Abstract:
The present invention concerns a dosing unit for an injection device ( 100 ) and an injection device incorporating the dosing unit. The dosing unit comprises a housing ( 102 ) extending along a longitudinal axis from a proximal housing end to a distal housing end, the distal housing end being adapted for connection with a variable volume reservoir, an injection mechanism for expelling a dose of a substance held in a connected variable volume reservoir, the injection mechanism being arranged at least partially in the housing ( 102 ) and comprising an injection button ( 157 ), a dose defining structure ( 140 ) configured to move from a start position to an end-of-dose position in response to a dose expelling operation of the injection button ( 157 ), and a piston rod ( 160 ) configured to move in a dose delivery direction from a first position to a second position in response to a movement of the dose defining structure ( 140 ) from the start position to the end-of-dose position, and a dose delivered indicator ( 109 ) configured to move axially in a distal direction from a dose ready position to a dose delivered position in response to the movement of the dose defining structure ( 140 ) from the start position to the end-of-dose position, wherein during movement from the dose ready position to the dose de livered position a portion of the dose delivered indicator ( 109 ) emerges increasingly from the distal housing end.

Description:
FIELD OF THE INVENTION 
       [0001]    The present invention relates to dose delivery devices for administration of medicinal substances. 
       BACKGROUND OF THE INVENTION 
       [0002]    Most modern devices for multiple dose delivery of pharmaceutical substances comprise a dose setting mechanism that allows a user to selectively set a dose to be dispensed from a substance containing reservoir. Some treatment regimens require setting and administration of a dose of drug that varies over time, whereas other treatment regimens require repeated setting and administration of a fixed dose of drug. In some cases the fixed dose may need to be adjusted over time, for example during a dosage titration period. 
         [0003]    A common type of drug delivery device is the so-called pen injector which is a pen-shaped injection device used for intermittent subcutaneous administration of an active agent. Typically, such a pen injector allows the user to turn a dial about a general longitudinal axis to set a desired dose. If by accident too high a dose is set the dial may be reversed and the dose dialled down until the correct dose is reached. A pen injector may be a purely mechanical construction or it may be an electro-mechanical device, e.g. comprising an electronic memory module. 
         [0004]    To be in compliance, as well as to avoid overdosing, it is important to pay particular attention during the dose setting procedure. In everyday life a busy schedule may give rise to negligence towards the various preparations leading up to a drug administration, in particular for people who are seasoned in self-administration. If the device used for administration of the drug does not offer an automatic storing of the ejected dose an inattentive user may be left in doubt after the administration as to the size of the dose actually received. 
         [0005]    Accordingly, for drug delivery devices of the type which do not have an electronic memory it is desirable to provide a solution that enables the user to see, subsequent to a dose administration, which dose was just delivered from the device. 
         [0006]    U.S. Pat. No. 3,905,366 (Callahan et al.) discloses a syringe for injection of medicinal liquids which syringe has means for determining the quantity delivered during injection. The syringe has a scale and a comparison mark arranged for relative displacement so that they may be reset to zero before each injection so as to permit a determination of each dose. For example, a scale carrier is slidably arranged on a vial adapted for insertion into a syringe frame such that the zero value may be brought in line with the front edge of a piston before an injection is commenced. 
         [0007]    The position of the front edge of the piston relative to the scale after the injection thus directly informs the user of the dose expelled. However, the reliability of this dose expelled indication stands or falls with the precision with which the user positions the scale relative to the piston in the first place. An inattentive user may position the scale such that the zero value is somewhat offset from the front edge of the piston, inevitably resulting in a misleading post dose reading. 
         [0008]    US 2012/0046613 (Sanofi-Aventis Deutschland GmbH) discloses a more modern type of drug delivery device in the form of a cartridge based pen injector. A piston in the cartridge is movable by a piston rod to expel doses of a contained drug. The piston rod is provided with consecutive numbers along its axis to indicate, through a window aperture in the device housing, delivered dose or remaining dose left in the cartridge. 
         [0009]    While this device allegedly provides for an indication of a delivered dose because a dose related number on the piston rod is visible through the window aperture when the piston rod is halted, it appears that after the very first delivered dose indication every subsequent indication will reflect an accumulated dose rather than a delivered dose, as the piston rod successively advances in the cartridge, driving the piston towards the distal end thereof. This means that for each subsequent dose administration the user is required to remember the previously displayed number and to subtract this previously displayed number from the currently displayed number to obtain the indication of the dose delivered. Furthermore, since the dose related numbers are arranged on the piston rod and the piston rod only moves in one direction for the emptying of the cartridge it appears impossible with this construction to reset the numbers providing the dose related indication such that every post dose indication directly reflects the dose delivered. 
       SUMMARY OF THE INVENTION 
       [0010]    It is an object of the invention to eliminate or reduce at least one drawback of the prior art, or to provide a useful alternative to prior art solutions. 
         [0011]    In particular, it is an object of the invention to enable the provision of a drug delivery device offering a dose expelled indication which incontestably reflects an actually delivered dose, regardless of the level of attention of the user during setting and/or administration of the dose. 
         [0012]    It is a further object of the invention to provide such a device which consistently conveys a direct indication of the dose delivered, i.e. which enables a post dose reading of the just delivered dose after each dose administration. 
         [0013]    In the disclosure of the present invention, aspects and embodiments will be described which will address one or more of the above objects and/or which will address objects apparent from the following text. 
         [0014]    In a drug delivery device embodying the principles of the invention and comprising a housing extending along a longitudinal axis, and a dose delivery mechanism for delivering drug from a variable volume reservoir, the dose delivery mechanism comprises an actuator movable in a dose delivery direction from a first position to a second position in order to effect delivery of a dose of the drug, and a dose delivered indicator operatively coupled with the actuator during dose delivery and configured to move axially in a distal direction from a dose ready position to a dose delivered position in correlation with the actuator&#39;s movement from the first position to the second position, and at least during a final part of the distal movement of the dose delivered indicator a portion thereof extends from the housing. At least one dose related indicium may be arranged immovably with respect to the housing, whereby the dose delivered indicator visibly changes position relative to the at least one dose related indicium during movement from the dose ready position to the dose delivered position. 
         [0015]    The drug delivery device may e.g. be an injection device for delivering a bolus dose of drug, an infusion device for delivering a dose of drug over a prolonged period of time, an inhaletion device for delivering a dose of drug to the respiratory system, or indeed any type of drug administration device capable of expelling a substance from a variable volume reservoir. 
         [0016]    In one aspect of the invention a dosing unit for an injection device as defined by claim  1  is provided. 
         [0017]    A dosing unit is thus provided comprising: a housing extending along a longitudinal axis from a proximal housing end to a distal housing end, where the distal housing end is adapted for being connected with a variable volume reservoir (such as e.g. a cartridge with a slidable piston and a self-sealing penetrable septum, or a pouch), and an injection mechanism for expelling a dose of substance from the variable volume reservoir, when the variable volume reservoir is connected with the distal housing end. The injection mechanism comprises an injection button, e.g. protruding from the proximal housing end, a dose defining structure which is adapted to move from a start position to an end-of-dose position in response to a specific operation of the injection button, and a piston rod adapted to move in a dose expelling direction from a first position to a second position in response to a movement of the dose defining structure from the start position to the end-of-dose position. The specific operation of the injection button (which may e.g. include a depression of the injection button against the housing) can thus be termed a dose expelling operation, as the movement of the piston rod from the first position to the second position is configured to reduce the volume of a variable volume reservoir connected with the housing and accordingly cause an expelling of substance therefrom. 
         [0018]    An injection mechanism as the above described is commonly known in various forms in the art of injection devices. For example, in WO 2009/092807 a dose defining structure is disclosed which comprises a piston rod drive element that, responsive to a depression of an injection button and a resulting release of a spring, moves along the longitudinal axis of the injection device from one plateau to another, slaving the piston rod. The distance between the two plateaus thus defines the size of the dose being expelled. In WO 2006/045528 a rotatable piston drive member causes a specific helical advancement of a piston rod which is determined by the respective start and end positions of a helically displaceable dose indicator barrel being coupled thereto. The drive member rotates automatically when a torsion spring is released by manipulation of a dedicated locking member. Further examples are disclosed in e.g. WO 99/38554, WO 2005/039676 and WO 2012/089616. 
         [0019]    The dosing unit further comprises a dose delivered indicator which is configured to move axially in a distal direction (i.e. away from the proximal housing end) from a dose ready position, in which a dose of drug is ready to be expelled, to a dose delivered position, in which the dose of drug has been expelled, in response to the movement of the dose defining structure from the start position to the end-of-dose position. During the movement from the dose ready position to the dose delivered position a portion of the dose delivered indicator emerges increasingly from the distal housing end. 
         [0020]    The emergence of the dose delivered indicator from the distal housing end is a verification that the piston rod has actually undergone a movement in the dose expelling direction relative to the housing, and the degree of visibility of the dose delivered indicator is directly correlated with the distance travelled by the piston rod, enabling an estimation or a determination of the dose expelled from a connected variable volume reservoir. 
         [0021]    The dose delivered indicator may form part of the injection mechanism and be operatively coupled with the piston rod during dose expelling such that a driving force is imposed on the piston rod in response to the dose delivered indicator undergoing relative motion with respect to the housing. For example, rotational motion may be imparted to the piston rod, e.g. via an intermediate component, when the dose delivered indicator undergoes translational motion relative to the housing. In that case the piston rod may be threadedly engaged with a nut member arranged fixedly in the housing, whereby the rotational motion is converted to a helical advancing motion relative to the housing. 
         [0022]    If the dose delivered indicator forms part of the injection mechanism a minimum number of components is needed to obtain the post dose indication. 
         [0023]    The dosing unit may be designed for manual or automatic actuation of the piston rod. In case of the latter, an energy providing unit, such as e.g. a spring structure, may be arranged to bias the dose delivered indicator in the distal direction. Such an energy providing unit may then be activatable to convey stored energy to the piston rod and thereby cause a dose expelling which is practically effortless to the user. 
         [0024]    The dosing unit may be adapted to form part of an injection device of the prefilled and disposable type, i.e. where a variable volume reservoir, such as a cartridge, is permanently coupled with the housing, or of the loadable, e.g. re-useable type, i.e. where a variable volume reservoir, such as a cartridge, can be coupled with the housing by a user in a repeatable manner, e.g. via a displaceable reservoir holder adapted to receive and releasably retain the variable volume reservoir. The injection device may even be a single shot injector which is configured to deliver only one, predetermined (e.g. by the manufacturer) or settable, dose of drug from a pre-coupled or loaded variable volume reservoir. 
         [0025]    At least one dose related indicium, such as e.g. a number or a line or a colour change, may be provided on the portion of the dose delivered indicator which emerges increasingly from the distal housing end during the movement of the dose delivered indicator from the dose ready position to the dose delivered position. This will enable the user to verify that a certain dose has been expelled. For example, if the injection device is a fixed dose device capable of expelling one or more doses of a predetermined size a single line or a similar form of indication may be arranged on the dose delivered indicator at a position which becomes visible exteriorly of the housing only when the predetermined dose has been expelled. 
         [0026]    In particular embodiments of the invention, e.g. related to dosing units for injection devices which offer setting and delivery of a plurality of different doses, the at least one dose related indicium comprises a scale which indicates progression in the proximal direction. The scale is provided on the portion of the dose delivered indicator which is able to emerge increasingly from the distal housing end and is arranged in correlation with the resulting distance travelled by the piston rod. Hence, as the dose delivered indicator emerges increasingly from the distal housing end during dose expelling the scale displays indicia which indicate a gradual increase of the dose delivered. At the end of the dose delivery the scale may e.g. be used to directly read off a number which then corresponds to the size of the dose that was expelled. 
         [0027]    The dose delivered indicator may further be movable from the dose delivered position to the dose ready position. During this reverse movement the dose delivered indicator is decoupled from the piston rod, whereby the actuator remains in position while the dose delivered indicator is being reset. This feature is especially useful if the dosing unit is for use in a multishot injection device which is capable of expelling a plurality of doses from a pre-coupled or loaded variable volume reservoir, because it provides for a direct indication of the last delivered dose after each dose administration, which is far more convenient to the user than indications of accumulated doses, as the user needs neither remember the last indicated number during the dose administration nor subtract it subsequently from the new indicated number. 
         [0028]    The dosing unit may further comprise a dose setting mechanism for defining the extent of movement of the piston rod from the first position to the second position. The dose setting mechanism may comprise the dose defining structure and a dose setting button operable to move the dose defining structure relative to the housing, e.g. to bring the dose defining structure to the start position. The dose defining structure may comprise dose setting indicia for indicating the size of a set dose, and the housing may comprise a window for inspection of at least one of the dose setting indicia at a time. In particular embodiments of the invention the dose defining structure comprises a scale drum having the dose setting indicia arranged helically on an exterior surface portion. 
         [0029]    At least a subset of the dose setting indicia may successively pass by the window during dose delivery, thereby continuously indicating a remaining dose to be delivered. This allows the user to verify that the dose delivery is progressing properly. 
         [0030]    In another aspect of the invention an injection device is provided comprising a dosing unit as described above, a variable volume reservoir comprising an outlet and a movable wall, such as e.g. a cartridge sealed by a penetrable self-sealing septum and a slidable piston, and a reservoir holder for retaining the variable volume reservoir in an axially fixed position relative to the distal housing end, in which position the piston rod abuts the movable wall. 
         [0031]    The increasing emergence of the dose delivered indicator from the distal housing end allows the user to visually inspect the progression of the dose expelling from the variable volume reservoir. In the end-of-dose position the dose has been expelled completely (or as completely as physically possible), and the position, or the extent, of the visible portion of the dose delivered indicator serves to indicate that the dose expelling has been successfully carried out (in case the variable volume reservoir is an elastomeric piston the entire dose may not be completely expelled until a few seconds after the dose delivered indicator has reached the end-of-dose position and the piston, which is being compressed during its advancement, has relaxed). Hence, notably, the degree of visibility of the dose delivered indicator correlates with the amount of drug having been expelled from the variable volume reservoir. This also enables the user to check if the intended dose has actually been delivered, or if e.g. a clogging of the fluid pathway from the variable volume reservoir to the injection site has occurred. 
         [0032]    The reservoir holder may be a separate element which is configured for axial fixation with respect to the distal housing end, and which is capable of receiving and axially fixing the variable volume reservoir with respect to the housing, e.g. like a cartridge holder known in the art of pen injection devices for the treatment of diabetes. Such a cartridge holder is typically provided with a cartridge receiving space and a needle mounting portion for receiving a needle assembly in such a manner that a portion of an injection needle penetrates the self-sealing septum of the cartridge when the needle assembly is mounted on the needle mounting portion. Alternatively, the reservoir holder may be integrated in the housing. 
         [0033]    The injection device may further comprise at least one dose delivered indicium arranged on the variable volume reservoir, or on the reservoir holder. The at least one dose delivered indicium is immovably positioned distally of the distal housing end, when the variable volume reservoir is connected with the housing, so as to allow the user to inspect the relative position of the dose delivered indicator and the at least one dose delivered indicium following a dose delivery procedure. 
         [0034]    The at least one dose delivered indicium may comprise a line, a numeral, a letter, a colour change, or any other visible and/or tactile indication. The at least one dose delivered indicium may be arranged to be approached, and potentially reached, by a portion of the dose delivered indicator, such as e.g. the end portion of the dose delivered indicator, during the distal movement of the dose delivered indicator from the dose ready position to the dose delivered position. In case a scale is provided on the dose delivered indicator the at least one dose delivered indicium may be arranged to provide for a reading of the scale. 
         [0035]    Particularly, the at least one dose delivered indicium may comprise a dose delivered scale arranged on the variable volume reservoir or on the reservoir holder, the dose delivered scale indicating progression in the distal direction, and the dose delivered indicator may be configured to slide along the dose delivered scale during its movement from the dose ready position to the dose delivered position. Thereby, the dose delivered indicator serves as a bar which indicates a level on the dose delivered scale that corresponds to the dose having been expelled from the variable volume reservoir. Thereby, a mechanical dose expelled indicator is provided which is intuitively read as it resembles the well-known mercury-in-glass thermometer. 
         [0036]    The dose delivered scale may comprise numerals indicating a range which corresponds to, e.g. equals, the range indicated by the dose setting indicia on the dose defining structure. This will provide a complete correspondence between the scale used for the dose setting and the scale used for the reading of the delivered dose. 
         [0037]    In some embodiments of the invention the reservoir holder comprises a body which extends distally from the distal housing end along the longitudinal axis, and a longitudinal groove in the body which groove is configured for sliding reception of the dose delivered indicator. Such a solution provides for a slender injection device construction which may be attractive to some users. 
         [0038]    The injection device may further comprise a protective cap mountable onto, and dismountable from, the housing. The protective cap may be structured to interface with the dose delivered indicator and move the dose delivered indicator from the dose delivered position to the dose ready position during mounting of the protective cap onto the housing after dose delivery. Thereby, since the mounting of the protective cap following a dose administration is part of the customary handling procedure for this type of drug delivery device an automatic resetting of the dose delivered indicator is obtained without an introduction of any additional handling steps. 
         [0039]    For example, the protective cap may be adapted to be mounted onto the distal housing end to cover the variable volume reservoir and/or the reservoir holder. The mounting of the protective cap onto the distal housing end may involve at least a relative axial motion between the protective cap and the housing, such as e.g. a relative translation or a relative helical motion. The protective cap may comprise a first interface portion and the dose delivered indicator may comprise a second interface portion adapted for interaction with the first interface portion during a portion of the at least a relative axial motion between the protective cap and the housing. In particular, the first interface portion may comprise a rim, and the second interface portion may comprise a distal abutment surface, whereby the rim will abut the distal abutment surface and urge the dose delivered indicator proximally during mounting of the protective cap onto the distal housing end. 
         [0040]    In the present context the term “piston rod” denotes an actuator device of the type commonly known in the art of injection devices, i.e. an elongated structure capable of exerting a driving force on a movable wall of a reservoir. It is emphasized that the “piston rod” may include a distal coupling element, sometimes referred to in the art as a “piston rod foot” or a “piston washer”. 
         [0041]    Further, in the present context, any statement related to the cap being mounted on or onto the housing should be interpreted to cover both the cap being mounted on or onto the housing and the cap being mounted on or onto a part coupled with the housing, such as e.g. a reservoir holder. When the cap is mounted onto the distal housing end it means that the cap is mounted onto the housing at the distal housing end. 
         [0042]    In the present specification, reference to a certain aspect or a certain embodiment (e.g. “an aspect”, “a first aspect”, “one embodiment”, “an exemplary embodiment”, or the like) signifies that a particular feature, structure, or characteristic described in connection with the respective aspect or embodiment is included in, or inherent of, at least that one aspect or embodiment of the invention, but not necessarily in/of all aspects or embodiments of the invention. It is emphasized, however, that any combination of the various features, structures and/or characteristics described in relation to the invention is encompassed by the invention unless expressly stated herein or clearly contradicted by context. 
         [0043]    The use of any and all examples, or exemplary language (e.g., such as, etc.), in the text is intended to merely illuminate the invention and does not pose a limitation on the scope of the same, unless otherwise claimed. Further, no language or wording in the specification should be construed as indicating any non-claimed element as essential to the practice of the invention. 
     
    
     
       BRIEF DESCRIPTION OF THE DRAWINGS 
         [0044]    In the following the invention will be further described with references to the drawings, wherein 
           [0045]      FIG. 1  is a perspective view of a portion of an injection device according to an embodiment of the invention, 
           [0046]      FIG. 2  is a perspective view detailing elements of a drive mechanism in the injection device, 
           [0047]      FIGS. 3-7  are perspective views of the portion of the injection device in different states during use, and 
           [0048]      FIGS. 8 a - c    are perspective views of the entire injection device in different states during an injection. 
       
    
    
       [0049]    In the figures like structures are mainly identified by like reference numerals. 
       DESCRIPTION OF EXEMPLARY EMBODIMENTS 
       [0050]    When in the following relative expressions, such as e.g. “upwards” and “downwards” and “clockwise” and “counter-clockwise”, are used these refer to the appended figures and not necessarily to an actual situation of use. The shown figures are schematic representations for which reason the configuration of the different structures as well as their relative dimensions are intended to serve illustrative purposes only. 
         [0051]      FIG. 1  is a perspective view of a portion of an injection device  100  according to an embodiment of the invention, specifically of a proximal portion of the injection device  100 , carrying a dose engine. The injection device  100  is in a pre-use state and portions of some elements thereof have been removed from the figure to provide a detailed overview of the construction. 
         [0052]    The injection device  100  is of the so-called pen injector type and has a tubular housing  102  extending along a longitudinal general axis and accommodating a number of functional components. The housing  102  is coupled with a drug containing cartridge (not shown) in a manner conventionally known in the art, i.a. meaning that the cartridge during use of the injection device  100  is at least axially fixed with respect to the housing  102 . Central to the function of the injection device  100  is an axially extending piston rod  160  which is in threaded engagement with a nut  162  that is both axially and rotationally fixed in the housing  102 . 
         [0053]    The distal end portion of the piston rod  160  is coupled to a piston (not shown) in the cartridge such that any advancing axial motion of the piston rod  160  is transferred to the piston, essentially for pressurisation of the cartridge, as is also conventionally known in the art. 
         [0054]    It is noted that all rotational movements described in the below and referred to as clockwise or counter-clockwise are described as seen from the distal end of the piston rod  160  (i.e. from left to right in  FIG. 1 ). 
         [0055]    The housing  102  is provided with an interior thread  128  which cooperates with an exterior helical track segment  142  on a scale drum  140 , allowing the scale drum  140  to undergo a well-defined helical motion in the housing  102 . The scale drum  140  carries a plurality of dose indicia  141  for indicating to a user the particular size of a set dose. The dose indicia  141  are successively viewable through a window  199  in the housing  102  when the scale drum  140  travels along the interior thread  128  e.g. from a proximal “zero dose” position to a distal “maximum dose set” position. The proximal “zero dose” position is defined by a proximal stop surface (not visible) providing a rotational stop for proximal motion of the scale drum  140  at the proximal end of the interior thread  128 , whereas the “maximum dose set” position is defined by a distal stop surface (not visible) providing a rotational stop for distal motion of the scale drum  140  at the distal end of the interior thread  128 . 
         [0056]    The scale drum  140  is rotationally locked to a dial  130  via a longitudinal interior projection  144  (see  FIG. 4 ) and an axially extending spline  135  on the exterior surface of the dial  130 . While rotationally interlocking the scale drum  140  and the dial  130  this splined connection allows relative axial motion between the two. The dial  130  is at its distal end portion axially locked to a coupling piece  173  which comprises an axially aligned leg  171  with a radially inwardly facing toothed surface  172 . At the proximal end portion of the dial  130  a push button  157  is arranged, which is axially locked to but rotationally decoupled from the dial  130 , and the two together serve as an injection button. Further, a sleeve  131  extends axially from an inner end face  103  of the dial  130 . The sleeve  131  has a toothed inner surface and is configured to be brought into and out of rotational interlocking engagement with a toothed end portion  122  of a dose preparation tube  120  which extends axially within the housing  102 . 
         [0057]    The dose preparation tube  120  has a threaded end portion  123  opposite the toothed end portion  122 . The threaded end portion  123  interfaces with a drive nut  195  in a non-self-locking thread engagement. The drive nut  195  forms part of an actuation rod  109 , the function of which will be described in detail below. The actuation rod  109 , which is axially displaceable but rotationally fixed with respect to the housing  102 , has a longitudinal extension  196  which ends in an abutment face  197 . The longitudinal extension  196  is transversally offset from a main portion of the actuation rod  109  and is adapted to slide along a cartridge holder (not shown in  FIG. 1 ) both during dose delivery and dose preparation. The cartridge holder is attached to a distal portion of the housing  102  and serves to hold and protect the cartridge in a manner conventionally known in the art. 
         [0058]    A pre-tensioned compression spring  150  is arranged to act between the inner end face  103  and the actuation rod  109 , constantly biasing the dial  130  and the push button  157  proximally, out of the housing  102 , and the actuation rod  109  distally. In the shown pre-use state of the injection device  100  distal motion of the actuation rod  109  is prevented by a lock member  180  abutting a transversal surface  198  of the actuation rod  109 . The lock member  180  is pivotally arranged on the nut  162  but is in  FIG. 1  prevented from pivoting by an edge portion of a button coupling rod  175  which is axially displaceable but rotationally fixed with respect to the housing  102 . The button coupling rod  175  has a toothed straight edge  178 , which is in engagement with a transmission wheel  170 , and a longitudinal extension  176 , which is transversally offset from the toothed straight edge  178  and which ends in an abutment face  177 . The transmission wheel  170  is further in engagement with the toothed surface  172 , such that the coupling piece  173 , the button coupling rod  175 , and the transmission wheel  170  together provide a double rack and pinion drive. 
         [0059]    In the present situation, given that the actuation rod  109  is prevented from undergoing distal motion in the housing  102  due to the lock member  180 , the bias of the spring  150  on the dial  130  causes the dial  130  to exert a pulling force on the coupling piece  173  which then via the double rack and pinion structure is converted to a distal movement of the button coupling rod  175 , unless a counter-acting force is applied to the abutment face  177 . Although not shown in  FIG. 1 , in the depicted pre-use state of the injection device  100  a removable protective cap is securely mounted onto a cap receiving portion at the distal end portion of the housing  102  such that a portion of the cap abuts the abutment face  177  and resists the bias conveyed to the longitudinal extension  176 , thereby maintaining the button coupling rod  175  in position. The injection device  100  is thus in fact stably locked in a tensioned state. As will be explained in more detail below once the retaining force on the abutment face  177  is removed the relaxation of the spring  150  will cause the dial  130  and the push button  157  to translate proximally. A stop surface  136  on the dial  130  limits the proximal motion of the dial  130  and the push button  157  relative to the housing  102 . 
         [0060]      FIG. 2  is a detailed view of the piston rod advancement mechanism as employed in the injection device  100 . A rotatable piston rod guide  163  couples the nut  162  and the dose preparation tube  120  via an inner groove  167  for axial interlocking connection with the nut  162  and an inner groove  168  for axial interlocking connection with the threaded end portion  123 . The piston rod guide  163  has a distal pawl  164 , which in combination with a plurality of circumferentially spaced apart indentations  187  on the nut  162  provide a distal ratchet mechanism, and a proximal pawl  166  which in combination with a plurality of circumferentially spaced apart indentations  126  on the dose preparation tube  120  provide a proximal ratchet mechanism. The distal ratchet mechanism allows clockwise rotation of the piston rod guide  163  relative to the nut  162  but prevents counter-clockwise rotation of the piston rod guide  163 . The proximal ratchet mechanism allows relative rotation between the dose preparation tube  120  and the piston rod guide  163  when the dose preparation tube  120  is rotated counter-clockwise, but prevents relative rotation between the dose preparation tube  120  and the piston rod guide  163  when the dose preparation tube  120  is rotated clockwise. The double ratchet comprised of the distal ratchet mechanism and the proximal ratchet mechanism thus allows the dose preparation tube  120  to drag the piston rod guide  163  along in the clockwise direction and to rotate freely in the counter-clockwise direction while the piston rod guide  163  remains stationary. 
         [0061]    The piston rod guide  163  further has a radially inwardly directed protrusion (not visible) for engagement with an axial groove  169  on the piston rod  160 . The piston rod  160  and the piston rod guide  163  are thus rotationally interlocked but capable of relative axial motion. 
         [0062]    The functionality of the dose setting and delivery mechanisms will now be described with reference to  FIGS. 3-7 . When taking the injection device  100  into use the protective cap is firstly removed. This removes the retaining force on the abutment face  177  and allows the spring  150  to expand. The spring  150  thus urges the dial  130  with the push button  157  proximally until the stop surface  136  abuts the interior end wall of the housing  102 , and the double rack and pinion drive accordingly forces the button coupling rod  175  a distance distally. The end result of this is illustrated by  FIG. 3 . 
         [0063]    The proximal motion of the dial  130  also causes the sleeve  131  to disengage from the toothed end portion  122 . The dial  130  is thus now capable of being rotated without affecting the dose preparation tube  120 . A dose is set by rotation of the dial  130  relative to the housing  102 . Due to the spline connection between the dial  130  and the scale drum  140  and the threaded interface between the scale drum  140  and the housing  102  when the dial  130  is dialled counter-clockwise the scale drum  140  displaces helically downwards in the housing  102  in response, and when the dial  130  is dialled clockwise the scale drum  140  displaces helically upwards in the housing  102 . In  FIG. 4  the dial  130  has been dialled to set a dose of “72” units. 
         [0064]    Dose delivery is executed by depression of the push button  157 , as illustrated in  FIG. 5 . The push button  157  may actually be depressed a certain distance without causing more than a reversed motion of the double rack and pinion drive and a compression of the spring  150 . A discontinuation of the depression force in this instance will simply cause the spring  150  to return the push button  157  to its proximal most position. However, once the button coupling rod  175 , during its proximal displacement, reaches a specific axial position in the housing  102  an end surface  179  passes the fulcrum of the lock member  180  and the lock member  180  will be free to pivot, whereby the pre-tensioned spring  150  will be released and as a result force the actuation rod  109  distally. As the lock member  180  pivots to allow passage of the actuation rod  109  the button coupling rod  175  becomes prevented from distal motion in the housing  102  due to the lock member  180  being prevented from returning to the original position by the actuation rod  109 . At this point if the user releases the pressure on the push button  157  the dial  130  will consequently be prevented from proximal motion and will thus stay inside the housing  102 . 
         [0065]    The depression of the push button  157  also leads to a rotational re-engagement of the sleeve  131  and the toothed end portion  122 . This happens before the flipping over of the lock member  180 , such that when the spring  150  is released and the actuation rod  109  is suddenly propelled distally the dial  130  and the dose preparation tube  120  are rotationally interlocked. Due to the threaded engagement between the drive nut  195  and the threaded end portion  123  the distal movement of the actuation rod  109  causes the dose preparation tube  120  to spin clockwise. 
         [0066]    The clockwise rotation of the dose preparation tube  120  causes a clockwise rotation of the piston rod guide  163 , due to the above described double ratchet mechanism, and thereby also of the piston rod  160 . The threaded engagement between the piston rod  160  and the nut  162  thus results in a helical advancement of the piston rod  160 , whereby the piston (not shown) is advanced axially in the cartridge (not shown) to expel a volume of drug through an attached injection needle (not shown). The volume expelled is determined by the position of the scale drum  140  in the housing  102  at the time of release of the spring  150  because the clockwise rotation of the dose preparation tube  120  also causes a clockwise rotation of the dial  130  and thereby of the scale drum  140 , and the rotation of the three continues until the scale drum  140  meets the proximal stop surface which defines the “zero dose” position. This end-of-dose state of the injection device  100  is illustrated in  FIG. 6 . 
         [0067]    It is noted that as the injection progresses the actuation rod  109  is moved further distally and the axial end position of the abutment face  197  corresponding to the “zero dose” position of the scale drum  140  is uniquely correlated with the distance travelled by the scale drum  140  from its position at release of the spring  150  to the proximal stop surface. 
         [0068]    In the end-of-dose state of the injection device  100  the push button  157  is prevented from proximal motion and therefore has to stay depressed in the housing  102 . Hence, it is not possible to set a dose at this point. It is common practice when handling injection devices to re-mount the protective cap following an injection. In the course of re-mounting the protective cap onto the cap receiving portion of the injection device  100  a portion of the cap, such as e.g. a segment of the cap rim or a protrusion, abuts the abutment face  197  and pushes the actuation rod  109  proximally with respect to the housing  102 . 
         [0069]    The resulting proximal movement of the drive nut  195  causes the dose preparation tube  120  to spin counter-clockwise, relative to the housing  102  but also relative to the piston rod guide  163  due to the double ratchet mechanism, so the piston rod  160  is left unaffected. The counter-clockwise rotation of the dose preparation tube  120  causes a corresponding counter-clockwise rotation of the dial  130  which leads to a downward helical displacement of the scale drum  140 . 
         [0070]    The proximal movement of the drive nut  195  also causes a compression of the spring  150  which is progressive until the actuation rod  109  reaches the axial position where the transversal surface  198  passes the fulcrum of the lock member  180 . At this position of the actuation rod  109  the lock member  180  is free to pivot and thus no longer functions as a block for distal motion of the button coupling rod  175 . So, as the spring  150  seeks to relax and constantly biases the inner end face  103  in the proximal direction, the dial  130  is urged proximally, pulling the coupling piece  173 , and the double rack and pinion drive consequently urges the button coupling rod  175  distally, causing the lock member  180  to flip over and abut the transversal surface  198 . The spring  150  will displace the dial  130  proximally a small distance until the abutment face  177  abuts the protective cap and further distal motion of the button coupling rod  175  thereby is prevented. This corresponds to the state of the injection device  100  shown in  FIG. 7 . In this state the lock member  180  stably prevents distal motion of the actuation rod  109 , as it is prevented from pivoting by the button coupling rod  175 . As long as the protective cap remains mounted on the cap receiving portion a depression of the push button  157  only leads to an additional compression of the spring  150  which has no effect on the secured injection mechanism. At termination of the push force the spring  150  will return to the slightly less compressed state shown in  FIG. 7 . 
         [0071]    Notably, when the protective cap is re-mounted on the cap receiving portion the actuation rod  109  is returned to the exact same axial position within the housing  102  that it initially assumed before the dose ejection was commenced. Due to the threaded interface between the drive nut  195  and the threaded end portion  123  this means that the dose preparation tube  120  is consequently returned rotationally to the exact same angular position relative to the housing  102  that it initially assumed before the dose ejection was commenced. The dose preparation tube  120  has thus during re-mounting of the protective cap undergone the exact opposite rotation to the one it underwent during the dose delivery, and since the dose preparation tube  120  and the dial  130  are rotationally interlocked so has the dial  130 . Consequently, due to the splined connection between the dial  130  and the scale drum  140  and the threaded connection between the scale drum  140  and the housing  102 , the scale drum  140  has been returned to the position it assumed immediately before the push button  157  was depressed and the spring  150  was released. In other words, by the re-mounting of the protective cap onto the cap receiving portion a setting of the last ejected dose has automatically been performed. 
         [0072]    In fact, every time the protective cap is mounted onto the cap receiving portion the dose preparation tube  120  will be returned, in the above described manner, to the initial angular position, which can be defined as a dose prepared position within the housing  102 , thereby bringing the injection device  100  in a “DOSE PREPARED” state. 
         [0073]    When the user dismounts the protective cap before the next injection the dial  130  and the push button  157  will re-protrude from the housing  102  and the sleeve  131  will disengage from the toothed end portion  122 , as described above in connection with  FIG. 3 . The user can now either choose to simply position the injection device  100  at the desired skin site and press the push button  157  to deliver the same dose as was last delivered, or adjust the dose size by turning the dial  130  in the appropriate direction before performing the injection procedure. 
         [0074]    In case the user chooses to adjust the dose, and thereby set a new dose, the scale drum  140  will change position within the housing  102  and assume a new position corresponding to the desired dose viewed through the window  199 . Because the dial  130  is decoupled from the toothed end portion  122  the repositioning of the scale drum  140  will not affect the dose preparation tube  120 . Only when the push button  157  is subsequently depressed and the sleeve  131  reengages with the toothed end portion  122  the scale drum  140  and the dose preparation tube  120  become coupled to undergo correlated movements relative to the housing  102 , provoked by the spring  150 , as previously described. During these correlated movements the scale drum  140  will again reach the “zero dose” position and abruptly stop further expansion of the spring  150  and distal motion of the actuation rod  109 . When this happens the axial end-of-dose position of the abutment face  197  relative to the housing  102  will be different from its previous end-of-dose position and, consequently, the dose preparation tube  120  will have undergone a different angular displacement than the one it underwent during the previous dose delivery. Nevertheless, when the cap is re-mounted on the cap receiving portion the actuation rod  109  will once again be returned to the same axial position as before, since that axial position is defined by the position of the cap portion abutting the abutment face  197  relative to the housing  102  when the cap is securely mounted. Due to the engagement between the drive nut  195  and the threaded end portion  123  the reversed motion of the actuation rod  109  will lead to a reversed motion of the dose preparation tube  120 , which will again lead to a reversed motion of the scale drum  140 . Thereby, the dose preparation tube  120  is returned to the exact same angular position relative to the housing  102  that it assumed before the dose ejection (the dose prepared position), and the scale drum  140  is returned to the position in which the new dose is viewed through the window  199 . 
         [0075]      FIGS. 8 a -8 c    show the entire injection device  100  in different states during dose setting and delivery with a view to further visualise the dose delivered indicator according to the present invention. A cartridge holder  114  is attached to the distal end of the housing  102 . The cartridge holder  114  carries a cartridge (not visible) which holds a volume of a medical substance. A needle hub  116  is attached to the distal end of the cartridge holder  114 . The needle hub  116  supports a double pointed injection needle  117  which in the current position provides for fluid communication with the interior of the cartridge, as conventionally known in the art. Numerals  148  are provided along the exterior surface of the cartridge holder  114 , together forming a post dose scale  149 . The post dose scale  149  is arranged next to an axial groove  119  that is angularly aligned with the longitudinal extension  196 . 
         [0076]      FIG. 8 a    depicts a situation just before depression of the push button  157 . Following removal of the cap (not shown) the dial  130  has been turned and a dose of “ 48 ” units has been set, as seen through the window  199 . The abutment face  197  is flush with the distal end of the housing  102  and therefore barely visible, indicating that no dose has been expelled. 
         [0077]      FIG. 8 b    depicts a situation after depression of the push button  157 , where the lock member  180  has flipped over to release the spring  150 , and an ejection of the medical substance through the injection needle  117  is ongoing. The actuation rod  109  is displaced distally under the force of the spring  150 , whereby the longitudinal extension  196  is slid distally in the axial groove  119 . Through the window  199  the user can see how many units are left of the administration. At the same time the post dose scale indicates the number of units already expelled during the current dose delivery, because the axial position of the abutment face  197  is correlated with the position of the scale drum  140 , as previously described. 
         [0078]    In  FIG. 8 c    the entire set dose has been delivered through the injection needle  117  and the scale drum  140  has reached the “zero dose” position. In this situation the post dose scale  149  reads “ 48 ” and thereby gives the user the opportunity to verify the size of the dose that was just delivered, a feature not previously available in all-mechanical injection devices. This opportunity provides an effortless additional control measure for the user to check her/his dose regimen compliance, a valuable extra tool to ensure that the dose received was within an acceptable range. When it comes to delivery of high potency drugs, such as e.g. insulin for the treatment of diabetes, it is crucial to avoid any uncertainty regarding the dosing. 
         [0079]    When the protective cap is being re-mounted over the cartridge holder  114  and secured to the cap receiving portion a portion of the cap abuts the abutment face  197  and causes the longitudinal extension  196  to slide proximally in the axial groove back to the position indicated in  FIG. 8   a.    
         [0080]    Apart from the dose delivered indicator and the automatic setting of the last ejected dose in response to a mounting of the protective cap the injection device  100  possesses a user interface which clearly indicates to its surroundings the possibilities of operation as well as a feed-forward to the next step in the use sequence. When the protective cap is on the injection device  100  the push button  157  is depressed which signals to the user that the system is “closed” or “passive” or “not to be operated”, simply because no operation of a dose setting button or an injection button is possible. When the protective cap is removed and the dial  130  emerges automatically from the housing  102 , carrying the push button  157 , this signals to the user that a following step is to either set or inject a dose of the medical substance (depending on whether an injection needle  117  is already in position on the cartridge holder  114 ). Both operators are ready for manipulation. When the push button  157  is eventually depressed to deliver a set dose the dial  130  is locked within the housing  102  due to the double rack and pinion drive and the arrangement of the lock member  180 , signalling to the user that no further operation is required in connection with the current dose delivery procedure. When the protective cap is re-mounted the dial  130  and the push button  157  remains substantially depressed, and the injection device  100  is again “passive”. 
         [0081]    Notably, in case the protective cap is off and the dial  130  protrudes from the housing  102  if the cap is re-mounted without the push button  157  having been depressed to release the spring  150  then the double rack and pinion drive will simply cause the dial  130  to move back into the housing  102  and thus re-establish the “closed” appearance of the injection device  100 . 
         [0082]    As is clear from the above the lock member  180  functions as a binary switch lock between the dose setting mechanism and the dose delivery mechanism in the sense that when the piston rod  160  is advanced during dose delivery no dose setting or adjustment is possible because the dial  130  is inoperably and inescapably contained within the housing  102 , and when the dial  130  protrudes from the housing  102  and is manipulable by the user the spring  150  is securely retained by the immovable actuation rod  109 , preventing any advancement of the piston rod  160 . 
         [0083]    The particular arrangement of the lock member  180 , the button coupling rod  175 , the actuation rod  109 , and the spring  150  guarantees that there are only two stable positions for the lock member  180 ; a position in which axial motion of the actuation rod  109  is allowed while proximal motion of the dial  130  is prevented, and a position in which axial (and rotational) motion of the dial  130  is allowed while distal motion of the actuation rod  109  is prevented. In the former position the lock member  180  is retained by the actuation rod  109  until the actuation rod  109  during proximal movement relative to the housing  102  reaches the position where the transversal surface  198  passes the fulcrum of the lock member  180 , at which point the lock member  180  pivots into locking abutment with the transversal surface  198  due to the distally directed force on the button coupling rod  175  provided by the spring  150  via the dial  130  and the double rack and pinion structure. In the latter position the lock member  180  is retained by the button coupling rod  175  until the button coupling rod  175  during proximal movement relative to the housing  102  reaches the position where the end surface  179  passes the fulcrum of the lock member  180 , at which point the lock member  180  pivots into locking abutment with the end surface  179  due to the distally directed force on the actuation rod  109  provided by the spring  150 .