Plunger and drug delivery device

Abstract

The present disclosure relates to a plunger (40) configured to transmit force from an energy source (30) to a piston (23) of a primary vessel (24). The plunger (40) includes a plunger rod (41) configured to receive force from the energy source (30). The plunger rod (41) has an inner surface (41.1) that defines a cavity (41.2). A support element (41.4) adapted to restrain the energy source (30) within the cavity (41.2) projects radially inward from the inner surface (41.1) into the cavity. [Selected figure] Figure 3

Description

[Technical field]

[0001] The present disclosure generally relates to a plunger for a drug delivery device and to a drug delivery device having such a plunger. [Background technology]

[0002] Many drug delivery devices include a drug cartridge having a piston for expelling the drug, the piston being driven by a plunger under the force of an energy source such as a spring. Summary of the Invention [Problem to be solved by the invention]

[0003] It is an object of the present disclosure to provide an improved plunger for a drug delivery device, and an improved drug delivery device having such a plunger. [Means for solving the problem]

[0004] This object is achieved by a plunger according to patent claim 1 and by a drug delivery device according to patent claim 11.

[0005] Exemplary embodiments are provided in the dependent claims.

[0006] According to one aspect of the disclosure, a plunger is configured to transfer a force from an energy source to a piston of a primary reservoir, the plunger including a plunger rod configured to receive a force from the energy source, the plunger rod having an inner surface defining a cavity, and a support element extending radially inwardly from the inner surface into the cavity, the support element adapted to restrain the energy source within the cavity.

[0007] In particular, the plunger rod has a longitudinal axis and an inner surface that defines an elongated cavity along the longitudinal axis. A support element adapted to restrain an energy source within the elongated cavity projects radially inward from the inner surface into the elongated cavity and radially supports the energy source within the elongated cavity. Further, the plunger rod is configured as a one-piece plunger rod. According to another disclosure, the support element is an internal, integral member of the one-piece plunger rod.

[0008] A relatively large force is required for the piston to deliver drugs, especially highly viscous drugs, through the narrow lumen of the needle. Therefore, an energy source, such as a spring arranged on the plunger, drives the piston, but must provide a sufficiently large force to move the piston. Therefore, when delivery is initiated, for example, a glass or plastic cartridge, or a finger flange of the cartridge, is subjected to a large load and is at risk of breaking. When the spring is extended during injection, for example in the plunger rod, it is stuck on the plunger, which causes friction between the plunger and the spring. This causes undesirable scraping noise during injection. The support element prevents undesirable scraping noise during injection. Furthermore, the support element prevents buckling of the spring coils, etc., that extend into the free extra space along the inner surface of the plunger rod.

[0009] In an exemplary embodiment, the support elements are formed as internal ribs on the inner surface, specifically, these ribs are straight elements with rounded edges.

[0010] In another exemplary embodiment, the plurality of support elements are distributed about the inner surface of the cavity. Specifically, the support elements are distributed symmetrically or uniformly about the inner surface of the cavity.

[0011] According to another aspect, the edges at the open ends of the cavities have chamfers or rounded corners. In addition, the inner diameter of the cavities increases in the region of the open ends of the cavities in the direction towards the open ends.

[0012] In an exemplary embodiment, the support element is integrally formed with the plunger rod. Specifically, the support element is formed on the plunger rod by one-component molding, two-component molding, or three-component molding. Further, the support element is formed on the inner surface of an internal elongated cavity of the plunger rod.

[0013] The present disclosure further relates to a drug delivery device including a primary container or container defining a drug cavity for receiving a drug, having an outlet and a piston or pistons slidably disposed within the drug cavity. The drug delivery device further includes a plunger as described above, and an energy source disposed to apply a force to an inner surface of the plunger rod.

[0014] In an exemplary embodiment, the energy source is a spring. Furthermore, the cartridge or container is pre-filled with a drug, such as an emergency drug, such as an allergy drug or a drug for diabetics, such as hypoglycemia, or a biologic, among others. The drug delivery device is, for example, an auto-injector, a pen injector, or a syringe.

[0015] In another embodiment, a piston or stopper slides inside the container to inject the drug. In addition, the drug delivery device includes an actuator means for automatically injecting said drug into the patient.

[0016] The drug delivery devices described herein are configured to inject a drug or agent into a patient. For example, delivery may be subcutaneous, intramuscular, or intravenous. Such devices may be operated by the patient or a caregiver, such as a nurse or physician, and may include various types of safety syringes, pen injectors, or auto-injectors. The devices may include cartridge-based systems, in which a sealed ampoule must be pierced prior to use. The volume of agent delivered by these various devices may range from about 0.5 to about 2 ml. Yet another device may include a large volume device ("LVD") or patch pump, configured to adhere to the patient's skin for a period of time (e.g., about 5, 15, 30, 60, or 120 minutes) to deliver a "large" volume of agent (usually about 2 ml to about 5 ml).

[0017] The devices described herein can also be customized to operate with a particular drug and within required specifications. For example, the device can be customized to inject the drug within a particular time (e.g., about 3 to about 20 seconds for an autoinjector, about 10 to about 60 minutes for an LVD). Other specifications can include low or minimal levels of pain, or specific conditions regarding human factors, shelf life, shelf life, bioavailability, environmental issues, etc. Such differences can result from a variety of factors, such as the viscosity range of the drug, which can be, for example, about 3 cP to about 50 cP. As a result, drug delivery devices often include hollow needles with sizes ranging from about 25 to about 31 gauge. Common sizes are 27 and 29 gauge.

[0018] The delivery devices described herein may also include one or more automated features. For example, one or more of needle insertion, drug injection, and needle retraction may be automated. Energy for one or more automated steps may be provided by one or more energy sources. The energy sources may include, for example, mechanical, pneumatic, chemical, or electrical energy. For example, the mechanical energy source may include a spring, a lever, an elastomer, or other mechanical mechanism for storing or releasing energy. One or more energy sources may be combined into a single device. The device may further include gears, valves, or other mechanisms for converting energy into movement of one or more components of the device.

[0019] One or more automated features of an auto-injector can be activated via an activation mechanism. Such activation mechanisms can include one or more of a button, a lever, a needle sleeve, or other activation components. Activation can be a single step process or a multi-step process. That is, a user may need to activate one or more activation mechanisms to effect an automated feature. For example, to inject a medication, a user may depress a needle sleeve relative to the body. In other devices, a user is required to depress a button and retract a needle shield to inject.

[0020] Additionally, such actuation may activate one or more mechanisms. For example, an actuation sequence may activate at least two of needle insertion, drug injection, and needle retraction. Some devices may also require a specific sequence of steps to cause one or more automated functions to occur. Other devices may operate with independent sequences of steps.

[0021] Some delivery devices can include one or more features of a safety syringe, a pen injector, or an auto-injector, For example, a delivery device can include a mechanical energy source configured to automatically inject a medication (as typically found in an auto-injector) and a dose setting mechanism (as typically found in a pen injector).

[0022] Further scope of applicability of the present disclosure will become apparent from the following detailed description. It should be understood, however, that the detailed description and specific examples, while illustrating exemplary embodiments of the present disclosure, are given by way of illustration only, since various changes and modifications within the spirit and scope of the present disclosure will become apparent to those skilled in the art from this detailed description.

[0023] The present disclosure will be better understood from the following detailed description and the accompanying figures, which are provided by way of illustration only and are not intended to limit the present disclosure. [Brief description of the drawings]

[0024] [Figure 1A] FIG. 1 is a schematic diagram of a drug delivery device. [Figure 1B] FIG. 1 is a schematic diagram of a drug delivery device. [Diagram 2] 1 is a schematic diagram of an embodiment of a plunger of a drug delivery device. [Diagram 3] FIG. 2 is a longitudinal cross-sectional view of the plunger. [Figure 4] FIG. [Diagram 5] FIG. 2 is an enlarged perspective view of a cross section of the plunger. [Figure 6] FIG. 2 is a top view of the open end of the plunger. [Figure 7] FIG. 2 is an enlarged perspective view of the top surface of the plunger. DETAILED DESCRIPTION OF THE PREFERRED EMBODIMENTS

[0025] In all the figures, corresponding parts are designated by the same reference symbols.

[0026] An exemplary drug delivery device 10 according to some embodiments of the present disclosure is shown in Figures 1A and 1B.

[0027] As mentioned above, the device 10 is configured to inject a drug or medication into the body of a patient.

[0028] The device 10 typically includes a housing 11 that houses a reservoir (eg, a syringe 24 or container) that contains the agent to be injected, and the necessary components to facilitate one or more steps of the delivery process.

[0029] The device 10 may also include a cap assembly 12. The cap assembly 12 may be removably attached to the housing 11, specifically to the distal or front end D of the device 10. Typically, a user must remove the cap assembly or cap 12 from the housing 11 before operating the device 10.

[0030] As shown, the housing 11 is substantially cylindrical and has a substantially constant diameter along a longitudinal axis X. The housing 11 has a distal region 20 and a proximal region 21. The term "distal" refers to a position relatively closer to the site of injection and the term "proximal" refers to a position relatively further from the site of injection.

[0031] The device 10 may also include a needle sleeve 13 coupled to the housing 11, allowing movement of the sleeve 13 relative to the housing 11. For example, the sleeve 13 may move in a longitudinal direction parallel to the longitudinal axis X. Specifically, proximal movement of the sleeve 13 allows the needle 17 to extend from the distal region 20 of the housing 11. Insertion of the needle 17 may occur via a number of mechanisms. For example, the needle 17 may be fixedly positioned relative to the housing 11 and may be initially positioned within the extended needle sleeve 13. Proximal movement of the sleeve 13 by positioning the distal end of the sleeve 13 relative to the patient's body and moving the housing 11 distally will expose the distal end of the needle 17. Such relative movement allows the distal end of the needle 17 to extend into the patient's body. Because the needle 17 is manually inserted via the patient manually moving the housing 11 relative to the sleeve 13, such insertion is referred to as a "manual" insertion.

[0032] Another form of insertion is "automatic", whereby the needle 17 moves relative to the housing 11. Such insertion can be triggered by movement of the sleeve 13 or by another form of actuation, such as, for example, a button 22. As shown in Figures 1A and 1B, the button 22 is located at the proximal or rear end P of the housing 11. However, in other embodiments, the button 22 can be located on the side of the housing 11. In another embodiment, the button 22 is eliminated and replaced by, for example, a sleeve trigger mechanism. This is provided, for example, by pressing the needle sleeve 13 inside the housing when the drug delivery device is placed on the side to be injected.

[0033] Other manual or automated functions may include drug injection or needle retraction, or both. Injection is the process in which the bung or piston 23 is moved from a proximal position within the container or syringe 24 to a more distal position within the syringe 24 to force the medication from the syringe 24 through the needle 17.

[0034] In some embodiments, an energy source, such as, for example, drive spring 30, is disposed on plunger 40 and compressed prior to activation of device 10. A proximal end of drive spring 30 is secured within proximal region 21 of housing 11, and a distal end of drive spring 30 can be configured to exert a compressive force on a proximal face of piston 23. After activation, at least a portion of the energy stored in drive spring 30 is applied to the proximal face of piston 23. This compressive force can act on piston 23 to move piston 23 in a distal direction. Such distal movement acts to compress the liquid medicament within syringe 24 and out of needle 17.

[0035] After injection, needle 17 may be retracted into sleeve 13 or into the housing. Retraction may occur when sleeve 13 moves distally as the user removes device 10 from the patient's body. This may occur because needle 17 remains in a fixed position relative to housing 11. Sleeve 13 is locked once the distal end of sleeve 13 moves past the distal end of needle 17 and needle 17 is covered. Such locking may include locking sleeve 13 against any proximal movement relative to housing 11.

[0036] Another form of needle retraction can occur when the needle 17 is moved relative to the housing 11. Such movement can occur when the syringe within the housing 11 is moved proximally relative to the housing 11. This proximal movement can be achieved through the use of a retraction spring (not shown) located in the distal region 20. The compressed retraction spring, when activated, can provide sufficient force to the syringe 24 to move it proximally. After sufficient retraction, any relative movement between the needle 17 and the housing 11 is locked by a locking mechanism. Additionally, the button 22 or other components of the device 10 can be locked as needed.

[0037] In some embodiments, the housing may include a window 11a through which the syringe 24 can be monitored.

[0038] FIG. 2 is a schematic diagram of an exemplary embodiment of a plunger 40 of the drug delivery device 10.

[0039] The plunger 40 is configured to transmit force from the spring 30 as an energy source to the piston 23 of the drug syringe 24. The plunger 40 includes a plunger rod 41. The plunger rod 41 includes a connecting element 42 at its distal end. The connecting element 42, e.g. a pin such as a threaded pin, is adapted to couple to the piston 23 by a press fit and / or a friction fit. The plunger 40 is formed as a one-piece plunger rod.

[0040] At its proximal end, the plunger rod 41 includes a connecting element 43, such as a protrusion 43.1 and / or an opening 43.2, for releasably connecting the plunger rod 41 to the needle sleeve 13 and / or the housing 11 for actuating the drug delivery device 10.

[0041] The plunger rod 41 further has a generally hollow cylindrical shape. At a distal end, the plunger rod 41 is closed. At an opposite proximal end, the plunger rod 41 is open and has an open end 41.5.

[0042] Figure 3 is a longitudinal cross-sectional view of plunger 40. Plunger rod 41 has an inner surface 41.1 that defines a cavity 41.2 configured to receive a force from an energy source, such as drive spring 30. Drive spring 30 is shown in Figures 1A and 1B.

[0043] The drive spring 30 is positioned to exert a force on a proximally facing surface 41.3 of the plunger rod 41. In the illustrated embodiment, the drive spring 30 is a compression spring that is positioned within the hollow plunger rod 41, e.g., within the cavity 41.2, and acts on a proximally facing surface 41.3 that is positioned within the plunger rod 41.

[0044] In alternative embodiments, the proximally facing surface 41.3 is located at the distal end of the plunger rod 41, or at another location along the surface of the plunger rod 41. The drive spring 30 is located proximal to the housing 11 in which the drug cartridge or syringe or primary container 24 is held (as shown in FIGS. 1A and 1B). A trigger mechanism, such as, for example, a button 22 (shown in FIGS. 1A and 1B), is positioned to operably prevent or allow movement of the plunger rod 41.

[0045] The inner surface 41.1 further includes a support element 41.4 adapted to restrain the spring 30 within the plunger 40, specifically within the cavity 41.2 of the plunger rod 41. In particular, the support element 41.4 is configured to press against the spring 30. The support element 41.4 allows the spring 30 to be held firmly in place within the plunger cavity 41.2 and prevents rattling noises due to the movement of the spring during injection. Furthermore, it also prevents buckling of the coils of the spring 30 into the extra space within the plunger rod 41.

[0046] The support element 41.4 projects radially inwardly from the inner surface 41.1 into the cavity 41.2. Furthermore, the support element 41.4 has a length L1 which corresponds to the length L2 of the cavity 41.2. Alternatively, the support element 41.4 has a length which is shorter than the length of the cavity 41.2. In this case, the support element 41.4 is arranged at least in the region of the open end 41.5 of the plunger rod 41 and extends inside the cavity 41.2.

[0047] In the exemplary embodiment, the support elements 41.4 are formed as internal ribs 41.6 on the inner surface 41.1. Specifically, the ribs 41.4 are straight elements with rounded edges. Specifically, the tops of the ribs 41.4 are rounded.

[0048] FIG. 4 is a cross-sectional view of the plunger 40. As can be clearly seen, a plurality of support elements 41.4 are distributed around the inner surface 41.1 of the cavity 41.2. Specifically, the support elements 41.4 are symmetrically distributed around the inner surface 41.1. Due to the symmetrical arrangement of the support elements 41.4, the misalignment of the spring 30 disposed in the cavity 41.2 is reduced, thereby resulting in a rattle-free arrangement of the spring 30 inside the plunger rod 41. Furthermore, due to the press-fit or friction-fit connection of the spring 30 in the cavity 41.2 by the symmetrically arranged support elements 41.4, the spring 30 operates smoothly and does not generate noise during injection.

[0049] FIG. 5 is an enlarged perspective view of a cross section of plunger 40 with shortened, rounded support elements 41.4 symmetrically distributed around the inner surface 41.1 of cavity 41.2.

[0050] The length L1 of the shortened support element 41.4 is shorter than the length L2 of the cavity 41.2. Furthermore, the height H of the support element 40 decreases from the open end 41.5 of the plunger rod 41 towards the inside of the cavity 41.2. This results in an initial clamping contact of the spring 30 in the cavity 41.2 in the region of the open end 41.5, e.g. at the start of an injection, when the spring 30 contacts the inner surface 41.1 of the plunger 40.

[0051] Alternatively, the height H of the support element 41.4 increases from the open end 41.5 towards the inside of the cavity 41.2, thereby ensuring that the spring 30 is held firmly inside the plunger rod 41 during the entire process of injection and all movements of the drive spring 30.

[0052] 6 is a top view of open end 41.5 of plunger 40, and FIG. 7 is an enlarged perspective view of the top of plunger 40. As shown in FIG.

[0053] The plunger rod 41 further includes an edge 41.7 at the open end 41.5 of the cavity 41.2. The edge 41.7 has a chamfer 41.8. The chamfer 41.8 serves to eliminate sharp edges at the open end 41.5 and allow the drive spring 30 to catch as it extends.

[0054] The plunger rod 41 is further configured such that the inner diameter d1 of the cavity 41.2 increases in the region 41.9 of the open end 41.5. Such a gradual increase in the inner diameter d1, particularly at the open end 41.5 of the plunger 40, eliminates sudden movements and allows the spring 30 to be quickly and smoothly introduced into the free space and thus into the plunger rod 41.

[0055] The above-mentioned support element 41.4 is integrally formed with the plunger rod 41. In particular, the support element 41.4 is formed on the plunger rod 41 by two-component or three-component molding.

[0056] In accordance with the above disclosure, the inner or internal support element 41.4 within the plunger core or cavity 41.2 reduces the clearance for the spring 30 and prevents the spring 30 from buckling as it expands during injection. In addition, the trailing or proximal edge 41.7 of the plunger 40 is beveled to eliminate sharp angles, allowing the spring 30 to be better captured and move more smoothly within the plunger rod 41.

[0057] The term "drug" or "medication" as used herein is used herein to describe one or more pharmacologic active compounds. As described below, a drug or medicament can include at least one small molecule or macromolecule, or a combination thereof, in various types of formulations for treating one or more diseases. Exemplary pharmacologic active compounds can include small molecules; polypeptides, peptides, and proteins (e.g., hormones, growth factors, antibodies, antibody fragments, and enzymes); carbohydrates 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 vectors, plasmids, or molecular delivery systems such as liposomes. Mixtures of one or more of these drugs are also contemplated.

[0058] The term "drug delivery device" encompasses any type of device or system configured to administer a drug to the human or animal body. Without limitation, the drug delivery device can be an injection device (e.g., a syringe, pen injector, auto-injector, large volume device, pump, perfusion system, or other device configured for intraocular, subcutaneous, intramuscular, or intravascular delivery), a skin patch (e.g., osmotic, chemical, microneedle), an inhaler (e.g., nasal or pulmonary), an implant (e.g., coated stent, capsule), or a delivery system for the gastrointestinal tract. The drugs described herein can be particularly useful in injection devices that include a needle, e.g., a small gauge needle.

[0059] The drug or agent can be contained within a primary package or "drug container" adapted for use in a drug delivery device. The drug container can be, for example, a cartridge, syringe, reservoir, or other container configured to provide a chamber suitable for storage (e.g., short-term or long-term storage) of one or more pharma- ceutical active compounds. For example, in some cases, the chamber can be designed to store the drug for at least one day (e.g., from one day to at least 30 days). In some cases, the chamber can be designed to store the drug for about one month to about two years. Storage can be at room temperature (e.g., about 20°C) or at refrigerated temperatures (e.g., from about -4°C to about 4°C). In some cases, the drug container can be or include a dual-chamber cartridge configured to store two or more components of a drug formulation (e.g., a drug and a diluent, or two different types of drugs) separately, one in each chamber. In such cases, the two chambers of the dual-chamber cartridge can be configured to allow mixing between the two or more components of the drug or agent before and / or during administration into the human or animal body. For example, the two chambers can be configured such that they are in fluid communication with one another (e.g., by a conduit between the two chambers) to allow for mixing of the two components by a user prior to administration, if desired. Alternatively, or in addition, the two chambers can be configured to allow for mixing of the components as they are being administered into the human or animal body.

[0060] The drug delivery devices and drugs described herein can be used to treat and / or prevent many different types of disorders.Exemplary disorders include, for example, diabetes or complications associated with diabetes, such as diabetic retinopathy, thromboembolism, such as deep vein thromboembolism or pulmonary thromboembolism.Further exemplary disorders are acute coronary syndrome (ACS), angina pectoris, myocardial infarction, cancer, macular degeneration, inflammation, hay fever, atherosclerosis and / or rheumatoid arthritis.

[0061] Exemplary drugs for the treatment and / or prevention of diabetes or complications associated with diabetes include insulin, e.g., human insulin, or a human insulin analog or derivative, glucagon-like peptide (GLP-1), a GLP-1 analog or GLP-1 receptor agonist, or an analog or derivative thereof, a dipeptidyl peptidase-4 (DPP4) inhibitor, or a pharma- ceutically acceptable salt or solvate thereof, or any mixture thereof. As used herein, the term "derivative" refers to any substance that is sufficiently structurally similar to the original substance so that it can have a similar function or activity (e.g., therapeutic efficacy).

[0062] Exemplary insulin analogs are Gly(A21),Arg(B31),Arg(B32) human insulin (insulin glargine); Lys(B3),Glu(B29) human insulin; Lys(B28),Pro(B29) human insulin; Asp(B28) human insulin; human insulin in which the proline at position B28 is replaced by Asp, Lys, Leu, Val, or Ala, and in position B29, Lys may be replaced by Pro; Ala(B26) human insulin; Des(B28-B30) human insulin; Des(B27) human insulin and Des(B30) human insulin.

[0063] Exemplary insulin derivatives include, for example, B29-N-myristoyl-des(B30) human insulin; B29-N-palmitoyl-des(B30) human insulin; B29-N-myristoyl human insulin; B29-N-palmitoyl human insulin; B28-N-myristoyl-LysB28ProB29 human insulin; B28-N-palmitoyl-LysB28ProB29 human insulin; B30-N-myristoyl-ThrB29Ly sB30 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 include, for example: Lixisenatide / AVE0010 / ZP10 / Lyxumia, Exenatide / Exendin-4 / Byetta / Bydureon / ITCA650 / AC-2993 (a 39 amino acid peptide produced by the salivary glands of the Gila monster), Liraglutide / Victoza, Semaglutide, Taspoglutide, Syncria / Albiglutide, Dulaglutide, glutide, rExendin-4, CJC-1134-PC, PB-1023, TTP-054, Langlenatide / HM-11260C, CM-3, GLP-1 Erigen, ORMD-0901, NN-9924, NN-9926, NN-9927, Nodexen, Viador-GLP-1, CVX -096, ZYOG-1, ZYD-1, GSK-2374697, DA-3091, MAR-701, MAR709, ZP-2929, ZP-3022, TT-401, BHM-034, MOD-6030, CAM-2036, DA-15864, ARI-2651, ARI-2255, Exenatide-XTEN and Glucagon-Xten.

[0064] An exemplary oligonucleotide is, for example: mipomersen / Kynamro, a cholesterol-lowering antisense therapeutic for the treatment of familial hypercholesterolemia.

[0065] Exemplary DPP4 inhibitors are Vildagliptin, Sitagliptin, Denagliptin, Saxagliptin, Berberine.

[0066] Exemplary hormones include pituitary or hypothalamic hormones or regulatory active peptides and their antagonists, such as gonadotropins (follitropin, lutropin, chorion gonadotropins, menotropins), somatropins (somatropins), desmopressin, terlipressin, gonadorelin, triptorelin, leuprorelin, buserelin, nafarelin, and goserelin.

[0067] Exemplary polysaccharides include glycosaminoglycans, hyaluronic acid, heparin, low molecular weight heparin, or very low molecular weight heparin, or derivatives thereof, or sulfated forms of the above polysaccharides, such as polysulfated forms, and / or pharmaceutically acceptable salts thereof. An example of a pharmaceutically acceptable salt of polysulfated low molecular weight heparin is enoxaparin sodium. An example of a hyaluronic acid derivative is HylanG-F20 / Synvisc, sodium hyaluronate.

[0068] 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 that retain the ability to bind antigen. The antibody can be polyclonal, monoclonal, recombinant, chimeric, non-immunoglobulin or humanized, fully human, non-human (e.g., murine), or single chain antibody. In some embodiments, the antibody has effector function and can fix complement. In some embodiments, the antibody has reduced ability to bind or cannot bind Fc receptors. For example, the antibody can be an isotype or subtype, an antibody fragment, or a variant that does not support binding to Fc receptors, e.g., it has a mutated or deleted Fc receptor binding region.

[0069] The term "fragment" or "antibody fragment" refers to a polypeptide derived from an antibody polypeptide molecule (e.g., antibody heavy and / or light chain polypeptides) that does not include the full-length antibody polypeptide, but still includes at least a portion of the full-length antibody polypeptide that is capable of binding to an antigen. An antibody fragment can include a truncated portion of a full-length antibody polypeptide, but the term is not limited to such truncated fragments. Antibody fragments that are 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, triabodies, tetrabodies), minibodies, chelating recombinant antibodies, tri- or bibodies, intrabodies, nanobodies, small modular immunopharmaceuticals (SMIPs), binding domain immunoglobulin fusion proteins, camelized antibodies, and VHH-containing antibodies. Further examples of antigen-binding antibody fragments are known in the art.

[0070] The term "complementarity determining region" or "CDR" refers to short polypeptide sequences in 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 in the variable regions of both heavy and light chain polypeptides that are not CDR sequences, but are primarily responsible for maintaining the correct positioning of CDR sequences to allow antigen binding. Although framework regions themselves are usually not directly involved in antigen binding, as is known in the art, certain residues in the framework regions of a particular antibody may be directly involved in antigen binding or may affect the ability of one or more amino acids in the CDRs to interact with the antigen.

[0071] Exemplary antibodies are anti-PCSK-9 mAb (e.g., Alirocumab), anti-IL-6 mAb (e.g., Sarilumab), and anti-IL-4 mAb (e.g., Dupilumab).

[0072] The compounds described herein can be used in pharmaceutical preparations that include (a) the compound or its pharmaceutically acceptable salt, and (b) a pharmaceutically acceptable carrier.The compounds can also be used in pharmaceutical preparations that include one or more other active pharmaceutical ingredients, or in pharmaceutical preparations in which the compound or its pharmaceutically acceptable salt is the only active ingredient present.Thus, the pharmaceutical preparations of the present disclosure encompass any preparation that is made by mixing the compounds described herein and a pharmaceutically acceptable carrier.

[0073] Pharmaceutically acceptable salts of any of the drugs described herein are also contemplated for use in the drug delivery device. Pharmaceutically acceptable salts are, for example, acid addition salts and base salts. Acid addition salts are, for example, HCl or HBr salts. Base salts are, for example, salts with a cation selected from an alkali or alkaline earth metal, for example Na+, or K+, or Ca2+, or an ammonium ion N+(R1)(R2)(R3)(R4), where R1 to R4 are each independently: 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. Further examples of pharma-ceutically acceptable salts are known to those skilled in the art.

[0074] Pharmaceutically acceptable solvates are, for example, hydrates or alkanolates, such as methanolates or ethanolates.

[0075] Those skilled in the art will understand that modifications (addition and / or removal) of the various components of the materials, formations, devices, methods, systems, and embodiments described herein may be made without departing from the full scope and spirit of the present disclosure, which includes such modifications and all equivalents thereof. [Explanation of symbols]

[0076] 10 Drug Delivery Devices 11. Housing 11a Window 12 Cap Assembly 12.1 Needle Shield 12.2 Caps 13 Needle sleeve 17 needles 20 Distal Region of the Drug Delivery Device 21 Proximal Region of Drug Delivery Device 22 Buttons 23 Piston 24 Syringes or containers or cartridges 30 Energy sources such as drive springs 40 Plunger 41 Plunger rod 41.1 Inner surface 41.2 Cavity 41.3 Proximally Facing Surface 41.4 Supporting elements 41.5 Open end 41.6 Ribs 41.7 Edges 41.8 Chamfer 41.9 area 42 Connection elements 43 Connecting Elements 43.1 Projections 43.2 Openings D Distal or front end d1 diameter L1, L2 length P Proximal or dorsal end X Longitudinal Axis

Claims

1. A plunger (40) configured to transmit force from an energy source (30) to a piston (23) of a main container (24), comprising: A plunger rod (41) configured to receive a force from an energy source (30), the plunger rod (41) having a longitudinal axis and an inner surface (41.1) defining an elongated cavity (41.2) along the longitudinal axis, wherein: a support element (41.4) adapted to restrain the energy source (30) within the elongated cavity (41.2), protruding radially inwardly from the inner surface (41.1) into the elongated cavity (41.2) and providing radial support for the energy source (30) within the elongated cavity (41.2); wherein the energy source (30) is a spring.

2. 2. The plunger (40) according to claim 1, wherein the support element (41.4) has a length (L1) corresponding to the length (L2) of the cavity (41.2).

3. 3. The plunger (40) according to claim 1 or 2, wherein the support element (41.4) is formed as an internal rib (41.6) on the inner surface (41.1).

4. 4. The plunger (40) according to claim 3, wherein the ribs (41.6) are straight elements with rounded edges.

5. A plunger (40) according to any one of the preceding claims, wherein a plurality of support elements (41.4) are distributed around the inner surface (41.1) of the cavity (41.2).

6. A plunger (40) according to any one of the preceding claims, wherein the support elements (41.4) are symmetrically distributed around the inner surface (41.1) of the cavity (41.2).

7. A plunger (40) according to any one of the preceding claims, wherein the edge (41.7) at the open end (41.5) of the cavity (41.2) has a chamfer (41.8).

8. A plunger (40) according to any one of the preceding claims, wherein the inner diameter (d1) of the cavity (41.2) increases in the region (41.9) of the open end (41.5) of the cavity (41.2).

9. A plunger (40) according to any one of the preceding claims, wherein the support element (41.4) is integrally formed with the plunger rod (41).

10. The plunger (40) according to any one of the preceding claims, wherein the support element (41.4) is formed on the plunger rod (41) by two-component or three-component moulding.

11. A drug delivery device (10), comprising: a primary container (24) defining a drug cavity for receiving a drug; a piston (23) slidably disposed within an outlet (17) and a main vessel (24); A plunger (40) according to any one of claims 1 to 10, and an energy source (30) disposed within the elongated cavity of the plunger rod (41) for applying a force to an inner surface (41.1) of the plunger rod (41), wherein the energy source (30) is a spring.

12. The drug delivery device (10) of claim 11, wherein the cartridge (24) is pre-filled with the drug.

13. The drug delivery device (10) of claim 11 or 12, which is an auto-injector, a pen-injector, or a syringe.

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