Patent Publication Number: US-9901680-B2

Title: Spring driven injection device

Description:
CROSS-REFERENCE TO RELATED APPLICATIONS 
     This application is a 35 U.S.C. § 371 National Stage application of International Application PCT/EP2013/063250 (published as WO 2014/001319), filed Jun. 25, 2013, which claimed priority of European Patent Application 12174289.4, filed Jun. 29, 2012; this application claims priority under 35 U.S.C. § 119 of U.S. Provisional Application 61/667,069; filed Jul. 2, 2012. 
    
    
     THE TECHNICAL FIELD OF THE INVENTION 
     The invention relates to a torsion spring driven injection device for injection of multiple set doses. In particular, the invention relates to a torsion spring driven injection device of the type where the injection needle is shielded during injection and where the axial movement of the needle shield releases the injection of the set dose. 
     DESCRIPTION OF RELATED ART 
     An automatic torsion spring driven injection device is disclosed in EP 338,806. In one embodiment, the injection needle is covered by a telescopically movable needle shield. When the shield is pressed against the skin of a user, a compression spring drives the body of the pen forward such that the tip of the injection needle penetrates the skin of the user, and a torsion spring is released to perform an injection of the liquid drug contained in the injection device. In such shield triggered injection devices, the step of pressing an injection button has been eliminated and the injection needle is hidden during injection, however, exchanging the injection needle is troublesome as the user needs to remove the needle shield in order to gain access to the injection needle. 
     A different spring driven pen-shaped injection device having a shielded injection needle is known from U.S. Pat. No. 7,112,187. The injection device disclosed is an automatic spring-driven injection in which an actuation spring provided inside the housing thrusts the piston rod forward during injection. An important characteristic of such automatic injection device is that no element move out from the injection device during dose setting. Thus, the injection device has a constant length during operation. This particular injection device has a mode selector which is rotated to select one out of three different modes. In one mode the shield is locked and in a different mode the shield is unlocked. In the unlocked position, the shield can be moved axially between an extended and a retracted position. In the retracted position a user has access to the distal end of the injection device and is thus able to attach or remove an injection needle. Further, the mode selector can be rotated to an injection position, in which position the set dose is released when the shield is moved to its retracted position during injection. 
     For automatic spring driven injection devices for multiple injections of set doses in which the triggering of the injection is made by the backward movement of the needle shield a particular challenge is present. In order to exchange the injection needle, the needle shield needs to be axially removed from the hub of the injection needle such that the user can rotate or twist the hub in order to couple or decouple the injection needle. However, when performing the injection, the needle shield must trigger the release of the dose when only the distal part of the needle cannula is penetrated into the body. 
     In EP 338,806 this is solved by simply removing the needle shield during changing of the injection needle whereas in U.S. Pat. No. 7,112,187 it is done by a complicated mechanism involving a mode selector. However, in both examples it is difficult to explain the user how to handle the injection device as the user has to perform many different steps and remember which steps in the sequence of executing the injection he or she has fulfilled. 
     A further manual injection device in which the cartridge is disconnected from the injection needle by axial movement of the cartridge is described in WO 2011/051366. 
     DESCRIPTION OF THE INVENTION 
     It is an object of the present invention to provide a spring driven injection device for multiple automatic injections of set doses which are very simple to handle and which do not require any, or only very little, explanation to the user but wherein the working of the injection device is self-explanatory. 
     It is particularly an object of the present invention to provide a shield triggered automatic injection device which facilitates easy exchange of the injection needle without accidentally pushing on the needle shield during needle shift and thereby activating the injection process. 
     The invention is defined in claim  1 . 
     Accordingly, in one aspect of the present invention, an injection device for torsion spring driven injection of a liquid drug is provided. 
     The torsion spring driven injection device comprises:
         A housing storing all the mechanical components of the injection deivce including the cartridge containing the liquid drug. The cartridge is axially fixated to the housing, such that the cartridge cannot move axially in relation to the housing.   A dose setting arrangement for setting the size of the dose to be injected. The dose setting arrangement includes a proximally mounted dose setting button which the user rotates to set the size of the dose to be injected.
           A torque spring drive mechanism for driving the set dose out from the cartridge. The drive mechanism includes a torsion spring which is strained by the user when setting a dose and released to inject the set dose. It has proven to be beneficial if a certain amount of prestraining is preloaded into the torsion spring such that small sizes of drug can be injected without the spring force necessarily having to return to zero for each individual injection. The torsion spring can alternatively be fully preloaded when the injector is delivered to the user such that the user does not need to strain the torsion spring at all. The preload is thus sufficient to empty the drug cartridge through a number of doses as in U.S. Pat. No. 7,112,187.   
           A torsion spring which applies its torque to rotate a piston rod guide which then during its rotation moves the piston rod axially forward to press the liquid drug out through the injection needle mounted to the injection device.   A telescopically movable needle shield for covering the distal end of the injection needle in a situation of use. The needle shield is further adapted to release at least portion of the torque of the torsion spring when moved axially, and   a needle holder for carrying the injection needle.       

     The needle holder is slidable mounted in the housing such that the needle holder carrying the injection needle and the housing carrying the cartridge can be moved axially in relation to each other such that the proximal end of the injection needle can be moved into and out of engagement with the septum of the cartridge. 
     In addition, the needle shield activating the injection can be moved axially in relation to both the housing and the needle holder, whereby the needle holder carrying the injection needle can be moved to an extended position while the shield can be moved to a retracted position thus enabling easy exchange of the injection needle. 
     Firstly when an injection sequence is initiated, the needle holder is in its distal position extending out from the needle shield such that a user can exchange the injection needle. 
     When setting a dose, the needle shield is released to be moved into its extended position covering the distal end of the injection needle. 
     When pressed against the skin, the needle shield and the needle holder moves proximately such that the proximal end of the needle shield penetrates the septum of the cartridge where after the injection is automatically performed. 
     When removing the shield form the surface of the skin, the shield remains in its retracted position and the needle holder automatically slides forward such that the proximal end of injection needle decouples form the septum of the cartridge and the user can once again gain access to the injection needle. 
     Thus, having a housing to which the cartridge is fixed and a needle shield telescopically and axially movable in relation thereto together with a needle holder which is axial movable both in relation to the housing and to the shield provides for optimal handling of the injection needle. As explained the shield can be retracted and the needle holder pushed distally which presents the injection needle for manual handling by the user. 
     Also since the needle holder is axial movable, the proximal end of the needle cannula decouples instantly from the cartridge as the shield is removed from the surface of the skin, it is therefore no longer necessary to maintain the injection needle inserted into the skin of the user as no more drug will flow through the injection needle once the non-patient end is removed from the septum of the cartridge. Also when the injection needle is decoupled, air will not be sucked into the cartridge through the lumen of the injection needle why the so-called air-shot or flow-check usually performed prior to injection in order to remove air from the cartridge is no longer necessary. 
     The torsion spring is preferably encompassed between the housing and the piston rod guide such that the piston rod guide is able to rotate under influence of the torsion spring. However one or more other elements can be present between the housing and the piston rod guide. In one example the torsion spring might be connected to a spring base element which is secured to the housing. 
     Further, a rotatable drive tube for rotating the piston rod guide can be present. The drive tube can be connected to the torsion spring such that the drive tube can be rotated by the user to strain the torsion spring and released to rotate the piston rod guide. This would require a ratchet mechanism for holding the torque introduced into the torsion spring. 
     A clutch or activator coupling the drive tube to the piston rod guide would also be recommendable. Such clutch is movable between a first position in which the clutch is rotational locked to the housing e.g. by a toothed interface and a second position in which the clutch is rotational released from the housing and rotational coupled to both the drive tube and to the piston rod guide such that the torque of the torsion spring is transferred via the drive tube to the piston rod guide. Thus, in the first position the clutch is secured to the housing whereas the clutch in the second position is coupled to the drive tube which is released to rotate the piston rod guide. 
     The piston rod guide further engages the piston rod either via a keyed engagement or via a threaded engagement. In the first case the piston rod guide will rotate the piston rod distally ( in this case the piston rod is threaded to the housing). In the second case the piston rod will move distally without rotation when the piston rod guide is rotated (in this case the piston rod is keyed to the housing). 
     A helical compression spring is provided between the housing and the needle shield urging the needle shield in the distal direction to cover the distal end of the injection needle. However, the needle shield is engaged with the helically movable scale drum whenever the scale drum is in its zero position i.e. when no dose is set and the number “0” is displayed in the window displaying the set dose size. 
     This engagement is preferably made between hooks, indentations or the like on the needle shield engaging cooperating hooks or the like provided in the scale drum. 
     The needle shield slides on an outside surface of the needle holder. The needle holder is provided with a plurality of flexible arms extending vertically and engaging the needle shield thus preventing axial movement of the needle shield in relation to the needle holder. These arms are preferably positioned such that the arms bend inward whenever an injection needle is mounted onto the needle holder. When the arms are bended inwardly i.e. when an injection needle is mounted, the needle shield can slide freely on the needle holder. In this way the needle shield is prevented from moving into its extended position when no injection needle is mounted. 
     When the needle shield during injection moves from its extended position to its retracted position it moves with it the needle holder due to hook means provided on the needle shield and engaging the needle holder. 
     Since the needle holder carries the injection needle, the needle cannula is also moved in the proximal direction such that the proximal end of the injection needle penetrates the septum of the cartridge allowing the liquid drug in the cartridge to flow through the injection needle. 
     At the same time the axial and proximally movement of the needle holder activates the release of the torsion spring to drive the drive mechanism by axially moving the clutch or activator. 
     During the expelling of the set dose, the scale drum rotates back to its zero position. When the scale drum at the end of the injection reaches its zero position with the number “0” showing in the window, the needle holder is released from the needle shield such that the needle holder can move axially in the distal direction under influence of a spring provided between the needle holder and the housing. 
     In its zero position the scale drum abuts with a protrusion of the needle holder to release the needle holder from the shield such that the needle holder can slide axially in the distal direction. 
     In a different embodiment, the invention relates to a torsion spring driven drug delivery device of a liquid drug comprising:
         A housing storing a cartridge containing the liquid drug to be injected.   A needle holder to which an injection needle can be mounted,   A needle shield for covering the injection needle during use, and       

     wherein, the needle shield is slidable relatively to the needle holder and which needle holder is provided with a number of flexible arms preventing axial movement of the needle shield when no injection needle is mounted on the needle shield and which arms are moved into alignment with the needle holder when an injection needle is mounted on the needle holder thereby allowing the needle shield to move axially relatively to the needle holder. 
     In this way, the needle shield can only slide relatively to and on the needle holder when an injection needle has been mounted onto the needle holder. 
     When no injection needle is mounted, the needle shield is preferably secured in its proximal retracted position allowing a user to change the injection needle, and when an injection needle is mounted and the flexible arms are pressed into alignment with the needle shield, the needle shield can pass in its sliding movement towards its distal position. 
     However, in a further embodiment of the invention, the needle shield is either alone or in addition prevented from axial movement by engagement between the needle shield and the scale drum. In this further embodiment, the spring driven delivery device comprises:
         A housing storing a cartridge containing the liquid drug to be injected.   A scale drum threadely engaged with the housing to perform an helical movement away from a zero position during setting of a dose.   A needle shield for covering the injection needle during use, which needle shield can slide axially in relation to the housing, and       

     wherein the scale drum engages and locks the needle shield when in the zero position. 
     Whenever the scale drum is in its zero position, i.e. the position in which no dose has been set, and the cipher “0” appears in the window or display of the injection device, engagement means on the scale drum arrests the needle shield and secures it from axial movement. 
     When a user dials a dose and the scale drum moves away from its zero position, these engagement means releases and set the needle shield free to move whereby the needle shield is slidable into a position in which it covers the injection needle. 
     In a further embodiment of the invention, the needle shield can be biased by a compression spring to move in the distal direction when released from scale drum. 
     A further embodiment combines the two previous embodiments and thus requires the user to both mount an injection needle to move the flexible arms away from the needle shield and to set a dose to release the needle shield. When these two actions have been performed, the needle shield is slidable into its extended position covering the distal end of the injection needle. 
     DEFINITIONS 
     An “injection pen” is typically an injection apparatus having an oblong or elongated shape somewhat like a pen for writing. Although such pens usually have a tubular cross-section, they could easily have a different cross-section such as triangular, rectangular or square or any variation around these geometries. 
     The term “Needle Cannula” is used to describe the actual conduit performing the penetration of the skin during injection. A needle cannula is usually made from a metallic material such as e.g. stainless steel and connected to a hub to form a complete injection needle also often referred to as a “needle assembly” or simply an “injection needle” A needle cannula could however also be made from a polymeric material or a glass material. The hub also carries the connecting means for connecting the needle assembly to an injection apparatus and is usually moulded from a suitable thermoplastic material. The “connection means” could as examples be a luer coupling, a bayonet coupling, a threaded connection or any combination thereof e.g. a combination as described in EP 1,536,854. 
     Needle assemblies specially designed for pen injections systems are defined in ISO standard No. 11608, part 2, and are often referred to as “pen needles”. Pen needles have a front-end for penetrating into the skin of the user and a back-end for penetrating into the cartridge containing the drug. 
     As used herein, the term “drug” is meant to encompass any drug-containing flowable medicine capable of being passed through a delivery means such as a hollow needle in a controlled manner, such as a liquid, solution, gel or fine suspension. Representative drugs includes pharmaceuticals such as peptides, proteins (e.g. insulin, insulin analogues and C-peptide), and hormones, biologically derived or active agents, hormonal and gene based agents, nutritional formulas and other substances in both solid (dispensed) or liquid form. 
     “Scale drum” is meant to be a cylinder shaped element carrying indicia indicating the size of the selected dose to the user of the injection pen. The cylinder shaped element making up the scale drum can be either solid or hollow. “Indicia” is meant to incorporate any kind of printing or otherwise provided symbols e.g. engraved or adhered symbols. These symbols are preferably, but not exclusively, Arabian numbers from “0” to “9”. In a traditional injection pen configuration the indicia is viewable through a window provided in the housing. When reference is made to a “zero position” of the scale drum, this does not necessarily mean that the number “0” is present, however it merely refers to the position of the scale drum in which no dose has been set. 
     “Cartridge” is the term used to describe the container containing the drug. Cartridges are usually made from glass but could also be moulded from any suitable polymer. A cartridge or ampoule is preferably sealed at one end by a pierceable membrane referred to as the “septum” which can be pierced e.g. by the back-end of an injection needle. The opposite end is typically closed by a plunger or piston made from rubber or a suitable polymer. The plunger or piston can be slidable moved inside the cartridge. The space between the pierceable membrane and the movable plunger holds the drug which is pressed out as the plunger decreased the volume of the space holding the drug. However, any kind of container—rigid or flexible—can be used to contain the drug. 
     Since a cartridge usually has a narrower neck portion into which the rubber plunger cannot be moved, not all of the drug contained inside the cartridge can be expelled. The term “initial quantum” therefore refers to the initial quantum of the injectable content. The term “remaining content” in the same way refers to the remaining injectable content. 
     Further the term defines a piercing member adapted to penetrate the skin of a subject for the purpose of delivering or removing a liquid. 
     Using the term “Automatic” in conjunction with injection device means that, the injection device is able to perform the injection without the user of the injection device during dosing deliver the force to expel the drug. The force is typically delivered by an electric motor or by a spring as herein described which spring is strained by the user during dose setting. Such springs are usually prestrained in order to avoid problems of delivering very small doses. Alternatively, the spring can be preloaded by the manufacturer with a preload sufficient to empty the drug cartridge though a number of doses. Typically the user activates a latch or a button on the injection device to release the force accumulated in the spring when carrying out the injection. 
     All references, including publications, patent applications, and patents, cited herein are incorporated by reference in their entirety and to the same extent as if each reference were individually and specifically indicated to be incorporated by reference and were set forth in its entirety herein. 
     All headings and sub-headings are used herein for convenience only and should not be constructed as limiting the invention in any way. 
     The use of any and all examples, or exemplary language (e.g. such as) provided herein, is intended merely to better illuminate the invention and does not pose a limitation on the scope of the invention unless otherwise claimed. No language in the specification should be construed as indicating any non-claimed element as essential to the practice of the invention. 
     The citation and incorporation of patent documents herein is done for convenience only and does not reflect any view of the validity, patentability, and/or enforceability of such patent documents. 
     This invention includes all modifications and equivalents of the subject matter recited in the claims appended hereto as permitted by applicable law. 
    
    
     
       BRIEF DESCRIPTION OF THE DRAWINGS 
       The invention will be explained more fully below in connection with a preferred embodiment and with reference to the drawings in which: 
         FIG. 1  show a perspective view of the injection device prior to use. 
         FIG. 2  show a perspective view of the injection device with the cap removed. 
         FIG. 3  show a perspective view of the injection device with the injection needle mounted. 
         FIG. 4  show a perspective view of the injection device with the needle shield in its extended position. 
         FIG. 5  show a perspective view of the injection device during injection. 
         FIG. 6  show a perspective view of the injection following injection. 
         FIG. 7.1-7.8  show a schematic view of the various sequences of performing an injection using the injection device according to the invention. 
         FIG. 8  show a cross sectional view of the injection device according to a first example. 
         FIG. 9  show an exploded view of the injection device in  FIG. 8 . 
         FIG. 10  show a detailed cross sectional view of the engagement between the needle shield and the scale drum. 
         FIG. 11  show a detailed cross sectional view of the needle shield released from the scale drum. 
         FIG. 12  show a detailed cross sectional view of the connecting means of the needle holder without an injection needle attached. 
         FIG. 13  show a detailed cross sectional view of the connecting means of the needle holder with an injection needle attached. 
         FIG. 14  show a detailed cross sectional view of the activation mechanism during injection. 
         FIG. 15  show a different detailed cross sectional view of the activation mechanism. 
         FIG. 16  show a detailed cross sectional view of the activation mechanism upon activation. 
         FIG. 17  show a detailed cross sectional view of the proximal end of the injection device. 
         FIG. 18  show a perspective view of the mechanism releasing the needle holder following injection. 
         FIG. 19  show a cross sectional view of the injection device according to a second example. 
         FIG. 20  show an exploded view of the injection device in  FIG. 19 . 
         FIG. 21  show a cross sectional view of the injection mechanism according to the  FIGS. 19-20  in the non-dosing position. 
         FIG. 22  show a cross sectional view of the injection mechanism according to the  FIGS. 19-20  when releasing a set dose. 
         FIG. 23  show a side view of the interior of the injection device of the  FIGS. 19-20  with the needle holder locked to the needle shield. 
         FIG. 24  show a perspective view of  FIG. 22 . 
         FIG. 25  show a side view of the interior of the injection device of the  FIGS. 19-20  with the needle holder released from the needle shield and the needle shield locked to the scale drum. 
         FIG. 26  show a perspective view of  FIG. 24 . 
     
    
    
     The figures are schematic and simplified for clarity, and they just show details, which are essential to the understanding of the invention, while other details are left out. Throughout, the same reference numerals are used for identical or corresponding parts. 
     DETAILED DESCRIPTION OF EMBODIMENT 
     When in the following terms as “upper” and “lower”, “right” and “left”, “horizontal” and “vertical”, “clockwise” and “counter clockwise” or similar relative expressions are used, these only refer to the appended figures and not to an actual situation of use. The shown figures are schematic representations for which reason the configuration of the different structures as well as there relative dimensions are intended to serve illustrative purposes only. 
     In that context it may be convenient to define that the term “distal end” in the appended figures is meant to refer to the end of the injection device which usually carries the injection needle whereas the term “proximal end” is meant to refer to the opposite end pointing away from the injection needle and carrying the dose dial button as depictured in the  FIGS. 1 to 6 . 
       FIG. 1  to  FIG. 7  discloses a torsion spring driven injection device during its different stages. The features and the working modes disclosed in the  FIGS. 1 to 7  is common for both examples. 
     When delivered to a user, the injection device  1  has a cap  2  secured to the distal end of the housing  3  as disclosed in  FIG. 1 . Further, the injection device  1  has a dose setting button  4  at its proximal end and a window  5  provided in the housing  3  through which the user can visually inspect the size of the dose being set by rotating the dose setting button  4 . 
       FIG. 2  discloses the injection device  1  with the cap  2  removed. In this mode, the user can inspect the drug contained in the injection device through the inspection opening  6 . The shield  20  is in its retracted position and the user has full access to the connecting means  31  provided distally on the needle holder  30 . 
     In this mode the axial movement of the shield  20  in the distal direction is hindered by two flexible arms  32  provided on the needle holder  30  and shown in details on  FIG. 12-13 . These flexible arms  32  are provided in conjunction with the connecting means  31  such that once an injection needle  100  is connected to the connection means  31 , this injection needle  100  pushes the flexible arms  32  inwardly to allow passage of the axial movable shield  20  in the distal direction. 
     In  FIG. 3 , the user has attached an injection needle  100  to the connecting means  31 . The injection needle  100  is a conventional pen needle  100  (see  FIG. 12 ) comprising a hub  102  to which a metallic needle cannula  101  is secured. The needle cannula  101  has a distal end  103  for penetrating the skin of a user and a proximal end  104  for entering into a cartridge  105  contained in the injection device  1 . 
     When a user dials a dose by rotating the dose setting button  4  (indicated by the arrow S in  FIG. 4 ), the shield  20  is automatically moved into its extended position as disclosed in  FIG. 4 . In this extended position the shield  20  visually covers the distal end  103  of the needle cannula  101 , at least when the injection device  1  is viewed radially i.e. when vied from the side. 
     An injection is hereafter performed simply by pressing the distal end of the shield  20  softly against the skin of the user. This is indicated with the arrow I in  FIG. 5 . The distal part  103  of the needle cannula  101  penetrates through the skin of the user, and the shield  20  when moving into its retracted position automatically activates the injection of the set dose as will be explained later. 
     Following injection, when the distal end  103  of the needle cannula  101  is removed from the skin of the user as disclosed in  FIG. 6 , the shield  20  is maintained in its retracted position and the needle holder  30  moves axially into its extended position making it possible for the user to exchange the injection needle  100 . 
     The various sequences of an injection are schematically disclosed in  FIG. 7 . The details will be further explained in the following. 
     In  FIG. 7.1 , the cap  2  has been removed and the injection needle  100  has been connected to the connection means  31  of the needle holder  30 . No dose has been dialled as can be seen in the window  5 . 
     In  FIG. 7.2  the user dials a dose, and the shield  20  is moved forward to cover the distal end  103  of the injection needle  101 . 
     In  FIG. 7.3  the shield  20  is pressed against the skin S of a user. 
     In  FIG. 7.4 , the distal end  103  of the needle cannula  101  has penetrated through the skin S of the user and the needle holder  30  and the shield  20  locks to each other and moves axially together as further disclosed in  FIG. 15 . 
     In  FIG. 7.5 , the proximal end  104  of the needle cannula  101  has penetrated through the septum  106  of the cartridge  105 . The injection itself is being executed in this position, indicated by the number “ 0 ” appearing in the window  5 . Once the scale drum in returned to zero it locks the shield to the housing (via the scale drum). 
     In  FIG. 7.6  the needle holder  30  is forced forward which decouples the proximal end  104  of the needle cannula  101  from the cartridge  105 . 
     In  FIG. 7.7  this decoupling is fulfilled and in  FIG. 7.8  the needle holder  30  locks to the housing  3 . 
     FIRST EXAMPLE 
     The operation of the injection device  1  according to a first example will be explained in details in conjunction with the  FIGS. 8 to 18 . 
     The mechanics of the injection device  1  is contained in an outer housing  3 , which is preferably made from two parts, a distal cartridge holder  3   a  which is permanently secured to a proximal housing part  3   b  to form one housing  3 . An intermediate part  7  carrying a partition  8  is provided between the cartridge holder  3   a  and the proximal housing part  3   b.  Alternatively the housing  3  can be formed as one unitary unit. 
     As identified before, the distal end of the housing  3  carries a shield  20  and a needle holder  30  whereas the proximal end of the housing  3  carries the dose setting button  4 . 
     The distal cartridge holder part  3   a  further stores the cartridge  105  which is a conventional cartridge  105  having a septum  106  at its distal end and an axially movable plunger  107  slidable provided at its proximal end. By moving the plunger  107  in the distal direction, the volume of the area between the septum  106  and the plunger  107  is reduced with the volume being pressed out through the needle cannula  101  of the injection needle  100 . 
     The cartridge  105  is axially locked to the housing  3 . The proximal end  109  of the cartridge  105  abuts the partition  8  as disclosed in  FIG. 10-11  and the shoulders  108  of the cartridge  105  abut inwardly pointing protrusions  9  internally in the housing  3  such that the cartridge  105  cannot slide axially in relation to the housing  3 . In order to obtain the tolerances of the cartridge a number of distally pointing fingers  12  can be provided on the partition  8 . These fingers  12  preferably has a sloping surface to press against the proximal end  109  of the cartridge  105  as disclosed in  FIG. 11 . The inwardly pointing protrusions  9  securing the cartridge  105  distally can be provided at a distal end of the opening  6 , they could however be provided wherever needed. Alternatively the cartridge  105  can be moulded to the housing  3 . 
     In order to move the plunger  107  forward a drive mechanism is provided which mechanism comprises a threaded piston rod  40  which at its distal end presses against the plunger  107  preferably with a washer  43  provided between the piston rod  40  and the plunger  107 . 
     The intermediate housing part  7  with its internal partition  8  is inrotatable secured to the housing  3  preferably between the two housing parts  3   a,    3   b.  The intermediate housing part  7  could alternatively be moulded as an integral part of the housing  3 . The outside thread  41  of the piston rod  40  engages an internal thread  10  provided centrally in the intermediate housing part  7  such that whenever the piston rod  40  is rotated it moves axially in relation to the intermediate housing part  7  a distance determined by the number of revolutions of the piston rod  40  and the pitch of the threads  10 ,  41 . 
     The piston rod  40  is further provided with an axial stretching track  42  which is engaged by a piston rod guide  50  such that whenever the piston rod guide  50  rotate, the piston rod  40  rotates simultaneously and is screwed forward in the thread connection  10 / 41 . 
     The needle holder  30  is as disclosed in  FIG. 12-13  provided with a number of flexible arms  32  which are pressed outwardly by the inherent force of the flexible arms  32 . In this outwardly pointing position, the flexible arms  32  abuts the shield  20  in a pair of grooves  21  provided on a flange  22  of the shield  20  such that the shield  20  is prevented from moving distally relatively to the needle mount  30 , as indicated in  FIG. 2 . In this position a user can mount the injection needle  100  to the connection means  31 . When the injection needle  100  is mounted onto the connecting means  31 , the flexible arms  32  will bend and be brought into alignment with the outside surface of the connecting means  31  of the needle holder  30  and the shield  20  can slide freely relatively to the needle mount  30  as depictured in  FIG. 13 . 
     In order to visually indicate the size of the dose being set by rotating the dose setting button  4  a scale drum  60  is provided. The scale drum  60  is provided with an external thread  61  engaging a similar thread provided internally in the housing  3  as seen in  FIG. 10 . 
     The dose setting button  4  engages the drive tube  70  at its proximal end via a ratchet mechanism which is described in details in the not yet published PCT/EP 2013/055403 to Novo Nordisk NS, which is hereby incorporated by reference. This ratchet mechanism as disclosed in  FIG. 17  comprises a spring base  80  which is permanently secured to the housing  3  and has an internal toothing engaging the ratchet arms  86  of the ratchet element  85 . 
     The ratchet element  85  is further provided with an internal toothing  87  engaging a similar toothing  71  externally provided on the drive tube  70  such whenever a user rotates the dose setting button  4  to set a dose, the dose setting button  4  rotates the ratchet element  85  and together with it the drive tube  70 . 
     The dose setting button  4  engages directly with the ratchet element  85  which rotates together with the dose setting button  4  both when setting a dose and when lowering the set dose by rotating the dose setting button  4  in the opposite direction. The dose setting button  4  further has an internally provided protrusion which is able to move the ratchet arm  86  out of engagement with the internal toothing of the spring base  80  when the dose is being lowered. 
     A torsion spring A is provided between the drive tube  70  and the spring base  80 , which torsion spring A is strained whenever the drive tube  70  is rotated in the dose setting direction. The spring base  80  could alternatively be a part of the housing  3  in which case the torsion spring A would be encompassed between the housing  3  and the drive tube  70 . 
     Besides the torsion spring A delivering the torsional force to perform the injection, two other springs are provided. A helical spring B applying an axial force is provided between a flange  28  on the shield  20  and the internal partition  8  of the intermediate part  7  of the housing  3  urging the shield  20  in the distal direction and a second axially working helical spring C is provided between a flange  33  provided distally on the needle mount  30  and the housing  3  urging the needle mount  30  in the distal direction. The helical spring C can rest against the distal side of the internal protrusions  9  inside the housing part  3   a  securing the cartridge  105  as disclosed in  FIG. 8 . 
     The drive tube  70  is on an outside surface provided with an axial groove  72  being engaged by a corresponding raised bar  62  internally in the scale drum  60 , such that the scale drum  60  follows rotation of the drive tube  70  and can move axially in relation to the drive tube  70 . Since the scale drum  60  is threaded to the housing  3  it performs a helical movement whenever rotated. Externally the scale drum  60  is provided with a series of indicia indicating the size of the dose which indicia can be viewed through the window  5  in the housing  3 . 
     As disclosed in  FIGS. 10-11 , the distal end the scale drum  60  is internally provided with hooks  63  engaging similar indentations  23  provided proximally on a pair of identical arms  24   a,b  provided proximally on the shield  20 . 
     The shield  20  is urged in the distal direction by the helical spring B which is encompassed between the partition  8  of the intermediate housing part  7  and the shield  20  thus applying a distally orientated force on the shield  20 . The shield  20  is further provided with an axial surface  25  which is guided by a similar axial surface  11  provided along the inspection opening  6  inside the housing  3  such that the shield  20  is guided solely axially without the possibility of rotating relatively to the housing  3 . 
     Whenever the scale drum  60  is in its most distal position, the hooks  63  will engage the indentations  23  on the shield  20  and thus prevent the helical spring B form urging the shield  20  in the distal direction ( FIG. 10 ), however when the scale drum  60  is rotated to set a dose as disclosed in  FIG. 11 , the indentations  23  are released from the hooks  63  and the shield  20  travels in the distal direction under the force applied by the helical spring B. Thus, when a user dials a dose as depictured in  FIG. 4  (arrow D), the shield  20  is released to move in the distal direction to cover the distal end  103  of the needle cannula  101 . 
     End-Of-Content 
     An end of content mechanism disclosed in  FIG. 17  comprises an EOC tube  45  and an EOC ring  55 . The EOC ring  55  carries an outside thread  56  which is threaded inside the EOC tube  45  and is axially guided on the drive tube  70  by having an internal protrusion  57  guided in an axial track  73  on the drive tube  70 . 
     Further the EOC tube  45  has an internal flange  49  which is captured by hooks  75  provided on the drive tube  70  allowing the EOC tube  45  to slide a short distance axially in relation to the drive tube  70 . 
     Whenever a dose is set, the drive tube  70  is rotated and the EOC tube  45  is held inrotatable by having teeth  46  engaging similar teeth inside the spring base  80 . The EOC ring  55  is thereby dialled up the EOC tube  45  a distance which relates to the size of the set dose. During expelling of the dose, the drive tube  70  is moved axially in relation to the EOC tube  45  as will be explained later, the result being that the distal toothing  47  on the EOC tube engages a similar toothing in the drive tube  70  such that the drive tube  70  and the EOC tube  45  rotates simultaneously during dosing whereby the EOC ring  55  remains in its relative position. The position of the EOC ring  55  in the internal thread of the EOC tube  45  is therefore an expression of the accumulated set doses. 
     The helical length of the internal thread of the EOC tube is made such that the EOC ring  55  reaches the end of the internal thread of EOC tube  45  when the cartridge  105  is empty, or at least empty for its usable content. At this point the EOC ring  55  abuts the end of the internal thread and prevents further rotation of the drive tube  70 , thus no further dose can be set. 
     The EOC tube  45  can further be provided with teeth  48  engaging similar teeth in the spring base  80  providing dose clicks as the EOC tube  45  rotates with the drive tube  70  during dosing. 
     Dose Setting 
     When a user sets a dose by rotating the dose dial button  4  as indicated in  FIG. 4 , the rotation of the dose setting button  4  causes the ratchet element  85  to also rotate. This rotation is transferred to the drive tube  70  via the toothing  71 ,  87 . 
     As the drive tube  70  is rotated the torsion spring A encompassed between the spring base  80  and the drive tube  70  is strained. The torsion thereby being built up in the torsion spring A is held by the ratchet arms  86  engaging the internal toothing of the spring base  80 . The ratchet arms  86  can be actively released in order to dial down the size of the set dose. 
     As the drive tube  70  is rotated, the scale drum  60  rotate and move helically thus indicating the size of the set dose in the window  5 . 
     As the scale drum  60  starts to rotate, the hooks  63  of the scale drum  60  moves out of the engagement with the indentations  23  of the shield  20  which is then free to move axially under the influence of the helical spring B. The shield  20  thus moves to a position covering the distal end  103  of the needle cannula  101  as depictured in  FIG. 4 . 
     Once the user has set the size of the dose to be injected, the injection device  1  is set and ready to perform an injection. 
     Activation 
     In order to release the torque applied to the torsion spring A and thereby to perform an injection, the shield  20  is pressed against the skin of the user as indicated by the arrow I in  FIG. 5  which will trigger the injection as explained below. 
     The needle holder  30  is provided with an identical set of flexible arms  34   a,b . These arms  34   a,b  are blocked in the axial direction by an internal flange  13  provided inside the housing  3  as disclosed in  FIG. 14-16 . 
     Further, the shield  20  is provided with two identical arms  24   a,b  carrying the indentations  23 . These arms  24   a,b  are each further provided with a protrusion  26  as best seen in  FIG. 16 . As the shield  20  travels in the proximal direction, this protrusion  26  presses the flexible arms  34   a,b  inwardly such that the flexible arms  34   a,b , can slide under the internal flange  13  of the housing  3  as in  FIG. 14  and thus allow the needle shield  30  to slide axially. 
     The needle holder  30  is further provided with a second pair of identical arms  35   a,b . These arms  35   a,b  carries proximally an extension  36 . 
     The arms  24   a,b  of the shield  20  each carry a radial protrusion  27  which peripherally follows the outside surface of the cartridge  105 . As the shield  20  is moved axially in the proximal direction, the radial protrusions  27  abuts the extension  36  and further axial movement of the shield  20  will thus force the needle holder  30  to move along with the shield  10  in the proximal direction as the arms  34   a,b  in this position is able to escape under the flange  13 . 
     As both the shield  20  and the needle holder  30  slides in the proximal direction, the proximal end  104  of the needle cannula  101  penetrates through the septum  106  of the cartridge  105  since the cartridge  105  which proximally rest against the partition  8  of the intermediate part  7  is prevented from axial movement. 
     Dose Release 
     Once the proximal end  104  of the needle cannula  101  has penetrated through the septum  106  of the cartridge  105  and the distal end  102  has penetrated through the skin of the user, the set dose is released in the following manner. 
     The axial track of the piston rod  40  is engaged by the piston rod guide  50  as disclosed in  FIG. 16 . The piston rod guide  50  is further provided with an external toothing  51  (see e.g.  FIG. 11 ) engaging a similar toothing  74  internally in the drive tube  70 . The drive tube  70  and the piston rod guide  50  can slide axially relatively such they can shift between a position in which the toothing  74  of the drive tube  70  engages with the toothing  51  of the piston rod guide  50  such that the piston rod guide  50  follows the rotation of the drive tube  70  and a position in which the drive tube  70  and the piston rod guide  50  is disengaged. 
     Distally, the piston rod guide  50  is engaged by the activator  90 . 
     The activator  90  has a central part  91  which engages the piston rod guide  50  such that the activator  90  can move the piston rod guide  50  axially while the piston rod guide  50  can rotate relatively to the activator  90 . Distally, the activator is provided with two identical legs  92   a,b.    
     During activation as the needle holder  30  is moved in the proximal direction by the shield  20 , the proximal end of the arms  34   a,b  abuts the arms  92   a,b  of the activator  90  and slides the activator  90  in the proximal direction. 
     This axial movement of the activator  90  pushes the piston rod guide  50  into engagement with the drive tube  70 . 
     The central part  91  of the activator  90  is provided proximally from this wall partition  8  and the legs  92   a,b , extend through openings in the partition  8 . The partition  8  is further provided with a toothing  14  ( FIG. 8 ) which engages a similar toothing  53  internally in the piston rod guide  50  such that the piston rod guide  50  is prevented from rotation relatively to the partition  8  (and the housing  3 ) as long as the piston rod guide  50  axially abuts the partition  8 . 
     As the arms  34   a,b  axially moves the piston rod guide  50  out of engagement with the toothing  14  of the partition  8  and into engagement with the drive tube  70  it also moves the drive tube  70  slightly in the proximal direction. This axial movement of the drive tube  70  moves the proximal toothing  71  of the drive tube  70  out of its engagement with the internal toothing  87  of the ratchet  85  as shown in  FIG. 17 . As the ratchet element  85  prevents the torque of the torsion spring A from being released, the torsion spring A is now able to rotate the drive tube  70  which rotates with it the piston rod guide  50  and thereby the piston rod  40  to perform an ejection of the liquid drug. 
     After Dosing 
     Due to the engagement between the axial groove  72  of the drive tube  70  and the raised bar  62  of the scale drum  60 , the scale drum  60  rotates back to its zero position during injection. As the scale drum  60  returns to its zero position as shown in  FIG. 18 , the raised bar  62  engages an axial surface  93  provided externally on the activator  90 . The impact of the scale drum  60  with the activator  90  makes the activator  90  rotate an angle. This rotation makes the arms  92   a,b  of the activator  90  move under a peripheral extension  36   e  provided peripheral on the extension  36  which lifts the extension  36  and thereby the proximal end of the arms  35   a,b  over the radial protrusion  27 . In order to enhance this lifting, both the arms  92   a,b  and the extension  36   e  are preferably provided with an inclined surface as depictured in  FIG. 18 . The helical spring C urging an axial force on the needle holder  30  now pushes the needle holder  30  in the distal direction such that the proximal end  104  of the needle cannula  101  is moved out of its engagement with the septum  106  of the cartridge  105 . When setting a dose the activator  90  is rotated back to its initial position. 
     The needle shield  20  is in the zero position locked to the scale drum  60  due to the engagement  63 / 23  and is thus hindered from moving axially. The result being as shown in  FIG. 6 , that the needle shield  20  remains in its retracted position and the needle holder  30  moves into its most distal position thereby making it possible for the user to exchange the injection needle  100   
     SECOND EXAMPLE 
     A second example which essentially works the same way as the first example is disclosed in the  FIGS. 19-26 . 
     Whenever possible the individual elements of the second example are numbered with the same number as in the first example, however, having the number “1” or “10” in front. The same apply for elements performing the same or similar activity. 
     As in  FIG. 9  the second example is disclosed in an exploded view in  FIG. 20 . 
     As disclosed the housing  1003  is made up from three housing parts; a distal cartridge holder part  1003   a  holding a cartridge  1105 , a proximal housing part  1003   b  which at its most proximal end is provided with a dose setting button  1004  and an intermediate housing part  1007  connecting the cartridge part  1003   a  and the proximal housing part  1003   b.  The cartridge holder part  1003   a  is further, in the non-use situation, covered by a removable cap  1002 . 
     The intermediate housing part  1007  is further provided with a distal extension  115  which will be explained later and a proximal extension  116 . The proximal extension  116  has at its most proximal end a pointer which will appear in the scale window  1005  when the housing  1003  is assembled (best seen in  FIG. 21-22 ). Further, the proximal extension  116  can carry an inwardly pointing thread segment  117  for engaging the external thread  161  on the scale drum  160 . 
     The proximal housing part  1003   a  is provided with two opposite located openings  1006  (one of which is depictured in  FIG. 20 ) into which two frames  111  are press fitted. One or both of these frames  111  are internally provided with a holding mechanism  1009  for holding the neck part  1108  of the cartridge  1105 . The proximal end  1109  of the cartridge  1105  is secured against the partition  1008  of the intermediate part  1007  such that the cartridge  1105  is fixed in the housing  1003 . 
     Movable relatively to the housing  1003  is the shield  120  which cover the injection needle during injection and the needle holder  130  having connecting means  131  for securing an injection needle to the needle holder  130 . The needle holder  130  is further provided with a flexible arm  132  preventing proximal movement of the shield  120  relatively to the needle holder  130  when no injection needle is mounted on the needle holder  130 . 
     Further, a torsion spring A supplies the torque for performing an injection whereas a compression spring B urges the shield  120  in the distal direction and another compression spring C urges the needle holder  130  in the distal direction. 
     The torsion spring A is encompassed between the spring base  180  and the drive tube  170 . The spring base  180  is permanently fixed to the proximal housing part  1003   b  but could alternatively be moulded as an integral part of the housing  1003 . 
     The compression spring B is encompassed between a flange (or similar)  128  on the shield  120  and the internal partition  1008  of the intermediate housing part  1007 . The flange  128  could alternatively be a number of knobs supporting the spring B. 
     The compression spring C is made from a suitable polymer and is moulded as an integral part of the needle holder  130  and encompassed between the needle holder  130  and the partition  1008  of the intermediate housing part  1007 . The partition  1008  can e.g. be provided with a hole  114  for securing the moulded compression spring C. 
     The intermediate housing part  1007  further has an internal thread  110  through which the piston rod  140  is screwed forward when rotated. 
     A scale drum  160  for showing the size of the set dose is via an outside thread  161  threaded to the proximal housing part  1003   b  or to the threaded segment  117  of the proximal extension  116  of the intermediate housing part  1007  (or it can be threaded to both as a security measure) such that the scale drum  160  moves helically when rotated. Internally the scale drum  160  is provided with a raised bar  162  axially guided in a corresponding axial groove or the like  172  provided externally on the drive tube  170 . The raised bar  162  and axial groove  172  engagement could of cause be vice versa in respect of the parts. 
     The scale drum  160  is further provided with a hook  163  which holds the shield  120  in its retraced position when the scale drum  160  is in its most distal position i.e. when no dose is set. 
     The proximally provided dose setting button  1004  is internally rotatable connected to the ratchet element  185  such that rotation of the dose setting button  104  is transformed into rotation of the ratchet element  185 . The ratchet element  185  is urged in the distal direction by a compression spring D provided between the proximal end of the ratchet element  185  and the dose setting button  1004 . This spring D is preferably moulded integrally with the ratchet element  185  as depictured in  FIG. 19 . The dose setting button  1004  is further rotatable connected to the housing  1003  such that it can rotate relative to the proximal housing part  1003   b  but not move axially. 
     The ratchet element  185  is further provided with a ratchet arm  186  which engages an internally toothing  181  provided internally in the spring base  180 . The engagement of the ratchet arm  186  with the internal toothing  181  prevents the ratchet element  185  from counter rotating. However, the dose setting button  1004  is internally provided with a protrusion  1010  ( FIG. 19 ) which can move the ratchet arm  186  inwardly when the dose setting button  1004  is rotated oppositely to lower the set dose. In this way the ratchet element  185  can rotate step by step in the opposite direction during dial-down of the dose and under influence of the torsion spring A. 
     Dose Setting 
     When setting a dose, as depictured in  FIG. 21 , the user simply rotates the dose setting button  1004  which in turn rotates the ratchet element  185 . Rotation of the ratchet element  185  is transferred to a rotation of the drive tube  170  as the inner toothed surface  174  of the drive tube  170  is in engagement with the outer tooting  187  provided on the ratchet element  185 . The rotation of the drive tube  170  strains the torsion spring A. The torque build up in the torsion spring A is held by the engagement of the ratchet arm  186  with the internal toothing  181  of the spring base  180 . 
     The scale drum  160  rotates together with the drive tube  170  such that the user can view the set dose through the window  105  provided in the proximal housing part  103   b.    
     Once the scale drum  160  is rotated away from its “zero” position the hook  163  is rotated out of its engagement with the indentation  123  (see  FIG. 23-26 ) provided on the shield  120  which is then urged distally by the compression spring B. 
     The needle holder  130  is further urged forward by the compression spring C such that the back-end of the injection needle is maintained outside the septum  1106  of the cartridge  1105  when not injecting. 
     Injecting 
     In order to inject the set dose, the distal end of the shield  120  is pressed against the skin of the user. 
     When the user starts to press the shield  120  against the skin, the front-end  103  of the injection needle  100  penetrates through the skin while the back-end  104  of the injection needle is out of contact with the septum  1106  of the cartridge  1105  as the needle holder  130  is in its distal position. In this position, the needle holder  130  is prevented from moving proximally by the engagement of the protrusion  134   a  carried on the flexible arm  134  against an inwardly pointing protrusion  113  (see  FIG. 20 ) provided on the frame  111 . 
     However, once the front-end  103  of the injection needle  100  is fully inserted into the skin as depictured in  FIG. 7.4 , the shield  120  will force the protrusion  134   a  out of its engagement with the inwardly pointing protrusions  113  of the frame  111  since the vertical protrusion  134   b  of the flexible arm  134  is guided in a track  126  in the shield  120 . The shape of this track  126  moves the protrusion  134   a  (via  134   b ) out of its engagement with the inwardly pointing protrusion  113  on the frame  111  where after the shield  120  and the needle holder  130  move axially together. 
     The shield  120  and needle holder  130  moves together since the protrusion  136  provided on the arm  135  locks to the hook  127  proximally provided on the shield  120 . Axial movement of the shield  120  is thus transferred to the needle holder  130 . This is best seen in  FIG. 23-24  which depictures the situation occurring during dose expelling and just before the scale drum  160  reaches its zero position. The hook  127  engages the protrusion  136  thus transferring axial movement of the shield  120  to axial movement of the needle holder  130 . 
     The arm  135  carrying the protrusion  136  is guided into position by the curved wall  129  leading up to the hook  127 . Oppositely the arm  135  is supported by the curved extension  115  on the intermediate housing part  1007 . 
     When the shield  120  is fully retracted, as depictured in  FIG. 7.5 , the back-end  104  of the injection needle  100  has penetrated through the septum  1106  and into the cartridge  1105  and the release of the dose will be activated. 
     Dose Release 
     Proximally on the needled holder  130  one or more release arms  137  are provided. These release arms  137  extent parallel with the flexible arm  135 . When the shield  120  and the needle holder  130  is in their proximal position, the release arms  137  moves the clutch  190  as depictured in  FIG. 22 . This brings the external toothing  191  on the clutch  190  into engagement with a similar toothing  174  provided internally in the drive tube  170  such that the drive tube  170  and the clutch  190  rotate together. 
     During dose setting, the ratchet element  185  rotates the drive tube  170  via the engagement of the externally provided toothing  187  engaging the toothing  174  internally in the drive tube  170 , see  FIG. 21 . 
     Further, during dose setting, the ratchet element  185  rotate together with the dose setting button  1004 , but during dosing both the dose setting button  1004  and the ratchet element  185  remains non-rotatable. When the clutch  190  is moved proximally by the arms  137 , the ratchet element  185  is also moved proximally against the bias of a proximally moulded spring arm D provided proximally on the ratchet element  185  and resting against an inside surface of the dose setting button  1004 . 
     This proximal movement of the ratchet element  185  releases the coupling between the toothing  174  of the drive tube  170  and the toothing  187  provided on the ratchet element  185  such that the drive tube  170  is free to rotate under influence of the torque of the torsion spring A. 
     The rotation of the drive tube  170  is transferred to a rotation of the clutch  190  by the coupling between the internal toothing  174  on the drive tube  170  and the toothing  191  externally and proximally on the clutch  190 . 
     I.e. when the clutch  190  slides proximally (moves from the position in  FIG. 21  to the position of  FIG. 22 ) the toothing  174  of the drive tube  170  releases the engagement with the toothing  187  of the ratchet element  185  and couples to the toothing  191  of the clutch  190 . 
     A further toothing  171  is also provided internally in drive tube  170 , which toothing  171  operates against click arms  188  provided externally on the ratchet element  185  to provide dose clicks during injection i.e. when the drive tube  170  rotate relatively to the ratchet element  185 . 
     Please note that in the  FIGS. 21-22  part of the clutch  190  is not visible due to the cross sectional view. However, the clutch  190  is fully depictured in  FIG. 19   
     Further, the rotation of the clutch  190  is transferred to a rotation of the piston rod guide  150  as the toothed outer surface  151  of the piston rod guide  150  is in engagement with the internal toothing  194  of the clutch  190  when the clutch  190  is moved proximally during dosing as disclosed in  FIG. 22 . 
     As seen in  FIG. 21-22  this internal toothing  194  of the clutch  190  is in engagement with a toothing  118  on the intermediate housing member  1007  when the injection device is not activated. 
     The rotation of the piston rod guide  150  is transferred to a rotation of the piston rod  140  as the piston rod guide  150  engages a longitudinal track in the piston rod  140 . 
     Pressure Relief 
     The pressure relief mechanism is similar to the one disclosed in EP 12-188471 by Novo Nordisk NS and serves the purpose of allowing axial movement of the rubber plunger  1107  of the cartridge  1105  and thus also of the piston rod  140 . Such axial movement of the rubber plunger occurs e.g. as a result of temperature variations. 
     The pressure relief mechanism comprises of the clutch  190 , the piston rod guide  150 , a click element  165  and a leaf spring E. 
     If the liquid drug inside the cartridge  1105  expands due to increasing temperatures, the piston rod  140  will be forced proximally by the rubber plunger  1107  inside the cartridge  1105 , which will push the piston rod foot  143  and thus the piston rod  140  proximally. This will generate a rotation of the piston rod  140  as the piston rod  140  is threaded to the thread  1008  of the intermediate part  1007 . 
     This will force the piston rod guide  150  to rotate as the piston rod guide  150  is keyed to the piston rod  140 . 
     The click element  165  is externally provided with a plurality of click fingers  166  which operates in a toothing  195  provided internally in the clutch  190 . This toothing  195  is adapted to prevent rotation of the click element  165  in one direction and adapted to have reluctance to rotation in the opposite direction (due to the inherent outwardly flexibility of the click fingers  166 ). 
     The direction having the reluctance is the one being used when the piston rod  140  move proximally as the temperature rises. 
     The leaf spring E is encompassed between the piston rod guide  150  and the click element  155  such that one leg of the leaf spring D is attached to the piston rod guide  150  and the other leg is attached to the click element  165  thus a torque will be introduced in the leaf spring E when the piston rod guide  150  and the click element  165  rotate relative to each other independently of the direction of this rotation. 
     When the piston rod  140  move proximately and the piston rod guide  150  rotates, the leaf spring E is tighten until the rotational reluctance of the click element  165  is overcome where after the click fingers  166  will move to the subsequent teeth of the toothing  195 . The result being that the piston rod guide  150  can perform an unlimited rotation in the expanding direction. 
     When the temperature decreases and the rubber plunger move distally the torque introduced in the leaf spring E will rotate the piston rod guide  150  since the toothing  195  prevents the click element  165  from rotation in this opposite direction. The result being that the piston rod  140  is rotated forward. 
     End-Of-Content 
     The End-of-Content mechanism is a so-called non-axial movable cycloid End-of-Content mechanism which is disclosed in details in EP 13-153628 by Novo Nordisk NS. 
     The End-of-Content mechanism comprises an End-of-Content ring  155  which internally rides on an outside surface of the clutch  190  and externally is connected to a toothed ring  175  provided inside drive tube  170  such that the End-of-Content ring  155  rotate when the drive tube  170  is rotated relatively to the clutch  190 . 
     During dose setting the drive tube  170  is rotated and the clutch  190  is static thus the End-on-Content ring  155  is rotated. During dosing the drive tube  170  and the clutch  190  rotate together thus maintaining the End-of-Content ring  155  in the same relative position. 
     Due to the cycloid gearing the End-of-Content ring  155  is rotated a greater angle for each angular rotation of the drive tube  170  thereby counting the rotational movement of the drive tube  170 . The total allowable angular movement of the End-of-Content ring  155  is predetermined such that the End-of-Content ring  155  encounters a stop just before the injectable content of the cartridge  1105  has been set. Once the End-of-Content ring  155  reaches its stop, the drive tube  170  cannot be rotated further thus no further dose can be set. 
     The End-of-Content mechanism thereby counting the accumulated set and ejected doses and stopping further dose setting when this accumulated value equals the initial injectable amount of liquid drug in the cartridge  1105 . 
     After Dosing 
     Following dose release the user removes the shield  120  from the skin as disclosed in  FIG. 7.8 . 
     This makes the needle holder  130  move distally under the influence of the compression spring C as depictured in  FIG. 23-24  such that the back-end  104  of the attached pen-needle  100  is pulled out of the septum  1106  of the cartridge  1105 . 
     As the scale drum  160  approaches its zero position as depictured in  FIG. 23-24 , the surface  164  on the scale drum  160  encounters the protrusion  136  and pushes it out of its engagement with the hook  127  such that the needle holder  130  can move distally independently of the shield  120 . 
     To make sure that the needle holder  130  do not return until the shield  120  has been fully removed from the skin of the user, the protrusion  136  is hindered by axial movement by the supporting surface  115  until the shield  120  has moved a little distance in the distal direction (the distance is indicated by the arrow Z in  FIG. 23 ). The axial movement being the axial distance Z between hook  163  and indentation  123  seen in  FIG. 23 . Only when the shield  120  has moved to the hooked position ( FIG. 25 ) is the distance to the supporting surface  115  sufficient to allow the protrusion  136  to be fully released where after the needle holder  130  returns to its extended position. 
     Also following injection, the hook  163  provided on the scale drum  160  once again engages the indentation  123  provided proximately on the shield  120  thus preventing further axial movement of the shield  120  as depictured in  FIG. 24-25 . 
     This mechanism is further disclosed in European patent application No.: EP 13-170422 by Novo Nordisk NS. 
     Some preferred embodiments have been shown in the foregoing, but it should be stressed that the invention is not limited to these, but may be embodied in other ways within the subject matter defined in the following claims