with the threads  86  of the plunger rod  74 , and because of the rotational lock of the plunger rod with the guide nut  94 , the plunger rod  74  is axially advanced, which causes it to move the stopper  36  inside the medicament container  26  and to force the medicament through the medicament delivery member, e.g. the nebulizing nozzle  38  and the mouth-piece  20 . 
         [0068]    It is to be understood that the embodiment described above and shown in the drawings is to be regarded only as a non-limiting example of the invention and that it may be modified in many ways within the scope of the patent claims.