Piston Extension Rod for Injector Piston Attachment

Abstract

The present invention relates to a piston extension rod 1 for the attachment of a piston into an injector, the injector comprising a container having a longitudinal axis and an inner wall, a cavity (10) having an opening (22) and a base (20), and a piston (3) having elastomeric properties with a deformable sealing element (11), the deformable sealing element abutting against the inner wall (13) of the cylinder and sealing an annular gap between the piston and the inner wall of the cylinder, the piston extension rod having a total length which is at least 5% longer than the total piston cavity length of the piston measured from the piston cavity base (20) to the piston cavity opening (22), the piston extension rod for positioning the piston accelerating towards the container outlet end, entering the piston cavity (10), the impact surface (19) of the piston extension rod colliding with the piston cavity base (20) during an accelerating movement of at least 25 mm / min, so that during the collision between the piston extension rod and the piston, the collision and the continuous velocity in the direction of the container outlet end extend the piston along the longitudinal axis of the container, causing a contraction of the deformable sealing element (11) of the piston perpendicular to the longitudinal axis of the container, eliminating the contact of the sealing element with the inner wall of the container, enabling a passage for air (14) in the space between the piston and the chemical solution (23), and the contraction for stopping at the final piston position results in the re - establishment of the piston seal against the inner wall of the container.

Description

Technical Field

[0001] The present invention relates to a method for attaching a piston for an injector, the attachment method enabling positioning of the piston inside the gas filling compartment of the injector by its mechanical interaction with the piston. The piston attachment method comprises a novel piston extension rod according to the present invention and is intended for an optimized attachment of the piston in syringes, pre-filled syringes (PFS), and cartridges for the delivery of pharmaceutical compositions such as vaccines or biological agents.

Background Art

[0002] Known injectors are often constructed to be fillable and the piston is attached by an automatic filling and attachment device. Piston attachment relates to the method for attaching the piston, which is performed by different methods depending on the type of syringe in question. In one example, a conventional disposable syringe typically comprises a container, a piston, and a piston rod, and the piston is attached onto the piston rod before the piston rod having the piston is inserted into the container in order to reach the inner bottom of the container by the container outlet, or the piston can be attached in the container and then the piston rod can be attached.

[0003] In another example, a piston for a prefilled syringe (PFS) is attached after the container is filled, which is designed both to allow the piston to enter the PFS and to be positioned close to the drug without physical resistance from the air present between the top surface of the drug and the container opening, and is done by either a vacuum or mechanical attachment, where the physical resistance is an issue to be overcome during piston attachment in a drug-filled PFS as it prevents the piston from being properly attached by compressing it. The mechanical piston attachment, also known as vent tubing, was the first method introduced for PFS piston attachment and is done by inserting the piston into the tube after significant compression and then pushing the piston through the tube into the correct position in the PFS. This method ensures that excess air inside the PFS can bypass through the gap between the inner wall of the container and the outer wall of the tube, and that the piston can be positioned with a residual air volume typically in the range of 1 - 5 mm.

[0004] The vacuum piston attachment was developed as an alternative to the breakable vent tubing, where the intense compression and forces involved often result in damage to the piston sealing element and can damage the polytetrafluoroethylene (PTFE) coating used in more advanced pistons for sensitive biological formulations. Furthermore, vent tubing has an issue with compatibility for silicone-free applications as it cannot perform piston attachment and actuation through the vent tube without adding a lubricant, usually silicone, which due to excessive friction and significant temperature rise would cause significant damage to the piston sealing element.

[0005] Vacuum piston attachment is performed by automated equipment that includes a vacuum pump to create a vacuum in the container between the PFS finger flange and the top surface of the drug. The space, which defines the volume of air, when converted to a sufficient vacuum, pulls the piston into the container and further into the intended position just above the top surface of the drug. As opposed to vent tubing, vacuum attachment enables attachment with less residual air and even so-called bubble-free filling, which is advantageous for certain oxygen-sensitive drug applications. For larger containers and special applications with a smaller volume relative to the size of the container, vacuum alone may not be sufficient to pull the piston into the intended position, and thus, in such cases, an auxiliary vacuum attachment is utilized. The auxiliary vacuum attachment combines the vacuum attachment with the physical support of a push rod for positioning the piston.

[0006] Auxiliary vacuum is also used for PFS applications without silicone, which result in a higher coefficient of friction without lubrication of the piston and container compared to silicone-treated PFS.

[0007] Existing attachment methods are well known and utilized within the pharmaceutical industry. However, there are several scenarios and applications where the described plugging techniques are not sufficient.

[0008] The issues with vacuum attachment occur when the fill volume is substantially smaller than the physical total volume of the container in use. In an example, an injectable volume of 0.05 - 0.165 ml of eye drops is made from a 0.5 ml container body, leaving a residual volume of air of approximately 0.49 ml - 0.34 ml. The configuration requires a significant amount of vacuum to move the piston downward only by the distance from the container opening to the surface of the eye drops. As the vacuum increases, there is a real risk that the drug will be exposed to excessive temperatures and even boil, reducing the efficiency of the drug or even causing damage. At the same time, eye drops must never be exposed to silicone, and thus, the combination of a small fill volume and a silicone-free application requires an attachment method that addresses both issues.

[0009] U.S. Patent No. 5,411,489 discloses a filled syringe and a filled cartridge for administering various fluids to a patient. The objective of U.S. Patent No. 5,411,489 is to address the problem of inadequate sliding characteristics in filled syringes stored over long time periods, which is caused by the need to obtain a good leak-proof seal. The syringe comprises a barrel, a cup-shaped plunger, a plunger actuating cylinder, and a plunger rod. The plunger rod of U.S. Patent No. 5,411,489 has a tip with a convex surface at the distal end, a knob at the proximal end located outside the plunger actuating cylinder, and also a flange at the proximal end. The plunger rod is inserted into the plunger actuating cylinder and is configured to push against the inner wall of the cup-shaped plunger to deform the plunger. The syringe is filled with a drug or the like from a tapered tip to which a hypodermic needle can be attached after inserting the plunger into the syringe barrel.

[0010] WO 2019 / 199901 discloses a plunger and their use in a drug delivery device such as a filled syringe, a cartridge, or an auto-injector. The drug delivery device can be in an "expanded state" or a "storage mode" and can be changed to a "clamped state" or a "dosing mode" having a plunger. The plunger rod for the drug delivery device has an axial protrusion inserted into a cavity in the plunger, and when a sufficient distal force is applied via the plunger rod, this causes the axial protrusion to apply a distal force onto an engagement surface in the cavity. The plunger then extends axially along a stretch zone, slightly clamping the plunger around the stretch zone, and the clamping of the plunger reduces the radial compression onto the sidewall of the medical barrel, thereby enabling the plunger to be advanced downward more easily while maintaining a liquid-tight seal and container closure integrity.

[0011] WO2019 / 185101 discloses an injector having a stopper with a cavity, the location and design of which provides a reduced break-loose force (BLF) for the injector as compared to an injector having a stopper without a cavity.

[0012] In the field of filled syringes, there is a need for a simplified procedure for attaching a piston in a syringe that reduces the risk of damaging the pharmaceutical solution in the syringe. The present invention aims to address this need. SUMMARY OF THE INVENTION

[0013] The present invention is achieved by providing a novel method for attaching a piston in a pre-filled syringe (PFS). The method comprises providing an injector comprising a cylinder having a longitudinal axis and an inner wall, and a pharmaceutical solution defining a top surface of the drug; providing a piston having a cavity extending from a cavity opening to a cavity base so as to define the full length of the piston cavity, and a deformable sealing element; inserting the piston into the cylinder such that the deformable sealing element abuts against the inner wall of the cylinder and seals an annular gap between the piston and the inner wall of the cylinder; providing a piston extension rod having a full length and a collision surface that is at least 5% longer than the full length of the piston cavity; inserting the piston extension rod into the cavity of the piston and causing the base of the piston cavity to collide with the collision surface at a speed of at least 25 mm / min to extend the piston along the longitudinal axis of the cylinder, causing contraction of the deformable sealing element and creating a vent path for air in the space between the piston and the top surface of the drug; maintaining the speed of the piston extension rod to move the piston to a final piston position and comprising.

[0014] For example, the present invention provides a method of attaching a piston in a filled injector, the method comprising: providing an injector comprising a cylinder having an inner wall and an inner diameter and having an outlet at an outlet end opposite the working end, wherein the cylinder contains a chemical solution defining an upper surface; providing a piston having a piston body having a working surface opposite the outlet surface, an axial length between the working surface and the outlet surface, and a transverse diameter, wherein the piston body defines a piston cavity opening having an access diameter, and the piston comprises a deformable sealing element surrounding a stopper body at an axial location from the working surface and having an outer diameter larger than the transverse diameter; the piston comprising a piston cavity extending from the piston cavity opening to the base of the piston cavity, the piston cavity defining a total cavity length; providing a piston extension rod having a diameter not greater than the access diameter and a length at least 5% longer than the total cavity length, wherein the piston extension rod has an impact surface at an end thereof; inserting the piston into the cylinder at the working end such that the deformable sealing element seals an annular gap between the stopper body and the inner wall of the cylinder; inserting the piston extension rod into the piston cavity opening and causing the impact surface to impact the base of the piston cavity at a speed of at least 25 mm / min; moving the piston extension rod longitudinally from the working end of the cylinder to the outlet end of the cylinder to contract the deformable sealing element and create a passage for air between the deformable sealing element and the inner wall of the cylinder; maintaining the speed of the piston extension rod to move the piston to a final piston position; For example, moving the piston extension rod longitudinally from the working end of the cylinder to the outlet end of the cylinder causes the piston to extend longitudinally and contract the deformable sealing element, creating a passage for air between the deformable sealing element and the inner wall of the cylinder.

[0015] In this method, a piston is attached within a filled syringe. In this context, "attach" may also be referred to as "insert", and the two terms may be used interchangeably. Further, "piston" may also be referred to as "stopper", and the two terms may be used interchangeably. The piston cavity base is collided with the collision surface of the piston extension rod at a speed of at least 25 mm / min. The piston extension rod is generally accelerated from no speed to the collision speed, and thus, the speed may also be referred to as "accelerated movement", and the two terms may be used interchangeably in this context. The piston extension rod may also be abbreviated as PER, and the two terms may be used interchangeably in the context of this disclosure. The piston has a piston cavity opening. The "piston cavity opening" may also be referred to as the "cavity inlet" or the "piston cavity inlet", and these terms may be used interchangeably in the context of this disclosure. Generally, the piston cavity opening may have an access diameter. From this, for example, this method may also be considered as a method of inserting a piston into a cylinder, and this method providing an injector comprising a cylinder having an inner wall and an inner diameter, and an outlet at an outlet end opposite to the working end; a stopper having a stopper body having a working surface opposite to the outlet surface, an axial length between the working surface and the outlet surface, and a transverse diameter, wherein the stopper body defines a cavity inlet having an access diameter, the stopper comprising a deformable sealing element surrounding the stopper body in an axial location from the working surface and having an outer diameter larger than the transverse diameter, the stopper comprising a piston cavity extending from the cavity inlet to the base of the piston cavity, the piston cavity defining the total cavity length, providing a piston extension rod having a diameter less than or equal to the access diameter and a length at least 5% longer than the total cavity length, wherein the piston extension rod has a collision surface at an end of the piston extension rod, Inserting a piston into the cylinder at the working end such that a deformable sealing element seals the annular gap between the stopper body and the inner wall of the cylinder; Inserting a piston extension rod into the cavity inlet and causing the impact surface to collide with the base of the piston cavity with an accelerating movement of at least 25 mm / min; Deforming the deformable sealing element and moving the piston extension rod longitudinally from the working end to the outlet end of the cylinder to create a passage for air between the deformable sealing element and the inner wall of the cylinder; Comprising. For example, the piston can be moved to the final piston position.

[0016] The step of inserting the piston into the cylinder can use a dedicated tool. For example, the piston can be pre-inserted into the insertion tube before being inserted into the cylinder. The insertion tube can have an inner diameter that is the same as the inner diameter of the cylinder, or slightly smaller or larger than the inner diameter of the cylinder. For example, the inner diameter of the insertion tube can be in the range of 90% - 110% of the inner diameter of the cylinder. The length of the insertion tube is generally in the range of 80% - 200%, for example 100% - 150% of the length of the piston. By using the insertion tube, the insertion of the piston into the cylinder can be performed faster than when the insertion tube is not used, thereby providing a faster process for attaching the piston into the filled syringe.

[0017] When the piston is inserted into the cylinder, the piston extension rod is inserted into the cavity of the piston, and the piston cavity base is caused to collide with the collision surface of the piston extension rod at a speed of at least 25 mm / min. This speed ensures that the piston is extended along the longitudinal axis of the cylinder, while at the same time causing the contraction of the deformable sealing element, which in turn creates a vent path for air in the space between the piston and the upper surface of the drug. Thereby, the piston can be moved closer to the upper surface of the drug, and the air between the upper surface of the drug and the piston can be removed while the piston moves to the final piston position. In addition to the ability to bypass air from the PFS, the present invention introduces further significant advantages. The contraction of the sealing element allows for low friction without imparting normal strain and stress to the sealing element known from existing piston attachment systems. This method eliminates the need for a vacuum, including the investment in a vacuum system and the costs associated with the operation of the vacuum system.

[0018] Due to the low-friction attachment, the attachment speed can be significantly increased, thus making it possible to increase the annual production volume per unit of time. The speed can be, for example, in the range of 50 mm / min to 120,000 mm / min. After the piston cavity base is caused to collide with the collision surface, the speed does not have to be constant while the piston moves to the final piston position, and the speed can vary within the range of 25 mm / min to 120,000 mm / min, for example, the speed can be in the range of 50 mm / min to 20,000 mm / min, for example, 50 mm / min to 10,000 mm / min, 100 mm / min to 5,000 mm / min, 200 mm / min to 2,000 mm / min, or 400 mm / min to 800 mm / min. The lower power consumption and higher production volume per unit of time have a significant positive impact on the operation profile compared to both vent tubing and vacuum attachment. The appropriate speed of the piston extension rod can be selected for each piston characteristic and PFS configuration, and the speed range of the piston extension rod can be from at least 50 mm / min to the maximum speed of the automatic filling and attachment system to which the piston extension rod is attached. 2 ​

[0019] The cylinder has an inner wall and the cylinder may further define an inner diameter. However, in this context, the term "diameter" does not imply that the corresponding element must have a circular cross-section, and any desired cross-sectional shape may be used for the corresponding element. Thus, the cross-section of the cylinder may be polygonal, for example, triangular, square, pentagonal, hexagonal, etc., and in this case, the term "diameter" refers to the cross-sectional dimension, for example, the maximum cross-sectional dimension for the corresponding cross-sectional shape. Correspondingly, the cavity opening and the piston extension rod are not limited to circular shapes, may have any desired shape, for example, have a piston extension rod, and the cavity opening may have a cross-section that is polygonal, for example, triangular, square, pentagonal, hexagonal, etc., and in this case, the term "diameter" will refer to the cross-sectional dimension, for example, the maximum cross-sectional dimension for the corresponding cross-sectional shape. The polygonal cross-section is not limited to a polygon having equal angles and side lengths, i.e., a regular polygon, and similarly, the cross-section may also be elliptical. The dimensions of the piston extension rod may also be asymmetric along its longitudinal axis suitable for interaction with the piston cavity.

[0020] The piston may be defined to have a piston body. Generally, the piston body does not interact with the inner wall of the cylinder, and the cross-sectional shape of the piston body can be freely selected regardless of the cross-sectional shape of the deformable sealing element. The piston body generally has a transverse diameter smaller than the inner diameter of the cylinder. The piston has a deformable sealing element. The deformable sealing element is configured to abut against the inner wall of the cylinder and seal the annular gap between the piston and the inner wall of the cylinder. Thus, the deformable sealing element generally surrounds the stopper body and has an outer diameter larger than the inner diameter of the cylinder. For example, the outer diameter of the deformable sealing element may be 1.5% to 10% larger than the inner diameter of the cylinder, for example, 2% to 5% larger. When the outer diameter of the deformable sealing element is at least 1.5% larger than the inner diameter of the cylinder, especially when the deformable sealing element has a Shore A hardness in the range of 40 to 75, the container closure integrity (CCI) is ensured.

[0021] The piston extension rod can be attached onto the connector. In particular, the piston extension rod can extend from the connector. The connector has a size that enables the connector to be inserted into the cylinder while attaching the piston in the injector. For example, the connector has a diameter smaller than the inner diameter of the cylinder. The connector can have any length as required. For example, the combined length of the connector and the piston extension rod can be sufficient to move the piston to the final piston position where the exit surface of the piston contacts the chemical solution in the cylinder, for example, to move the piston onto the drug upper surface of the chemical solution.

[0022] The piston has a piston cavity opening. The piston can be described as having an operating surface on the side opposite to the exit surface, where the piston cavity opening is located on the operating surface. The operating surface and the exit surface are located at both ends of the piston body, i.e., both ends of the axial dimension. When inserted into the cylinder, the axial dimension of the piston body substantially coincides with the longitudinal axis of the cylinder. The operating surface can also be said to be at the operating end of the piston body, and the exit surface can also be said to be at the exit end of the piston body. When inserted into the cylinder of the injector, the exit end of the piston body faces the exit of the injector.

[0023] The exit surface of the piston is the surface facing the chemical solution in the cylinder of the injector. In the example, the exit surface of the piston contacts the chemical solution in the cylinder at the final piston position. Thereby, the method enables there to be substantially no residual air in the filled injector between the piston and the chemical solution. This is particularly advantageous for eye drops where the injection volume is typically very small, for example, 0.05 ml to 0.165 ml in a cylinder with a nominal dosage of 0.5 ml.

[0024] The piston has a cavity. The cavity can also be referred to as the "piston cavity", and the two terms can be used interchangeably. The cavity is configured to receive the piston extension rod, but is not limited in its shape in other respects. The cavity and the piston rod for use with an injector can each include an engagement device and a complementary engagement device, and the engagement device and the complementary engagement device can be freely selected. For example, the piston rod for use with an injector can include male threads, such as helical male threads, and the cavity can correspondingly include complementary female threads, such as helical female threads, and these threads thereby provide the engagement device and the complementary engagement device, respectively.

[0025] In an example, the cavity has a generally cylindrical shape. For example, the cavity can have a diameter that is substantially equal to the access diameter. In another example, the cavity has a generally conical shape in which the diameter of the cavity narrows from the cavity opening toward the piston cavity base.

[0026] In a specific example, the piston has a cavity as defined in WO2019 / 185101. From this, for example, the piston may comprise a deformable sealing element that is deformable from the piston cavity opening, for example, from the working surface to an axial location, and may comprise a cavity section that is expanded to the axial location of the deformable sealing element, the expanded cavity section having an axial extension within the range of 5% to 70% of the total length of the piston cavity, for example, within the range of 5% to 50% of the total length of the piston cavity, and the expanded cavity section having, for example, a lateral expansion that is larger than the piston cavity opening, for example, the access diameter, over its axial extension. This example with the expanded cavity section may also be referred to as a BLF reduction cavity. In the example, the lateral expansion of the expanded cavity section is, for example, at least 50% of the outer diameter of the deformable sealing element over the axial extension of the expanded cavity section and is larger than the piston cavity opening, for example, the access diameter. In an example of the present disclosure, the expanded cavity section has a lateral expansion up to 90%, for example 80%, 70%, or 60% of the outer diameter of the deformable sealing element.For example, the piston may have a piston body having an operating surface on the side opposite to the outlet surface, an axial length between the operating surface and the outlet surface, and a transverse diameter, and the piston is provided, at an axial location from the operating surface, with a deformable sealing element made of, for example, a thermoplastic elastomer (TPE), the deformable sealing element surrounding the piston body and having an outer diameter larger than the transverse diameter, for example, the deformable sealing element having an axial extension within the range of 5% to 95% of the axial length of the piston body, the deformable sealing element sealing an annular gap between the piston body and the inner wall of the cylinder, and when the piston is inserted into the cylinder, the piston is provided with a cavity section expanded at the axial location of the deformable sealing element, the expanded cavity section having an axial extension within the range of 5% to 50% of the total length of the piston cavity, the expanded cavity section having, for example, across its axial extension, a piston cavity opening, for example, having a transverse diameter larger than the access diameter and within the range of 50% to 90% of the outer diameter of the deformable sealing element.

[0027] A piston, for example, the piston body, may have a tubular section for accommodating a piston rod or receiving a piston extension rod, and the tubular section extends from a piston cavity opening, for example, from the working surface of the piston, to an enlarged cavity section. When the piston has a tubular section, the piston cavity opening may have an access diameter. Specifically, when an injector having the piston of this example is fitted with a piston rod, a cavity may be formed at the interface between the piston body and the piston rod and / or at the interface between a deformable sealing element and the piston rod when the injector is ready for use. Generally, the enlarged cavity section is at least 50% of the outer diameter of the deformable sealing element and has a lateral expansion portion larger than the access diameter. In particular, the enlarged cavity section is larger than the access diameter. When the piston comprises an enlarged cavity section at the axial location of the deformable sealing element defined from the working surface, i.e., when there is an overlap between the axial location of the deformable sealing element and the cavity, and when the cavity has a diameter larger than the access diameter, especially when the diameter of the cavity is in the range of 50% - 90%, for example, 60% - 80% of the outer diameter of the deformable sealing element, the formation of an air escape path is obtained more easily than when the piston has a smaller-sized cavity. This is particularly relevant when the speed is relatively low, for example, in the range of 25 mm / min to 800 mm / min. This effect is also particularly relevant when the deformable sealing element has a Shore A hardness in the range of 40 - 75, and is even more relevant when the deformable sealing element is made of TPE, for example, when the piston is injection molded from TPE.Furthermore, when the injector comprises an enlarged cavity section as defined above, i.e., when the cavity has a diameter larger than the access diameter, in particular when the diameter of the cavity is in the range of 50% to 90%, for example 60% to 80%, of the outer diameter of the deformable sealing element, when the cavity has an axial extension within the range of 5% to 50% of the total length of the piston cavity, and when the tubular section for accommodating the piston rod or receiving the piston extension rod has the access diameter, the injector fitted with the piston and the appropriate piston rod will have a reduced breakout force (BLF) compared to an injector having a piston without an enlarged or BLF-reducing cavity section.

[0028] In another aspect, the present invention relates to a kit of parts comprising an injector, the injector having a cylinder with a longitudinal axis and an inner wall, for example a cylinder having an inner diameter, a piston having an operating surface on the side opposite the outlet surface and having a transverse diameter, wherein the piston comprises a deformable sealing element that surrounds the piston body in an axial location from the operating surface and has an outer diameter larger than the transverse diameter, and at the axial location of the deformable sealing element, a widened cavity section having an axial extension within the range of 5% to 50% of the total length of the piston cavity, the piston having a piston cavity that defines the total length of the piston cavity, i.e., a cavity extending from the piston cavity opening in the operating surface, i.e., from the piston cavity opening in the operating surface to the piston cavity base, the cavity comprising a tubular section extending from the piston cavity opening, i.e., from the operating surface, and having an access diameter, the widened cavity section having, for example, a transverse expansion that is larger than the access diameter, for example at least 50% of the outer diameter of the deformable sealing element, up to 90% of the outer diameter of the deformable sealing element, for example up to 80%, up to 70%, or up to 60% of the outer diameter of the deformable sealing element, and a piston extension rod having a diameter less than or equal to the access diameter and a length that is at least 5% longer than the total length of the piston cavity, for example, the piston extension rod extending from a connector. The piston may have an axial length, for example, between the operating surface and the outlet surface. The deformable sealing element is generally configured to seal the annular gap between the piston body and the inner wall of the cylinder when the piston is inserted into the cylinder.

[0029] The kit of parts may comprise any additional elements such as an actuator, a processor unit, and the like, for carrying out the method of the present invention. In an example, the deformable sealing element has a Shore A hardness in the range of 40 to 75. For example, the deformable sealing element may be made of TPE. For example, the piston may be injection molded from TPE as a single part, for example. In an example, the piston extension rod comprises a backstop located at the end opposite the impact surface. The backstop has a lateral size with respect to the piston extension rod, which is larger than the piston cavity opening, for example, the access diameter. The lateral dimension of the backstop is smaller than the inner diameter of the cylinder. Thereby, it is prevented that the piston is pushed too deeply into the cylinder of the filled injector. For example, the piston extension rod may have a length in the range of 10% to 30% of the total cavity length.

[0030] It can be said that the tubular section is configured to receive the piston extension rod, and the tubular section generally extends from the piston cavity opening to the cavity section widened therefrom.

[0031] In an example, the piston extension rod has a diameter, and the access diameter is in the range of 10% to 500% larger than the diameter of the piston extension rod. Further, the piston extension rod may have a length that is 5% to 80% longer than the total length of the piston cavity, for example, 5% to 50% longer than the total length of the piston cavity.

[0032] The deformable sealing element can be made from any suitable elastomeric material. In an example, the deformable sealing element, and optionally the piston body as well, are made from TPE, for example, by injection molding from TPE. Any TPE can be used for the pistons of the present invention, for example, also for the deformable sealing element and the piston body. Suitable TPEs include SBCs, such as hydrogenated - H - SBC - (SEBS - styrene - ethylene - butylene - styrene or the like) or non - hydrogenated (SBS - styrene - butadiene - styrene) or alloys thereof and other compatible polymers, for example, COC elastomers, or styrene - butadiene (SB), styrene - isoprene - styrene (SIS), styrene - isoprene - butadiene - styrene (SIBS), styrene - ethylene - ethylene - propylene - styrene (SEEPS), or alloys of any of these compounds. Preferred SBCs are those known under the trademark Evoprene, as commercially available from AlphaGary Corporation (Leominster, MA, USA) and Mexichem Specialty Compounds. Evoprene is described in the booklet "EVOPRENE (trademark) Thermoplastic Elastomer (TPE) Compounds - GENERAL INFORMATION" (issued by AlphaGary, July 2007), and the preferred Evoprene (trademark) polymers are Evoprene (trademark) Super G, Evoprene (trademark) G, Evoprene (trademark) GC, and Evoprene (trademark) HP, respectively described in the booklets "EVOPRENE (trademark) SUPER G Thermoplastic Elastomer (TPE) Compounds", "EVOPRENE (trademark) G Thermoplastic Elastomer (TPE) Compounds", "EVOPRENE (trademark) GC Thermoplastic Elastomer (TPE) Compounds", and "EVOPRENE (trademark) HP Thermoplastic Elastomer (TPE) Compounds" (issued by AlphaGary, July 2007).The content of all the referenced brochures by AlphaGary is hereby incorporated by reference into this specification. Other relevant elastomers include COC elastomers, such as TOPAS® Elastomer E-140. TPEs can be selected based on the permeability of gases, such as oxygen, and generally, especially for pistons of filled syringes, it is preferred that the gas permeability be as low as possible. SIBS TPEs generally have very low gas permeability and are, therefore, suitable for pistons of filled syringes. Other relevant elastomer materials include rubbers, such as natural rubber, synthetic rubbers (polyisoprene rubber, butyl rubber, halobutyl rubber), silicone rubber, and the like, as well as thermoplastic vulcanizates (TPV).

[0033] The elastomer material can be defined in terms of its hardness, for example, indicating the elasticity of the elastomer material and with respect to a Shore durometer that measures the hardness of the elastomer material, where the higher the durometer, the harder the compound. Materials defined by Shore A hardness are preferred, and the Shore A hardness can be in the range of 40 to 75. The measurement of Shore A hardness is well known to those skilled in the art, and in particular, the Shore A hardness is generally recorded in accordance with the ISO868 standard.

[0034] TPE can also be defined by its compression set value (typically expressed as a percentage) which corresponds to the deformation remaining after the force applied to it has been removed. The compression set value is typically recorded at a specified temperature over a specified time period, for example, in the range of 18 to 96 hours or 22 to 72 hours, according to, for example, the ISO815 standard. In the context of the present invention, the compression set is generally recorded at "ambient temperature", for example, in the range of 10°C to 40°C. However, the temperature range can also extend beyond ambient temperature, for example, to 23°C to 100°C. Generally, the higher the temperature, the shorter the time associated with recording the compression set. The compression set should generally be as low as possible, but for the stopper or part of the stopper of the present invention, the compression set can be, for example, in the range of 15% to 40% at ambient temperature. At a higher temperature, for example, 100°C, the compression set will typically be higher, for example, up to 50%. However, the compression set at ambient temperature is preferably in the range of 10% to 40%. The compression set value is generally associated with a filled injector when the stopper is inserted into the cylinder and thus compressed when the filled injector is stored over a long time period. The stopper, for example, the stopper body and the deformable sealing element, also have a Shore A hardness in the range of 30 to 90, for example, 50 to 90, and a compression set value in the range of at least 25%, for example, 25% to 35%, when the BLF of the filled injector of the present invention will decrease, for example, during storage over at least 5 days, and thus the stopper of the present invention is particularly advantageous for filled injectors.

[0035] The deformable sealing element is preferably convex. In this context, the term "convex" means that a straight line between any two points within the deformable sealing element does not intersect the surface of the deformable sealing element. Any convex shape is contemplated, but the deformable sealing element preferably has a point representing the maximum extension from the central axis of the stopper, for example, a point within the axial plane of the stopper.

[0036] In certain examples, the deformable sealing element is made from a TPE having a Shore A hardness in the range of, for example, 40 to 75. This enables the piston to be inserted into the cylinder and moved to its final piston position in the absence of external lubricant.

[0037] The present invention provides a piston extension rod for piston attachment into an injector, the injector comprising a cylinder having a longitudinal axis and an inner wall, and a piston having an elastomeric property having a cavity and a deformable sealing element, the deformable sealing element abutting against the inner wall of the cylinder and sealing an annular gap between the piston and the inner wall of the cylinder, the piston extension rod for piston positioning accelerating towards the container outlet end, entering the piston cavity, the lowermost surface of the piston extension rod colliding with the base of the piston cavity during the accelerating movement, such that during the movement of the piston extension rod, the piston extension rod extends the piston along the longitudinal axis of the cylinder, causing contraction of the deformable sealing element of the piston, eliminating contact of the sealing element with the inner wall of the container, enabling escape of air in the space between the piston and the injectable liquid, and the contraction for stopping at the final piston position results in re - establishment of piston sealing against the inner wall of the container.

[0038] A piston attachment method with a novel attachment component called a piston extension rod enables precise attachment without vacuum or the use of piston compression by venting tubing. According to a preferred example, the piston extension rod can be cylindrical along its longitudinal axis parallel to the longitudinal axis of the container. In other examples, it can be oval, square, or rectangular as required for cooperation with a specific piston cavity. In a further example, the piston extension rod can have outward protrusions or inward grooves to correspond to the interaction with the piston cavity, and the protrusions and / or grooves are established along the longitudinal axis of the piston extension rod. According to the present invention, the piston extension rod has a length along its longitudinal axis parallel to the longitudinal axis of the container that exceeds the piston cavity depth along the longitudinal axis of the container by at least 5%. In particular, it is preferred that only the impact surface of the piston extension rod, i.e., at the base of the piston cavity, impacts the piston. For example, the piston extension rod may not have a portion or section, such as a backstop, that can impact the surface of the piston having an inlet to the cavity. However, the piston extension rod can also have a backstop, and the backstop can control the maximum extension of the piston during attachment. During piston attachment, the piston extension rod will accelerate and enter the piston cavity. When the piston extension rod accelerates and moves downward to reach the base of the piston cavity, the acceleration of the piston extension rod extends the piston upon impact with the base of the piston cavity and continues the final positioning of the piston near the upper surface of the drug. The piston extension is caused by the acceleration of the piston extension rod and the impact of the fixed piston with its cavity base in combination with the elastomeric properties of the piston. Simultaneously with the extension, the piston extension causes a contraction of the piston perpendicular to the longitudinal axis of the container, thereby completely or partially releasing the piston sealing element from contact with the inner wall of the container and ultimately creating the necessary escape path for the excess air present between the piston and the upper surface of the drug.The contraction of the piston is a natural result of the piston extension function and the elastomeric component of the piston that contracts when extended. The contraction is caused by an impact from the piston extension rod into the piston cavity base at its rest position, but the contraction is maintained by a combination of the speed of the piston extension rod during final piston positioning and the reciprocating force friction caused by compressed air, which will accelerate through the escape path created between the contracted sealing element and the inner wall of the container. The contraction is maintained and only stops when the speed is reduced and the piston extension is reduced, stopping completely when the piston extension is zero, while the sealing ability between the piston sealing element and the inner wall of the container is restored and fully re-established at the final position of the piston.

[0039] In an aspect, the present invention provides a method of inserting a piston into a cylinder, such as an injector, particularly into the cylinder of an injector for delivering a pharmaceutical composition comprising a pharmaceutical solution. The method comprises providing an injector having a cylinder with an inner wall and an inner diameter and having an outlet at an outlet end opposite the working end, and a stopper having a stopper body having a working surface opposite the outlet surface, an axial length between the working surface and the outlet surface, and a transverse diameter, wherein the stopper body defines a cavity inlet having an access diameter, the stopper comprises a deformable sealing element surrounding the stopper body at an axial location from the working surface and having an outer diameter larger than the transverse diameter, the stopper comprises a piston cavity extending from the cavity inlet to the base of the piston cavity, the piston cavity defining the total cavity length, providing a piston extension rod having a diameter less than or equal to the access diameter and a length at least 5% longer than the total cavity length, wherein the piston extension rod has an impact surface at an end of the piston extension rod, inserting the piston into the cylinder at the working end such that the deformable sealing element seals an annular gap between the stopper body and the inner wall of the cylinder, Inserting a piston extension rod into the cavity inlet and causing it to collide with the base of the piston cavity at an accelerated movement of at least 25 mm / min on the collision surface; Moving the piston extension rod longitudinally from the working end of the cylinder to the outlet end of the cylinder to deform the deformable sealing element and create a passage for air between the deformable sealing element and the inner wall of the cylinder; It is provided. The piston extension rod is inserted into the cavity inlet and causes the collision surface to collide with the base of the piston cavity at an accelerated movement of at least 25 mm / min. However, it should be understood that it is the accelerated movement of at least 25 mm / min that causes the deformation of the deformable sealing element and creates a passage for air between the deformable sealing element and the inner wall of the cylinder. Therefore, it is contemplated that after the piston extension rod is inserted into the cavity inlet at a low speed, i.e., a movement of less than 25 mm / min, so that the collision surface collides with the base of the piston cavity, the speed is increased to reach an accelerated movement of at least 25 mm / min, which is within the scope of the present invention. Correspondingly, it is also possible to stop the movement of the piston extension rod after it is inserted into the cavity inlet. For example, the piston extension rod can be inserted into the cavity inlet at a high speed or a low speed, and then the movement can be stopped regardless of how much the piston extension rod is inserted into the cavity inlet. When the piston extension rod is inserted into the cavity inlet at a low speed, it is particularly relevant that the piston extension rod does not have a portion or section, such as a backstop, that can collide with the surface of the piston having the cavity inlet. For example, the piston extension rod can have a backstop located at a distance from the collision surface that is at least 10% longer than the piston cavity length. For example, the distance from the collision surface to the backstop can be at least 20% longer than the piston cavity length or at least 30% longer than the piston cavity length. In an example, the piston extension rod does not have a backstop. In an example, after the piston extension rod is inserted into the cavity inlet at a movement of less than 25 mm / min, the movement can be increased to an accelerated movement of at least 50 mm / min, at least 100 mm / min, at least 200 mm / min, or at least 400 mm / min.

[0040] Thereby, the piston extension rod, i.e., at the collision surface, i.e., pushes the piston through the collision surface and moves the piston. The movement of the piston using the piston extension rod causes deformation of the deformable sealing element, thereby creating a passage for air between the deformable sealing element and the inner wall of the cylinder. In this context, the accelerated movement can also be called speed, and the two terms can be used interchangeably. Generally, an accelerated movement of at least 25 mm / min is sufficient to deform the deformable sealing element and create a passage for air between the deformable sealing element and the inner wall of the cylinder. However, the greater the accelerated movement, the greater the deformation and the greater the passage for air. In other examples, the accelerated movement can be in the range of 50 mm / min to 10,000 mm / min, for example, 100 mm / min to 5,000 mm / min, 200 mm / min to 2,000 mm / min, or 400 mm / min to 800 mm / min.

[0041] The access diameter is equal to or greater than the diameter of the piston extension rod. In this context, this means that the piston extension rod can be inserted into the piston through the cavity inlet. From this, it is also contemplated that the access diameter can be smaller than the diameter of the piston extension rod. For example, the access diameter can be 5% smaller than the diameter of the piston extension rod. However, the exact ratio between the access diameter and the diameter of the piston extension rod is not critical, but it is preferred that the access diameter is at least 5% larger than the diameter of the piston extension rod. When the piston extension rod has a diameter smaller than the access diameter, the difference in diameter creates flexibility in the material of the piston, so that the piston can be extended more easily in the longitudinal direction of the cylinder. From this, when there is no space between the piston extension rod and the material of the piston, for example, when the access diameter is less than or equal to the diameter of the piston extension rod, an escape path for air is created more easily between the deformable sealing element and the inner wall of the cylinder than when the access diameter is greater than the diameter of the piston extension rod. The access diameter can be, for example, in the range of 10% larger than the diameter of the piston extension rod to 500% larger than the diameter of the piston extension rod. For example, it can be at least 10% larger than the diameter of the piston extension rod, or at least 20% larger than the diameter of the piston extension rod, or at least 30% larger than the diameter of the piston extension rod, or at least 50% larger than the diameter of the piston extension rod, or at least 100% larger than the diameter of the piston extension rod, or at least 200% larger than the diameter of the piston extension rod, or at least 400% larger than the diameter of the piston extension rod.

[0042] The method is particularly useful when the injector is an injector for the delivery of a pharmaceutical composition comprising a medicament solution. Therefore, the method allows the piston to be inserted into the injector while simultaneously removing the air between the piston and the surface of the medicament solution. This is particularly relevant for pre-filled syringes, especially pre-filled syringes intended for the delivery of small doses of, for example, eye drops.

[0043] This method enables, in particular, the insertion of a piston into an injector, i.e., into the cylinder of an injector, without the need for lubrication, such as silicone lubrication. An injector without silicone lubrication can have a piston made from a TPE such as SEBS, SBS, etc. In a particular example, the stopper comprises a cavity in the axial location of a deformable sealing element, the cavity having a lateral expansion portion that is larger than the access diameter of the cavity inlet. Such a stopper is described in WO2019 / 185101, the content of which is incorporated herein by reference. The presence of a cavity, such as a cavity having a lateral expansion portion larger than the access diameter of the cavity inlet, in the axial location of a deformable sealing element allows for even greater flexibility, thereby creating an easier escape path for air. The piston can have a single deformable sealing element, and a collision between the piston extension rod and the collision surface during an accelerating movement of at least 25 mm / min can create an escape path for air. The piston can also have two or more deformable sealing elements. When the piston has two or more deformable sealing elements, each sealing element abuts against the inner wall of the cylinder, whereby the deformation of the piston caused by the collision between the piston extension rod and the base of the piston cavity is greater than when the piston has a single deformable sealing element, and thus, an accelerating movement of at least 25 mm / min is sufficient to create an escape path for air when the piston has two or more deformable sealing elements.

[0044] In addition to the ability to bypass air from the PFS, the present invention introduces further significant derived advantages. The shrinkage of the sealing element enables low-friction, and in some cases even zero-friction, piston attachment without the normal strains and stresses on the sealing element known from existing piston attachment systems. The present invention eliminates the need for a vacuum, including the investment in the vacuum system and the costs associated with the operation of the vacuum system. Due to the low-friction attachment, the attachment speed can be significantly increased, thus enabling a greater annual production volume per unit of time. Lower power consumption per unit of time and higher production volume will have a significant positive impact on the operating profile compared to not only the vent tubing but also the vacuum attachment. The appropriate speed of the piston extension rod can be selected for each piston characteristic and PFS configuration, and the speed range of the piston extension rod is from at least 50 mm / min to the maximum speed of the automatic filling and attachment system to which the piston extension rod is attached. 2 It will have a significant positive impact on the operating profile. The appropriate speed of the piston extension rod can be selected for each piston characteristic and PFS configuration, and the speed range of the piston extension rod is from at least 50 mm / min to the maximum speed of the automatic filling and attachment system to which the piston extension rod is attached.

[0045] The piston extension rod can also function for manual piston attachment, but is preferably an integrated component for an automatic piston attachment system, such as a desktop system for multiple syringe filling and piston attachment lines or a larger piston attachment system.

[0046] For automatic attachment, the piston extension rod can be incorporated as a new or existing component in a new or existing PFS attachment system, replacing existing attachment components such as rods and pins for vent tubing and auxiliary vacuum attachment.

[0047] Existing filling and attachment systems are relatively similar to comply with common standards including ISO11040, where the most common brands are Bausch&Stroebel, Bosch, Syntegon, Groninger, Optima Packaging, Kaehle, and Colanar.

[0048] The piston extension rod can be manufactured from any desired material, such as metal, preferably hardened steel, but can also be manufactured from plastic compounds that are considered suitable for the purpose.

[0049] The piston extension rod is compatible with an elastomeric piston having a cavity, and such pistons are typically within the Shore A durometer range for an injector. These pistons typically have Shore A values in the range of 40 - 75. The axial dimension of the piston extension rod can vary in relation to the specific piston with which it cooperates. Its length is at least 5% longer than the piston cavity measured along the longitudinal axis of the container from the cavity base to the cavity opening, but the width of the piston extension rod will vary with the piston cavity diameter.

[0050] A reduction in the width of the piston extension rod at the lowest piston extension rod surface that impacts the piston cavity base implies an increase in the extension portion, while an increase in width will reduce the piston extension portion. The piston extension rod can incorporate a backstop that limits its stroke, and the backstop can be implemented in several ways, including a plate that interacts with the top surface of the piston as a physical brake, thereby limiting excessive extension of the piston.

[0051] For each individual injector / piston configuration, factors such as piston size, material hardness, thickness, coating, number of sealing elements, total sealing area, and container material that can affect the dimensions of the piston extension rod, the piston extension rod can be modified. The piston extension rod has the ability to achieve proper piston extension by varying its speed, but also by extending its length up to an increase of more than 5% of the total length of the piston cavity.

[0052] The injector piston is an elastomeric component having at least one deformable sealing element and can be made of any suitable elastomeric material such as natural rubber, TPE, styrene-butadiene block copolymer, polyisoprene, polybutadiene, ethylene propylene rubber, ethylene propylene diene rubber, silicone elastomer, fluoroelastomer, polyurethane elastomer, halobutyl rubber, and nitrile rubber, and can further be coated with PTFE or a similar coating type for friction reduction.

[0053] The piston attachment is carried out after filling the syringe, and the syringe is vertically positioned with the container outlet in a downward position and filled with an injectable liquid from its container opening in an upward position.

[0054] In an example, a standard 1 ml long glass PFS has a nominal volume, which is smaller than the total volume of the container to accommodate the piston and a portion of the piston rod attached into the piston after attachment of the piston. The nominal volume represents a stroke of about 32 mm, and the remaining stroke of about 21 mm represents the amount of air above the injectable liquid that must be bypassed so that the piston is attached closest to the drug upper surface.

[0055] It is further contemplated that the method of the present invention can also be used to attach a vial stopper into a vial. From this, in another aspect, the present invention relates to a method of attaching a vial stopper into a vial. The vial stopper has a cavity as generally defined for the piston, and any feature related to the piston to be attached into the cylinder of the injector is related to attaching the vial into the vial stopper.

[0056] Any embodiment of the present invention can be used in any aspect of the present invention, and any advantage for a particular embodiment is equally applicable when the embodiment is used in a particular aspect.

Brief Description of the Drawings

[0057]

Fig. 1a

Fig. 1b

Fig. 2

Fig. 3

Fig. 4

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Fig. 7

Fig. 8

Fig. 9

Fig. 10

Fig. 11

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Fig. 13

Embodiments for Carrying Out the Invention

[0058] The present invention is not limited to the embodiment(s) illustrated in the drawings. Therefore, when reference signs follow the features mentioned in the appended claims, it should be understood that such signs are included only for the purpose of enhancing the understanding of the claims and in no way limit the claims.

[0059] As used in this specification and the claims, the term "comprising" means "consisting at least in part of". When interpreting the descriptions in this specification and the claims that include the term "comprising", other features may exist in each description in addition to the features preceded by this term. Related terms such as "comprise" and "comprised" should be interpreted similarly.

[0060] The attachment process can be changed according to each application. The automatic attachment system often starts with pre-positioning to fix a piston just inside the top of a container that is often attached by a separate tool, followed by a two-step attachment that includes the actual downward movement and final positioning of the piston by placement pins or rods. The piston extension rod functions during the downward movement and final positioning of the piston and thus functions properly regardless of the pre-positioning configuration. Therefore, the piston extension rod is independent of the pre-positioning of the piston, and no example of pre-positioning affects other rights related to the invention of the piston extension rod and merely serves as an explanation.

[0061] Figures 1a and 1b show a piston extension rod 1 having a backstop 7 and a connector 21 for attachment on an automatic machine, and a rounded impact surface 19 of the piston extension rod 1 for cooperating with a piston cavity base 20 during piston positioning. The impact surface can have different shapes and, instead of being rounded, may be flat or pointed depending on the shape of the piston cavity base 20. Reducing the width of the piston extension rod 1 with respect to the piston cavity base 20 increases the extension portion, while increasing the width with respect to the piston cavity base 20 will result in a decrease in the extension portion.

[0062] Figure 2 shows the piston 3 after being pre-positioned inside the upper part 5 of the drug filling container, the air 14 between the piston outlet surface 15 and the upper surface 16 of the drug solution, the cavity opening 22, the piston cavity base 20, and the drug solution 23. The piston outlet surface 15 can also be referred to as the piston front surface 15.

[0063] Figure 3 shows an alternative piston 3 pre-positioned immediately above and outside the cavity opening 22, and the piston 3 held in place by a dedicated tool exemplified as an insertion tube 102 in Figure 3. The insertion tube 102 has an inner wall 103.

[0064] Figures 1 and 2 are, therefore, merely examples of pre-positioning. The pre-positioning is before the downward movement and final positioning by the piston extension rod 1 according to the present invention.

[0065] Figure 4 shows a piston extension rod 1 configured for the final positioning of the piston 3, which piston is a SEBS piston having a cavity 10 shown as an expanded cavity 10 and two sealing elements 11 with a Shore A hardness of 72. It can be seen that the piston extension rod 1 is positioned inside the pre-positioned piston 3 when it is just about to collide with or before colliding with the piston cavity base 20 during acceleration.

[0066] The piston extension rod 1 has a length 4 that exceeds the piston cavity length 6 by about 30%, and in this configuration, has a backstop 7 that limits the longitudinal extension of the piston 3.

[0067] Figure 5 shows the piston 3 in motion and extended after a collision between the collision surface 19 of the piston extension rod 1 and the piston cavity base 20, and its extended piston configuration is maintained during the movement of the piston extension rod 1 and the piston, for example, continuous movement. Also shown is the contraction of the piston in response to the extension of the piston, where the piston sealing element 11 is pushed away from their seals with the inner wall 13 of the container, resulting in an open passage 12 between the sealing element 11 and the inner wall 13 of the container for air to bypass.

[0068] Figure 6 shows the final positioning of the piston 3, where the extension and contraction of the piston are stopped and the complete seal of the piston sealing element 11 is re-established towards the inner wall 13 of the container.

[0069] Figure 7 shows an example of the piston 3 for attachment by the method of the present invention. The piston 3 has a piston body 31 having an operating surface 151 and an outlet surface 15, and its operating surface 151 is provided with a cavity opening 22, and the cavity 10 has a spiral female thread 221.

[0070] Figures 8 to 10 show an injector 100 having a piston 3, which illustrates the method of the present invention. Figures 8 to 10 show a cylinder 101 and illustrate the outlet end 17 and the working end 18 of the cylinder. From this, in Figure 8, the piston 3 is inserted into the cylinder 101 and is ready for attachment in the present method. In Figure 9, the piston cavity base 20 is made to collide with the collision surface 19 of the piston extension rod 1 to extend the piston 3 in the longitudinal dimension of the cylinder 101, whereby the piston 3 is contracted to create an open passage 12 between the deformable sealing element 11 and the inner wall 13 of the cylinder 101, so that air 14 can exit from the space between the piston 3 and the upper surface 16 of the chemical solution. In Figure 10, the piston 3 is in its final position such that the outlet surface 15 of the piston contacts the chemical solution in the cylinder 101. Example

[0071] In the example, the method is appropriately modified but otherwise carried out with conventional vent pipe equipment, where the vent pipe is replaced by a simple fixture for holding the piston. The piston placed is relatively upwardly disposed relative to the cylinder opening before the piston extension rod starts to deform. Specifically, the piston is placed in an insertion tube having an inner diameter slightly larger than the inner diameter of the syringe in this case. The steps of the process are shown in Figure 11, where the reference number of item C is understood to be related to items A, B, and D - H. A shows the filled cylinder 101 before the insertion of piston 3, B shows the piston 3 inserted into the insertion tube 102. C shows the piston extension rod 1 extending from the connector 21 and inserted into the cavity (not shown in Figure 11) of the piston 3. D shows the piston extension rod 1 being moved at a speed intended to illustrate the contraction of a deformable sealing element (not shown in Figure 11), and the arrows respectively show the moving direction and contraction of the piston extension rod 1. E shows that the piston 3 has been moved to its final position before the movement of the piston extension rod 1 stops. F and G show the piston 3 in its final position where the deformable sealing element abuts against the inner wall 13 of the cylinder and the piston extension rod 1 has been removed. H shows the injector 100 in its final filled stage. This setup is illustrated in Figure 12. In this setup, an attachment speed of 300 mm / second is used, and the acceleration and deceleration are at least 10 mm / second 2 was carried out.

[0072] The relevant parameters are provided in Table 1 with reference to Figure 13.

[0073]

Table 1

[0074] The method of the present invention has thus been applied via high - speed industrial machinery having a speed of up to 60,000 units / hour, but the method can also be carried out using smaller benchtop equipment in isolators for small - batch or customized applications.

Description of Symbols

[0075] 1 Piston extension rod 100 Injector 101 Cylinder 102 Insertion tube 103 Inner wall of the insertion tube 10 Cavity 11 Deformable sealing element of the piston 12 Open passage 13 Inner wall of the cylinder 14 Air 15 Outlet surface of the piston 151 Actuating surface of the piston 16 Upper surface of the chemical solution 17 Outlet end of the cylinder 18 Actuating end of the cylinder 19 Collision surface 20 Base of the piston cavity 21 Connector 22 Cavity opening 221 Spiral female thread 23 Chemical solution 3 Piston 31 Piston body 4 Length 5 Upper part of the container 6 Piston cavity length 7 Backstop

Claims

1. A method for attaching a piston in a filled injector, the method comprising: providing an injector comprising a cylinder having a longitudinal axis and an inner wall, and a chemical solution defining a drug upper surface; providing a piston having a cavity extending from a piston cavity opening to a piston cavity base so as to define the full length of the piston cavity, and a deformable sealing element; inserting the piston into the cylinder such that the deformable sealing element abuts against the inner wall of the cylinder and seals an annular gap between the piston and the inner wall of the cylinder; providing a piston extension rod having a full length at least 5% longer than the full length of the piston cavity and a collision surface; inserting the piston extension rod into the cavity of the piston and causing the base of the piston cavity to collide with the collision surface at a speed of at least 25 mm / min to extend the piston along the longitudinal axis of the cylinder, causing contraction of the deformable sealing element to create a vent path for air in the space between the piston and the drug upper surface; maintaining the speed of the piston extension rod to move the piston to a final piston position A method for attaching a piston in a filled injector.

2. The method for attaching a piston in a filled injector according to claim 1, wherein the piston comprises a deformable sealing element at an axial location from the piston cavity opening, and a cavity section expanded at the axial location of the deformable sealing element, the expanded cavity section having an axial extension within a range of 5% to 70% of the full length of the piston cavity, and the expanded cavity section having a lateral expansion larger than the piston cavity opening.

3. The method for attaching a piston in a filled injector according to claim 2, wherein the lateral expansion of the expanded cavity section is within a range of 50% to 90% of the outer diameter of the deformable sealing element.

4. The piston has a tubular section for receiving the piston extension rod, the tubular section extending from the piston cavity opening to the cavity section widened from the piston cavity opening, a method for attaching a piston in a filled injector according to claim 2 or 3.

5. The piston extension rod has a diameter, and the piston cavity opening has a diameter 10% to 500% larger than the diameter of the piston extension rod, a method for attaching a piston in a filled injector according to any one of claims 1 to 4.

6. The cylinder has an inner diameter and an outlet at an outlet end opposite to the working end, the piston has a piston body with a transverse diameter smaller than the inner diameter of the cylinder, and the deformable sealing element surrounds a stopper body and has an outer diameter 1.5% to 10% larger than the inner diameter of the cylinder, a method for attaching a piston in a filled injector according to any one of claims 1 to 5.

7. The piston has a working surface on the side opposite to the outlet surface, and the outlet surface of the piston contacts the chemical solution in the cylinder at the final piston position, a method for attaching a piston in a filled injector according to any one of claims 1 to 6.

8. The piston extension rod has a length 5% to 50% longer than the total length of the piston cavity, a method for attaching a piston in a filled injector according to any one of claims 1 to 7.

9. The speed is in the range of 50 mm / min to 120,000 mm / min, a method for attaching a piston in a filled injector according to any one of claims 1 to 8.

10. The piston extension rod has outward projections and / or grooves suitable for interaction with the piston cavity on its longitudinal axis, a method for attaching a piston in a filled injector according to any one of claims 1 to 9.

11. At least one of the deformable sealing element and the piston and the deformable sealing element has a Shore A hardness in the range of 40 to 75, a method for attaching a piston in a filled injector according to any one of claims 1 to 10.

12. A method for attaching a piston in a filled injector according to any one of claims 1 to 11, wherein at least one of the deformable sealing element and the piston and the deformable sealing element is made of a thermoplastic elastomer.

13. A kit of parts comprising an injector, wherein the injector comprises a cylinder having a longitudinal axis and an inner wall, a piston having a working surface on the side opposite to the outlet surface and a piston body having a transverse diameter, wherein the piston comprises a deformable sealing element that surrounds the piston body and has an outer diameter larger than the transverse diameter in an axial location from the working surface, and an expanded cavity section having an axial extension within a range of 5% to 50% of the total length of the piston cavity at the axial location of the deformable sealing element, the piston having a cavity that extends from a piston cavity opening to a piston cavity base so as to define the total length of the piston cavity, the cavity comprising a tubular section that extends from the piston cavity opening and has an access diameter, and the expanded cavity section having a transverse expansion portion larger than the access diameter, a piston extension rod having a diameter not exceeding the access diameter and a length at least 5% longer than the total length of the piston cavity and is provided with a kit of parts.

14. The kit of parts according to claim 13, wherein the transverse expansion portion of the expanded cavity section is within a range of 50% to 90% of the outer diameter of the deformable sealing element.

15. The kit of parts according to claim 13 or 14, wherein the tubular section extends from the piston cavity opening to the expanded cavity section.

16. The kit of parts according to any one of claims 13 to 15, wherein the piston extension rod has a diameter, and the access diameter is within a range 10% to 500% larger than the diameter of the piston extension rod.

17. The kit of parts according to any one of claims 13 to 16, wherein the piston extension rod has a length 5% to 50% longer than the total length of the piston cavity.

18. The piston extension rod has outward projections and / or grooves suitable for interaction with the piston cavity along its longitudinal axis, the kit of parts according to any one of claims 13 to 17.

19. The deformable sealing element, or the piston and the deformable sealing element, have a Shore A hardness in the range of 40 to 75, the kit of parts according to any one of claims 13 to 18.

20. At least one of the deformable sealing element and the piston and the deformable sealing element is made of a thermoplastic elastomer, the kit of parts according to any one of claims 13 to 19.

21. The piston extension rod extends from a connector, the kit of parts according to any one of claims 13 to 20.

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