Drug injection device

Abstract

A drug injection device includes: a body configured to receive a drug cartridge; a needle sleeve axially movable relative to the body; a needle holder holding a needle; and a displacement element coupled to the needle holder and disengagedly coupled to the needle sleeve; wherein, when the needle sleeve is axially displaced in a proximal direction by a predetermined distance, the needle hub and the needle are axially displaced in the proximal direction.

Description

Technical Field

[0001] This invention relates to a pharmaceutical delivery device. Background Technology

[0002] The drug injection device can be in the form of a syringe, in which the drug is delivered in a tubular tube having a plunger and an outlet connected to a needle. Before injection, the user manually connects the needle to the reservoir. Attaching the needle to the syringe requires some skill, which can be difficult for individuals with poor coordination, such as patients with some degree of loss of sensation in their hands.

[0003] While it is possible to provide an injection device in which the needle is pre-attached to the medication cartridge, in some cases it is desirable to provide a device in which the needle remains separate from the medication until the moment the user wishes to begin the injection. Summary of the Invention

[0004] According to a first embodiment, a drug injection device is provided, comprising: a body configured to receive a drug cartridge; a needle sleeve axially movable relative to the body; a needle holder holding a needle; and a displacement element coupled to the needle holder and disengagedly coupled to the needle sleeve; wherein, when the needle sleeve is axially displaced a predetermined distance in a proximal direction, the needle seat and the needle are axially displaced in the proximal direction.

[0005] Further axial movement of the needle sleeve in the proximal direction beyond the predetermined distance can cause the needle sleeve to disengage from the displacement element.

[0006] The displacement element may include at least one ramp surface.

[0007] The displacement element may include at least one slot.

[0008] The needle sleeve may include at least one pin arranged to slide through the slot when the displacement element and the needle sleeve are in rotational alignment.

[0009] The further axial movement of the needle sleeve can cause the pin to rotate relative to the ramp surface, aligning the pin with the slot, thereby causing the needle sleeve to disengage from the displacement element.

[0010] The needle sleeve may have two pins arranged opposite to each other in a circumferential direction on the inner circumferential wall of the needle sleeve, and the displacement element has two corresponding slots for receiving the two pins arranged opposite to each other in a circumferential direction.

[0011] The device may include a drug cartridge, wherein axial displacement of the needle hub and needle in the proximal direction causes the proximal end of the needle to pierce the cartridge diaphragm.

[0012] The drug cartridge may include a male portion, the needle holder may include a female portion, and wherein the male and female portions are configured to form a frictional fit after the needle holder has been displaced by the predetermined distance.

[0013] The needle holder may further include a lip to prevent axial displacement of the needle hub and needle relative to the drug cartridge after the displacement portion has been axially displaced beyond the predetermined distance.

[0014] The device may include a pharmaceutical cartridge containing a pharmaceutical agent.

[0015] According to a second embodiment, a method for operating a drug injection device is provided, the method comprising: pushing a needle sleeve connected to a displacement element in a disengageable manner in a proximal axial direction, thereby causing proximal movement of the needle seat and the needle, wherein the proximal end of the needle pierces a permeable barrier of the drug cartridge.

[0016] Further proximal axial displacement of the needle sleeve can cause the needle sleeve to disengage from the displacement element. Attached Figure Description

[0017] To fully understand the present invention, embodiments of the present invention will be described with reference to the accompanying drawings, wherein:

[0018] Figure 1A and 1B This is a side view of an auto-injector device according to an embodiment of the present invention;

[0019] Figure 2 This is a side cross-sectional view of the device shown in Figure 1;

[0020] Figure 3 This is an elevation view of the displacement section;

[0021] Figure 4 yes Figure 3 The side view of the displacement section is shown.

[0022] Figure 5 This is a side cross-sectional view of the device when the needle holder is attached to the medication cartridge; and

[0023] Figure 6 This is a side cross-sectional view of the device during injection. Detailed Implementation

[0024] Embodiments of the present invention provide a mechanism for inserting a needle from an injection device, such as an auto-injector or syringe, into a cartridge containing a drug to be injected. Providing such a mechanism allows the cartridge to be sealed until the user wishes to begin injection. Providing an automated mechanism for inserting the needle into the cartridge also reduces the amount of needle handling required by the user prior to injection. In fact, in embodiments of the invention, the user does not need to contact the needle during the steps of inserting the needle into the cartridge and subsequently actuating the injection.

[0025] The drug delivery devices described herein can be configured to inject medications into a patient. For example, delivery can be subcutaneous, intramuscular, or intravenous. Such devices can be operated by a patient or caregiver (e.g., a nurse or physician) and can include various types of safety syringes, pen syringes, or autoinjectors. The device may include a cartridge-based system that requires puncturing a sealed ampoule before use. The volume of medication delivered using these various devices can range from about 0.5 ml to about 2 ml. 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 medication (typically about 2 ml to about 10 ml).

[0026] The device described herein can also be customized to operate within required specifications, depending on the specific drug being administered. For example, the device can be customized to inject the drug over a specific time period (e.g., approximately 3 to 20 seconds for an autoinjector, and approximately 10 to 60 minutes for an LVD). Other specifications may include minimal or no discomfort, or certain conditions related to human factors, shelf life, expiration date, biocompatibility, environmental considerations, etc. These variations can arise from various factors, such as the viscosity of the drug, which ranges from approximately 3 cP to approximately 50 cP. Therefore, drug delivery devices typically include hollow needles ranging in size from approximately 25 to approximately 31. Common sizes are 27 and 29.

[0027] The delivery device described herein may also include one or more automated functions. 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. Energy sources may include, for example, mechanical energy, pneumatic energy, chemical energy, or electrical energy. For example, a mechanical energy source may include a spring, rod, elastomer, or other mechanical mechanism that stores or releases energy. One or more energy sources may be combined into a single device. The device may further include gears, valves, or other mechanisms that convert energy into movement of one or more components of the device.

[0028] One or more automated functions of an autoinjector can be activated via an activation mechanism. Such an activation mechanism may include one or more of a button, lever, needle sleeve, or other activation components. Activation of the automated function can be a single-step or multi-step process. That is, the user may need to activate one or more activation components to produce the automated function. For example, in a single-step process, the user may press the needle sleeve against its body to produce an injection of a drug. Other devices may require multi-step activation of the automated function. For example, the user may need to press a button and retract the needle sheath to produce an injection.

[0029] Furthermore, activation of one automation function can activate one or more subsequent automation functions, thus forming an activation sequence. For example, activation of the first automation function can activate at least two of needle insertion, drug injection, and needle retraction. Some devices may also require a specific sequence of steps for one or more automation functions to occur. Other devices can operate through a series of independent steps.

[0030] Some delivery devices may include one or more functions of a safety syringe, pen syringe, or autoinjector. For example, a delivery device may include a mechanical energy source (as commonly found in autoinjectors) configured to automatically inject a drug and a dosage setting mechanism (as commonly found in pen syringes).

[0031] According to some embodiments of this disclosure, the exemplary drug delivery device 10 is in Figure 1A and 1B As shown in the diagram. The device 10 described above is configured to inject a drug into a patient. The device 10 includes a body 11, which typically houses a reservoir (e.g., a syringe) containing the drug to be injected and components necessary to facilitate one or more steps of the delivery process. The device 10 may also include a cap assembly 12, which can be detachably attached to the body 11. Typically, the user must remove the cap 50 from the housing 11 before operating the device 10.

[0032] As shown, the body 11 is generally cylindrical and has a diameter that is generally constant along the longitudinal axis X. The shell 11 has a distal region 120 and a proximal region 121. The term "distal" refers to the position closer to the injection site, while the term "proximal" refers to the position farther from the injection site.

[0033] The device 10 may also include a needle sleeve 51, which is coupled to the body 11 to allow the sleeve 51 to move relative to the body 11. For example, the sleeve 51 may move in a longitudinal direction parallel to the longitudinal axis X. In particular, movement of the sleeve 51 in the proximal direction may allow the needle 17 to extend from the distal region 120 of the body 11.

[0034] Insertion of the needle 17 can occur via multiple mechanisms. For example, the needle 17 can be fixed relative to the housing 11 and initially located within the extended needle sleeve 51. Proximal movement of the sleeve 51, caused by positioning the distal end of the sleeve 51 against the patient's body and moving the body 11 in a distal direction, exposes the needle 17. Such relative movement allows the distal end of the needle 17 to extend into the patient's body. This insertion is referred to as "manual" insertion because the needle 17 is inserted manually via patient-manual movement of the body 11 relative to the sleeve 51.

[0035] Another form of insertion is "automatic," whereby pin 17 moves relative to body 11. This insertion can be triggered by movement of sleeve 51 or by another form of activation (e.g., button 122). Figure 1A and 1B As shown, button 122 is located at the proximal end of body 11. However, in other embodiments, button 122 can be arranged on the side of body 11.

[0036] Other manual or automatic features may include drug injection or needle retraction, or both. Injection is the process of moving the stopper or piston 123 from a proximal position within the syringe (not shown) to a more distal position within the syringe to force medication from the syringe through the needle 17. In some embodiments, a drive spring (not shown) is compressed prior to activation of the device 10. The proximal end of the drive spring may be fixed within the proximal region of the body 11, and the distal end of the drive spring may be configured to apply a compressive force to the proximal surface of the piston 123. Upon activation, at least a portion of the energy stored in the drive spring may be applied to the proximal surface of the piston 123. This compressive force may act on the piston 123, causing it to move distally. This distal movement compresses the liquid medication within the syringe, forcing it out of the needle 17.

[0037] After injection, the needle 17 can be retracted into the sleeve 51 or the body 11. Retraction can occur as the sleeve 51 moves distally as the user removes the device 10 from the patient's body. This can occur while the needle 17 remains in a fixed arrangement relative to the body 11. Once the distal end of the sleeve 51 has passed the distal end of the needle 17 and the needle 17 is covered, the sleeve 51 can be locked. This locking can include locking any proximal movement of the sleeve 51 relative to the body 11.

[0038] Another form of needle retraction can occur when the needle 17 moves relative to the body 11. This movement can occur if the syringe within the body 11 moves proximally relative to the body 11. This proximal movement can be achieved using a retraction spring (not shown) located in the distal region 120. When activated, the compressed retraction spring provides sufficient force to the syringe to move it proximally. After sufficient retraction, any relative movement between the needle 17 and the body 11 can be locked using a locking mechanism. Alternatively, the button 122 or other components of the device 10 can be locked as needed.

[0039] Figure 2 A side cross-section view of an auto-injector device 10 according to an embodiment of the present invention is shown.

[0040] The auto-injector device 10 includes a cartridge 19, which is held in place by a cartridge holder 20. The cartridge holder 20 and the cartridge 19 are connected to and fixed relative to the body 11 of the device 10. The cartridge 19 has a cartridge body 21, a neck 22, and a head 23. The head 23 is wider than the neck 22, thus forming a flanged end. The neck 22 and the head 23 contain channels that allow the medication to pass through and receive the needle 17 once the needle is inserted. The head 23 is provided with a permeable barrier, such as a diaphragm 24, to close the channels and seal the contents of the medication cartridge 19. The cartridge body 21, neck 22, and head 23 may be generally cylindrical. However, alternative shapes may be used.

[0041] The needle retainer 18 of the needle 17 is axially movable relative to the body 11 and the cartridge 19. The needle retainer has a generally cup-shaped portion 18a and a channel through which the needle 17 passes. The cup-shaped portion 18a is shaped to engage with the head 23 of the cartridge 19. The cup-shaped portion 18a includes a lip 18b for clamping onto the head 23 to prevent the needle retainer 18 from detaching from the cartridge 19 after it has been attached to the cartridge 19.

[0042] The device 10 includes a tubular needle sleeve 51. The needle sleeve 51 is a protective sleeve to prevent undesirable exposure of the needle 17. The needle sleeve has a shape generally similar to the body and is hollow and generally cylindrical. The needle sleeve 51 is fitted within the body 11. The needle sleeve 51 is arranged to slide axially relative to the body 11. The needle sleeve 51 has an aperture 25 at its distal end to allow the needle to contact the patient's skin.

[0043] Figure 2 The device shown depicts the components of the device in their initial position before the needle is inserted into the drug cartridge in preparation for injecting the drug into the user.

[0044] like Figure 3 and 4As shown, the needle holder displacement element 52 has a generally circular cross-section. The needle holder displacement element 52 includes two sloping semicircular surfaces 53, which are separated by grooves 54 arranged opposite to each other in the circumferential direction. The central portion of the needle holder displacement element 52 includes a tubular portion 55 arranged to receive the needle 17 and the needle holder 18.

[0045] The inner surface of the needle sleeve 51 is provided with needle sleeve pins 56. In this embodiment, two pins 56 are provided, which are opposite to each other in the circumferential direction. In use, when the needle sleeve 51 moves along... Figure 2 When pushed in the direction indicated by the thick arrow, i.e., towards the proximal end of device 10, the needle sleeve pin 56 pushes the needle holder displacement member 52. The engagement between the needle sleeve pin 56 and the semi-circular surface 53 of the needle holder displacement member 52 causes axial movement of the needle holder displacement member 52 toward the medication cartridge 19. The needle holder displacement member 52 accommodates the distal portion of the needle holder 18 in its tubular portion 55. Thus, the axial movement of the needle holder displacement member 52 causes axial movement of the needle holder 18 and the needle 17 toward the medication cartridge 19.

[0046] Figure 5 The diagram shows a side cross-sectional view of the autoinjector device 10 as the user pushes the needle sleeve 51 in the proximal direction, as indicated by the thick arrow. The needle sleeve 51 is coaxial with respect to the body and slides along the interior of the body 11 of the device 10. After axial movement of a predetermined distance, the cup-shaped portion 18a of the needle holder 18 is fitted onto the head 23 of the cartridge 19. The diameters of the cup-shaped portion 18a and the head 23 of the cartridge 19 are arranged to ensure a tight frictional fit between the needle holder 18 and the cartridge 19. Furthermore, a lip 18b extending around the cup-shaped portion 18a of the needle holder also serves to secure the needle holder 18 to the cartridge 19. The lip 18b has a tapered leading edge to allow the cup-shaped portion to fit onto the head 23. However, once the needle holder 18 is fitted onto the cartridge 19, axial movement (in the distal direction) of the needle holder away from and separation from the cartridge 19 is prevented by the lip and the frictional fit.

[0047] like Figure 5 As shown, needle 17 pierces the septum 24 of the medication cartridge 19, thereby forming a channel for the medication to flow from the medication cartridge 19 to the distal end of needle 17. Both ends of needle 17 are sharp. The proximal end is sharp enough to allow needle 17 to pass through the septum 24 of the medication cartridge 19. The distal end of needle 17 is sharp enough to allow the needle to pass through the patient's skin.

[0048] The attachment of the needle holder 18 to the medication cartridge 19 can provide audible feedback, such as a clicking sound, to notify the user that the needle has been inserted into the medication cartridge 19.

[0049] Once the needle 17 has been inserted into the drug cartridge 19 and the attached needle holder 18, the device is ready to begin drug injection. The distal end of the device 10 can then be positioned against the injection site on the patient's skin.

[0050] Figure 6 A side cross-sectional view of the autoinjector device 10 is shown when the needle sleeve 51 moves more than the predetermined distance relative to the body 11 in the direction proximal to the thick arrow.

[0051] This relative movement can be caused by the user grasping the body 11 and pushing the needle sleeve 51 toward the proximal end of the device 10. Alternatively, the distal end of the needle sleeve 51 can be held against the injection site against the patient's skin. When the user pushes the device 10 against the injection site, the outer wall of the body 11 slides over the needle sleeve 51, causing the needle sleeve 51 to retract relative to the body 11.

[0052] Since the needle 17 and needle holder 18 are no longer connected to the needle sleeve 51, but are fixed relative to the medication cartridge 19 and the body 11, this further axial movement of the needle sleeve 51 causes the needle 17 to protrude from the hole 25 in the distal end of the needle sleeve 51. If the device 10 has already been placed against the injection site, the needle 17 pierces the patient's skin.

[0053] Once the needle retainer 18 is secured to the head of the medication cartridge 19, the needle retainer displacement member 52 does not shift axially. Therefore, any subsequent proximal axial force applied to the needle sleeve 51 causes the needle sleeve pin 56 to rotate against the ramp surface 53 of the needle retainer displacement member 52. The needle sleeve pin 56 becomes aligned with a groove 54 located in the needle retainer displacement member 52. An axial force applied to the needle sleeve 51 causes the needle sleeve pin 56 to pass through the groove 54 located in the needle retainer displacement member 52. Thus, the needle sleeve 51 disengages from the needle retainer 18.

[0054] Further axial movement of the needle sleeve 51 relative to the body 11 causes the needle 17 to be exposed from the distal end of the needle sleeve, as... Figure 6 As shown. Figure 6 The configuration shown illustrates the scenario where the device 10 remains against the injection site 57. Further axial movement of the needle sleeve 51 causes the needle 17 to be inserted into the patient's skin.

[0055] While the above embodiments of the present invention refer to an auto-injector device, it should be understood that other embodiments can be used in conjunction with other drug delivery devices (e.g., syringes).

[0056] The terms "drug" or "pharmaceutical preparation" are used synonymously herein and describe a pharmaceutical preparation containing one or more active pharmaceutical ingredients (APIs) or pharmaceutically acceptable salts or solvates thereof and optionally a pharmaceutically acceptable carrier. In the broadest sense, an active pharmaceutical ingredient ("API") is a chemical structure that has a biological effect on humans or animals. In pharmacology, a drug or pharmaceutical preparation is used for the treatment, cure, prevention, or diagnosis of a disease, or for the purpose of otherwise enhancing physical or mental health. Drugs or pharmaceutical preparations may be used for a limited duration or periodically for chronic diseases.

[0057] As described below, a drug or pharmaceutical product may include at least one small or large molecule or combination thereof in multiple formulations for the treatment of 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 may be incorporated into molecular delivery systems such as vectors, plasmids, or liposomes. Mixtures of one or more of these drugs are also covered.

[0058] The term "drug delivery device" should include any type of device or system configured to dispense a drug into a human or animal. Without limitation, a drug delivery device can be an injection device (e.g., a syringe, pen syringe, autoinjector, large-volume device, pump, infusion system, or other device configured for intraocular, subcutaneous, intramuscular, or intravascular delivery), a skin patch (e.g., a microneedle for penetrating chemicals), an inhaler (e.g., for the nose or lungs), an implantable device (e.g., a coated stent, capsule), or a delivery system for the gastrointestinal tract. Combinations of the drugs described herein with injection devices including needles (e.g., hypodermic needles with a size 24 or higher) may be particularly useful.

[0059] Drugs or pharmaceutical preparations may be contained within primary packaging or "drug containers" suitable for use in conjunction with drug delivery devices. Drug containers may be, for example, cartridges, syringes, reservoirs, or other containers configured to provide suitable chambers for storing (e.g., short-term or long-term storage) one or more pharmaceutically active compounds. For example, in some cases, the chambers may be designed to store the drug for at least one day (e.g., from 1 day to at least 30 days). In some cases, the chambers may be designed to store the drug for about one month to about two years. Storage may be carried out at room temperature (e.g., about 20°C) or at freezing temperature (e.g., from about -4°C to about 4°C). In some cases, drug containers may be dual-chamber cartridges or may include dual-chamber cartridges configured to independently store two or more components of a drug formulation (e.g., drug and diluent, or two different types of drugs), one component per chamber. In such cases, the two chambers of the dual-chamber cartridge may be configured to allow mixing between the two or more components of the drug or pharmaceutical preparation before and / or during administration to a human or animal. For example, the two chambers can be configured such that they are in fluid communication with each other (e.g., via a conduit between the two chambers) and allow mixing of the two components when needed by the user prior to dispensing. Alternatively, or additionally, the two chambers can be configured to allow mixing while these components are being dispensed into a human or animal.

[0060] Drugs or agents contained in drug delivery devices as described herein can be used to treat and / or prevent many different types of medical conditions. Examples of conditions include, for example, diabetes or diabetes-related complications such as diabetic retinopathy, and thromboembolic diseases such as deep vein or pulmonary thromboembolism. Other examples of diseases are acute coronary syndrome (ACS), angina pectoris, myocardial infarction, cancer, macular degeneration, inflammation, hay fever, atherosclerosis, and / or rheumatoid arthritis. Examples of APIs and drugs are those described in manuals such as Rote Liste 2014, such as, but not limited to, main group 12 (antidiabetic drugs) or 86 (oncology drugs), and those described in Merck Index, 15th edition.

[0061] Examples of APIs used to treat and / or prevent type 1 or type 2 diabetes or complications associated with type 1 or type 2 diabetes include insulin, such as human insulin or human insulin analogs or derivatives, glucagon-like peptide-1 (GLP-1), GLP-1 analogs or GLP-1 receptor antagonists or their analogs or derivatives, dipeptidyl peptidase-4 (DPP4), or pharmaceutically acceptable salts or solvates thereof, or any mixture thereof. As used herein, the terms “analyte” and “derivative” refer to any substance that is structurally sufficiently similar to the original substance to have substantially similar function or activity (e.g., therapeutic efficacy). In particular, the term “analyte” refers to a polypeptide having a molecular structure that is formally derived from the structure of a naturally occurring peptide, such as human insulin, by the deletion and / or exchange of at least one amino acid residue present in a naturally occurring peptide and / or by the addition of at least one amino acid residue. The added and / or exchanged amino acid residues may be encoding amino acid residues, other naturally occurring residues, or purely synthetic amino acid residues. Insulin analogs are also referred to as “insulin receptor ligands”. In particular, the term "derivative" refers to a polypeptide having a molecular structure that can be formally derived from a naturally occurring peptide, such as the structure derived from human insulin, wherein one or more organic substituents (e.g., fatty acids) are bound to one or more amino acids. Optionally, one or more amino acids present in a naturally occurring peptide may have been missing and / or replaced by other amino acids, including non-coding amino acids, or may include non-coding amino acids that have been added to a naturally occurring peptide.

[0062] Exemplary insulin analogs are Gly(A21), Arg(B31), Arg(B32) human insulin (glargine insulin); 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 the Lys at position B29 is replaced by Pro; Ala(B26) human insulin; de(B28-B30) human insulin; de(B27) human insulin and de(B30) human insulin.

[0063] Exemplary insulin derivatives include, for example, B29-N-myristoyl-de(B30) human insulin; Lys(B29)(N-tetradecanoyl)-de(B30) human insulin (detemir insulin, B29-N-palmitoyl-de(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-γ-glutamyl)-de(B30) human insulin; B29-N-ω-carboxypentadecanoyl-γ-L-glutamyl-de(B30) human insulin (degludec insulin, ); B29-N-(N-lithochyl-γ-glutamyl)-de(B30) human insulin; B29-N-(ω-carboxyheptandecyl)-de(B30) human insulin and B29-N-(ω-carboxyheptandecyl) human insulin.

[0064] Exemplary GLP-1, GLP-1 analogs, and GLP-1 receptor agonists include, for example, Lixisenatide (Lixisenatide). Exenatide (Exendin-4) Liraglutide (a 39-amino acid peptide produced by the salivary glands of the venomous lizard) Semaglutide, Taspoglutide, Albiglutide Dulaglutide(dulaglutide) rExendin-4, CJC-1134-PC, PB-1023, TTP-054, Langlenatide / HM-11260C, CM-3, GLP-1Eligen, 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.

[0065] An example oligonucleotide is mipomersen. An antisense therapy for lowering cholesterol to treat familial hypercholesterolemia.

[0066] Exemplary DPP4 inhibitors are Vildagliptin, Sitagliptin, Denagliptin, Saxagliptin, and Berberine.

[0067] Exemplary hormones include pituitary hormones or hypothalamic hormones or regulatory active peptides and their antagonists, such as gonadotropins (follicle-stimulating hormone, luteinizing hormone, human chorionic gonadotropin, menotropin), somatropine (growth hormone), desmopressin, terlipressin, gonadorelin, triptorelin, leuprorelin, buserelin, nafarelin, and goserelin.

[0068] Exemplary polysaccharides include mucopolysaccharides, 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 polysaccharides 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 Hylan GF 20 (Sinvitro). ), a type of sodium hyaluronate.

[0069] As used herein, the term "antibody" refers to an immunoglobulin molecule or its antigen-binding portion. Examples of antigen-binding portions of immunoglobulin molecules include F(ab) and F(ab)2 fragments, which retain the ability to bind 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 function and can fix complement. In some embodiments, antibodies do not have or have a reduced ability to bind Fc receptors. For example, antibodies can be isotypes or subtypes, antibody fragments, or mutants that do not support binding to Fc receptors, for example, having a mutagenic or missing Fc receptor-binding region. The term "antibody" also includes antigen-binding molecules based on tetravalent bispecific tandem immunoglobulins (TBTI) and / or antibody-like binding proteins with dual variable regions having cross-binding region orientation (CODV).

[0070] The term "fragment" or "antibody fragment" refers to a polypeptide derived from an antibody polypeptide molecule (e.g., an antibody heavy and / or light chain polypeptide) that does not contain a full-length antibody polypeptide but still contains at least a portion of a full-length antibody polypeptide capable of binding to an antigen. An antibody fragment may contain a cleaved portion of a full-length antibody polypeptide, but the term is not limited to that cleaved fragment. Antibody fragments effective in this invention 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., biantibodies, triantibodies, tetraantibodies), microantibodies, chelated recombinant antibodies, tribodies or bibodies, endoantibodies, nanobodies, small modular immunopharmaceuticals (SMIPs), binding domain immunoglobulin fusion proteins, camel-derived antibodies, and antibodies containing VHH. Other examples of antigen-binding antibody fragments are known in the art.

[0071] The term "complementarity-determining region" or "CDR" refers to a short polypeptide sequence within the variable region of both the heavy and light chain polypeptides, which is primarily responsible for mediating specific antigen recognition. The term "frame region" refers to an amino acid sequence within the variable region of both the heavy and light chain polypeptides; it is not a CDR sequence and is primarily responsible for maintaining the correct positioning of the CDR sequence to allow antigen binding. As is known in the art, although frame regions themselves do not directly participate in antigen binding, certain residues within the frame regions of some antibodies can directly participate in antigen binding or influence the ability of one or more amino acids in the CDR to interact with the antigen.

[0072] Exemplary antibodies include anti-PCSK-9 mAb (e.g., Alirocumab), anti-IL-6 mAb (e.g., Sarilumab), and anti-IL-4 mAb (e.g., Dupilumab).

[0073] Pharmaceutically acceptable salts of any API described herein are also considered for use in drug delivery devices for drugs or pharmaceutical preparations. Pharmaceutically acceptable salts include, for example, acid addition salts and basic salts.

[0074] Those skilled in the art will understand that various modifications (additions and / or removals) can be made to the APIs, formulations, devices, methods, systems and embodiments described herein without departing from the full scope and spirit of the invention, the scope and spirit of which cover such modifications and any and all equivalents thereof.

Claims

1. A drug injection device, comprising: The main body and a cartridge holder fixed relative to the main body and configured to receive the cartridge of the medicine. A needle sleeve, which is coupled to the body and is axially movable relative to the body. Needle retainer, the needle retainer retains the needle, and A displacement element, which is connected to the needle holder and disconnectably connected to the needle sleeve; The needle sleeve is movable from a first position to a second position in the proximal direction relative to the body during use. In the first position, the needle sleeve is engaged with the displacement element, and in the second position, the needle sleeve is disengaged from the displacement element. The needle sleeve moves along a proximal axial direction, causing proximal movement of the needle holder and the needle, thereby enabling the proximal end of the needle to pierce the permeable barrier of the drug cartridge, and wherein the needle sleeve moves further along a proximal axial direction and disengages from the displacement element to allow further proximal axial movement of the needle sleeve relative to the needle holder.

2. The apparatus of claim 1, wherein further axial movement of the needle sleeve in the proximal direction beyond a predetermined distance causes the needle sleeve to disengage from the displacement element.

3. The apparatus according to claim 1 or 2, wherein the displacement element comprises at least one ramp surface.

4. The apparatus of claim 3, wherein the displacement element comprises at least one slot.

5. The apparatus of claim 4, wherein the needle sleeve includes at least one pin arranged to slide through the slot when the displacement element and the needle sleeve are in rotational alignment.

6. The apparatus of claim 5, wherein the further axial movement of the needle sleeve causes a rotational movement of the pin relative to the ramp surface, such that the pin aligns with the slot, thereby causing the needle sleeve to disengage from the displacement element.

7. The apparatus according to claim 5 or 6, wherein the needle sleeve has two pins arranged opposite to each other in a circumferential direction on the inner peripheral wall of the needle sleeve, and the displacement element has two corresponding slots for receiving the two pins arranged opposite to each other in a circumferential direction.

8. The device according to any of the preceding claims, the device comprising a drug cartridge, wherein axial displacement of the needle holder and the needle in the proximal direction causes the proximal end of the needle to pierce the cartridge diaphragm.

9. The apparatus of claim 8, wherein the drug cartridge includes a male portion, the needle holder includes a female portion, and wherein the male and female portions are configured to form a frictional engagement after the needle holder has been displaced a predetermined distance.

10. The apparatus of claim 9, wherein the needle holder further comprises a lip that prevents subsequent axial displacement of the needle holder and the needle relative to the medication cartridge after the displacement portion has been axially displaced by the predetermined distance.

11. The apparatus according to any of the preceding claims, wherein the apparatus comprises a pharmaceutical cartridge containing a pharmaceutical agent.

12. Methods for operating a drug injection device, The drug injection device includes: The main body and a cartridge holder fixed relative to the main body and configured to receive the cartridge of the medicine. A needle sleeve, which is coupled to the body and is axially movable relative to the body. Needle retainer, the needle retainer holds the needle, A displacement element, the displacement element being coupled to the needle holder and disconnectably coupled to the needle sleeve, the method comprising: Moving the needle sleeve along the proximal axis causes proximal movement of the needle holder and the needle, wherein the proximal tip of the needle pierces the permeable spacer of the medication cartridge, and The needle sleeve is further moved along the proximal axis and disengaged from the displacement element to allow further proximal axial movement of the needle sleeve relative to the needle holder.

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