TW201330890A - Auto-injector - Google Patents

Abstract

Described is an injection device (1) for administering a dose of a medicament (M) comprising a carrier (7) adapted to contain a syringe (3) having a hollow injection needle (4) and a stopper (6), a drive spring (8), a plunger (9) adapted to forward load of the drive spring (8) to the stopper, and a noise component (28) adapted to generate an audible and/or tactile feedback by impacting a component of the injection device (1) when the stopper (4) is located at a proximal end of the syringe (3). In a first state, a resilient arm (30) on the plunger (9) is maintained in engagement with the noise component (28) by the carrier (7). In a second state, the arm (30) disengages the noise component (28) and deflects at least partially into an aperture (7.22) in the carrier (7).

Description

Autoinjector

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

The administration of an injection system is a procedure that poses several risks and challenges to both the user and the medical practitioner both psychologically and physiologically.

Injection devices (i.e., devices capable of delivering drugs from a medicament container) are typically grouped into two categories - a manual device and an auto-injector.

In a manual device, the user must provide mechanical energy to drive fluid through the needle. This is typically achieved by some form of button/plunger that must be continuously pressed by the user during injection. This approach has many disadvantages for the user. If the user stops pressing the button/plunger, the injection will also stop. This means that if the device is not properly used (ie, the plunger is not fully pressed to its end position), the user will deliver an insufficient dose. The injection force may be too high for the user, especially if the patient is old or has sensitivity problems.

The extension of the button/plunger may be too large. Therefore, the user may not be able to touch a fully extended button. The combination of injection force and button extension causes the hand to tremble/shake, which in turn increases discomfort as the inserted needle moves.

The purpose of autoinjectors is to make it easier for patients to self-administer injection therapy. Current therapies delivered by self-administered injections include diabetes (insulin and newer GLP-1 grade drugs), biased Pain, hormone therapy, anticoagulant drugs, etc.

Autoinjectors are devices that completely or partially replace the activities involved in the delivery of non-oral drugs from standard syringes. These activities may include removing a protective syringe cover, inserting a needle into a patient's skin, injecting a drug, removing the needle, shielding the needle, and preventing reuse of the device. This overcomes many of the shortcomings of manual devices. The possibility of injection force/button extension, hand sway, and delivery of incomplete doses is reduced. Triggering can be done by a number of means, such as a trigger button or the needle reaching its depth of injection. In some devices, the energy of the transport fluid is provided by a spring.

US 2002/0095120 A1 discloses an automatic injection device that automatically injects a pre-measured amount 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 upon release. A piston is then forced into the inside of the ampoule by a tension spring to propel the contents of the ampoule. After the fluid has been injected, the torque stored in the tension spring is released and the needle is automatically retracted to its original storage position.

High-viscosity drugs require a powerful force to drive them through relatively thin needles. In order to achieve these forces, a strong drive spring is required. This can cause the user to experience high impact when the needle is inserted into the skin, and the user feels strong when triggering the injection.

One of the objects of the present disclosure is to provide an improved autoinjector.

This object is achieved by an autoinjector as described in claim 1 of the patent application.

Preferred embodiments of the invention are provided in the scope of the claims of the appended claims.

In the context of this specification, the terminology refers to the direction toward the patient during an injection, while the terminology refers to the opposite direction away from the patient. Inward terminology refers to the radial direction toward one of the longitudinal axes of the autoinjector, while the outward term refers to the opposite direction radially away from the longitudinal axis.

In an exemplary embodiment, an injection device for administering a dose of a medicament comprises a carrier adapted to contain a syringe having a hollow injection needle and a stopper, a drive spring, and a a plunger adapted to deliver a load of the drive spring to the stop, and a noise assembly adapted to generate an audible and/or by impacting a component of the injection device when the stopper is positioned at a proximal end of the syringe Or tactile feedback. In the first state, a resilient arm on the plunger is maintained in engagement with the noise component by the carrier. In the second state, the arm is disengaged from the noise component and at least partially flexed into an opening in the carrier.

In an exemplary embodiment, in an intermediate state, the plunger moves relatively proximally relative to the carrier, allowing the arms to flex radially and out of the noise assembly.

In an exemplary embodiment, the injection device further includes a spring that applies a biasing force to the noise assembly.

In an exemplary embodiment, the components of the injection device to which the noise component impacts are a base, a casing, a trigger button, a carrier, and/or a plunger.

In an exemplary embodiment, the arm train includes a ramped inner hub adapted to engage an outwardly eleventh ramp on the noise assembly.

In an exemplary embodiment, the assembly has a physical shape and/or design and/or material suitable for amplifying and/or transmitting a sound.

In an exemplary embodiment, the noise component includes an elongate portion and a distal portion that is configured to impact the assembly.

Further scope of applicability of the present invention will be apparent from the following detailed description. It is to be understood that the detailed description and specific embodiments of the invention may

A ramped joint in the context of this specification is a joint between two components, at least one of which has a ramp for engaging another component in such a manner that when the components are axially pushed against each other When one of the components is flexed to the side, if the component is not prevented from flexing sideways.

Figures 1a and 1b show two longitudinal sections of an autoinjector 1 in a different cross-sectional plane, the different cross-sectional planes being approximately 90° rotated from each other, wherein the autoinjector 1 is in an initial state prior to the start of an injection. The autoinjector 1 includes a base 2. In the following, the base 2 is generally considered to be fixed in position, so the action of the other components is described with respect to the base 2. A syringe 3 having a hollow injection needle 4, such as a Hypak syringe, is disposed in a proximal portion of the autoinjector 1. When the autoinjector 1 or the syringe 3 is assembled, a protective needle cover (not shown) is attached to the needle 4. A stopper 6 is configured to seal the syringe 3 distally and to displace a drug M through the hollow needle 4. Syringe 3 It is held in a tubular carrier 7 and supported at its proximal end. The carrier 7 is slidably disposed in the base 2.

A drive spring 8 in the form of a compression spring is disposed in a distal portion of the carrier 7. A plunger 9 is used to deliver the force of the drive spring 8 to the stopper 6.

The drive spring 8 is supported between a distal end face 10 of the carrier 7 and a thrust face 11 disposed distally of the plunger 9.

The carrier 7 is a key component for accommodating the syringe 3, the drive spring 8 and the plunger 9, and the syringe 3, the drive spring 8 and the plunger 9 are components required for ejecting the medicine M from the syringe 3. These components can therefore be referred to as a drive sub-assembly.

The base 2 and the carrier 7 are disposed in a tubular casing 12. A trigger button 13 is disposed at a distal end of the casing 12. In a plunger release mechanism 27, a peg 14 is attached to the trigger button 13 in the proximal direction P between the two resilient arms 15 originating from and extending distally from the thrust surface 11 of the plunger 9 in the drive spring 8. A distal end surface projects to prevent it from deflecting toward each other in an initial state A as shown in Fig. 14A. In Figure 14A, only one of the malleable arms 15 is shown with an exemplary principle. Outwardly, the resilient arms 15 are captured in respective first recesses 16 in a distal carrier sleeve 17 that are distally attached to the distal end face 10 and disposed within the drive spring 8. The engagement of the malleable arm 15 in the first recess 16 prevents axial translation of the plunger 9 relative to the carrier 7. The malleable arm 15 has a slope shape such that it is deflected inwardly when the plunger 9 and the carrier 7 are relatively moved between the load of the drive spring 8, and is prevented by the pile 14 in the initial state A.

The carrier 7 is locked to the base 2 by a stop mechanism 18, shown in more detail in Figures 10A through 10D, to prevent relative translation.

The trigger button 13 is initially engaged to the casing 12 by a button release mechanism 26 and cannot be pressed. The button release mechanism 26 is shown in detail in Figs. 15A to 15C. Referring now to Figure 15A, the button release mechanism 26 includes a tough proximal beam 13.1 on the trigger button 13, and the proximal beam 13.1 has an outer first ramp 13.2 and an inner second ramp 13.3. In an initial state A shown in Fig. 15A, the inner second ramp 13.3 is engaged in a ramp-shaped carrier member 7.4 of the carrier 7 to prevent the trigger button 13 from moving out of the distal end D. The trigger button 13 abuts against the casing 12 and the carrier 7 in a proximal direction, and thus is prevented from being pressed in the proximal direction P.

Referring again to Figures 1A and 1B, a control spring 19 in the form of another compression spring is disposed about the carrier 7 and acts between a first first collar 20 and a distal second collar 21. The control spring 19 is used to move the carrier 7 in the proximal direction P and thus drive the secondary assembly for the needle to extend or to move it in the distal direction D for the needle to retract.

Prior to the state shown in Figures 1A and 1B, a cover 22 is attached to the proximal end of the sheath 12 and the protective needle cover remains in place over the needle 4 and the needle hub. An inner sleeve 22.1 of the cover 22 is disposed inside the base 2 and above the protective needle cover. In the inner sleeve 22.1, a spur 23 is attached. The spine 23 is engaged to protect the needle cover for joint axial translation.

One of the operating sequences of the autoinjector 1 is as follows: A user pulls the cover 22 from the proximal end of the casing 12. The spurs 23 engage the protective needle cover to the cover 22. Therefore, the protective needle cover is also covered 22 was removed when removed. 1A and 1B show an autoinjector 1 in which a cover 22 and a needle cover are removed. The carrier 7 and the syringe 3 are prevented from moving in the proximal direction P by the stop mechanism 18 being in a state A as shown in Fig. 10A. Referring now to Figure 10A, the shackle mechanism 18 includes a tough beam 2.1 on the base 2 having a first beam head 2.2 projecting inwardly. The first beam head 2.2 has a near third slope 2.3. The stop mechanism 18 further includes a diamond-shaped ramp member 7.1 on the carrier 7, the diamond-shaped ramp member 7.1 having a near fourth ramp 7.2 and a far fifth ramp 7.3. In state A, a rounded distal side of the first beam head 2.2 abuts the ramp member 7.1 in the distal direction D against the movement of the carrier 7 relative to the base 2 in the proximal direction P. A rib on the casing 12 is provided to prevent the resilient arm 2.1 from flexing outwardly, thereby also preventing movement of the carrier 7 relative to the base 2.

Referring again to Figures 1A and 1B, the user grasps the sheath 12 and places the base 2 so as to project from the sheath 12 against the injection site at the proximal end P, such as the skin of a patient. As the autoinjector 1 is pressed against the injection site, the base 12 translates in a proximal direction P relative to the base 2 into an advanced position, as shown in Figures 2A and 2B. The second collar 21 is locked to the casing 12 and moved relative to the base 2 with respect to the base 2 and relative to all other components of the autoinjector 1 , thereby slightly compressing the control spring 19 against the first collar 20, Since the needle extension control mechanism 24 is located in a state A as detailed in FIG. 11A, it is prevented from moving in the proximal direction P by the base 2. Referring now to Figure 11A, a resilient member in the shape of an arrow 20.1 is disposed proximally on the first collar 20. The first collar 20 with arrow 20.1 is loaded by the compressed control spring 19 Lower in the proximal direction P is forced. An outwardly directed sixth ramp 20.2 on arrow 20.1 interacts in an inward direction I with a second, distal seventh ramp 2.4 on the base 2 that causes the arrow 20.1 to slope, with the arrow 20.1 facing inwardly against the carrier 7 Be prevented. Therefore, the first collar 20 cannot translate in the proximal direction P.

Arrow 20.1 can have a different geometry than Figures 11A and 11F, such as the rounded arrow 20.1 of Figures 1-9. The function of arrow 20.1 is not affected by this variant.

Referring again to Figures 2A and 2B, since a syringe retraction control mechanism 25 is in a state A as detailed in Figure 12A, the second collar 21 is locked to the casing. Referring now to Figure 12A, the syringe retraction control mechanism 25 includes a tough proximal beam 21.1 on the second collar 21, the proximal beam 21.1 has a second beam head 21.2, and the second beam head 21.2 has an inner hub 21.3 and a distal end. The outer eighth slope is 21.4. The far outer eighth slope 21.4 is engaged in a sloped second casing element 12.2 in an inward direction I in such a way that the second beam head 21.1 is ramped, wherein the second collar 21 is in the forward direction D Under the load of the spring 19, it is prevented by the inner hub 21.3 leaning inward against the carrier 7.

Referring again to Figures 2A and 2B, if the user wants to remove the casing 12 from the injection site, the control spring 19 expands to return the autoinjector 1 to the initial state after the cover 22 is removed, as shown in Figures 1A and 1B.

In the state shown in Figures 2A and 2B, the carrier 7 is prevented from moving in the proximal direction P by the stop mechanism 18, however, since the casing 12 is in its advanced position, the ribs on the casing 12 are also Has been moved Moreover, the tough beam 2.1 is no longer prevented from flexing outward, and the stop mechanism 18 is unlocked. The movement of the casing 12 relative to the carrier 7 that is locked to the base 2 by the shackle mechanism 18 causes the button release mechanism 26 to switch to a state B as shown in Figure 15B. As the casing 12 is moved, the trigger button 13 remains against the carrier 7, wherein the inner second ramp 13.3 on the proximal beam 13.1 is engaged in a ramp-shaped carrier element 7.4 disposed in the carrier 7. As the casing 12 is further translated in the proximal direction P, it supports the proximal beam 13.1 to the outside and thus locks the trigger button 13 to the carrier 7. The trigger button 13 now protrudes from the distal end D of the casing 12 and is ready to be pressed.

In the state shown in FIGS. 2A and 2B, the user presses the trigger button 13 in the proximal direction P. As the trigger button 13 abuts against the carrier 7, the carrier 7 is pushed against the base 2 in the proximal direction P, and the carrier 7 and the base 2 interact in the stop mechanism 18. The force applied by the user against the trigger button 13 is resolved through the base 2 to the injection site rather than between the trigger button 13 and the casing 12. When the user pushes the trigger button 13, the stop mechanism 18 provides a resistance. Once the user applies a force that exceeds a predetermined value, the stop mechanism 18 is released, causing an injection cycle. Referring now to Figure 10B, showing the stop mechanism 18 in a state B, the ductile beam 2.1 on the base 2 begins to bow under the load of the rhomboid ramp member 7.1 from the carrier 7 to store the elastic energy. Despite the near fourth slope 7.2 on the ramp member 7.1, the friction between the contact surface of the first beam head 2.2 and the near fourth ramp 7.2 prevents movement of the first beam head 2.2 in the outward direction O until ductile deformation The straightening force of beam 2.1 is large enough to be overcome. At this point, the ductile beam 2.1 deflects in the outward direction O and moves out of the carrier path. In addition, the carrier 7 is thus allowed to translate in the proximal direction P. When the carrier 7 is moved far enough in the proximal direction P, the rhomboid ramp member 7.1 on the carrier 7 passes under the first beam head 2.2 and thus allows it to relax and move back in the inward direction I distally to the rhomboid ramp member 7.1 Rearward, it is in a state C as shown in Fig. 10C while being translated with respect to the base 2 in the distal direction D with the restraining carrier 7.

Once the carrier 7 slides far enough relative to the first collar 20 in the proximal direction P, the needle extension control mechanism 24 switches to a state B as shown in Figure 11B. In Fig. 11B, the carrier 7 has been translated in the proximal direction P in such a manner that the arrow 20.1 on the first collar 20 is no longer supported inwardly. This effect can be achieved by a second recess 7.5 in the carrier 7. The arrow 20.1 is now deflected in the inward direction I into the second recess 7.5 under the load of the control spring 19 to reach a state C as shown in Fig. 11C. The first collar 20 is now decoupled from the base 2. Instead, arrow 20.1 couples first collar 20 to carrier 7 by engaging a distal tenth ramp 7.6 on carrier 7 at a proximal end of second recess 7.5 with an inward ninth ramp 20.3. Therefore, the control spring 19 continues to move the carrier 7 from this point in the proximal direction P. Although the user advances the needle 4 to a proportion of its transition, the control spring 19 is inserted into the tube before the needle 4 protrudes from the proximal end P. Therefore, what the user experiences is pressing a button instead of manually inserting a needle.

The stop mechanism 18 relies on the user to apply a force rather than a displacement. Once the applied force exceeds the force required to switch the jaws, the user will fully push the trigger button 13 to ensure that the first collar 20 will always switch. If the user does not pass the trigger, the trigger button 13 returns to its unused state. Ready to use, as shown in Figures 2A and 2B. This feature prevents the autoinjector 1 from reaching in an undefined state.

3A and 3B show the autoinjector 1 in which the trigger button 13 is sufficiently pressed for the control spring 19 to be coupled to the carrier 7 and continues to move the carrier 7 forward, but has not yet abutted against the casing 12.

The carrier 7 coupled to the first collar 20 is driven by the control spring 19 to translate in the proximal direction P. As the syringe 3 is configured for axial movement in conjunction with the carrier 7, the syringe 3 and the needle 4 are also translated to cause the needle 4 to protrude from the proximal end P and be inserted into the injection site. The trigger button 13 is returned to its initial position relative to the casing 12, wherein the proximal beam 13.1 is deflected in the outward direction O by engaging a slope in the carrier element 7.4 by the inner second ramp 13.3, so that the proximal beam 13.1 flexes It is inserted into the first casing element 12.1 and latched from the carrier 7 to the casing 12. The carrier 7 is further translated in the proximal direction P to prevent the proximal beam 13.1 from flexing inwardly, so that the outer first ramp 13.2 cannot be disengaged from the first casing element 12.1.

Immediately before the needle 4 reaches the full insertion depth, as shown in Figures 4A and 4B, the pegs 14 on the trigger button 13 are sufficiently pulled out from between the malleable arms 15 on the carrier 7 to allow the tough arms 15 to flex inwardly. . Therefore, the plunger release mechanism 27 reaches the state B shown in Fig. 14B, in which the malleable arm 15 is no longer supported inward by the pegs 14. Since the malleable arm 15 is wedge-shapedly engaged in the first recess 16, it is deflected in the inward direction I under the load of the drive spring 8, reaching the state C shown in Fig. 14C. Therefore, the plunger 9 is released from the carrier 7 and driven by the drive spring 8 in the proximal direction P, ready to discharge the drug M. Pulling the pegs 14 from between the malleable arms 15 The force is provided by the control spring 19, while the force required to flex the tough arms 15 without being engaged with the carrier 7 is provided by the drive spring 8.

When the plunger 9 moves and closes a gap for the stopper 9, the movement of the carrier 7 in the proximal direction P is accomplished by the control spring 19 that urges the first collar 20. As the carrier 7 moves relative to the base 2 during extension of the needle, the needle extension mechanism 24 reaches a state D as shown in Figure 11D. The arrow 20.1 has moved along with the carrier 7 and remains flexed inwardly by the base 2, thus preventing the first collar 20 from disengaging from the carrier 7. Arrow 20.1 must be able to flex in the outward direction O to allow for retraction, as discussed below. To allow for outward flexing, arrow 20.1 moves proximally beyond the portion of base 2 shown in Figures 11A through 11F next to an opening 2.5 in base 2. However, as long as the casing 2 is held against the injection site and is not allowed to return more than a predetermined distance in the distal direction D under the load of the control spring 19, the arrow 20.1 will be in its second half for the action of the needle extension. During this period, a first rib 12.3 on the casing 12 is kept from flexing in the outward direction O (not shown in Figs. 11A to 11F, see Figs. 4A to 7A).

The needle 4 is now fully inserted into the injection site as shown in Figures 5A and 5B. The time between when the trigger button 13 is pressed and the needle 4 is fully inserted is short, however, several mechanical operations occur at this time. The depth of the needle extension is defined by the carrier 7 relative to the base 2 rather than to the casing 2, so if the user retracts or fails to hold the autoinjector 1 against the skin, only the casing 2 will move in the distal direction D, The injection depth remains constant.

Once the plunger 9 has been closed under the force of the drive spring 8 for the stop In the gap of 6, the stopper 6 is pushed in the proximal direction P in the syringe 3, and the drug M is displaced through the needle 4.

Immediately after the stopper 6 has almost reached the end of the discharge of the syringe 3 as shown in Figs. 6A and 6B, a feedback assembly 28 is released. It is most obvious that the tolerance stacking due to the syringe 3 is such that the feedback must always be released before the drug is completely drained. Otherwise, the feedback will not always be released for a particular combination of components. The feedback assembly 28 includes an elongate portion 28.1, the elongate portion 28.1 being a resilient arm 15 disposed on the plunger 9 and a distal portion of a proximal extension 14.1 disposed against the peg 14 of the trigger button 13 Between 28.2. The two second ductile arms 30 are derived from the plunger 9 and extend in the distal direction D. A feedback spring 29 is configured to bias the feedback assembly 28 in the distal direction D relative to the plunger by bracingly supporting a rib on the plunger 9 and distally against the distal end portion 28.2 of the feedback assembly 28. 9 bias.

Please note that the feedback assembly 28 is not shown in Figures 15A, 15B and 15C for clarity, as it does not affect the function of the button release mechanism 26. 13A, 13B and 13C schematically illustrate a feedback release mechanism 31 for releasing the feedback assembly 28. Referring now to Figure 13A, the feedback release mechanism 31 includes a second resilient arm 30. A ramp-shaped inner hub 30.1 is disposed on each of the second flexible arms 30, and the second flexible arms 30 are coupled to the length of the feedback assembly 28 in such a manner that the second flexible arms 30 are flexed in the outward direction O under the load of the feedback spring 29. One of the eleventh slopes 28.3 on each of the shaped portions 28.1. In the first state A of the feedback release mechanism 31, the second resilient arm 30 is prevented from being deflected outward by the outward support of the carrier 7, This prevents the feedback assembly 28 from translating relative to the plunger 9. Thus, the feedback assembly 28 moves with the plunger 9 and remains in the state A until immediately after the drug is completely expelled and the stopper 6 has almost reached the bottom of the syringe 3, as shown in Figures 6A and 6B. At this point, the plunger 9 has been translated in the proximal direction P relative to the carrier 7 to the extent that the second flexible arm 30 reaches an opening 7.22 in the carrier 7 and is no longer supported externally by the carrier 7. The feedback release mechanism 31 has thus arrived at an intermediate state B as shown in Figure 13B. Due to the ramped engagement between the ramped inner hub 30.1 and the outward eleventh ramp 28.3, the second resilient arm 30 flexes outwardly under the load of the feedback spring 29, thereby disengaging the feedback assembly 28 from the plunger 9 and permitting the feedback assembly 28 The second state C shown in Fig. 13C is driven by the feedback spring 29 to move in the distal direction D. Thus, the feedback assembly 28 is accelerated in the distal direction D, and the distal portion 28.2 impacts on the proximal extension 14.1 of the peg 14 on the trigger button 13, and the hearing and tactile feedback of the drug delivery is completed for the user (please Compare Figures 7A and 7B).

7A and 7B show the autoinjector 1 in which the stopper 6 has completely bottomed out in the syringe 3.

As described above, the user can cause the casing 12 to move in the distal direction D by the force of the control spring 19 by several centimeters without affecting the position of the needle 4 as long as the action is lower than a predetermined distance. If the user wishes to end the injection at any time, it must allow the casing 12 to move beyond the distance in the distal direction D. 8A and 8B show the autoinjector 1 extending, for example, when the base is raised from the injection site, wherein the casing 12 extends in the distal direction D such that the base 2 projects from the proximal end of the casing 12. With the shell 12 Being moved, the first collar 20 releases the carrier 7, and then the second collar 21 is released from the casing 12 and the carrier 7 is pulled in the distal direction D. Since the retraction will fail if the two collars 20, 21 are simultaneously attached to the carrier 7, the order of this switching is very important. The switching of the collars 20, 21 is separated by a significant displacement of the casing 12 to overcome this effect.

The switching of the first collar 20 is shown in Figures 11E and 11F. In Fig. 11E, for example, during removal of the autoinjector 1 from the injection site, the sheath 12 has been allowed to move in the distal direction D under the load of the control spring 19. The first rib 12.3 (not shown, see Figure 8A) is removed from the rear of the arrow 20.1. The first collar 20 is still pushed by the control spring 19 in the proximal direction P. Since the inwardly located ninth ramp 20.3 on arrow 20.1 is engaged with the far tenth ramp 7.6 on the carrier 7, the arrow 20.1 is deflected in the outward direction O into the opening 2.5 of the base 2 (shown in Figures 11A to 11F), The needle extension control mechanism 24 reaches a state E as shown in FIG. 11E, decoupling the first collar 20 from the carrier 7 and latching it to the base 2.

For example, when removed from the injection site, as the casing 12 is further moved relative to the base in the distal direction D, the syringe retraction control mechanism 25 is switched from its state A (cf. FIG. 12A) to the one shown in FIG. 12B. status. The casing 12 and the second collar 21 locked to the casing 12 are moved together in the distal direction D, and the carrier 7 is held in place by the shackle mechanism 18 in its state C as described above (cf. Fig. 10C). Due to this action, the inner hub 21.3 on the second beam head 21.2 of the proximal beam 21.1 on the second collar 21 no longer abuts against the carrier 7. Instead, the second beam head 21.1 is ramp-engaged under the load of the control spring 19 to the ramp-like second casing element 12.2, the inner hub 21.3 is deflected in the inward direction I into a third recess 7.7 in the carrier 7. The syringe retraction control mechanism 25 thus reaches a state C as shown in Figure 12C, wherein the second collar 21 is decoupled from the casing 12 and coupled to the carrier 7. Due to the small sliding force exerted by the second collar 21, when the needle extension control mechanism 24 has been switched to the state E, the carrier 7 is pulled in the distal direction D when the sheath 12 is translated in the distal direction D, at the needle Before the cylinder retraction control mechanism 25 is switched to the state C, the stagnation mechanism 18 applies a small blocking force to the movement of the carrier 7. If the carrier 7 is moved too far in the distal direction D before the second collar 21 is switched, the sleeve 12 is escaping out of the transition to prevent retraction before the inner hub 21.3 can flex into the third recess 7.7.

Starting from position C of the stop mechanism 18 (cf. Fig. 10C), the carrier 7 and thus the rhomboid ramp member 7.1 are translated in the distal direction D under the load of the control spring 19. Thus, in a manner that causes the ductile beam 2.1 to flex in the inward direction I, the far fifth ramp 7.3 of the rhomboid ramp member 7.1 engages the third slope 2.3 on the first beam head 2.2 of the ductile beam 2.1. This applies a small blocking force to the movement of the carrier 7 required to ensure that the second collar 21 is switched to the carrier 7. Once the first beam head 2.2 is completely within the slope member 7.1 in a state D as shown in Figure 10D, the ductile beam 2.1 and the rhomboid ramp member 7.1 are laterally offset to allow the ductile beam 2.1 to pass without contacting the rhomboid ramp member. 7.1.

The control spring 19 is grounded at its proximal end in the casing by the first collar 20 abutting against the base 2. The distal end of the control spring 19 moves the second collar 21 in the distal direction D, which is attached to the syringe 3 with the carrier 2 and thus the needle 4, overcoming the stop mechanism 8, as shown in Figure 10D. Please note that once the user allows the sleeve 12 to translate sufficiently far enough, the needle 4 is retracted by the auto-injector 1 and unlike the auto-injector with the needle guard, the user is required to remove the auto-injector from the injection site, thus The user himself pulls the needle out of the skin to allow the needle guard to advance.

Note that the space between the rib on the plunger 9 where the feedback spring 29 is grounded and the distal end portion 28.2 of the feedback assembly 28 is greater than the free length of the feedback spring 29 prior to retraction. This means that as the carrier 7 is retracted (i.e., the distance between the plunger 9 and the feedback assembly 28 is reduced), the feedback spring 29 does not need to be recompressed and therefore does not provide any blocking force.

To prevent the feedback assembly 28 from rattling at the end of the dose and before retracting, it is contemplated that the free length of the feedback spring 29 is equal to the space between the plunger 9 and the distal end portion 28.2 of the feedback assembly 28. In this example, during retraction, the feedback spring 29 will need to be recompressed, reducing the force that drives the last portion of the retraction. However, the feedback spring 29 is at a very low ratio and has been calculated to be within acceptable tolerance limits.

9A and 9B, when the distal collar 21 encounters a first backstop 12.4 on the base 12, the retraction terminates. The arrow 20.1 on the first collar 20 is supported inwardly by the carrier 7 in a state F as shown in Fig. 11F and thus prevents deflection in the inward direction I. The outwardly facing sixth ramp 20.2 of arrow 20.1 is engaged behind the first rib 12.3 on the base 12 to prevent the casing 12 from being pushed again in the proximal direction P. A gap may be provided between the arrow 20.1 and the first rib 12.3 to allow for tolerances.

The stop mechanism 18 returns to the state A as in FIG. 10A, and as it initially locks the carrier 7 in position relative to the base 2, however, since the casing 12 cannot move relative to the base 2, it cannot Was unlocked.

A signature 20.4 on the first collar 20 can now be seen via an indicator window 32 in the casing 12 indicating that the autoinjector 1 has been used.

16 is an isometric view of an alternative embodiment of the plunger release mechanism 27. The plunger release mechanism 27 prevents movement of the plunger 9 in the proximal direction P relative to the carrier 7 until the carrier 7 is moved in the proximal direction P for the needle to extend. Unlike the plunger release mechanism 27 of FIG. 14, wherein the relative movement of the carrier 7 and the trigger button 13 is utilized to trigger the release of the plunger 9, the alternative embodiment of FIG. 16 is by the carrier 7 relative to the second collar 21. Move to release the plunger 9. Figure 16 shows the plunger release mechanism 27 before the plunger is released. The second collar 21 is shown to be transparent to improve clarity. The plunger 9 is pushed by the drive spring 8 in the proximal direction P. In order to advance the plunger 9, it must rotate about a twelfth ramp 7.8 on the carrier 7. A ramp member 9.1 on the plunger 9 is configured to engage the twelfth ramp 7.8. The rotation of the ramp member 9.1 is blocked by an inner longitudinal rib 21.5 on the second collar 21 of the slot in the longitudinal opening 7.9 of the carrier 7. The carrier 12 and the second collar 21 are held in the same position, i.e., coupled to each other for joint axial translation. When the trigger button 13 is pressed, the carrier 13 and the plunger 9 which are the portions that drive the secondary assembly are first pressed by the user against the trigger button 13, and then controlled by the first collar 20 The spring 19 moves in the proximal direction P as described above. Once the carrier 7 has moved far enough in the proximal direction P relative to the second collar 21, the ramp member 9.1 on the collar 9 is disengaged from the longitudinal rib 21.5 on the second collar 21 and can be ramped due to its load under the drive spring 8. The shape is joined to the twelfth ramp 7.8 and rotated past the proximal end of the longitudinal rib 21.5. Therefore, the drive spring 8 urges the plunger 9 in the proximal direction P to expel the medicine M.

17 is a longitudinal section of an alternative embodiment of the button release mechanism 26. The button release mechanism 26 of Fig. 17 is firstly subjected to the button release mechanism 26 of Fig. 15 except that the grounding portion of the trigger button 13 is switched between the carrier 7 and the casing 12 to provide a revealing button 13 appearance when the skin is in contact. A trigger button 13 that is locked but protrudes from the distal end of the casing 12. Once the carrier 7 has moved in the distal direction D when the base 2 is in contact with the skin, it is possible to press the trigger button 13 and activate the autoinjector 1. This ensures a certain sequence of operations.

In the embodiment of Figure 17, the trigger button 13 has two proximal beams 13.1 each having a ramped outer hub 13.4. In the initial state shown in Fig. 17, the ramp-shaped outer hub 13.4 is engaged in the respective fourth recess 12.5 in the casing 12. The proximal beam 13.1 is supported inwardly by the carrier 7 by means of the proximal beam 13.1 without inward deflection, preventing the ramped outer hub 13.4 from being disengaged from the fourth recess 12.5. In order to prevent the carrier 7 from moving further in the proximal direction P in the initial state, the inner projection 13.5 on the proximal beam 13.1 is abutted against a second rib 7.10 on the carrier 7. Once the carrier 7 has moved in the distal direction D when the base 2 is in contact with the skin, a first window 7.11 in the base 7 is moved to the rear of the inner projection 13.5 to allow the proximal beam 13.1 to be ramped due to its actuation of the trigger button 13. In the fourth recess 12.5 Flexing inward. The proximal beam 13.1 is now supported outward by the casing 12 and remains joined to the carrier 7 even when the needle 4 is retracted. The trigger button 13 therefore does not return to its initial position, indicating that the autoinjector 1 has been used.

18A and 18B show two longitudinal sections of an alternative embodiment of the shackle mechanism 18. Thus, the first beam head 2.2 moves about the rhomboid ramp member 7.1 and can be referred to as a "runway" mechanism. The stop mechanism 18 of Figures 10A through 10D has multiple functions of controlling the movement of the carrier 7 relative to the base 2. The alternative stop mechanism 18 of Figures 18A and 18B uses three clips 7.12, 7.13, 2.6 to produce the same effect.

The first clip 7.12 is configured as an outwardly biased ductile beam on the carrier 7 extending from the carrier 7 in the proximal direction P. The first clip 7.12 is configured to prevent the carrier 7 from being moved in the proximal direction P before the base 2 is pressed, or to be translated when the sheath 12 is in contact with the skin. The first clip 7.12 is composed of two segments in a side-by-side configuration. A first segment 7.14 prevents the carrier 7 from moving in the proximal direction P by abutting the base 2 against a recess. A second section 7.15 is configured to protrude outwardly from the clip head, which is configured to be inwardly sloped by a ramp feature 122.6 on the base 12 for releasing the first clip 7.12, thereby when the sleeve 12 is in contact with the skin The carrier 7 is unlocked from the base 2 when the proximal direction P is translated. A longitudinal slot 2.7 in the base 2 is configured to allow the second section 7.15 to slide in the proximal direction P once the lock has been released. A slight friction between the first clip 7.12 and the base 2 provides the retarding force required to ensure retraction.

The second clip 7.13 is configured as a tough beam extending on the carrier 7 in the distal direction D, having a third outwardly protruding portion including a proximal slope Beam head 7.16. The third beam head 7.16 acts as a back stop against a third rib 2.9 on the base 2 to prevent the base 7 from moving from its initial position in the distal direction D. Before the syringe 3 is inserted into the carrier 7, the carrier 7 and the base 2 are assembled at this position with the second clip 7.13, which is facilitated by the near slope on the third beam head 7.16. The syringe 3 locks the clip in place by preventing inward deflection, thus creating a fixed stop.

The third clip 2.6 is a tough beam that extends over the base 2 in the distal direction D. A ramped fourth beam head 2.8 on the third clip 2.6 is configured to be engaged inwardly into a fifth recess 7.17 in the carrier 7. Once the first clip 7.12 is unlocked, the user can load the third clip 2.6 by pressing the trigger button 13 against the carrier 7 in the proximal direction P. The third clip 2.6 is compressed by the load, i.e., bent outwardly and suddenly released due to its ramp-like engagement to the carrier 7, providing a stop function similar to that shown in Figure 10B.

Fig. 19 is a longitudinal section of a third embodiment of the shackle mechanism 18, which is a modification of the embodiment of Figs. 18A and 18B. In this embodiment, the stop function of the third clip 2.6 has been added to the first clip 7.12. The locking between the casing 12 and the carrier 7 is released in the same manner, but is provided by the first clamp 7.12 flexing inwardly to a second level, without the use of a second segment 7.15. The base 2 of the slot 2.7 achieves this effect. Instead, once the second section 7.15 is inwardly ramped by the ramp feature formation 12.6 on the casing 12, it must be further sloped inside the base 2 when subjected to axial loading between the base 2 and the carrier 7. And suddenly released its joint.

20 is a longitudinal section of an alternative embodiment of the feedback release mechanism 31. Unlike the feedback release mechanism of FIG. 13 in which the feedback spring 29 acts between the plunger 9 and the feedback assembly 28, in the embodiment shown in FIG. 20, the feedback spring 29 acts between the casing 12 and the feedback assembly 28. During the extension of the needle, as the feedback assembly 28 moves with the carrier 7 relative to the casing 12, the feedback spring 29 is compressed. When the feedback assembly 28 is released by the plunger 9 a moment before the end of the dose, the feedback assembly 28 moves in the distal direction D and impacts the trigger button 13. In addition to FIG. 13, since the feedback spring 29 is grounded in the casing 12 instead of the plunger 9, the feedback spring 29 is not recompressed during retraction of the needle.

21A and 21B show a longitudinal section of an alternative embodiment of the needle extension control mechanism 24 that is also configured to perform the slamming function of the shackle mechanism 18 when the needle is retracted and the needle is extended. Figure 22 shows the corresponding isometric view. A fourth clip 20.5 on the first collar 20 is configured as a tough beam having a beam head having an inwardly facing thirteenth ramp 20.6 for engaging a fourth rib 7.18 on the carrier 7 and The shell 12 is supported outwardly to maintain the first collar 20 bonded to the carrier 7 prior to use during needle extension and during drug expulsion. When the casing 12 moves in the distal direction relative to the carrier, such as when the user lifts the casing 12 away from the injection site at the end of the injection, a sixth recess 12.7 in the casing 12 moves outwardly to the fourth clamp 20.5. Rear, and the fourth clip 20.5 is allowed to be released when the carrier 7 is pulled by the second collar 21 in the distal direction D. Since the fourth clip 20.5 must be ramped outward, a small force is required to release the fourth clip 20.5, which provides a stop for retraction.

A fifth clip 2.10 on the base 2 abuts against a block 20.7 on the first collar 20 prior to use, while preventing the first collar 20 and thus the carrier 7 coupled to the first collar 20 from being near Move in direction P. For release, the fifth clip 2.10 must be turned outward and flexed above block 20.7. The outward deflection of the fifth clip 2.10 is initially prevented by the sleeve 12. Once the casing 12 has moved in contact with the skin, a second window 12.8 in the casing 12 emerges outwardly from the fifth clamp 2.10 to permit flexing outward. Since the fourth clip 20.5 does allow the carrier 7 to translate in the proximal direction P relative to the first collar 20 but not in the reverse direction, when the carrier 7 is pushed in the proximal direction P when the button is pressed, the fifth clip 2.10 is then deflected by a fourteenth ramp 7.19 on the carrier 7. The needle extension is provided by the fact that it must flex the fifth clip 2.10 when it is loaded by the controlled spring 19.

23A and 23B show a longitudinal section of a third embodiment of the needle extension control mechanism 24, which is also configured to perform the function of the shackle mechanism 18. Figure 24 is an isometric view of the needle extension control mechanism 24 of Figure 23 . This embodiment is similar to that shown in Figures 21A, 21B and 22. The difference is that the fifth clip 2.10 is disposed on the first collar 20 and the block 20.7 is disposed on the base 2, that is, its position has been switched, so the first collar 20 has two clips 2.10 and 20.5.

The fourth clip 20.5 is the same as that of FIG. 21B. It keeps the first collar 20 attached to the carrier 7 until the trigger needle is retracted, ensuring that the full needle extension length or depth is reached and maintained until it is displaced rearward relative to the base by the sheath in the distal direction, such as when Skin removal automatically The syringe 1 is used to initiate the retraction cycle.

The fifth clip 2.10 provides a stop for the needle extension and releases the first collar 20 from the base 2, causing the needle to extend. The fifth clip 2.10 is prevented from abutting against the base 2 by the block 20.7 to prevent the first clip 20 and thus the carrier 7 coupled to the first collar 20 from moving in the proximal direction P prior to use. For release, the fifth clip 2.10 must be turned outward and flexed above block 20.7. The outward deflection of the fifth clip 2.10 is initially prevented by the sleeve 12. Once the casing 12 has moved in contact with the skin, the second window 12.8 in the casing 12 emerges outwardly from the fifth clamp 2.10 and is allowed to flex outwardly. Since the fourth clip 20.5 does allow the carrier 7 to translate in the proximal direction P relative to the first collar 20 but not in the reverse direction, when the carrier 7 is pushed in the proximal direction P when the button is pressed, the fifth clip 2.10 is then deflected by the fourteenth ramp 7.19 on the carrier 7. The needle extension is provided by the fact that it must flex the fifth clip 2.10 when it is loaded by the controlled spring 19.

25A and 25B show a longitudinal section of a third embodiment of the feedback release mechanism 31. This embodiment does not require a dedicated feedback spring to operate. The plunger 9 includes a proximal ramp rib 9.2 that is configured to open the two seventh clips 7.21 on the carrier 7 immediately before the end of the dose. When the near ramp rib 9.2 has moved past the seventh clip 7.21, it bounces back and strikes the plunger 9 to produce a sound. The tubular shape of the carrier 7 helps to transmit sound. Fig. 25A shows the feedback release mechanism 31 before release. Fig. 25B shows the feedback release mechanism 31 after release. By lifting the seventh clip 7.21 to the far side of the near-sloping rib 9.2 one by one, the seventh clip on the carrier 7 is 7.21. The near face is axially offset to facilitate assembly.

Figures 26A and 26B show longitudinal sections of another embodiment of the autoinjector 1 in different cross-sectional planes, the different cross-sectional planes being rotated approximately 90° to each other, wherein the autoinjector 1 is in an initial state prior to use. The autoinjector 1 is substantially the same as that described in Figures 1 to 15. However, in addition to the autoinjectors of Figures 1 through 15, the autoinjector 1 of this embodiment has a wrap sleeve trigger instead of a trigger button.

The wrap sleeve trigger 12 is the same assembly as the casing 12, except that Figures 1 through 15 have a closed distal end face 12.10. An internal trigger button 13 is disposed at the distal end of the sleeve trigger member 12. Except for Figures 1 through 15, the trigger button 13 is not visible in any state and does not protrude from the casing 12. In the initial state, a gap 33 is provided between the distal end face 12.10 of the sleeve triggering member 12 and the inner trigger button 13, allowing partial movement of the sleeve triggering member 12 without interfering with the trigger button 13.

Since the autoinjector 1 is otherwise identical to the autoinjector of Figures 1 to 15, it operates substantially in the same manner except for the following differences: as the base 2 is placed against the injection site, the sleeve trigger 12 moves over the sleeve. The first phase translates in the proximal direction P relative to the base 2 into the advanced position, while removing the gap 33 between the distal end face 12.10 of the sleeve trigger 12 and the inner trigger button 13. As in the embodiment of Figures 1 to 15, this action unlocks the stop mechanism 18 and the trigger button 13. As the user continues to press the sleeve trigger 12 in the second phase of the sleeve travel thereby propelling it in the proximal direction P, the distal face 12.10 is struck against the internal trigger button 13 thereby pressing it until the first The collar 20 is from the base 2 The spring force is released and controlled to be coupled to the carrier 7. The carrier 7 is then advanced until the inner trigger button 13 stops on the other rib in the casing 12 and the plunger release mechanism 27 is released (note that the peg 14 is shorter in this embodiment).

From the user's point of view, the stop mechanism 18 is configured to provide a resistance when the user reaches the second stage of the sleeve travel. Internally, there is no difference between this point and the embodiment of Figures 1 to 15.

The needle extension is triggered by the user fully advancing the sleeve trigger 12 during the second phase of the sleeve travel, thereby fully pressing the inner trigger button 13 and overcoming the sling mechanism, as in the embodiment of Figures 1-15.

As the control spring 19 takes over when the button is pressed to fully advance the carrier 7 for the needle to extend, the internal trigger button 13 bottoms out on an inner fifth rib 12.11 of the sleeve trigger 12 and the internal trigger button 13 is locked back to the lock The sleeve trigger 12 is as in Figure 15C.

The embodiment of Figures 26A and 26B can also be combined with the alternative features shown in Figures 16-25.

Figure 27 is a longitudinal section of the distal end of the autoinjector 1 having an alternative feedback release mechanism 31 prior to actuation in the first position. A plunger 9 for acting on a syringe or stopper (not shown) is held in a syringe carrier 7. A trigger button 13 is disposed above the distal end of the syringe carrier 7. A drive spring 8 is disposed in the carrier 7 and is distally grounded in the carrier 7 and bears proximally against a thrust surface 11 on the plunger 9. A distal plunger sleeve 17 is attached distally to the thrust face 11 and is disposed inside the drive spring 8. A feedback component 28 includes a configuration disposed within the distal plunger sleeve 17. The elongate portion 28.1 and a distal pin 28.4 that is completely seated within the carrier 7 in the first position and therefore invisible and invisible to the user.

A feedback spring 29 is configured to bias the feedback assembly 28 relative to the plunger 9 in the distal direction D by the proximal support against the thrust surface 11 and distally against the feedback assembly 28.

Both the drive spring 8 and the feedback spring 29 are prestressed. The plunger 9 is joined to the carrier 7 by a plunger release mechanism (not shown). The plunger release mechanism can be configured as one of the above embodiments.

The distal plunger sleeve 17 includes two ramped latches 17.1 that hold the feedback assembly 28 by engaging a ramped surface 28.5 thereof. The latch 17.1 is supported externally by a thickened wall portion 7.23 of the carrier 7 in a manner that prevents it from being deflected outwardly by a ramp under the force from the feedback spring 29. Therefore, the feedback component 28 cannot be released in this configuration.

28 is a longitudinal section of the distal end of the autoinjector 1 having the alternative feedback release mechanism 31 of FIG. 27 released in the second position.

The plunger 9 has been released by the plunger release mechanism and thus translated in the proximal direction P for displacement of the stopper. During the proximal movement of the plunger 9, the ramp-like latch 17.1 on the distal plunger sleeve 17 has left the thickened wall portion 7.23 and enters a widened portion due to the ramping action of the force from the feedback spring 29. Allow it to flex outwards. The feedback assembly is advanced in the distal direction D by the feedback spring 29 via the distal end of the carrier 7, wherein the distal pin 28.4 will eventually protrude from the distal end of the trigger button 13 via an aperture 13.7 thereof when the feedback assembly 28 reaches the second position. . The distal pin 28.4 can thus be seen by the user. If the user still keeps his thumb Pressing on the trigger button 13 can also touch the distal pin 28.4 with its thumb. Still, the slanted surface 28.5 that hits the trigger button 13 from the inside produces an audible feedback and a tactile impact. In another exemplary embodiment, the distal pin 28.4 can have an end surface that lies in one of the same planes as a distal end surface of the trigger button 13 when the feedback assembly 28 reaches the second position. One of the impact mechanisms of the feedback assembly 28 on a proximal surface of the trigger button 13 provides an audible and tactile feedback to the user.

The distal plunger sleeve 17 can have one or more resilient ramp-like latches 17.1. At least one resilient ramp-like latch 17.1 can be similarly coupled directly to the thrust face 11 on the plunger 9, so the distal plunger sleeve 17 would not be required.

The trigger button 13 can be connected to the carrier 7 or a casing (not shown) surrounding the carrier 7. The trigger button 13 does not necessarily have to remain in the same longitudinal position relative to the carrier 7. Instead, at the end of the dose, the trigger button 13 can still be at the end of the casing (not shown), while the carrier 7 with all of its internal components has been advanced within the casing. For this purpose, the feedback spring 29 and the feedback assembly 28 must be designed to be strong and elongated to ensure that the feedback assembly 28 still reaches the trigger button 13 at the dose end, so that the distal pin 28.4 can protrude from the trigger button 13.

The feedback assembly 28 can be designed to be released a moment before the plunger 9 and the stopper reach their end of the dose position, preferably before the event.

The noise assembly 28 according to Figures 27 and 28 can be combined with the embodiment shown in Figures 1 to 26, wherein each trigger button 13 or wrap sleeve trigger 12 will be provided with an aperture 13.7 and the feedback assembly 28 will have a distal end Pin 28.4. Can be relied on by the feedback release mechanism 31 of Figures 27 and 28 The feedback release mechanism 31 shown in other embodiments achieves the release of the feedback assembly 28.

The noise release mechanism 31 according to Figures 27 and 28 can be applied in the same manner to other types of auto-injectors. For example, the syringe carrier 7 can be used as part of a casing or housing rather than being disposed within an additional casing. Similarly, the aperture 13.7 can be disposed in a sleeve or a portion of the sleeve trigger rather than the trigger button 13.

The distal pin 28.4 can have a different color than the trigger button 13, such as red, to improve the visual indication that the user knows that the dose endpoint has been reached and that the device is in use.

Needless to say, of course, in all the ramp-like joints between the two components described in the above embodiments, there may be only one slope on one component or the other component or a slope on both components without significantly affecting the slope. The effect of a joint.

As used herein, the terms "pharmaceutical" and "pharmaceutical" refer to a pharmaceutical formulation containing at least one pharmaceutically active compound, wherein in one embodiment, the pharmaceutically active compound has a molecular weight of up to 1500 Da and/or is a peptide, a mixture of a protein, a polysaccharide, a vaccine, a DNA, an RNA, an enzyme, an antibody or a fragment thereof, a hormone or an oligonucleotide, or a pharmaceutically active compound described above, wherein in another embodiment The pharmaceutically active compound can be used to treat and/or prevent diabetes or complications associated with diabetes such as diabetic retinopathy, thrombotic disorders such as deep veins or pulmonary thrombosis, acute Coronary coronary syndrome (ACS), angina pectoris, myocardial infarction, cancer, macular degeneration, inflammation, hay fever, arteriosclerosis and/or rheumatoid arthritis, wherein in another embodiment, the pharmaceutically active compound comprises at least one peptide For treating and/or preventing diabetes or complications associated with diabetes such as diabetic retinopathy, wherein in another embodiment, the pharmaceutically active compound comprises at least one human insulin or a human insulin analog or derivative, Glucagon peptide (GLP-1) or an analog or derivative thereof, or insulinotropic hormone-3 or insulinotropic hormone-4 or an insulin secretagogue-3 or an analogue of insulinotropic secretion-4 Or a derivative.

Insulin analogues such as Gly (A21), Arg (B31), Arg (B32) human insulin; Lys (B3), Glu (B29) human insulin; Lys (B28), Pro (B29) human insulin; Asp (B28 Human insulin; human insulin, wherein the proline in position B28 is replaced by Asp, Lys, Leu, Val or Ala and wherein Lys can be substituted by Pro in position B29; Ala (B26) human insulin; Des (B28-B30) Human insulin; Des (B27) human insulin and Des (B30) human insulin.

Insulin derivatives such as B29-N-mercapto-des (B30) human insulin; B29-N-palmitino-des (B30) human insulin; B29-N-mercapto human insulin; B29-N- Palmitoyl human insulin; B28-N-mercapto LysB28ProB29 human insulin; B28-N-palmitino-LysB28ProB29 human insulin; B30-N-mercapto-ThrB29LysB30 human insulin; B30-N-palmital -ThrB29LysB30 human insulin; B29-N-(N-palmitino-Y-glutamyl)-des(B30) human insulin; B29-N-(N-stone-y-glutamyl)- Des (B30) human insulin; B29-N-(ω-carboxyheptyl)-des (B30) human insulin and B29-N-(ω-carboxyheptadecanyl) human insulin.

Insulin-secretin-4 such as insulin-secretin-4-(1-39), sequence H-His-Gly-Glu-Gly-Thr-Phe-Thr-Ser-Asp-Leu-Ser-Lys-Gln -Met-Glu-Glu-Glu-Ala-Val-Arg-Leu-Phe-Ile-Glu-Trp-Leu-Lys-Asn-Gly-Gly-Pro-Ser-Ser-Gly-Ala-Pro-Pro-Pro a peptide of -Ser-NH2).

The insulinotropic-4 derivative is, for example, a list selected from the group consisting of H-(Lys)4-des Pro36, des Pro37 insulin secretagin-4(1-39)-NH2, H-(Lys)5-des Pro36, des Pro37 Insulin Secretin-4(1-39)-NH2, des Pro36 Insulin Secretin-4 (1-39), des Pro36[Asp28] Insulin Secretin-4 (1-39), des Pro36[IsoAsp28] Insulin Secretin-4 (1-39), des Pro36[Met(O)14, Asp28] Insulin Secretin-4 (1-39), des Pro36[Met(O)14, IsoAsp28] Insulin secretin-4 (1-39), Des Pro36[Trp(O2)25, Asp28] Insulin Secretin-4 (1-39), des Pro36 [Trp(O2)25, IsoAsp28] Insulin Secretin-4 (1-39), des Pro36[Met (O)14 Trp(O2)25, Asp28] Insulin Secretin-4 (1-39), des Pro36[Met(O)14 Trp(O2)25, IsoAsp28] Insulin Secretin-4 (1-39) ); or des Pro36 [Asp28] insulin secretin-4 (1-39), des Pro36 [IsoAsp28] insulin secretin-4 (1-39), des Pro36 [Met (O) 14, Asp28] insulin Secretin-4 (1-39), des Pro36[Met(O)14, IsoAsp28] Insulin Secretin-4 (1-39), des Pro36[Trp(O2)25, Asp28] Insulin Secretin-4 (1-39), des Pro36[Trp(O2)25, IsoAsp28] Insulin Secretin-4 (1-39), des Pro36[Met(O)14 Trp(O2)25, Asp28] Insulin Secretin- 4(1-39), des Pro36[Met(O)14 Trp(O2)25, IsoAsp28] Insulin secretin-4 (1-39), wherein the group -Lys6-NH2 can be bound to insulinotropic secretion C-terminal of the -4 derivative; Or an insulinotropic secretion-4 derivative of the following sequence: des Pro36 insulin secretagin-4(1-39)-Lys6-NH2 (AVE0010), H-(Lys)6-des Pro36[Asp28] insulin secretion -4(1-39)-Lys6-NH2, des Asp28 Pro36, Pro37, Pro38 insulin secretin-4(1-39)-NH2, H-(Lys)6-des Pro36, Pro38[Asp28] insulinotropic Secretin-4(1-39)-NH2, H-Asn-(Glu)5des Pro36, Pro37, Pro38[Asp28] Insulin Secretin-4(1-39)-NH2, des Pro36, Pro37, Pro38[Asp28 Insulin secretin-4(1-39)-(Lys)6-NH2,H-(Lys)6-des Pro36,Pro37,Pro38[Asp28]insulin-secretin-4(1-39)-(Lys 6-NH2,H-Asn-(Glu)5-des Pro36,Pro37,Pro38[Asp28]insulin secretin-4(1-39)-(Lys)6-NH2,H-(Lys)6-des Pro36[Trp(O2)25, Asp28] Insulin Secretin-4(1-39)-Lys6-NH2, H-des Asp28 Pro36, Pro37, Pro38[Trp(O2)25] Insulin Secretin-4 (1 -39)-NH2,H-(Lys)6-des Pro36, Pro37, Pro38[Trp(O2)25, Asp28] Insulin secretin-4(1-39)-NH2, H-Asn-(Glu)5 -des Pro36, Pro37, Pro38[Trp(O2)25, Asp28] Insulin Secretin-4(1-39)-NH2, des Pro36, Pro37, Pro38[Trp(O2)25, Asp28] Insulin Secretin-4(1-39)-(Lys)6-NH2, H-(Lys)6-des Pro36, Pro37, Pro38[Trp(O2)25, Asp28] Insulin secretin-4(1-39)-(Lys)6-NH2,H-Asn-(Glu)5- Des Pro36, Pro37, Pro38[Trp(O2)25, Asp28] Insulin Secretin-4(1-39)-(Lys)6-NH2,H-(Lys)6-des Pro36[Met(O)14, Asp28] Insulin Secretin-4(1-39)-Lys6-NH2, des Met(O)14, Asp28 Pro36, Pro37, Pro38 Insulin Secretin-4(1-39)-NH2, H-(Lys) 6-desPro36, Pro37, Pro38[Met(O)14, Asp28] Insulin Secretin-4(1-39)-NH2, H-Asn-(Glu)5-des Pro36, Pro37, Pro38[Met(O) 14, Asp28] Insulin Secretin-4(1-39)-NH2, des Pro36, Pro37, Pro38[Met(O)14, Asp28] Insulin Secretin-4(1-39)-(Lys)6- NH2,H-(Lys)6-des Pro36, Pro37, Pro38[Met(O)14, Asp28] Insulin Secretin-4(1-39)-(Lys)6-NH2, H-Asn-(Glu) 5-des Pro36, Pro37, Pro38[Met(O)14, Asp28] Insulin Secretin-4(1-39)-(Lys)6-NH2, H-Lys6-des Pro36[Met(O)14, Tro (O2)25, Asp28] Insulin Secretin-4(1-39)-Lys6-NH2, H-des Asp28 Pro36, Pro37, Pro38[Met(O)14, Trp(O2)25] Insulin Secretin-4(1-39)-NH2, H-(Lys)6-des Pro36, Pro37, Pro38[Met(O)14, Asp28] Insulin Secretin-4 (1 -39)-NH2,H-Asn-(Glu)5-des Pro36, Pro37, Pro38[Met(O)14, Trp(O2)25, Asp28] Insulin secretin-4(1-39)-NH2, Des Pro36, Pro37, Pro38[Met(O)14, Trp(O2)25, Asp28] Insulin Secretin-4(1-39)-(Lys)6-NH2,H-(Lys)6-des Pro36, Pro37, Pro38[Met(O)14, Trp(O2)25, Asp28] Insulin Secretin-4(S1-39)-(Lys)6-NH2, H-Asn-(Glu)5-des Pro36, Pro37 , Pro38[Met(O)14, Trp(O2)25, Asp28] Insulin secretin-4(1-39)-(Lys)6-NH2; or any of the above insulinotropic-4 derivatives A pharmaceutically acceptable salt or solvate.

Hormones such as pituitary hormones or hypothalamic hormones or regulatory active peptides and their antagonists, such as Rote Liste, 2008 edition, listed in Chapter 50, such as Gonadotropine (Follitropin) Lutropin, Choriongonadotropin, Menotropin, Somatropine (Somatropin), Desmopressin, Tenlipressin, Ge Gonadorelin, Triptorelin, Leuprorelin, Buserelin, Nafarilin (Nafarelin), Goserelin.

The polysaccharide is, for example, a glycosaminoglycan, hyaluronic acid, heparin, low molecular weight heparin or ultra low molecular weight heparin or a derivative thereof, or a sulfated hydrazine such as a polysulfated form of the above polysaccharide, and/or a pharmaceutically acceptable salt thereof. An example of a pharmaceutically acceptable salt of polysulfated low molecular weight heparin is enoxaparin sodium.

The anti-system is a ball plasma protein (~150 kDa), also known as immunoglobulin, which shares a basic structure. Since it has a sugar chain added to an amino acid residue, it is a glycoprotein. The basic functional unit of each antibody is an immunoglobulin (Ig) monomer (containing only one Ig unit); the secreted antibody may also be a dimeric having two Ig units, like IgA, having four Ig units. A tetrameric, like the teleost fish IgM, or a pentameric with five Ig units, like a mammalian IgM.

The Ig single system is a "Y" shaped molecule consisting of four polypeptide chains; two identical heavy chains and two identical light chains, linked by a disulfide bond between the cysteine residues. Each heavy chain is approximately 440 amino acids long; each light chain is approximately 220 amino acids long. The heavy and light chains each contain an intrachain disulfide bond that stabilizes their folding. Each chain consists of structural domains called Ig domains. These subdomains contain between about 70 and 110 amino acids and are classified into different classes (eg, variable or V, and fixed or C) depending on their size and function. It has a characteristic immunoglobulin fold in which the two beta sheets form a "sandwich" shape that is held together by the interaction between the retained cysteine and other charged amino acids.

There are five types of mammalian Ig heavy chains, designated as alpha, delta, epsilon, gamma and mu. The type of heavy chain that is present defines the isotype of the antibody; these chains are found in IgA, IgD, IgE, IgG, and IgM antibodies, respectively.

Different heavy chains have different sizes and compositions; alpha and gamma contain approximately 450 amino acids and δ contains approximately 500 amino acids, while μ and ε have approximately 550 amino acids. Each heavy chain has two regions, a fixed region (C _H ) and a variable region (V _H ). In one species, the imprinted regions are substantially identical in all antibodies of the same isotype, but are different in different isotypes of antibodies. The heavy chain γ, α, and δ have a fixed region composed of three columnar Ig domains, and a hinge region for adding flexibility; the heavy chain μ and ε have four immunoglobulin domains. One of the fixed areas. The variable regions of the heavy chain differ in the antibodies produced by different B cells, but are identical for all antibodies produced by a single B cell or a B cell clone. The variable region of each heavy chain is approximately 110 amino acids long and consists of a single Ig domain.

In mammals, there are two types of immunoglobulin light chains, designated as λ and κ. A light chain has two successive sub-domains: a fixed sub-domain (CH) and a variable sub-domain (VL). The approximate length of a light chain is 211 to 217 amino acids. Each antibody contains two light chains that are always identical; only one type of light chain, kappa or lambda, is present in each antibody in a mammal.

Although the general structure of all antibodies is very similar, the unique properties of a given antibody depend on the variable (V) region, as described above. More specifically, three variable loop systems, each on the light (VL) and heavy (VH) chains, are responsible for binding to the antigen, ie for antigen specificity. These circuits are called complementary Decision Area (CDR). Since the CDR lines from the VH and VL domains contribute to the antigen binding site, it is the combination of heavy and light chains that is not the sole one to determine the final antigen specificity.

An "antibody fragment" contains at least one antigen-binding fragment as defined above and exhibits substantially the same function and specificity as the intact antibody from which the fragment is derived. The Ig prototype was chopped into three fragments using limited proteolytic digestion of papaya peptone. Two identical amino terminal fragments each containing a complete L chain and about half of the H chain are antigen-binding fragments (Fab). A third fragment of a carboxyl terminal half having a similar size but comprising a double chain having an interchain disulfide bond is a crystallizable fragment (Fc). Fc contains carbohydrates, complementary binding, and FcR binding sites. The restricted peptone digestive system produces a single F(ab')2 fragment containing a Fab block and a hinge region, including an H-H interchain disulfide bond. F(ab')2 is bivalent for antigen binding. The disulfide bond of F(ab')2 can be chopped to obtain Fab'. Also, the variable regions of the heavy and light chains can be fused together to form a single-chain variable fragment (scFv).

Pharmaceutically acceptable salts are, for example, acid addition salts and base salts. The acid addition salt is, for example, a HCl or HBr salt. The alkali salt is, for example, a salt having a cation selected from the group consisting of a strong base or a basic such as Na+, or K+, or Ca2+, or a monoammonium ion N+(R1)(R2)(R3)(R4), Wherein R1 to R4 independently of each other represent: hydrogen, an optionally substituted C1-C6-alkyl group, an optionally substituted C2-C6-alkenyl group, a selectively substituted C6-C10-aryl group, or an optional one. Sex substituted C6-C10-heteroaryl. Other examples of pharmaceutically acceptable salts are described in the "Remington Pharmaceutical Sciences" "17", Alfonso R. Gennaro (eds.), Mark Publishing Company, Easton, Pennsylvania, 1985, and the Encyclopedia of Pharmaceutical Sciences.

Pharmaceutically acceptable solvates are, for example, hydrates.

1‧‧‧Autoinjector

2‧‧‧Base

2.1‧‧‧Tough beams

2.2‧‧‧First beam head

2.3‧‧‧ Near third slope

2.4‧‧‧ far seventh slope

2.5‧‧‧Opening

2.6‧‧‧ third clip

2.7‧‧‧ slots

2.8‧‧‧four beam head

2.9‧‧‧ Third rib

2.10‧‧‧ fifth clip

2.11‧‧‧ sixth clip

3‧‧‧Syringe

4‧‧‧ hollow injection needle

5‧‧‧Protection needle cover

6‧‧‧stop

7‧‧‧ Carrier

7.1‧‧‧Ramp components

7.2‧‧‧ Near fourth slope

7.3‧‧‧ far fifth slope

7.4‧‧‧Carrier conditions

7.5‧‧‧Second recess

7.6‧‧‧ far tenth slope

7.7‧‧‧ Third recess

7.8‧‧‧ twelfth slope

7.9‧‧‧Vertical opening

7.10‧‧‧second rib

7.11‧‧‧ first window

7.12‧‧‧First clip

7.13‧‧‧Second clip

7.14‧‧‧ first paragraph

7.15‧‧‧ second paragraph

7.16‧‧‧ Third beam head

7.17‧‧‧First recess

7.18‧‧‧4th rib

7.19‧‧‧fourteenth slope

7.20‧‧‧15th slope

7.21‧‧‧ seventh clip

7.22‧‧‧Opening

7.23‧‧‧ Thickened wall section

8‧‧‧Drive spring

9‧‧‧Plunger

9.1‧‧‧Ramp components

9.2‧‧‧ Near ramp ribs

10‧‧‧ Carrier end face

11‧‧‧ thrust surface

12‧‧‧shell

12.1‧‧‧First casing assembly

12.2‧‧‧Second casing assembly

12.3‧‧‧First rib

12.4‧‧‧First back stop

12.5‧‧‧4th recess

12.6‧‧‧ Slope feature structure

12.7‧‧‧ seventh recess

12.8‧‧‧ second window

12.9‧‧‧ third window

12.10‧‧‧ distal end

12.11‧‧‧ fifth rib

13‧‧‧ trigger button

13.1‧‧‧ Near beam

13.2‧‧‧Outer first slope

Second slope in 13.3‧‧

13.4‧‧‧Slope-like outer hub

13.5‧‧‧ Inner protruding parts

13.6‧‧‧Second back stop

13.7‧‧‧Aperture

14‧‧‧Pegs

14.1‧‧‧ Near Extension

15‧‧‧Tough arms

16‧‧‧First recess

17‧‧‧ far carrier sleeve

17.1‧‧‧Resilient slope-like latch

18‧‧‧掣止机构

19‧‧‧Control spring

20‧‧‧First collar

20.1‧‧‧ arrow

20.2‧‧‧The sixth slope to the outside

20.3‧‧‧The ninth slope

20.4‧‧‧Scratch

20.5‧‧‧ fourth clip

20.6‧‧‧near the thirteenth slope

20.7‧‧‧ Block

20.8‧‧‧ fifth clip

21‧‧‧Second collar

21.1‧‧‧ Near beam

21.2‧‧‧Second beam head

21.3‧‧‧ Inner hub

21.4‧‧‧Outside the eighth slope

21.5‧‧‧ longitudinal ribs

22‧‧‧ Cover

22.1‧‧‧Inner sleeve

23‧‧‧thorn

24‧‧‧Needle extension control mechanism

25‧‧‧Syringe retraction control mechanism

26‧‧‧ button release mechanism

27‧‧‧Plunger release mechanism

28‧‧‧Return components

28.1‧‧‧Long section

28.2‧‧‧ distal part

28.3‧‧‧The eleventh slope outside

28.4‧‧‧Remote pin

28.5‧‧‧Slope-like surface

29‧‧‧Feedback spring

30‧‧‧Second tough arm

30.1‧‧‧Ramp-shaped inner hub

31‧‧‧Feedback release mechanism

32‧‧‧ indicator window

33‧‧‧ gap

D‧‧‧Remote/distant direction

I‧‧‧Inward direction

M‧‧‧ drugs

O‧‧‧Outward

P‧‧‧ proximal/near direction

Figure 1 shows two longitudinal sections of a cap and a self-injecting syringe after removal of the protective needle cover; Figure 2 shows two longitudinal sections of the autoinjector with the sheath moving in a proximal direction relative to the base; Figure 3 shows the autoinjector Two longitudinal sections, one of which is pressed; Figure 4 shows two longitudinal sections of the autoinjector during advancement of the needle; Figure 5 shows two longitudinal sections of the autoinjector with the needle in an extended proximal position; Figure 6 shows the drug delivery period Two longitudinal sections of the autoinjector; Figure 7 shows two longitudinal sections of the autoinjector, wherein the stopper is positioned adjacent to a proximal end of the syringe; Figure 8 shows two longitudinal sections of the autoinjector, wherein the housing is opposite to the housing after delivery The base moves in the distal direction; Figure 9 shows two longitudinal sections of the autoinjector with the needle retracted into a needle safe position; Figure 10 shows one of four different states for controlling a carrier relative to the base of the autoinjector Schematic diagram of the movement mechanism of the movement; Figure 11 shows a schematic view of a needle extension control mechanism for controlling the movement of a first collar in one of six different states; Figure 12 shows a schematic view of the syringe retraction control mechanism in one of three different states; Figure 13 shows A schematic diagram of one of three different states for indicating a feedback release mechanism of an injection end point; Figure 14 shows a schematic view of one of the plunger release mechanisms in three different states; Figure 15 shows one of the button release mechanisms in three different states Figure 16 is an isometric view of an alternative embodiment of the plunger release mechanism; Figure 17 is a longitudinal section of an alternative embodiment of the button release mechanism; Figure 18 shows an alternative embodiment of the stop mechanism 1 is a longitudinal section of a third embodiment of the shackle mechanism; FIG. 20 is a longitudinal section of an alternative embodiment of the feedback release mechanism; and FIG. 21 is a longitudinal section of an alternative embodiment of the needle extension control mechanism It is also configured to perform the function of the stop mechanism when the needle is retracted and the needle is extended; FIG. 22 is an isometric view of the needle extension control mechanism of FIG. 21; and FIG. 23 is the first embodiment of the needle extension control mechanism a longitudinal section of the third embodiment, which is also configured to perform the function of the shackle mechanism; and FIG. 24 is an isometric view of the needle extension control mechanism of FIG. 23; Figure 25 shows a longitudinal section of a third embodiment of the feedback release mechanism; Figure 26 is another embodiment of the autoinjector with a wrap sleeve trigger instead of a trigger button; Figure 27 is the distal end of an autoinjector A longitudinal section in which an alternative feedback release mechanism is before actuation; and Figure 28 is a longitudinal section of the distal end of the autoinjector with the alternative feedback release mechanism of Figure 27 after release.

7‧‧‧ Carrier

7.22‧‧‧Opening

9‧‧‧Plunger

28‧‧‧Return components

28.1‧‧‧Long section

28.3‧‧‧The eleventh slope outside

30‧‧‧Second tough arm

30.1‧‧‧Ramp-shaped inner hub

31‧‧‧Feedback release mechanism

D‧‧‧Remote/distant direction

O‧‧‧Outward

P‧‧‧ proximal/near direction

Claims (7)

An injection device (1) for administering a dose of a drug (M), comprising: a carrier (7) adapted to contain a syringe (3) having a hollow injection needle (4) and a stopper (6); a drive spring (8); a plunger (9) adapted to deliver the load of the drive spring (8) to the stopper; and a noise component (28) Adapting to generate an audible and/or tactile feedback by impacting a component of the injection device (1) when the stopper (4) is positioned at a proximal end of the syringe (3), wherein In one state, a resilient arm (30) on the plunger (9) is maintained in engagement with the noise component (28) by the carrier (7), wherein in a second state, the arm (30) is disengaged from the noise The assembly (28) is at least partially deflected into an opening (7.22) in the carrier (7). The injection device of claim 1, wherein in an intermediate state, the plunger (9) moves proximally relative to the carrier (7) while allowing the arm (30) to flex radially and Get out of the noise component (28). The injection device according to any one of claims 1 to 2, further comprising: A spring (29) that applies a biasing force to the noise assembly (28). The injection device according to any one of claims 1 to 3, wherein the component of the injection device (1) on which the noise-supplied component (28) is impacted is a base (2), a casing (12), a trigger button (13), the carrier (7), and/or the plunger (9). The injection device of any one of claims 1 to 4, wherein the arm (30) comprises a ramped inward boss (30.1) adapted to engage the noise component (28) ) on the eleventh slope (28.3). The injection device of any one of claims 1 to 5, wherein the assembly has a physical shape and/or design and/or material suitable for amplifying and/or transmitting a sound. The injection device of any one of claims 1 to 6, wherein the noise component (28) comprises an elongate portion (28.1) and a distal portion (28.2) configured to impact the assembly.