Abstract:
The invention relates to an auto-injector for administering a dose of a liquid medicament, comprising:
       an elongate housing, a syringe with needle and a stopper,   a drive spring for pushing the needle from a covered position into an advanced position, for operating the syringe and for retracting the syringe,   activating means for locking or releasing the spring means. A retraction sleeve is axially movable arranged in the housing. The drive spring bears with its proximal end against a thrust face of a decoupling member. At least one resilient decoupling arm is arranged at the decoupling member for bearing against a first shoulder of the plunger. At least one aperture is arranged in the retraction sleeve allowing the decoupling arms to be flexed outward thus allowing the first shoulder to slip past the decoupling arm. The aperture is arranged to be angularly misaligned with respect to the decoupling arm and to rotate so as to align with the decoupling arms upon translation of the retraction sleeve out of the proximal position in distal direction.

Description:
CROSS REFERENCE TO RELATED APPLICATIONS 
       [0001]    The present application is a continuation application of U.S. patent application Ser. No. 13/807,041, filed Dec. 27, 2012 which is a 35 U.S.C. 371 National Application of PCT/EP2011/060505 filed Jun. 22, 2011, which claims priority to European Patent Application No. 10167492.7 filed Jun. 28, 2010 the entire contents of which are incorporated entirely herein by reference. 
     
    
     TECHNICAL FIELD 
       [0002]    The invention relates to an auto-injector for administering a dose of a liquid medicament according to the preamble of claim  1 . 
       BACKGROUND 
       [0003]    Administering an injection is a process which presents a number of risks and challenges for users and healthcare professionals, both mental and physical. 
         [0004]    Injection devices (i.e. devices capable of delivering medicaments from a medication container) typically fall into two categories—manual devices and auto-injectors. 
         [0005]    In a manual device—the user must provide the mechanical energy to drive the fluid through the needle. This is typically done by some form of button/plunger that has to be continuously pressed by the user during the injection. There are numerous disadvantages to the user from this approach. If the user stops pressing the button/plunger then the injection will also stop. This means that the user can deliver an underdose if the device is not used properly (i.e. the plunger is not fully pressed to its end position). Injection forces may be too high for the user, in particular if the patient is elderly or has dexterity problems. 
         [0006]    The extension of the button/plunger may be too great. Thus it can be inconvenient for the user to reach a fully extended button. The combination of injection force and button extension can cause trembling/shaking of the hand which in turn increases discomfort as the inserted needle moves. 
         [0007]    Auto-injector devices aim to make self-administration of injected therapies easier for patients. Current therapies delivered by means of self-administered injections include drugs for diabetes (both insulin and newer GLP-1 class drugs), migraine, hormone therapies, anticoagulants etc. 
         [0008]    Auto-injectors are devices which completely or partially replace activities involved in parenteral drug delivery from standard syringes. These activities may include removal of a protective syringe cap, insertion of a needle into a patient&#39;s skin, injection of the medicament, removal of the needle, shielding of the needle and preventing reuse of the device. This overcomes many of the disadvantages of manual devices. Injection forces/button extension, hand-shaking and the likelihood of delivering an incomplete dose are reduced. Triggering may be performed by numerous means, for example a trigger button or the action of the needle reaching its injection depth. In some devices the energy to deliver the fluid is provided by a spring. 
         [0009]    US 2002/0095120 A1 discloses an automatic injection device which automatically injects a pre-measured quantity of fluid medicine when a tension spring is released. The tension spring moves an ampoule and the injection needle from a storage position to a deployed position when it is released. The content of the ampoule is thereafter expelled by the tension spring forcing a piston forward inside the ampoule. After the fluid medicine has been injected, torsion stored in the tension spring is released and the injection needle is automatically retracted back to its original storage position. 
         [0010]    The spring means is a single compression spring arranged to be grounded at a distal end in the housing for advancing the needle and for injecting the dose of medicament via a plunger and wherein the compression spring is arranged to have its ground in the housing switched to its proximal end for retracting the syringe. 
       SUMMARY 
       [0011]    It is an object of the present invention to provide an improved auto-injector arranged to retract the needle into a safe position even if the injection is interrupted before the entire dose has been delivered. 
         [0012]    The object is achieved by an auto-injector according to claim  1 . 
         [0013]    Preferred embodiments of the invention are given in the dependent claims. 
         [0014]    In the context of this specification the term proximal refers to the direction pointing towards the patient during an injection while the term distal refers to the opposite direction pointing away from the patient. 
         [0015]    According to the invention, an auto-injector for administering a dose of a liquid medicament comprises:
       an elongate housing arranged to contain a syringe with a hollow needle and a stopper for sealing the syringe and displacing the medicament, the housing having a distal end and a proximal end with an orifice intended to be applied against an injection site, wherein the syringe is slidably arranged with respect to the housing,   spring means capable of, upon activation:
           pushing the needle from a covered position inside the housing into an advanced position through the orifice and past the proximal end,   operating the syringe to supply the dose of medicament, and   retracting the syringe with the needle into the covered position after delivering the medicament,   
           activating means arranged to lock the spring means in a pressurized state prior to manual operation and capable of, upon manual operation, releasing the spring means for injection.       
 
         [0022]    According to the invention the spring means is a single drive spring in the shape of a compression spring arranged to be grounded at a distal end in the housing for advancing the needle and for injecting the dose of medicament. The force of the drive spring is forwarded to the needle and/or the syringe via a plunger. The drive spring is arranged to have its ground in the housing switched to its proximal end for retracting the syringe when the injection of the medicament is at least nearly finished. 
         [0023]    The single drive spring is used for inserting the needle, fully emptying the syringe and retracting the syringe and needle to a safe position after injection. Thus a second spring for withdrawing the syringe and needle, which is a motion with an opposite sense compared to advancing the syringe and injecting the dose, is not required. While the distal end of the drive spring is grounded the proximal end moves the syringe forward for inserting the needle and carries on to the injection by pushing on the stopper. When the injection is at least nearly finished the drive spring bottoms out at its proximal end, resulting in the proximal end being grounded in the housing. At the same time the distal end of the drive spring is released from its ground in the housing. The drive spring is now pulling the syringe in the opposite direction. 
         [0024]    According to the invention the plunger is arranged for pushing the syringe and/or the stopper in proximal direction. At least one resilient decoupling arm (preferably two) is arranged at the decoupling member. The decoupling arm exhibits an inner ramped surface for bearing against a first shoulder of the plunger in proximal direction. The resilient decoupling arm is supportable by an inner wall of the retraction sleeve in order to prevent the decoupling arm from being flexed outward and slip past the first shoulder. In this state the plunger may be pushed in proximal direction by the decoupling member pushing against the first shoulder in order to insert the needle and inject the dose. At least one aperture is arranged in the retraction sleeve allowing the decoupling arm to be flexed outward by the first shoulder thus allowing the first shoulder to slip past the decoupling arm in distal direction. This may happen when the injection is at least nearly finished. The decoupled plunger allows the syringe and needle to be retracted since it is no longer bearing against the decoupling member. 
         [0025]    The aperture in the retraction sleeve extends at least almost to the position of the decoupling arm in the as delivered state up to the decoupling arms position at the end of dose. The aperture is arranged to be angularly misaligned with respect to the decoupling arm when the retraction sleeve is in its proximal position so the plunger does not decouple from the decoupling member. The aperture and the retraction sleeve are also arranged to rotate so as to align the aperture with the decoupling arms upon translation of the retraction sleeve out of the proximal position in distal direction so the plunger and decoupling member decouple from each other thus allowing retraction of the plunger, stopper syringe and needle. Hence, the syringe and the needle may be retracted at any point of the injection cycle. 
         [0026]    The auto-injector according to the invention has a particularly low part count compared to most conventional auto-injectors. The use of just one drive spring reduces the amount of metal needed and thus consequently reduces weight and manufacturing costs. 
         [0027]    The rotation into the aligned position may be achieved by a cam track arranged in the housing and a cam follower in the retraction sleeve. The cam track may be essentially parallel to a longitudinal axis of the auto-injector with a short angled section at its proximal end. 
         [0028]    Alternatively the cam track may be arranged in the retraction sleeve and the cam follower in the housing. 
         [0029]    An interlock sleeve may be telescoped in the proximal end of the housing, the interlock sleeve translatable in longitudinal direction between a proximal position and a distal position and biased in proximal direction in a manner to protrude from the housing in the proximal position. In its proximal position the interlock sleeve is arranged to be coupled to the syringe in the syringe&#39;s retracted position for joint axial movement. In its distal position the interlock sleeve is arranged to allow decoupling of the syringe. 
         [0030]    In the as delivered state of the auto-injector the interlock sleeve is in its proximal position protruding from the proximal end of the housing. The syringe and needle are in their retracted position. As the interlock sleeve and the syringe are coupled for joint axial movement the syringe and needle cannot advance even if the spring means were inadvertently released by operating the activating means. Thus the needle remains in its covered position. In order to trigger an injection, the auto-injector has to be pressed with its proximal end against an injection site, e.g. a patient&#39;s skin in a manner to translate the interlock sleeve in distal direction into the housing. Thus the syringe is decoupled or allowed to decouple from the interlock sleeve and may now translate so as to move the needle into its advanced position for piercing the patient&#39;s skin. Before the syringe and needle actually translate in proximal direction the activating means has to be operated so as to release the drive spring. The probability for inadvertent operation of the auto-injector thus decreases due to the requirement of two user actions, pressing the auto-injector against the injection site and operating the activating means. 
         [0031]    It is desirable to trigger the retraction of the needle when the contents of the syringe have been entirely delivered to the patient, i.e. when the stopper has bottomed out in the syringe. Automatically triggering the retraction when the stopper exactly reaches the end of its travel is a problem due to tolerances when manufacturing the syringe and stopper. Due to these tolerances the position of the stopper relative to the means triggering retraction at the end of its travel is not repeatable. Consequently, in some cases the stopper would prematurely bottom out so the retraction would not be triggered at all. In other cases the retraction would be triggered before the stopper bottomed so residual medicament would remain in the syringe. 
         [0032]    The retraction could automatically be triggered a certain amount of time or travel before the stopper bottoms out in the syringe. However this reliable retraction would be traded off for residual medicament in the syringe. 
         [0033]    Thus, in a preferred embodiment the interlock sleeve is furthermore arranged to prevent release of the distal ground of the drive spring when in the distal position. This means, the drive spring remains distally grounded as long as the auto-injector is kept pressed against the injection site so the needle retraction can only start when the auto-injector is removed from the injection site and the interlock sleeve consequently returns into its proximal position and thus releases the distal ground. Full delivery of the medicament and reliable retraction are thus achieved by waiting for the user action of removing the auto-injector from the injection site. 
         [0034]    For this purpose the interlock sleeve may be engaged to the retraction sleeve by at least one resilient wedge arranged at the proximal end of the retraction sleeve. The housing has a respective recess for accommodating the resilient wedge when the retraction sleeve is in its proximal position. The interlock sleeve in its distal position may be arranged to support the resilient wedge from inside so as to prevent it from translating in distal direction. Thus, when the interlock sleeve is pressed against the injection site, the retraction sleeve is kept from retracting. Only after removal of the auto-injector from the injection site and consequent translation of the interlock sleeve into its proximal position the retraction sleeve may translate in distal direction and retract the needle into the housing. 
         [0035]    A tubular syringe carrier may be arranged for holding the syringe and supporting it at its proximal end. Supporting the syringe at the proximal end is preferred over support at the finger flanges since the finger flanges are more frangible under load while the proximal or front end of the syringe is more robust. The syringe and the syringe carrier are arranged for joint axial translation. The syringe carrier is telescoped in the interlock sleeve, wherein at least one resilient second latch is arranged in the housing near the proximal end. In the as delivered state the resilient second latches extend inwards in a manner to prevent the syringe carrier from translating in proximal direction. The resilient second latches are arranged to be disengaged from the syringe carrier upon translation of the interlock sleeve in distal direction. 
         [0036]    In a preferred embodiment at least one latch is provided for axially fixing the retraction sleeve in a maximum proximal position. The decoupling member is arranged to decouple the latch when being moved in proximal direction nearly into a maximum proximal position. When decoupled, the retraction sleeve is allowed to move in distal direction and retract the needle by means of the spring force which is no longer grounded at its distal end. Thus, retraction can only occur if the latches have been released and if the auto-injector has been removed from the injection site. 
         [0037]    The syringe may be arranged for joint axial movement with a syringe holder which is slidably arranged in the retraction sleeve. The syringe holder is provided with at least one (preferably two) resilient syringe holder arm arranged distally, the syringe holder arm having a respective inclined surface for bearing against a second shoulder, which is arranged at the plunger proximally from the first shoulder. The syringe holder arm is supportable by an inner surface of the housing in order to prevent it from being flexed outward. Thus, when the trigger button is pressed the spring force forwarded by the plunger does not yet press against the stopper but against the syringe for forwarding it. Consequently, a so called wet injection is avoided, i.e. the liquid medicament is not leaking out of the hollow needle before the needle is inserted. A widened portion is provided in the housing for allowing the syringe holder arms to flex outwards when the syringe holder has nearly reached a maximum proximal position thus allowing the second shoulder to slip past the syringe holder arm and to switch load of the drive spring from the syringe to the stopper. This allows for defining the moment to start injecting the medicament. 
         [0038]    A stud may be arranged at the distal end of the plunger. The retraction sleeve may have one or more resilient arms distally from the end face for holding the stud. The stud and/or the resilient arms have ramp features. Thus the resilient arms may be pushed apart by the stud when the plunger is moved in proximal direction. The activating means comprise a trigger button arranged at the distal end of the auto-injector. The trigger button is axially moveable and has a rigid retainer for preventing each resilient arm from being flexed outward when the trigger button is in a maximum distal position. Upon pushing the trigger button in proximal direction the retainers are moved in proximal direction in a manner to allow the resilient arms to be flexed out by the stud biased by the drive spring in proximal direction. Thus the stud is allowed to slip past the resilient arms in proximal direction under load of the drive spring in order to start a needle insertion/injection/retraction cycle. The main advantages of this trigger mechanism are its simplicity, the low part count and a high reliability. 
         [0039]    In another embodiment the activating means comprises a trigger button arranged at the distal end of the auto-injector. The trigger button is locked, thereby preventing actuation when the interlock sleeve is in its proximal position in an as delivered state and wherein translation of the interlock sleeve unlocks the trigger button so as to allow actuation. 
         [0040]    This results in an auto-injector with a sequenced operation. In the as delivered state the interlock sleeve is in its proximal position protruding from the proximal end of the housing. The syringe and needle are in their retracted position. In order to trigger an injection the auto-injector has to be pressed with its proximal end against the injection site in a manner to translate the interlock sleeve in distal direction into the housing. This translation allows the trigger button to be actuated for eventually releasing the drive spring and start an injection cycle. The probability for inadvertent operation of the auto-injector decreases due to the requirement of two sequenced user actions, pressing the auto-injector against the injection site and operating the activating means. 
         [0041]    The connection from the interlock sleeve at the proximal end to the trigger button at the distal end may be established by the interlock sleeve or a part of it extending through the entire auto-injector to the trigger button. This may result in a complex design since interaction with the mechanisms for advancing the needle, injecting the dose and retracting the needle have to be avoided. In a preferred embodiment the interlock sleeve is coupled to the plunger for joint axial translation in the as delivered state. A distal end of the plunger is arranged to interact with the trigger button in a manner to lock and/or unlock it. Extending the interlock sleeve to the distal end with the aforesaid drawbacks may thus be avoided. Furthermore the auto-injector may be designed less bulky. In the as delivered state the first shoulder of the plunger is preferably situated a small distance proximally from the ramped surface of the decoupling arm. The plunger is thus allowed to be translated this distance in distal direction without moving the decoupling member. 
         [0042]    In its proximal position the interlock sleeve may be arranged to be coupled to the syringe carrier in the syringe&#39;s retracted position. As the interlock sleeve and the syringe are coupled for joint axial movement the syringe and needle cannot advance even if the spring means were inadvertently released or the if the auto-injector were vigorously shaken. Thus the needle remains in its covered position. The interlock sleeve in its distal position is arranged to allow decoupling of the syringe carrier. The actual decoupling occurs upon release of the drive spring and the resulting translation of the syringe carrier in proximal direction with the interlock sleeve being held in distal position by the injection site. The syringe is now translated so as to move the needle into its advanced position for piercing the patient&#39;s skin. In the as delivered state the interlock sleeve, the syringe carrier, the syringe, the syringe holder and the plunger are floating as a single part in the auto-injector. 
         [0043]    The auto-injector may also be embodied without the syringe holder. In this case the interlock sleeve would be coupled to the plunger via the syringe carrier, the syringe and the stopper in the as delivered state. 
         [0044]    Decoupling the interlock sleeve from the syringe carrier may be achieved by at least one resilient clip provided in the interlock sleeve. A respective recess for each clip is arranged in the syringe carrier so as to allow the clip to engage the syringe carrier. The clip is outwardly supported by the housing in the as delivered state thus preventing it from disengaging the syringe carrier. At least one ramp is arranged to disengage the clip from the recess when the syringe carrier and the interlock sleeve are pushed against each other in longitudinal direction with the interlock sleeve in its distal position. 
         [0045]    In the as delivered state the position of the trigger button, the retraction sleeve and the decoupling member may be as follows:
       The retraction sleeve is in its proximal position and engaged with the decoupling member so as to prevent release of the drive spring.   The trigger button is in its distal position preventing disengagement of the retraction sleeve from the decoupling member.   The trigger button is latched to the retraction sleeve so as to prevent actuation of the trigger button.       
 
         [0049]    The plunger may be arranged to de-latch the trigger button from the retraction sleeve upon translation of the plunger in distal direction so as to allow actuation of the trigger button. At least one ramp may be provided for disengaging the retraction sleeve from the decoupling member under load of the drive spring when the trigger button is actuated. 
         [0050]    A central shaft may extend from the trigger button in proximal direction towards the plunger, the central shaft having a shoulder for abutting against at least one resilient clip arranged on the retraction sleeve in the as delivered state. At least one bar may extend distally from the distal end of the plunger, the bar arranged to disengage the resilient clip from the central shaft upon translation of the plunger in distal direction. 
         [0051]    At least one catch may be arranged on the retraction sleeve for engaging a respective catch on the decoupling member in the as delivered state. At least one dog on the trigger button is arranged to support one of the catches prior to actuation of the trigger button so as to prevent disengagement of the catches. The dog is arranged to be translated upon actuation of the trigger button so as to no longer support the catch and allow disengagement of the catches under load of the drive spring in order to start the injection cycle. 
         [0052]    Usually the hollow needle is equipped with a protective needle shield for keeping the needle sterile and preventing it from being mechanically damaged. The protective needle shield is attached to the needle when the auto-injector or the syringe is assembled. 
         [0053]    Preferably a cap is provided at the proximal end of the housing. A sheet metal clip is attached to the cap for joint axial movement and independent rotation. The sheet metal clip is arranged to extend through an orifice into the interlock sleeve when the cap is attached to the interlock sleeve. The sheet metal clip incorporates at least two barbs snapped into a circumferential notch or behind a shoulder of the protective needle shield. This allows for automatically engaging the sheet metal clip with the protective needle shield during assembly. When the cap is removed from the interlock sleeve in preparation of an injection the protective needle shield is reliably removed without exposing the user too high a risk to injure themselves. 
         [0054]    The cap may be attachable to the housing by a screw connection. This allows for a low force removal of the protective needle shield. 
         [0055]    The housing may have at least one viewing window for inspecting the syringe. 
         [0056]    The auto-injector may preferably be used for subcutaneous or intra-muscular injection, particularly for delivering one of an analgetic, an anticoagulant, insulin, an insulin derivate, heparin, Lovenox, a vaccine, a growth hormone, a peptide hormone, a proteine, antibodies and complex carbohydrates. 
         [0057]    The cap with the sheet metal spring may also be applied with other auto-injectors and injection devices. 
         [0058]    Further scope of applicability of the present invention will become apparent from the detailed description given hereinafter. However, it should be understood that the detailed description and specific examples, while indicating preferred embodiments of the invention, are given by way of illustration only, since various changes and modifications within the spirit and scope of the invention will become apparent to those skilled in the art from this detailed description. 
     
    
     
       BRIEF DESCRIPTION OF THE DRAWINGS 
         [0059]    The present invention will become more fully understood from the detailed description given herein below and the accompanying drawings which are given by way of illustration only, and thus, are not limiting of the present invention, and wherein: 
           [0060]      FIG. 1A  is a longitudinal section of an auto-injector with a single drive spring for advancing a syringe with a needle, injecting a dose of medicament and retracting the syringe and needle, the auto-injector as-delivered, 
           [0061]      FIG. 1B  is another longitudinal section of the auto-injector shown in  FIG. 1A , 
           [0062]      FIG. 2A  is a longitudinal section of the auto-injector with a skin interlock sleeve pressed against an injection site, 
           [0063]      FIG. 2B  is another longitudinal section of the auto-injector shown in  FIG. 2A , 
           [0064]      FIG. 3A  is a longitudinal section of another auto-injector with a modified trigger button, 
           [0065]      FIG. 3B  is another longitudinal section of the auto-injector shown in  FIG. 3A , 
           [0066]      FIG. 4  is a detail view of the trigger button of  FIG. 3A  prior to actuation, 
           [0067]      FIG. 5A  is a detail view of the trigger button of  FIG. 3A  upon actuation, 
           [0068]      FIG. 5B  is another detail view of the trigger button of  FIG. 3A  upon actuation, 
           [0069]      FIG. 6A  is an isometric view of an embodiment of the auto-injector with the capability to immediately retract the syringe upon removal of the auto-injector from the injection site, 
           [0070]      FIG. 6B  is another isometric view of the embodiment of the auto-injector shown in  FIG. 6A , 
           [0071]      FIG. 7  is a longitudinal section of the auto-injector of  FIG. 6A , 
           [0072]      FIG. 8  is a cross section of the auto-injector of  FIG. 7  in the section plane VIII-VIII, and 
           [0073]      FIG. 9  is an isometric detail view of a trigger button. 
       
    
    
       [0074]    Corresponding parts are marked with the same reference symbols in all figures. 
       DETAILED DESCRIPTION 
       [0075]      FIGS. 1A-1B  show two longitudinal sections in different section planes of an auto-injector  1 , the different section planes approximately 90° rotated to each other. The auto-injector  1  comprises an elongate housing  2 . A syringe  3 , e.g. a Hypak syringe, with a hollow needle  4  is arranged in a proximal part of the auto-injector  1 . When the auto-injector  1  or the syringe  3  is assembled a protective needle shield may be attached to the needle (not illustrated). A stopper  6  is arranged for sealing the syringe  3  distally and for displacing a liquid medicament M through the hollow needle  4 . The syringe  3  is held in a tubular syringe carrier  7  and supported at its proximal end therein. A single drive spring  8  in the shape of a compression spring is arranged in a distal part of the auto-injector  1 . A plunger  9  is arranged for forwarding the spring force of the drive spring  8 . 
         [0076]    Inside the housing  2  a retraction sleeve  10  is slidably arranged. Before the injection is triggered the retraction sleeve  10  is in a maximum proximal position and prevented from moving in distal direction D by means of stops  11  caught behind latches  12  in the housing  2 . A distal end of the drive spring  8  bears against an end face  13  of the retraction sleeve  10 . Due to the stops  11  and latches  12  the force of the drive spring  8  is thus reacted into the housing  2 . The proximal end of the drive spring  8  bears against a decoupling member  14  arranged around the plunger  9 . Distally from the end face  13  the retraction sleeve has two or more resilient arms  15  for holding a stud  16  and keeping it from being moved in proximal direction P. The stud  16  is arranged at the distal end of the plunger  9 . The stud  16  and the resilient arms  15  have corresponding ramp features for pushing the resilient arms  15  apart in order to allow the stud  16  and the plunger  9  to move in proximal direction P. 
         [0077]    The decoupling member  14  comprises a thrust face  17  for bearing against a proximal end of the drive spring  8 . Proximally from the thrust face  17  two or more resilient decoupling arms  18  are provided at the decoupling member  14 , the decoupling arms  18  having inner ramped surfaces bearing against a first shoulder  19  in the plunger  9  in proximal direction P. The resilient decoupling arms  18  are supported by an inner wall of the retraction sleeve  10  in this situation so they cannot flex outward and slip past the first shoulder  19 . 
         [0078]    A trigger button  20  is arranged at the distal end D of the auto-injector  1 . The trigger button  20  may be pushed in proximal direction P in order to start an injection. As long as the trigger button  20  is not pushed the resilient arms  15  are caught between two or more retainers  21  arranged at the trigger button  20  so the resilient arms  15  cannot flex outward and the stud  16  although proximally biased by the drive spring  8  cannot slip through. 
         [0079]    The syringe carrier  7  is engaged for joint axial movement with a syringe holder  22  which is slidably arranged in the retraction sleeve  10 . The syringe holder  22  is provided with two or more resilient syringe holder arms  23  arranged distally. The syringe holder arms  23  have a respective inclined surface for bearing against a second shoulder  24  in the plunger  9  arranged proximally from the first shoulder  19 . In the initial position shown in  FIGS. 1A-1B  the syringe holder arms  23  are supported by an inner surface of the housing  2  so they cannot flex outward and the second shoulder  24  cannot slip through. 
         [0080]    In order to support the syringe holder arms  23  at the housing  2  a respective number of apertures are provided in the retraction sleeve  10 . 
         [0081]    Two resilient wedges  10 . 1  are arranged at a proximal end of the retraction sleeve  10 . The housing  2  has two recesses  2 . 2  arranged to accommodate the resilient wedges  10 . 1  when the retraction sleeve  10  is in its proximal position. 
         [0082]    A skin interlock sleeve  25  is telescoped in the proximal end P of the housing  2 . The syringe carrier  7  in turn is telescoped in the interlock sleeve  25 . The interlock sleeve  25  is biased in proximal direction P by an interlock spring  26 . Two resilient second latches  27  are arranged in the housing  2  near the proximal end P. In the state as delivered the second latches  27  are relaxed and extend inwardly through respective apertures  25 . 1  in the interlock sleeve  25  in a manner to prevent the syringe carrier  7  from translating in proximal direction P by the syringe carrier  7  abutting against respective distal faces  27 . 1  of the second latches  27 . The syringe carrier  7 , the syringe  3  and the needle  4  can therefore not be forwarded when pushed by the plunger  9 . 
         [0083]    In order to start an injection the auto-injector  1  has to be pressed against the injection site, e.g. a patient&#39;s skin. As a result the interlock sleeve  25  translates in distal direction D into the housing  2  (see  FIGS. 2A-2B ). A proximal edge of the aperture  25 . 1  pushes against a proximal ramp  27 . 2  of the second latch  27  thereby flexing the second latch  27  outwards so the syringe carrier  7  comes clear of the distal faces  27 . 1  and may now translate in proximal direction P. When translated into the housing  2  as in  FIGS. 2A-2B  a distal end of the interlock sleeve  25  supports the resilient wedges  10 . 1  from inside so they cannot be flexed inwards thus preventing the retraction sleeve  10  from translating in distal direction D. 
         [0084]    The trigger button  20  can now be pushed to release the drive spring  8  in order to insert the needle  4  into the injection site and to inject the medicament M. 
         [0085]    If the auto-injector  1  is removed from the injection site without operating the trigger button  20  the interlock sleeve  25  will translate back into its proximal position under load of the interlock spring  26 . The second latches  27  will flex inwards and block the syringe carrier  7  so the auto-injector  1  is in its as delivered state again. 
         [0086]    The sequence of operation can be reversed in this embodiment, i.e. the trigger button  20  may be pushed before pressing the auto-injector  1  against the injection site. 
         [0087]    When the trigger button  20  is pushed the retainers  21  are pushed in proximal direction P so the resilient arms  15  are allowed to flex outward. Under load of the drive spring  8  the inclined surfaces of the stud  16  force the resilient arms  15  apart until the stud  16  can slip through. 
         [0088]    The second shoulder  24  pushes the syringe holder  22 , syringe carrier  7  and syringe  3  forward while no load is exerted onto the stopper  6 . The hollow needle  4  appears from the proximal end P and is inserted into an injection site, e.g. a patient&#39;s skin. 
         [0089]    The forward movement continues until the syringe holder  22  bottoms out at a first abutment  32  in the housing  2 . The travel from the initial position up to this point defines an injection depth, i.e. needle insertion depth. 
         [0090]    When the syringe holder  22  has nearly bottomed out the resilient syringe holder arms  23  have reached a widened portion  2 . 1  of the housing  2  where they are no longer supported by the inner wall of the housing  2 . However, since the force required to insert the needle  4  is relatively low the second shoulder  24  will continue to drive forward the syringe holder  22  until proximal travel is halted at the first abutment  32 . At this point the syringe holder arms  23  are flexed out by the continued force of the second shoulder  24  and allow it to slip through. Now the plunger  9  no longer pushes against the syringe holder  22  but against the stopper  6  for expelling the medicament M from the syringe  3  and injecting it into or through the patient&#39;s skin. 
         [0091]    When the stopper  6  has nearly bottomed out in the syringe  3  the decoupling member  14  has reached a position where it pushes against the latches  12  in a manner to decouple the retraction sleeve  10  from the housing  2 . Thus the drive spring  8  is no longer grounded with its distal end in the housing  2  by the latches  12 . Instead, as soon as the decoupling member  14  has bottomed out at a second abutment  33  the proximal end of the drive spring  8  gets grounded in the housing  2  while its distal end is pulling the retraction sleeve  10  in distal direction D. 
         [0092]    Just before the decoupling member  14  decouples the retraction sleeve  10  from the housing  2  the decoupling arms  18  reach an aperture  34  in the retraction sleeve  10  so they are no longer kept from being flexed outward. The decoupling arms  18  are thus pushed outward by the first shoulder  19  pushing against its ramped surfaces so the first shoulder  19  can slip through in distal direction D as soon as the decoupling member  14  has hit the second abutment  33 . 
         [0093]    Although the latches  12  are disengaged now, the retraction sleeve  10  may not yet slide in distal direction D because of the resilient wedges  10 . 1  being held in the recess  2 . 2  between the housing  2  and the interlock sleeve  25  as long as the interlock sleeve  25  is in its distal position by the auto-injector  1  being kept pushed against the injection site. 
         [0094]    If the auto-injector  1  is taken away from the injection site the interlock sleeve  25  will return to its proximal position (as in  FIG. 1 ) under load of the interlock spring  26  so the resilient wedges  10 . 1  are no longer supported from inside. Since the drive spring  8  tries to pull the retraction sleeve  10  in distal direction D, distal ramps of the resilient wedges  10 . 1  move along proximal ramps of the recesses  2 . 2  thereby flexing the resilient wedges inwards as the retraction sleeve  10  starts translating in distal direction. 
         [0095]    The syringe holder  22  is taken along in distal direction D by the retraction sleeve  10 , e.g. by a front face  35 . Thus the syringe  3  and needle  4  are retracted into a safe position inside the housing  2 , e.g. into the initial position. The plunger  9 , no longer bearing against the decoupling arms  18  is pulled back too. 
         [0096]    In the embodiment illustrated in  FIGS. 1A-1B  and  2 A- 2 B the latches  12  and the stops  11  at the retraction sleeve  10  are not absolutely required. Retraction can be triggered by removal of the auto-injector  1  from the injection site alone. However, the latches  12  and the stops  11  facilitate assembly of the auto-injector  1  and give an initial position to the retraction sleeve  10 . Furthermore, the stops  11  as well as lugs on the decoupling member  14  for disengaging the latches  12  and the stops  11  run in a slot  2 . 6  in the housing  2  thus preventing the retraction sleeve  10  and the decoupling member  14  from rotating. 
         [0097]      FIGS. 3A-3B  show two longitudinal sections in different section planes of another embodiment of an auto-injector  1 , the different section planes approximately 90° rotated to each other. The auto-injector  1  comprises an elongate housing  2 . A syringe  3 , e.g. a Hypak syringe, with a hollow needle  4  is arranged in a proximal part of the auto-injector  1 . When the auto-injector  1  or the syringe  3  is assembled a protective needle shield may be attached to the needle (not illustrated). A stopper  6  is arranged for sealing the syringe  3  distally and for displacing a liquid medicament M through the hollow needle  4 . The syringe  3  is held in a tubular syringe carrier  7  and supported at its proximal end therein. A single drive spring  8  in the shape of a compression spring is arranged in a distal part of the auto-injector  1 . A plunger  9  is arranged for forwarding the spring force of the drive spring  8 . 
         [0098]    Inside the housing  2  a retraction sleeve  10  is slidably arranged. Before the injection is triggered the retraction sleeve  10  is in a maximum proximal position abutting against a stop  2 . 4  in the housing  2 . A distal end of the drive spring  8  bears against an end face  13  of the retraction sleeve  10 . The proximal end of the drive spring  8  bears against a decoupling member  14  arranged around the plunger  9 . 
         [0099]    The decoupling member  14  comprises a thrust face  17  for bearing against a proximal end of the drive spring  8 . Proximally from the thrust face  17  two or more resilient decoupling arms  18  are provided at the decoupling member  14 , the decoupling arms  18  having inner ramped surfaces arranged for bearing against a first shoulder  19  in the plunger  9  in proximal direction P. In the as delivered state in  FIGS. 3A-3B  the first shoulder  19  is situated a small distance proximally from the ramped surfaces of the decoupling arms  18 . The resilient decoupling arms  18  may be supported by an inner wall of the retraction sleeve  10  for preventing them from being flexed outward and slip past the first shoulder  19 . Apertures  34  are provided in the retraction sleeve  10  for allowing the decoupling arms  18  to flex outwards. 
         [0100]    A trigger button  20  is arranged at the distal end D of the auto-injector  1 . The trigger button  20  is arranged to be pushed in proximal direction P in order to start an injection. 
         [0101]    The syringe carrier  7  is engaged for joint axial movement with a syringe holder  22  which is slidably arranged in the retraction sleeve  10 . The syringe holder  22  is provided with two or more resilient syringe holder arms  23  arranged distally. The syringe holder arms  23  have a respective inclined surface for bearing against a second shoulder  24  in the plunger  9  arranged proximally from the first shoulder  19 . In the initial position shown in  FIG. 3A  the syringe holder arms  23  are supported by an inner surface of the housing  2  so they cannot flex outward and the second shoulder  24  cannot slip through. In order to support the syringe holder arms  23  at the housing  2  a respective number of apertures are provided in the retraction sleeve  10 . 
         [0102]    Two resilient wedges  10 . 1  are arranged at a proximal end of the retraction sleeve  10 . The housing  2  has two recesses  2 . 2  arranged to accommodate the resilient wedges  10 . 1  when the retraction sleeve  10  is in its proximal position. 
         [0103]    A skin interlock sleeve  45  is telescoped in the proximal end P of the housing  2 . The syringe carrier  7  in turn is telescoped in the interlock sleeve  45 . The interlock sleeve  45  is biased in proximal direction P by an interlock spring  26 . 
         [0104]    In the as delivered state as shown in  FIG. 3B  the interlock sleeve  45  is coupled with the syringe carrier  7  by resilient clips  45 . 1  provided in the interlock sleeve  45 . The clips  45 . 1  are engaged in a respective recess in the syringe carrier  7  and outwardly supported by the housing  2  so they cannot flex outward. Hence, in the state as delivered, the interlock sleeve  45 , the syringe carrier  7  with the syringe  3  and the needle  4 , the syringe holder  22  and the plunger  9  are coupled for joined axial translation. The recess in the syringe carrier  7  and the clip  45 . 1  have ramps arranged to flex the clip  45 . 1  outwards when the syringe carrier  7  and the interlock sleeve  45  are pushed against each other in longitudinal direction. 
         [0105]    The syringe carrier  7 , the syringe  3  and the needle  4  can therefore not be forwarded when pushed by the plunger  9 . 
         [0106]    The trigger button  20  is secured on the housing  2  by means of clips  20 . 1  so it cannot translate in distal direction D further than shown in  FIG. 4 . A central shaft  20 . 2  extends from the trigger button  20  in proximal direction towards the plunger  9 . Another set of resilient clips  10 . 2  are arranged on the retraction sleeve  10  proximally from the end face  13  inside the drive spring  8  arranged for abutting against a shoulder  20 . 5  in the central shaft  20 . 2  in a manner to prevent the trigger button  20  from being actuated in the as delivered state (see  FIG. 9 ). The retraction sleeve  10  can not translate in proximal direction P due to its proximal end abutting against the stop  2 . 4 . The resilient clips  10 . 2  may be disengaged from the trigger button  20  by respective bars  9 . 1  extending distally from the distal end of the plunger  9  upon translation of the plunger  9  in distal direction D. A set of resilient catches  10 . 3  (shown in  FIG. 5B ) are arranged on the retraction sleeve  10  proximally from the end face  13  inside the drive spring  8  for engaging respective catches  14 . 1  extending distally from the decoupling member  14 . The catches  14 . 1  and  10 . 3  are engaged with each other in a manner to prevent the decoupling member  14  from translating in proximal direction P as long as the trigger button  20  is not pushed. This occurs by respective dogs  20 . 3  on the proximal end of the trigger button  20  inwardly supporting the catches  10 . 3  so they cannot flex inwards. The catches  14 . 1  are outwardly supported by the drive spring  8  so they cannot flex outwards. When the trigger button  20  is actuated the dogs  20 . 3  are translated in proximal direction P so the catches  10 . 3  may flex inwards into spaces  20 . 4  as ramped surfaces of the catches  10 . 3  and  14 . 1  slide along each other under load of the drive spring  8 . 
         [0107]    In order to start an injection the auto-injector  1  has to be pressed against the injection site, e.g. a patient&#39;s skin. As a result the interlock sleeve  45  translates in distal direction D into the housing  2  by a small distance taking with it the syringe carrier  7 , the syringe  3  with the needle  4 , the syringe holder  22  and the plunger  9  until the first shoulder  19  meets the ramped surfaces of the decoupling arms  18 . At the same time the clips  45 . 1  enter a space  2 . 3  in the housing  2  where they are no longer supported outwardly so they may now flex outwards for decoupling the interlock sleeve  45  from the syringe carrier  7 . 
         [0108]    When translated into the housing  2  a distal end of the interlock sleeve  45  supports the resilient wedges  10 . 1  from inside so they cannot be flexed inwards thus preventing the retraction sleeve  10  from translating in distal direction D. 
         [0109]    As the plunger  9  translates in distal direction D the bars  9 . 1  disengage the clips  10 . 2  so the trigger button  20  becomes unlocked and may now be actuated. 
         [0110]    If the auto-injector  1  is removed from the injection site without operating the trigger button  20  the interlock sleeve  45  will translate back into its proximal position under load of the interlock spring  26 . 
         [0111]    As the trigger button  20  is pushed dogs  20 . 3  no longer support catches  10 . 3  and so the catches  10 . 3  are flexed inwards into the spaces  20 . 4  as the ramped surfaces of the catches  10 . 3  and  14 . 1  slide along each other under load of the drive spring  8 . The drive spring  8  now advances the decoupling member  14  and thus the plunger  9  in proximal direction. 
         [0112]    The second shoulder  24  pushes the syringe holder  22 , syringe carrier  7  and syringe  3  forward while no load is exerted onto the stopper  6 . The hollow needle  4  appears from the proximal end P and is inserted into the injection site, e.g. a patient&#39;s skin. 
         [0113]    The forward movement continues until the syringe holder  22  bottoms out at a first abutment  32  in the housing  2 . The travel from the initial position up to this point defines an injection depth, i.e. needle insertion depth. 
         [0114]    When the syringe holder  22  has nearly bottomed out the resilient syringe holder arms  23  have reached a widened portion  2 . 1  of the housing  2  where they are no longer supported by the inner wall of the housing  2 . However, since the force required to insert the needle  4  is relatively low the second shoulder  24  will continue to drive forward the syringe holder  22  until proximal travel is halted at the first abutment  32 . At this point the syringe holder arms  23  are flexed out by the continued force of the second shoulder  24  and allow it to slip through. Now the plunger  9  no longer pushes against the syringe holder  22  but against the stopper  6  for expelling the medicament M from the syringe  3  and injecting it into or through the patient&#39;s skin. 
         [0115]    When the stopper  6  has bottomed out in the syringe  3 , the retraction sleeve  10  may not yet slide in distal direction D because of the resilient wedges  10 . 1  being held in the recess  2 . 2  between the housing  2  and the interlock sleeve  45  as long as the interlock sleeve  45  is in its distal position by the auto-injector  1  being kept pushed against the injection site. 
         [0116]    If the auto-injector  1  is taken away from the injection site the interlock sleeve  45  will return to its proximal position (as in  FIG. 3 ) under load of the interlock spring  26  so the resilient wedges  10 . 1  are no longer supported from inside. Since the drive spring  8  tries to pull the retraction sleeve  10  in distal direction D, distal ramps of the resilient wedges  10 . 1  move along proximal ramps of the recesses  2 . 2  thereby flexing the resilient wedges  10 . 1  inwards as the retraction sleeve  10  starts translating in distal direction D. 
         [0117]    The syringe holder  22  is taken along in distal direction D by the retraction sleeve  10 , e.g. by a front face  35 . Thus the syringe  3  and needle  4  are retracted into a safe position inside the housing  2 , e.g. into the initial position. The plunger  9 , no longer bearing against the decoupling arms  18  is pulled back too. 
         [0118]    The auto-injector  1  of  FIGS. 3A-B  is arranged to retract the syringe  3  and needle  4  at any time during the injection if pulled away from the skin. In  FIGS. 1A-1B  and  2 A- 2 B the retraction sleeve held by the interlock sleeve  25  if released before the end of injection will not retract the syringe  3  if the decoupling member  14  does not release the plunger  9  at the same time. The plunger  9  is only released at its end of travel when the decoupling member  14  meets the aperture  34 . 
         [0119]    In order to retract the syringe  3  before the end of injection the aperture  34  needs to be available at any time during plunger travel. The aperture  34  therefore extends right to the position of the decoupling arms  18  in the as delivered state. However, the aperture is angularly misaligned with respect to the decoupling arms  18  by a small angle so the decoupling member  14  and the plunger  9  cannot decouple. When the auto-injector  1  is removed from the injection site, the interlock sleeve  45  translates in proximal direction under load of the interlock spring  26  so the resilient wedges  10 . 1  are no longer supported from inside. Since the drive spring  8  tries to pull the retraction sleeve  10  in distal direction D, distal ramps of the resilient wedges  10 . 1  move along proximal ramps of the recesses  2 . 2  thereby flexing the resilient wedges inwards as the retraction sleeve  10  starts translating in distal direction. The retraction sleeve  10  is arranged to rotate in this situation by a small angle thus aligning the aperture  34  and the decoupling arms  18 , so the decoupling member  18  decouples from the plunger  9  and the syringe  3  and the needle  4  are retracted into a safe position inside the housing  2 . Decoupling member  14  and hence decoupling arms  18  are prevented from rotating in housing  2  by one or more lugs on decoupling part  14  which engage in longitudinal slots  2 . 6  in housing  2 , as shown in  FIGS. 6   a  and  6   b . In order to make the retraction sleeve  10  rotate a cam track  2 . 5  is arranged in the housing  2  and a cam follower  10 . 4  in the retraction sleeve  10  (see  FIGS. 6   a  and  6   b ). The cam track  2 . 5  is essentially parallel to the longitudinal axis of the auto-injector  1  with a short angled section at its proximal end. As long as the cam follower  10 . 4  runs in the parallel section of the cam track, the retraction sleeve  10  is prevented from rotating. 
         [0120]      FIG. 7  shows the auto-injector of  FIGS. 3A-3B  with the actuated trigger button  20 .  FIG. 8  is a cross section in the section plane VIII-VIII illustrating the angular misalignment before the retraction is triggered. 
         [0121]    In an alternative embodiment the auto-injector  1  of  FIGS. 3A-3B  may have the aperture  34  in the retraction sleeve  10  as in  FIGS. 1A-1B  and  2 A- 2 B. In this case the needle retraction would occur only at the end of dose. 
         [0122]    Likewise, the auto-injector  1  of  FIGS. 1A-1B  and  2 A- 2 B could be combined with the aperture  34 , the cam track  2 . 5  and the cam follower  10 . 4  of  FIGS. 3 to 8  in order to provide immediate needle retraction at any point during the injection cycle. 
         [0123]    The cam track may likewise be arranged in the retraction sleeve  10  and the cam follower in the housing  2 . 
         [0124]    The housing  2  may have at least one viewing window for inspecting the syringe  3 . 
         [0125]    The auto-injector  1  may preferably be used for subcutaneous or intra-muscular injection, particularly for delivering one of an analgetic, an anticoagulant, insulin, an insulin derivate, heparin, Lovenox, a vaccine, a growth hormone, a peptide hormone, a proteine, antibodies and complex carbohydrates. 
         [0126]    The aforementioned arrangement for coupling the plunger  9  to either, the syringe  3  or the stopper  6 , may be applied in any auto-injector having a plunger for forwarding a force of a drive means to a syringe with a stopper. The primary advantage of this arrangement ensures the load from the drive means is not transferred directly to the stopper until the needle is inserted in the patient, thus avoiding a wet injection. The arrangement comprises the syringe holder  22  and associated syringe holder arms  23 , a shoulder (e.g. the second shoulder  24 ) on the plunger  9 , the support of the holder arms  23  by an inner surface in order to prevent them from flexing out in a first position and, a widened portion  2 . 1  for allowing them to flex radially and to disconnect from the plunger when in a more proximal position. The spring means or other drive means, the ability to retract the syringe or to forward a needle shroud after injection and other features described herein are not required for the prevention of a wet injection.