Single-dose injection device

Abstract

The present invention relates to a pre-filled single dose injection device discharging one single dose of a predetermined fixed amount having an embedded cartridge, a piston rod having a predetermined travel distance, the position of the piston rod travel distance relative to a housing structure securing the cartridge being individually adjustable for each individual injection device.

Description

[Technical field]

[0001] The present invention relates to a single dose injection device for dispensing a single fixed dose of a predetermined amount of liquid medicament. More specifically, the present invention relates to an injection device designed to manually dispense a single fixed dose of a predetermined amount of liquid medicament from a cartridge pre-filled and encapsulated by the injection device manufacturer using a pre-filled cartridge, preferably by one stroke of an axially movable piston rod translating within the cartridge.

[0002] The present invention further relates to a method for assembling such a single dose injection device. [Background technology]

[0003] Syringes used to expel the entire contents of a cartridge in one stroke have been known for decades. An example of such a syringe is disclosed in US Pat. No. 5,399,633. Here, an exchangeable cartridge containing a liquid drug is inserted into a tubular housing structure, and a threaded nut element guiding a piston rod is screwed into the housing structure to axially fix the cartridge relative to the housing structure. The contents of the cartridge are expelled by moving the plunger distally within the cartridge. The axial movement of the plunger is performed by a user manually pushing the piston rod distally. The entire injectable amount contained in the cartridge is expelled as one single dose through a dual-tip needle assembly mounted on a needle interface provided distally on the housing structure. The forward movement of the piston rod is first stopped within the cartridge when the plunger reaches the distal neck of the cartridge, and therefore the proximal stop is not fixed, but depends on the physical shape of the cartridge and the elasticity of the plunger. The amount expelled as the plunger moves through the cartridge is therefore very highly dependent on the physical tolerances of the cartridge and the tolerances in the filling process.

[0004] Different examples of automatic spring-loaded injection devices in which cartridges can be used are provided in US Pat. No. 5,399,633. In this example, the cartridges used have differences in the filling volume due to tolerances and therefore also different axial positions of the plunger before use. Thus, when the cartridge is mounted in the housing structure, a gap may exist between the plunger and the piston rod. During injection, the piston rod may move in this free space without actually moving the plunger in the cartridge, which means that the axial movement of the piston rod is not directly translated into a similar movement of the plunger, which makes the amount of the ejected dose vary from cartridge to cartridge, depending on the tolerances that determine the position of the plunger in the individual cartridge. To compensate for this, the automatic injection mechanism can be adjusted to its relative axial position during assembly of the injection device.

[0005] A more conventional multi-dose insulin injection device is disclosed in US Pat. No. 5,399,633. In this injection device, a piston rod rotates within a threaded nut element to spiral distally during injection, thereby expelling an individually set dose. During assembly of the injection device, the nut element can be axially positioned relative to the housing. [Prior art documents] [Patent documents]

[0006] [Patent Document 1] U.S. Patent No. 2,753,867 [Patent Document 2] European Patent No. 3,628,352 [Patent Document 3] U.S. Patent Publication No. 2018 / 0140,776 Summary of the Invention

[0007] Hereafter, the object of the present invention is to provide a solution in which the amount dispensed when dispensing a single fixed dose is not dependent on the tolerances mentioned above.

[0008] This is preferably achieved by advancing the piston rod a predetermined travel distance in one single stroke of the piston rod, the physical location of which relative to the housing structure, and thus the cartridge embedded in the housing structure, being variable for each individual injection device.

[0009] The invention is further defined in claim 1. Advantageous embodiments are further defined in the dependent claims. Thus, in one aspect of the invention, a single dose injection device for delivering a predetermined amount of a liquid drug comprises: a housing structure containing a liquid agent to be dispensed, the housing structure holding a loaded cartridge embedded within and axially locked to the housing structure, the cartridge having a distal end sealed by a pierceable septum and a proximal end closed by a movable plunger having a distal front surface; a piston rod structure including a piston rod and a piston rod foot, the piston rod structure being translatable in a distal direction relative to the housing structure to move a plunger in a distal direction within the cartridge, the plunger being movable from a first position to a second position; The predetermined amount of liquid to be expelled is defined by the inner surface of the cartridge and the length that the distal front face of the plunger is moved during movement of the plunger from the first position to the second position, and a nut element that guides the piston rod structure is adjustably coupled to the housing structure.

[0010] Further in accordance with the present invention, the piston rod structure and the nut element comprise engagement means for releasably fixing the piston rod structure to the nut element in a starting position of the piston rod structure, the piston rod structure abutting the plunger at least in use; The stop position of the piston rod structure is defined by a stop means on the piston rod which operably engages with the nut element, such that the travel distance of the piston rod structure is defined as the axial distance the piston rod structure can translate when moving the plunger from a start position to a stop position during dose ejection, and the axial position of the nut element relative to the housing structure is individually adjustable for each individual injection device during assembly of the individual injection device, thereby adjusting the axial position of the travel distance of the piston rod structure to an adjusted position depending on the position of the plunger in the individual cartridge.

[0011] The piston rod travel distance is therefore the distance that the piston rod can travel from its start position to its stop position. However, it is important that the travel distance is translated one-to-one into the movement of the plunger, even though the plunger has a variable position in each individual cartridge. This is achieved by guiding the piston rod in a nut element that is adjustable relative to the housing structure. It is therefore possible to adjust the physical position of the travel distance for each individual injection device. The position of the travel distance is preferably adjusted so that the piston rod structure (including the piston rod foot) abuts the plunger in the start position of the piston rod.

[0012] The piston rod foot preferably abuts against the plunger in use. Due to temperature fluctuations, the abutment is not always fully established when the injection device is stored. However, as a starting position, in use, the piston rod foot abuts against the plunger.

[0013] Preferably, the actual physical location of the start position is determined by the physical design of the nut element, however the distance between the start and stop positions is critical to the length the piston rod travels during ejection, and the location of this distance, the travel distance, is adjustable for each individual injection device.

[0014] The travel distance is a fixed distance, but the position of the travel distance relative to the housing structure is adjustable, as described herein. Once the cartridge is secured to the housing structure, the position of the travel distance relative to the cartridge and within the cartridge relative to the plunger is also adjustable.

[0015] Thus, the position of the nut element, and therefore the travel distance, is individually adjustable for each individual injection device, and the position of the travel distance can be adjusted to accommodate the individual position of the plunger within each cartridge.

[0016] The piston rod is coupled to the nut element with a releasable coupling, a position defining a start position such that the piston rod can move out of the start position and begin ejection, and a stop position for the piston rod is defined by a stop surface on the piston rod, which in the stop position engages and abuts the nut element.

[0017] The distance between the start and stop positions is the travel distance that the piston rod travels relative to the housing structure including the nut element and cartridge during one single ejection, and may also be referred to as the stroke length of the piston rod.

[0018] The piston rod structure is releasably secured to the nut element by releasable engagement means which secure the piston rod in a releasable position from which it can be easily released by applying pressure to the proximal end of the piston rod. In one embodiment, the engagement means between the piston rod and the nut element comprises a number of radial arms provided on either the piston rod or the nut element which engage with the other of the piston rod or the nut member.

[0019] In a preferred embodiment, the radial arms are provided on the piston rod and the nut element comprises an angled front portion which is engaged by the radial arms when the piston rod is in its starting position, the angled front portion preferably being inclined in the proximal position to better prevent the piston rod from moving in the proximal direction when assembled.

[0020] Alternatively, the engagement means between the piston rod and the nut element comprises a number of further radial arms provided on the piston rod which frictionally engage with a recessed inner surface on the nut element at the starting position of the piston rod.

[0021] In a different embodiment, the engagement means between the piston rod and the nut element comprises a number of radial gripping teeth provided on either the piston rod or the nut element for engaging with the other of the piston rod or the nut member. In this embodiment, the radial gripping teeth are preferably provided on the piston rod and the nut element is provided with an angled surface which is engaged by the radial gripping teeth when the piston rod is in its starting position. The gripping teeth can have any desired size and shape.

[0022] The physical location of the start position is determined by the physical design of the nut element, in one embodiment a proximal flange is provided which defines the start position of the piston rod and which engages a stop means on the piston rod at the stop position.

[0023] The adjustment of the nut element relative to the housing structure can be envisaged in several different ways. It can be a strictly linear adjustment or it can be a helical adjustment. In a preferred embodiment, the nut element is adjusted axially relative to the housing structure, preferably at the threaded connection between the nut element and the housing structure.

[0024] After adjustment, the nut element can be secured to the housing structure in a number of different ways. In one embodiment, the nut element and the housing structure can be welded together, for example, by laser welding. In a different embodiment, a ratchet interface can be used, which can be specifically a one-way ratchet.

[0025] In one embodiment, the housing structure includes threads on an inner surface that engage corresponding threads on an outer surface of the nut element. These threads can be either full threads or thread segments. In one embodiment, the pitch of the threads is configured such that the nut element moves in a distal direction when the nut element rotates counterclockwise on the threaded connection, thereby obtaining an adjusted position.

[0026] Axial friction knobs can be provided on the flanges of the threads to maintain the nut element in the adjusted position. These knobs can have any desired size and shape necessary to hold the nut element from rotating in the opposite direction and away from the adjusted position. As an alternative to or in addition to the axial friction knobs, ratchet interfaces can be provided. Such ratchet interfaces can be formed as one or more flexible teeth that operate with a toothed rib so that rotation is permitted in both directions of rotation. To further prevent the nut element from unscrewing the ratchet interface, a one-way ratchet interface can be provided between the nut element and the housing structure. Such one-way ratchet interfaces can operate together with the described friction knobs, but can also operate without the friction knobs.

[0027] Such a one-way ratchet may be provided in one embodiment as a flexible ratchet carrier provided on one of the nut element or the housing structure, and an axial rib structure provided on the other of the nut element and the housing structure. The flexible ratchet carrier may thus be engaged with the axial rib structure to form a one-way ratchet. For this purpose, the ratchet carrier may be provided with one or more teeth for the actual engagement. The flexible ratchet carrier is preferably formed as an arm or as a beam configuration. The nut element and the housing structure are thus irreversibly connected in the assembled state. However, as mentioned above, the flexible ratchet carrier may be provided as a ratchet interface that allows rotation in both directions.

[0028] In a second aspect of the invention, there is provided a method of assembling a single dose injection, the method comprising the steps of individually adjusting the axial position of a nut element for each individual injection device during assembly, thereby adjusting the axial position of the travel distance of the piston rod structure relative to the housing structure to an adjusted position in which the piston rod structure abuts the plunger.

[0029] Therefore, for each individual injection device, the position of the nut element is adjusted to an adjusted position in which the piston rod structure, i.e. the piston rod or the piston rod foot, abuts against the plunger in the cartridge so that the stroke of the piston rod is transferred to the same linear movement of the plunger. By having this adjustability of the nut element and therefore the travel distance of the piston rod, it is possible to prevent part of the movement of the piston rod from taking place in the air gap space that sometimes exists between the plunger and the piston rod structure due to the variable position of the plunger in the individual cartridge.

[0030] In a third aspect, the present invention relates to a plurality of single dose injection devices for delivering a predetermined amount of a liquid drug according to any of the apparatus claims, each of the plurality of single dose injection devices being individually assembled and adjusted according to the method claims.

[0031] Definition: An "injection pen" or "injection pen" is an injection device that typically has an oval or elongated shape somewhat resembling a writing pen. Such pens usually have a tubular cross section, but can easily have different cross sections, such as triangular, rectangular or square, or any variation around these geometric shapes.

[0032] The term "needle cannula" is used to describe the actual conduit that penetrates the skin during injection. The needle cannula is usually made from a metallic material such as stainless steel and is connected to a hub to form the complete injection needle, often also called the "needle assembly". However, the needle cannula may also be made from a polymeric or glass material. The hub also carries a connection means for connecting the needle assembly to the injection device, and is usually moulded from a suitable thermoplastic material. The "connection means" may be, by way of example, a luer coupling, a bayonet coupling, a threaded connection, or any combination thereof.

[0033] The term "needle unit" is used to describe one single needle assembly carried in a container. Such containers typically have a closed distal end and an open proximal end sealed by a removable seal. The interior of such containers is typically sterilized so that the needle assembly is ready for use. Needle units specifically designed for pen injection systems are defined in ISO Standard No. 11608, Part 2, and are often referred to as "pen needles." Pen needles are typically double-pointed, with a front end for penetrating the user's skin and a rear end for penetrating the medicament-containing cartridge so that fluid communication is established during injection.

[0034] As used herein, the term "liquid drug" is meant to encompass any drug-containing flowable pharmaceutical product that can be passed through a delivery means, such as a hollow needle cannula, in a controlled manner, such as a liquid, solution, gel, or fine suspension. Exemplary drugs include pharmaceutical products such as peptides, proteins (e.g., insulin, insulin analogs, and C-peptide), as well as hormones, biologically derived or active agents, hormone and gene-based drugs, nutritional formulas, and other substances in solid (formulation) or liquid form.

[0035] "Cartridge" is a term used to describe the container that actually holds the medication, often referred to as the primary packaging. Cartridges are usually made of glass, but may be molded from any suitable polymer. The cartridge or ampoule is preferably sealed at one end by a pierceable membrane, called a "septum," which can be pierced, for example, by the non-patient end of a needle cannula. Such septums are usually self-sealing, meaning that when the needle cannula is removed from the septum, the opening created during piercing is automatically sealed by its inherent elasticity. The opposite end of the cartridge is typically closed by a movable "plunger," a piston-like element made of rubber or a suitable polymer. The plunger is slidably moved within the cartridge, preferably in a distal direction, during use. The space between the pierceable membrane and the movable plunger holds the liquid drug, which is pushed out as the plunger reduces the amount of space that holds the liquid drug. Cartridges used for both prefilled and durable injection devices are typically filled with a predetermined amount of liquid drug at the factory by the manufacturer. Many cartridges currently available contain 1.5 ml or 3 ml of liquid drug.

[0036] Because the cartridge typically has a narrower distal neck portion into which the plunger cannot move, not all of the liquid agent contained within the cartridge can actually be expelled. Thus, the terms "initial amount" or "substantially used" refer to the injectable volume contained within the cartridge, and therefore not necessarily the total volume.

[0037] The term "pre-filled injection device" refers to an injection device in which a cartridge containing a liquid medicament is permanently embedded within the injection device such that it cannot be removed without permanently destroying the injection device. Once the pre-filled amount of liquid medicament in the cartridge is used, the user typically discards the entire injection device. Typically, the cartridge, filled by the manufacturer with a specific amount of liquid medicament, is fixed within a cartridge holder that is later permanently connected within a housing structure such that the cartridge cannot be replaced.

[0038] This is in contrast to "durable injection devices," which allow the user to replace the liquid-containing cartridge whenever it becomes empty. Prefilled injection devices are usually sold in packages containing two or more injection devices, whereas durable injection devices are usually sold one at a time. When using prefilled injection devices, the average user may require 50-100 injection devices per year, whereas with durable injection devices, one single injection device may be used for several years, however, the average user will require 50-100 new cartridges per year.

[0039] All references cited in this specification, including publications, patent applications, and patents, are incorporated by reference in their entirety to the same extent as if each reference was individually and specifically indicated to be incorporated by reference and was set forth in its entirety herein.

[0040] All headings and sub-headings are used herein for convenience only and should not be construed as limiting the invention in any way.

[0041] The use of any and all examples or exemplary phrases (such as those below) provided herein is intended merely to clarify the invention and does not limit the scope of the invention unless otherwise specified. No language in the specification should be construed as indicating any non-claimed element as essential to the practice of the invention.

[0042] Citation and incorporation of patent documents herein is done for convenience only and does not reflect any view of the validity, patentability and / or enforceability of such patent documents.

[0043] This invention includes all modifications and equivalents of the subject matter recited in the claims appended hereto as permitted by applicable law.

[0044] The invention is explained in more detail below in connection with preferred embodiments and with reference to the drawings. [Brief description of the drawings]

[0045] [Figure 1A-1B] 1A and 1B show perspective views of the injection device with (FIG. 1A) and without (FIG. 1B) a protective cap. [Diagram 2] FIG. 2 shows an exploded view of the injection device. [Diagram 3] FIG. 3 shows a cross-sectional view of the injection device when assembled and prior to ejection of a single fixed dose. [Figure 4A-4B] Figures 4A and 4B show two different views of the housing structure: In Figure 4B, the housing structure is cut open along the central longitudinal axis. [Figure 4C] FIG. 4C shows a cross-sectional view of another embodiment of an injection device. [Figure 4D] FIG. 4D shows a section of the injection device of FIG. 4C. [Figure 5A-5B] Figures 5A and 5B show two different views of the nut element: in Figure 5B, the nut element is cut open along its central longitudinal axis; [Figure 5C] FIG. 5C shows a close-up view of a distal portion of the nut element in an alternative embodiment. [Figures 6A-6C] Figures 6A-6C show different views of the piston rod, and Figure 6B is an enlarged view of the enclosed section of Figure 6A. [Figure 7] FIG. 7 is a perspective view of the injection device. [Figure 8] FIG. 8 shows a cross-sectional view of a pen needle suitable for the disclosed injection device. [Figure 9A] FIG. 9A shows a cross-sectional view of a nut element attached to a housing structure. [Figure 9B] FIG. 9B shows a cross-sectional view of the injection device assembled and ready for administration. [Figure 9C] FIG. 9C shows a cross-sectional view of the injection device after administration. DETAILED DESCRIPTION OF THE PREFERRED EMBODIMENTS

[0046] The figures are schematic and simplified for clarity, showing only the details essential to an understanding of the invention, and omitting other details. The same reference numbers are used throughout for the same or corresponding parts.

[0047] When the terms "upper" and "lower", "right" and "left", "horizontal" and "vertical", "clockwise" and "counterclockwise" or similar relative expressions are used in the following, these merely refer to the attached drawings and do not necessarily refer to actual usage situations. The drawings shown are schematic representations, so that the configuration of the different structures, as well as their relative dimensions, are intended to serve illustrative purposes only.

[0048] In that context, it may be convenient to define that the term "distal end" in the accompanying figures is meant to refer to the end of the injection device which supports the injection needle, and that the term "proximal end" is meant to refer to the opposite end which carries the injection button, as shown in Figure 3. Distal and proximal are meant along an axial orientation extending along the longitudinal axis (X) of the injection device, as also disclosed in Figure 3.

[0049] In the following examples, when referring to clockwise and reverse or counterclockwise directions, it is understood that the injection device is viewed from a position distal to the injection device. Thus, a clockwise direction is a rotation following a normal clockwise arm, and a counterclockwise direction is a rotation in the opposite direction.

[0050] The following terms are used throughout the following detailed description to describe the various movements performed by the injection device described in the examples.

[0051] "Translational motion" means strictly linear motion without any rotation.

[0052] "Rotational motion" is any rotational motion about a center, which may be the midpoint of a single planar axis or central axis having a longitudinal extension.

[0053] By "axial motion" is meant any motion in an axial direction. Such motion can be strictly translational or can include rotational motion, thus resulting in "helical motion", which means a combination of axial and rotational motion.

[0054] "Telescopic" is meant to encompass situations where a movable element moves out of and / or into a base element. The telescopic motion can be translational or can include rotation, making the telescopic motion helical.

[0055] Figures 1A and 1B disclose an injection device according to the present invention. A housing structure 1 is provided with a protective cap 30 distally and an injection button 40 proximally. In Figure 1B, the protective cap 30 covering the distal part of the injection device has been removed as is normally done before performing an injection. As best seen in Figure 1A, the protective cap 30 has an area 31 with a different surface texture or rib-like structure 32 (best seen in Figure 4C), which allows the user to better grip the protective cap 30 when removing it. The housing structure 1 is preferably provided with an anti-roll mechanism 9 to prevent the injection device from rolling when resting on a flat or slightly inclined surface such as a table or the like.

[0056] As can be seen in Figures 2 and 3, the injection device comprises a housing structure 1, which may be formed from one or more parts. The housing structure 1 axially secures a cartridge 10 containing the liquid agent to be injected, and is distally provided with a needle interface 2 for securing a needle assembly 20 to the housing 1. The distal needle interface 2 is preferably covered by a removable protective cap 30 when the injection device is not in active use. Proximally, the housing 1 is provided with a push-like injection button 40 operable by a user to perform an injection. The injection button 40 is directly coupled to a piston rod 50, such that any translational movement of the injection button 40 in the distal direction is immediately converted into a similar translational movement of the piston rod 50 as will be described.

[0057] The needle assembly 20 used is a standard pen needle as disclosed in FIG. 8. In such known pen needles, the needle cannula 21 is fixed in the needle hub 22 such that when the needle assembly 20 is mounted on the needle interface 2, the proximal part 23 of the needle cannula 21 faces proximally to penetrate into the cartridge 10. The opposite distal part of the needle cannula 21 is provided with a sharp distal point 24 capable of penetrating the skin of the user during an injection. The needle hub 22 proximally forms an enclosure 25 surrounding the proximal part 23 of the needle cannula 21. This enclosure 25 usually carries means for connecting the needle hub 22 to an injection device so that the proximal part 23 of the needle cannula 21 penetrates into the cartridge 10 when the needle assembly 20 is connected. The needle hub 22 extends distally into a tower 26 that supports the needle cannula 21.

[0058] In one embodiment, needle cannula 21 may be a gauge 29 (G29) needle cannula and the length of the distal portion of needle cannula 21 that is inserted into the skin may be 4 mm, as measured from needle hub 22 to sharp distal point 24. The distal portion of needle cannula 21 may further have a conical shape.

[0059] Inside the housing structure 1, the cartridge 10 is positioned as disclosed in Figure 3. The cartridge 10 comprises a distally pierceable septum 11 through which the needle cannula 21 penetrates when attached. At the opposite proximal end, the cartridge 10 is closed by a movable plunger 12, preferably made from a suitable polymer, having a distal surface 13 in contact with the liquid medicament within the cartridge 10. The space between the distal surface 13 of the movable plunger 12, the septum 11 and the inner surface 14 of the cartridge 10 contains the liquid medicament, as best seen in Figure 3. The volume expelled during injection is defined by the inner surface 14 of the cartridge 10, and the axial length of the distal surface 13 of the movable plunger 12 is moved during dose expulsion.

[0060] The septum 11 is fixed to the cartridge 10 by a metal cap 15 which is bent around a neck 16 of the cartridge 10, as is generally known from cartridges.

[0061] The housing structure 1 disclosed in Figures 4A and 4B is, in one embodiment, provided with a number of milling ribs 7 or the like at its distal end, designed to secure the cartridge 10 to the housing structure 1. When the cartridge 10 is pressed into the housing structure 1 during assembly, deformation of these milling ribs 7 against a metal cap 15 on the cartridge 10 secures the cartridge 10 to the housing structure 1. In different embodiments, alternative means can be provided to secure the cartridge 10 to the housing structure 1. The cartridge 10 only needs to be axially secured to the housing structure. In a preferred alternative, the housing structure 1 is provided with several inwardly directed knobs that grip the rear of the neck 16 of the cartridge 10, thereby axially securing the cartridge 10 to the housing structure. Such knobs can be combined with the disclosed milling ribs 7.

[0062] A different alternative for fixing the cartridge 10 to the housing structure 1 is disclosed in Fig. 4C. In this embodiment, the injection device comprises a housing structure 1 having the same elements as the first embodiment as illustrated in Fig. 4C, namely a protective cap 30 having ribs 32, a cartridge 10, an injection button 40, a piston rod 50 and a nut element 60.

[0063] FIG. 4D discloses an enlargement from FIG. 4C, in which the nut element 60 is provided with several inwardly directed longitudinal milling flanges 67 that engage the proximal end of the cartridge 10 when the nut element 60 is threaded into the housing structure 1, as described. The cartridge 10 is thus axially locked between the housing structure 1 and the milling flanges 67 on the nut element 60, axially locking the cartridge 10 to the housing structure 1. The milling flanges 67 are therefore partially milled by the proximal end of the cartridge 10 as the nut element 60 moves into engagement with the housing structure 1. In one embodiment, four such milling flanges 67 are provided, although any number can be used. In the disclosed embodiment, the milling ribs 7 shown in FIG. 4B and / or the inwardly directed knobs described above are not necessarily required, but may be applied as desired.

[0064] During injection, the plunger 12 is moved distally within the cartridge 10 by a piston rod 50 which, in the disclosed embodiment, is provided distally with a separate piston rod foot 45 to better distribute the force on the plunger 12. In one embodiment, the piston rod foot 45 may be integrally molded with the piston rod 50.

[0065] The piston rod 50 engages and is guided by a nut element 60 which is axially adjustable relative to the housing structure 1 as will be described.

[0066] As best seen in Figure 4A, the housing structure 1 is provided on its outer surface with one or more protrusions 3 that secure a protective cap 30 in a releasable engagement. Additionally, the housing structure 1 has a window 4 through which a user can inspect the contents of the cartridge 10. Most distally, the housing structure 1 is provided with a needle interface 2 for connecting a needle assembly 20 to the housing structure 1, which in the disclosed embodiment is a combination of a threaded interface and a bayonet interface, although any type of needle interface means could be used.

[0067] In addition to the grinding ribs 7 provided on the inner surface of the housing structure 1, several longitudinal ribs 8 are also provided for supporting the cartridge 10. Furthermore, the housing structure 1 has its inner surface provided with an internal thread 5 for fixing a nut element 60, as will be explained. Distal to the internal thread 5, a toothing is provided which includes several axial ribs 6 which engage with the nut element 60.

[0068] 5A and 5B, includes an external thread segment 65 on an outer surface for engaging with an internal thread 5 in the housing structure 1 such that the nut element 60 can be rotated relative to the housing structure 1 in a rotation that moves the nut element 60 axially relative to the housing structure 1. As disclosed, any number of thread segments 65 can be provided, or alternatively, one full thread can be provided.

[0069] In one embodiment disclosed in FIG. 5C, the thread 5 and / or the thread segment 65 may be provided with axial friction knobs 69 that engage to further secure the engagement between the two threads (the internal thread 5 of the housing structure 1 and the thread segment 65 on the nut element 60). The friction knobs 69 are provided axially on the radial flanges of the threads 5, 65 and thus serve to frictionally secure the housing structure 1 and the nut element 60 to one another. The friction knobs 69 disclosed in FIG. 5C may be provided in any size and number required. The presence of these friction knobs 69 also allows the engagement between the nut element 60 and the housing structure 1 to be adjusted in very fine increments, depending on the rotation distance between the individual friction knobs 69.

[0070] Distally, the nut element 60 is provided with a number of flexible ratchet carriers 66 that bend radially and engage with axial ribs 6 in the housing structure 1 such that the nut element 60 can only rotate in one rotational direction relative to the housing structure 1. These flexible ratchet carriers 66 could be provided as flexible arms as disclosed in Figures 5A and 5B, or as beam structures as disclosed in Figure 5C or any other suitable structure.

[0071] In the disclosed embodiment, the nut element 60 can rotate counterclockwise (when viewed from a distal position), and the thread interface 5, 65 (between the internal thread 5 on the housing structure 1 and the external thread segment 65 on the nut element 60) has a pitch direction such that rotation of the nut element 60 in the permitted counterclockwise direction moves the nut element 60 in a distal direction inside the housing structure 1.

[0072] However, the flexible ratchet carrier 66 need not be implemented as a one-way ratchet, but can be configured to allow rotation in both directions of rotation.

[0073] On its outer surface, the nut element 60 is provided with a number of outwardly facing support flanges 61 that rest against the inner surface of the housing structure 1. As best seen in Figures 5A and 5B, four such outwardly facing support flanges 61 are provided, although any number may be used.

[0074] The nut element 60 is further provided with several radial openings 62 that can be aligned with the proximal-most end of the cartridge 10 when installed as best seen in Figure 3. However, if the assembly method of Figures 4C-4D is used, these radial openings 62 can be provided in different locations, as seen in Figures 4C-4D. At the proximal end, the nut element 60 is provided with a recessed inner surface 63 for receiving the piston rod 50. This recessed inner surface is provided distally with an angled front portion 64 that slopes toward the inner surface of the nut element 60, which terminates proximally in a proximal flange 68.

[0075] Additionally, the inner surface of the nut element 60 is provided with a number of longitudinal support ribs for supporting the cartridge 10 .

[0076] 6A-6C disclose a piston rod 50 which proximally carries an injection button 40 which is disclosed in detail in FIG.

[0077] The injection button 40 disclosed in FIG. 7 is provided with several radial openings 41 that engage with a similar number of radial snaps 51 on the piston rod 50 so that the injection button 40 and the piston rod 10 move axially in unison. These snaps 51 are carried on a number of flexible arms 52 so that the piston rod 50 and the injection button 40 can be easily click-fit together. Alternatively, the injection button 40 and the piston rod 50 can be molded as one single element. The injection button 40 is further provided with circular ridges 42, 43 that guide the injection button 40 against the inner surface of the housing structure 1. Alternatively, these ridges 42, 43 can be provided as knobs or similar support structures. Proximally, the injection button 40 is preferably provided with a concave surface to accommodate the user's fingers during injection.

[0078] Further, the disclosed piston rod 50 is provided with a first set of flexible radial arms 53 and a second set of flexible radial arms 54. The second set of flexible radial arms 54 are on an outer surface which in one embodiment are provided with flat surfaces 55 each terminating distally in radial gripping teeth 56. This is best seen in the enlarged view of Figure 6B. These flat surfaces are replaced in a further embodiment disclosed in Figures 4C-4D by a set of further radial arms 58 which may carry radial gripping teeth 56.

[0079] When the piston rod 50 is attached to the nut element 60 as seen in FIG. 3, the flat surfaces 55 of the second set of radial arms 54 rest against the recessed inner surface 63 of the nut element 60. In this position, the radially gripping teeth 56 grip against the angled front 64 such that the position of the piston rod 50 relative to the nut element 60 is fixed. This defines the starting position of the piston rod 50 as will be explained. However, the starting position is not necessarily physically located at the engagement point, but the engagement point defines the starting position of the piston rod. Additionally, a radial stop surface 57 is provided on the piston rod 50, thus defining the stopping position and therefore the possible length of travel distance (TD) and therefore the amount expelled, as will be explained.

[0080] Alternatively, the piston rod 50 can be molded without the radially gripping teeth 56. In such an embodiment, the proximal end of the first set of radial arms 53 engages with the angled front 64 to define the starting position of the piston rod 50. Thus, the piston rod 50 abuts the plunger 12 in the cartridge 10, preferably distal to the piston rod foot 45, and the proximal end of the first set of radial arms 53 engages with the angled front 64 on the nut element 60, thereby defining the starting position of the piston rod 50. Because temperature changes of the liquid agent can change the position of the plunger 12 during storage, a slight clearance between the proximal end of the first set of arms 53 and the angled front 64 of the nut element 60 is permitted without changing the fact that the piston rod 50 (and / or foot 45) abuts the plunger 12 at an adjusted starting position, as described.

[0081] In the latter embodiment disclosed in Figures 4C-4D, the angled front 64 is preferably made with a 90 degree radial incline, or a slight incline towards the proximal end. This may make it nearly impossible for the proximal end of the first set of radial arms 53 to slide proximally out of engagement with the nut element 60. The piston rod 50 may therefore follow the nut element 60 proximally as the nut element 60 rotates relative to the housing structure 1 at the threaded connection 5, 65, and once the piston rod 50 (or foot 45) abuts the plunger 12, further advancement of the nut element 60 may be impossible.

[0082] In the embodiment disclosed in Fig. 4C-D, the piston rod 50 may be shaped without radial gripping teeth 56 such that the further radial arms 58 frictionally engage the recessed inner surface 63, thereby defining the delineation point of piston rod movement. The two sets of flexible radial arms 53, 54 may include any number of flexible arms in each set. However, in the disclosed embodiment, two flexible arms are provided in each set of radial arms 53, 54. As shown, the flexible radial arms 53, 54 are flexible in a direction that only allows movement of the piston rod 50 towards the distal end of the housing structure 1. When the piston rod 50 is mounted in the nut element 60 as disclosed in Fig. 3, the first set of arms 53 prevents the piston rod 50 from moving in a proximal direction by being blocked by the nut element 60.

[0083] In Fig. 3 it is disclosed that the piston rod 10 is positioned in a start position relative to the housing structure 1. In this position the piston rod 50 (and / or the foot 45) abuts the plunger 12. A travel distance (TD) is the distance that the piston rod 50 (and thus the injection button 40) is allowed to travel relative to the housing structure 1, and therefore the cartridge 10 is also shown in Fig. 3, which is at least axially fixed to the housing structure 1. The axial position of this travel distance (TD) relative to the housing structure 1 can be adjusted by adjusting the position of the nut element 60, as will be explained below.

[0084] 9B-9C is located at the proximal-most end of the nut element 60. The actual physical position is therefore determined by the physical design of the nut element 60. However, independent of the design of the nut element 60, the starting position of the piston rod 50 is the position where the piston rod 50 (and / or foot 45) abuts the plunger 12.

[0085] The travel distance (TD) thus represents the distance that the piston rod 50 can move from its start position to its stop position. This length of the travel distance (TD) is therefore a fixed distance, but the physical location of the travel distance (TD) can be changed by adjusting the position of the nut element 60 relative to the housing structure 1 depending on the position of the plunger 12 within the individually filled cartridge 10.

[0086] Assembly of the injection apparatus: Different tolerances apply when filling individual cartridges 10 with liquid medicament. There are tolerances in the amount of liquid medicament filled into cartridge 10 from the fill line, and there are tolerances in the physical dimensions on cartridge 10. Cartridge 10 is typically filled by filling cartridge 10 with liquid medicament from the distal end of cartridge 10. Thus, plunger 12 is positioned in the distal portion of cartridge 10 before and during filling, and plunger 12 moves proximally to a position where the correct amount of medicament is loaded into cartridge 10. When filled, the distal end of the cartridge is sealed by septum 11. Therefore, due to various tolerances, the end position of plunger 12 when filled will vary from cartridge 10 to cartridge 10.

[0087] Furthermore, because cartridges 10 are typically formed from glass, the physical tolerances are relatively large. Different tolerances result in slightly different axial positions of plunger 12 within individual cartridges 10 after the liquid drug is loaded into the cartridges 10.

[0088] After the cartridge 10 is filled with the liquid agent, the cartridge 10 is pushed distally into the housing structure 1 such that the metal bends 15 on the cartridge 10 are pressed into the milled ribs 7 of the housing structure 1 as disclosed in Figure 9A, or alternatively, when the nut element 60 is positioned, it is pushed into the housing structure by the milled flanges 67 provided in the nut element 60. In the final position, the cartridge 10 is firmly secured to the housing structure 1 at least axially.

[0089] When the cartridges 10 are positioned and secured within the housing structure 1, the position of the plunger 12 is measured electronically by a computerized sensor system such that the exact position of the plunger 12 within each individual cartridge 10 is registered.

[0090] Once the position of the plunger 12 has been measured, the nut element 60 is screwed into the thread 5 within the housing structure 1 to a position where the piston rod 50 (when installed), or preferably the piston rod foot 45, engages the plunger 12. The axial position of the nut element 60 is therefore individually adjustable to an adjusted position during assembly of the injection device. The adjusted position is the position where the piston rod 50 (and / or the foot 45) abuts the plunger 50, which is also the starting position of the piston rod travel.

[0091] 9A discloses the position of the nut element 60 before the thread segments 65 engage with the threads 5 in the housing structure 1. In this position, the ratchet carrier 66 has not yet engaged with the axial rib 6 of the internal toothed ring in the housing structure 1.

[0092] When the nut element 60 is rotated to its adjusted position, the piston rod 50 is forced into the nut element 60 to a position where the first set 53 or radial or gripping arms 56 engage the angled front 64. This engagement defines the start position of the travel distance (TD). As best seen in Figures 3 and 9B, the start position is defined by the engagement between the first set 53 of radial arms and the angled front or gripping arms 56 and the angled front 64, all of which are physically located at the proximal end of the proximal flange 68 of the nut element 60.

[0093] Alternatively, the piston rod 50 can first be positioned in a releasable fixed position within the nut element 60 before the nut element 60 is screwed into the housing structure 1, and the nut element 60 can be rotated until the piston rod 50 (or the piston rod foot 45) abuts the plunger 12 within the cartridge 10.

[0094] In the disclosed embodiment, the nut element 60 is provided with several ratchet carriers 66 which engage with axial ribs 6 within the housing structure 1 such that the nut element 60 can rotate in only one rotational direction in the threaded connection between the threads 5 within the housing structure 1 and the thread segments 65 provided on the nut element 60.

[0095] In one embodiment, the pitch of the threads 5 in the housing structure 1 and the pitch of the thread segments 65 on the nut element 60 can be, for example, 2 mm, such that the nut element 60 is moved distally 2 mm per rotation. In such a configuration, for example, when 40 axial ribs 6 are provided in the housing structure 1, the nut element 60 can advance in increments of 0.05 mm (2 mm advance up to 40 ribs per rotation).

[0096] The permissible direction of rotation is the direction that moves the nut element 60 in the distal direction. Thus, when the nut element 60 reaches its adjusted position, it is not possible to rotate the nut element 60 in the proximal direction, since the ratchet interface 6, 66 only allows rotation in one direction. In an alternative embodiment, the nut element 60 can be irreversibly fixed to the housing structure 1 in the adjusted position, preferably by welding the nut element 60 to the housing structure 1, for example by using laser welding. For this purpose, the housing structure 1 can be provided with a transparent area, an opening or the like, to allow energy from a laser beam to be delivered to the area where the nut element 60 and the housing structure 1 have a physical contact point.

[0097] Once the nut element 60 is positioned in the adjusted position, the piston rod 50 is inserted as disclosed in Fig. 9B. In the adjusted position, the first set of radial arms 53 or radial gripping teeth 56 on the piston rod 50 grip behind the angled front portion 64 in the nut element 60 defining the start position shown in Fig. 9B. However, due to the axial extension that exists between the angled front portion 64 and the proximal flange 68 of the nut element 60, the start position is physically located at the proximal end of the proximal flange 68 but is defined by the engagement of the first set of radial arms 53 and the angled front portion 64 or the gripping arms 56 and the angled front portion 64.

[0098] The starting point of the piston rod travel may also be defined by frictional engagement of a further radial arm 58 and a recessed inner surface 63, as disclosed in Figures 4C-4D.

[0099] When the nut element 60 is in the adjusted position and the piston rod 50 is attached in the starting position, the distal end of the piston rod 50 preferably physically contacts the proximal rear side of the plunger 12 such that there is no physical distance between the piston rod 50 and the plunger 12. However, some loosening is allowed due to temperature fluctuations.

[0100] In the disclosed embodiment, a separate piston rod foot 45 is provided that can be inserted into the cartridge 10 prior to inserting the piston rod 50. When such a piston rod foot 45 is used, physical contact is between the piston rod foot 45 and the plunger 12.

[0101] When the piston rod 50 is inserted as disclosed in Fig. 9B, the first set of radial arms 53 are positioned distal to the angled front portion 64 and bent towards the inner surface of the nut element 60, thereby guiding and stabilizing the axial movement of the piston rod 50 during injection. The first set of radial arms 53 also prevent the piston rod 50 from moving in the proximal direction, but allow the piston rod 50 to move a small distance when the liquid agent expands due to temperature fluctuations within the cartridge 10. However, it is not possible for a user to move the piston rod 50 in the proximal direction and thereby disassemble the injection device.

[0102] Once the injection device has been assembled as disclosed in FIG. 9B, it is ready for use, sterilized, individually packaged in sterile packaging, and delivered to the end user.

[0103] During injection, the user applies pressure on the injection button 40. This is indicated by the arrow "P" in FIG. 9C. This pressure moves the injection button 40, and thereby the piston rod 50, in a distal direction. Axial movement of the piston rod 50 is permitted until the stop surface 57 on the piston rod 50 abuts the proximal end of the nut element 50, as disclosed in FIG. 9C. Once the piston rod 50 is within the stop position, the second set of flexible arms 54 engage against the angled surface 64 such that the piston rod 50 cannot move in a proximal direction.

[0104] As shown in Figures 9B and 9C, the axial movement of the piston rod 50 from a start position to a stop position determines the distance the piston rod 50 can travel in one single stroke. The position of this travel distance (TD) relative to the housing structure 1 and cartridge 10 is adjustable by adjusting the position of the nut element 60 relative to the housing structure 1. Preferably, the position of the travel distance (TD) is adjusted such that the piston rod 50 is in physical contact with the plunger 12 at the start position. The absence of an air gap between the piston rod 50 (and / or foot 45) and the plunger 12 ensures that the total stroke length of the piston rod 50 translates one-to-one into plunger travel.

[0105] The volume expelled during injection is determined by a first position of the plunger 12 before injection, disclosed in FIG. 9B, and a second position of the plunger 12 after injection, disclosed in FIG. 9C, combined with the internal dimensions of the individual cartridge 10.

[0106] When the piston rod 50 (or the piston rod foot 45) initially abuts against the plunger 12 in the first position, the travel distance (TD) of the piston rod 50 is converted into a similar movement of the plunger 12 within the cartridge 10, and therefore the length of the travel distance (TD), i.e., the distance between the start and stop positions of the piston rod 50, and the length between the first and second positions of the plunger 12, are the same.

[0107] Although some preferred embodiments have been shown above, it is emphasized that the present invention is not limited thereto and can be embodied in other ways within the scope of the subject matter defined in the following claims. The key issue reflected in the claims is to avoid that after assembly, an air gap exists between the plunger and the piston rod foot, and part of the travel distance (TD) is consumed by this air gap and therefore not fully transferred to the plunger travel. [Table 1]

Claims

1. A single - dose injection device for delivering a predetermined amount of a liquid agent, a housing structure (1) for fixing a cartridge (10) containing the liquid agent, wherein the cartridge (10) is axially locked to the housing structure (1), and the cartridge (10) has a distal end sealed by a pierceable partition (11) and a proximal end closed by a movable plunger (12) having a distal front face (13), the housing structure (1); a piston rod structure (50, 45) including a piston rod (50) and a piston rod foot (45), which is translationally movable in a distal direction relative to the housing structure (1), thereby moving the plunger (12) in the distal direction within the cartridge (10), and the plunger (12) is movable from a first position to a second position, the piston rod structure (50, 45); the predetermined amount of the liquid agent to be discharged is defined by the inner surface (14) of the cartridge (10) and the length by which the distal front face (13) of the plunger (12) is moved during the movement of the plunger (12) from the first position to the second position, and a nut element (60) for guiding the piston rod structure (50, 45) is adjustably coupled to the housing structure (1), a single - dose injection device, the piston rod structure (50, 45) and the nut element (60) are provided with engaging means (53, 56, 58; 63, 64) for removably fixing the piston rod structure (50, 45) to the nut element (60) at the starting position of the piston rod structure (50, 45), and the piston rod structure (50, 45) abuts against the plunger (12) at least during use, the stopping position of the piston rod structure is defined by a stopping means (57) on the piston rod (50) that operatively engages with the nut element (60), such that the moving distance (TD) of the piston rod structure (50, 45) is defined as the axial distance by which the piston rod structure (50, 45) is translationally movable when moving the plunger (12) from the starting position to the stopping position during dose discharge, The axial position of the nut element (60) relative to the housing structure (1) is individually adjustable for each individual injection device during the assembly of the individual injection device, whereby the axial position of the movement distance (TD) of the piston rod structure (50, 45) is adjusted to a position adjusted depending on the position of the plunger (12) within the individual cartridge (10). Single-dose injection device, characterized in that.

2. The engaging means (53, 64) between the piston rod (50) and the nut element (60) comprises a plurality of radial arms (53) provided on either the piston rod (50) or the nut element (60) and engaging with the other of the piston rod (50) or the nut element (60). The single-dose injection device according to claim 1.

3. The radial arm (53) is provided on the piston rod (50), and the nut element (60) comprises an angled surface (64) engaged by the radial arm (53) when the piston rod (50) is in its starting position. The single-dose injection device according to claim 2.

4. The engaging means (58, 63) between the piston rod (50) and the nut element (60) comprises a plurality of further radial arms (58) provided on the piston rod (50) and engaging with the recessed inner surface (63) on the nut element (60) at the starting position of the piston rod (50). The single-dose injection device according to claim 1.

5. The engaging means (56, 64) between the piston rod (50) and the nut element (60) comprises a plurality of radial gripping teeth (56) provided on either the piston rod (50) or the nut element (60) and engaging with the other of the piston rod (50) or the nut element (60). The single-dose injection device according to claim 1.

6. The radial gripping teeth (56) are provided on the piston rod (50), and the nut element (60) comprises an angled surface (64) engaged by the radial gripping teeth (56) when the piston rod (50) is in its starting position. The single-dose injection device according to claim 5.

7. The single - dose injection device according to claim 1, wherein the nut element (60) proximally physically defines the starting position of the piston rod (50) and engages with the stop means (57) on the piston rod (50) at the stop position, and comprises a proximal flange (68).

8. The single - dose injection device according to claim 1, wherein the nut element (60) is axially adjustable relative to the housing structure (1) by a threaded connection (5, 65).

9. The single - dose injection device according to claim 8, wherein the housing structure (1) comprises an internal thread (5) on an inner surface that engages with a corresponding thread (65) on the outer surface of the nut element (60).

10. The single - dose injection device according to claim 9, wherein the flange of the thread (5, 65) comprises an axial friction knob (69).

11. The single - dose injection device according to claim 8, wherein a one - way ratchet interface (6, 66) is provided between the nut element (60) and the housing structure (1).

12. The single - dose injection device according to claim 1, wherein one of the nut element (60) or the housing structure (1) comprises a flexible ratchet carrier (66), and the other of the nut element (60) and the housing structure (1) comprises an axial rib structure (6).

13. The single - dose injection device according to claim 1, wherein the nut element (60) and the housing structure (1) are irreversibly connected in an assembled state.

14. A method of assembling a single - dose injection device, wherein the single - dose injection device comprises a housing structure (1) for fixing a cartridge (10) containing a liquid agent, wherein the cartridge (10) is axially locked to the housing structure (1), the cartridge (10) has a distal end sealed by a pierceable septum (11) and a proximal end closed by a movable plunger (12) having a distal front face (13), and a housing structure (1), A piston rod structure (50, 45) including a piston rod (50) and a piston rod foot (45), which is translatable in a distal direction relative to the housing structure (1), thereby moving the plunger (12) in the distal direction within the cartridge (10), and the plunger (12) is movable from a first position to a second position, the piston rod structure (50, 45). A predetermined amount of the agent to be discharged is defined by the inner surface (14) of the cartridge (10) and the length by which the front surface (13) of the plunger (12) is moved during the movement of the plunger (12) from the first position to the second position, and A single-dose injection device in which a nut element (60) for guiding the piston rod (50) is adjustably coupled to the housing structure (1). The piston rod structure (50, 45) and the nut element (60) are provided with engaging means (53, 56, 58; 63, 64) for removably fixing the piston rod structure (50, 45) to the nut element (60) at the starting position of the piston rod structure (50, 45), and the piston rod structure (50, 45) abuts against the plunger (12). The stop position of the piston rod structure (50, 45) is defined by a stop means (57) on the piston rod (50) that operably engages with the nut element (60), and as a result, the movement distance (TD) of the piston rod structure (50, 45) is defined as the axial distance that the piston rod structure (50, 45) is translatable when moving the plunger (12) from the starting position to the stop position during dose discharge. The axial position of the nut element (60) relative to the housing structure (1) is individually adjustable for each individual injection device during the assembly of the individual injection device, thereby adjusting the axial position of the movement distance (TD) of the piston rod structure (50, 45) to a position adjusted depending on the position of the plunger (12) within the individual cartridge (10), a single-dose injection device. The method includes adjusting the axial position of the nut element (60) for each individual injection device during assembly, thereby adjusting the axial position of the travel distance (TD) of the piston rod structure (50, 45) relative to the housing structure (1) to an adjusted position where the piston rod structure (50, 45) abuts against the plunger (12). A method characterized by that.

15. A plurality of single-dose injection devices for delivering a predetermined amount of a liquid agent according to claim 1, wherein each of the plurality of single-dose injection devices is individually assembled and adjusted according to the method according to claim 14. A plurality of single-dose injection devices.

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