Closure integrity kit for prefilled syringes, retaining clips, and plunger rods

Abstract

The prefilled syringe is provided with a locking clip, which, when attached, prevents longitudinal movement of the plunger within the syringe barrel, thereby securing the stopper within the barrel to ensure the integrity of the container closure and maintain the sterility of the syringe contents during conditions such as refrigeration and transportation, or transportation involving large pressure changes, such as air transportation. The locking clip may include notches on the locking clip that receive a corresponding number of bumps formed on the plunger rod, or may be formed with an internal cavity to allow it to slide over and snap onto the flange of the syringe barrel, displaying a pattern of bumps or stoppers to secure the plunger rod, stopper, and syringe barrel together. Rotation of the plunger rod to the desired position releases the plunger, allowing normal administration of the medical liquid from the syringe assembly.

Description

[Technical Field]

[0001] CROSS-REFERENCE TO RELATED APPLICATIONS This application claims priority to European Patent Application No. 22306727.3, filed November 23, 2022, entitled "Closure Integrity Retention Kit, Retaining Clip, and Plunger Rod for Pre-Filled Syringes," the entire disclosure of which is incorporated herein by reference in its entirety. Background of the Invention Field of Disclosure The present disclosure relates generally to pre-filled syringes. More specifically, the present disclosure relates to a retaining clip and plunger rod used with a pre-filled syringe to maintain the closure integrity of the liquid contents of the syringe during transportation or storage. [Background technology]

[0002] 2. Description of Related Art Prefilled syringes and prefillable syringes are well known in the medical field for administering liquids such as medications or saline solutions. Conventional syringes typically include a syringe barrel with an opening at the distal end and a plunger assembly inserted through the opposite proximal end of the barrel. The plunger assembly typically includes an elongated plunger rod extending outward from the barrel and a plunger head or stopper disposed at the distal end of the plunger rod. The stopper or plunger stopper is typically made of an elastomeric material and includes a body adapted for attachment to the distal end of the plunger rod, a tail disposed at its proximal end, and a head disposed at its distal end. The outer cylindrical wall of the body defines a plurality of annular, outwardly protruding ribs adapted to ensure the integrity of the syringe's container closure when the stopper is inserted into the syringe. Additionally, the elongated plunger rod includes a finger flange at its proximal end that extends outwardly from the syringe barrel when the plunger assembly is inserted into the syringe barrel.

[0003] During delivery of the medication to a patient after a period of transportation and / or storage, the opening of the syringe barrel at the distal end is adapted for fluid communication with the patient, for example, via a needle already attached to the syringe barrel (a stacked needle syringe barrel), or via a hypodermic needle attached to the distal end of the syringe barrel (a Luer syringe barrel), or via a Luer fitting (a needleless access device) attached to the distal end of the syringe barrel and connected to the patient's fluid line. When a user applies force to move the plunger assembly through the syringe barrel toward the distal end of the syringe barrel, the contents of the syringe are thereby drawn through the opening at the distal end and out of the syringe barrel for delivery to the patient. Such operations are well known in the medical field, and medical professionals are well accustomed to using such common liquid delivery procedures using prefilled syringes.

[0004] Prefilled syringes offer the convenience of quickly delivering contents to patients without the need to first draw and measure the volume of medication from a separate container.At the same time, there is a need to maintain the sterility of the medication in the prefilled syringe and the integrity of the container closure, especially over a long period of time and during exposure to various storage and transport conditions.In some situations, prefilled syringes are exposed to low temperatures or even below freezing.This can occur intentionally when the contents of the prefilled syringe need to be stored at low temperatures.This can also occur as a result of storing and transporting in cold regions without any temperature control or insulation of the syringe container.In addition, in some situations, prefilled syringes are transported by air, which can be subject to certain conditions such as reduced pressure, which can be accompanied by low temperatures.

[0005] In a typical scenario, once a syringe is filled with a predetermined amount of a desired medication, the stopper is positioned away from the distal end of the barrel by a distance characterized by the barrel diameter, the liquid volume, and, at least in some circumstances, the volume of air between the stopper and the liquid. Filling the syringe and attaching the stopper typically occurs at a predetermined temperature, e.g., room temperature or a lower temperature such as 5°C for temperature-sensitive medications, and in a clean environment. Once outside the clean environment, sterilization may occur. The sterile barrier may be defined as the proximal-most sealing rib of the stopper. The height of the sterile barrier may also be defined as the maximum cumulative distance the stopper may move from its position toward the proximal end of the syringe during syringe storage and / or transportation before risking compromising the sterility of the medication and the syringe interior. Significant rearward movement of the stopper is highly undesirable because it can move into a non-sterile portion of the barrel, thereby compromising the container closure integrity (CCI) and compromising the sterility of the syringe medication.

[0006] Prior to administering the liquid contents from the syringe, the risk and extent of unintended stopper movement along the syringe barrel is - The extent of pressure changes (overpressure and / or underpressure) during syringe storage and transport - temperature range during storage and transportation of syringes, - the inner diameter of the syringe barrel, -Stopper design and material, - The sliding performance of the stopper on a particular barrel, - the amount of liquid in the syringe, and - the amount of air in the syringe (headspace), if any; This is due to several factors, such as:

[0007] Therefore, a need exists for a syringe or component design that can limit or completely prevent undesired movement of the stopper inside the barrel during storage and transport of the pre-filled syringe and prior to its intended use.

[0008] Cold temperatures can affect the position of the stopper within the barrel in various ways, depending on the ratio of liquid in the syringe to air (headspace) below the stopper. If the syringe is mostly filled with liquid medication and there is no air between the liquid and the stopper, freezing the liquid causes it to expand by almost 10% in volume, as when liquid water turns to ice. In a typical example of a 17 mm water height (1 ml of water stored in a 1 ml syringe), the water height can expand by almost 1.7 mm, creating pressures as high as 900 MPa on the stopper and triggering its movement away from the tip of the syringe. If the stopper were fixed in place, the significant pressure could result in barrel failure and / or leakage of the syringe contents or sterility failure. After thawing, the stopper may return to its initial position.

[0009] On the other hand, a large headspace and small liquid volume may cause the stopper to move in the opposite direction during refrigeration due to a decrease in air pressure in the syringe and gas headspace contraction. After thawing, the stopper may return to its initial position.

[0010] Another concern during storage and transportation is changes in environmental pressure, for example, during air transport or during transportation / storage in areas of varying altitudes (atmospheric pressure is altitude dependent). In particular, reduced pressure can cause the stopper to move away from the tip of the syringe.

[0011] Another concern during storage and transportation is exposure of the syringe packaging to mechanical stress, which may inadvertently result in the application of unintended longitudinal forces to the plunger rod, causing the stopper to change position within the syringe barrel. Summary of the Invention [Problem to be solved by the invention]

[0012] Therefore, there is a need for a pre-filled syringe design that can prevent the stopper from moving away from the tip of the syringe toward the flange at the open end of the barrel until at least a predetermined level of force is applied to the stopper. There is also a need for a pre-filled syringe design that prevents the stopper from moving toward the tip of the syringe. Indeed, even if this area of ​​the syringe is sterilized, movement in the opposite direction when the system returns to its initial equilibrium state (returning to room temperature after refrigerated storage or to normal pressure after air transport) will compromise the integrity of the closure of the container, since this area is no longer guaranteed to be sterilized.

[0013] Additionally, a need exists for a pre-filled syringe design that can provide the above limitations on stopper movement despite variations in liquid content fill volume, headspace volume, and other parameters and characteristics during the manufacturing process. Summary of the Invention The present disclosure provides a syringe plunger rod fixation system configured to prevent partial or complete longitudinal movement of the plunger rod relative to the barrel of the syringe once applied, thereby providing fixation of the plunger stopper within the barrel as a way to ensure that the closure integrity of the container is maintained and to maintain the sterility of the syringe contents. [Means for solving the problem]

[0014] According to one aspect of the present invention, a kit with a removable plunger retaining clip for use with a syringe plunger is provided, comprising a plunger rod having an elongated body with a plurality of spaced ridges positioned thereon. The ridges are positioned on or between longitudinal walls of the plunger rod, which generally form an X-shape in cross section and define four quadrants between the walls. Each ridge is fabricated to have a generally triangular shape and spans the space from one quadrant wall to the other. The side of each ridge facing the finger flange at the proximal end of the plunger is positioned at an acute angle to the longitudinal axis of the plunger rod, and the other side is oriented approximately perpendicular to the longitudinal axis of the rod. This prevents any movement of the plunger rod toward the tip of the barrel, as described in more detail below.

[0015] The locking clip is configured to complement the design of the plunger rod. Its spring-loaded design includes a pair of V-shaped arms connected via a hinge at the center of the arms, forming a normally closed clamp, with each arm having a first end and a second end. In its normal position, the first end of one arm is biased to contact the first end of the other arm. Pressing the second end of each arm toward each other separates the first ends. One or both of the first ends includes multiple notches corresponding in size and spacing to the multiple ridges on the plunger rod. When the locking clip is placed on the plunger rod, the notches on the clip arms engage with the ridges on the rod, securing the clip's position on the plunger rod. When positioned against the barrel flange, the shape of the ridges and corresponding notches on the clip are designed to prevent the stopper from moving toward the distal end of the syringe. Furthermore, the shape of the ridge and corresponding notch can prevent the stopper from moving away from the distal end of the syringe, such as during refrigerated storage, when the syringe has a large headspace and a small liquid volume. Specifically, during refrigerated storage, if the stopper's movement is hindered, the stopper cannot move distally, resulting in a drop in headspace pressure. Subsequently, during thawing, the pressure in the headspace increases, but no movement away from the distal end of the syringe occurs because the pressure simply returns to its original equilibrium state.

[0016] Removal of the locking clip (by the end user) is achieved by moving the second ends of each arm together and causing the first ends of each arm to separate, thereby allowing the plunger rod to disengage from the ridge and the locking clip to be laterally removed from the syringe.

[0017] According to another aspect of the present invention, a kit is provided that includes a removable locking clip that engages both the plunger rod and the barrel of a syringe, more specifically, the flange at the proximal end of the barrel. When the locking clip is placed over the plunger rod and engages the flange of the barrel at the open proximal end of the barrel, the position of the plunger rod is fixed relative to the barrel. To accomplish this, the locking clip is further provided with a flange-engaging extension having a cutout slot, the cutout slot being sized to allow the flange of the barrel to be placed within the cutout slot and interlock with the remainder of the locking clip. The locking clip also includes a curved rest pad configured to be placed on the outer surface of the cylindrical portion of the barrel to better define the position of the locking clip relative to the plunger rod and the barrel itself. Similar to the previous aspect of the present invention, the locking clip described herein prevents the stopper from moving toward the distal end of the syringe. It allows the plunger rod to move longitudinally away from the distal end of the syringe only when a force exceeds a predetermined threshold. The predetermined force threshold level is defined by the value of the acuteness of the ridge sides and the number of ridges, as explained in more detail below.

[0018] According to yet another aspect of the present invention, a kit is provided with a further design of snap-on locking clip, configured to removably engage both the barrel flange and the plunger rod. A slide-in cavity is formed within the disk-shaped locking clip, which is wide enough to accommodate the entire diameter of the barrel flange. When positioned from the side of the flange and at least partially or completely over the syringe barrel flange, the snap-on locking clip securely snaps into place. The locking clip is also configured to slide into a slot created in the wall of the plunger rod. When engaged with the clip, the plunger rod cannot move longitudinally along the syringe barrel, thereby fixing the position of the stopper within the barrel. The location of the slot in the wall of the plunger rod is selected to ensure a preferred position of the stopper within the barrel once the syringe is filled with a desired amount of liquid contents. A detent or a friction fit between the locking clip and the barrel flange is used to hold the locking clip in place.

[0019] According to yet another aspect of the present invention, the retention of the locking clip in place is ensured by positioning the locking clip on the barrel flange and through the slot in the plunger rod, then twisting the plunger rod. A protrusion is provided extending from the locking clip along the longitudinal axis of the syringe toward the thumb press flange at the proximal end of the plunger rod. The locking clip is formed with a ramp adjacent to the protrusion. Twisting the plunger rod causes the slot in the rod to engage with the ramp and snap into place when the slot disengages from the ramp, thereby securing all components together. Twisting the rod in the opposite direction releases the rod from the locking clip, allowing the plunger assembly to be pushed to inject the medication.

[0020] The above and other features and advantages of the present disclosure, as well as the manner in which they are achieved, will become more apparent, and the disclosure itself will be better understood, with reference to the following description of embodiments of the present disclosure, taken in conjunction with the accompanying drawings. [Brief explanation of the drawings]

[0021] [Figure 1] 1 is a perspective view of a kit component according to a first embodiment of the present invention; FIG. [Figure 2] FIG. [Figure 3] FIG. 2 is a cross-sectional view of a locking clip on a plunger rod of the first embodiment of the present invention. [Figure 4] 1 is an enlarged perspective view of a fastening clip according to a first embodiment of the present invention; [Figure 5] FIG. 1 is a perspective view of a plunger according to a first embodiment of the present invention. [Figure 6] FIG. 2 is a perspective view of an assembled kit according to a second embodiment of the present invention. [Figure 7] FIG. 10 is an enlarged view of a locking clip attached to a syringe barrel and plunger rod according to a second embodiment of the present invention. [Figure 8] FIG. 8 is another perspective view of the same as FIG. 7. [Figure 9] FIG. 10 is a perspective view of a fixing clip according to a second embodiment of the present invention. [Figure 10] 8 is a cross-sectional view of the fastening clip taken along plane AA of FIG. 7. [Figure 11] FIG. 10 is a perspective view of a locking clip assembled to a syringe and plunger according to a third embodiment of the present invention. [Figure 12] FIG. [Figure 13] FIG. 13 is a cross-sectional top view of the same taken along plane BB seen in FIG. 12. [Figure 14] FIG. 10 is a perspective view of a plunger rod according to a third embodiment of the present invention. [Figure 15] FIG. 10 is a perspective bottom view of a fastening clip according to a third embodiment of the present invention. [Figure 16] FIG. [Figure 17] 10A-10C are perspective views of a plunger rod in different orientations according to a third embodiment of the present invention. [Figure 18] FIG. 10 is a perspective view of a fastening clip according to a fourth embodiment of the present invention. [Figure 19A] FIG. 10 is a top view of the locking clip in the rotation stage of assembly with the plunger rod of the fourth embodiment of the present invention. [Figure 19B] FIG. 10 is a top view of the locking clip at another rotation stage of assembly with the plunger rod of the fourth embodiment of the present invention. [Figure 19C] FIG. 10 is a top view of the locking clip in yet another rotational stage of assembly with the plunger rod of the fourth embodiment of the present invention. DETAILED DESCRIPTION OF THE INVENTION

[0022] Corresponding reference characters indicate corresponding parts throughout the several views. The exemplifications set forth herein illustrate exemplary embodiments of the present disclosure, and such exemplifications should not be construed as limiting the scope of the present disclosure in any way. Detailed Description of the Preferred Embodiments of the Invention Other than in the examples, or unless otherwise indicated, all numerical values ​​expressing quantities of ingredients, material properties, and the like used in the specification, claims, and drawings should be understood to be modified in all instances by the term "about." Accordingly, unless otherwise indicated, the numerical parameters set forth in the following specification and appended claims are approximations that may vary depending upon the desired properties sought to be obtained by the present invention. At the very least, and not as an attempt to limit the application of the doctrine of equivalents to the scope of the claims, each numerical parameter should be construed in light of the number of reported significant digits and by applying ordinary rounding techniques.

[0023] Notwithstanding that the numerical ranges and parameters setting forth the broad scope of the invention are approximations, the numerical values ​​set forth in the specific examples are reported as precisely as possible. However, any numerical value inherently contains certain errors necessarily resulting from the standard deviation found in their respective testing measurements. Furthermore, when numerical ranges of varying scope are set forth herein, it is contemplated that any combination of these values ​​inclusive of the recited values ​​may be used.

[0024] For purposes of explanation hereinafter, terms such as "upper," "lower," "right," "left," "vertical," "horizontal," "top," "bottom," "lateral," "longitudinal," and their derivatives will refer to the present invention as oriented in the drawings. However, it should be understood that the present invention may contemplate various alternative variations, unless expressly specified to the contrary. It should also be understood that the specific devices illustrated in the accompanying drawings and described in the following specification are merely exemplary embodiments of the present invention. Accordingly, specific dimensions and other physical characteristics related to the embodiments disclosed herein are not to be considered limiting.

[0025] In the following description, "distal" generally refers to the direction toward the end of the syringe assembly that contacts a patient and / or is adapted to engage another device, such as a needle assembly and an IV connection assembly, and "proximal" refers to the opposite direction of distal, i.e., the direction away from the end of the syringe assembly that is adapted to engage another device. For purposes of this disclosure, the above references will be used to describe the components of a syringe assembly according to this disclosure.

[0026] A first embodiment of the present invention is shown in more detail in Figures 1-5. Kits of the present invention generally include a syringe barrel 10, a plunger rod 20, and a locking clip 30. Syringe barrel 10 has a cylindrical, elongated body with a distal end 12 and a proximal end 14. Distal end 12 includes an exit opening and / or a mechanism for attachment of another medical device, such as a needleless access device or a needle. The exit opening at distal end 12 can be made in a luer style or with a permanently attached needle (referred to as a stack needle).

[0027] Syringe barrel 10 may be formed from glass or may be injection molded by various techniques from a thermoplastic material such as, for example, polypropylene, polyethylene, alicyclic polyolefin, cycloolefin copolymer (COC), polyester, or polycarbonate, although it should be understood that syringe barrel 10 may be made from other suitable materials and by other applicable techniques.

[0028] Syringe barrel 10 sizes and capacities ranging from 1 milliliter to 10 milliliters or more are available. The length and diameter of syringe barrel 10 can vary depending on the syringe capacity. The proximal end of syringe barrel 10 is normally open but is intended to be closed after filling with a medication and accepts plunger rod 20 with a stopper incorporated at its distal end. Syringe barrel 10 has an outwardly extending flange 16. In the drawings, flange 16 is shown as circular, but other shapes for flange 16 are also within the scope of the present disclosure, as flange 16 is also configured to be easily grasped by a medical professional.

[0029] In some designs, syringe barrel 10 is made with a plain sidewall, while in other designs it may also include markings, such as graduations, disposed on the sidewall to provide an indication as to the level or amount of liquid contained within syringe barrel 10. Such markings may be provided on the exterior or interior surface of syringe barrel 10, or may be integrally formed or integrated into the sidewall of syringe barrel 10. In other embodiments, alternatively or in addition, the markings may also provide a description of the syringe's contents or other identifying information, such as maximum and / or minimum fill lines.

[0030] The syringe kit of the present invention is useful as a prefilled syringe and, therefore, can be provided for end use with a fluid, such as a medication or drug, prefilled by a pharmaceutical company and contained within syringe barrel 10. In this manner, the syringe kit can be manufactured, assembled, prefilled with a medication, and sterilized for delivery, storage, and used by an end user without the end user needing to fill the syringe with the medication from a separate vial prior to use, as described in detail below. In such an embodiment, the syringe kit can further include a cap 18 or another sealing member disposed over the opening at distal end 12 to seal the fluid contained within syringe barrel 10.

[0031] A plunger rod 20 may also be provided as part of a kit of the present invention. The plunger rod 20 has an elongated body extending from a distal end to a proximal end provided with a finger flange 22. The distal end of the plunger rod 20 is configured to be attached to a stopper (not shown), which may be positioned inside the syringe barrel 10, for example, by having a threaded attachment 21. The stopper is preferably made of an elastomeric material selected from the group consisting of natural rubber, synthetic rubber, thermoplastic elastomer, or a combination thereof. The stopper may be partially or completely coated with, for example, polytetrafluoroethylene (PTFE), ethylene tetrafluoroethylene (ETFE), or the like. The stopper is fabricated (with a constant compression) to match the inner diameter of the syringe barrel 10 and is configured to be attached to the plunger rod 20. Although not shown in the drawings, in other embodiments of the present invention, the stopper may be provided as a single body together with the plunger rod. The plunger rod 20 may be manufactured by injection molding from a thermoplastic material, although it does not necessarily have to be the same material as the syringe barrel 10. For example, the plunger rod 20 may be made from polypropylene, polystyrene, polylactic acid (PLA), etc.

[0032] In some designs of the first aspect of the present invention, the elongated body of plunger rod 20 is X-shaped in cross section and is formed by four side walls 24, 25, and 26 that extend radially away from the center of the longitudinal axis of plunger rod 20 between distal end 21 and proximal end 22 of plunger rod 20. The side walls are formed at 90-degree angles to each other and define four quadrants therebetween. Figures 2 and 5 show three of the four side walls 24, 25, and 26 as an example of this design. Other designs of plunger rod 20, such as cylindrical elongated bodies, elongated bodies made with other cross-sectional shapes, such as omega-shaped (Ω-shaped), are within the scope of this disclosure.

[0033] One or more ridges 27 are formed extending laterally from the elongated body of the plunger rod 20. The ridges 27 may be formed along with the plunger rod 20 during its manufacture. The elongated body of the plunger rod 20 may have anywhere from 1 to 50 or more ridges 27 formed thereon, e.g., at least 1, at least 2, at least 3, at least 4, at least 5, at least 10, at least 15, at least 20, at least 25, at least 30, at least 40, at least 45, at least 50, or more ridges. The ridges 27 may be positioned along a portion, a majority, or the entire length of the plunger rod 20.

[0034] The ridges 27 may be formed along one quadrant (as illustrated in FIG. 1 ), two diagonally opposed quadrants (as illustrated in FIG. 3 ), three quadrants, or all four quadrants of the plunger rod 20. When formed along multiple quadrants, the ridges 27 are radially aligned with adjacent ridges (see, e.g., FIG. 3 ), so that rotation of the plunger rod does not result in a longitudinal change in the position of each ridge 27 from one quadrant to the next along the longitudinal axis of the plunger rod 20. In other embodiments, the ridges 27 may be provided on one or more surfaces or edges of the sidewalls 24, 25, 26.

[0035] As can be seen in the drawings, in one exemplary design, multiple ridges 27 are evenly spaced along plunger rod 20. One ridge 27 may be spaced a mm from another ridge (see FIG. 3), where a can be from about 0.3 mm to about 20 mm, e.g., every 0.3 mm, 0.5 mm, 1 mm, 1.5 mm, 2 mm, 2.5 mm, 3 mm, 3.5 mm, 4 mm, 4.5 mm, 5 mm, 5.5 mm, 6 mm, 6.5 mm, 7 mm, 8 mm, 9 mm, 10 mm, 11 mm, 12 mm, 13 mm, 14 mm, 15 mm, 16 mm, 17 mm, 18 mm, 19 mm, 20 mm, or any other suitable distance therebetween, although the invention is not limited in this respect.

[0036] Each ridge 27 may have the same width and the same spacing b before the next ridge 27. The spacing b between the end of one ridge 27 and the beginning of the adjacent ridge may range from 0 mm to about 15 mm, for example, 0 mm, 0.5 mm, 1 mm, 1.5 mm, 2 mm, 2.5 mm, 3 mm, 3.5 mm, 4 mm, 4.5 mm, 5 mm, 6 mm, 7 mm, 8 mm, 9 mm, 10 mm, 11 mm, 12 mm, 13 mm, 14 mm, 15 mm, or any other suitable length therebetween.

[0037] Each ridge 27 may be triangular, as seen in the drawings, or any other suitable shape. As best seen in FIG. 5, the triangle of each ridge 27 may span the space between two adjacent side walls 24 and 25. The body of each ridge 27 is defined by a first side 28 facing the proximal end 22 of the plunger rod 20 and a second side 29 facing the distal end of the plunger rod. The second side 29 is oriented approximately perpendicular to the longitudinal axis of the plunger rod 20, while the first side 28 is oriented at approximately an acute angle α with respect to the longitudinal axis of the plunger rod, as seen in FIG. 3. The angle α may be selected from about 10 degrees to about 70 degrees, for example, 10 degrees, 15 degrees, 20 degrees, 25 degrees, 30 degrees, 35 degrees, 40 degrees, 45 degrees, 50 degrees, 55 degrees, 60 degrees, 65 degrees, 70 degrees, or any other suitable angle therebetween.

[0038] A first embodiment of the fastening clip 30 of the present invention will now be described in more detail with reference to FIGS. 1, 2, and 3, and particularly with reference to FIG. 4. Broadly speaking, the fastening clip 30 comprises a pair of hinged, V-shaped arms 32 and 36 that form a spring-loaded, normally closed clamp, as seen in FIG. 4. In the example of FIG. 4, the arms 32 and 36 are attached to each other at their midsections via a flexible living hinge 39. This design is advantageous because the entire fastening clip 30 can be formed as a single body using, for example, injection molding techniques and a suitable thermoplastic material, such as those mentioned above. Other examples not shown in the drawings may include designs in which two separate arms form the fastening clip and are held together by a metal spring configured to bias the ends of the arms on one side of the clip. Other examples of fastening clips not shown in the drawings may include designs to suit customer assembly needs. For example, the arms 32 and 36 may not be symmetrical to suit a particular customer's assembly practices.

[0039] 1 and 2 show plunger rod 20 partially withdrawn from syringe barrel 10 so that locking clip 30 is spaced from flange 16 to more clearly illustrate the attachment of locking clip 30 to plunger rod 20. However, in the actual attached position of locking clip 30, the distal end of locking clip 30 would abut flange 16 of syringe barrel 10.

[0040] Referring again to FIG. 4, the thickness of the material at location 49 and the bulk material properties limit the force required to separate the arms. First arm 32 has first end 34 and second end 33, and second arm 36 defines first end 38 and second end 37. As seen in FIG. 4, in the normally closed, neutral position of the locking clip, distal edge 35 of first end 34 of first arm 32 is positioned near distal edge 39 of first end 38 of second arm 36. At least one of distal edge 35, distal edge 39, first end 34, and first end 38 includes at least one notch 31 positioned along its length, as seen in the drawing. The size, spacing, and depth of notches 31 are fabricated to correspond to the size, spacing, and depth of each plunger rod ridge 27, as can best be seen in FIG. 3. In that case, placement of the locking clip 30 on the plunger rod 20 results in at least one ridge 27 being positioned within at least one corresponding notch 31 .

[0041] In some designs of the first embodiment of the present invention, the size of each notch 31 exactly matches the size of each ridge 27, but is made the other way around, with the height and width of the ridge 27 limiting the depth and width of the notch 31. In other designs, as seen in FIG. 3 , the interior space of each notch 31 may be somewhat wider than the width of the ridge 27, defining a play or gap of length c between each ridge 27 when positioned within the notch 31. The gap length c may vary between 0 and 5 mm, e.g., 0 mm, 0.5 mm, 1 mm, 1.5 mm, 2 mm, 2.5 mm, 3 mm, 3.5 mm, 4 mm, 4.5 mm, 5 mm, or any other suitable distance. One advantage of providing some space within the notch 31 is that the locking clip 30 can be positioned on the plunger rod 20 while still allowing the plunger rod 20 a small degree of movement up to the limit of length c. This is useful to compensate for some of the assembly variations of the components during manufacturing, such as tolerance build-up from the molding and assembly process.

[0042] The second ends 33, 37 of each arm 32, 36 may be made to have a generally straight shape, but as seen in FIG. 4, the first ends 34, 38 of each arm 32, 36 are made to have an arched shape. This is done to allow the locking clip 30 to cover the opposing side walls 24, 26 of the plunger rod 20 and to allow the distal ends 35, 39 to approach each other. In this case, the range of the arch depth d (see FIG. 4) depends on the size of the corresponding opposing side walls 24, 26 of the plunger rod 20. Depending on the size of the plunger rod 20, dimension d can be at least about 3 mm to about 30 mm or more, e.g., at least 3 mm, at least 4 mm, at least 5 mm, at least 6 mm, at least 7 mm, at least 9 mm, at least 10 mm, at least 12 mm, at least 14 mm, at least 16 mm, at least 18 mm, at least 20 mm, at least 22 mm, at least 24 mm, at least 26 mm, at least 28 mm, or at least 30 mm, as defined by the corresponding plunger rod of the kit of the present invention.

[0043] The first ends 34, 38 of each arm 32, 36 may each have a beveled leading edge 74, 78. When the locking clip 30 is moved toward the plunger rod 20 transversely to the longitudinal axis of the plunger rod 20, the beveled leading edges 74, 78 engage the plunger rod 20. The contact force between the plunger rod 20 and the beveled leading edges 74, 78 causes the first ends 34, 38 of the arms 32, 36 to move apart, allowing the locking clip 30 to fully seat on the plunger rod 20. Thus, an operator and / or assembly equipment does not need to press the second ends 33, 37 of the arms 32, 36 together to attach the locking clip 30 to the plunger rod 20.

[0044] During the manufacturing process of a prefilled syringe, the syringe barrel 10 is first filled with a liquid medicament or drug, and then the plunger stopper and plunger rod 20 are assembled by insertion into the interior space of the syringe barrel 10. Herein, the empty syringe assembly is referred to as a prefillable syringe, but after the syringe barrel is filled with liquid contents and assembled with the plunger assembly, it is referred to as a ready-to-use prefilled syringe.

[0045] The prefillable syringe assembly of the present invention can be filled with a number of medical fluids, including various types of saline solutions such as normal saline and hypertonic saline, any suitable liquid medication, vaccine, or any other liquid medication or medical fluid content intended to treat, prevent, or alleviate a symptom, or side effect of a disease, or condition as defined by a medical professional.

[0046] Sterilization of the fillable syringe and / or the pre-filled syringe containing the appropriate medical liquid content is carried out as part of the manufacturing process using any number of sterilization techniques.For example, the fillable syringe can be provided in a sterile state on the one hand, and the stopper can be provided in a sterile state on the other hand.The filling and assembly of the pre-filled syringe can be carried out in a sterile environment, which can eliminate the need for sterilization after assembly.However, in some embodiments, a sterilization process such as steam sterilization can be carried out after the filling and assembly of the pre-filled syringe.

[0047] After filling the syringe barrel and assembling the plunger assembly, the plunger rod 20 protrudes from the open proximal end 14 of the syringe barrel 10, and the locking clip 30 is positioned on the plunger rod 20 so that it extends laterally beyond the confines of the syringe barrel 10. The location of the locking clip is selected so that one side abuts the flange 16 of the syringe barrel 10. This position ensures that the plunger rod 20 is prevented from moving inward, thereby preventing leakage. The distal end 12 of the syringe barrel 10 is covered and sealed with a cap 18, further isolating the interior volume of the syringe barrel 10 from the external environment and protecting the sterility of the liquid contents.

[0048] Prior to intended use of the prefilled syringe and administration of the liquid medication to a patient, a medical professional is instructed to first remove the locking clip 30 from the plunger rod 20 by pressing the second ends 33, 37 of both arms 32, 36 of the locking clip 30 together, causing its first ends 34, 38 to move apart. As the distal ends 39 and 35 are moved away from each other, the ridges 27 are released from the corresponding notches 31, and the locking clip 30 can be moved laterally away from the plunger rod 20. Once the locking clip 30 is removed, the medical fluid can be administered by depressing the flange 22 to move the stopper toward the distal end 12 of the syringe barrel 10.

[0049] The retaining clip 30 may be discarded, at which point the entire or desired portion of the medical liquid contents has been administered. If the liquid is to be administered incrementally, the retaining clip 30 may optionally be reattached to the plunger rod 20 and positioned against the flange 16, thereby better retaining the position of the stopper within the syringe barrel 10.

[0050] Details of the second embodiment of the present invention will now be described and are best seen in Figures 6-9. While the first embodiment of the present invention (shown in Figures 1-5) can prevent the plunger rod 20 and stopper from moving toward the distal end 12 of the syringe barrel 10, for example, during transportation and storage of the prefilled syringe, it may not be able to prevent their unintended movement in the opposite direction, away from the distal end 12. A more secure locking of the plunger rod 20 with the syringe barrel 10 is needed to eliminate the risk of any significant movement of the stopper in any direction while within the syringe barrel 10 and better maintain the sterility of its medical liquid contents.

[0051] The locking clip 30 of the second embodiment of the present invention includes a flange-engaging extension 40 extending from at least one or both of the second ends 33 and 37 of the arms 32 and 36 on the same side. Extension 43 is formed with and extends from second end 33, and extension 47 is formed with and extends in the same general direction from second end 37. A notched slot 44 is provided between extension 40 and the body of the locking clip 30. The depth and width of notched slot 44 are selected to be at least sufficient to receive flange 16 therein upon positioning the locking clip 30 of the second embodiment of the present invention over a syringe barrel 10.

[0052] 9, a curved rest pad 42 may optionally be provided as part of extension 40. The dimensions and extent of curvature of rest pad 42 are selected to match the outer diameter of syringe barrel 10 such that rest pad 42 rests on the outer surface of syringe barrel 10 when locking clip 30 is placed on plunger rod 20, as seen in FIGS.

[0053] The use of the locking clip 30 of the second embodiment of the present invention is similar to that of the first embodiment in that it is positioned to engage the plunger rod 20 in the same manner. The difference is that by its positioning, the locking clip 30 of the second embodiment also engages the flange 16 of the syringe barrel 10, thereby fixing the position of the plunger rod 20 relative to the syringe barrel 10 and not allowing the stopper to move in either direction toward or away from the distal end 12 of the syringe barrel 10.

[0054] The shape of the ridge is selected to completely prevent movement of the plunger rod 20 toward the distal end 12 of the syringe barrel 10 (except for a small amount of play defined by dimension c), and furthermore, the locking clip 30 of the second aspect of the present invention is useful for allowing the plunger rod 20 to move away from the distal end 12 of the syringe barrel 10 only when the outward force on the stopper exceeds a predetermined threshold level.

[0055] Similar to the embodiment shown in Figure 5, the first side 28 of each ridge 27 forms a generally acute angle α with respect to the longitudinal axis of the plunger rod, as seen in Figure 3. The angle α may be selected from about 10 degrees to about 70 degrees, e.g., 10 degrees, 15 degrees, 20 degrees, 25 degrees, 30 degrees, 35 degrees, 40 degrees, 45 degrees, 50 degrees, 55 degrees, 60 degrees, 65 degrees, 70 degrees, or any suitable angle therebetween. The angle α plays an important role in limiting the threshold force at which the plunger rod 20 can be moved away from the distal end of the syringe barrel 10.

[0056] When encountering pressure changes (such as due to refrigeration and / or altitude changes), the expansion of the liquid contents of the syringe can exert significant pressure on the stopper of plunger rod 20. In response, plunger rod 20 can cause ridge 27 to apply some lateral force to notch 31, depending on angle a and other dimensions of the ridge / notch geometry and the mechanical elastic properties of the material used to fabricate locking clip 30. All of the above factors define a threshold force that, when exceeded, will cause the arms of locking clip 30 to open, allowing plunger rod 20 to move away from distal end 12 of syringe barrel 10. That is, exceeding the threshold force causes locking clip 30 to temporarily disengage from ridge 27, move distally along plunger rod 20 a distance equal to the length c between ridges 27, and re-engage with ridge 27 at a more distal location on plunger rod 20. The width of the ridges 27 also limits the range of outward movement of the plunger rod 20, allowing the locking clip 30 to close back onto the plunger rod 20 and the notches 31 to engage with an adjacent set of ridges 27. In various designs of the locking clips and corresponding plunger rods 20 of the kits of the present invention, the threshold force level required to move the plunger rod 20 away from the distal end of the syringe barrel 10 is selected to be greater than at least 0.5 kgf or greater so as to maintain the plunger rod 20 in place when the force on the stopper falls below the threshold level. In further designs, the threshold level is selected to be at least 1 kgf, at least 1.5 kgf, at least 2 kgf, at least 2.5 kgf, at least 3 kgf, or more, although the present invention is not limited in this respect. As will be appreciated by those skilled in the art, a higher threshold force ensures better stability of the stopper within the syringe barrel 10.

[0057] The relative position of plunger rod 20 with respect to locking clip 30 may also serve as an indicator that the contents of syringe barrel 10 have been compromised and should not be administered to a patient. For example, significant movement of locking clip 30 from its initial position on plunger rod 20 to its final position prior to removal of locking clip 30 indicates an unintended increase in pressure within syringe barrel 10. Such an increase in pressure may indicate that the contents of syringe barrel 10 have been compromised and should be discarded. For example, an indicator mark may be provided on plunger rod 20 at a predetermined distance (e.g., 2 mm) from the initial, safe position of locking clip 30. If locking clip 30 moves beyond the indicator mark, it is assumed that the prefilled syringe has been compromised.

[0058] The third embodiment of the locking clip 50 of the present invention will now be described in detail and is best seen in FIGS. 11-17. The plunger rod 20 of this design is provided with at least one or more open slots formed through its side walls. For example, FIG. 14 shows the plunger rod 20 with a first open slot 61 in side wall 24. Corresponding open slots are shown in side walls 25 and 26. In this design, one open slot is provided in all four side walls of the elongated body of the plunger rod 20. The location of the open slot defines the locking position of the plunger rod 20 when assembled with the syringe barrel 10, as described in more detail below. To facilitate more flexible use of the kit of the present invention, additional rows of open slots 62 may be provided in the side walls 24, 25, and 26 of the plunger rod 20 along its length. Each of the additional rows of open slots may define an additional fixed position for the plunger rod within the syringe barrel 10, which may be useful when different amounts of medical fluid need to be stored using the kit of the present invention or when different headspace sizes exist.

[0059] The width and depth of open slots 61, 62 are selected to be large enough to slideably accommodate protrusion 58 of locking clip 50 therethrough, as described in more detail below. Both width and depth can independently range from about 1 mm to about 10 mm, e.g., at least 1 mm, at least 2 mm, at least 3 mm, at least 4 mm, at least 5 mm, at least 6 mm, at least 7 mm, at least 8 mm, at least 9 mm, or other suitable distances. One or both dimensions of each open slot are selected so as not to compromise the mechanical integrity of the plunger rod during storage, shipping, assembly, and use to administer medical fluid from the syringe, as would be understood by one skilled in the art.

[0060] The locking clip 50 of the third embodiment of the present invention comprises an upper wall 52 and a lower wall 54 attached to and spaced from the upper wall 52 along a common periphery of the upper wall 52. The upper and lower walls 52, 54 define a cavity 53 formed therebetween with a side opening in a central portion of the locking clip 50. To enhance its mechanical integrity, additional internal side walls 55 may be fabricated to connect both the upper and lower walls together, but these side walls 55 are positioned so as not to reduce the width of the cavity 53 below the minimum allowable width defined by the width or diameter of the barrel flange 16.

[0061] Side opening 53 of locking clip 50 is fabricated to accommodate the various elements of syringe barrel 10, barrel flange 16, and plunger rod 20, as previously described. Top wall 52 is fabricated with a centrally located side opening wide enough to receive a portion of the plunger rod with open slot 61. Two side projections 58 are formed to narrow the side opening in top wall 52. These side projections 58 are sized to pass through open slot 61 in plunger rod 20, as best seen in FIG. 11 . When locking clip 50 is removably positioned on syringe barrel 10 with plunger rod 2 inserted therein, lateral projections 58 engage side walls 24, 25, 26 both above and below open slot 61, preventing plunger rod 20 from moving in either direction along syringe barrel 10.

[0062] Bottom wall 54 has a larger side opening wide enough to receive the exterior surface of the cylindrical syringe barrel against semicircular arch 56, as best seen in Figures 15 and 16. The shape of semicircular arch 56 is created to extend from one ridge 57 on one side of arch 56 to another ridge 57 on the other side. The ridges 57 on either side of arch 56 together form a snap-in detent, which is designed to allow the cylindrical portion of syringe barrel 10 to removably snap onto and stay in place.

[0063] The interior cavity 53 of the locking clip 50 is configured to receive the barrel flange 16 therein, as seen in Figures 11 and 12. When the locking clip 50 is positioned over the flange 16 and snapped into place, it cannot move along the syringe barrel 10.

[0064] During the manufacturing process of the syringe assembly, the stoppered plunger rod 20 is first placed into the syringe barrel 10. The one or more open slots 61 are then aligned to be at or slightly above the barrel flange 16. The locking clip 50 is then advanced from the side of the syringe assembly until the syringe barrel snaps into a detent formed in the bottom wall 54. The positioning of the locking clip 50 on the flange 16 provides for the locking of both the plunger rod 20 and the syringe barrel 10 to the locking clip 50, which thus secures all components of the kit together and prepares the syringe assembly for storage and transportation.

[0065] When the medical practitioner is ready to administer the medical fluid from the syringe assembly, the medical practitioner rotates the plunger rod 20 so that the side walls 24, 25, 26 move away from the lateral protrusions 58. As shown in FIG. 17 , such rotation can be approximately 45° from the initial position of the plunger rod 20. The plunger rod 20 can then be pushed distally to administer the medical fluid from the syringe assembly. As the plunger rod 20 is pushed, the side walls 24, 25, 26 slide laterally against the lateral protrusions 58. Thus, the lateral protrusions 58 are sized and shaped to fit within the spaces between adjacent side walls 24, 25, 26.

[0066] Next, the fourth embodiment of the present invention will be described in more detail and is shown in FIGS. 18-19. The fourth embodiment of the present invention solves one rare situation, seen in FIG. 17, that can reduce the effectiveness of the third embodiment of the present invention. When the four side walls of the plunger rod 20 are rotated in a certain way, the side walls of the plunger rod 20 are no longer constrained by the locking clip 50, and the stopper can still find a way to move in either direction along the syringe barrel. That is, as described above with reference to FIG. 17, the plunger rod 20 can be unintentionally rotated into a position for injection. When this happens, the V-shaped lateral protrusions 58 can slide along the open space in any one of the four quadrants along the plunger rod 20.

[0067] To address this issue, the locking clip 50 of the fourth embodiment of the present invention includes a stopper 59 that extends perpendicular to and above the top wall 52 (see FIG. 18 ). The stopper 59 may have a tapered, ramp-in surface configured to cooperate with portions of the open slot 61 in the plunger rod 20. When the locking clip 50 is positioned in place on the syringe assembly, the plunger rod 20 may be in one of several radial orientations, as shown schematically in FIGS. 19A, 19B, and 19C. FIG. 19A illustrates a radial orientation of the plunger rod 20 in which the sidewall 24 of the plunger rod 20 disengages from the clip 50, allowing the plunger rod 20 to move in and out of the syringe barrel 10. Thus, the plunger rod 20 may be pushed to deliver the medical fluid. To secure the syringe, plunger rod 20 is rotated clockwise such that sidewall 24 first engages stopper 59 (see FIG. 19B), providing resistance to further rotation as stopper 59 extends slightly beyond the size of open slot 61. Continued rotation of plunger rod 20 results in movement of sidewall 24 past stopper 59, securing plunger rod 20 in position.

[0068] Rotating the plunger rod 20 in the opposite direction, back to the orientation shown in FIG. 19A, unlocks the plunger rod 20, allowing the medical fluid to be dispensed from the syringe assembly by pushing the plunger rod 20.

[0069] While this disclosure has been described as having exemplary designs, the disclosure may be further modified within the spirit and scope of the disclosure. Accordingly, this application is intended to cover any variations, uses, or adaptations of the disclosure using its general principles. Further, this application is intended to cover such departures from the disclosure as come within known or customary practice in the art to which this disclosure pertains and which fall within the scope of the appended claims.

Claims

1. 1. A kit for maintaining the sterility of a prefilled syringe, the kit comprising: A syringe barrel (10); a plunger rod (20) attached to a stopper for use with the syringe barrel (10), the plunger rod (20) comprising an elongate body having an attachment distal end and a proximal end configured to be attached to the stopper, the elongate body extending along a longitudinal axis between the distal end and the proximal end, the plunger rod (20) further comprising one or more ridges (27) extending laterally from the elongate body and spaced apart along the elongate body; a locking clip (30) comprising one or more notches (31) that match in size and spacing with the one or more ridges (27) of the plunger rod (20), the locking clip (30) being configured to be removably attached to the plunger rod (20) such that the one or more ridges (27) of the plunger rod (20) are positioned within the one or more notches (31) of the locking clip (30); Inserting the plunger rod (20) and the stopper into the syringe barrel (10) and filling the syringe barrel with a medical fluid causes the locking clip (30) to extend outwardly from the plunger rod (20) and beyond the syringe barrel (10), thereby preventing unintended longitudinal movement of the plunger rod (20) and the stopper along the syringe barrel (10); The locking clip (30) comprises a pair of hinged V-shaped arms (32, 36) forming a normally closed clamp, each arm (32, 36) defining a first end (34, 38) and a second end (33, 37), one or more notches (31) positioned in the first end (34, 38) of at least one arm (32, 36), the first end (34, 38) of the arm (32, 36) being such that the locking clip (30) is aligned with the longitudinal axis of the plunger rod (20). the locking clip (30) includes angled leading edges (74, 78) that engage with the plunger rod (20) when moved transversely to the axis toward the plunger rod (20), and the force of contact between the plunger rod (20) and the angled leading edges (74, 78) causes the first ends (34, 38) of the arms (32, 36) to move apart, allowing the locking clip (30) to be fully seated on the plunger rod (20).

2. 2. The kit of claim 1, wherein the elongated body of the plunger rod (20) comprises four side walls (24, 25, 26) extending radially from a center to form an X-shaped cross-sectional profile, the side walls (24, 25, 26) positioned at 90 degrees to one another to define four quadrants therebetween, and one or more ridges (27) extending laterally in at least one of the quadrants.

3. 3. The kit of claim 2, wherein a plurality of ridges (27) are disposed along the plunger rod (20) in at least one of the same quadrant of the elongated body, at least two opposing quadrants of the elongated body of the plunger rod (20), and all four quadrants of the elongated body of the plunger rod (20).

4. 3. The kit according to claim 2, wherein each protuberance (27) has a triangular shape extending from one side wall (24, 25, 26) of the elongated body to an adjacent side wall (24, 25, 26) within the same quadrant, and the triangular shape of each protuberance (27) is defined by a first side (28) and a second side (29) between adjacent side walls (24, 25, 26) of the plunger rod (20), the first side (28) facing the proximal end of the plunger rod (20) and the second side (29) facing the distal end of the plunger rod (20).

5. 2. The kit of claim 1, wherein the second end (33, 37) of each arm (32, 36) is configured as a finger-engagement end engageable by a user, and the second ends (33, 37) of the arms (32, 36) are configured to be pressed together to move the first ends (34, 38) of both of the arms (32, 36) apart and enable removal of the locking clip (30) from the plunger rod (20).

6. 2. The kit of claim 1, wherein the securing clip (30) is integrally formed, the arms (32, 36) are connected by a living hinge (39), and movement of both second ends (33, 37) of each arm (32, 36) toward each other causes the respective first ends (34, 38) of each arm (32, 36) to move away from each other.

7. 2. The kit according to claim 1, wherein each notch (31) is made with dimensions that match or exceed the dimensions of the corresponding protuberance (27) on the plunger rod (20).

8. 8. The kit according to claim 7, wherein the notches (31) are made wider than the corresponding protuberances (27) to form a gap therebetween when the locking clip (30) is placed on the plunger rod (20).

9. 2. The kit of claim 1, wherein the syringe barrel (10) comprises a barrel flange (16) at its proximal open end, and the locking clip (30) further comprises a flange-engaging extension (40) extending from a second end (33, 37) of one or both of the pair of arms (32, 36) forming the locking clip (30).

10. 10. The kit of claim 9, wherein the locking clip (30) further defines a notched slot (44) formed on the extension (40) thereof and sized to receive the barrel flange (16) of the syringe barrel (10) therein upon placement of the locking clip (30) on the plunger rod (20) of the kit.

11. 11. The kit of claim 10, wherein the flange-engaging extension (40) of the locking clip (30) further comprises a curved rest pad (42) sized to be positioned against an exterior surface of the syringe barrel (10).

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