JP2014530691A - Automatic syringe - Google Patents

Abstract

An injection device for administering a dose of medicament is described, comprising a case having a proximal end and a distal end, a carrier adapted to receive a syringe, and a trigger button. In the first state, the trigger button is coupled to the case and / or carrier and abuts the distal end of the case. In the intermediate state, the case moves proximally with respect to the carrier and the trigger button, and the trigger button engages the carrier. In the second state, the trigger button and carrier move proximally relative to the case and the trigger button disengages from the carrier and case.

Description

  The present invention relates to an automatic syringe for administering a dose of a drug.

  Injecting is a process that poses a number of risks and challenges, both mentally and physically, to the user and medical professional.

  Injection devices (ie, devices that can deliver drugs from drug containers) are typically divided into two categories: manual devices and automatic injectors.

  In a manual device, the user must provide mechanical energy to pass the fluid through the needle. This is usually done by some form of button / plunger that must be continuously pressed by the user during the injection. Users have a great deal of inconvenience with this approach. If the user stops pressing the button / plunger, the injection will also stop. This means that if the device is not used properly (ie, the plunger is not fully pushed to its end position), the user may deliver an underdose. The injection power may be too high for the user, especially if the patient is elderly or has dexterity problems.

  Button / plunger extension may be too large. Thus, it may be inconvenient for the user to reach a fully extended button. The combination of injection force and button extension can cause hand tremors / shakes, resulting in increased discomfort due to movement of the inserted needle.

  The automatic injector device aims to make self-administration of injection therapy easier for the patient. Current therapeutics delivered by self-administration injection include diabetes (insulin and newer GLP-1 class drugs), migraine, hormonal therapy, anticoagulant drugs, and the like.

  An automatic injector is a device that completely or partially replaces the work required for parenteral drug delivery from a standard syringe. These operations may include removing the protective syringe cap, inserting the needle into the patient's skin, injecting the drug, removing the needle, shielding the needle, and preventing reuse of the device. This device overcomes many of the disadvantages of manual devices. Injection force / button extension, hand shake, and the possibility of delivering incomplete doses are reduced. Activation can be done by a number of means, for example, by a trigger button or movement to the needle injection depth. In some devices, the energy to deliver the fluid is provided by a spring.

  U.S. Patent No. 6,053,077 discloses an automatic injection device that automatically injects a pre-measured amount of fluid medication when a tension spring is released. The tension spring moves the ampoule and needle from the stowed position to the deployed position when it is released. The ampoule contents are then discharged by a tension spring that pushes the piston forward inside the ampoule. After the fluid medicament is injected, the torsional force accumulated in the tension spring is released and the injection needle is automatically pulled back to its original retracted position.

  High viscosity drugs require a strong force to be released through a relatively thin needle. To obtain such force, a strong drive spring is required. For this reason, the impact felt by the user when inserting the needle into the skin becomes stronger, and the force felt by the user when starting the injection becomes stronger.

US Patent Application Publication No. 2002 / 0095120A1

  An object of the present invention is to provide an improved automatic injector.

  This object is achieved by an automatic injector according to claim 1.

  Preferred embodiments of the invention are given in the dependent claims.

  In the context of this specification, the term proximal refers to the direction toward the patient upon injection, and the term distal refers to the direction away from the patient. The term inward refers to the radial direction toward the longitudinal axis of the auto-injector, while the term outward refers to the direction away from the longitudinal axis in the radial direction.

  In one exemplary embodiment, an injection device for administering a dose of a medicament comprises a case having a proximal end and a distal end, a carrier adapted to receive a syringe, and a trigger button. . In the first state, the trigger button is coupled to the case and / or carrier and abuts the distal end of the case. In the intermediate state, the case moves proximally relative to the carrier and the trigger button, and the trigger button engages the carrier. In the second state, the trigger button and carrier move proximally relative to the case, and the trigger button disengages from the carrier and case.

  In one exemplary embodiment, the trigger button includes a deflectable beam adapted to engage the case and the carrier. The case includes a case detent adapted to engage the beam. The beam includes a first bevel adapted to engage the case detent. The carrier includes a carrier detent adapted to engage the beam. The beam includes a second bevel adapted to engage the carrier detent. In the first state, the beam engages a case detent and / or a carrier detent. In the second state, the beam engages the case detent and abuts the carrier. In the intermediate state, the beam engages the carrier detent and abuts the case.

  Further scope of applicability of the present invention will become apparent from the detailed description provided hereinafter. However, although the detailed description and specific examples illustrate preferred embodiments of the present invention, various changes and modifications within the spirit and scope of the invention will be apparent to those skilled in the art from this detailed description. Thus, it should be understood that this is merely exemplary.

  The present invention will become more fully understood from the detailed description given below and the accompanying drawings. The drawings are shown merely by way of illustration and therefore do not limit the invention.

A and B are two longitudinal sections of the auto-injector after removing the cap and protective needle sheath. A and B are two longitudinal sections of an auto-injector with the case moved proximally relative to the chassis. A and B are two longitudinal sections of the auto-injector with the trigger button depressed. A and B are two longitudinal sectional views of the automatic injector when the needle is advanced. A and B are two longitudinal sections of the auto-injector with the needle in the extended proximal position. A and B are two longitudinal sectional views of an automatic injector during drug delivery. A and B are two longitudinal sections of an auto-injector with a stopper located near the proximal end of the syringe. A and B are two longitudinal sections of an auto-injector with the case moved distally relative to the chassis after delivery. A and B are two longitudinal sections of an auto-injector with the needle retracted to the needle safety position. FIGS. 4A to 4D are schematic views showing a detent mechanism for controlling the movement of the carrier relative to the chassis of the auto-injector in four different states. A to F are schematic views showing a needle extension mechanism for controlling the movement of the first collar in six different states. AC is a schematic diagram showing the syringe retraction control mechanism in three different states. A to C are schematic views showing the feedback release mechanism for indicating the end of injection in three different states. A to C are schematic views showing the plunger release mechanism in three different states. A to C are schematic views showing the button release mechanism in three different states. FIG. 6 is an isometric view of an alternative embodiment of a plunger release mechanism. FIG. 6 is a longitudinal cross-sectional view of an alternative embodiment of a button release mechanism. A and B are longitudinal sectional views of an alternative embodiment of a detent mechanism. It is a longitudinal cross-sectional view of 3rd Embodiment of a detent mechanism. FIG. 6 is a longitudinal cross-sectional view of an alternative embodiment of a feedback release mechanism. A and B are longitudinal cross-sectional views of an alternative embodiment of a needle extension control mechanism that is also arranged to perform the function of a detent mechanism for needle retraction and needle extension. FIG. 22 is an isometric view of the needle extension control mechanism of FIG. 21. A and B are longitudinal cross-sectional views of a third embodiment of the needle extension control mechanism, which is also arranged to perform the function of the detent mechanism. FIG. 24 is an isometric view of the needle extension control mechanism of FIG. 23. A and B are longitudinal sectional views of a third embodiment of the feedback release mechanism. A and B are another embodiment of an auto-injector having a wrap sleeve trigger instead of a trigger button. FIG. 6 is a longitudinal cross-sectional view of the distal end of the auto-injector before the alternative feedback release mechanism is activated. FIG. 28 is a longitudinal cross-sectional view of the distal end of the auto-injector after the alternate feedback release mechanism of FIG. 27 is released.

  Corresponding parts are designated with the same reference symbols in all figures.

  In the terminology herein, tilted engagement means that at least one of the two components is bent aside when they are pushed against each other in the axial direction unless they are prevented from bending aside. The engagement between the two components having a bevel to engage the other component.

  1a and 1b show two longitudinal sections in different cross-sectional planes of the auto-injector 1, these different cutting planes being rotated about 90 ° relative to each other, the auto-injector 1 being in the initial state before starting the injection It is in. The automatic injector 1 includes a chassis 2. In the following, the chassis 2 is generally considered to be fixed in place, so that the movement of the other components is described with respect to the chassis 2. A syringe 3 having a hollow injection needle 4 (for example, a Hypak syringe) is disposed in the proximal portion of the automatic injector 1. A protective needle shield (not shown) is attached to the needle 4 when the automatic injector 1 or syringe 3 is assembled. A stopper 6 is arranged for sealing the syringe 3 distally and for displacing the drug M through the hollow needle 4. The syringe 3 is held in a tubular carrier 7 and supported at its proximal end therein. The carrier 7 is slidably disposed in the chassis 2.

  A drive spring 8 in the form of a compression spring is arranged at the distal part of the chassis 7. The plunger 9 serves to transfer the force of the drive spring 8 to the stopper 6.

  The drive spring 8 is loaded between the distal carrier end face 10 of the carrier 7 and a thrust face 11 arranged distal to the plunger 9.

  The carrier 7 is a main element that houses the syringe 3, the drive spring 8, and the plunger 9 that are components necessary for discharging the medicine M from the syringe 3. Accordingly, these components can be referred to as drive subassemblies.

  The chassis 2 and the carrier 7 are arranged in a tubular case 12. The trigger button 13 is disposed at the distal end of the case 12. In the plunger release mechanism 27, the peg 14 extends from the distal end face of the trigger button 13 in the proximal direction P between the two elastic arms 15 starting from the thrust face 11 of the plunger 9 inside the drive spring 8 and extending distally. To prevent them from bending toward each other in the initial state A shown in FIG. 14A. In FIG. 14A, only one of the elastic arms 15 is shown to illustrate the principle. Outwardly, the resilient arm 15 is captured in the first recess 16 of each of the distal carrier sleeves 17 attached distal to the distal carrier end face 10 and is arranged inside the drive spring 8. When the elastic arm 15 is engaged with the first recess 16, the translational movement of the plunger 9 in the axial direction with respect to the carrier 7 is prevented. The elastic arm 15 is inclined so as to bend inward by the relative movement between the plunger 9 and the carrier 7 under the load of the drive spring 8, but this is prevented by the peg 14 in the initial state A. .

  The carrier 7 is locked to the chassis 2 by a detent mechanism 18 shown in more detail in FIGS. 10A to 10D to prevent relative translational movement.

  The trigger button 13 is initially engaged with the case 12 by the button release mechanism 26 and cannot be depressed. The button release mechanism 26 is shown in detail in FIGS. 15A-15C. Referring now to FIG. 15A, the button release mechanism 26 includes a resilient proximal beam 13.1 on the trigger button 13, the proximal beam 13.1 having an outwardly facing first bevel 13.2. It has a second slope 13.3 facing. In the first state A shown in FIG. 15A, the inward second bevel 13.3 is engaged with the inclined carrier detent 7.4 of the carrier 7 so that the trigger button 13 is at the distal end. It cannot be moved away from D. The trigger button 13 abuts both the case 12 and the carrier 7 proximally and is therefore not pushed down in the proximal direction P.

  Referring again to FIGS. 1A and 1B, a control spring 19 in the form of another compression spring is disposed around the carrier 7 between the proximal first collar 20 and the distal second collar 21. Operate. The control spring 19 is used to move the carrier 7 and thus the drive subassembly in the proximal direction P for needle extension and in the distal direction D for needle retraction.

  Prior to the situation shown in FIGS. 1A and 1B, a cap 22 is attached to the proximal end of the case 12 and the protective needle sheath is still in place over the needle 4 and needle hub. The inner sleeve 22.1 of the cap 22 is placed inside the chassis 2 over the protective needle sheath. The inner sleeve 22.1 has a barb 23. The barbs 23 are engaged with a protective needle sheath to obtain a concentric translational motion.

  A series of operations of the automatic injector 1 is as follows.

  The user pulls the cap 22 out of the proximal end of the case 12. Barge 23 joins the protective needle sheath to cap 22. Thus, when the cap 22 is removed, the protective needle sheath is also removed. 1A and 1B show the auto-injector 1 with the cap 22 and needle sheath removed. The carrier 7 and the syringe 3 are prevented from moving in the proximal direction P by the detent mechanism 18 in state A as in FIG. 10A. Referring now to FIG. 10A, the detent mechanism 18 comprises an elastic beam 2.1 on the chassis 2 with a first beam head 2.2 protruding inwardly. The first beam head 2.2 has a proximal third bevel 2.3. The detent mechanism 18 further comprises a rhombus ramp member 7.1 on the carrier 7 having a proximal fourth ramp 7.2 and a distal fifth ramp 7.3. In state A, the rounded distal side of the first beam head 2.2 abuts the beveled member 7.1 in the distal direction D and the carrier 7 is in the proximal direction P relative to the chassis 2. Stop moving. In order to prevent the elastic beam 2.1 from deflecting outwards, ribs are provided on the case 12 so that the carrier 7 also does not move relative to the chassis 2.

  Referring again to FIGS. 1A and 1B, the user grasps the case 12 and places the chassis 2 protruding from the case 12 at the proximal end P against the injection site (eg, the patient's skin). When the automatic injector 1 is pressed against the injection site and pushed, the case 12 translates in a proximal direction P relative to the chassis 2 to the advanced position shown in FIGS. 2A and 2B. The second collar 21 is locked to the case 12 and moved with the case 12 relative to the chassis 2 and with respect to almost all other components of the auto-injector 1, thereby being shown in detail in FIG. 11A. The control spring 19 is slightly compressed against the first collar 20 which is prevented from moving in the proximal direction P by the chassis 2 by the needle extension control mechanism 24 in the closed state A. Referring now to FIG. 11A, an arrowhead-shaped elastic member 20.1 is disposed proximally on the first collar 20. The first collar 20 with the arrowhead 20.1 is pushed in the proximal direction P under the load of the compressed control spring 19. The outward slope 20.2 on the arrowhead 20.1 interacts with the distal seventh slope 2.4 of the chassis 2 to tilt the arrowhead 20.1 in the inward direction I. The direction I is blocked by an arrowhead 20.1 that contacts the carrier 7 inward. Accordingly, the first collar 20 cannot translate in the proximal direction P.

  The arrowhead 20.1 can have a shape different from that of FIGS. 11A-11F, such as the rounded arrowhead 20.1 of FIGS. The function of the arrowhead 20.1 is not affected by this deformation.

  2A and 2B again, the second collar 21 is locked to the case by the syringe retraction control mechanism 25 in the state A shown in detail in FIG. 12A. Referring now to FIG. 13A, the syringe retraction control mechanism 25 includes a resilient proximal beam 21.1 on the second collar 21 that includes an inward boss 21.3 and a distal end. It has a second beam head 21.2 with an outwardly facing eighth bevel 21.4. The distal outward eighth bevel 21.4 causes the second beam head 21.2 to be inclined in the inward direction I by the second collar 21 which is loaded with the control spring 19 in the distal direction D. Then, the second case detent 12.2 that is inclined is engaged, but the warping in the inward direction I is prevented by the inward boss 21.3 that abuts the carrier 7 inward.

  Referring again to FIGS. 2A and 2B, when the user moves the case 12 away from the injection site, the control spring 19 is extended and the automatic injector 1 is removed after the cap 22 has been removed. Return to the initial state as shown in 1B.

  In the situation as in FIGS. 2A and 2B, the carrier 7 is still prevented from moving in the proximal direction P by the detent mechanism 18, but when the case 12 is in its advanced position, The detent mechanism 18 is unlocked because the ribs are also moving and the outward deflection of the elastic beam 2.1 is no longer impeded. When the case 12 moves with respect to the carrier 7 locked to the chassis 2 by the detent mechanism 18, the button release mechanism 26 is switched to the intermediate state B shown in FIG. 15B. When the case 12 is moved, the trigger button 13 is engaged with the incline second bevel 13.3 on the proximal beam 13.1 engaged with the bevel carrier detent 7.4 located on the carrier 7. Thus, it remains in contact with the carrier 7. When the case 12 is further translated in the proximal direction P, it supports the proximal beam 13.1 on the outside, thereby locking the trigger button 13 to the carrier 7. The trigger button 13 now protrudes from the distal end D of the case 12 and is ready to be pushed.

  2A and 2B, the user depresses the trigger button 13 in the proximal direction P. Since the trigger button 13 abuts the carrier 7, the carrier 7 pushes the chassis 2 in the proximal direction P, and the carrier 7 and the chassis 2 interact in the detent mechanism 18. The force exerted by the user pressing the trigger button 13 is converted over the injection site through the chassis 2 rather than between the trigger button 13 and the case 12. The detent mechanism 18 provides resistance when the user presses the trigger button 13. If the user applies a force exceeding a predetermined value, the detent mechanism 18 is released and the injection cycle begins. Next, referring to FIG. 10B showing the detent mechanism 18 in the state B, the elastic beam 2.1 on the chassis 2 starts to bend under the load from the rhombus slope member 7.1 on the carrier 7 and is elastic. Accumulate energy. Despite the proximal fourth slope 7.2 on the slope member 7.1, between the contact surface of the first beam head 2.2 and the contact face of the proximal fourth slope 7.2 Friction prevents the first beam head 2.2 from moving in the outward direction O until the straightening force of the elastically deformed beam 2.1 is large enough to overcome the friction. At this point, the elastic beam 2.1 is deflected in the outward direction O and moves out of the path of the carrier 7, thereby allowing the carrier 7 to translate in the proximal direction P. When the carrier 7 travels far enough in the proximal direction P, the rhombic ramp member 7.1 on the carrier 7 passes under the first beam head 2.2, so that the beam head 2.2 is relaxed. And return to the inward direction I at the distal rear of the rhombus slope member 7.1 in the state C shown in FIG. 10C, and at the same time, the carrier 7 translates in the distal direction D with respect to the chassis 2. Exercise is suppressed.

  When the carrier 7 slides far enough in the proximal direction P with respect to the first collar 20, the needle extension control mechanism 24 is switched to state B as shown in FIG. 11B. In FIG. 11B, the carrier 7 has been translated in the proximal direction P such that the arrowhead 20.1 on the first collar 20 is no longer supported inside. This can be achieved by the second recess 7.5 in the carrier 7. The arrowhead 20.1 is then deflected inwardly into the second recess 7.5 under the load of the control spring 19 and reaches a state C as shown in FIG. 11C. Here, the first collar 20 is decoupled from the chassis 2. Instead, the arrowhead 20.1 couples the first collar 20 to the carrier 7 with an inwardly facing ninth bevel 20.3 and the distal tenth bevel 7.6 on the carrier 7 is second. Engages the proximal end of the recess 7.5. Accordingly, the control spring 19 continues to move the carrier 7 in this direction in the proximal direction P. The user advances the needle 4 by a certain percentage of its stroke, but before the needle 4 protrudes from the proximal end P, the control spring 19 takes over the insertion. Thus, what the user experiences is not to insert the needle manually, but to press a button.

  The detent mechanism 18 relies on the user applying force rather than applying displacement. After the applied force exceeds the force necessary to change the detent orientation, the user fully presses the trigger button 13 to ensure that the orientation of the first collar 20 changes. If the user fails to move the detent, the trigger button 13 returns to its unused, ready to use state as shown in FIGS. 2A and 2B. This function prevents the automatic injector 1 from reaching an indefinite state.

  FIGS. 3A and 3B show that the trigger button 13 is depressed enough to allow the control spring 19 to couple to the carrier 7 and continue to move the carrier 7 forward, but still against the case 12. The auto-injector 1 of the state which is not is shown.

  The carrier 7 coupled to the first collar 20 is driven by the control spring 19 to translate in the proximal direction P. Since the syringe 3 is arranged so as to obtain a coaxial translation with the carrier 3, the syringe 3 and the needle 4 also translate, so that the needle 4 protrudes from the proximal end P and is inserted into the injection site. Will be. The trigger button 13 returns to its initial position with respect to the case 12, whereby the proximal beam 13.1 engages the inward second ramp 13.3 that engages the ramp in the carrier detent 7.4. Is deflected in the outward direction O, so that the proximal beam 13.1 is deflected into the first case detent 12.1 and latches from the carrier 7 to the case 12. The carrier 7 further translates in the proximal direction P to prevent inward deflection of the proximal beam 13.1, so the outwardly facing first bevel 13.2 is the first case detent 12. 1 cannot be disengaged.

  Just before the needle 4 reaches the full insertion depth as shown in FIGS. 4A and 4B, the peg 14 on the trigger button 13 is moved between the elastic arms 15 on the carrier 7 and the elastic arms 15 are It is pulled out enough to be able to deflect in the direction. Accordingly, the plunger release mechanism 27 reaches state B shown in FIG. 14B where the resilient arm 15 is no longer supported on the inside by the peg 14. Due to the inclined engagement of the elastic arm 15 in the first recess 16, the elastic arm 15 is deflected in the inward direction I under the load of the drive spring 8, and reaches the state C shown in FIG. 14C. The plunger 9 is thus released from the carrier 7 and is driven in the proximal direction P by the drive spring 8 and is ready to discharge the drug M. The force for pulling out the peg 14 from between the elastic arms 15 is provided by the control spring 19, while the force necessary to deflect the elastic arm 15 from engagement with the carrier 7 is provided by the drive spring 8.

  While the plunger 9 moves and closes the gap to the stopper 6, the movement of the carrier 7 in the proximal direction P is completed by the control spring 19 pushing the first collar 20. When the carrier 7 moves with respect to the chassis 2 during needle extension, the needle extension mechanism 24 reaches the state D shown in FIG. 11D. The arrowhead 20.1 is moving with the carrier 7, but is still deflected inwardly by the chassis 2, thereby preventing the first collar 20 from being disengaged from the carrier 7. The arrowhead 20.1 must be able to deflect in the outward direction O to allow the retraction described below. In order to allow outward deflection, the arrowhead 20.1 advances proximally over the portion of the chassis 2 shown in FIGS. However, as long as the case 12 remains pressed against the injection site under the load of the control spring 19 and cannot return beyond the predetermined distance in the distal direction D, the arrowhead 20.1 is due to its needle extension. During approximately the second half of the movement, the first rib 12.3 of the case 12 (not shown in FIGS. 11A to 11F, see FIGS. 4A to 7A) prevents it from deflecting in the outward direction O.

The needle 4 is then fully inserted into the injection site as shown in FIGS. 5A and 5B.
Although the time between the trigger button 13 being pressed and the needle 4 being fully inserted is very short, several mechanical operations are performed within this time. The needle extension depth is defined by the carrier 7 with respect to the chassis 2 and not with respect to the case 12, so that even if the user has stumbled or does not hold the auto-injector 1 firmly on the skin, Only the case 12 moves in the distal direction D, and the injection depth remains constant.

  As soon as the plunger 9 receives the force of the drive spring 8 and closes the gap to the stopper 6, the stopper 6 is pushed in the proximal direction P in the syringe 3 to displace the medicine M via the needle 4.

  As shown in FIGS. 6A and 6B, the feedback component 28 is released just before the end of the discharge of the medicament, where the stopper 6 has almost reached the bottom of the syringe 3. Due to the accumulation of tolerances (most notably with the syringe 3), the feedback must always be released before the drug is completely drained. Otherwise, the feedback may not necessarily be released depending on the particular combination of members. The feedback component 28 is disposed between the resilient arm 15 on the plunger 9 and the distal end portion 28.2 disposed to abut the proximal extension 14.1 on the peg 14 of the trigger button 13. Provided with an elongated portion 28.1. The two second elastic arms 30 start from the plunger 9 and extend in the distal direction D. The feedback spring 29 causes the feedback component 28 to move relative to the plunger 9 by bearing the rib of the plunger 9 proximally and by bearing the distal end portion 28.2 of the feedback component 28 distally. Arranged to bias in the distal direction D.

  Note: The feedback component 28 does not affect the function of the button release mechanism 26 and is not shown in FIGS. 15A, 15B and 15C for clarity of illustration. A feedback release mechanism 31 for releasing the feedback component 28 is schematically illustrated in FIGS. 13A, 13B and 13C. Referring now to FIG. 13A, the feedback release mechanism 31 includes a second elastic arm 30. Inclined inward bosses 30.1 are arranged on the respective second elastic arms 30. The inclined inward bosses 30.1 are directed outwardly when the second elastic arms 30 are loaded by the feedback spring 29. Engaged with each outwardly facing eleventh bevel 28.3 on the elongate portion 28.1 of the feedback component 28 in such a way as to be deflected O. In the initial state A of the feedback release mechanism 31, the second elastic arm 30 is prevented from being deflected outward by the support on the outside of the carrier 7, so that the translational movement of the feedback component 28 relative to the plunger 9 is prevented. Be blocked. Thus, the feedback component 28 moves with the plunger 9 and remains in state A until just before the drug is completely released, as the stopper 6 has almost reached the bottom of the syringe 3, as shown in FIGS. 6A and 6B. is there. At this point, the plunger 9 is in the proximal direction P relative to the carrier 7 so that the second resilient arm 30 reaches the opening 7.22 in the carrier 7 and is therefore no longer supported outside by the carrier 7. It has been translated. Therefore, the feedback release mechanism 31 has reached the state B shown in FIG. 13B. Due to the inclined engagement between the inclined inward boss 30.1 and the outward eleventh inclined surface 28.3, the second elastic arm 30 is deflected outward under the load of the feedback spring 29, thereby The feedback component 28 is disengaged from the plunger 9, and the feedback component 28 is driven by the feedback spring 29 in the state C shown in FIG. . Thus, the feedback component 28 is accelerated in the distal direction D and the distal end portion 28.2 collides with the proximal extension 14.1 of the peg 14 on the trigger button 13 and drug delivery is almost complete. Audible and tactile feedback is provided to the user (see FIGS. 7A and 7B).

  7A and 7B show the automatic injector 1 with the stopper 6 reaching the bottom of the syringe 3 completely.

  As described above, the user moving the case 12 several millimeters in the distal direction D under the force of the control spring 19 affects the position of the needle 4 as long as the movement is less than a predetermined distance. It is possible. If at any time it is desired to terminate the injection, the user must allow the case 12 to move in the distal direction D beyond that distance. FIGS. 8A and 8B show the auto-injector 1 with the chassis extended, for example when lifted from the injection site, with the case 12 protruding in the distal direction D such that the chassis 2 protrudes from the proximal end of the case 12. Moved to the end. As the case 12 moves, the first collar 20 releases the carrier 7 and then the second collar 21 is released from the case 12 and pulls the carrier 7 in the distal direction D. This switching order is critical because both collars 20, 21 cannot be retracted if they are attached to the carrier 7 at the same time. This criticality is overcome by separating the switching of the collars 20, 21 due to the large displacement of the case 12.

  The switching of the first collar 20 is shown in FIGS. 11E and 11F. In FIG. 11E, the case 12 is allowed to move in the distal direction D under the load of the control spring 19 during, for example, removal of the automatic injector 1 from the injection site. The first rib 12.3 (not shown, see FIG. 8A) is removed from the rear outside of the arrowhead 20.1. The first collar 20 is still pushed in the proximal direction P by the control spring 19. The inward ninth slope 20.3 on the arrowhead 20.1 engages the distal tenth slope 7.6 on the carrier 7 so that the arrowhead 20.1 is in the outward direction O. 2 opening 2.5 (shown in FIGS. 11A-11F), the needle extension control mechanism 24 reaches state E as shown in FIG. 11E, and the first collar 20 is It is decoupled from the carrier 7 and hooked to the chassis 2.

  When the case 12 is further moving in the distal direction D with respect to the chassis, for example, by removal from the injection site, the syringe retraction control mechanism 25 is in the state B shown in FIG. 12B from its state A (see FIG. 12A). Switch to. The case 12 and the second collar 21 locked to the case 12 move together in the distal direction, and the carrier 7 is brought into position by the detent mechanism 18 in its state C (see FIG. 10C) as described above. Retained. Due to this movement, the inward boss 21.3 on the second beam head 21.2 of the proximal beam 21.1 on the second collar 21 no longer hits the carrier 7 inside. Instead, the inward boss 21.3 is tilted into the second case detent 12.2 by the second beam head 21.1 being inclinedly engaged under the load of the control spring 19, so that It is deflected in the inward direction I into the third recess 7.7. Accordingly, the syringe retraction control mechanism 25 reaches the state C as shown in FIG. 12C in which the second collar 21 is decoupled from the case 12 and coupled to the carrier 7. Since there is a small sliding force applied by the second collar 21, before the syringe retraction control mechanism 25 switches to state C, the detent mechanism 18 applies a small braking force to the movement of the carrier 7, thereby When the needle extension control mechanism 24 has already been switched to the state E, the carrier 7 is pulled in the distal direction D by the translational movement in the distal direction D of the case 12. If the carrier 7 moves too far in the distal direction D before the second collar 21 switches, the case 12 will have an inward boss 21.3 into the third recess 7.7 that prevents retraction. It moves out of the way before it can deflect.

  Starting from position C of the detent mechanism 18 (see FIG. 10C), the carrier 7 and hence the rhombus ramp member 7.1 translates in the distal direction D under the load of the control spring 19. Accordingly, the distal fifth slope 7.3 of the rhombus slope member 7.1 deflects the elastic beam 2.1 in the inward direction I such that the first beam head 2 of the elastic beam 2.1. Engage with the proximal third bevel 2.3 on .2. As a result, a small braking force necessary to ensure that the second collar 21 is switched to the carrier 7 is applied to the movement of the carrier 7. As soon as the elastic boom 2.1 and the rhomboid ramp member 7.1 are deflected completely inward from the ramp member 7.1 in the state D shown in FIG. The elastic beam 2.1 is offset laterally so that it can pass without contacting the rhomboid slope member 7.1.

  The control spring 19 is grounded at its proximal end in the case by a first collar 20 abutting against the chassis 2. The distal end of the control spring 19 moves the second collar 21 with the carrier 7 and hence with the syringe 3 with the needle 4 in the distal direction D to overcome the detent mechanism 18 as shown in FIG. 10D. . Needle 4 is used in contrast to an auto-injector with a needle shield that requires the user to remove the auto-injector from the injection site, thereby allowing the needle shield to be advanced by itself by pulling the needle out of the skin. Note that as soon as one allows the case 12 to translate sufficiently far away, it will be withdrawn by the auto-injector 1.

  Note that prior to retraction, the spacing between the ribs of the plunger 9 and the distal end portion 28.2 of the feedback component 28 on which the feedback spring 29 is based is longer than the free length of the feedback spring 29. I want. This means that when the carrier 7 is retracted (ie, reducing the distance between the plunger 9 and the feedback component 28), the feedback spring 29 does not need to be recompressed and therefore does not provide any braking force. means.

  In order to prevent the feedback component 28 from rattling at the end of the dose and before retraction, the free length of the feedback spring 29 is between the rib of the plunger 9 and the distal end portion 28.2 of the feedback component 28. It may be considered to be equal to the interval of. In this case, upon retraction, the feedback spring 29 needs to be recompressed, thereby reducing the force driving the last part of retraction. Nevertheless, the feedback spring 29 has a very low rate and is calculated to be within acceptable tolerance limits for reliable retraction.

  The retraction ends when the distal collar 21 contacts the first rear stop 12.4 on the case 12, as in FIGS. 9A and 9B. The arrowhead 20.1 on the first collar 20 is supported on the inside by the carrier 7 in the state F shown in FIG. 11F, thereby preventing it from deflecting in the inward direction I. An outwardly facing sixth bevel 20.2 of the arrowhead 20.1 engages behind the first rib 12.3 of the case 12 and prevents the case 12 from being pushed again in the proximal direction P. . A margin can be provided by providing a gap between the arrowhead 20.1 and the first rib 12.3.

  The detent mechanism 18 returns to state A as shown in FIG. 10A and locks the carrier 7 in place relative to the chassis 2 as initially, but the case 12 cannot move relative to the chassis 2. So this time it can not be unlocked.

  Here, the tab 20.4 of the first collar 20 is visible through the indicator window 32 of the case 12, indicating that the syringe 1 has been used.

  FIG. 16 is an isometric view of an alternative embodiment of the plunger release mechanism 27. The plunger release mechanism 27 prevents the plunger 9 from moving in the proximal direction P relative to the carrier 7 until the carrier 7 is moved in the proximal direction P for needle extension. In contrast to the plunger release mechanism 27 of FIG. 14 where the relative movement of the carrier 7 and trigger button 13 is used to trigger the release of the plunger 9, in the alternative embodiment of FIG. The plunger 9 is released by moving relative to the collar 21. FIG. 16 shows the plunger release mechanism 27 before releasing the plunger. The second collar 21 is shown transparently to improve clarity. The plunger 9 is pushed in the proximal direction P by the drive spring 8. In order to move the plunger 9 forward, the plunger 9 must be rotated about the twelfth slope 7.8 of the carrier 7. The slope member 9.1 of the plunger 9 is arranged to engage the twelfth slope 7.8. The rotation of the ramp member 9.1 is prevented by the inner longitudinal rib 21.5 on the second collar 21 splined as a longitudinal opening 7.9 of the carrier 7. The case 12 and the second collar 21 remain in the same position, i.e. are coupled to each other for a concentric parallel movement. When the trigger button 13 is pressed, the carrier 7 and plunger 9 that are part of the drive subassembly are initially pushed by the user pressing the trigger button 13 and then the control spring 19 is the first as described above. Moving in the proximal direction P by taking over via the collar 20. When the carrier 7 moves far enough in the proximal direction P with respect to the second collar 21, the beveled member 9.1 on the collar 9 moves away from the longitudinal ribs 21.5 on the second collar 21 and the drive spring 8. Can be rotated past the proximal end of the longitudinal rib 21.5 by engaging with the twelfth slope 7.8 under the load of. Thus, the drive spring 8 advances the plunger 9 in the proximal direction P to inject the drug M.

  FIG. 17 is a longitudinal cross-sectional view of an alternative embodiment of the button release mechanism 26. Unlike the button release mechanism 26 of FIG. 15 which shows the appearance of the exposure trigger button 13 in skin contact by switching the basis of the trigger button 13 between the carrier 7 and the case 12, the button release mechanism 26 of FIG. Start with a trigger button 13 that is locked but protrudes from the distal end of the case 12. When the carrier 7 is moved in the distal direction D by skin contact with the chassis 2, it is possible to depress the trigger button 13 and activate the automatic injector 1. This ensures ordered operation.

  In the embodiment of FIG. 17, the trigger button 13 has two proximal beams 13.1, each with an angled outward boss 13.4. In the initial state shown in FIG. 18, the inclined outward boss 13.4 is engaged with each fourth recess 12.5 in the case 12. The disengagement of the inclined outward boss 13.4 from the fourth recess 12.5 means that the carrier 7 supports the proximal beam 13.1 inward so that the proximal beam 13.1 does not deflect inwardly. Is prevented by. The inward projection 13.5 on the proximal beam 13.1 abuts against the second rib 7.10 on the carrier 7 so as to prevent the carrier 7 from moving further in the proximal direction P in the initial state. . As the carrier 7 moves in the distal direction D due to skin contact with the chassis 2, the first window 7.11 of the carrier 7 moves behind the inward projection 13.5 so that the proximal beam 13.1 is When the trigger button 13 is pushed down, it can be deflected inward by being inclinedly engaged with the fourth recess 12.5. Here, the proximal beam 13.1 is supported on the outside by the case 12 and remains engaged with the carrier 7 even if the needle 4 is retracted. Therefore, the trigger button 13 does not return to its initial position, indicating that the auto-injector 1 has been used.

  18A and 18B show two longitudinal sections of an alternative embodiment of the detent mechanism 18. The detent mechanism 18 of FIGS. 10A-10D, sometimes referred to as a “race track” mechanism because of the first beam head 2.2 moving around the rhombus slope member 7.1, controls the movement of the carrier 7 relative to the chassis 2. Has multiple functions. The alternative detent mechanism 18 of FIGS. 18A and 18B uses three clips 7.12, 7.13, 2.6 to produce the same effect.

  The first clip 7.12 is arranged on the carrier 7 as an outwardly biased elastic beam and extends from the carrier 7 in the proximal direction P. The first clip 7.12 is arranged to prevent the carrier 7 from moving in the proximal direction P before the chassis 2 is pushed down, but before the case 12 is translated by skin contact. The first chip 7.12 is composed of two parts arranged side by side. The first portion 7.14 abuts the chassis 2 at the recess to prevent the carrier 7 from moving in the proximal direction P. The second portion 7.15 is arranged as an outwardly projecting clip head which is arranged to be inclined inwardly by a ramp feature 12.6 on the chassis 12 to release the first clip 7.12. Thus, when the case 12 is translated in the proximal direction P by skin contact, the carrier 7 is unlocked from the chassis 2. The longitudinal slot 2.7 of the chassis 2 is arranged so that the second part 7.15 can slide in the proximal direction P after being unlocked. The slight frictional force between the first clip 7.12 and the chassis 2 is the braking force necessary to ensure retraction.

  The second clip 7.13 is arranged as an elastic beam on the carrier 7 extending in the distal direction D and has a third beam head 7.16 protruding outward with a proximal bevel. The third beam head 7.16 functions as a rear stop against the third rib 2.9 on the chassis 2 to prevent the carrier 7 from moving in the distal direction D from its initial position. The carrier 7 and the chassis 2 are combined in this position with the second clip 7.13 before inserting the syringe 3 into the carrier 7, which is a proximal bevel on the third beam head 7.16. By making it easier. The syringe 3 locks the clip in place by preventing inward deflection, thereby creating a fixed stop.

  The third clip 2.6 is an elastic beam on the chassis 2 that extends in the distal direction D. An inclined fourth beam head 2.8 on the third clip 2.6 is arranged to engage the fifth recess 7.17 of the carrier 7 on the inside. When the first clip 7.12 is unlocked, the user can load the third clip 2.6 by depressing the trigger button 13 and pushing the carrier 7 in the proximal direction P. it can. The third clip 2.6 is loaded with compression, that is, bends outward and is suddenly released by tilting engagement with the carrier 7 to provide a detent function similar to that shown in FIG. 10B. can get.

  FIG. 19 is a longitudinal cross-sectional view of a third embodiment of a detent mechanism 18 that is a variation of the embodiment of FIGS. 18A and 18B. In this embodiment, a detent function for the third clip 2.6 is added to the first clip 7.12. The lock between the case 12 and the carrier 7 is released in the same way, but the detent is obtained by deflecting the first clip 7.12 to the inward second level, which is the second This is realized by the chassis 2 without the slot 2.7 for the portion 7.15 of FIG. Instead, the second portion 7.15 is tilted inward by the ramp function 12.6 on the case 12 and then tilted further inward inside the chassis 2 due to the axial load between the chassis 2 and the carrier 7. Must be done so that these engagements are suddenly released.

  FIG. 20 is a longitudinal cross-sectional view of an alternative embodiment of the feedback release mechanism 31. In contrast to the feedback release mechanism 31 of FIG. 13 in which the feedback spring 29 acts between the plunger 9 and the feedback component 28, in the embodiment shown in FIG. 20, the feedback spring 29 is the case 12 and the feedback component 28. Act between. During needle extension, the feedback spring 29 is compressed as the feedback component 28 moves with the carrier 7 relative to the case 12. When the feedback component 28 is released by the plunger 9 just before the end of the dose, the feedback component 28 moves in the distal direction D and hits the trigger button 13. Unlike FIG. 13, the feedback spring 29 is not recompressed when the needle is retracted because the foundation is placed on the case 12, not the plunger 9.

  21A and 21B show a longitudinal section of an alternative embodiment of a needle extension control mechanism 24 that is also arranged to perform a detent function on the detent mechanism 18 for needle retraction and needle extension. FIG. 22 shows a corresponding isometric view. A fourth clip 20.5 on the first collar 20 with a beam head having an inwardly proximal thirteenth bevel 20.6 for engaging a fourth rib 7.18 on the carrier 7 It is arranged as an elastic beam and is supported on the outside by the case 12 in order to keep the first collar 20 engaged with the carrier 7 before use, when the needle is extended and when the drug is released. When the case 12 moves distally with respect to the carrier, for example, when the user lifts the case 12 away from the injection site at the end of the injection, the sixth recess 12.7 in the case 12 becomes the fourth clip. When the carrier 7 is moved outwardly rearward of 20.5 and pulled in the distal direction D by the second collar 21, it becomes possible to release the fourth clip 20.5. Since the fourth clip 20.5 has to be inclined outward, a small force is required to release the fourth clip 20.5, thereby providing a back detent.

  The carrier in which the fifth clip 2.10 on the chassis 2 abuts the block 20.7 on the first collar 20 before use, and the first collar 20 and therefore the first collar 20 is engaged. 7 is prevented from moving in the proximal direction P. To release, the fifth clip 2.10 must be deflected outward and above block 20.7. Outward deflection of the fifth clip 2.10 is initially prevented by the case 12. As the case 12 moves due to skin contact, the second window 12.8 of the case 12 appears outside the fifth clip 2.10. Allowing outward deflection. Next, when the carrier 7 is pushed in the proximal direction P by depressing the button, the fifth clip 2.10 causes the translational movement of the carrier 7 relative to the first collar 20 by the fourth clip 20.5. In the proximal direction P, not vice versa, so that it is deflected by the fourteenth slope 7.19 on the carrier 7. Detent against needle extension is achieved by having the fifth clip 2.10 have to deflect when it is loaded by the control spring 19.

  23A and 23B show a longitudinal cross section of a third embodiment of the needle extension control mechanism 24 that is also arranged to perform the function of the detent mechanism 18. FIG. 24 is an isometric view of the needle extension control mechanism 24 of FIG. This embodiment is similar to that shown in FIGS. 21A, 21B and 22. The difference is that the fifth clip 2.10 is arranged on the first collar 20 and the block 20.7 is arranged on the chassis 2, i.e. their position has been switched. Thus, there are two clips 2.10 and 20.5 on the first collar 20.

  The fourth clip 20.5 is exactly the same as that of FIG. 21B. The fourth clip 20.5 keeps the first collar 20 connected to the carrier 7 until the needle retraction is activated, thereby reaching a sufficient injection extension length or depth and Displacement of the case in the rearward direction relative to the chassis ensures that the retraction cycle begins (eg, when the auto-injector 1 is removed from the skin) and is maintained.

  The fifth clip 2.10 provides a detent against needle extension, releasing the first collar 20 from the chassis 2 and starting needle insertion. The fifth clip 2.10 abuts the block 20.7 on the chassis 2 so that the first collar 20 and thus the carrier 7 engaged with the first collar 20 is in the proximal direction P before use. To stop moving. To release, the fifth clip 2.10 must be deflected outward and above block 20.7. Outward deflection of the fifth clip 2.10 is initially prevented by the case 12. As the case 12 moves due to skin contact, the second window 12.8 of the case 12 appears outside the fifth clip 2.10. Allowing outward deflection. Next, when the carrier 7 is pushed in the proximal direction P by depressing the button, the fifth clip 2.10 causes the translational movement of the carrier 7 relative to the first collar 20 by the fourth clip 20.5. In the proximal direction P, not vice versa, so that it is deflected by the fourteenth slope 7.19 on the carrier 7. Detent against needle extension is achieved by having the fifth clip 2.10 have to deflect when it is loaded by the control spring 19.

  25A and 25B show a longitudinal section of a third embodiment of the feedback release mechanism 31. FIG. This embodiment functions without the need for a dedicated feedback spring. The plunger 9 comprises a proximal inclined rib 9.2 arranged to spread the two seventh clips 7.21 on the carrier 7 just before the end of the dose. When the proximal inclined rib 9.2 moves past the seventh clip 7.21, the seventh clip 7.21 suddenly returns and collides with the plunger 9 to generate sound. The tubular shape of the carrier 7 helps to convey the sound. FIG. 25A shows the feedback release mechanism 31 before release. FIG. 25B shows the feedback release mechanism 31 after release. The proximal face of the seventh clip 7.21 on the carrier 7 is easy to assemble by lifting the seventh clips 7.21 one by one over the distal side of the proximal inclined rib 9.2. So that it is offset in the axial direction.

  FIGS. 26A and 26B show longitudinal sections in different cross-sectional planes of another embodiment of the auto-injector 1, which are rotated about 90 degrees relative to each other so that the auto-injector 1 is in its initial state before use. is there. The automatic injector 1 is essentially the same as that shown in FIGS. However, unlike the auto-injector of FIGS. 1-15, the auto-injector 1 of this embodiment has a wound sleeve trigger instead of a trigger button.

  The winding sleeve trigger 12 is the same component as the case 12 but has a closed distal end surface 12.10 unlike that of FIGS. An internal trigger button 13 is located at the inner distal end of the sleeve trigger 12. Unlike FIGS. 1-15, the trigger button 13 is not visible in any state and does not protrude from the case 12. In the initial state, the gap 33 is provided between the distal end face 12.10 of the sleeve trigger 12 and the internal trigger button 13 so that the sleeve trigger 12 can move somewhat without interfering with the trigger button 13. It has become.

  The auto-injector 1 is otherwise not different from the auto-injector of FIGS. 1-15 and operates essentially the same except for the following.

  As the chassis 2 is applied to the injection site, the sleeve trigger 12 translates in the proximal direction P relative to the chassis 2 in the first stage of the sleeve stroke and moves to the advanced position, and the distal of the sleeve trigger 12 The gap 33 between the end face 12.10 and the internal trigger button 13 is removed. As in the embodiment of FIGS. 1-15, this movement causes the detent mechanism 18 and the trigger button 13 to be unlocked. If the user continues to depress the sleeve trigger 12 in the second stage of the sleeve stroke, then the sleeve trigger 12 is further advanced in the proximal direction P and the distal end face 12.10 hits the internal trigger button 13. , Thereby trigger button 13 is depressed until first collar 20 is released from chassis 2 and the control spring force is coupled to carrier 7. Carrier 7 then advances until internal trigger button 13 stops on another rib in case 12 and plunger release mechanism 27 is released (note that peg 14 is shorter in this embodiment). ).

  From the user's point of view, the detent mechanism 18 is arranged such that a resistance is provided when the user reaches the second stage of the sleeve stroke. Internally, there is no difference from the embodiment of FIGS.

  Needle extension is activated by the user who fully advances the sleeve trigger 12 in the second stage of the sleeve stroke, thereby causing the internal trigger button 13 to be fully depressed, in the embodiment of FIGS. Overcoming such a detent mechanism.

  The control spring 19 takes over the button depression and advances the carrier 7 completely for needle extension, so that the internal trigger button 13 reaches the bottom at the fifth rib 12.11 inside the sleeve trigger 12, As shown in the third state shown in FIG. 15C, the switch is reversed and locked to the sleeve trigger 12.

  The embodiment of FIGS. 26A and 26B can also be combined with the alternative features shown in FIGS.

  FIG. 27 is a longitudinal cross-sectional view of the distal end of the auto-injector 1 with the alternative feedback release mechanism 31 in the first position before activation. A plunger 9 acting on a syringe or stopper (not shown) is held in the syringe carrier 7. A trigger button 13 is placed on the distal end of the syringe carrier 7. A drive spring 8 is arranged in the carrier 7, the foundation is placed in the carrier 7 distally and bears the thrust surface 11 on the plunger 9 proximally. A distal plunger sleeve 17 is attached distally to the thrust surface 11 and is located inside the drive spring 8. The feedback component 28 includes an elongate portion 28.1 disposed in the distal plunger sleeve 17 and a distal end pin 28.4, the distal end pin 28.4 being in a first position. The whole is located in the carrier 7 and therefore cannot be seen or touched by the user.

  A feedback spring 29 is arranged to bias the feedback component 28 in the distal direction D relative to the plunger 9 by bearing the thrust surface 11 proximally and bearing the feedback component 28 distally. .

  Prestress is applied to both the drive spring 8 and the feedback spring 29. The plunger 9 is engaged with the carrier 7 by a plunger release mechanism (not shown). The plunger release mechanism can be arranged as in one of the embodiments described above.

  The distal plunger sleeve 17 comprises two resilient tilt latches 17.1 that hold the feedback component 28 by engaging its tilted surface 28.5. The latch 17.1 is supported on the outside by the thickened wall portion 7.22 of the carrier 7 so that it is not deflected outward by the action of the bevelled force from the feedback spring 29. Thus, the feedback component 28 cannot be released in this configuration.

  FIG. 28 is a longitudinal cross-sectional view of the distal end of the automatic injector 1 with the alternative feedback release mechanism 31 of FIG. 27 in the second position after release.

  The plunger 9 is released by the plunger release mechanism, and therefore translates in the proximal direction P to displace the stopper. While the plunger 9 moves proximally, the tilt latch 17.1 on the distal plunger sleeve 17 leaves the thickened wall portion 7.22 and enters the widened portion to force force from the feedback spring 29. The tilting action received can be deflected outward. The feedback component is driven by a feedback spring 29 through the distal end of the carrier 7 and advanced in the distal direction D, so that the distal end pin 28.4 eventually has the feedback component 28 in the second position. When the position is reached, it protrudes from the distal end of the trigger button 13 through its hole 13.7. Thus, the distal end pin 28.4 is visible to the user. If the user still presses trigger button 13 with his thumb, he can also touch distal end pin 28.4 with his thumb. Furthermore, the inclined surface 28.5 hitting the trigger button 13 from the inside can generate both audible feedback and tactile impact.

  The distal plunger sleeve 17 can have one or more elastic tilt latches 17.1. The at least one elastic tilt latch 17.1 can likewise be directly connected to the thrust surface 11 on the plunger 9, so that the distal plunger sleeve 17 is not required.

  The trigger button 13 can be coupled to the carrier 7 or to a case (not shown) surrounding the carrier 7. The trigger button 13 does not necessarily have to stay at the same vertical position with respect to the carrier 7. Instead, at the end of the dose, the trigger button 13 can still be located at the end of the case (not shown) and the carrier 7 has been advanced inside the case with all its internal components. . For this purpose, the feedback spring 29 and the feedback component 28 are such that the feedback component 28 is reasonably strong and long at the end of the dose so that the distal end pin 28.4 can protrude from the trigger button 13. It must be ensured that the trigger button 13 is still reached.

  The feedback component 28 can be designed to be released before the plunger 9 and stopper reach their end of dose, preferably just prior to this event.

  The noise component 28 according to FIGS. 27 and 28 can be combined with the embodiment shown in FIGS. 1 to 26, each trigger button 13 or winding sleeve trigger 12 comprising a hole 13.7 and feedback. Component 28 has a distal end pin 28.4. Release of the feedback component 28 can be accomplished by the feedback release mechanism 31 of FIGS. 27 and 28, or by one of the feedback release mechanisms 31 shown in other embodiments.

  The noise release mechanism 31 according to FIGS. 27 and 28 can be similarly applied to other types of automatic injectors. For example, the syringe carrier 7 may be used as part of the case or housing rather than being placed in an extra case. Similarly, the hole 13.7 may be located in a portion of the case or winding sleeve trigger rather than in the trigger button 13.

  The distal end pin 28.4 has a different color than the trigger button 13 to improve the visual indication to the user that the end of the dose has been reached and that the device has been used. For example, it can have a red color.

  In all inclined engagements between the two components described in the above embodiments, one or the other component can have only one bevel without significantly affecting the effect of the inclined engagement. Needless to say, or both components may have slopes.

The term “drug” or “agent” as used herein means a pharmaceutical formulation comprising at least one pharmaceutically active compound,
Here, in one embodiment, the pharmaceutically active compound has a molecular weight of up to 1500 Da and / or a peptide, protein, polysaccharide, vaccine, DNA, RNA, enzyme, antibody or fragment thereof, hormone Or an oligonucleotide, or a mixture of the above-mentioned pharmaceutically active compounds,
Here, in a further embodiment, the pharmaceutically active compound is diabetic or diabetes related complications such as diabetic retinopathy, thromboembolism such as deep vein thromboembolism or pulmonary thromboembolism, acute coronary syndrome (ACS), useful for the treatment and / or prevention of angina pectoris, myocardial infarction, cancer, macular degeneration, inflammation, hay fever, atherosclerosis and / or rheumatoid arthritis,
Here, in a further embodiment, the pharmaceutically active compound comprises at least one peptide for the treatment and / or prevention of diabetes-related complications such as diabetes or diabetic retinopathy,
Here, in a further embodiment, the pharmaceutically active compound is at least one human insulin or human insulin analogue or derivative, glucagon-like peptide (GLP-1) or analogue or derivative thereof, or exendin-3 or exendin -4 or exendin-3 or analogs or derivatives of exendin-4.

  Insulin analogues include, for example, Gly (A21), Arg (B31), Arg (B32) human insulin; Lys (B3), Glu (B29) human insulin; Lys (B28), Pro (B29) human insulin; Asp ( B28) human insulin; proline at position B28 is replaced with Asp, Lys, Leu, Val, or Ala, and at position B29, human insulin where Lys may be replaced with Pro; Ala (B26) human insulin; Des (B28-B30) human insulin; Des (B27) human insulin, and Des (B30) human insulin.

  Insulin derivatives include, for example, B29-N-myristoyl-des (B30) human insulin; B29-N-palmitoyl-des (B30) human insulin; B29-N-myristoyl human insulin; B29-N-palmitoyl human insulin; B28- N-myristoyl LysB28ProB29 human insulin; B28-N-palmitoyl-LysB28ProB29 human insulin; B30-N-myristoyl-ThrB29LysB30 human insulin; B30-N-palmitoyl-ThrB29LysB30 human insulin; B29-N- (N-palmitoyl-Y) -Des (B30) human insulin; B29-N- (N-ritocryl-Y-glutamyl) -des (B30) human insulin; B29-N- (ω Carboxyheptadecanoyl) -des (B30) human insulin, and B29-N-(a ω- carboxyheptadecanoyl) human insulin.

  Exendin-4 is, for example, H-His-Gly-Glu-Gly-Thr-Phe-Thr-Ser-Asp-Leu-Ser-Lys-Gln-Met-Glu-Glu-Glu-Ala-Val-Arg-Leu Exendin-4 (1-39, which is a peptide of the sequence -Phe-Ile-Glu-Trp-Leu-Lys-Asn-Gly-Gly-Pro-Ser-Ser-Gly-Ala-Pro-Pro-Pro-Ser-NH2 ).

Exendin-4 derivatives are, for example, compounds of the following list:
H- (Lys) 4-desPro36, desPro37 exendin-4 (1-39) -NH2,
H- (Lys) 5-desPro36, desPro37 exendin-4 (1-39) -NH2,
desPro36 exendin-4 (1-39),
desPro36 [Asp28] exendin-4 (1-39),
desPro36 [IsoAsp28] exendin-4 (1-39),
desPro36 [Met (O) 14, Asp28] exendin-4 (1-39),
desPro36 [Met (O) 14, IsoAsp28] Exendin- (1-39),
desPro36 [Trp (O2) 25, Asp28] exendin-4 (1-39),
desPro36 [Trp (O2) 25, IsoAsp28] exendin-4 (1-39),
desPro36 [Met (O) 14, Trp (O2) 25, Asp28] exendin-4 (1-39),
desPro36 [Met (O) 14Trp (O2) 25, IsoAsp28] Exendin-4 (1-39); or desPro36 [Asp28] Exendin-4 (1-39),
desPro36 [IsoAsp28] exendin-4 (1-39),
desPro36 [Met (O) 14, Asp28] exendin-4 (1-39),
desPro36 [Met (O) 14, IsoAsp28] Exendin- (1-39),
desPro36 [Trp (O2) 25, Asp28] exendin-4 (1-39),
desPro36 [Trp (O2) 25, IsoAsp28] exendin-4 (1-39),
desPro36 [Met (O) 14, Trp (O2) 25, Asp28] exendin-4 (1-39),
desPro36 [Met (O) 14, Trp (O 2) 25, IsoAsp 28] Exendin-4 (1-39),
(Wherein the group -Lys6-NH2 may be attached to the C-terminus of the exendin-4 derivative);

Or an exendin-4 derivative of the following sequence:
desPro36 exendin-4 (1-39) -Lys6-NH2 (AVE0010),
H- (Lys) 6-desPro36 [Asp28] Exendin-4 (1-39) -Lys6-NH2,
desAsp28Pro36, Pro37, Pro38 exendin-4 (1-39) -NH2,
H- (Lys) 6-desPro36, Pro38 [Asp28] Exendin-4 (1-39) -NH2,
H-Asn- (Glu) 5desPro36, Pro37, Pro38 [Asp28] Exendin-4 (1-39) -NH2,
desPro36, Pro37, Pro38 [Asp28] Exendin-4 (1-39)-(Lys) 6-NH2,
H- (Lys) 6-desPro36, Pro37, Pro38 [Asp28] Exendin-4 (1-39)-(Lys) 6-NH2,
H-Asn- (Glu) 5-desPro36, Pro37, Pro38 [Asp28] Exendin-4 (1-39)-(Lys) 6-NH2,
H- (Lys) 6-desPro36 [Trp (O2) 25, Asp28] exendin-4 (1-39) -Lys6-NH2,
H-desAsp28Pro36, Pro37, Pro38 [Trp (O2) 25] exendin-4 (1-39) -NH2,
H- (Lys) 6-desPro36, Pro37, Pro38 [Trp (O2) 25, Asp28] exendin-4 (1-39) -NH2,
H-Asn- (Glu) 5-desPro36, Pro37, Pro38 [Trp (O2) 25, Asp28] exendin-4 (1-39) -NH2,
desPro36, Pro37, Pro38 [Trp (O2) 25, Asp28] exendin-4 (1-39)-(Lys) 6-NH2,
H- (Lys) 6-desPro36, Pro37, Pro38 [Trp (O2) 25, Asp28] exendin-4 (1-39)-(Lys) 6-NH2,
H-Asn- (Glu) 5-desPro36, Pro37, Pro38 [Trp (O2) 25, Asp28] exendin-4 (1-39)-(Lys) 6-NH2,
H- (Lys) 6-desPro36 [Met (O) 14, Asp28] exendin-4 (1-39) -Lys6-NH2,
desMet (O) 14, Asp28Pro36, Pro37, Pro38 exendin-4 (1-39) -NH2,
H- (Lys) 6-desPro36, Pro37, Pro38 [Met (O) 14, Asp28] exendin-4 (1-39) -NH2,
H-Asn- (Glu) 5-desPro36, Pro37, Pro38 [Met (O) 14, Asp28] exendin-4 (1-39) -NH2;
desPro36, Pro37, Pro38 [Met (O) 14, Asp28] Exendin-4 (1-39)-(Lys) 6-NH2,
H- (Lys) 6-desPro36, Pro37, Pro38 [Met (O) 14, Asp28] exendin-4 (1-39)-(Lys) 6-NH2,
H-Asn- (Glu) 5desPro36, Pro37, Pro38 [Met (O) 14, Asp28] Exendin-4 (1-39)-(Lys) 6-NH2,
H-Lys6-desPro36 [Met (O) 14, Trp (O2) 25, Asp28] Exendin-4 (1-39) -Lys6-NH2,
H-desAsp28, Pro36, Pro37, Pro38 [Met (O) 14, Trp (O2) 25] exendin-4 (1-39) -NH2,
H- (Lys) 6-desPro36, Pro37, Pro38 [Met (O) 14, Asp28] exendin-4 (1-39) -NH2,
H-Asn- (Glu) 5-desPro36, Pro37, Pro38 [Met (O) 14, Trp (O2) 25, Asp28] Exendin-4 (1-39) -NH2,
desPro36, Pro37, Pro38 [Met (O) 14, Trp (O2) 25, Asp28] Exendin-4 (1-39)-(Lys) 6-NH2,
H- (Lys) 6-desPro36, Pro37, Pro38 [Met (O) 14, Trp (O2) 25, Asp28] Exendin-4 (S1-39)-(Lys) 6-NH2,
H-Asn- (Glu) 5-desPro36, Pro37, Pro38 [Met (O) 14, Trp (O2) 25, Asp28] Exendin-4 (1-39)-(Lys) 6-NH2;
Or a pharmaceutically acceptable salt or solvate of any one of the aforementioned exendin-4 derivatives.

  The hormones include, for example, gonadotropin (folytropin, lutropin, corion gonadotropin, menotropin), somatropin (somatropin), desmopressin, telluripressin, gonadorelin, triptorelin, leuprorelin, buserelin, nafarelin, goserelin, etc., Rote Liste, 2008 Pituitary hormones or hypothalamic hormones or regulatory active peptides and antagonists thereof.

  Polysaccharides include, for example, glucosaminoglycan, hyaluronic acid, heparin, low molecular weight heparin, or ultra low molecular weight heparin, or derivatives thereof, or sulfated forms of the above-described polysaccharides, such as polysulfated forms, and Or a pharmaceutically acceptable salt thereof. An example of a pharmaceutically acceptable salt of polysulfated low molecular weight heparin is sodium enoxaparin.

  Antibodies are globular plasma proteins (about 150 kDa), also known as immunoglobulins that share a basic structure. These are glycoproteins because they have sugar chains attached to amino acid residues. The basic functional unit of each antibody is an immunoglobulin (Ig) monomer (including only one Ig unit), and the secretory antibody is also a dimer having two Ig units such as IgA, teleost It can also be a tetramer with 4 Ig units, such as IgM, or a pentamer with 5 Ig units, like mammalian IgM.

  An Ig monomer is a “Y” -shaped molecule composed of four polypeptide chains, two identical heavy chains and two identical light chains joined by a disulfide bond between cysteine residues. It is. Each heavy chain is about 440 amino acids long and each light chain is about 220 amino acids long. Each heavy and light chain contains intrachain disulfide bonds that stabilize these folded structures. Each chain is composed of structural domains called Ig domains. These domains contain about 70-110 amino acids and are classified into different categories (eg, variable or V, and constant or C) based on their size and function. They have a characteristic immunoglobulin fold that creates a “sandwich” shape in which two β-sheets are held together by the interaction between conserved cysteines and other charged amino acids.

  There are five types of mammalian Ig heavy chains represented by α, δ, ε, γ and μ. The type of heavy chain present defines the isotype of the antibody, and these chains are found in IgA, IgD, IgE, IgG, and IgM antibodies, respectively.

Different heavy chains differ in size and composition, α and γ contain about 450 amino acids, δ contain about 500 amino acids, and μ and ε have about 550 amino acids. Each heavy chain has two regions: a constant region (C _H ) and a variable region (V _H ). In one species, the constant region is essentially the same for all antibodies of the same isotype, but different for antibodies of different isotypes. Heavy chains γ, α, and δ have a constant region composed of three tandem Ig domains and a hinge region to add flexibility, and heavy chains μ and ε are four immunoglobulins -It has a constant region composed of domains. The variable region of the heavy chain is different for antibodies produced by different B cells, but is the same for all antibodies produced by a single B cell or B cell clone. The variable region of each heavy chain is approximately 110 amino acids long and is composed of a single Ig domain.

  In mammals, there are two types of immunoglobulin light chains, denoted λ and к. The light chain has two consecutive domains, one constant domain (CL) and one variable domain (VL). The approximate length of the light chain is 211-217 amino acids. Each antibody has two light chains that are always identical, and there is only one type of light chain κ or λ for each mammalian antibody.

  Although the general structure of all antibodies is very similar, the unique properties of a given antibody are determined by the variable (V) region, as detailed above. More specifically, three variable loops for each light chain (VL) and three variable loops in the heavy chain (HV) are involved in antigen binding, ie its antigen specificity. These loops are called complementarity determining regions (CDRs). Since CDRs from both the VH and VL domains contribute to the antigen binding site, it is the combination of heavy and light chains that determines the final antigen specificity, not either alone.

  “Antibody fragments” comprise at least one antigen-binding fragment as defined above and exhibit essentially the same function and specificity as the complete antibody from which the fragment is derived. Limited protein digestion with papain cleaves the Ig prototype into three fragments. Two identical amino terminal fragments, each containing one complete light chain and about half the heavy chain, are antigen-binding fragments (Fabs). A third fragment that is equivalent in size but contains a carboxyl terminus at half the positions of both heavy chains with interchain disulfide bonds is a crystallizable fragment (Fc). Fc includes a carbohydrate, a complementary binding site, and an FcR binding site. Limited pepsin digestion yields a single F (ab ') 2 fragment containing both the Fab piece and the hinge region containing the H-H interchain disulfide bond. F (ab ') 2 is divalent for antigen binding. The disulfide bond of F (ab ') 2 can be cleaved to obtain Fab'. In addition, the variable regions of the heavy and light chains can be condensed to form a single chain variable fragment (scFv).

  Pharmaceutically acceptable salts are, for example, acid addition salts and basic salts. Examples of acid addition salts include HCl or HBr salts. The basic salt is, for example, a cation selected from alkali or alkaline earth metals, such as Na +, or K +, or Ca2 +, or ammonium ions N + (R1) (R2) (R3) (R4) (wherein R1-R4 are independently of each other: hydrogen, optionally substituted C1-C6 alkyl group, optionally substituted C2-C6 alkenyl group, optionally substituted C6-C10 aryl group, or optionally substituted C6 Meaning a C10 heteroaryl group). Additional examples of pharmaceutically acceptable salts can be found in “Remington's Pharmaceutical Sciences” 17th edition, Alfonso R. et al. Gennaro (eds.), Mark Publishing Company, Easton, Pa. U. S. A. 1985, and Encyclopedia of Pharmaceutical Technology.

  A pharmaceutically acceptable solvate is, for example, a hydrate.

DESCRIPTION OF SYMBOLS 1 Auto-injector 2 Chassis 2.1 Elastic beam 2.2 1st beam head 2.3 Proximal 3rd slope 2.4 Distal 7th slope 2.5 Opening 2.6 Third clip 2.7 Slot 2.8 f Fourth beam head 2.9 Third rib 2.10 Fifth clip 2.11 Sixth clip 3 Syringe 4 Hollow injection needle 5 Protective needle sheath 6 Stopper 7 Carrier 7 .1 Slope Member 7.2 Proximal Fourth Slope 7.3 Distal Fifth Slope 7.4 Carrier Detent 7.5 Second Recess 7.6 Distal Tenth Slope 7.7 Third recess 7.8 Twelve slope 7.9 Vertical opening 7.10 Second rib 7.11 First window 7.12 First clip 7.13 Second clip 7.14 First Portion 7.15 second portion 7.16 third beam head 7.17 fifth recess 7.18 Fourth rib 7.19 Fourteenth slope 7.20 Fifteenth slope 7.21 Seventh clip 7.22 Opening 7.23 Thickened wall portion 8 Drive spring 9 Plunger 9.1 Slope member 9 .2 Proximal Inclined Rib 10 Carrier End Surface 11 Thrust Surface 12 Case 12.1 First Case Detent 12.2 Second Case Detent 12.3 First Rib 12.4 First Back Stop 12. 5 4th recessed part 12.6 Slope function 12.7 6th recessed part 12.8 2nd window 12.9 3rd window 12.10 Distal end surface 12.11 5th rib 13 Trigger button 13. 1 Proximal Beam 13.2 Outward First Slope 13.3 Inward Second Slope 13.4 Inclined Outward Boss 13.5 Inward Projection 13.6 Second Back Stop 13.7 Hole 14 pegs 14.1 Proximal extension 15 Elasticity 16 First recess 17 Distal carrier sleeve 17.1 Elastic tilt latch 18 Detent mechanism 19 Control spring 20 First collar 20.1 Arrowhead 20.2 Outward sixth bevel 20.3 Inward 9th slope 20.4 tab 20.5 fourth clip 20.6 inward proximal 13th slope 20.7 block 20.8 fifth clip 21 second collar 21.1 proximal beam 21.2 Second Beam Head 21.3 Inward Boss 21.4 Distal Eighth Slope 21.5 Vertical Rib 22 Cap 22.1 Inner Sleeve 23 Return 24 Needle Extension Control Mechanism 25 Syringe Retraction Control Mechanism 26 Button release mechanism 27 Plunger release mechanism 28 Feedback component 28.1 Elongate portion 28.2 Distal end portion 28.3 Eleventh bevel facing outward 28.4 Distal end pin 28.5 Slope 29 Feedback spring 30 Second elastic arm 30.1 Inclined inward boss 31 Feedback release mechanism 32 Indicator window 33 Clearance D Distal end, distal direction I Inward direction M Drug O Outward direction P Proximal End, proximal direction

Claims (9)

In an injection device for administering a dose of a drug (M)
A case (12) having a proximal end and a distal end;
A carrier (7) adapted to receive a syringe (3);
A trigger button (13),
Here, in the first state, the trigger button (13) is coupled to the case (12) and / or the carrier (7) and abuts the distal end of the case (12);
In the intermediate state, the case (12) moves proximally relative to the carrier (7) and the trigger button (13), the trigger button (13) engages the carrier (7),
In the second state, the trigger button (13) and carrier (7) move proximally with respect to the case (12), and the trigger button (13) disengages from the carrier (7) and case (12). The injection device.   The injection device according to claim 1, wherein the trigger button (13) comprises a deflectable beam (13.1) adapted to engage the case (12) and the carrier (7).   The injection device according to claim 2, wherein the case (12) comprises a case detent (12.1) adapted to engage the beam (13.1).   The injection device according to claim 3, wherein the beam (13.1) comprises a first bevel (13.2) adapted to engage the case (12.1).   The injection device according to claim 2, wherein the carrier (7) comprises a carrier detent (7.4) adapted to engage the beam (13.1).   The injection device according to claim 5, wherein the beam (13.1) comprises a second bevel (13.3) adapted to engage the carrier detent (7.4).   3. The injection device according to claim 2, wherein in the first state the beam (13.1) engages the case (12.1) and / or the carrier detent (7.4).   4. The injection device according to claim 3, wherein in the second state the beam (13.1) engages the case detent (12.1) and abuts the carrier (7).   6. The injection device according to claim 5, wherein in the intermediate state the beam (13.1) engages the carrier detent (7.4) and abuts the case (12).

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