Audible indicator

Abstract

The present application relates to an audible indicator, in particular to an audible indicator (13) for a drug delivery device (1), the audible indicator (13) comprising a spring element (13.10) configured to be in one of a relaxed state (S1) and a biased state (S2), wherein the audible indicator (13) comprises a rotatable element (13.1) coupled to the spring element (13.10), wherein when the spring element (13.10) changes from the biased state (S2) to the relaxed state (S1), the spring element (13.10) releases stored energy to rotate the rotatable element (13.1), so that the rotatable element (13.1) hits a surface to generate an audible signal.

Description

[0001] This invention application is a divisional application based on an invention patent application with an application date of August 23, 2017, application number 201780052187.1 (international application number PCT / EP2017 / 071194) and name “Auditory Indicator”. Technical Field

[0002] The present disclosure relates to audible indicators for drug delivery devices. Background Art

[0003] Administering an injection is a process that presents many risks and challenges for the user and medical professional (mentally and physically). Injection devices are generally divided into two categories - manual devices and automatic injectors. In traditional manual devices, manual force is required to drive the drug through the needle. This is usually done by a button / plunger of some form that must be pressed continuously during the injection. There are many disadvantages to this solution. For example, if the button / plunger is released prematurely, the injection will stop and the expected dose may not be delivered. In addition, the force required to press the button / plunger may be too high (for example, if the user is an elderly person or a child). And, aligning the injection device, administering the injection, and still holding the injection device during the injection may require flexibility, but some patients (for example, elderly patients, children, arthritis patients, etc.) may not have the required flexibility.

[0004] Auto-injector devices are intended to make self-injection easier for patients. Conventional auto-injectors may provide the force used to perform the injection via a spring, and a trigger button or other mechanism may be used to activate the injection. Auto-injectors may be single-use devices or reusable devices.

[0005] Furthermore, it is desirable to administer a full dose to achieve the complete effect of the agent in the patient.

[0006] Therefore, there remains a need for an audible indicator for a drug delivery device. Current indicators may be too quiet or too bulky to be used with current auto-injectors and other drug delivery devices. The audible indicator described in the present application solves one or more of these problems. Summary of the invention

[0007] It is an object of the present disclosure to provide an improved audible indicator for use on a drug delivery device.

[0008] This object is achieved by the acoustic indicator according to the invention.

[0009] Exemplary embodiments are provided in the present invention.

[0010] According to the present disclosure, an audible indicator for use on a drug delivery device includes a spring element configured to be in one of a relaxed state and a biased state, wherein the audible indicator further includes a rotatable element coupled to the spring element and rotatable about a pivot, wherein when the spring element changes from the biased state to the relaxed state, the spring element releases stored energy to rotate the rotatable element so that the rotatable element strikes a surface to generate an audible signal.

[0011] In the context of the present application, the relaxed state is a state in which the spring element has a lower potential energy, and the biased state is a state in which the spring element has a higher potential energy than in the relaxed state. When the spring element changes from the biased state to the relaxed state, the stored energy is released from the spring element.

[0012] The audible indicator can be used to indicate to the patient or user that the full dose of the medicament in the drug delivery device is exhausted. Thus, the drug delivery device is improved to achieve reliable indication of the end of drug delivery and the complete effectiveness of the drug in the patient's body.

[0013] In an exemplary embodiment, the spring element engages in a slot in the rotatable element, thereby coupling the spring element to the rotatable element for joint rotation. The rotatable element can thereby be rotated by the spring element from a biased state to a relaxed state, the spring element being movable from the relaxed state to the biased state by rotation of the rotatable element.

[0014] In an exemplary embodiment, the rotatable element comprises a first leg and a second leg which are arranged substantially in the shape of an L. This allows a space-saving arrangement of the audible indicator in the drug delivery device.

[0015] In an exemplary embodiment, the rotatable element comprises a pivot bore configured to be rotatably mounted on a bearing pin. The bearing pin may be fixed in the drug delivery device, for example, fixed to its housing. Alternatively, the rotatable element may comprise a pivot shaft configured to be mounted in a bore, and the bore may be arranged in the drug delivery device, for example, arranged in its housing.

[0016] In an exemplary embodiment, the first leg comprises a curved section near the pivot hole towards the free end. Although the first leg may have a substantially straight section between the intersection of the first and second legs and the pivot hole for abutting the housing of the drug delivery device in the pre-release state, a curved section may be provided on the first leg near the pivot hole towards the free end of the first leg to allow rotation of the rotatable element in the release state until the end face of the free end abuts the front housing, so that the rotatable element has two well-defined positions within the drug delivery device.

[0017] In an exemplary embodiment, the pivot hole comprises a V-shaped slot which allows the pivot hole to click onto the bearing pin in a lateral direction, i.e. the V-shaped slot may extend in a radial direction from the axis of the pivot hole, and in order to click the pivot hole onto the bearing pin, the pivot hole and the bearing pin are aligned with their axes substantially parallel, the V-shaped slot faces the bearing pin and the pivot hole is moved towards the bearing pin until the axis of the pivot hole and the axis of the bearing pin are substantially co-linear. This facilitates assembly of the audible indicator into the drug delivery device.

[0018] In an exemplary embodiment, the spring element comprises a beam and a flag protruding substantially at a right angle from one end of the beam, wherein the flag is adapted to engage in the slot. In an exemplary embodiment, the spring element has a substantially straight shape in a relaxed state and is configured to be resiliently flexed out of the straight shape to form a curved shape in a biased state.

[0019] In an exemplary embodiment, the free end of the second leg is adapted to abut the plunger radially inwardly to maintain the audible indicator in the pre-release state.

[0020] In an exemplary embodiment, the rotatable element and / or the spring element is a metal component, in particular a sheet metal component, which can be produced in a stamp-bend production process. This allows a particularly cost-effective production of the acoustic indicator.

[0021] In an exemplary embodiment, a drug delivery device includes a housing, a plunger, and an audible indicator including a spring element configured to be in one of a relaxed state and a biased state.

[0022] - wherein the audible indicator comprises a rotatable element, which is coupled to a spring element and is rotatable about a pivot,

[0023] - wherein when the spring element changes from a biased state to a relaxed state, the spring element releases stored energy to rotate the rotatable element so that the rotatable element hits the surface of the housing to generate an audible signal. This may also provide tactile feedback to a user of the drug delivery device holding the drug delivery device with their hand.

[0024] The housing may be adapted to hold a medicament container, such as a syringe.

[0025] The elastic force member can be changed from a biased state to a relaxed state by the movement of the plunger for displacing medicine from the medicament container. For example, when the plunger moves toward the distal position or reaches the distal position at the end of the medicament delivery process, the elastic force member can be changed from a biased state to a relaxed state.

[0026] In an exemplary embodiment, the rotatable element comprises a pivot bore configured to be rotatably mounted on a bearing pin. The bearing pin may be fixed in the drug delivery device, for example, fixed to its housing. Alternatively, the rotatable element may comprise a pivot shaft configured to be mounted in a bore, and the bore may be arranged in the drug delivery device, for example, arranged in its housing.

[0027] The housing may include a front housing and a rear housing, and a bearing pin may be arranged on one of the front housing and the rear housing, and the rotatable element may collide / impact the other of the front housing and the rear housing. In other embodiments, the rotatable element may collide / impact the one of the front housing and the rear housing on which the bearing pin is arranged. In yet another embodiment, the housing may be a single piece.

[0028] In an exemplary embodiment, the pivot hole comprises a V-shaped slot which allows the pivot hole to be latched onto the bearing pin in a lateral direction, i.e. the V-shaped slot may extend in a radial direction from the axis of the pivot hole, and in order to latch the pivot hole onto the bearing pin, the pivot hole and the bearing pin are aligned with their axes substantially parallel, the V-shaped slot faces the bearing pin and the pivot hole is moved towards the bearing pin until the axis of the pivot hole and the axis of the bearing pin are substantially collinear. This facilitates assembly of the audible indicator into the drug delivery device.

[0029] In an exemplary embodiment, the rotatable element includes a first leg and a second leg arranged substantially in an L-shape, wherein a free end of the second leg is adapted to abut the plunger radially inwardly to maintain the audible indicator in a pre-release state.

[0030] In an exemplary embodiment, apertures are provided in the housing for retaining the beams.

[0031] A method of producing an audible indicator for a drug delivery device, the method may include:

[0032] - forming a spring element configured to be in one of a relaxed state and a biased state,

[0033] - forming a rotatable element adapted to be coupled to the spring element and rotatable about a pivot,

[0034] The spring element and the rotatable element are produced in one press-bending production process on a press-bending robot. This allows a particularly cost-effective production of the acoustic indicator.

[0035] Further applicability of the present invention will become apparent from the detailed description given below. However, it should be understood that while indicating exemplary embodiments of the present invention, the detailed description and specific examples are given by way of illustration only, because various changes and modifications within the spirit and scope of the present invention will become apparent to those skilled in the art based on the detailed description.

[0036] Specifically, the present invention relates to the following:

[0037] 1. An audible indicator (13) for a drug delivery device (1), the audible indicator (13) comprising a spring element (13.10) configured to be in one of a relaxed state (S1) and a biased state (S2),

[0038] - wherein the audible indicator (13) comprises a rotatable element (13.1) which is coupled to the spring element (13.10) and is rotatable about a pivot,

[0039] - When the spring element (13.10) changes from the biased state (S2) to the relaxed state (S1), wherein the spring element (13.10) releases stored energy to rotate the rotatable element (13.1), the rotatable element (13.1) hits a surface to generate an audible signal.

[0040] 2. The audible indicator (13) according to claim 1,

[0041] Wherein the spring element (13.10) engages in a slot (13.8) in the rotatable element (13.1).

[0042] 3. The audible indicator (13) according to one of items 1 or 2, wherein the rotatable element (13.1) comprises a first leg (13.2) and a second leg (13.3) which are arranged substantially in an L-shape.

[0043] 4. Audible indicator (13) according to any of the preceding clauses, wherein the rotatable element (13.1) comprises a pivot hole (13.4).

[0044] 5. Audible indicator (13) according to items 3 and 4, wherein the first leg (13.2) comprises a curved section (13.9) towards the free end (13.5) in the vicinity of the pivot hole (13.4).

[0045] 6. Audible indicator (13) according to item 4 or 5, wherein the pivot hole (13.4) comprises a V-shaped slot (13.14).

[0046] 7. An audible indicator (13) according to any of the preceding items, wherein the spring element (13.10) comprises a beam (13.11) and a marking portion (13.12), wherein the marking portion (13.12) protrudes substantially at a right angle from one end of the beam (13.11), wherein the marking portion (13.12) is adapted to engage in the narrow slot (13.8).

[0047] 8. An audible indicator (13) according to any one of the preceding items, wherein the spring element (13.10) has a substantially straight shape in the relaxed state (S1) and is configured to deflect away from the straight shape in a resilient manner to form a curved shape in the biased state (S2).

[0048] 9. Acoustic indicator (13) according to any of the preceding clauses, wherein the rotatable element (13.1) and / or the spring element (13.10) is a metal component, in particular a sheet metal component.

[0049] 10. A drug delivery device (1) comprising a housing (2), a plunger (10) and an audible indicator (13), the audible indicator (13) comprising a spring element (13.10) configured to be in one of a relaxed state (S1) and a biased state (S2),

[0050] - wherein the audible indicator (13) comprises a rotatable element (13.1) which is coupled to the spring element (13.10) and is rotatable about a pivot,

[0051] - When the spring element (13.10) changes from the biased state (S2) to the relaxed state (S1), the spring element (13.10) releases stored energy to rotate the rotatable element (13.1), so that the rotatable element (13.1) hits the surface of the housing (2) to generate an audible signal.

[0052] 11. The drug delivery device (1) according to claim 10,

[0053] The spring element (13.10) is allowed to change from the biased state (S2) by movement of the plunger (10).

[0054] 12. The drug delivery device (1) according to claim 11, wherein at the end of the drug delivery process, the spring element (13.10) is changed from the biased state (S2) to the relaxed state (S1) by the movement of the plunger (10).

[0055] 13. A drug delivery device (1) according to any one of items 10 to 12, wherein the rotatable element (13.1) comprises a pivot hole (13.4), which is configured to be rotatably mounted on a bearing pin (2.3) arranged on the housing (2).

[0056] 14. A drug delivery device (1) according to item 13, wherein the pivot hole (13.4) comprises a V-shaped slot (13.14) allowing the pivot hole (13.4) to be latched laterally onto the bearing pin (2.3).

[0057] 15. A drug delivery device (1) according to any one of items 10 to 14, wherein the rotatable element (13.1) comprises a first leg (13.2) and a second leg (13.3) arranged substantially in an L-shape, wherein the free end (13.13) of the second leg (13.3) is suitable for radially inwardly abutting the plunger (10) to keep the audible indicator (13) in a pre-release state.

[0058] 16. Drug delivery device according to item 15, wherein an aperture (2.4) is provided in the housing (2) for retaining the spring element (13.10).

[0059] 17. A method of producing an audible indicator (13) for a drug delivery device (1), the method comprising:

[0060] - forming a spring element (13.10) which is configured to be in one of a relaxed state (S1) and a biased state (S2),

[0061] - forming a rotatable element (13.1) adapted to be coupled to the spring element (13.10) and rotatable about a pivot,

[0062] The spring element (13.10) and the rotatable element (13.1) are produced in a press-bending production process on an automatic press-bending machine. BRIEF DESCRIPTION OF THE DRAWINGS

[0063] The present disclosure will be more fully understood from the detailed description and accompanying drawings given below, which are given by way of illustration only and not limiting of the present disclosure, and in which:

[0064] Figure 1 is a schematic perspective partial cross-section of a drug delivery device including an audible indicator,

[0065] Figure 2 is a schematic exploded view of the auditory indicator,

[0066] Figure 3 is a schematic diagram of the auditory indicator,

[0067] Figure 4 is a schematic diagram of an audible indicator in a pre-release state located in a drug delivery device, and

[0068] Figure 5 is a schematic diagram of an audible indicator located in a drug delivery device in a released state.

[0069] Throughout the Figures, corresponding parts are marked with the same reference numerals. DETAILED DESCRIPTION

[0070] In the present application, when the term "distal section / end" is used, this refers to the section / end of the device or the section / end of a component thereof which is closest to the drug delivery site of the patient when the device is in use. Correspondingly, when the term "proximal section / end" is used, this refers to the section / end of the device or the section / end of a component thereof which is directed away from the drug delivery site of the patient during use of the device.

[0071] Figure 1 An exemplary embodiment of a drug delivery device 1 which may be configured as an autoinjector is shown.

[0072] In this exemplary embodiment, the drug delivery device 1 comprises a housing 2 having a front housing 2.1 and a rear housing 2.2. The housing 2 is suitable for holding a drug container 3, such as a syringe. (The drug container is hereinafter referred to as "syringe 3"). The syringe 3 may be a pre-filled syringe containing a drug M and having a needle 4 arranged at the distal end of the syringe 3, in particular a 1.0 ml pre-filled syringe. In another exemplary embodiment, the drug container 3 may be a cartridge comprising a drug M and engaged with a detachable needle (e.g., by a thread, a bayonet, friction, etc.).

[0073] The drug delivery device 1 further comprises a protective needle shield 5 coupled to the needle 4. For example, the protective needle shield 5 is removably coupled to the needle 4. The protective needle shield 5 may be a rubber needle shield or a rigid needle shield consisting of a rubber and a full or partial plastic shell.

[0074] For sealing the syringe 3 in the proximal direction and for displacing the medicament M contained in the syringe 3 through the needle 4, a stopper 6 arranged inside the syringe 3 is provided.

[0075] In the embodiment shown, the drug delivery device 1 comprises a needle shield 7 which is sleeve-coupled to the housing 2 and which is movable between a first extended position relative to the housing 2 in which the needle 4 is covered and a retracted position relative to the housing 2 in which the needle 4 is exposed. Furthermore, a shield spring 8 is arranged to bias the needle shield 7 against the housing 2 in the distal direction.

[0076] In addition, a drive spring 9 is arranged in the housing 2. The plunger 10 is used to transmit the force of the drive spring 9 to the stopper 6. The plunger 10 can be hollow, wherein the drive spring 9 is arranged in the plunger 10 to bias the plunger 10 in the distal direction to the housing 2. In another exemplary embodiment, the plunger 10 can be solid and the driver 9 can engage the proximal end of the plunger 10. In the embodiment shown, the drive spring 9 is wound around the outer diameter of the plunger 10 and extends in the syringe 3.

[0077] In addition, the drug delivery device 1 comprises a cap 11, which can be removably arranged at the distal end of the housing 2, in particular at the distal end of the front housing 2.1. The cap 11 may include a clamping structure 11.1 that facilitates the removal of the cap 11, for example by twisting and / or pulling the cap 11 off the housing 2. The cap 11 may further include a clamping element 11.2, such as a barb, a hook, a narrowing section, etc., arranged to engage the protective needle shield 5, the housing 2 and / or the needle shield 7.

[0078] In the illustrated embodiment, the plunger release mechanism 12 is arranged to prevent release of the plunger 10 before the needle shield 7 is retracted relative to the housing 2 , and to release the plunger 10 once the needle shield 7 is sufficiently retracted.

[0079] Furthermore, the shield locking mechanism 14 is arranged to prevent the needle shield 7 from being retracted relative to the housing 2 when the cap 11 is in place, thereby avoiding inadvertent activation of the drug delivery device 1 during shipping or packaging, for example if it is dropped. The shield locking mechanism 14 may comprise one or more compliant beams 11.3 on the cap 11 and a corresponding number of apertures 7.6 in the needle shield 7 adapted to receive each compliant beam 11.3.

[0080] When the cap 11 is attached to the drug delivery device 1, the compliant beam 11.3 abuts against a radial stop 2.15 on the housing 2, which prevents the compliant beam 11.3 from disengaging from the aperture 7.6. In addition, when the cap 11 is attached to the drug delivery device 1, a rib 11.4 on the cap 11 abutting against the housing 2 limits the axial proximal movement of the cap 11 relative to the housing 2.

[0081] When the cap 11 is pulled away from the housing 2 in the distal direction, the compliant beam 11.3 may abut the edge of the aperture 7.6 and deflect to disengage from the aperture 7.6, thereby allowing the cap 11 and the protective needle sheath 5 attached thereto to be removed. In an exemplary embodiment, the compliant beam 11.3 and / or the aperture 7.6 may be tilted to reduce the force necessary to disengage the compliant beam 11.3 from the aperture 7.6.

[0082] The drug delivery device 1 further comprises an audible indicator 13 which produces audible feedback to the user or patient indicating that the medicament delivery is complete. In other words, the audible indicator 13 is provided to indicate to the user or patient that the full dose of medicament M is consumed.

[0083] The drug delivery device 1 may further comprise a carrier 16 allowing accurate support of the syringe 3 during and after assembly. The carrier 16 is adapted to mount, position and retain the syringe 3 in the housing 2.

[0084] In the subsequent Figure 2-5 , the auditory indicator 13 will be described in more detail.

[0085] Figure 2 and 3 is a schematic diagram of the auditory indicator 13, wherein Figure 2 An exploded view of the audible indicator 13 is shown, Figure 3 The audible indicator 13 is shown in a partially assembled state. Figure 4 shows the audible indicator 13 in the drug delivery device 1 in the pre-release state, Figure 5 The audible indicator 13 in the drug delivery device 1 is shown in the released state.

[0086] The audible indicator 13 comprises a rotatable element 13.1 which may be comprised of sheet metal. The rotatable element 13.1 may comprise a first leg 13.2 and a second leg 13.3 arranged substantially in an L-shape. The first leg 13.2 may comprise a pivot bore 13.4 arranged to be rotatably mounted on a bearing pin 2.3 which may be arranged in the rear housing 2.2 such that the second leg 13.3 points substantially radially inwardly. When the rotatable element 13.1 is located on the bearing pin 2.3, a free end 13.5 of the first leg 13.2 may be angled and have an end face 13.6 pointing substantially radially outwardly. An end of the first leg 13.2 opposite the free end 13.5 is connected to the second leg 13.3 to form an interface 13.7 and comprises a slot 13.8. Although the first leg 13.2 may have a substantially straight section between the junction 13.7 and the pivot hole 13.4 for abutting the front housing 2.1 in the pre-release state, a curved section 13.9 may be provided on the first leg 13.2 near the pivot hole 13.4 toward the free end 13.5 to allow the rotatable element 13.1 to rotate in the release state until the end face 13.6 abuts the front housing 2.1.

[0087] Alternatively, instead of the pivot bore 13.4, the rotatable element 13.1 may comprise any kind of pivot, such as a pivot shaft configured to be mounted in a bore (which may be arranged in the drug delivery device 1, such as in the housing 2 thereof).

[0088] The audible indicator 13 further comprises a spring element 13.10, which comprises a beam 13.11 and a marking portion 13.12 protruding substantially at a right angle from one end of the beam 13.11. The marking portion 13.12 is adapted to engage in a slot 13.8 in the rotatable element 13.1 so that the spring element 13.10 can rotate the rotatable element 13.1. The beam 13.11 is adapted to be retained in an aperture 2.4 in the rear housing 2.2. The spring element 13.10 can have a substantially rectilinear shape in the relaxed state S1 and can be deflected in a resilient manner out of the rectilinear shape to form a curved shape in the biased state S2.

[0089] The free end 13.13 of the second leg 13.3 is adapted to abut the plunger 10 radially inwardly before the plunger 10 is released to maintain the audible indicator in a pre-release state in which the spring element 13.10 is in the biased state S2 (see Figure 4 ) and biases the second leg 13.3 inwardly towards the plunger 10. The end face 13.6 is radially spaced apart from the front housing 2.1.

[0090] To deliver the medicament M through the needle 4 into the injection site (e.g., the patient's skin), the plunger 10 is moved in the distal direction relative to the drive spring 9 to a distal position due to the activation of the drive spring 9. The activation of the drive spring 9 can be initiated by pressing a button or by depressing the needle shield 7 (such as it is pushed against the injection site), thereby causing the plunger release mechanism 12 to release the plunger 10.

[0091] As the plunger 10 is released, the plunger 10 is driven by the drive spring 9 and advances in the distal direction D. At the end of the dose or immediately before this, the plunger 10 has traveled in the distal direction D so that it no longer engages the second leg 13.3, whereby it can move further inwards under the bias of the spring element 13.10, so that the rotatable element 13.1 rotates and the end face 13.6 hits the front housing 2.1, generating an audible feedback. The volume of the audible feedback depends on the preload of the spring element 13.10 in its biased state S2. The spring element 13.10 relaxes and returns to its relaxed state S1. The user or patient who recognizes the audible signal knows that the drug delivery process is complete and a full dose has been delivered.

[0092] The rotatable element 13 . 1 and the spring element 13 . 10 can be metal parts, in particular sheet metal parts, which are produced in a press-bending production process.

[0093] The pivot hole 13.4 may be partially open and include a V-shaped slot 13.14 which allows the pivot hole 13.4 to be latched laterally onto the bearing pin 2.3.

[0094] The term "drug" or "medicament" is used herein to describe one or more pharmaceutically active compounds. As described below, a drug or medicament may include at least one small or large molecule or a combination thereof in a variety of formulation types for treating one or more diseases. Exemplary pharmaceutically active compounds may include small molecules; polypeptides; peptides and proteins (e.g., hormones, growth factors, antibodies, antibody fragments, and enzymes); sugars and polysaccharides; and nucleic acids, double-stranded or single-stranded DNA (including naked and cDNA), RNA, antisense nucleic acids such as antisense DNA and RNA, small interfering RNA (siRNA), ribozymes, genes, and oligonucleotides. Nucleic acids can be incorporated into molecular delivery systems such as vectors, plasmids, or liposomes. Mixtures of one or more of these drugs are also contemplated.

[0095] The term "drug delivery device" should encompass any type of device or system configured to distribute drugs into a human or animal body. Without limitation, the drug delivery device can be an injection device (e.g., a syringe, a pen-type syringe, an auto-injector, a large volume device, a pump, an infusion system, or other devices configured for intraocular, subcutaneous, intramuscular, or intravascular delivery), a skin patch (e.g., osmotic, chemical, micro needle), an inhaler (e.g., for the nose or lungs), an implantable device (e.g., a coated stent, a capsule), or a supply system for the gastrointestinal tract. The drugs described herein can be particularly useful together with an injection device comprising a needle (e.g., a small gauge needle).

[0096] The drug or medicament may be contained in a primary package or "drug container" suitable for use with a drug delivery device. The drug container may be, for example, a cartridge, a syringe, a storage device, or other containers configured to provide a suitable chamber for storing (e.g., short-term or long-term storage) more than one pharmaceutically active compound. For example, in some cases, the chamber may be designed to store the drug for at least one day (e.g., 1 day to at least 30 days). In some cases, the chamber may be designed to store the drug for about 1 month to about 2 years. Storage may be performed at room temperature (e.g., about 20°C) or at a freezing temperature (e.g., about -4°C to about 4°C). In some cases, the drug container may be or may include a dual-chamber cartridge, which is configured to store two or more components of a drug formulation (e.g., a drug and a diluent, or two different types of drugs), one component per chamber. In such a case, the two chambers of the dual-chamber cartridge may be configured to allow mixing between the two or more components of the drug or medicament before and / or during distribution into a human or animal body. For example, the two chambers may be configured so that they are in fluid communication with each other (e.g., by means of a conduit between the two chambers) and allow mixing of the two components when the user desires before dispensing. Alternatively or in addition, the two chambers may be configured to allow mixing when the components are being dispensed into a human or animal body.

[0097] The drug delivery devices and medicaments described herein can be used to treat and / or prevent a variety of different types of conditions. Exemplary conditions include, for example, diabetes or complications associated with diabetes such as diabetic retinopathy, thromboembolic conditions such as deep vein or pulmonary thromboembolism. Other exemplary conditions are acute coronary syndrome (ACS), angina, myocardial infarction, cancer, macular degeneration, inflammation, hay fever, atherosclerosis and / or rheumatoid arthritis.

[0098] Exemplary drugs for treating and / or preventing diabetes or complications associated with diabetes include insulin, such as human insulin or human insulin analogs or derivatives, glucagon-like peptide (GLP-1), GLP-1 analogs or GLP-1 receptor agonists, or analogs or derivatives thereof, dipeptidyl peptidase-4 (DPP4) inhibitors or pharmaceutically acceptable salts or solvates thereof, or any mixtures thereof. As used herein, the term "derivative" refers to any substance that is structurally similar to the original substance so as to have substantially similar functions or activities (e.g., therapeutic efficacy).

[0099] Exemplary insulin analogs are Gly(A21), Arg(B31), Arg(B32) human insulin (glargine); Lys(B3), Glu(B29) human insulin; Lys(B28), Pro(B29) human insulin; Asp(B28) human insulin; human insulin wherein the proline at position B28 is replaced by Asp, Lys, Leu, Val or Ala and wherein the Lys at position B29 is replaced by Pro; Ala(B26) human insulin; Des(B28-B30) human insulin; Des(B27) human insulin and Des(B30) human insulin.

[0100] Exemplary insulin derivatives are, 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-Th rB29LysB30 human insulin; B30-N-palmitoyl-ThrB29LysB30 human insulin; B29-N-(N-palmitoyl-γ-glutamyl)-Des(B30) human insulin; B29-N-(N-lithocholyl-γ-glutamyl)-Des(B30) human insulin; B29-N-(ω-carboxyheptadecanoyl)-Des(B30) human insulin and B29-N-(ω-carboxyheptadecanoyl) human insulin. Exemplary GLP-1, GLP-1 analogs and GLP-1 receptor agonists are, for example: Lixisenatide / AVE0010 / ZP10 / Lyxumia, Exenatide / Exendin-4 / Byetta / Bydureon / ITCA 650 / AC-2993 (a 39-amino acid peptide produced by the salivary glands of the Gila monster), Liraglutide / Victoza, Semaglutide, Taspoglutide, Syncria / Albiglutide, Dulaglutide, rExendin-4, CJC-1134-PC, PB-1023, TTP-054, Langlenatide / HM-11260C, CM-3, GLP-1Elige n, ORMD-0901, NN-9924, NN-9926, NN-9927, Nodexen, Viador-GLP-1, CVX-096, ZYOG-1, ZYD-1, GSK-2374697, DA-3091, MAR-701, MAR 709, ZP-2929, ZP-3022, TT-401, BHM-034, MOD-6030, CAM-2036, DA-15864, ARI-2651, ARI-2255, Exenatide-XTEN and Glucagon-Xten.

[0101] An exemplary oligonucleotide is, for example, mipomersen / Kynamro, a cholesterol-lowering antisense therapy used to treat familial hypercholesterolemia.

[0102] Exemplary DPP4 inhibitors are Vildagliptin, Sitagliptin, Denagliptin, Saxagliptin, Berberine.

[0103] Exemplary hormones include pituitary hormones or hypothalamic hormones or regulatory active peptides and their antagonists, such as gonadotropins (Follitropin, Lutropin, Choriongonadotropin, Menotropin), somatropine (Somatropin), desmopressin, terlipressin, gonadorelin, triptorelin, leuprorelin, buserelin, nafarelin and goserelin.

[0104] Exemplary polysaccharides include glycosaminoglycans, hyaluronic acid, heparin, low molecular weight heparin or ultra-low molecular weight heparin or derivatives thereof, or sulfated polysaccharides such as polysulfated forms of the above-mentioned polysaccharides and / or pharmaceutically acceptable salts thereof. The example of a pharmaceutically acceptable salt of polysulfated low molecular weight heparin is enoxaparin sodium. The example of a hyaluronic acid derivative is Hylan GF 20 / Synvisc, a sodium hyaluronate.

[0105] The term "antibody" as used herein refers to an immunoglobulin molecule or an antigen binding portion thereof. Examples of antigen binding portions of immunoglobulin molecules include F(ab) and F(ab')2 fragments, which retain the ability to bind to antigens. Antibodies can be polyclonal, monoclonal, recombinant, chimeric, deimmunized or humanized, full-length human, non-human (e.g., murine) or single-chain antibodies. In some embodiments, antibodies have effector functions and can fix complement. In some embodiments, antibodies do not have or have a reduced ability to bind to Fc receptors. For example, an antibody can be an isotype or subtype, an antibody fragment or a mutant that does not support binding to an Fc receptor, such as an Fc receptor binding region that has been mutated or deleted.

[0106] The term "fragment" or "antibody fragment" refers to a polypeptide derived from an antibody polypeptide molecule (e.g., an antibody heavy chain and / or light chain polypeptide), which does not include a full-length antibody polypeptide but still includes at least a portion of a full-length antibody polypeptide capable of binding to an antigen. An antibody fragment may include a cleavage portion of a full-length antibody polypeptide, but the term is not limited to the cleavage fragment. Antibody fragments useful in the present disclosure include, for example, Fab fragments, F(ab')2 fragments, scFv (single-chain Fv) fragments, linear antibodies, monospecific or multispecific antibody fragments such as bispecific, trispecific and multispecific antibodies (e.g., diabodies, triantibodies, tetrabodies), miniantibodies, chelated recombinant antibodies, trifunctional antibodies (tribodies) or bifunctional antibodies (bibodies), intrabodies, nanobodies, small modular immunopharmaceuticals (SMIPs), binding domain immunoglobulin fusion proteins, camelized antibodies, and antibodies containing VHH. Other examples of antigen-binding antibody fragments are known in the art.

[0107] The term "complementarity determining region" or "CDR" refers to short polypeptide sequences within the variable regions of both heavy and light chain polypeptides that are primarily responsible for mediating specific antigen recognition. The term "framework region" refers to amino acid sequences within the variable regions of both heavy and light chain polypeptides that are not CDR sequences and are primarily responsible for maintaining the correct positioning of the CDR sequences to allow antigen binding. As is known in the art, although the framework regions themselves are not directly involved in antigen binding, some residues within the framework regions of certain antibodies may be directly involved in antigen binding or may affect the ability of one or more amino acids in the CDR to interact with the antigen.

[0108] Exemplary antibodies are anti-PCSK-9 mAb (eg, Alirocumab), anti-IL-6 mAb (eg, Sarilumab), and anti-IL-4 mAb (eg, Dupilumab).

[0109] The compounds described herein can be used in pharmaceutical preparations comprising (a) the compound or a pharmaceutically acceptable salt thereof and (b) a pharmaceutically acceptable carrier. The compounds can also be used in pharmaceutical preparations comprising one or more other active pharmaceutical ingredients, or in pharmaceutical preparations in which the compounds of the present invention or a pharmaceutically acceptable salt thereof are the only active ingredients. Accordingly, the pharmaceutical preparations of the present invention encompass any preparations made by mixing the compounds described herein and a pharmaceutically acceptable carrier.

[0110] The pharmaceutically acceptable salt of any drug described herein may also be considered for use in a drug delivery device. Pharmaceutically acceptable salts are, for example, acid addition salts and basic salts. Acid addition salts are, for example, HCl or HBr salts. Basic salts are, for example, salts with alkali metal or alkaline earth metal cations selected from the group consisting of: for example, Na+ or K+, or Ca2+, or ammonium ions N+(R1)(R2)(R3)(R4), wherein R1-R4 independently mean: hydrogen, optionally substituted C1-C6 alkyl, optionally substituted C2-C6 alkenyl and optionally substituted C6-C10 aryl, or optionally substituted C6-C10 heteroaryl. Other examples of pharmaceutically acceptable salts are known to those skilled in the art.

[0111] Pharmaceutically acceptable solvates are, for example, hydrates or alkanolates such as methanolates or ethanolates.

[0112] Those skilled in the art will appreciate that modifications (additions and / or removals) may be made to the various components / components of the materials, formulations, apparatus, methods, systems, and embodiments described herein without departing from the overall scope and spirit of the present disclosure, which encompasses such modifications and any and all equivalents thereof.

[0113] Reference numerals list

[0114] 1 Drug delivery devices

[0115] 1.1 Driver Subassemblies

[0116] 2 Housing

[0117] 2.1 Front housing

[0118] 2.2 Rear housing

[0119] 2.3 Bearing pin

[0120] 2.4 Orifice

[0121] 2.15 Radial stop

[0122] 3. Pharmaceutical containers and syringes

[0123] 4-pin

[0124] 5 Protective needle guard

[0125] 6. Stopper

[0126] 7-pin shield

[0127] 7.6 Orifice

[0128] 8 Guard spring

[0129] 9 Drive spring

[0130] 10 Plunger

[0131] 11 Hat

[0132] 11.1 Clamping structure

[0133] 11.2 Clamping elements

[0134] 11.3 Compliant Beams

[0135] 11.4 Ribs

[0136] 12 Plunger release mechanism

[0137] 13. Auditory Indicator

[0138] 13.1 Rotatable Elements

[0139] 13.2 First Leg

[0140] 13.3 Second Leg

[0141] 13.4 Pivot hole

[0142] 13.5 Free end

[0143] 13.6 End face

[0144] 13.7 Handover

[0145] 13.8 Slots

[0146] 13.9 Curved Segments

[0147] 13.10 Spring elements

[0148] 13.11 Beam

[0149] 13.12 Logo Department

[0150] 13.13 Free end

[0151] 13.14 V-shaped slot

[0152] 14 Shield locking mechanism

[0153] D Distal direction

[0154] P proximal direction

[0155] S1 Relaxed state

[0156] S2 Bias State

Claims

1. An audible indicator (13) for a drug delivery device (1), the audible indicator (13) comprising a spring element (13.10) configured to be in one of a relaxed state (S1) and a biased state (S2), - wherein the audible indicator (13) comprises a rotatable element (13.1) which is coupled to the spring element (13.10) and is rotatable about a pivot, - when the spring element (13.10) changes from the biased state (S2) to the relaxed state (S1), wherein the spring element (13.10) releases stored energy to rotate the rotatable element (13.1), so that the rotatable element (13.1) hits a surface of a housing (2) of a drug delivery device (1) configured to include the audible indicator (13) to generate an audible signal, wherein the rotatable element (13.1) and the spring element (13.10) are sheet metal parts, wherein the rotatable element (13.1) comprises a slot (13.8), and wherein the spring element (13.10) engages in the slot (13.8) in the rotatable element (13.1), wherein the rotatable element (13.1) comprises a first leg (13.2) and a second leg (13.3) arranged substantially in an L-shape, wherein the rotatable element (13.1) comprises a pivot hole (13.4), The spring element (13.10) comprises a beam (13.11) and a marking portion (13.12), wherein the marking portion (13.12) protrudes from one end of the beam (13.11), wherein the marking portion (13.12) is adapted to engage in the slot (13.8), wherein the spring element (13.10) has a substantially straight shape in the relaxed state (S1) and is configured to deflect in a resilient manner away from the straight shape to form a curved shape in the biased state (S2), and The spring element (13.10) and the rotatable element (13.1) are produced in a press-bending production process on an automatic press-bending machine.

2. Audible indicator (13) according to claim 1, wherein the first leg (13.2) comprises a curved section (13.9) towards the free end (13.5) in the vicinity of the pivot hole (13.4).

3. The audible indicator (13) according to claim 1, wherein the pivot hole (13.4) comprises a V-shaped slot (13.14).

4. The audible indicator (13) according to claim 1, wherein the marking portion (13.12) protrudes at a right angle from the one end of the beam (13.11).

5. An audible indicator (13) according to any one of claims 1 to 4, wherein the audible indicator (13) is configured such that at or immediately before the end of a dose, the plunger (10) of the drug delivery device (1) travels so far in the distal direction (D) that it is no longer engaged with the rotatable element (31.1), whereby the rotatable element (31.1) is able to move further inwards under the bias of the spring element 13.10, so that the rotatable element (13.1) rotates and hits the housing (2) to generate the audible signal.

6. A drug delivery device (1) comprising a housing (2), a plunger (10) and an audible indicator (13), the audible indicator (13) comprising a spring element (13.10) configured to be in one of a relaxed state (S1) and a biased state (S2), - wherein the audible indicator (13) comprises a rotatable element (13.1) which is coupled to the spring element (13.10) and is rotatable about a pivot, - when the spring element (13.10) changes from the biased state (S2) to the relaxed state (S1), wherein the spring element (13.10) releases stored energy to rotate the rotatable element (13.1), so that the rotatable element (13.1) hits the surface of the housing (2) to generate an audible signal, wherein the rotatable element (13.1) and the spring element (13.10) are sheet metal parts, wherein the rotatable element (13.1) comprises a slot (13.8), and wherein the spring element (13.10) engages in the slot (13.8) in the rotatable element (13.1), wherein the rotatable element (13.1) comprises a first leg (13.2) and a second leg (13.3) arranged substantially in an L-shape, wherein a free end (13.13) of the second leg (13.3) is adapted to abut radially inwardly against the plunger (10) to hold the audible indicator (13) in a pre-release state, The rotatable element (13.1) comprises a pivot hole (13.4), wherein the pivot hole (13.4) is configured to be rotatably mounted on a bearing pin (2.3) arranged on the housing (2), The spring element (13.10) comprises a beam (13.11) and a marking portion (13.12), wherein the marking portion (13.12) protrudes from one end of the beam (13.11), wherein the marking portion (13.12) is adapted to engage in the slot (13.8), wherein the spring element (13.10) has a substantially straight shape in the relaxed state (S1) and is configured to deflect in a resilient manner away from the straight shape to form a curved shape in the biased state (S2), and The spring element (13.10) and the rotatable element (13.1) are produced in a press-bending production process on an automatic press-bending machine.

7. The drug delivery device (1) according to claim 6, wherein the spring element (13.10) is allowed to change from the biased state (S2) by movement of the plunger (10).

8. The drug delivery device (1) according to claim 7, wherein at the end of a drug delivery process, the spring element (13.10) is changed from the biased state (S2) to the relaxed state (S1) by movement of the plunger (10) towards a distal position.

9. The drug delivery device (1) according to claim 6, wherein the pivot bore (13.4) comprises a V-shaped slot (13.14) allowing the pivot bore (13.4) to be latched laterally onto the bearing pin (2.3).

10. The drug delivery device according to claim 6, wherein: An aperture (2.4) for holding the spring element (13.10) is provided in the housing (2).

11. A drug delivery device (1) according to claim 6, wherein the housing (2) comprises a front housing (2.1) and a rear housing (2.2), and the bearing pin (2.3) is arranged on one of the front housing (2.1) and the rear housing (2.2), and the rotatable element (13.1) is configured to impact the other of the front housing (2.1) and the rear housing (2.2).

12. The drug delivery device (1) according to claim 6, wherein the housing (2) comprises a front housing (2.1) and a rear housing (2.2), and the bearing pin (2.3) is arranged on one of the front housing (2.1) and the rear housing (2.2), and The rotatable element (13.1) is configured to strike one of the front housing (2.1) and the rear housing (2.2) where the bearing pin (2.3) is arranged.

13. The drug delivery device (1) according to claim 6, wherein the housing (2) is a one-piece housing (2).

14. The drug delivery device (1) according to claim 6, The drug delivery device comprises a second spring element (13.10), which is configured to release stored energy to rotate the rotatable element (13.1), so that when the second spring element (13.10) changes from a biased state (S2) to a relaxed state (S1), the rotatable element (13.1) hits the surface of the housing (2) to generate an audible signal, which indicates the end of drug delivery by the drug delivery device (1).

15. The drug delivery device (1) according to claim 6, comprising a drug container (3), The drug container (3) comprises a drug (M).

16. The drug delivery device (1) according to claim 6, wherein the marking portion (13.12) protrudes substantially at a right angle from the one end of the beam (13.11).

17. A drug delivery device (1) according to any one of claims 6 to 16, wherein the drug delivery device (1) is configured such that at the end of a dose or immediately before the end of a dose, the plunger (10) travels so far in the distal direction (D) that it is no longer engaged with the rotatable element (31.1), whereby the rotatable element (31.1) is able to move further inwardly under the bias of the spring element (13.10), so that the rotatable element (13.1) rotates and hits the housing (2) to generate the audible signal.

18. A method of producing an audible indicator (13) for a drug delivery device (1), the method comprising: - forming a spring element (13.10) which is configured to be in one of a relaxed state (S1) and a biased state (S2), - forming a rotatable element (13.1) adapted to be coupled to the spring element (13.10) and capable of rotating about a pivot, wherein the spring element (13.10) and the rotatable element (13.1) are produced in a bending production process on an automatic bending machine, wherein the rotatable element (13.1) and the spring element (13.10) are sheet metal parts, wherein the rotatable element (13.1) comprises a slot (13.8), and wherein the spring element (13.10) engages in the slot (13.8) in the rotatable element (13.1), wherein the rotatable element (13.1) comprises a first leg (13.2) and a second leg (13.3) arranged substantially in an L-shape, wherein a free end (13.13) of the second leg (13.3) is adapted to abut radially inwardly against a plunger (10) of the drug delivery device (1) to maintain the audible indicator (13) in a pre-release state, The rotatable element (13.1) comprises a pivot hole (13.4) configured to be rotatably mounted on a bearing pin (2.3) arranged on a housing (2) of the drug delivery device (1), The spring element (13.10) comprises a beam (13.11) and a marking portion (13.12), wherein the marking portion (13.12) protrudes from one end of the beam (13.11), wherein the marking portion (13.12) is adapted to engage in the slot (13.8), and The spring element (13.10) has a substantially straight shape in the relaxed state (S1) and is configured to deflect away from the straight shape in a resilient manner to form a curved shape in the biased state (S2).

19. The method according to claim 18, wherein the first leg (13.2) comprises a curved section (13.9) near the pivot hole (13.4) towards the free end (13.5).

20. The method of claim 18, wherein the pivot bore (13.4) comprises a V-shaped slot (13.14).

21. The method according to claim 18, wherein the marking portion (13.12) protrudes at a right angle from the one end of the beam (13.11).

22. The method according to claim 18, wherein the rotatable element (13.1) is a flat portion extending only in a first plane.

23. A method according to claim 22, wherein the beam (13.11) of the spring element (13.10) is a flat portion extending only in the second plane.

24. The method according to claim 23, wherein the rotatable element (13.1) part and the spring element (13.10) are configured such that the first plane is arranged perpendicular to the second plane.

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