Patent Description:
Autoinjector devices aim to make self-injection easier for patients. A conventional autoinjector may provide the force for administering the injection by a spring, and a trigger button or other mechanism may be used to activate the injection. Autoinjectors may be single-use or reusable devices.

Furthermore, it is necessary to administer the full dose in order to achieve full effectiveness of the medicament within the patient.

<CIT> discloses a syringe comprising a cylindrical insert that defines a volume for inserting the syringe. The cylindrical insert is part of a plunger locking mechanism and comprises flexible arms that lock the plunger for axial movement in the proximal direction when the injection is completed. <CIT>, <CIT>, <CIT> and <CIT> also disclose a drug delivery device with an audible signal indicating completion of medicament delivery.

There remains a need for an improved drug delivery device.

It is an object of the present invention to provide an improved drug delivery device.

The object is achieved by a drug delivery device according to claim <NUM>.

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

According to the present invention, a drug delivery device, namely an autoinjector, comprises:.

The provided drug delivery device is improved due to the audible indicator which can be used for indicating to a patient or user that the full dose of medicament was spent. Thereby, noise is generated due to a deflection of the resilient element.

In another exemplary embodiment, the resilient element may initially be in the second configuration.

According to the invention, the resilient element is configured as a leaf spring comprising a proximal spring section coupled to a distal spring section.

The resilient element may be S-shaped which allows the resilient element to remain in a relaxed state until end of drug delivery. This enables less mechanical stress of the resilient element during storage and drug delivery.

The proximal spring section is fixed to the case, e. by a snap connection, wherein the distal spring end is configured as a free end of the resilient element.

Furthermore, the distal spring section may be bent radially inwards towards the plunger with respect to the proximal spring section. The distal spring section may be representing a ramp section for an increased proximal plunger circumference.

In an exemplary embodiment, the distal spring section of the resilient element may comprise a hook that is bent radially outwards relative to the distal spring section. The hook constitutes a stop area adapted to impact on the plunger in order to generate the audible and tactile signal.

In a further exemplary embodiment, the resilient element is radially spaced from a distal plunger section.

The resilient element comprises a single metal component for generating a recognizable audible signal.

Furthermore, the resilient element remains in the first configuration during medicament delivery until a proximal plunger section abuts the distal spring section.

When the proximal plunger section abuts the distal spring section, thereby reaching the distal spring end, the resilient element is allowed to relax radially inwards. As a result, the distal spring end hits an outer circumference of the proximal plunger section, thereby generating the audible signal.

According to the invention, the drug delivery device is configured as an autoinjector that comprises the case adapted to hold a medicament container, a needle shroud telescopically coupled to the case, a shroud spring biasing the needle shroud distally relative to the case, and a drive spring biasing the plunger from the proximal position towards the distal position for delivering a medicmanet from the medicament container.

In a further exemplary embodiment, the case comprises a syringe support for supporting an axial position of the medicament container relative to the case, wherein the syringe support comprises at least two support arms. In particular, the support arms are configured with different lengths, wherein one support arm is longer than the other support arm.

The resilient element may be coupled to the syringe support in a manner extending distally from one of the support arms.

Further scope of applicability of the present invention will become apparent from the detailed description given hereinafter. However, it should be understood that the detailed description and specific examples, while indicating exemplary embodiments of the invention, are given by way of illustration only, since various changes and modifications within the scope of the invention will become apparent to those skilled in the art from this detailed description.

The present invention will become more fully understood from the detailed description given herein below and the accompanying drawings which are given by way of illustration only, and thus, are not limitative of the present invention, and wherein:.

<FIG> shows a schematic perspective partial section of an exemplary embodiment of a drug delivery device <NUM> according to the present invention.

In the shown exemplary embodiment, the drug delivery device <NUM> is configured as an autoinjector device.

The drug delivery device <NUM> comprises a case <NUM> with a front case <NUM> and a rear case <NUM> and a longitudinal axis A extending from a proximal end towards a distal end. The case <NUM> is adapted to hold a medicament container <NUM>, such as a syringe. The medicament container is referred to hereinafter as the "syringe <NUM>". The syringe <NUM> may be a pre-filled syringe containing a medicament M and having a needle <NUM> arranged at a distal end of the syringe <NUM>. In another exemplary embodiment, the medicament container <NUM> may be a cartridge which includes the medicament M and engages a removable needle (e.g. by threads, snaps, friction, etc.). In the shown exemplary embodiment, the syringe <NUM> is held in the case <NUM> and supported at its proximal end therein by a syringe support <NUM> that is further described in <FIG>.

The drug delivery device <NUM> further comprises a protective needle sheath <NUM> that is coupled to the needle <NUM>. For example, the protective needle sheath <NUM> is removably coupled to the needle <NUM>. The protective needle sheath <NUM> may be a rubber needle sheath or a rigid needle sheath which is composed of rubber and a full or partial plastic shell.

For sealing the syringe <NUM> in a proximal direction P and for displacing a medicament M contained in the syringe <NUM> through the needle <NUM>, a stopper <NUM> is provided and arranged within the syringe <NUM>.

A needle shroud <NUM> is telescopically coupled to the case <NUM> and movable between a first extended position relative to the case <NUM> in which the needle <NUM> is covered and a retracted position relative to the case <NUM> in which the needle <NUM> is exposed. Furthermore, a shroud spring <NUM> is arranged to bias the needle shroud <NUM> distally against the case <NUM>.

In the shown exemplary embodiment, a drive spring <NUM> is arranged within the case <NUM>. A plunger <NUM> serves for forwarding a force of the drive spring <NUM> to the stopper <NUM>. The plunger <NUM> is hollow and comprises a proximal plunger section <NUM> and a distal plunger section <NUM>, wherein a diameter of the proximal plunger section <NUM> is larger than a diameter of the distal plunger section <NUM>. The drive spring <NUM> is arranged within the plunger <NUM> biasing the plunger <NUM> distally against the case <NUM> as illustrated in <FIG>. In another not shown exemplary embodiment, the plunger <NUM> may be solid and the drive spring <NUM> may engage a proximal end of the plunger <NUM>.

The plunger <NUM> is movable from a proximal position (as illustrated in <FIG>) towards a distal position (as illustrated in <FIG>) relative to the case <NUM> to drive the medicament M from the syringe <NUM> through the needle <NUM> into the patient.

Furthermore, the plunger <NUM> may be prevented from releasing prior to retraction of the needle shroud <NUM> relative to the case <NUM>. The plunger <NUM> may be configured to be released once the needle shroud <NUM> is sufficiently retracted. This is realized by a plunger release mechanism, which will not be described in more detail.

A cap <NUM> may be removably disposed at a distal end of the case <NUM>, in particular at a distal end of the front case <NUM>. The cap <NUM> may comprise grip features (not shown in detail) for facilitating a removal of the cap <NUM>, e.g., by twisting and/or pulling the cap <NUM> off the case <NUM> and for engaging the protective needle sheath <NUM>, the case <NUM> and/or the needle shroud <NUM>. The grip features may include a barb, a hook, a narrowed section, etc..

As long as the cap <NUM> is in place, the needle shroud <NUM> is prevented from retracting relative to the case <NUM> , thereby avoiding unintentional activation of the drug delivery device <NUM>, e.g., if dropped, during shipping or packaging, etc. This is realized by a shroud lock mechanism, which will not be described in more detail.

The drug delivery device <NUM> further comprises at least one audible indicator <NUM> for producing an audible feedback for a user or patient indicating completion of medicament M delivery. In other words: The audible indicator <NUM> is provided to indicate to a user or a patient that the full dose of medicament M was spent.

According to the exemplary embodiment, the drug delivery device <NUM> comprises one audible indicator <NUM> that is arranged within the rear case <NUM>.

The audible indicator <NUM> comprises a resilient element <NUM> and the proximal plunger section <NUM>. The audible indicator <NUM> will be described in more detail within the description of the following <FIG>.

<FIG> shows the resilient element <NUM> separately in a schematic perspective view.

According to the present embodiment, the resilient element <NUM> is configured as an S-shaped leaf spring comprising a proximal spring section <NUM>. <NUM> coupled to a distal spring section <NUM>.

The distal spring section <NUM>. <NUM> is angled from the proximal spring section <NUM>. <NUM> representing a ramp section for the plunger <NUM> and comprises a distal spring end <NUM>. The distal spring end <NUM>. <NUM> comprises a hook. The hook constitutes a stop area adapted to impact on an outer circumference of the plunger <NUM>.

Furthermore, the resilient element <NUM> may comprise a single metal component. For example, the single metal component is coupled to the distal spring end <NUM>.

<FIG> shows the resilient element <NUM> assembled within a drive sub assembly <NUM> of the drug delivery device <NUM>.

The drive sub assembly <NUM> is a sub assembly of the drug delivery device <NUM>, wherein the drug delivery device <NUM> further comprises a front sub assembly (not shown separately) to allow for flexibility as to the time and location of manufacture of the subassemblies and final assembly with the syringe <NUM>.

The rear case <NUM> comprises the syringe support <NUM> that is adapted to compensate variable lengths of the syringe <NUM> which occur due to manufacturing intolerances.

The syringe support <NUM> comprises two support arms <NUM>, <NUM> that are arranged opposite to each other and that project in a distal direction D from a proximal end of the rear case <NUM>. According to the present embodiment, the support arms <NUM>, <NUM> are configured with different lengths regarding the longitudinal axis A. In particular, a first support arm <NUM> is shorter than a second arm <NUM> in order to create space for an arrangement of the resilient element <NUM>.

In the shown embodiment, the resilient element <NUM> is coupled to the first support arm <NUM>. In particular, the proximal spring section <NUM>. <NUM> is coupled to the first support arm <NUM>. For example, the proximal spring section <NUM>. <NUM> is received within a guiding recess arranged on an inner side of the first support arm <NUM> and fixed by a snap connection.

Referring to the drug delivery device <NUM> illustrated in <FIG>, the proximal spring section <NUM>. <NUM> may run in parallel to the longitudinal axis A. The proximal spring section <NUM>. <NUM> is furthermore radially spaced from an outer circumference of the distal plunger section <NUM> when assembled as illustrated in <FIG>.

The distal spring section <NUM>. <NUM> projects distally from a free distal end of the first support arm <NUM> and is bent towards the outer circumference of the plunger <NUM> with respect to the.

proximal spring section <NUM>. In the assembled state, the distal spring section <NUM>. <NUM> is radially spaced from the outer circumference of the distal plunger section <NUM> and angled from the longitudinal axis A in a radial inward direction.

As the proximal spring section <NUM>. <NUM> is fixed to the first support arm <NUM>, the distal spring end <NUM>. <NUM> is configured as a free end of the resilient element <NUM>. The hook arranged on the distal spring end <NUM>. <NUM> is bent radially outwards away from the outer circumference of the plunger <NUM>. A free end of the hook runs in parallel to the longitudinal axis A in the assembled state of the resilient element <NUM>.

To support the axial position of the syringe <NUM> relative to the case <NUM> after assembly, in particular during storage, transportation and normal use, the syringe support <NUM> may comprise one or more supporting beams (not shown) that are biased radially inwards to accommodate the variable length of the syringe <NUM> in an assembled state.

<FIG> shows an enlarged view of a section of the drug delivery device <NUM> as described in <FIG> during movement of the plunger <NUM> from the proximal position towards the distal position. The distal movement of the plunger <NUM> is indicated by an arrow illustrated within the plunger <NUM>.

When the plunger <NUM> is in the proximal position, the resilient element <NUM> is in a first configuration which means in particular that the distal spring section <NUM>. <NUM> is in a relaxed state.

During movement of the plunger <NUM> from the proximal position towards the distal position, the distal spring section <NUM>. <NUM> is deflected radially outwards when the proximal plunger section <NUM> reaches the distal spring section <NUM>. The distal spring section <NUM>. <NUM> is deflected radially outwards due to the increased diameter of the proximal plunger section <NUM>. The deflection of the resilient element <NUM> is indicated by a further arrow pointing in a radial outward direction.

The distal spring section <NUM> is deflected until the proximal plunger section <NUM> passes the distal spring section <NUM>. <NUM> in the distal direction D as illustrated in <FIG>.

<FIG> shows a schematic sectional view of the drug delivery device <NUM>, wherein the plunger <NUM> is in the distal position.

Due to the radial outward bending of the distal spring end <NUM>. <NUM> away from the plunger <NUM>, the resilient element <NUM> is allowed to move into a second configuration. In the second configuration, the biased distal spring section <NUM>. <NUM> relaxes radially inwards when the distal spring end <NUM>. <NUM> is still at the same level of the proximal plunger section <NUM> with respect to the longitudinal axis A. The distal spring end <NUM>. <NUM> hits an outer circumference of the proximal plunger section <NUM>, thereby producing noise as an audible signal to indicate to a user that the full dose of medicament M was spent. The striking of the distal spring end <NUM>. <NUM> is indicated by an arrow pointing in the radial inward direction. The hitting noise generates an audible indication signal to a user that the full dose of medicament M was spent.

The skilled person readily understands that application of the audible indicator <NUM> is not limited to autoinjector devices. Instead, the audible indicator <NUM> may likewise be applied in a manually operated drug delivery device <NUM> for indicating that the plunger <NUM> has been completely moved into the distal position.

In an exemplary embodiment, when inserted in a drug delivery device <NUM>, the resilient element <NUM> may produce an audible signal with a volume of at least <NUM> dB(A), e.g. measured at a distance of approximately <NUM>. In a test setup, the drug delivery device <NUM> was placed in a sound-absorbing environment on a table with the needle shroud <NUM> ahead. An elastomeric layer was located between the needle shroud <NUM> and the table to acoustically decouple the drug delivery device <NUM> from the table. Two microphones (e.g. ROGA MI-<NUM> (IEPE)) were placed laterally from the the drug delivery device <NUM> opposite each other at a distance of <NUM>, respectively and <NUM> above the table. A first test was performed with a user holding and operating the drug delivery device <NUM> with the right hand closed around the drug delivery device <NUM>, wherein the fingers of the hand covered one side of the drug delivery device <NUM> directed towards one of the microphones and wherein the opposite side pointing towards the other microphone was covered by the palm of the hand. The volume of the audible signal on the finger side microphone was at least <NUM> dB(A) while the volume on the palm side microphone was lower than <NUM> dB(A). Another test was performed with a user holding and operating the drug delivery device <NUM> only with the fingertips of the right hand, wherein the palm of the hand was located between the drug delivery device <NUM> and one of the microphones; however, the drug delivery device <NUM> was not touched by the palm. The volume of the audible signal acquired by both microphones was at least <NUM> dB(A), wherein the volume detected by the palm side microphone was slightly lower than the volume detected by the other microphone.

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-ThrB29LysB30 human insulin; B30-N-palmitoyl- ThrB29LysB30 human insulin; B29-N-(N-palmitoyl-gamma-glutamyl)-des(B30) human insulin; B29-N-(N-lithocholylgamma-glutamyl)-des(B30) human insulin; B29-N-(ω-carboxyheptadecanoyl)-des(B30) human insulin and B29-N-(ω-carboxyheptadecanoyl) human insulin. Exemplary GLP-<NUM>, GLP-<NUM> analogues and GLP-<NUM> receptor agonists are, for example: Lixisenatide / AVE0010 / ZP10 / Lyxumia, Exenatide / Exendin-<NUM> / Byetta / Bydureon / ITCA <NUM> / AC-<NUM> (a <NUM> amino acid peptide which is produced by the salivary glands of the Gila monster), Liraglutide / Victoza, Semaglutide, Taspoglutide, Syncria / Albiglutide, Dulaglutide, rExendin-<NUM>, CJC-<NUM>-PC, PB-<NUM>, TTP-<NUM>, Langlenatide / HM-11260C, CM-<NUM>, GLP-<NUM> Eligen, ORMD-<NUM>, NN-<NUM>, NN-<NUM>, NN-<NUM>, Nodexen, Viador-GLP-<NUM>, CVX-<NUM>, ZYOG-<NUM>, ZYD-<NUM>, GSK-<NUM>, DA-<NUM>, MAR-<NUM>, MAR709, ZP-<NUM>, ZP-<NUM>, TT-<NUM>, BHM-<NUM>. MOD-<NUM>, CAM-<NUM>, DA-<NUM>, ARI-<NUM>, ARI-<NUM>, Exenatide-XTEN and Glucagon-Xten.

Basic salts are e.g. salts having a cation selected from an alkali or alkaline earth metal, e.g. Na+, or K+, or Ca2+, or an ammonium ion N+(R1)(R2)(R3)(R4), wherein R1 to R4 independently of each other mean: hydrogen, an optionally substituted C1-C6-alkyl group, an optionally substituted C2-C6-alkenyl group, an optionally substituted C6-C10-aryl group, or an optionally substituted C6-C10-heteroaryl group.

Claim 1:
A drug delivery device (<NUM>) comprising:
- a plunger (<NUM>), wherein the plunger (<NUM>) is slidable from a proximal position to a distal position, and
- an audible indicator (<NUM>) that comprises a resilient element (<NUM>),
wherein the resilient element (<NUM>) comprises a distal free end,
the resilient element (<NUM>) is in a first configuration when the plunger (<NUM>) is in the proximal position,
the resilient element (<NUM>) is deflected radially outwards to a second configuration during movement of the plunger (<NUM>) from the proximal position towards the distal position, and
wherein the resilient element (<NUM>) moves from the second configuration towards the first configuration when the plunger (<NUM>) moves towards or reaches the distal position, thereby generating an audible signal indicating completion of medicament (M) delivery, characterized in that:
the drug delivery device (<NUM>) is configured as an autoinjector device further comprising:
- a case (<NUM>) adapted to hold a medicament container (<NUM>),
- a needle shroud (<NUM>) telescopically coupled to the case (<NUM>),
- a shroud spring (<NUM>) biasing the needle shroud (<NUM>) distally relative to the case (<NUM>),
- a drive spring (<NUM>) biasing the plunger (<NUM>) from the proximal position towards the distal position for delivering a medicament (M) from the medicament container (<NUM>), the plunger (<NUM>) is disposed within the case (<NUM>),
the plunger (<NUM>) is slidable from the proximal position to the distal position within the case (<NUM>),
the resilient element (<NUM>) is configured as a single metal component leaf spring comprising a proximal spring section (<NUM>.<NUM>) coupled to a distal spring section (<NUM>.<NUM>), and
in that the proximal spring section (<NUM>.<NUM>) is fixed to the case (<NUM>).