EA042833B1 - SYSTEM AND METHOD FOR ASSEMBLY OF PISTON ROD AND SYRINGE - Google Patents

Description

Priority is claimed for U.S. Provisional Application No. 62/477,521, filed March 28, 2017, the entire contents of which are incorporated herein by reference.

The field of technology to which the invention belongs

The present invention relates generally to medical syringes, and more particularly to mechanisms and methods for connecting a plunger rod to a syringe assembly in the form of a medical syringe.

Prerequisites for the creation of the invention

A conventional medical syringe includes a syringe assembly containing a liquid such as a drug or a pharmaceutical product, and a piston rod connected to the syringe assembly. The plunger rod may be connected to the plunger located in the syringe barrel assembly after the syringe has been filled with liquid. The piston may include internal threads sized to fit into the external threads of the distal end of the piston rod. When the distal end of the piston rod is screwed onto the piston, the piston rod is connected to the syringe assembly. The force applied to the plunger rod can then drive the plunger through the syringe barrel to dispense the liquid contained in the syringe. The piston rod includes a proximal end of the rod having a flange which the operator can press with his thumb when grasping the syringe barrel between two fingers. Syringe assemblies are sized to hold different amounts of fluid, and plunger rods can also be sized to fit their counterpart in the syringe assembly. When connecting the piston rod to the piston, care must be taken not to apply excessive pressure, which can lead to premature release of fluid and / or a violation of the integrity of the seal of the sealed pre-filled syringe container. In a pre-filled syringe, the filling level of the liquid inside the syringe barrel may vary within a batch of pre-filled syringes, and thus the position of the plunger within the syringe barrel may also vary within a batch. Thus, existing systems that connect piston rods to pre-filled syringes must be able to accommodate fill level fluctuations to prevent premature release of fluid.

The conventional machine used to connect piston rods and syringe assemblies is fully automated and is designed to perform a series of process steps, including loading piston rods and syringe assemblies into the machine, using the machine, connecting the piston rod to the piston, and unloading the finished product from the machine. Fully automated technology is especially useful for preparing large batches of 2000 or more connected piston rods and syringe assemblies. In order to adjust a fully automated machine to assemble piston rods and syringe assemblies of a different size, referred to herein as a changeover process, the machine must be partially disassembled, adjusted and/or reassembled prior to use. This changeover process often requires a skilled operator to handle the many components involved in dismantling, adjusting and equipping and reassembling the machine, which can be a very time consuming procedure. Moreover, the prior art machine has a large footprint and is generally unmovable after the machine has been installed in a technology laboratory. The use of such a machine for large batches may be impractical when assembling small batches and simply assembling syringe assemblies of different sizes.

Brief description of the invention

According to a first exemplary aspect, a machine for connecting a plunger rod to a syringe assembly may include a selectable pivoting portion comprising a tray having a mounting portion sized to accommodate the syringe assembly and an open portion that is positioned above the mounting portion and dimensioned to accommodate the piston rod. The drive device may be operatively connected to the selectable rotary part and configured to move the tray from the first position to the second position to connect the plunger rod to the syringe assembly. The selectable pivot may be selected from separate and interchangeable first and second pivots, the first pivot containing a tray configured to receive a first size syringe assembly and the second pivot containing a tray sized to accommodate a second size syringe assembly. , which is different from the first size.

According to a second exemplary aspect, a method for using a machine to connect a plunger rod to a syringe assembly may include detaching the second pivot portion from the drive device and connecting the first pivot portion to the drive device after detaching the second pivot portion from the actuator, the first pivot portion contains the first movable tray, made with the possibility of placing the syringe assembly of the first size. Then, the method may include placing the first syringe assembly on the first movable tray of the first rotary part, and the first syringe assembly includes a distal end and a proximal end, a syringe barrel and a plunger located inside the syringe barrel. Then, the method may include placing the first piston rod on the first tray of the first rotary part, and the first

- 1 042833 plunger rod includes a distal end of the rod and a proximal end of the rod, and moreover, the distal end of the rod is located above the proximal end of the first syringe assembly and aligned axially with the piston. In addition, the method may include activating a drive device connected to the first rotary part to move the first tray from the first position to the second position while applying force to the first piston rod, which leads to the connection of the first piston rod with the first syringe assembly.

According to a third exemplary aspect, a machine for connecting a plunger rod to a syringe assembly may include a pivoting portion having a movable tray containing a mounting portion sized to accommodate the syringe assembly, and an open portion located above the mounting portion, sized suitable for accommodating the piston rod. The drive device may be operatively connected to the rotary part and configured to move the tray from the first position to the second position to connect the plunger rod to the syringe assembly. The machine may further comprise an elongated pressure plate adjacent to the pivot portion and defining an inlet end and an outlet end, the inlet end being sized to accommodate the proximal end of the piston rod and applying a downward force to the proximal end of the piston rod when the piston rod is moved from input end to output end. A constant tension spring may be connected to the pressure plate, wherein the constant tension spring imparts a downward force to the pressure plate such that the downward force is transferred to the piston rod by the pressure plate as the tray moves between the first position and the second position.

According to a fourth exemplary aspect, a machine for connecting a plunger rod to a syringe assembly may include a pivoting portion having a movable tray containing a mounting portion sized to accommodate the syringe assembly, and an open portion located above the mounting portion, sized suitable for accommodating the piston rod. The machine may include a drive device operatively connected to the rotary part and configured to move the tray from the first position to the second position to connect the plunger rod to the syringe assembly. The push plate may be positioned adjacent to the pivot so that the tray moves under the push plate when the tray is moved from the first position to the second position, the push plate being capable of applying a downward force to the piston rod located in the open portion of the tray when the tray moves from the first position to the second position. The drive device may include a lever operatively connected to the rotary part and configured to be controlled to step the tray from the first position to the second position.

According to a fifth exemplary aspect, a machine for connecting a plunger rod to a syringe assembly may comprise a pivoting portion having a movable tray containing a mounting portion sized to accommodate the syringe assembly, and an open portion located above the mounting portion sized suitable for accommodating the piston rod. The drive device may be operatively connected to the rotary part and configured to step the tray from the first position to the second position only once in an actuating action to connect the plunger rod to the syringe assembly.

According to a sixth exemplary aspect, a method for using a machine to connect a plunger rod to a syringe assembly may include placing the syringe assembly on a movable tray of the pivot portion, the syringe assembly comprising a distal end and a proximal end, a syringe barrel, and a plunger located inside syringe barrel at the proximal end of the syringe assembly. Then, the method may include placing a plunger rod on a tray, wherein the plunger rod may comprise a distal end of the stem and a proximal end of the stem, and wherein the distal end of the plunger rod is positioned above the proximal end of the syringe assembly and axially aligned with the plunger. The method may include actuating a drive device operatively connected to the rotary part. In addition, the method may include stepping the tray from the first position to the second position only once in response to activation of the actuator, wherein a force may be applied to one or both of the syringe assembly and the plunger rod when the tray is incremented from the first position to the second position. position for connecting the plunger rod to the syringe plunger assembly.

According to a seventh exemplary aspect, a machine for connecting a piston rod to a syringe assembly may include a pivoting portion having a movable tray containing a mounting portion sized to accommodate the syringe assembly, and an open portion located above the mounting portion sized suitable for accommodating the piston rod. The drive device may be operatively connected to the rotary part and configured to move the tray from the first position to the second position to connect the plunger rod to the syringe assembly. In addition, the friction element may be located adjacent to the rotary part and under the pressure plate, and the friction element may be made with

- 2 042833 the possibility of contact with the syringe barrel assembly, which is carried by the tray, when the tray is moved from the first position to the second position with the application of a turning force to the syringe assembly and the syringe assembly is rotated relative to the piston rod when the tray is moved from the first position to the second position.

According to an eighth exemplary aspect, a method for using a machine to connect a plunger rod to a syringe assembly may include placing the syringe assembly on a movable tray of the turntable, the syringe assembly comprising a distal end and a proximal end, a syringe barrel, and a plunger located inside syringe barrel at the proximal end of the syringe assembly. The method may include placing a piston rod on a tray, the piston rod comprising a distal end of the rod and a proximal end of the rod, and the distal end of the piston rod being located above the proximal end of the syringe assembly and axially aligned with the piston. Then, the method may include activating a drive device operatively connected to the pivot portion to move the tray from the first position to the second position, and rotating the syringe assembly relative to the plunger rod while moving the tray between the first position and the second position, resulting in a threaded connection of the first threaded connection. parts at the distal end of the plunger rod with the second threaded part of the syringe plunger assembly.

According to a ninth exemplary aspect, a machine for connecting a plunger rod to a syringe assembly may include a pivoting portion having a movable tray containing a mounting portion sized to accommodate the syringe assembly, and an open portion located above the mounting portion, sized suitable for accommodating the piston rod. The machine may include a drive device operatively connected to the rotary part and configured to step the tray from the first position to the second position only once in an activating action to connect the plunger rod to the syringe assembly. The push plate may be positioned adjacent to the pivot so that the tray moves under the push plate when the tray is moved from the first position to the second position, the push plate being capable of applying a downward force to the piston rod located in the open portion of the tray when the tray moves from the first position to the second position. The drive device may include a servo and a function switch for operative control of the servo, the servo being connected to the tray stepper via the rotary.

According to a tenth exemplary aspect, a machine for connecting a plunger rod to a syringe assembly may include a base and a pivoting portion attached to the base and movable relative to the base, the pivoting portion comprising a movable tray having a mounting portion sized to suit to accommodate the syringe assembly, and an open portion which is positioned above the mounting portion and which is sized to accommodate the plunger rod. The drive device can be connected to the rotary part and made with the possibility of stepping the tray from the first position to the second position. The machine may include a pressure plate resting on the base and located near the rotary part in such a way that the tray moves under the pressure plate when the tray is moved from the first position to the second position, and the pressure plate is configured to apply a downward force to the piston rod located in open part of the tray. The tray may have a tray axis that is in line with the longitudinal axes of the syringe assembly and plunger rod when the syringe assembly and plunger rod are located in the tray, with the axis of the tray at an angle greater than zero degrees relative to the vertical.

According to an eleventh exemplary aspect, a machine for connecting a plunger rod to a syringe assembly may include a pivoting portion having a movable tray containing a mounting portion sized to accommodate the syringe assembly, and an open portion located above the mounting portion sized suitable for accommodating the plunger rod, an actuating device operatively connected to the pivot portion and configured to move the tray from a first position to a second position to connect the plunger rod to the syringe assembly, and a pressure plate located adjacent the pivot portion such that the tray moves under the pressure plate when the tray is moved from the first position to the second position, and the pressure plate is configured to apply a downward force to the piston rod located in the open part of the tray when the tray is moved from the first position to the second position. The machine may include at least one of the following aspects (a) to (e). According to aspect (a), a constant tension spring may be operatively connected to the pressure plate, and the pressure plate may define an inlet portion configured to receive the proximal end of the piston rod when the tray is moved from the first position to the second position. The constant tension spring may impart a downward force applied by the pressure plate to the piston rod as the tray moves between the first position and the second position. According to aspect (b) the friction element can be located next to the rotary part and under the pressure plate. The friction element may be configured to contact the syringe barrel assembly carried by the tray when the tray is moved from the first position to the second position. The friction member may be configured to apply a turning force to the syringe barrel to rotate the syringe assembly relative to the plunger rod as the tray moves from the first position to the second position. According to aspect (c) the drive device may be operatively connected to the rotary part and configured to step the tray between the first position and the second position in response to the activating action. According to aspect (d) the tray may have a tray axis that is in line with the longitudinal axes of the syringe assembly and plunger rod when the syringe assembly and plunger rod are located in the tray. The axis of the tray can be located at an angle greater than zero degrees relative to the vertical. Finally, according to aspect (e), the pivot part can be selected from separate and interchangeable first and second pivot parts. The first pivoting portion may include a tray having a mounting portion sized to accommodate a first size syringe assembly, and the second pivoting portion may include a tray having a mounting portion sized to accommodate a second size syringe assembly.

In accordance with the twelfth exemplary aspect, a method of using a machine for connecting a plunger rod to a syringe assembly may include placing the syringe assembly on a movable tray of the rotary part, the syringe assembly comprising a distal end and a proximal end, a syringe barrel, and a plunger located inside syringe barrel at the proximal end of the syringe assembly. Then, the method may include placing a plunger rod on a tray, wherein the plunger rod may comprise a distal end of the stem and a proximal end of the stem, and wherein the distal end of the plunger rod is positioned above the proximal end of the syringe assembly and axially aligned with the plunger. The method may include actuating a drive device operatively connected to the rotary part. In addition, the method may include stepping the tray from the first position to the second position more than once in response to activation of the actuator, wherein a force may be applied to one or both of the syringe assembly and the plunger rod when the tray is incremented from the first position to the second position. position for connecting the plunger rod to the syringe plunger assembly.

In addition, according to any one or more of the above first to twelfth aspects and methods, the piston rod-syringe assembly connecting machine and method of using the machine may include any one or more of the following forms or method steps.

In a preferred form, the machine may include a selectable pressure plate positioned above the tray such that the tray moves under the selectable pressure plate when the tray is moved from the first position to the second position. The selectable pressure plate may be configured to apply a downward force to the piston rod located in the open portion of the tray when the tray is moved from the first position to the second position.

In a preferred form of the machine, the first rotary part may comprise a first pressure plate connected to the first rotary part, and the second rotary part may comprise a second pressure plate connected to the second rotary part, whereby the selectable pressure plate is connected to the selectable rotary part.

In a preferred form, the machine may comprise a quick change fixture and a table, wherein a selectable turntable can be releasably coupled to the table via the quick change attachment.

In a preferred form of the machine, the first rotary portion may comprise a first base and the second rotary portion may comprise a second base, wherein the drive device may comprise a servo configured to be operatively coupled to the first and second bases.

In a preferred form, the machine may include a selectable friction element adjacent to the selectable pivot. The selectable friction member may be configured to contact the syringe barrel assembly carried by the tray as the tray moves from the first position to the second position. The friction member may be configured to apply a turning force to the syringe barrel to rotate the syringe assembly relative to the plunger rod as the tray moves from the first position to the second position.

In a preferred form of the machine, the first rotary part may comprise a first guide plate connected to the first rotary part and carrying the first friction element, and the second rotary part may comprise a second guide plate connected to the second rotary part and carrying the second friction element, whereby the selectable friction element carried by a selectable guide plate connected to a selectable turntable.

In a preferred form, the machine may comprise a selectable constant tension spring.

- 4 042833 niem, functionally connected to a selectable pressure plate. The selectable pressure plate defining the inlet may be configured to accommodate the proximal end of the piston rod when the tray is moved from the first position to the second position. The selectable constant tension spring may impart a downward force to the piston rod applied by the selectable pressure plate as the tray moves between the first position and the second position.

In a preferred form, the machine may include a servo and a function switch for operatively controlling the servo, the servo being connected to the tray moving rotatable portion via the rotatable portion.

In a preferred form of the machine, the inlet end may comprise an inclined surface located above the outlet end with respect to the turning portion.

In a preferred form, the machine may comprise at least one guide rod, the pressure plate being movably connected to the at least one guide rod in a direction parallel to the longitudinal axis of the turntable.

In a preferred form, the machine may include a threaded rod for adjusting the pressure plate relative to the turntable, whereby the pressure plate can be adjusted in a direction parallel to the longitudinal axis of the turntable to accommodate piston rods at different heights.

In a preferred form, the machine may include a friction element adjacent to the turntable and below the pressure plate. The friction member may be configured to contact the syringe barrel assembly carried by the tray when the tray is moved from the first position to the second position. The friction element may be configured to apply a turning force to the syringe barrel to rotate the syringe assembly relative to the piston rod.

In a preferred form of the machine, the friction element may be fixedly fixed relative to the tray.

In a preferred form, the machine may include a guide plate and the friction element may be attached to the guide plate.

In the preferred form of the machine, the friction element may be an elongated cord.

In a preferred form of the machine, the friction element may be made of an elastomeric material.

In a preferred form of the machine, the drive device may be configured to incrementally move the tray between a first position and a second position in response to an actuating action.

In a preferred form of the machine, the drive device may only step the tray once per activation action.

In a preferred form of the machine, the drive device may step the tray two or more times in an actuating action.

In a preferred form of the machine, the drive device may include a lever with which the user manually steps the tray from the first position to the second position.

In a preferred form of the machine, the lever may be movably attached to the base of the turntable, and the lever may be configured to perform an actuating action when the lever is moved from an idle position to an activated position.

In a preferred form of the machine, the actuating device may comprise a motor-driven yoke located adjacent to the lever, the yoke being operable to move the lever between an idle position and an activated position.

In the preferred form of the machine, the drive device may include a movable bracket for moving the lever.

In a preferred form, the machine may include a push plate adjacent to the pivot so that the tray moves under the push plate when the tray is moved from a first position to a second position, the push plate being configured to apply a downward force to a piston rod located in open portion of the tray when the tray is moved from the first position to the second position.

In a preferred form, the machine may include a non-latching function switch, pressed simultaneously by two hands, designed to carry out an activating action.

In a preferred form of the machine, the drive device may comprise a lever operatively connected to the rotary part, the lever being designed to be operated manually for the purpose of performing the activating action.

In a preferred form of the machine, the drive device may include a lever by which the user manually steps the tray from the first position to the second position.

In a preferred form of the machine, the tray mounting portion may comprise a first roller and a second roller separated by a gap. The first and second rollers of the installation part can be made with the possibility of contact with the syringe barrel assembly and holding the syringe barrel in the gap when carried by the tray, and the first and second rollers provide scrolling of the syringe assembly when the tray is stepped from the first position to the second position.

In a preferred form of the machine, each of the first and second rollers may have a pivot axis, wherein the first roller is rotatable about the pivot axis of the first roller and the second roller is rotatable about the pivot axis of the second roller.

In the preferred form of the machine, the servo may be programmed to respond to the actuating action by moving the turntable, the actuating action comprising actuating a function switch.

In a preferred form of the machine, the servo may be programmed to step the tray more than once in response to an actuating action.

In a preferred form of the machine, the servo may be operably connected to another rotary part.

In a preferred form of the machine, the tray may have a tray axis that is in line with the longitudinal axes of the syringe assembly and plunger rod when the syringe assembly and plunger rod are located in the tray, the tray axis being at an angle greater than zero degrees relative to the vertical.

In a preferred form of the machine, the turntable may comprise a turntable with a turn axis that is parallel to the axis of the tray, whereby the turntable's turn axis is at an angle greater than zero degrees relative to the vertical.

In a preferred form of the machine, the base may comprise a bottom surface located at a first angle relative to the horizontal, with the longitudinal axis of the tray offset from the vertical by a first angle.

In a preferred form, the machine may include a movable base for the piston rod, connected to the rotary part. The piston rod base may be positioned above the tray and may include an opening sized to accommodate a flanged proximal end of the piston rod, the opening being axially aligned with the open portion of the tray. The base for the piston rod may be movable with the tray from the first position to the second position.

In a preferred form, the machine may comprise a retaining cap having an outwardly projecting tongue positioned to protrude into a hole in the piston rod base, the retaining cap being releasably attached to the piston rod base. The holding cover may be fixed with respect to the pivot part and positioned in the hole when the tray is in the first position.

In a preferred form, the machine may comprise a selectable movable piston rod base coupled to a selectable pivot.

In the preferred form of the machine, the piston rod base may be selected from separate and interchangeable first and second piston rod bases, the first piston rod base having an opening sized to accommodate a first size flanged end of the piston rod, and the second piston rod base The piston is sized to accommodate the flanged end of the second size piston rod that is different from the first size.

In a preferred form of the machine, the pivoting portion may be rotatably positioned relative to the pressure plate.

In a preferred form of the machine, the turntable may comprise a plurality of trays carried by the turntable.

In a preferred form, the machine may include an outlet chute adjacent to the turntable in the second tray position. The outlet chute may be configured to receive the plunger rod and syringe assembly from the tray after the plunger shaft is connected to the syringe assembly.

In a preferred form, the first pivot may comprise a first outlet spout connected to the first pivot, and the second pivot may include a second outlet spout coupled to the second pivot, whereby the selectable outlet spout is connected to the selectable pivot.

In a preferred form of the machine, the discharge chute may comprise a ramp, the ramp having a slot sized to accommodate the plunger rod and syringe assembly after the tray has been moved to the second position.

In a preferred form, the method may include applying a downward force to the proximal end of the first piston rod while moving the first tray from the first position to the second position.

In a preferred form, the method may include stepping the tray from the first position to the second position two or more times in response to activation of the drive device.

In a preferred form, the method may include attaching the first rotary part to the table by means of a quick change attachment, the table being connected to a drive device.

In a preferred form of the method, detaching the second pivot portion from the drive device may include detaching a quick change attachment securing the second pivot portion to the table.

In a preferred form of the method, disconnecting the second rotary part from the driving device may include disconnecting the servo of the driving device from the receiving element of the second rotary part.

In a preferred form of the method, the connection of the first rotary part with the drive device may include the connection of the servomotor of the drive device with the receiving element of the first rotary part.

In a preferred form, the method may include, prior to disconnecting the second rotary part from the drive device, placing the second syringe assembly on the second tray of the second rotary part, the second tray is adapted to receive the second syringe assembly of the second size, the second syringe assembly includes a distal end and a proximal end, a syringe barrel, and a plunger located within the syringe barrel, wherein the second tray of the second pivot portion is sized to accommodate a second size second syringe barrel. In addition, a preferred form of the method may include placing the second piston rod on the second tray of the second rotary part, and the second piston rod contains the distal end of the rod and the proximal end of the rod, and wherein the distal end of the rod is located above the proximal end of the second syringe assembly and aligned with the axis c piston. In a preferred form, the method may include activating an actuator connected to the second pivot to move the second tray from the first position to the second position while applying force to the second piston rod, which results in the second piston rod being connected to the second syringe assembly.

In a preferred form of the method, stepping of the tray may include rotating the turntable about a pivot axis of the turntable.

In a preferred form of the method, pivoting the pivot may include pivoting the pivot more than zero degrees to incrementally move the tray from the first position to the second position.

In a preferred form of the method, the actuation of the drive device may include moving a lever, the lever causing the tray to be stepped from a first position to a second position by means of a rotary portion.

In a preferred form of the method, activation of the actuator may include operating a function switch coupled to a servo, the servo being adapted to move the yoke to move the lever.

In a preferred form of the method, activation of the drive device may include operating a function switch connected to the servo, the servo being operatively connected to the turntable.

In a preferred form, the method may include applying a downward force to the proximal end of the piston rod while moving the tray from the first position to the second position.

In a preferred form of the method, applying a downward force to the proximal end of the piston rod may include moving the piston rod under a pressure plate adjacent to the pivot while moving the tray from the first position to the second position.

In a preferred form, the method may include applying a pivoting force to the syringe barrel assembly while moving the tray from the first position to the second position.

In a preferred form of the method, the application of a pivoting force may include bringing the syringe assembly into contact with a friction element adjacent the pivoting portion while moving the tray from the first position to the second position. The syringe assembly can be made with the possibility of rotation around the longitudinal axis of the tray.

In a preferred form, the method may include rotating the pivot about the axis of rotation of the pivot in a first direction to incrementally move the tray from the first position to the second position.

In a preferred form of the method, pivoting the syringe assembly may include pivoting the syringe assembly in a direction opposite to the first direction of the pivot, the axis of rotation of the pivot being parallel to the longitudinal axis of the tray.

- 7 042833

Brief description of graphic materials

It is believed that the present invention will become more apparent from the following description taken in conjunction with the accompanying drawings. Some of the graphics may be simplified by excluding selectable elements to show other elements more clearly. Such exclusions of elements in some drawings do not necessarily mean the presence or absence of specific elements in any of the exemplary embodiments, except as expressly expressed in the corresponding description. In addition, none of the figures on the graphic materials are depicted with the obligatory observance of scale.

In FIG. 1 is a front perspective view of a first exemplary piston rod mounting machine with a piston rod and syringe assembly disposed thereon in accordance with the principles of the present invention.

In FIG. 2 is a partial front perspective view of the first exemplary piston rod mounting machine of FIG. 1 with piston rod and syringe assembly in an intermediate configuration.

In FIG. 3 is a rear perspective view of the first exemplary piston rod mounting machine of FIG. 1 with piston rod and syringe assembly in connected configuration.

In FIG. 4 is a front perspective view of the first exemplary piston rod mounting machine of FIG. 1 with the first piston rod and syringe assembly in a disconnected configuration and the second piston rod and syringe assembly in a connected configuration.

In FIG. 5 is a top perspective view of the first exemplary piston rod mounting machine of FIG. 1 showing a first exemplary piston rod positioning base, an exemplary first piston rod retaining cap, and a fastener.

In FIG. 6 is a top perspective view of the first exemplary piston rod mounting machine of FIG. 1 with a second exemplary piston rod positioning base and a second piston rod retaining cap without attachment.

In FIG. 7 is a plan view of the first exemplary piston rod retaining cap of FIG. 5.

In FIG. 8 is a plan view of the second exemplary piston rod retaining cap of FIG. 6.

In FIG. 9 is a perspective view of the guide assembly of the first exemplary piston rod mounting machine of FIG. 1, wherein the guide assembly includes a pressure block for pre-applying force.

In FIG. 10 is a perspective view of the pressure block for pre-applying the force of the guide assembly according to FIG. 9.

In FIG. 11 is a top perspective view of an adaptive drive system for use with the first exemplary piston rod mounting machine of FIG. 1.

In FIG. 12 is a perspective view of a second exemplary piston rod mounting system comprising the machine of FIG. 1 connected to the adaptive drive system of FIG. eleven.

In FIG. 13 is a perspective view of a third exemplary system for mounting a piston rod in accordance with the principles of the present invention.

In FIG. 14 is a side view of the third exemplary system for mounting the piston rod of FIG. 13.

In FIG. 15 is a front view of the third exemplary system for mounting the piston rod of FIG. 13.

Detailed description of graphic materials

A piston rod installation system for connecting the piston rod to a pre-filled syringe assembly is illustrated and described in this document. In FIG. 1-4 show a first exemplary piston rod inserter 10, shown at various stages of connecting the piston rod 14 and the pre-filled syringe assembly 18. FIG. 5-10 show the various components of the machine 10 in greater detail, while FIGS. 11 and 12 show an adaptive system for retrofitting a manual machine 10 according to FIG. 1-4 into the second exemplary piston rod mounting system, which is semi-automated. A third exemplary system for mounting a piston rod is shown in FIG. 13-15 and may include any or all of the various components of the previous depicted embodiments for connecting the piston rod 14 to the syringe assembly 18. The term syringe assembly 18 may refer to a pre-filled syringe or an empty syringe.

In FIG. 1 shows a first example of a system 10 for mounting a piston rod for connecting the rod

- 8 042833 piston with syringe assembly 18. The system 10 for installing the piston rod is a machine having a rotary part 22 with a movable tray 26 and a drive device 30 functionally connected to the rotary part 22 and configured to move the tray 26 from the first position to second position. The tray 26 includes a mounting portion 34 sized to accommodate the syringe assembly 18 and an open portion 38 which is positioned above the mounting portion 34 and sized to accommodate the piston rod 14. The illustrated example shows that the turntable 22 is a turntable with a plurality of trays 26 carried by the turntable 22 and located around the perimeter of the carousel 22. For ease of reference, one tray 26 will be described as follows: the turntable 22 rotates the tray 26 between the first position and second position. As used herein, loaded tray 26 refers to tray 26 on which plunger rod 14 and syringe assembly 18 are located. in which the piston rod 14 and the syringe assembly 18 are located on the tray 26, but not yet connected to each other.

The second position P2 (shown in FIG. 3) refers to any position of the loaded tray 26 after the piston rod 14 has been connected to the syringe assembly 18. In the context of this document, the expression syringe assembly 46 with the rod attached refers to the final product in which the piston rod 14 connected to the syringe assembly 18. The piston rod 14 and the syringe assembly 18 may be loosely attached to the tray 26, detachably attached to it, or suitably mounted on it.

The function and operation of the machine 10 will be described when the tray 26 is in three consecutive positions: the first position P1, the position between the first position P1 and the second position P2, and the second position P2. The machine 10 is configured to connect the piston rod 14 and the pre-filled syringe assembly 18 by moving the tray 26 from the first position P1 shown in FIG. 1 through the intermediate position shown in FIG. 2 and finally to the second position P2 shown in FIG. 3, in which the piston rod 14 is connected to the syringe assembly 18. The drive device 30, located inside the base 48 of the machine 10, rotates the rotary part 22 and the loaded tray 26 around the axis of rotation of the rotary part 22. When the rotary part 22 rotates, the loaded tray 26 passes through a guide assembly 50 attached to the base 48. The guide assembly 50 includes a pre-force push block 54 that is configured to apply a constant downward force to the piston rod 14 when the piston rod 14 contacts the pressure plate 58. At the same time, , the friction element 60 (FIG. 9) of the guide assembly 50 engages and applies a turning force (e.g., torque) to the syringe assembly 18 to rotate the syringe assembly 18 relative to the piston rod 14 as the loaded tray 26 passes under the pressure plate 58 The combination of the downward force applied by the pressure plate 58 and the turning force applied by the friction member 60 effectively engages the piston rod 14 with the syringe assembly 18 by the time the loaded tray 26 reaches the second position P2. In FIG. 3, the syringe assembly 46 with the stem attached is in the second position P2, adjacent to the outlet chute 62, which houses the syringe assembly 46 with the stem attached. The tray 26 is configured to discharge the syringe assembly 46 with the stem attached when the pivot portion 22 is rotated again and the tray 26 is configured to receive the syringe assembly 46 with the stem attached into the discharge chute 62 as shown in FIG. 4. The rotary portion 22 described herein may be controlled or controlled by a rotary actuator, but in other embodiments, a linear actuator may be provided. For example, the rotary part 22 may be replaced by a linear assembly line, such as a conveyor belt, in which the tray 26 steps along a linear path. The turntable 22 may include one or more movable trays 26 that are connected to a linear drive mechanism that moves the trays 26 along a linear path. In this example, guide assembly 50 may be positioned relative to a linear conveyor belt or other linear conveyance so as to cooperate with movable trays 26 to connect piston rod 14 to syringe assembly 18.

As shown in FIG. 1, 3 and 4, the machine 10 is oriented at an angle when the base 48 of the machine 10 rests on a flat surface. As shown in FIG. 3, the axis of rotation A of the turntable 22 is located at an angle α relative to the vertical V, and the bottom surface 66 of the base 48 is located at an angle β relative to the horizontal H. The axis of rotation and/or longitudinal axis A of the turntable 22 is also parallel to the axis B of the tray, which is located on one line with the longitudinal axes C of the piston rod 14 and the syringe assembly 18, when the piston rod 14 and the syringe assembly 18 are located in the tray 26. The axis B of the tray and the axis A of rotation are located at an angle α, which is greater than zero degrees relative to the vertical V. B in one embodiment, the angle α may be 1 to 10 degrees, 5 to 10 degrees, 5 to 15 degrees, 5 to 20 degrees, 5 to 30 degrees, or any other suitable angle.

As mentioned earlier, the term tray 26 refers to the structure that houses the stem 14

- 9 042833 piston and syringe assembly 18. Each tray 26 includes a mounting part 34 formed by a pair of rollers 68, a hole 70 of the positioning base 72 for the piston rod, and an open part 38 formed by a disc 74 for gripping the piston rod. The rollers 68, the piston rod positioning base 72, and the piston rod gripping disc 74 are attached to the rotary portion 22 and are rotatable about the pivot axis A when the rotary portion 22 is driven by the driving device 30. The positioning base 72 includes a plurality of evenly spaced holes. 70, and the piston rod gripping disc 74 comprises a plurality of evenly spaced openings 38. The positioning base 72 and the gripping disc 74 are spaced apart and positioned relative to the rollers 68 such that each tray 26 is defined by one opening 70, one opening 38, and one mounting portion 34 which are axially oriented to receive the plunger rod 14 aligned with the syringe assembly 18. Each roller 68 is rotatable about a pin 76 extending along the central axis D of the roller 68, with each pin 76 attached to the lower section 24 of the turning part 22. Each roller 68 is located at a predetermined distance from the adjacent roller 68 with the formation of a gap G, as a result of which the barrel 78 of the syringe can enter the installation part 34 between two adjacent rollers 68 and be in contact with them. The first and second adjacent rollers 68 of the mounting portion 34 are configured to contact the syringe barrel 78 assembly 18 and hold the syringe barrel 78 in gap G when carried by the tray 26.

The rollers 68 are positioned to freely hold the syringe barrel 78 assembly 18 when the syringe assembly 18 is attached to or otherwise located on the machine 10 in the first position P1, and to release the syringe barrel 78 when the tray 26 moves towards the outlet. chute 62. In the disclosed embodiments, the oblique orientation of the rotary portion 22 allows the tray 26 to hold the syringe barrel 78 as the tray 26 is moved from the first position P1 to the second position P2. Additionally, the inclined orientation of the machine 10 allows the tray 26 to discharge the syringe assembly 46 with the attached stem into the outlet chute 62 after the tray 26 passes the second position P2. When the turn portion 22 is rotated again, the syringe assembly 46 with the stem attached enters the slot 64 of the discharge chute 62 and the syringe assembly 46 with the stem attached can travel down the ramp 63 where the syringe assembly 46 with the stem attached remains until withdrawn. Slot 64 is sized to accommodate a particular size syringe assembly 18 so that the syringe assembly 46 with the plunger rod attached can be easily moved down slope 63 for storage in discharge chute 62. The slope 63 may be sized and slope to hold a lot of syringe assembly 46 with the plunger rod attached.

Tray 26 dimensions are based on the requirements for syringe assembly 18 and piston rod 14. In particular, the mounting portion 34 is sized to accommodate a particular type/size of syringe assembly 18, and the opening 38 and opening 70 of tray 26 are also sized to accommodate a particular type/shape of plunger rod 14. In the illustrated example, the machine 10 is specifically designed to connect a plunger rod 14 and a syringe assembly 18 of a particular size. In other embodiments, machine 10 may be configured to accommodate piston rods 14 and syringe assemblies 18 of different sizes. The machine 10 may be designed to accommodate a single size syringe assembly, such as a 2.25 ml glass syringe assembly 18. Thus, the distance between two adjacent rollers 68 is such that a syringe assembly 18 having a 2.25 ml syringe barrel 78 can be loosely attached to the tray 26. Each opening 38 of the piston rod gripping disk 74 is designed to accommodate the rod body 82 specific size plunger used with 2.25 ml syringe assembly 18. For a piston rod 14 with an X-shaped cross section, the open portion 38 may include a plurality of protrusions designed to accommodate the body 82 of the piston rod and limit the rotational, angular and transverse movement of the piston rod 14 relative to axis C when moving the loaded tray 26 from the first position P1 to the second position P2. Rollers 68, on the other hand, are freely rotatable about axis D and allow syringe barrel 78 to rotate about axis B of tray 26 when friction member 60 contacts syringe barrel 78, as will be described in more detail below. The rollers 68, the piston rod gripping disk 74, and the piston rod positioning base 72 may be positioned to accommodate the piston rod body 82 of a particular height.

The machine 10 can accommodate a variety of different fill levels for a particular size syringe assembly 18 via interchangeable plunger rod positioning bases 72 and 86. As shown in FIG. 5-8, the piston rod positioning base 72 is selected from separate and interchangeable first and second piston rod positioning bases 72 and 86. The first piston rod positioning base 72 includes an opening 70 sized to accommodate the proximal end 90 of a particular size piston rod 14, and the second piston rod positioning base 86 includes an opening 104 sized to accommodate the proximal end 90 of a different size piston rod 14 . The first piston rod positioning base 72 and the corresponding piston rod retaining cap 84 shown in FIG. 5 and 7 can be interchanged with another positioning base

- 10 042833 and the associated holding cap 84 shown in FIG. 6 and 8. The first and second piston rod positioning bases 72 and 86 may differ in height to accommodate piston rods of different heights, and they can have differing sizes of openings 70 and 104 to accommodate two sizes of proximal ends 90 of the piston rod. In the depicted embodiment, the holes 70 of the first positioning base 72 have a smaller radius than the holes 104 of the second positioning base 86. Although not shown, the machine 10 can be configured to operate with any number of different positioning bases for the piston rod, and the machine 10 is not limited to the two embodiments described and depicted herein.

Let's return to Fig. 5 and 6, which show that the first positioning base 72 for the piston rod and the retaining cover 84 are detachably attached to the machine 10. The first positioning base 72 for the piston rod is connected to the rotary part 22 and is located above the disk 74 to grip the piston rod so that the holes 70 located around the perimeter of the positioning base 72 are on the same axis as the openings 38 of the disk 74 for gripping. Each opening 70 is sized to accommodate the flanged proximal end 90 of the piston rod 14 and provides enough space to allow the flanged proximal end 90 of the rod to fall through the opening 70 when the tray 26 is moved from the first position P1 to the second position P2. Retaining cap 84 is positioned on top of positioning base 72 and includes an outwardly projecting tongue 94 positioned to protrude into opening 70 when positioning base 72 and retaining cap 84 are attached to machine 10. Both retaining cap 84 and positioning base 72 for the piston rod are releasably attached to the machine 10 by means of a threaded fastener 98. While the positioning base 72 is movably connected to the rotary part 22 (so that the positioning base 72 rotates with the rotary part 22), the holding cover 84 and the threaded fastener 98 are fixed are attached to the machine 10 and do not rotate with the rotary part 22 about the axis A. The retaining cover 84 provides the function of holding the piston rod 14 when the piston rod 14 is first placed on the tray 26. As shown in FIG. 1 and 2, the flanged proximal end 90 of the piston rod 14 enters the hole 70 of the positioning base 72 and abuts against the part 96 of the tongue 94 that protrudes into the hole 70. The part 96 of the tongue 94 located in the hole 70 holds the piston rod 14 in a suspended state. above the syringe assembly 18 located on the mounting part 34. When the loaded tray 26 is moved from the first position P1, the positioning base 72 rotates relative to the protruding tongue 94 and the opening 70 of the tray 26 moves away from the part 96 to release the piston rod 14 from it. The flanged proximal end 90 of the piston rod 14 falls down through the opening 70 of the positioning base 72 and the distal end 156 of the piston rod 14 contacts the piston 158 located in the syringe barrel 78 as shown in FIG. 2.

In FIG. 7 shows the first side 100a of the retaining cap 84 which is associated with the first positioning base 72 for the piston rod, and FIG. 8 shows the second side 100b of the retaining cap 84 which is associated with the second positioning base 86 for the piston rod. In each depicted embodiment, the protruding tab 94 of the retaining cap 84 includes an asymmetrically contoured edge 101a and 101b, the shape of which can match the flanged ends 90 of the various piston rods 14. Each side 100a and 100b of the retaining cap 84 includes a specific mark or marks 102a and 102b associated with respective marks 103a and 103b on the positioning base 72 and 86 for the piston rod. The pickup disc 74 also includes marks 105a and 105b that align with marks 102a and 102b to ensure holes 70 and 104 and openings 38 are aligned when the trays 26 are assembled. As shown in FIG. 5, marks 102a, 103a, and 105a can provide a visual indication that the piston cap 84 is properly aligned with both the first piston rod positioning base 72 and the pickup disc 74. To replace the first positioning base 72 for the piston rod with the second positioning base 86 for the piston rod, the threaded fastener 98, which includes a manually operated knurled handle, is removed from the machine 10, and the retaining cover 84 and the first positioning base 72 are also removed. The second positioning base 86 is placed on the turntable 22 so as to align the marks 103b with the corresponding marks 105b on the pickup disc 74. The holding cover 84 is turned over so that the second side 100b faces away from the turning part 22, and then placed on top of the second positioning base 86 so that the marks 102b of the holding cover 84 are aligned with the marks 103b of the second positioning base 86 and the marks 105b of the disc 74 to capture. After properly assembled, the protruding tab 94 is placed inside the hole 104 of the tray 26 in the first position P1. In the depicted embodiments, the machine 10 includes a plunger rod retaining cover 84 and plunger rod positioning bases 72 and 86 for suspending the plunger rod 14 over the syringe assembly 18 when it is loaded into the tray 26 at the first position P1. In another embodiment, piston rod 14 and syringe assembly 18 may be loaded together such that piston rod 14 is not held by retaining cap 84 and

- 11 042833 positioning base 72 and 86, and the distal end 156 may instead abut against the piston 158 when the tray 26 is in the first position P1. In this case, the positioning base and 86 and the retaining cover 84 may optionally be attached to the machine 10 such that the tray 26 is not limited to the openings 70 and 104 of the positioning base 72 and 86.

Guide assembly 50 in FIG. 9 and 10 includes a pressure block 54 for pre-applying the force of the machine 10 attached to the feed guide assembly 110. The feed guide assembly 110 includes a plurality of support rods 114 that connect the rod holding guide 116, the top feed guide 118, the guide plate 120, the bottom feed the guide 122 and the bearing base 126. In general, the guide 116 for holding the rod, the upper feed guide 118, the guide plate 120 and the bottom feed guide 122 are contoured so that they partially surround the outer perimeter of the rotary part 22 and correspond to it. The carrier base 126 is attached to the base 48 of the machine 10, and the support rods 114 support the rest of the feed guide assembly 110 and the pressure block 54 for pre-force application. The top and bottom feed rails 118 and 120 comprise cut ends 119 and 121, respectively, to accommodate and guide the loaded tray 26 and to prevent jamming when turning the turntable 22. A syringe barrel guide 130 attached to the top feed rail 118 assists the feed rails 118 and 120 by providing a barrier from the proximal end 132 of the syringe assembly 18 as the loaded tray 26 moves through the guide assembly 50 to the second position P2. As shown in FIG. 2, the syringe barrel guide 130 is an L-bracket sized to accommodate and guide the proximal end 132 of the syringe assembly 18.

In FIG. 9 shows a friction element 60 attached to the inner end surface 134 of the guide plate 120 and located adjacent to the pivot portion 22 and under the push plate 58. moving the tray 26 from the first position P1 to the second position P2. The friction element 60 thus applies a turning force to the syringe barrel 78 to rotate the syringe assembly 18 relative to the piston rod 14. In the illustrated example, the friction element 60 is an elongated cord that extends along the inner edge surface 134 of the guide plate 120 such that the friction element 60 remains in contact with the syringe barrel 78 as the syringe assembly 18 is moved along at least part of its path. from the first position P1 to the second position P2. When the tray 26 is moved from the first position P1 to the second position P2, the syringe assembly 18 passes through the guide assembly 50 and comes into contact with the friction element 60 protruding from the inner end surface 134 of the guide plate 120. The friction element 60 contacts the syringe barrel 78 and drives to the rotation of the syringe barrel 78 and the syringe assembly 18 about the longitudinal axis B of the tray 26. According to this configuration, when the tray 26 carries the syringe assembly 18 in the first direction, the friction element 60 comes into contact with the syringe barrel 78 and applies a turning force to the barrel 78 of the syringe, which causes the syringe barrel 78 to rotate between the rollers 68 of the tray 26 in the direction opposite to the first direction of rotation of the rotary part 22. At this time, the piston rod 14 located in the open part 38 of the tray 26 does not rotate relative to the tray 26 or the syringe assembly 18, but instead receives a downward force from the pressure block 54 to pre-apply the force.

In a preferred example, the pressure plate 58 of the pre-forced pressure block 54 applies a constant force (eg, approximately 2 N in some embodiments) to the piston rod 14 and the friction element 60 causes the syringe barrel 78 to rotate no more than four times to connect the piston rod 14 and syringe assembly 18. The length of the friction element 60 may be determined based on the mating relationship between the piston 158 of the syringe assembly 18 and the piston rod 14. For example, piston 158 may complete three revolutions relative to piston rod 14 before threaded distal end 156 of piston rod 14 properly engages piston 158. If friction member 60 causes syringe assembly 18 to rotate more than necessary, excessive rotational force applied to syringe assembly 18 may adversely affect plunger 158, syringe barrel 78, or some other component of syringe assembly 18. Thus, the length of friction member 60 is based on the minimum number of revolutions that syringe assembly 18 must make about axis B. so that the piston 158 is connected to the piston rod 14 sufficiently during one step movement and without damage. The friction element 60 may be made of an elastic material, such as silicone rubber, unfilled rubber, latex, or other suitable material, which would cause the syringe assembly 18 to rotate relative to the tray 26 in contact with the friction element 60. In another embodiment, the friction element 60 may be located on the rollers 68 rather than on the inner end surface 134 of the guide plate 120. In this example, the guide plate 120 may be positioned such that a portion of the guide plate 120 is in contact with the friction element 60 located on the rollers 68, whereby the rollers 68 rotate the syringe assembly 18 as the tray 26 moves through the guide assembly 50.

In FIG. 9 and 10, the pre-force push block 54 includes a base plate 136 attached to a stem retaining guide 116, a push plate 58, a constant tension spring 138 connected to the push plate 58, and first and second guide rods 142. 58 is positioned adjacent to the pivot portion 22 such that the tray 26 moves under the pressure plate 58 when the tray 26 is moved from the first position P1 to the second position P2. In other words, the pivot portion 22 is pivotally positioned relative to the pressure plate 58. The pressure plate 58 is configured to apply a downward force to the piston rod 14 located in the open portion 38 of the tray 26. In particular, the pressure plate 58 defines the input end 144 (shown in Fig. 2) and the output end 148, and the input end 144 has dimensions that are suitable for receiving the proximal end 90 of the piston rod 14 and applying a downward force to the proximal end 90 of the piston rod 14 when moving the piston rod 14 from the input end 144 to the output end 148. A constant tension spring 138 is connected to the pressure plate 58 and imparts a downward force to the piston rod 14 via the pressure plate 58 as the tray 26 moves between the first position P1 and the second position P2. The pressure plate 58 is elongated and includes an inclined surface 145 at the input end 144 to accommodate the proximal end 90 of the rod without colliding with the body 82 of the piston rod 14.

The push plate 58 is movably connected to the first and second guide rods 142, whereby the push plate 58 can move along the rods 142 in a direction parallel to the pivot axis A. Guide rods 142 extend through the first and second openings of the pressure plate 58 and attach the pressure plate 58 to the pivot portion 22 in an adjustable manner, whereby the pressure plate 58 can be adjusted to accommodate the piston rods 14 and the pistons 158 at different heights. The tension spring 138 passes through the third opening of the pressure plate 58 and is attached to the top surface 150 of the pressure plate 58, so that a constant force, such as 2 N, is always applied to the piston rod 14. That is, as the piston rod 14 moves from the first position P1 to the second position P2, the proximal end 90 of the piston rod 14 applies an upward force to the pressure plate 58 that may raise the pressure plate 58 slightly. piston 158. A threaded rod 152 extends through a passage in base plate 136 and is configured to contact bottom surface 154 of pressure plate 58 to adjust the height of pressure plate 58 along guide rods 142.

The pressure plate 58 can be adjusted to accommodate different fill levels of syringe assemblies 18 that correspond to different positions of piston 158 in syringe barrel 78. For example, it may be desirable to fill the syringe assembly 18 over the capacity of the syringe assembly marked with the fill line to ensure that the plunger 158 is located at a position that is above the fill line at the distal end 133 of the syringe assembly 18. In another example, it may be desirable to fill the syringe in assembly 18 below the fill line, indicating the capacity of the syringe assembly, to ensure that the plunger 158 is located in a position that is below the fill line. To accommodate a different fill level or piston rod height, the position of the pressure plate 58 relative to the tray 26 can be adjusted by turning the threaded rod 152 in a clockwise or counterclockwise direction to raise or lower the pressure plate 58 accordingly. Ruler 153 may be attached to the guide assembly 50 and remain stationary relative to the pressure plate 58 while the pressure plate 58 is moved. A ruler 153 may be used to measure the distance that the pressure plate 58 must be adjusted to accommodate standard fill levels. For example, a syringe assembly 18 having a 1 ml volumetric capacity may be filled to a fill level below or above the 1 ml fill line. The fill level, determined by the strokes of the measuring scale on the barrel 78 of the syringe, may indicate how much it may be necessary to adjust the position of the pressure plate 58 beyond the standard fill levels. The machine 10 and systems described herein can be configured to handle any number of different syringe assemblies 18 and are not limited to the 1 ml and 2.25 ml sizes described herein.

According to the present invention, the machine 10 is configured to incrementally move the tray 26 to connect the piston rod 14 to the syringe assembly 18. In one incremental rotation, the distal end 156 of the piston rod 14 can be threaded to the internal threads of the piston 158 located at the proximal end 132 of the syringe assembly 18. For example, a loaded tray 26 moves the piston rod 14 to contact the pressure plate 58, while the friction element 60 comes into contact with the cylinder 78 of the syringe to scroll the syringe assembly 18. The combination of downward force applied to the piston rod 14 of the pressure plate plate 58, and a turning force applied to the syringe assembly 18 by friction element 60, allows the threaded distal end 156 of the piston rod 14 to engage with the threaded surface of the piston 158. In some embodiments, the machine may not include a pressure plate 58 at all, and in such embodiments, the connection of the piston rod 14 to the piston 158 can be carried out solely by means of a friction element 60 imparting a turning force to the syringe barrel 78. In still other embodiments, the machine 10 may not include a friction element 60 at all, and in these embodiments, the connection of the piston rod 14 to the piston 158 can be carried out solely by applying a downward force to the piston rod 14 via the pressure plate 58. In the latter configuration, the piston rod 14 does not may necessarily be screwed into the 158 piston, but rather just a friction fit.

The machine 10 is designed or programmed to step the tray 26 such that the loaded tray 26 moves between the first position P1 and the second position P2 in one movement of the turntable 22. tray 26 so that piston rod 14 and syringe assembly 18 are connected in less than three seconds. Each incremental movement of the tray 26 may include a rotation of the rotary portion 22 approximately one third of a full 360 degree turn, such as 120 degrees about the axis A of rotation. For example, the tray 26 at the first position P1 can be rotated about the axis A of the rotary part 22 approximately 120 degrees relative to the first position P1 to reach the second position P2. Depending on the position of the guide assembly 50 and the size of the turntable 22, the turntable 22 can be configured to incrementally move the tray 26 with a rotation of less than 120 degrees about axis A. In this way, the machine 10 limits user error or repeated starting and stopping of a continuously running machine. Machine 10 is configured to connect one piston rod 14 to one syringe assembly 18 at a time.

The drive device 30 may be designed or programmed to step the tray 26 by the rotary portion 22 only once per activation action. The activating action may be, for example, manual operation of the lever 160 of the actuator 30 or actuation of a switch. A single push on lever 160, for example, activates a servo or other mechanically driven system of drive device 30 to increment tray 26 between a first position P1 and a second position P2. The drive device 30 can be further programmed such that the rotary portion 22 does not rotate until the lever 160 is pressed again, or until some other activating action occurs. In other embodiments, the implementation of the machine 10 may be activated using another suitable mechanism other than the lever 160.

The lever 160 of the manual machine 10 shown in FIG. 1-6 is operatively connected to the rotary part 22 and is configured to step the tray 26 between the first position P1 and the second position P2. Lever 160 is movably attached to base 48 and located within slot 164. When lever 160 is moved from its rest position to the leftmost end of slot 164, pivot portion 22 rotates until arm 160 returns to its original rest position in slot 164 The lever 160 may be coupled to a mechanical or electrical actuator located in the base 48 that converts the movement of the lever 160 into a pivoting movement of the pivot 22. In another embodiment, the actuator 30 may be designed or programmed to increment the tray 26 for more than one times during the activating action. For example, the slot 164 of the lever 160 may be provided with marks to indicate to which positions the lever 160 can be moved to increment the tray 26 a certain number of times. For example, when the lever 160 is moved to the first activated position, the tray 26 makes one step movement; and when the lever 160 is moved to an additional, second activated position along the slot 164, the tray 26 makes two incremental movements.

In FIG. 11 and 12 depict an adaptive system 170 for retrofitting the manual machine 10 shown in FIG. 1-6 into a semi-automated system 170 for installing a piston rod. In FIG. 11 shows an adaptive system 170, and FIG. 12 shows a machine 10 according to FIG. 1-6, fixedly mounted on the executive platform 172 of the adaptive system 170. The executive platform 172 accommodates and attaches the base 48 of the machine 10 to the table 178. The rigid element 182 is movably attached to the table 178 and extends vertically from the table 178 through the semi-circular bracket 186. The rigid member 182 moves the semi-circular bracket 186, which is configured to move smoothly across the table surface 178 when the rigid member 182 is activated to move the lever 160. As shown in FIG. 12, the rigid member 182 is positioned adjacent to the arm 160 of the machine 10 when the arm 160 is in the idle or non-activated position. The semi-circular brace 186 is shaped to fit the perimeter of the base 48, which has a complex shape. The servo 190, attached to the table 178, is operatively connected to the rigid member 182 via a wire located under the table 178. The first and second function switches 194, momentarily operated by both hands, are attached to opposite sides of the table 178 and are positioned to enable the operator to involved

- 14 042833 function switches 194 at the same time. The function switches 194 are connected to the servo 190 and are configured to actuate the servo 190 only when the switches 194 are pressed simultaneously. path to contact lever 160 until lever 160 reaches the leftmost end of slot 164. Servo 190 can only be programmed to move rigid member 182 once when both function switches 194 are operated to increment tray 26. Alternatively, servo 194 can be programmed to step more than once, if desired. In this case, the control panel connected to the activation switches 194 and the servo 190 can also be configured to step the tray 26 more than once when the control panel switch is activated.

Adaptive system 170 shown in FIG. 11 and 12 is a piston rod mounting system capable of converting a manual piston rod mounting system 10 to a semi-automated system using the existing machine 10 shown in FIG. 1-6. In the following FIGS. 13-15 show a semi-automated system 310 for installing a piston rod in accordance with another embodiment of the present invention. The system 310 for installing the piston rod is similar to the machine 10 described above, except that the system 310 is semi-automated and contains a different drive device 330. The elements of the system 310 in FIG. 13-15, which are similar to the elements of machine 10, have the same reference numerals, but increased by 300. The description of many of these elements has been abbreviated or even omitted for brevity.

The piston rod mounting system 310 shown in FIG. 13-15 includes a machine 312 and an outlet chute 362 attached to a removable base plate 472. The base plate 472 is detachably attached to the table 478 via a plurality of quick change fasteners 480. The drive device 330 is operatively connected to the rotary portion 322 and is movable in steps. tray 326 carried by pivot 322 from first position P1 to second position P2 to connect piston rod 14 to syringe assembly 18. Piston rod 14 and syringe assembly 18 are not shown with piston rod mounting system 310, but may be located either attached to the machine 312 in the same or similar manner as described and depicted in the previous figures. The drive device 330 includes a servo 490, as well as first and second function switches 494 for operational control of the servo 490. The servo 490 shown in FIG. 14 and 15 is attached to the table 478 and located under the machine 312 so that the servo 490 can be directly connected to the rotary part 322.

To convert to a syringe assembly 18 of a different size, the pivot 322 may be selected from separate and interchangeable first and second pivots. The system 310 is configured to allow an operator to easily detach the selectable rotary portion 322 and/or the machine 312 from the servo 490, which is connected or detachably attached to the table 478, and to replace the selectable rotary portion 322 with a first rotary portion suitable for placing a syringe in the collection 18 different size. The first pivoting portion 322 includes a tray 326 having a mounting portion 334 sized to accommodate a first size syringe assembly 18, such as a 1 ml syringe, and the second pivoting portion includes a tray having a mounting portion sized to accommodate the syringe in the collection of a second size, such as a 2.25 ml syringe. The servo 490 of the driving apparatus 330 is configured to be connected to the base portion 328 of the first rotary portion 322 and the base portion of the second rotary portion. For example, the servo 490 may include a splined shaft 332 or other suitable device extending into a receptacle 336 located in the base portion 328 of the rotary portion 322. The receptacle 336 of both the first rotary portion 322 and the second rotary portion is configured to be coupled to the splined shaft. 332 of the servo 490 when the base 348 of the machine 312 is attached to the table 478. The machine 312 and the outlet chute 362 can be interchanged with the second machine and the second outlet chute. Each machine 312 may include an attached guide assembly 350 and a pre-force push block 354 configured to interact with the pivot 322 as described above with respect to the machine 10 of FIG. 1-6.

For example, the selectable pivot 322 may be selected by the operator based on the size of the syringe assembly 18 to be assembled. Each selectable rotary portion 322 may correspond to a selectable pressure plate 358, a selectable friction element 360, and a selectable guide plate 420. The first rotary portion 322 includes a first pressure plate 358 connected to the rotary portion 322, and the second rotary portion includes a second pressure plate connected to the second turning part. The first turning part 26 includes a first guide plate 420 connected to the first turning part 322 and carrying the first friction element 360, and the second turning part includes a second guide plate connected to the second turning part and carrying the second friction element. Accordingly, the selectable pressure plate 358 is connected to the selectable rotary portion 322, and the selectable friction element 360 is carried by the selectable guide plate 420 connected to the selectable rotary portion 322.

According to the preferred method of using the system 10 and 310 to install the piston rod, the method may include placing the syringe assembly 18 on the tray 26 and 326 of the rotary part 22 and 322, and the tray 26 and 326 of the rotary part 22 and 322 are sized that are suitable for receiving the syringe in the collection of 18 specific size. The syringe assembly 18 includes a distal end 133 and a proximal end 132, a syringe barrel 78, and a plunger 158 located within the syringe barrel 78. The piston rod 14 is located on the tray 26 and 326 of the rotary part 22 and 322, and the piston rod 14 contains the distal end 156 of the rod and the proximal end 90 of the rod, and the distal end 156 of the rod is located above the proximal end 132 of the syringe assembly 18 and is aligned axially with the piston 158. After the piston rod 14 and the first syringe assembly 18 have been placed on the tray 26 and 326, the method includes activating an actuator 30 and 330 connected to the pivot portion 22 and 322 to move the tray 26 and 326 from position P1 to a second position P2 with application of force to the piston rod 14, which leads to the connection of the piston rod 14 with the syringe assembly 18.

Activation of the drive device 30 and 330 includes rotating the rotary portion 22 and 322 so that the tray 26 and 326 steps from the first position P1 to the second position P2, with the syringe assembly 18 and the piston rod 14 located on the tray 26 and 326 in the first position P1, and the piston rod 14 is connected to the syringe assembly 18 in the second position P2. In addition, the method includes rotating the rotary part 22 and 322 about axis A. When the tray 26 and 326 is between the first and second positions P1 and P2, the method includes applying a downward force to the proximal end 90 of the piston rod 14 while moving the tray 26 and 326 from the first position P1 to the second position P2. Applying a downward force to the proximal end 90 of the piston rod 14 includes moving the piston rod 14 under the pressure plate 58 and 358 adjacent the pivot portion 22 and 322 while moving the tray 26 and 326 from the first position P1 to the second position P2. In addition, the method includes applying a turning force to the barrel 78 of the syringe assembly 18 while moving the tray 26 and 326 from the first position P1 to the second position P2. The application of the turning force includes bringing the syringe assembly 18 into contact with the friction element 60 and 360 adjacent to the pivot portion 22 and 322 while moving the tray 26 and 326 from the first position P1 to the second position P2. When turning the rotary part 22 and 322 in the first direction, the rotation of the syringe assembly 18 includes bringing the barrel 78 of the syringe into contact with the friction element 60 and 360 and turning the syringe assembly 18 in a direction opposite to the first direction of rotation of the rotary part 22 and 322.

To convert the machine 10 and 312 in the second and third systems 170 and 310 to install the piston rod shown in FIG. 11-15, the method further includes detaching the rotary portion, such as the second rotary portion, from the drive device 30 and 330. Optionally, the method may include detaching the second rotary portion from the table 478 by disengaging a plurality of quick release or quick change fasteners 480 to remove the second base plate. from the table 478. Further, disconnecting the second rotary part from the drive device 330 includes disconnecting the splined shaft 332 of the servo 490 from the receiving element of the second rotary part. In addition, the method includes connecting the first rotary part 22 and 322 to the drive device 30 and 330 after disconnecting the second rotary part from the drive device 30 and 330. Connecting the first rotary part 22 and 322 to the drive device 30 and 330 may include connecting the splined shaft 332 of the servo 490 with the receiving element 336 of the first rotary part 22 and 322. The first rotary part 22 and 322 contains the first movable tray 26 and 326, configured to receive the syringe assembly 18 of the first size. Additionally, the method may include attaching the first rotary portion 22 and 322 to the table 478 and/or base plate 472 via quick-change fasteners 480. The method further includes placing the first syringe assembly 18 and the first piston rod 14 on the first movable tray 26 and 326 of the first rotary portion 22 and 322. After placing the first piston rod 14 and the first syringe assembly 18 on the tray 26 and 326, the method includes activating an actuator 30 and 330 connected to the first rotary part 22 and 322 to move the first tray 26 and 326 from the first position P1 to the second position P2 by applying force to the first piston rod 14, which results in the connection of the first piston rod 14 with the first syringe assembly 18. As mentioned above, the method includes applying a downward force to the proximal end 90 of the first piston rod 14 and/or turning force to the syringe barrel 78 of the first syringe assembly while moving the first tray 26 and 326 from the first position P1 to the second position P2. The steps of the method can be repeated to change machine 10 and 312 to accommodate different sizes of syringe assemblies 18.

Before using the system 10, 170 and 310 to install the piston rod, the actuator 30 and 330 can be programmed to step the tray 26 and 326 through the rotary part 22 and 322 only once per activation action. Step movement of the tray 26 and 326 from the first position P1 to the second position P2 includes rotation of the rotary part 22 and 322 around the axis

- 16 042833

A rotation to connect the piston rod 14 and the syringe assembly 18. Rotation of the rotary part 22 and 322 may include turning the rotary part 22 and 322 less than 120 degrees to move the tray 26 and 326 from the first position P1 to the second position P2. Using the first exemplary machine 10, activating the drive device 30 includes manually moving a lever 160 to rotate the turntable 22 and step the tray 26 from the first position P1 to the second position P2. When using machine 10 with adaptive drive system 170 shown in FIG. 11 and 12, activating the actuator 30 includes actuating a function switch 194 coupled to the servo 190 to move the rigid member 182 and the brace 186 into engagement with the lever 160. In the third exemplary system 310, activating the actuator 330 includes actuating function switch 494 connected to the servo 490, which is connected to the rotary part 322.

In other embodiments, the implementation of the machine 10 and 312 may be configured to connect the piston rod and syringe piston assembly according to the relative position when docking the piston rod and piston. For example, the depicted machines 10 and 312 are designed to connect the threaded distal end 156 of the piston rod 14 to the threaded surface of the piston 158 by applying both a downward force to the piston rod 14 and a turning force to the syringe barrel 78. In another example, the piston rod mounting system 10 and 310 may be configured to couple the piston rod 14 to the piston 158, which snap-fit. In this example, each machine 10 and 312 may be configured to apply a downward force to the piston rod 14 to sufficiently connect the piston rod 14 and piston 158 without rotating the syringe assembly 18 relative to the tray 26 and 326. Friction element 60 and 360 can be removed from the guide plate 120 and 420 so that the syringe assembly 18 does not rotate relative to the tray 26 and 326 and the piston rod 14.

The piston rod installation systems described herein provide significant advantages over existing methods of operating automated piston rod installation systems. Manual and semi-automated systems have a significantly reduced footprint compared to existing automated machines designed to assemble large batches. The disclosed system is a cost effective and efficient alternative to the existing automated machine. The generally low demand for piston rod and syringe assemblies cannot meet the large capital investment required to purchase, operate and maintain expensive and complex automated machines designed to prepare large batches. However, the disclosed systems 10 and 310 are particularly suitable for the assembly of small batches of plunger rod and syringe assemblies in cases where access to fully automated machines is limited or not convenient. Further disclosed systems are configured to provide a step movement such that the plunger rod and syringe assembly are positioned on the pivot and connected before another plunger rod and syringe assembly is attached to or placed on the pivot. The stepping feature provides safety and reduces the chance of operator error by having systems pre-configured to assemble piston rods with syringe assemblies without the operator having to know each step of the work sequence or intervene in the equipment workflow between assembly steps. Additionally, two-handed momentary function switches ensure that the machine 10 and 312 cannot be used unless both hands of the operator operate the switches. In other words, the chance of accidentally using or turning on the machine will be greatly reduced, if not completely eliminated. The disclosed systems 10 and 310 are very easy to load, use and unload and do not require extensive training, special education or technical knowledge to use the equipment. Both of these features of the disclosed systems can contribute to the economics and availability of the piston rod and syringe assembly technology.

Semi-automated systems greatly simplify the application of the assembly and the process of adjusting and/or replacing components to assemble syringe assemblies of different sizes, materials and fill levels. For example, the conversion process to adapt existing machines to assemblies of syringe assemblies of more than one size is typically labor intensive and requires disassembly, retooling, and reassembly prior to using the machine. In contrast, certain components of the disclosed piston rod mounting systems can be easily replaced or adjusted in a matter of minutes and without the need for additional conversion equipment to assemble a syringe assembly of a different size. These features reduce the time and effort of skilled personnel, and increase convenience and efficiency.

- 17 042833

Information about the medicinal product

The above description has disclosed various systems and methods for using a piston rod and syringe assembly system. It should be understood that the system, machine, or methods may additionally provide for the use of a medicinal product listed below, with the proviso that the following list should not be construed as either inclusive of all drugs or as limiting. The drug is contained in the reservoir of the syringe barrel assembly. In some cases, the reservoir is the main container that is filled or pre-filled for drug treatment. The main container may be a pre-filled syringe.

For example, a syringe or syringe assembly can be filled with colony stimulating factors such as granulocyte colony stimulating factor (G-CSF). Such G-CSF-based agents include, without limitation, Neupogen® (filgrastim) and Neulasta® (pegfilgrastim). In various other embodiments, the drug delivery device may be used with various pharmaceuticals, such as an erythropoiesis stimulating agent (ESA), which may be in liquid or lyophilized form. ESA is any molecule that stimulates erythropoiesis such as Epogen® (epoetin-alpha), Aranesp® (darbepoetinalfa), Dynepo® (epoetin-delta), Mircera® (methoxypolyethylene glycol-epoetin-beta), Hematide®, MRK-2578 , INS-22, Retacrit® (epoetin zeta), Neorecormon® (epoetin beta), Silapo® (epoetin zeta), Binocrit® (epoetin alfa), epoetin alfa Hexal, Abseamed® (epoetin alfa), Ratioepo® (epoetin-theta), Eporatio® (epoetin-theta), Biopoin® (epoetin-theta), epoetin-alpha, epoetin-beta, epoetin-zeta, epoetin-theta and epoetin-delta, and molecules or variants thereof or analogs disclosed in the following patents or patent applications, all of which are incorporated herein by reference in their entirety: US patent No. 4703008; 5441868; 5547933; 5618698; 5621080; 5756349; 5767078; 5773569; 5955422; 5986047; 6583272; 7084245 and 7271689; and PCT Publication No. WO 91/05867; W095/05465; WO 96/40772; W000/24893; WO 01/81405 and WO 2007/136752.

ESA may be an erythropoiesis-stimulating protein. In the context of this document, the expression erythropoiesis-stimulating protein means any protein that directly or indirectly causes the activation of the erythropoietin receptor, for example, by binding to the receptor and causing its dimerization. Proteins that stimulate erythropoiesis include erythropoietin and its variants, analogs or derivatives, which bind to and activate the erythropoietin receptor; antibodies that bind to the erythropoietin receptor and activate the receptor; or peptides that bind to and activate the erythropoietin receptor. Erythropoiesis-stimulating proteins include, without limitation, epoetin-alpha, epoetin-beta, epoetin-delta, epoetin-omega, epoetin-iota, epoetin-zeta and their analogs, pegylated erythropoietin, carbamylated erythropoietin, peptidomimetic agents (including EMP1/hematide) and antibody mimetics. Exemplary erythropoietic-stimulatory proteins include erythropoietin, darbepoetin, erythropoietin agonist variants, and peptides or antibodies that bind and activate the erythropoietin receptor (and include compounds set forth in U.S. Patent Application Publication Nos. 2003/0215444 and 2006/0040858, each disclosed incorporated herein by reference in its entirety), as well as erythropoietin molecules, or variants or analogues thereof, disclosed in the following patents or patent applications, all of which are incorporated herein by reference in their entirety: US Pat. Nos. 4,703,008; 5441868; 5547933; 5618698; 5621080; 5756349; 5767078; 5773569; 5955422; 5830851; 5856298; 5986047; 6030086; 6310078; 6391633; 6583272; 6586398; 6900292; 6750369; 7030226; 7084245 and 7217689; U.S. Patent Application Publication No. 2002/0155998; 2003/0077753; 2003/0082749; 2003/0143202; 2004/0009902; 2004/0071694; 2004/0091961; 2004/0143857; 2004/0157293; 2004/0175379; 2004/0175824;

2004/0229318; 2004/0248815; 2004/0266690; 2005/0019914; 2005/0026834; 2005/0096461; 2005/0107297;

2005/0107591; 2005/0124045; 2005/0124564; 2005/0137329; 2005/0142642; 2005/0143292; 2005/0153879;

2005/0158822; 2005/0158832; 2005/0170457; 2005/0181359; 2005/0181482; 2005/0192211; 2005/0202538;

2005/0227289; 2005/0244409; 2006/0088906 and 2006/0111279; and PCT Publication No. WO 91/05867; W095/05465; W099/66054; W000/24893; WO 01/81405; W000/61637; WO 01/36489; WO 02/014356; WO02/19963; WO02/20034; WO 02/49673; WO 02/085940; WO 03/029291; W02003/055526; W02003/084477; WO2003/094858; WO2004/002417; WO2004/002424; WO2004/009627; WO2004/024761; WO2004/033651; WO2004/035603; WO2004/043382; WO2004/101600; WO2004/101606; WO2004/101611; WO2004/106373; W02004/018667; WO2005/001025; WO2005/001136; W02005/021579; WO2005/025606; WO2005/032460; W02005/051327; WO2005/063808; WO2005/063809; WO2005/070451; WO2005/081687; WO2005/084711; WO2005/103076; WO 2005/100403; WO2005/092369; WO 2006/50959; WO 2006/02646 and WO 2006/29094.

Examples of other pharmaceuticals for use with the device may include, but are not limited to, antibodies such as Vectibix® (panitumumab), Xgeva™ (denosumab), and Prolia™ (denosamab); other biologics such as Enbrel® (etanercept, TNF-receptor/Fc fusion protein, TNF blocker), Neulasta® (pegfilgrastim, pegylated filgrastim, pegylated G-CSF, pegylated

- 18 042833 hu-Met-G-CSF), Neupogen® (filgrastim, G-CSF, hu-MetG-CSF) and Nplate® (romiplostim); small molecule drugs such as Sensipar® (cinacalcet). The device can also be used with a therapeutic antibody, polypeptide, protein, or other chemical such as iron, such as ferumoxytol, iron complexed dextrans, ferrous gluconate, and sucrose-iron complex. The pharmaceutical preparation may be in liquid form or reconstituted from a lyophilized form.

Specific illustrative proteins include the specific proteins set forth below, including their fusions, fragments, analogs, variants, or derivatives:

OPGL-specific antibodies, peptibodies and related proteins, and the like. (also referred to as RANKL-specific antibodies, peptibodies, and the like), including fully humanized and human OPGL-specific antibodies, in particular fully humanized monoclonal antibodies, including, but not limited to, the antibodies described in PCT Publication No. WO 03 /002713, which is incorporated herein in its entirety with respect to OPGL-specific antibodies and antibody-related proteins, in particular those having the sequences set forth therein, in particular, without limitation, those designated therein as: 9H7; 18B2; 2D8; 2E11; 16E1 and 22B3, including OPGL-specific antibodies having either the light chain of SEQ ID NO:2 set forth therein in FIG. 2 and/or the heavy chain of SEQ ID NO:4 set forth therein in FIG. 4, all of which are individually and specifically incorporated herein by reference in their entirety, in their entirety as disclosed in the above publication;

myostatin binding proteins, peptibodies and related proteins, and the like, including myostatin-specific peptibodies, such as those described in U.S. Patent Application Publication No. 2004/0181033 and PCT Publication No. WO 2004/058988, which are incorporated herein. document by reference in its entirety, in particular in parts relating to myostatin-specific peptibodies, including, without limitation, peptitiles from the mTN8-19 family, including those under SEQ ID NO:305-351, including from TN8-19-1 to TN8-19-40, TN8-19 con1 and TN8-19 con2; mL2 family pepti bodies under SEQ ID NO:357-383; mL15 family under SEQ ID NO:384-409; mL17 family under SEQ ID NO:410-438; mL20 family under SEQ ID NO:439-446; mL21 family under SEQ ID NO:447-452; the mL24 families of SEQ ID NO:453-454 and those of SEQ ID NO:615-631, all of which are individually and specifically incorporated herein by reference in their entirety, as disclosed in the above publication;

IL-4 receptor-specific antibodies, peptibodies and related proteins, and the like, in particular those that inhibit activities mediated by IL-4 and/or IL-13 binding to the receptor, including those described in PCT- Publication No. WO 2005/047331 or PCT Application No. PCT/US2004/37242 and US Patent Application Publication No. 2005/112694, which are incorporated herein by reference in their entirety, in particular in parts relating to specific IL-4 receptor antibodies, in particular those antibodies as described therein, in particular and without limitation those designated therein as: L1H1; L1H2; L1H3; L1H4; L1H5; L1H6; L1H7; L1H8; L1H9; L1H10; L1H11; L2H1; L2H2; L2H3; L2H4; L2H5; L2H6; L2H7; L2H8; L2H9; L2H10; L2H11; L2H12; L2H13; L2H14; L3H1; L4H1; L5H1; L6H1, all of which are individually and specifically incorporated herein by reference in their entirety, in their entirety as disclosed in the above publication;

interleukin-1 receptor-1 (IL1-R1) specific antibodies, peptibodies and related proteins, and the like, including, without limitation, those described in US Patent Application Publication No. 2004/097712, which is incorporated herein by reference in its entirety in parts relating to binding proteins specific for IL1-R1, monoclonal antibodies, in particular in the first place, without limitation those designated herein as: 15CA, 26F5, 27F2, 24E12 and 10H7, all of which are separately and specifically incorporated herein by reference in their entirety, in their entirety as disclosed in the aforementioned publication;

Ang2-specific antibodies, peptibodies, and related proteins, and the like, including, without limitation, those described in PCT Publication No. WO 03/057134 and US Patent Application Publication No. 2003/0229023, each of which is incorporated herein. document by reference in its entirety, in particular in parts relating to Ang2-specific antibodies and peptocytes, and the like, primarily those having the sequences described therein, including without limitation: L1 ( N); L1(N)WT; L1 (N) 1K WT; 2xL1(N); 2xL1(N)WT; Con4 (N), Con4 (N) 1K WT, 2xCon4 (N) 1K; L1C; L1C 1K; 2xL1C; Con4C; Con4C 1K; 2xCon4C 1K; Con4-Ll (N); Con4-L1C; TN-12-9(N); C17 (N); TN8-8(N); TN8-14(N); Con 1 (N), as well as including antibodies to Ang 2 and compositions based on them, such as those described in PCT Publication No. WO 2003/030833, which is incorporated herein by reference in its entirety with respect to the same, in particular Ab526; Ab528; Ab531; Ab533; Ab535; Ab536; Ab537; Ab540; Ab543; Ab544; Ab545; Ab546; A551; Ab553; Ab555; Ab558; Ab559; Ab565; AbF1AbFD; AbFE; AbFJ; AbFK; AbG1D4; AbGC1E8; AbH1C12; AblA1; AblF; AblK, AblP

- 19 042833 and AblP with their various permutations as described therein, all of which are separately and specifically incorporated herein by reference in their entirety, in their entirety as disclosed in the above publication;

NGF-specific antibodies, peptibodies and related proteins, and the like, including but not limited to those described in US Patent Application Publication No. 2005/0074821 and US Patent No. 6,919,426, which are incorporated herein by the references in their entirety to NGF-specific antibodies and related proteins as used herein, including, but not limited to, NGF-specific antibodies referred to herein as 4D4, 4G6, 6H9, 7H2, 14D10, and 14D11, all of which are separately and specifically incorporated herein by reference in their entirety, in their entirety as disclosed in the above publication;

CD22-specific antibodies, peptibodies and related proteins, and the like, such as those described in US Pat. , specific for human CD22 antibodies, such as, without limitation, humanized and fully human antibodies, including, without limitation, humanized and fully human monoclonal antibodies, in particular, including, without limitation, specific for human CD22 IgG antibodies, such as, for example, , a dimer from the gamma chain of a humanized mouse hLL2 monoclonal antibody disulfide-linked to the kappa chain of a humanized mouse hLL2 monoclonal antibody, including but not limited to, for example, a fully humanized human CD22-specific antibody, epratuzumab, having the CAS registration number 501423-23-0;

IGF-1 receptor-specific antibodies, peptibodies and related proteins, and the like, such as those described in PCT Publication No. WO 06/069202, which is incorporated herein by reference in its entirety with respect to IGF receptor-specific -1 antibodies and related proteins, including, but not limited to, IGF-1 specific antibodies referred to herein as L1H1, L2H2, L3H3, L4H4, L5H5, L6H6, L7H7, L8H8, L9H9, L10H10, L11H11,

L12H12, L13H13, L14H14, L15H15, L16H16, L17H17, L18H18, L19H19, L20H20, L21H21, L22H22,

L23H23, L24H24, L25H25, L26H26, L27H27, L28H28, L29H29, L30H30, L31H31, L32H32, L33H33,

L34H34, L35H35, L36H36, L37H37, L38H38, L39H39, L40H40, L41H41, L42H42, L43H43, L44H44,

L45H45, L46H46, L47H47, L48H48, L49H49, L50H50, L51H51, L52H52, and IGF-1R binding fragments and derivatives thereof, all of which are individually and specifically incorporated herein by reference in their entirety, in their entirety as disclosed in the above publication .

Also non-limiting examples of anti-IGF-1R antibodies for use in the methods and compositions of the present invention include any and all of those described in:

(i) U.S. Patent Application Publication No. 2006/0040358 (published February 23, 2006), 2005/0008642 (published January 13, 2005), 2004/0228859 (published November 18, 2004), including without limitation , for example, antibody 1A (DSMZ Deposit No. DSM ACC 2586), antibody 8 (DSMZ Deposit No. DSM ACC 2589), antibody 23 (DSMZ Deposit No. DSM ACC 2588), and antibody 18 described therein;

(ii) PCT Publication Nos. WO 06/138729 (published December 28, 2006) and WO 05/016970 (published February 24, 2005), and Lu et al. (2004), J. Biol. Chem. 279:2856-2865, including but not limited to the 2F8, A12, and IMC-A12 antibodies described therein;

(iii) PCT Publication Nos. WO 07/012614 (published February 1, 2007), WO 07/000328 (published January 4, 2007), WO 06/013472 (published February 9, 2006), WO 05/058967 (published June 30, 2005) and WO 03/059951 (published July 24, 2003);

(iv) U.S. Patent Application Publication No. 2005/0084906 (published April 21, 2005), including, but not limited to, 7C10 antibody, C7C10 chimeric antibody, h7C10 antibody, 7H2M antibody, *7C10 chimeric antibody, GM 607 antibody, humanized antibody 7C10 version 1, humanized 7C10 antibody version 2, humanized 7C10 antibody version 3, and 7H2HM antibody described therein;

(v) U.S. Patent Application Publication Nos. 2005/0249728 (published November 10, 2005), 2005/0186203 (published August 25, 2005), 2004/0265307 (published December 30, 2004) and 2003/0235582 (published 25 December 2003) and Maloney et al. (2003), Cancer Res. 63:5073-5083, including, but not limited to, EM164, surface-altered EM164, humanized EM164, huEM164 v1.0, huEM164 v1.1, huEM164 v1.2, and huEM164 v1.3 antibody described therein;

(vi) U.S. Patent No. 7,037,498 (issued May 2, 2006), U.S. Patent Application Publication Nos. 2005/0244408 (published November 30, 2005) and 2004/0086503 (published May 6, 2004) and Cohen, et al. . (2005), Clinical Cancer Res. 11:2063-2073, for example, the CP-751871 antibody, including, without limitation, each of the antibodies produced by hybridomas having ATCC accession numbers PTA2792, PTA-2788, PTA-2790, PTA-2791, PTA-2789, PTA-2793 , and antibodies 2.12.1, 2.13.2, 2.14.3, 3.1.1, 4.9.2 and 4.17.3 described therein;

- 20 042833 (vii) US Patent Application Publication No. 2005/0136063 (published June 23, 2005) and

2004/0018191 (published January 29, 2004), including, without limitation, the 19D12 antibody and the antibody containing the heavy chain encoded by the polynucleotide in plasmid 15H12/19D12 HCA (γ4) deposited with ATCC under the number PTA-5214, and the light chain encoded by the polynucleotide in the plasmid

15H12/19D12 LCF (k) deposited with the ATCC under the number PTA-5220 described therein; and (viii) U.S. Patent Application Publication No. 2004/0202655 (published October 14, 2004), including but not limited to PINT-6A1, PINT-7A2, PINT-7A4, PINT-7A5, PINT-7A6, PINT- 8A1, PINT-9A2, PINT-11A1, PINT-11A2, PINT-11A3, PINT-11A4, PINT-11A5, PINT-11A7, PINT-11A12, PINT12A1, PINT-12A2, PINT-12A3, PINT-12A4 and PINT- 12A5 described therein; each and every one of which is incorporated herein by reference in its entirety, in particular with respect to the aforementioned antibodies, peptocytes and related proteins, and the like, which target IGF-1 receptors;

B-7 related protein-1 specific antibodies, peptibodies, related proteins, and the like. (B7RP-1 is also referred to in the literature as B7H2, ICOSL, B7h and CD275), in particular B7RP-specific fully human IgG2 monoclonal antibodies, in particular a fully human IgG2 monoclonal antibody that binds an epitope in the first immunoglobulin-like domain of B7RP-1, in the first in turn, those that inhibit the interaction of B7RP-1 with its natural receptor, ICOS, on activated T cells, in particular, in the first place, all of the above refer to those disclosed in US Patent Application Publication No. 2008/0166352 and PCT- Publication No. WO 07/011941, which are incorporated herein by reference in their entirety with respect to such antibodies and related proteins, including, without limitation, antibodies designated as follows: 16H (having the light chain variable region and variable region sequences heavy chain under SEQ ID NO:1 and SEQ ID NO:7, respectively, described therein); 5D (having the light chain variable region and heavy chain variable region sequences of SEQ ID NO:2 and SEQ ID NO:9, respectively, described therein); 2H (having the light chain variable region and heavy chain variable region sequences of SEQ ID NO:3 and SEQ ID NO:10, respectively, described therein); 43H (having the light chain variable region and heavy chain variable region sequences of SEQ ID NO:6 and SEQ ID NO:14, respectively, described therein); 41H (having the light chain variable region and heavy chain variable region sequences of SEQ ID NO:5 and SEQ ID NO:13, respectively, described therein) and 15H (having the light chain variable region and heavy chain variable region sequences of SEQ ID NO: 4 and SEQ ID NO:12, respectively, described therein), all of which are separately and specifically incorporated herein by reference in their entirety, in their entirety as disclosed in the above publication;

IL-15 specific antibodies, peptibodies and related proteins, and the like, such as, in particular, humanized monoclonal antibodies, in particular, antibodies such as those disclosed in US Patent Application Publications No. 2003/0138421; 2003/023586 and 2004/0071702; and US Pat. IL-15 HuMax and related proteins such as, for example, 146B7;

IFN-gamma specific antibodies, peptibodies and related proteins, and the like, in particular human IFN-gamma specific antibodies, in particular fully human anti-IFN-gamma antibodies such as, for example, those described in U.S. Patent Application Publication No. 2005/0004353, which is incorporated herein by reference in its entirety with respect to IFN-gamma specific antibodies, in particular, for example, antibodies referred to therein as 1118; 1118*; 1119; 1121 and 1121*. The complete heavy and light chain sequences of each of these antibodies, as well as the sequences of the variable regions and complementarity determining regions of their heavy and light chains, are separately and specifically incorporated herein by reference in their entirety, in their entirety as disclosed in the above publication and in Thakur et al. . (1999), Mol. Immunol. 36:1107-1115. In addition, the description of the properties of these antibodies, presented in the above publication, is also incorporated into this document by reference in its entirety. Specific antibodies include those having a heavy chain of SEQ ID NO:17 and a light chain of SEQ ID NO:18; antibodies having a heavy chain variable region of SEQ ID NO:6 and a light chain variable region of SEQ ID NO:8; antibodies having a heavy chain under SEQ ID NO:19 and a light chain under SEQ ID NO:20; antibodies having a heavy chain variable region of SEQ ID NO:10 and a light chain variable region of SEQ ID NO:12; antibodies having a heavy chain under SEQ ID NO:32 and a light chain under SEQ ID NO:20; antibodies having a heavy chain variable region of SEQ ID NO:30 and a light chain variable region of SEQ ID NO:12; antibodies having the heavy chain sequence of SEQ ID NO:21 and the light chain sequence of SEQ ID NO:22; antibodies having a heavy chain variable region of SEQ ID NO:14 and a light chain variable region of SEQ ID NO:16; antibodies having a heavy chain of SEQ ID NO:21 and a light chain of SEQ ID NO:33; and antibodies having a heavy chain variable region of SEQ ID NO:14 and a light chain variable region of SEQ ID NO:31 disclosed in the above publication. The specific antibody in question is the 1119 antibody disclosed in the above US patent application publication and having the full heavy chain sequence of SEQ ID NO:17 disclosed therein and having the full light chain sequence of SEQ ID NO:18 disclosed therein;

TALL-1 specific antibodies, peptibodies and related proteins, and the like. and other binding proteins specific for TALL, such as those described in US Patent Application Publication Nos. 2003/0195156 and 2006/0135431, each of which is incorporated herein by reference in its entirety with respect to TALL-1 binding proteins, in particular molecules from the table. 4 and 5B, all of which are individually and specifically incorporated herein by reference in their entirety, in their entirety as disclosed in the above publications;

parathyroid hormone (PTH) specific antibodies, peptibodies and related proteins, and the like, such as those described in US Pat. that bind PTH;

thrombopoietin receptor (TPO-R) specific antibodies, peptibodies and related proteins, and the like, such as those described in US Pat. to proteins that bind TPO-R;

hepatocyte growth factor (HGF) specific antibodies, peptibodies and related proteins, etc., including those that target the HGF/SF:cMet (HGF/SF:c-Met) signaling pathway axis, such as human monoclonal antibodies that neutralize hepatocyte growth factor/scattering factor (HGF/SF) described in US Patent Application Publication No. 2005/0118643 and PCT Publication No. WO 2005/017107, huL2G7 described in US Patent No. 7220410, and OA -5d5, as described in US Pat.

TRAIL-R2 specific antibodies, peptibodies, related proteins, and the like, such as those described in US Pat. bind TRAIL-R2;

activin A-specific antibodies, peptibodies, related proteins, and the like, including, without limitation, those described in US Patent Application Publication No. 2009/0234106, which is incorporated herein by reference in its entirety, in particular , in parts related to proteins that bind Activin A;

TGF-beta specific antibodies, peptibodies, related proteins, and the like, including, without limitation, those described in US Pat. No. 6,803,453 and US Patent Application Publication No. 2007/0110747, all of which are incorporated herein by links in their entirety, in particular, in parts relating to proteins that bind TGF-beta;

amyloid-beta specific antibodies, peptibodies, related proteins, and the like, including, without limitation, those described in PCT Publication No. WO 2006/081171, which is incorporated herein by reference in its entirety, in particular, in parts relating to proteins that bind beta-amyloid proteins. One contemplated antibody is an antibody having a heavy chain variable region comprising SEQ ID NO:8 and a light chain variable region having SEQ ID NO:6 as disclosed in the above publication;

c-Kit-specific antibodies, peptibodies, related proteins, and the like, including, without limitation, those described in US Patent Application Publication No. 2007/0253951, which is incorporated herein by reference in its entirety, to in particular, in parts relating to proteins that bind c-Kit and/or other stem cell factor receptors;

OX40L-specific antibodies, peptibodies, related proteins, and the like, including, without limitation, those described in US Patent Application Publication No. 2006/0002929, which is incorporated herein by reference in its entirety, in particular, in parts relating to proteins that bind 0X40L and/or other ligands of the 0X40 receptor; and other illustrative proteins, including Activase® (alteplase, tPA); Aranesp® (darbepoetinalfa); Epogen® (epoetin-alpha or erythropoietin); GLP-1, Avonex® (interferon beta-1a); Bexxar® (tositumomab, anti-CD22 monoclonal antibody); Betaseron® (interferon-beta); Campath® (alemtuzumab, an anti-CD52 monoclonal antibody); Dynepo® (epoetin delta); Velcade® (bortezomib); MLN0002 (anti-α4™7 mAb); MLN1202 (CCR2 chemokine receptor mAb); Enbrel® (etanercept, TNF-receptor/Fc fusion protein, TNF blocker); Eprex® (epoetin-alpha); Erbitux® (cetuximab, anti-EGFR/HER1/c-ErbB-1 antibody); Genotropin® (somatropin, human growth hormone); Herceptin® (trastuzumab, HER2/neu receptor (erbB2) mAb); Humatrope® (somatropin, human growth hormone); Humira® (adalimu

- 22 042833 mab); insulin in solution; Infergen® (interferon alfacon-1); Natrecor® (nesiritide; recombinant human B natriuretic peptide (hBNP); Kineret® (anakinra); Leukine® (sargramostim, rhuGM-CSF); LymphoCide® (epratuzumab, anti-CD22 mAb); Benlysta™ (lymphostat-B, belimumab, mAb to BlyS); Metalyse® (tenecteplase, t-PA analogue); Mircera® (methoxy polyethylene glycol-epoetin-beta); Mylotarg® (gemtuzumab ozogamicin); Raptiva® (efalizumab); Cimzia® (certolizumab pegol, CDP 870); Soliris ™ (eculizumab); pexelizumab (complement C5 antibody); Numax® (MEDI-524); Lucentis® (ranibizumab); Panorex® (17-1A, edrecolomab); Trabio® (lerdelimumab); TheraCim hR3 (nimotuzumab) ; Omnitarg (pertuzumab, 2C4); Osidem® (IDM-1); OvaRex® (B43.13); Nuvion® (visilizumab); cantuzumab mertansin (huC242-DM1); NeoRecormon® (epoetin-beta); Neumega® (oprelvekin , human interleukin-11); Neulasta® (pegylated filgrastim, pegylated G-CSF, pegylated hu-Met-G-CSF); Neupogen® (filgrastim, G-CSF, hu-MetG-CSF); Orthoclone OKT3® (muromonab- CD3, anti-CD3 monoclonal antibody); Procrit® (epoetin-alpha); Remicade® (infliximab, anti-TNFa monoclonal antibody); Reopro® (abciximab, anti-GP lIb/Ilia monoclonal antibody); Actemra® (mAb for IL6 receptor); Avastin® (bevacizumab), HuMax-CD4 (zanolimumab); Rituxan® (rituximab, anti-CD20 mAb); Tarceva® (erlotinib); Roferon-A®-(interferon alfa-2a); Simulect® (basiliximab); Prexige® (lumiracoxib); Synagis® (palivizumab); 146B7-CHO (anti-IL15 antibody, see US Pat. No. 7,153,507); Tysabri® (natalizumab, anti-integrin a4 mAb); Valortim® (MDX-1303, B. anthracis protective antigen mAb); ABthrax™; Vectibix® (panitumumab); Xolair® (omalizumab); ETI211 (mAb to MRSA); IL-1 trap (Fc portion of human IgG1 and extracellular domains of both components of the IL-1 receptor (type I receptor and receptor accessory protein)); VEGF trap (VEGFR1 Ig domains fused to Fc IgGl); Zenapax® (daclizumab); Zenapax® (daclizumab, anti-IL-2Ra mAb); Zevalin® (ibritutomab tiuxetan); Zetia® (ezetimibe); Orencia® (atacicept, TACI-Ig); monoclonal antibody to CD80 (galiximab); anti-CD23 mAb (lumiliximab); BR2-FC (huBR3/huFc fusion protein, soluble BAFF antagonist); CNTO 148 (golimumab, anti-TNFa mAb); HGS-ETR1 (mapatumumab; human TRAIL receptor mAb); HuMax-CD20 (ocrelizumab, anti-human CD20 mAb); NgMax-EGFR (zalutumumab); M200 (volociximab, mAb to integrin α5β 1); MDX-010 (ipilimumab, anti-CTLA-4 and VEGFR-1 (IMC18F1) mAb; anti-BR3 mAb; C. difficile C toxin A and toxin B mAb, MDX-066 (CDA-1) and MDX-1388); dsFv conjugates to CD22-PE38 (CAT-3888 and CAT-8015); anti-CD25 mAb (HuMax-TAC); anti-CD3 mAb (NI-0401); adecatumumab; mAb to CD30 (MDX-060); MDX-1333 (anti-IFNAR antibody); anti-CD38 mAb (HuMax CD38); mAb to CD40L; mAb to Crypto; anti-CTGF antibody for use in idiopathic pulmonary fibrosis in a phase I study (FG-3019) from Fibrogen; mAb to CTLA4; mAb to eotaxin-1 (CAT-213); mAb to FGF8; mAb to ganglioside GD2; mAb to ganglioside GM2; anti-human GDF-8 mAb (MYO-029); mAb to the GMCSF receptor (CAM-3001); mAb to HepC (HuMax HepC); mAb to IFNa (MEDI-545, MDX-1103); mAb to IGF1R; anti-IGF-1R mAb (HuMax-Inflam); mAb to IL12 (AWT-874); mAb to IL12/IL23 (CNTO 1275); mAb to IL13 (CAT-354); mAb to IL2Ra (HuMax-TAC); mAb to the IL5 receptor; mAb for integrin receptors (MDX-018, CNTO 95); mAb to IP10 used in ulcerative colitis (MDX-1100); anti-LLY antibody; BMS-66513; mannose receptor/hCGe mAb (MDX-1307); dsFv conjugate to mesothelin-PE38 (CAT-5001); mAb to PD1 (MDX-1106 (ONO-4538)); anti-PDGFRa antibody (IMC-3G3); anti-TGFβ mAb (GC-1008); mAb to human TRAIL receptor-2 (HGS-ETR2); mAb to TWEAK; mAb to VEGFR/Flt-1; mAb to ZP3 (HuMax-ZP3); NVS antibody #1 and NVS antibody #2.

An anti-sclerostin antibody such as, but not limited to, romosozumab, blososumab, or BPS 804 (Novartis) may also be included. In addition, therapeutic agents such as rilotumumab, bixalomer, trebananib, ganitumab, conatumumab, motesaniba diphosphate, brodalumab, vidupiprant, panitumumab, denosumab, NPLATE, PROLIA, VECTIBIX, or XGEVA may be included. In addition, a monoclonal antibody (IgG) that binds human proprotein convertase subtilisin-kexin type 9 (PCSK9) can be included in the device, for example, as described in US Pat. Wo 2008/057458, Wo 2008/057459, Wo 2008/063382, Wo 2008/133647, Wo 2009/100297, Wo 2009/100318, Wo 2011/037791, Wo 2011/053759, Wo 2011/053783, Wo 2008/125623, Wo 2008/125623, Wo 2011/072263, Wo 2009/055783, Wo 2012/05444438, WO 2010/029513, Wo 2011/111007, Wo 2010/077854, Wo 2012/088313, Wo 2012/101251, Wo 2012/101252, WO 2012/101253, WO 2012/109530 and WO 2001/031007.

The talimogen lagerparepvec or other oncolytic HSV for the treatment of melanoma or other types of cancer may also be included. Examples of oncolytic HSV include, without limitation, the talimogen lagerparepvec (US Pat. Nos. 7,223,593 and 7,537,924); OncoVEXGALV/CD (US Pat. No. 7981669); OrienX010 (Lei et al. (2013), World J. Gastroenterol., 19:5138-5143); G207, 1716; NV1020; NV12023; NV1034 and NV1042 (Vargehes et al. (2002) Cancer Gene Ther. 9(12):967-978).

Also included are TIMP. TIMPs are endogenous tissue inhibitors of metalloproteinases (TIMPs) and play an important role in many natural processes. TIMP-3 is expressed by various cells and/or present in the extracellular matrix; it inhibits all major cartilage-destroying metalloproteases and may be involved in the development of many destructive diseases

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Claims (25)

connective tissue, including rheumatoid arthritis and osteoarthritis, as well as cancer and cardiovascular conditions. The amino acid sequence of TIMP-3 and the nucleic acid sequence of the DNA molecule that encodes TIMP-3 are disclosed in US Pat. No. 6,562,596 issued May 13, 2003, the disclosure of which is incorporated herein by reference. A description of mutations in TIMP can be found in US Patent Application Publication No. 2014/0274874 and PCT Publication No. WO 2014/152012. Also included are antibodies that antagonize the human calcitoningen-related peptide (CGRP) receptor and a bispecific antibody molecule that targets the CGRP receptor and other targets associated with the development of headache. Additional information regarding these molecules can be found in PCT Application No. WO 2010/075238. In addition, a bispecific T cell recruiter (BiTe) antibody, such as blinatumomab, can be used in the device. Alternatively, a high molecular weight APJ agonist such as apelin or analogues thereof may be included in the device. Information related to such molecules can be found in PCT Publication No. WO 2014/099984. In certain embodiments, the drug formulation comprises a therapeutically effective amount of an antibody to thymic stromal lymphopoietin (TSLP) or TSLP receptor. Examples of anti-TSLP antibodies that can be used in such embodiments include, without limitation, those described in US Pat. Examples of anti-TSLP receptor antibodies include, but are not limited to, those described in US Pat. No. 8,101,182. In particularly preferred embodiments, the drug formulation contains a therapeutically effective amount of an anti-TSLP antibody designated as A5 in US Pat. No. 7,982,016. Although piston rod mounting systems, machine, methods and elements thereof have been described by way of the exemplary embodiments, they are not limited thereto. The detailed description is to be interpreted as being by way of example only, and does not set forth every possible embodiment of the present invention, since it would be impractical, if not impossible, to set forth every possible embodiment. Numerous alternative embodiments can be implemented using current technology or technology developed after the filing date of this patent, which nevertheless fall within the scope of the claims defining the scope of the present invention. It should be understood that the scope of legal protection of the present invention is determined by the wording of the claims set forth further at the end of this patent. The appended claims are to be interpreted broadly to include other variations and embodiments which may be made by those skilled in the art without departing from the scope and scope of equivalent systems, machines, methods, and components thereof. CLAIM 1. A machine for connecting a plunger rod to a syringe assembly, comprising: a pivoting portion having a movable tray comprising a mounting portion sized to accommodate the syringe assembly and an open portion located above the mounting portion sized to accommodate the plunger rod; a drive device operatively connected to the rotary part and configured to move the tray from the first position to the second position for connecting the plunger rod to the syringe assembly; an elongated pressure plate located adjacent to the pivot portion and defining an upstream end and an downstream end, the upstream end being sized to accommodate the proximal end of the piston rod and applying a downward force to the proximal end of the piston rod as the piston rod is moved from the upstream end to the output end; and a constant tension spring connected to the pressure plate, the constant tension spring imparting a downward force to the pressure plate such that the downward force is transmitted to the piston rod by the pressure plate when the tray is moved between the first position and the second position. 2. The machine according to claim 1, characterized in that the input end comprises an inclined surface located above the output end relative to the turning part. 3. The machine according to claim 1 or 2, characterized in that it further comprises at least one guide rod, wherein the pressure plate is movably connected to at least one guide rod in a direction parallel to the longitudinal axis of the rotary part. 4. The machine according to claim 3, characterized in that it additionally contains a threaded rod that provides adjustable installation of the pressure plate relative to the rotary part, as a result of which the pressure plate can be adjusted in a direction parallel to the longitudinal axis of the rotary hour - 24 042833 tee, to accommodate the piston rods at different heights. 5. The machine according to any one of claims 1 to 4, characterized in that it further comprises a friction element located near the rotary part and under the pressure plate, and the friction element is configured to contact the syringe barrel assembly, which is carried by the tray, when moving tray from the first position to the second position, and the friction element is configured to apply a turning force to the syringe barrel to rotate the syringe assembly relative to the piston rod. 6. The machine according to claim 5, characterized in that it further comprises a guide plate and a friction element attached to the guide plate, the friction element being an elongated cord of elastomeric material. 7. The machine according to any one of claims 1 to 6, characterized in that the drive device is operatively connected to the rotary part and is configured to step the tray between the first position and the second position in response to the activating action. 8. The machine according to any one of claims 1 to 7, characterized in that it further comprises a movable base for the piston rod connected to the rotary part, and the base for the piston rod is located above the tray and contains an opening, the dimensions of which are suitable for accommodating the flange of the proximal end of the rod piston, and the hole is aligned along the axis with the open part of the tray, the base for the piston rod is made with the possibility of moving with the tray from the first position to the second position; a retaining cap having an outwardly protruding tongue disposed to protrude into a hole in the piston rod base, the retaining cap being releasably attached to the piston rod base; and moreover, the holding cover is fixed with respect to the rotary part and is located in the hole when the tray is in the first position. 9. Machine according to claim 8, characterized in that the piston rod base is selected from separate and interchangeable first and second piston rod bases, wherein the first piston rod base comprises an opening sized to accommodate a first size flanged end of the piston rod. , and the second piston rod base is sized to accommodate the flanged end of the piston rod of a second size that is different from the first size. 10. The machine according to any one of claims 1 to 9, characterized in that the tray has a tray axis that is in line with the longitudinal axes of the syringe assembly and the piston rod when the syringe assembly and the piston rod are located in the tray, and the axis of the tray located at an angle greater than zero degrees relative to the vertical. 11. The machine according to claim 10, characterized in that the rotary part contains a rotary carousel with an axis of rotation, which is parallel to the axis of the tray, as a result of which the axis of rotation of the rotary part is located at an angle greater than zero degrees relative to the vertical. 12. Machine according to any one of claims 1 to 11, characterized in that the turning part is rotatable relative to the pressure plate. 13. The machine according to any one of claims 1 to 12, characterized in that the installation part of the tray contains a first roller and a second roller separated by a gap, and the first and second rollers of the installation part are made with the possibility of contact with the syringe barrel assembly and holding the syringe barrel in clearance when carried by the tray, wherein the first and second rollers rotate the syringe assembly while stepping the tray from the first position to the second position. 14. A machine according to any one of claims 1 to 13, characterized in that the turning part comprises a plurality of trays carried by the turning part. 15. The machine according to any one of claims 1 to 14, characterized in that it further comprises an outlet chute located near the rotary part in the second position of the tray, and the outlet chute is configured to receive the piston rod and syringe assembly from the tray after connecting the piston rod complete with syringe. 16. The machine according to any one of claims 1 to 15, characterized in that the rotary part is selected from separate and interchangeable first and second rotary parts, and the first rotary part contains a tray having a mounting part, the dimensions of which are suitable for receiving a syringe assembly of the first size , and the second rotary part contains a tray having a mounting part, the dimensions of which are suitable for receiving a syringe assembly of the second size. 17. A machine for connecting a piston rod to a syringe assembly, comprising: a pivoting portion having a movable tray comprising a mounting portion sized to accommodate the syringe assembly and an open portion located above the mounting portion sized to accommodate the plunger rod; a water device operatively connected to the pivot part and configured to move the tray from the first position to the second position to connect the plunger rod to the syringe assembly; - 25 042833 a pressure plate positioned adjacent to the pivoting part so that the tray moves under the pressure plate when the tray is moved from the first position to the second position, the pressure plate being configured to apply a downward force to the piston rod located in the open part of the tray when the tray is moved from the first position to the second position; and at least one of the following (a)-(e): (a) a constant tension spring operatively coupled to the pressure plate, the pressure plate defining an upstream portion configured to accommodate the proximal end of the piston rod when the tray is moved from the first position to the second position, the constant tension spring imparting a downward force to the piston rod applied by means of the pressure plate when the tray is moved between the first position and the second position; (b) a friction element located adjacent to the pivot portion and under the pressure plate, the friction element being configured to contact the syringe barrel assembly carried by the tray when the tray is moved from a first position to a second position, the friction element being configured to apply a turning force to the syringe barrel to rotate the syringe assembly relative to the piston rod while moving the tray from the first position to the second position; (c) moreover, the drive device is operatively connected to the rotary part and is configured to step the tray between the first position and the second position in response to the activating action; (d) wherein the tray has an axis of the tray that is in line with the longitudinal axes of the syringe assembly and the plunger rod when the syringe assembly and the piston rod are located in the tray, and the axis of the tray is located at an angle greater than zero degrees relative to the vertical; and (e) wherein the rotary part is selected from separate and interchangeable first and second rotary parts, wherein the first rotary part contains a tray having a mounting part, the dimensions of which are suitable for accommodating a syringe assembly of the first size, and the second rotary part contains a tray having a mounting part , sized to accommodate a size 2 syringe assembly. 18. The machine according to claim 17, characterized in that it further comprises a guide plate and a friction element attached to the guide plate, the friction element being an elongated cord of elastomeric material. 19. The machine according to claim 17 or 18, characterized in that it further comprises a movable base for the piston rod connected to the rotary part, and the base for the piston rod is located above the tray and contains an opening, the dimensions of which are suitable for accommodating the flange of the proximal end of the piston rod, moreover, the hole is aligned along the axis with the open part of the tray, the base for the piston rod is made with the possibility of moving with the tray from the first position to the second position; a retaining cap having an outwardly protruding tongue disposed to protrude into a hole in the piston rod base, the retaining cap being releasably attached to the piston rod base; and moreover, the holding cover is fixed with respect to the rotary part and is located in the hole when the tray is in the first position. 20. A machine according to any one of claims 17 to 19, characterized in that the drive device allows the tray to be stepped only once per activation action. 21. The machine according to any one of claims 17 to 20, characterized in that the driving device comprises a servomotor and a function switch for operational control of the servomotor, the servomotor being connected to the turntable for moving the tray via the turntable. 22. The machine according to any one of claims 17 to 21, characterized in that the drive device includes a lever with which the user manually steps the tray from the first position to the second position. 23. The machine according to claim 22, characterized in that the drive device includes a movable bracket designed to move the lever. 24. Machine according to any one of claims 17 to 23, characterized in that the turning part is rotatable relative to the pressure plate. 25. The machine according to claim 17, characterized in that the drive device provides stepping movement of the tray two or more times during the activating action. -