Injector device

An injector device is configurable between a safe state and an operable state and comprises a housing having a distal end and a proximal end; a medicament cartridge disposed within the housing; a needle unit comprising a needle and being disposed in the distal end of the housing; a sleeve displaceable along a longitudinal axis of the device between a first position in which the sleeve conceals the needle and a second position in which the needle is exposed from an end of the sleeve; a locking mechanism configured to prevent displacement of the sleeve when the device is in the safe state; and a button disposed in the proximal end of the housing, the button being configured to switch the device between the safe state and the operable state by releasing the locking mechanism when the button is pressed from an initial position into a depressed position during use.

CROSS REFERENCE TO RELATED APPLICATIONS

The present application is the national stage entry of International Patent Application No. PCT/EP2019/053085, filed on Feb. 8, 2019, and claims priority to Application No. EP 18305143.2, filed on Feb. 12, 2018, the disclosures of which are incorporated herein by reference.

TECHNICAL FIELD

The present disclosure relates to an injector device for a medicament.

BACKGROUND

Cartridge injection devices, for example cartridge auto-injectors, typically have a sleeve which conceals a needle for subcutaneous medicament delivery into a patient. The sleeve is usually displaced along a longitudinal axis of the device to expose the needle either during or prior to injection.

SUMMARY

It is an object of the present disclosure to provide an injector device configurable between a safe state and an operable state comprising:a housing having a distal end and a proximal end;a medicament cartridge disposed within the housing;a needle unit comprising a needle, the needle unit being disposed in the distal end of the housing;a sleeve displaceable along a longitudinal axis of the device between a first position in which the sleeve conceals the needle and a second position in which the needle is exposed from an end of the sleeve;a locking mechanism which prevents displacement of the sleeve when the device is in the safe state; anda button disposed in the proximal end of the housing, the button being configured to switch the device between the safe state and the operable state by releasing the locking mechanism to allow displacement of the sleeve when, in use, the button is pressed from an initial position into a depressed position.

Therefore the sleeve is secured to prevent exposure of the needle prior to movement of the button into the depressed position. This prevents premature exposure of the needle and accidental injury.

The injector may further comprise a plunger displaceable to drive medicament from the cartridge through the needle; and a plunger mechanism triggerable to displace the plunger during operation of the device.

Therefore the plunger can be mechanically, rather than manually, operated to ensure consistent delivery characteristics.

With the injector device in the safe state, the cartridge may be spaced from the needle unit, wherein the button is configured to move the cartridge onto the needle unit to fluidly connect the needle with the cartridge when, in use, the button is pressed from the initial position to the depressed position.

Therefore, prior to use of the device, the needle unit and needle are spaced from the cartridge. This has the advantage that the cartridge remains sealed up until the time that the device is required for use.

The sleeve may be configured to trigger the plunger mechanism when, during use, the sleeve is moved from the first position to the second position.

Therefore medicament is automatically delivered during injection.

The plunger mechanism may comprise: a coil spring which, when the plunger mechanism is triggered, provides a force to displace the plunger; and a spring retaining mechanism which prevents premature displacement of the plunger prior to the plunger mechanism being triggered.

The spring retaining mechanism may comprise a coupling and a retaining pin; the coupling being arranged to couple the spring to the retaining pin, prior to the plunger mechanism being triggered.

The coupling may comprise a slot which cooperates with the retaining pin.

The retaining pin may be held in cooperation with the slot by the sleeve and wherein axial movement of the sleeve between the first position and the second position aligns the retaining pin with an opening in the sleeve such that the retaining pin is displaceable out of the slot.

The retaining pin may extend from a cantilever spring arm which is configured to bias the retaining pin out of the slot.

Contacting surfaces of the slot and the retaining pin may be arranged such that the retaining pin is displaceable out of the slot by axial movement of the coupling.

Therefore the plunger mechanism is simply operated so that medicament is automatically delivered during injection.

The locking mechanism may comprise a hook that depends from a wall of the device and wherein the hook abuts the sleeve to prevent the sleeve moving relative to the housing when the button is in the initial position.

The button may be configured to act on the hook, when during use, it is moved from the initial position to the depressed position, to displace the hook out of abutting relation with the sleeve.

The injector device may further comprise a reservoir of medicament in the medicament cartridge.

These and other aspects of the disclosure will be apparent from and elucidated with reference to the embodiments described hereinafter.

DETAILED DESCRIPTION

A drug delivery device, as described herein, may be configured to inject a medicament into a patient. For example, delivery could be sub-cutaneous, intra-muscular, or intravenous. Such a device could be operated by a patient or care-giver, such as a nurse or physician, and can include various types of safety syringe, pen-injector, or auto-injector. The device can include a cartridge-based system that requires piercing a sealed ampule before use. Volumes of medicament delivered with these various devices can range from about 0.5 ml to about 2 ml. Yet another device can include a large volume device (“LVD”) or patch pump, configured to adhere to a patient's skin for a period of time (e.g., about 5, 15, 30, 60, or 120 minutes) to deliver a “large” volume of medicament (typically about 2 ml to about 10 ml).

In combination with a specific medicament, the presently described devices may also be customized in order to operate within required specifications. For example, the device may be customized to inject a medicament within a certain time period (e.g., about 3 to about 20 seconds for auto-injectors, and about 10 minutes to about 60 minutes for an LVD). Other specifications can include a low or minimal level of discomfort, or to certain conditions related to human factors, shelf-life, expiry, biocompatibility, environmental considerations, etc. Such variations can arise due to various factors, such as, for example, a drug ranging in viscosity from about 3 cP to about 50 cP. Consequently, a drug delivery device will often include a hollow needle ranging from about 25 to about 31 Gauge in size. Common sizes are 17 and 29 Gauge.

The delivery devices described herein can also include one or more automated functions. For example, one or more of combining the needle and cartridge, needle insertion, medicament injection, and needle retraction can be automated. Energy for one or more automation steps can be provided by one or more energy sources. Energy sources can include, for example, mechanical, pneumatic, chemical, or electrical energy. For example, mechanical energy sources can include springs, levers, elastomers, or other mechanical mechanisms to store or release energy. One or more energy sources can be combined into a single device. Devices can further include gears, valves, or other mechanisms to convert energy into movement of one or more components of a device.

The one or more automated functions of an auto-injector may each be activated via an activation mechanism. Such an activation mechanism can include an actuator, for example, one or more of a button, a lever, a needle sleeve, or other activation component. Activation of an automated function may be a one-step or multi-step process. That is, a user may need to activate one or more activation components in order to cause the automated function. For example, in a one-step process, a user may depress a needle sleeve against their body in order to cause injection of a medicament. Other devices may require a multi-step activation of an automated function. For example, a user may be required to depress a button and retract a needle shield in order to cause injection.

In addition, activation of one automated function may activate one or more subsequent automated functions, thereby forming an activation sequence. For example, activation of a first automated function may activate at least two of combining the needle and cartridge, needle insertion, medicament injection, and needle retraction. Some devices may also require a specific sequence of steps to cause the one or more automated functions to occur. Other devices may operate with a sequence of independent steps.

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

According to some embodiments of the present disclosure, an exemplary drug delivery device10is shown inFIGS.1A and1B. Device10, as described above, is configured to inject a medicament into a patient's body. Device10includes a housing11which typically contains a cartridge that defines a reservoir containing the medicament to be injected, and the components required to facilitate one or more steps of the delivery process.

The device10can also include a cap12that can be detachably mounted to the housing11. Typically, a user must remove cap12from housing11before device10can be operated.

As shown, housing11is substantially cylindrical and has a substantially constant diameter along the longitudinal axis A-A. The housing11has a distal region D and a proximal region P. The term “distal” refers to a location that is relatively closer to a site of injection, and the term “proximal” refers to a location that is relatively further away from the injection site.

Device10can also include a needle sleeve19coupled to housing11to permit movement of sleeve19relative to housing11. For example, sleeve19can move in a longitudinal direction parallel to longitudinal axis A-A. Specifically, movement of sleeve19in a proximal direction can permit a needle17to extend from distal region D of housing11.

Insertion of needle17can occur via several mechanisms. For example, needle17may be fixedly located relative to housing11and initially be located within an extended needle sleeve19. Proximal movement of sleeve19by placing a distal end of sleeve19against a patient's body and moving housing11in a distal direction will uncover the distal end of needle17. Such relative movement allows the distal end of needle17to extend into the patient's body. Such insertion is termed “manual” insertion as needle17is manually inserted via the patient's manual movement of housing11relative to sleeve19.

Injection is the process by which a bung or piston14is moved from a proximal location to a more distal location within the reservoir of the cartridge18in order to force a medicament from the cartridge18through needle17. In some embodiments, a drive spring (not shown) is under compression before device10is activated. A proximal end of the drive spring can be fixed within proximal region P of housing11, and a distal end of the drive spring can be configured to apply a compressive force to a proximal surface of piston14. Following activation, at least part of the energy stored in the drive spring can be applied to the proximal surface of piston14. This compressive force can act on piston14to move it in a distal direction. Such distal movement acts to compress the liquid medicament within the cartridge18, forcing it out of needle17.

Following injection, needle17can be retracted within sleeve19or housing11. Retraction can occur when sleeve19moves distally as a user removes device10from a patient's body. This can occur as needle17remains fixedly located relative to housing11. Once a distal end of sleeve19has moved past a distal end of needle17, and needle17is covered, sleeve19can be locked. Such locking can include locking any proximal movement of sleeve19relative to housing11.

FIGS.2A to2Cshow another injector device20. The injector device20is configurable between a safe state and an operable state and comprises: an elongate housing21having a distal end D and a proximal end P; a medicament cartridge22disposed within the housing21; a needle unit23comprising a needle24, the needle unit23being disposed in the distal end D of the housing21; and a button25disposed in the proximal end P of the housing21.

The device further comprises a sleeve28which is displaceable along the longitudinal axis A-A of the device20between a first position in which the sleeve28conceals the needle24, as illustrated inFIG.2A, and a second position in which the needle24is exposed from an end of the sleeve28, as shown inFIG.2C.

The sleeve28slides telescopically with respect to the housing21and is biased into the first position by a spring42. The spring42is disposed between the sleeve28and an inner surface of the housing21so that it is concealed during use of the device20. A locking mechanism47is provided to prevent displacement of the sleeve28when the device is in the safe state.

The button25is configured to switch the device from the safe state into the operable state by releasing the locking mechanism47to allow displacement of the sleeve28, when, in use, the button25is pressed from an initial position into a depressed position.

The button25is further configured to move the cartridge22onto the needle unit23to fluidly connect the needle24with the cartridge22as it is pressed into the depressed position.FIG.2Bshows the button25in the depressed position.

The cartridge22has a distal end sealed by a foil cap or rubber bung29, which is adjacent the needle unit23, and a proximal end sealed by a plunger26. A middle of the needle24is gripped by the needle unit23, which itself is fixed in place relative to the housing21so that, during use, when the button25is depressed a proximal end of the needle24penetrates the foil or rubber seal29to communicate with a reservoir of medicament30provided in the cartridge22.

The device further comprises a plunger mechanism27triggerable to displace the plunger26during operation of the device20and drive medicament30from the cartridge22. The plunger mechanism27is disposed between the button25and the cartridge22and comprises a spring35, in this case a coil spring, which, when the plunger mechanism27is triggered, is displaced along the longitudinal axis A-A of the device to displace the plunger26and drive medicament30from the cartridge22. The plunger mechanism27also comprises a spring retaining mechanism37comprising a coupling34and a retaining pin50. The spring retaining mechanism37is configured to prevent displacement of the plunger26before the plunger mechanism27is triggered; in which condition, the coupling34connects the spring35to the retaining pin50to retain the spring35and prevent it displacing the plunger26.

In the illustrated example, the coupling34consists of a tubular shaft34having a closed distal end36which faces the plunger26. The spring35is received within the shaft34with a distal end of the spring35abutted against the closed distal end36of the shaft34and a proximal end of the spring35abutted against an internal surface of the housing21. When the plunger mechanism27is triggered, the spring35is released from a coiled position and reacts against the internal surface of the housing21and the closed end36of the shaft34to displace the shaft34and the plunger26. The mechanism27may further be provided with a centring pin38which locates within the coil spring35to keep it aligned to the longitudinal axis A-A as it extends from the hollow portion of the shaft34.

The retaining pin50is moveable between a first position, in which the retaining pin50is configured to retain the spring35in the coiled position, and a second position, in which the retaining pin50is displaced to release the spring35. In the first position—as most clearly illustrated byFIG.3—the retaining pin50cooperates with a slot51in the shaft34to fix the shaft34in an axial direction relative to the housing21, via an arm52, which attaches the retaining the pin50to the housing21.

The arm52is cantilevered from an internal surface of the housing21and is readily deformable so that the retaining pin50may be displaced out of cooperation with the slot51in the shaft34when the arm52is bent along its length. The arm52may be resiliently deformable so that it is inherently biased into the second position or, alternatively, the abutting surfaces of the retaining pin50and the slot51in the shaft34may be inclined so that the axial force generated by the spring35has a component that acts outward on the retaining pin50, that is a component that acts transverse to the axis A-A of the device.

In either case, the retaining pin50is held in the first position by a portion53of the sleeve28. Specifically, the portion53of the sleeve28abuts a rear end of the pin50which prevents it being displaced out of the slot51in the shaft34when the sleeve28is in the first position. An opening54adjacent said portion53of the sleeve28is aligned with the retaining pin50when the sleeve28is moved to the second position so that the pin50is displaceable out of the slot51in the shaft34and into the opening54in the sleeve28. In this way, movement of the sleeve28from the first position to the second position triggers the plunger mechanism27.

During use of the device, the button25is pressed into the depressed position to engage the needle unit23and cartridge22and release the locking mechanism27. The device is then in the operable state in which the sleeve28is displaceable relative to the housing21. The user can therefore press the distal end D of the device up against an injection site to displace the needle shield28and expose the needle24. This causes penetration of the injection site with the needle24. After a predetermined insertion distance of the needle24into a subcutaneous region of the injection site, the opening54in the sleeve is aligned with the retaining pin50, thereby triggering injection as described above.

Another injector device is shown inFIG.4, in which like features retain the same reference numbers. On this device, the spring retaining mechanism37instead comprises a collar39, the collar39being rotatable about the longitudinal axis A-A between a locked position, in which the spring35is locked in place, and an unlocked position, in which the spring35is free to displace the plunger26.

The spring retaining mechanism further comprises locking arms40which cooperate with the collar39to hold the shaft34against the force of the spring35, prior to operation of the device20. The locking arms40are integral with the button25and extend therefrom into the housing21. Ends of the arms40are provided with a protrusion41that each extend through a corresponding opening in the shaft34to prevent the shaft34moving in the axial direction independently of the button25. In this way, the shaft34and plunger mechanism27are coupled to the button25when the collar is in the locked position.

The arms are inherently biased away from the shaft34but, with the collar39in the locked position, are held against the shaft34by the collar39. Rotation of the collar39into the unlocked position aligns slots in the collar39with each of the locking arms40so that they spring outwards through said slots and away from the longitudinal axis A-A. This action disengages the protrusions41from the holes in the shaft34, thus allowing the spring35to displace the plunger26.

The plunger mechanism27is coupled to the button25by the locking arms, as described above, so that when the button25is depressed from the first position to the depressed position, the plunger mechanism27moves from an initial position, in which the plunger mechanism27is initially spaced from the sleeve28, into a primed position in which the collar39of the plunger mechanism27abuts the sleeve28.

Specifically, a follower surface of the collar39abuts a distal edge (not shown) of the sleeve28, which distal edge is inclined relative to a direction perpendicular to the longitudinal axis A-A, so that, during axial displacement of the sleeve28, the collar39is rotated by said inclined edge about the axis A-A from the locked position into the unlocked position.

During use, the button25is pressed into the depressed position to move the plunger mechanism27into the primed position and engage the needle unit23and cartridge22; subsequently the distal end D of the device20is pressed up against an injection site of the user, displacing the needle shield28and causing the needle24to penetrate the user's skin, whereupon the displaced needle shield28triggers the plunger mechanism27and starts the injection event.

In this example, a restraint element31extends from an internal wall of the housing21adjacent the needle holder23to provide haptic feedback as the cartridge22engages the needle unit23. The restraint element may consist of a lip31, as shown, which extends internally from the housing21toward the longitudinal axis A-A and into the path of the cartridge22. The lip31has a degree resilient deformability so that when the user operates the button25, the cartridge22pushes past the lip31which resists in a manner that is discernible to the user to signify that the cartridge22and the needle unit23have combined. With the button25in the depressed position, the lip31locates in a neck33of the cartridge to secure the cartridge22in the needle unit23.

The particular arrangement of the locking mechanism47of the device illustrated byFIG.4is shown in detail inFIG.5. As illustrated, the locking mechanism comprises a hook43that depends from a wall44of the device20. In particular, the hook43may be a portion of wall44that is bent away from an inner face of the housing21toward the longitudinal axis A-A to obstruct the distal edge45of the sleeve28, when the device is in the safe state. In such an example the button25will be provided with a releasing means46. In the illustrated example the releasing means46is an arm46which is integrally formed with the button25and extends into the housing21. The arm46is configured to slide over the hook43to displace it outwards as the button25is moved from the first position to the depressed position, thereby allowing free movement of the sleeve28.

In another unillustrated example, the hook may abut the collar39to prevent rotation of the collar39when the button25is in the initial position, thereby preventing the plunger mechanism27being triggered before the cartridge22has engaged the needle unit23.

Referring again to the example illustrated byFIGS.2A to3, the locking mechanism47again comprises a hook43which extends toward the longitudinal axis A-A when the device is in the safe state. In this example, the hook43obstructs a second opening55in the sleeve28. The hook43is displaced outwards of the longitudinal axis A-A and out of the second opening55of the sleeve28as the button25is pressed into the depressed position in use. Specifically, an arm56extends from the button25, into the device and into contact with a proximal end of the cartridge22so that the cartridge22and button25move together, the button25being pressable by an amount necessary to engage the cartridge22with the needle unit23. A protrusion57is provided on the arm56which interacts with the hook43as the button25is pressed, displacing it outward to allow movement of the sleeve28.

The injector device may further comprise a reservoir of medicament in the medicament cartridge.

The terms “drug” or “medicament” are used herein to describe one or more pharmaceutically active compounds. As described below, a drug or medicament can include at least one small or large molecule, or combinations thereof, in various types of 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); carbohydrates and polysaccharides; and nucleic acids, double 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 contemplated.

The term “drug delivery device” shall encompass any type of device or system configured to dispense a drug into a human or animal body. Without limitation, a drug delivery device may be an injector device (e.g., syringe, pen injector, auto injector, large-volume device, pump, perfusion system, or other device configured for intraocular, subcutaneous, intramuscular, or intravascular delivery), skin patch (e.g., osmotic, chemical, micro-needle), inhaler (e.g., nasal or pulmonary), implantable (e.g., coated stent, capsule), or feeding systems for the gastro-intestinal tract. The presently described drugs may be particularly useful with injector devices that include a needle, e.g., a small gauge needle.

The drug or medicament may be contained in a primary package or “drug container” adapted for use with a drug delivery device. The drug container may be, e.g., a cartridge, syringe, reservoir, or other vessel configured to provide a suitable chamber for storage (e.g., short- or long-term storage) of one or more pharmaceutically active compounds. For example, in some instances, the chamber may be designed to store a drug for at least one day (e.g., 1 to at least 30 days). In some instances, the chamber may be designed to store a drug for about 1 month to about 2 years. Storage may occur at room temperature (e.g., about 20° C.), or refrigerated temperatures (e.g., from about −4° C. to about 4° C.). In some instances, the drug container may be or may 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 instances, the two chambers of the dual-chamber cartridge may be configured to allow mixing between the two or more components of the drug or medicament prior to and/or during dispensing into the human or animal body. For example, the two chambers may be configured such that they are in fluid communication with each other (e.g., by way of a conduit between the two chambers) and allow mixing of the two components when desired by a user prior to dispensing. Alternatively or in addition, the two chambers may be configured to allow mixing as the components are being dispensed into the human or animal body.

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

Exemplary drugs for the treatment and/or prophylaxis of diabetes mellitus or complications associated with diabetes mellitus include an insulin, e.g., human insulin, or a human insulin analogue or derivative, a glucagon-like peptide (GLP-1), GLP-1 analogues or GLP-1 receptor agonists, or an analogue or derivative thereof, a dipeptidyl peptidase-4 (DPP4) inhibitor, or a pharmaceutically acceptable salt or solvate thereof, or any mixture thereof. As used herein, the term “derivative” refers to any substance which is sufficiently structurally similar to the original substance so as to have substantially similar functionality or activity (e.g., therapeutic effectiveness).

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

The term “antibody”, as used herein, refers to an immunoglobulin molecule or an antigen-binding portion thereof. Examples of antigen-binding portions of immunoglobulin molecules include F(ab) and F(ab′)2 fragments, which retain the ability to bind antigen. The antibody can be polyclonal, monoclonal, recombinant, chimeric, de-immunized 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 or no ability to bind an Fc receptor. For example, the antibody can be an isotype or subtype, an antibody fragment or mutant, which does not support binding to an Fc receptor, e.g., it has a mutagenized or deleted Fc receptor binding region.

The compounds described herein may be used in pharmaceutical formulations comprising (a) the compound(s) or pharmaceutically acceptable salts thereof, and (b) a pharmaceutically acceptable carrier. The compounds may also be used in pharmaceutical formulations that include one or more other active pharmaceutical ingredients or in pharmaceutical formulations in which the present compound or a pharmaceutically acceptable salt thereof is the only active ingredient. Accordingly, the pharmaceutical formulations of the present disclosure encompass any formulation made by admixing a compound described herein and a pharmaceutically acceptable carrier.

Pharmaceutically acceptable salts of any drug described herein are also contemplated for use in drug delivery devices. Pharmaceutically acceptable salts are for example acid addition salts and basic salts. Acid addition salts are e.g. HCl or HBr salts. 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. Further examples of pharmaceutically acceptable salts are known to those of skill in the arts.

Pharmaceutically acceptable solvates are for example hydrates or alkanolates such as methanolates or ethanolates.