Sequential drug delivery syringe

Abstract

A dual chamber sequential delivery syringe facilitates selective drug mixing, dosing and administration through a catheter or other vascular access device (VAD), as well as post-administration catheter irrigation using a single syringe instrument. The syringe barrel includes an outlet, such as a luer connector, a variable volume primary chamber, and a secondary chamber pre-filled with fluid. A pushrod operated telescopic actuator in conjunction with a medicament stopper disposed within the barrel interior forms a valve for selectively isolating the secondary fluid chamber from fluid communication with the primary fluid chamber and / or the outlet of the syringe barrel. Opening of the valve is automatically accomplished by continuous advancement of the push rod.

Description

Technical Field

[0001] The present disclosure generally relates to a dual-chamber sequential drug delivery syringe for administering two fluids, or for administering and flushing catheters and other vascular accessing devices (VADs), or for mixing and administering fluids; and a method for sequential drug delivery via a single syringe. Background Art

[0002] VADs are commonly used therapeutic devices and include I.V. catheters. VADs are generally classified into two types: peripheral catheters and central venous catheters. If not properly maintained, VADs can become blocked. To ensure proper use of VADs and prevent blockage, practice standards have been developed. These standards include cleaning procedures, commonly referred to as flushing procedures or flushing the catheter.

[0003] VAD practice standards generally recommend performing flushing procedures after catheter placement, before fluid infusion, and before and after drug administration, blood sampling, blood transfusion, and parenteral nutrition. The goals of these flushing procedures are to confirm catheter patency, avoid drug incompatibility, ensure complete drug dose administration, prevent thrombosis, and minimize the risk of bloodstream infection. Flushing procedures require different types and amounts of flushing solutions. Commonly used flushing solutions are saline and / or heparin lock solutions. The type and amount of flushing solution vary depending on the specific type of catheter. A flushing solution volume between 5 ml and 10 ml is most common, but the range can be from 1 ml to 20 ml.

[0004] For flushing procedures, an I.V. line refers to a system that includes a VAD (a set of tubing with a clamp) and can terminate in a port or valve. The most common type of port is covered by a pierceable septum or a pre-cut septum and is known in the art and sometimes referred to as a "PRN", derived from the Latin pro re nata, meaning "as needed". The septum is preferably made of rubber or another elastomeric material, which allows insertion of a sharp needle cannula to infuse fluid or withdraw fluid from the catheter. After withdrawing the needle cannula, the septum seals itself. Ports with pre-cut septa are used with a blunt cannula or the truncated conical end of a syringe barrel. The end of the syringe or the blunt cannula (which is usually attached to the syringe) is gently pushed through the pre-cut septum to establish fluid communication.

[0005] An I.V. valve (another type of terminal I.V. access device that does not require a needle with a sharp tip) is initiated through the frustoconical end of a syringe barrel (e.g., a Luer connector) to allow fluid communication between the interior of the syringe and the catheter. These valves can include structures for delivering fluid from a storage compartment within the valve to the catheter and are referred to in the art as positive displacement valves.

[0006] Removing debris or residues is referred to as "flushing" or "irrigation" and prevents the deposition and accumulation of blood, blood residues, and IV medications within the catheter or other VAD device. Such accumulation can lead to partial or complete blockage of the fluid pathway within the catheter system and may also require costly and potentially dangerous methods for flushing the affected catheter or replacing the catheter entirely. Typically, such blockages result in treatment interruptions, which can compromise patient care. The accumulation of residues within the catheter can also increase the risk of infection by providing a growth medium for microorganisms.

[0007] As will be understood by those skilled in the art, flushing techniques involve injecting a flushing solution (e.g., a saline solution) into the VAD to clear debris and blockages. The injection is typically achieved by advancing a plunger rod into a pre-filled syringe barrel, thereby expelling the flushing solution into the VAD. When such techniques are used in conjunction with a catheter, turbulence is introduced within the catheter, thereby dislodging any debris or residues attached to the catheter. Flushing techniques require the application of a substantially constant pressure or force on the plunger rod in the distal direction. Conventional or smooth flushing techniques can also include the application of a substantially linearly increasing or decreasing pressure or force on the plunger rod in the distal direction.

[0008] After flushing, the practitioner can then administer a dose of a medical fluid, which is either in a vial from which it needs to be withdrawn or in a separate pre-filled syringe. However, connecting multiple devices to the VAD introduces connectors into the unsterile external environment, thereby introducing the possibility of transmitting catheter-related bloodstream infections (CRBSIs), which can be costly and potentially fatal. To reduce CRBSI cases and to ensure the proper use and maintenance of VADs, practice standards have been developed, which include disinfection and cleaning procedures.

[0009] In clinical practice, intravenous drugs are administered, followed by an IV flush, typically using two separate syringes. Flushing is performed after drug administration because residual drug may remain in the luer portion of the drug delivery syringe as well as in the catheter. Without a subsequent flushing procedure, it may not be possible to deliver the full drug dose to the patient. Some drugs are time-sensitive for administration and should not remain in the catheter until a subsequent medical administration flushes the residual amount of the previous drug through the line. A second syringe is used for sequential flushing to address the residual drug delivery issue, but using a second flushing syringe has certain drawbacks, namely: potential drug delivery errors and the inability to track drug delivery in the case of a flushing procedure. Potential drug delivery can occur because the most commonly used ones are colorless, like saline and other flushing solutions. If the healthcare professional administering the drugs is distracted during the procedure, it may happen that the flushing solution cannot be delivered after drug delivery.

[0010] There is a need for a syringe assembly that has means for both flushing a VAD and administering a dose of medical fluid, thereby reducing the risk of CRBSI. There is also a need for such a single syringe that is used for administering intravenous drugs, followed by an IV flush, to increase clinician efficiency and reduce the costs associated with maintaining syringe inventory and medical waste disposal. There is also a need for such a single syringe that is used for mixing drugs in powder form and then administering the mixed drugs to a patient. Summary of the Invention

[0011] A dual-chamber sequential drug delivery syringe facilitates selective drug mixing, metering, and administration through a catheter or other vascular access device (VAD), as well as post-administration catheter flushing using a single syringe instrument. The syringe disclosed herein is used as a sequential syringe, where one chamber is pre-filled with saline or other flushing solution and the other chamber is pre-filled with a drug or filled on-site by a healthcare professional. In other embodiments, the sequential drug delivery syringe is used as a drug mixing syringe, with one chamber pre-filled with saline or another diluent and the other chamber pre-filled with a powdered / lyophilized drug. The syringe barrel includes an outlet (such as a Luer connector), a main fluid chamber, and a secondary fluid chamber. A telescoping actuator assembly (which is coupled to a plunger stopper) acts as an isolation valve for selectively opening or blocking a through-passage formed in the drug stopper. The telescoping actuator assembly selectively isolates the secondary chamber from the main chamber only by the advancement of the syringe plunger. In medical procedures where both flushing and drug administration through a catheter or other VAD are required, using a syringe of the type disclosed herein reduces the need for multiple infusions and withdrawals with multiple single-function syringes. Using the disclosed syringe advantageously reduces the risk of patient infection, reduces costs associated with syringe inventory and subsequent waste disposal, and shortens the time required for a clinician to complete the relevant medical procedure.

[0012] One aspect of the present disclosure relates to a sequential delivery syringe that includes a hollow syringe barrel that defines an inner wall, a proximal barrel end, and a distal barrel end. The distal end of the barrel includes a connector that defines an exit lumen therethrough. The exit lumen is in fluid communication with the interior of the barrel. The interior of the barrel is defined by the open proximal end, the distal end, and the inner wall of the barrel. The syringe includes a plunger disposed within the interior of the barrel, having a proximal end that extends beyond the proximal end of the barrel and a distal end. The syringe includes a secondary or saline stopper disposed within the interior of the barrel, having a proximal axial end coupled to the distal end of the plunger and a distal axial end that defines a distal cavity. A primary or drug stopper is disposed within the interior of the barrel, between the secondary stopper and the distal end of the barrel. The primary or drug stopper has a proximal axial end that defines a proximal cavity, a distal axial end that defines a distal cavity having a seating surface, and a through-channel that is in fluid communication with both its proximal and distal cavities. A telescoping actuator assembly is oriented with respect to the respective cavities of the primary and secondary stoppers. The actuator assembly functions as a valve to isolate the proximal cavity of the primary stopper from its distal cavity. The actuator assembly includes a reciprocable actuator oriented within the through-channel of the primary stopper. The actuator projects into the proximal and distal cavities of the primary / drug stopper and has an outer peripheral surface that engages the through-channel with a sliding friction and a radially projecting proximal axial face that is oriented within the corresponding distal cavity of the primary stopper (in an orientation opposite to the seating surface). The actuator assembly further includes a tube having an outer peripheral surface that is coupled to and disposed within the distal cavity of the secondary stopper and an inner wall that surrounds and engages the outer peripheral surface of the actuator with a sliding friction. The syringe has a main fluid chamber within the interior of the barrel, defined between the distal end surface of the primary stopper and the exit lumen at the distal end of the barrel. The volume of the main fluid chamber can be selectively varied by translation of the plunger. The syringe has a secondary fluid chamber within the interior of the barrel, defined between the distal end surface of the secondary stopper and the through-channel of the primary stopper. When the proximal axial face of the actuator is spaced apart from the seating surface of the primary stopper, the volume of the secondary fluid chamber can be selectively varied by translation of the plunger. In this syringe embodiment, when the proximal axial face of the actuator is spaced apart from the seating surface of the primary stopper, the secondary fluid chamber is in fluid communication with the main fluid chamber and the exit lumen of the syringe, and when the proximal axial face of the actuator is in abutting contact with the seating surface of the primary stopper, the secondary fluid chamber is isolated from the main fluid chamber. When using the syringe, retracting the plunger tensions the telescoping actuator assembly, causing the proximal axial face of the actuator to move correspondingly rearward into abutting contact with the seating surface of the primary stopper and retracting the drug stopper / primary stopper. When using the syringe, advancing the plunger alone advances the primary or drug stopper, causing the proximal axial face of the actuator to move correspondingly forward away from abutting contact with the seating surface of the primary stopper, advancing the secondary or saline stopper, and causing the telescoping actuator assembly to collapse within the respective distal cavity of the secondary stopper and the proximal cavity of the primary stopper.

[0013] In some embodiments of the syringe disclosed herein, its secondary chamber is pre-filled with a flushing solution. Ideally, a clinician can use the primary chamber to administer a drug into a patient's VAD and immediately use the secondary chamber to flush the VAD without removing the syringe from the VAD. In the embodiments of the syringe disclosed herein, a clinician can administer the drug through the VAD in a single continuous push of a single plunger and then immediately flush the VAD.

[0014] Another aspect of the present disclosure relates to a sequential drug delivery syringe. The syringe includes a hollow syringe barrel that defines an inner wall, a proximal barrel end, and a distal barrel end. The distal end of the barrel includes a connector that defines an exit lumen therethrough, where the exit lumen is in fluid communication with the interior of the barrel. The interior of the barrel is defined by an open proximal end, a distal end, and an inner wall. A plunger is disposed within the interior of the barrel and has a proximal end that extends beyond the proximal end of the barrel and a distal end. A secondary stopper or saline stopper is disposed within the interior of the barrel and has a proximal axial end coupled to the distal end of the plunger and a distal axial end that defines a distal cavity therein. A primary stopper or drug stopper is disposed within the interior of the barrel between the secondary stopper and the distal end of the barrel. The primary stopper has a proximal axial end that defines a proximal cavity, a distal axial end that defines a distal cavity having a seating surface, and a through-channel that is in fluid communication with both the proximal and distal cavities. The syringe also has a telescoping actuator assembly that is oriented with respect to the respective cavities of the primary and secondary stoppers. The telescoping actuator assembly includes a plurality of nested tubes that are in sliding frictional engagement with one another; each nested tube has an outer peripheral surface and an inner wall respectively. The outer peripheral surface of the most proximal oriented tube of the nested tubes is coupled to and within the distal cavity of the secondary stopper, where the inner wall of the most proximal oriented tube is in sliding frictional engagement with the outer peripheral surface of an adjacent tube captured therein. A reciprocable actuator is oriented within the through-channel of the primary stopper. The actuator includes a collet bushing having an annular bushing edge, the radially projecting proximal axial face of the annular bushing edge being in an opposite orientation to the mating annular seating surface of the primary stopper. The collet bushing has a plurality of collet bushing fingers that project away from the proximal axial face of the annular bushing edge and are in frictional contact with the surface that defines the through-channel. The distal end of each bushing finger projects into the proximal cavity of the primary stopper. The distal ends of the collet bushing fingers are coupled to a platform that is oriented on the distal end of the actuator shaft. The outer surface of the proximal end of the actuator shaft is in sliding frictional engagement with the inner wall of the most distal oriented tube. The seating surface of the primary stopper is captured between the collet bushing and the platform. The syringe defines a main fluid chamber within the interior of the barrel between the distal end surface of the primary stopper and the exit lumen at the distal end of the barrel. The volume of the main fluid chamber can be selectively varied by translation of the plunger. The syringe defines a secondary fluid chamber within the interior of the barrel between the distal end surface of the secondary stopper and the through-channel of the primary stopper. The volume of the secondary fluid chamber can be selectively varied by translation of the plunger when the proximal axial face of the annular bushing edge of the collet bushing is spaced apart from the seating surface of the primary stopper. In this syringe, when the proximal axial face of the annular bushing edge of the collet bushing is spaced apart from the seating surface of the primary stopper, the secondary fluid chamber is in fluid communication with the main fluid chamber and the exit lumen of the syringe, and when the proximal axial face of the annular bushing edge is in abutting contact with the seating surface of the primary stopper, the secondary fluid chamber is isolated from the main fluid chamber.When using the syringe, pulling back the plunger tightens the telescoping actuator assembly, causing the proximal axial face of the collet bushing to move correspondingly rearward, abutting against the seating surface of the primary stopper and withdrawing said stopper. When the syringe is in use, individually advancing the plunger advances the primary stopper, causing the proximal axial face of the collet bushing of the actuator to move correspondingly forward, away from abutting contact with the seating surface of the primary stopper, advancing the secondary stopper, and causing the telescoping actuator assembly to collapse within the corresponding distal cavity of the secondary stopper and the proximal cavity of the primary stopper.

[0015] In some syringe embodiments of the present disclosure, an inwardly radially projecting barrel ring is formed on the inner wall of the barrel, and a path seal prevents fluid from flowing back from the primary chamber to the secondary chamber. The path seal has an inner circumferential surface surrounding the outer surface of the tube of the actuator assembly, and an outer circumferential surface in fluid-tight contact with the proximal cavity of the primary stopper.

[0016] Other aspects of the present disclosure relate to a method for manufacturing the sequential delivery syringe disclosed herein, which is achieved by inserting the collet bushing fingers into the through-channel of the primary stopper such that they project into the proximal cavity. After inserting the collet bushing, the platform of the actuator assembly is coupled to the ends of the collet bushing fingers, capturing the primary stopper between the annular edge of the collet bushing and the cross-shaped platform. Next, the most proximally oriented tube of the actuator assembly is coupled within the distal cavity of the secondary stopper, either before or after coupling the plunger to the secondary stopper. The now-coupled primary stopper, actuator assembly, secondary stopper, and plunger are inserted into the interior of the syringe barrel.

[0017] The corresponding features of the aspects and exemplary embodiments of the present disclosure described herein can be applied jointly or individually in any combination or sub-combination. Description of the Drawings

[0018] In the following detailed description, exemplary embodiments of the present disclosure are further described in conjunction with the accompanying drawings, in which:

[0019] Figure 1 is a cross-sectional view of an embodiment of a dual-chamber syringe, where the secondary chamber is pre-filled with fluid and the primary drug delivery chamber is collapsed;

[0020] Figure 2 is Figure 1 an enlarged cross-sectional view of the distal portion of the syringe;

[0021] Figure 3 is Figure 1 an exploded view of the syringe;

[0022] Figure 4 is Figure 1 an axial end view of the drug stopper of the syringe;

[0023] Figure 5 is Figure 1 Perspective view of the telescoping actuator assembly of the syringe in its fully extended configuration;

[0024] Figure 6 is Figure 5 Cross-sectional view of the telescoping actuator assembly;

[0025] Figure 7 is Figure 1 Perspective view of the telescoping actuator assembly of the syringe in its fully collapsed configuration; another embodiment of a dual-chamber syringe, wherein each chamber contains fluid;

[0026] Figure 8 shows removal of trapped air from Figure 1 the prefilled chamber of the syringe;

[0027] Figure 9 is Figure 8 Magnified cross-sectional view of the distal portion of the syringe;

[0028] Figures 10 - 13 are exemplary sequential steps that respectively show aspiration of a drug in the Figure 8 drug chamber or main chamber of the syringe, followed by dispensing / infusing the drug, followed by activating or opening the fluid path of the prefilled chamber or secondary chamber, and finally delivering a flush fluid from the secondary chamber;

[0029] Figure 14 is a perspective view of an embodiment of a dual-chamber drug mixing syringe, wherein the secondary chamber is prefilled with a diluent and the main drug delivery chamber is prefilled with a powdered / lyophilized drug;

[0030] Figure 15 is Figure 14 Cross-sectional view of the syringe.

[0031] For ease of understanding, the same reference numerals are used, where possible, to identify the same elements common to the figures. The figures are not drawn to scale. Detailed Description

[0032] Aspects of the dual-chamber syringe embodiments disclosed herein facilitate selective drug mixing, metering, and administration through a catheter or other vascular access device (VAD), as well as post-administration catheter flushing using a single syringe instrument. Generally, in each disclosed embodiment, the syringe barrel includes an outlet (such as a Luer connector), a variable-volume main fluid chamber, and a secondary chamber pre-filled with a fluid (such as a saline flush fluid). A push-rod actuated telescoping actuator assembly is coupled to a secondary or saline plunger plug, which, in combination with a main or drug plunger disposed within the barrel interior, functions as an isolation valve for selectively blocking or opening a through-channel formed in the drug plunger. The telescoping actuator assembly selectively isolates the secondary fluid chamber only upon retraction of the syringe push-rod to avoid fluid communication with the main fluid chamber and / or the outlet of the syringe barrel. The telescoping actuator assembly selectively opens the through-channel only upon advancement of the syringe push-rod.

[0033] The isolated secondary chamber configuration advantageously facilitates the use of pre-packaged drugs or flush solutions in the chamber, whereby a clinician can use an empty main chamber to aspirate and dispense a drug and then immediately deliver a pre-packaged flush solution from the secondary chamber. In other embodiments, the syringes disclosed herein are used as drug mixing syringes, having a powdered drug pre-packaged in the main chamber and a diluent solution pre-packaged in the secondary chamber. In some embodiments, a single push stroke on the syringe push-rod automatically and sequentially delivers the drug contained in the main chamber, followed by the flush solution, into the VAD.

[0034] In this disclosure, following convention, the distal end of a device is the end closest to the patient, e.g., for delivering one or more drugs to the patient, and the proximal end of the device is the end farthest from the patient and closest to the clinician or other healthcare practitioner. Regarding the terms used in this disclosure, the following definitions are provided.

[0035] As used herein, the use of "a", "an", and "the" includes both singular and plural.

[0036] As used herein, the term "Luer connector" refers to a connecting collar that is a standard way of attaching syringes, catheters, hubbed needles, IV tubing, etc. to each other. A Luer connector consists of a male interlocking tube and a female interlocking tube, which are slightly tapered so that they hold together better with just a simple press / twist fit. The Luer connector may optionally include an additional external threaded edge to allow them to be more secure. The male end of the Luer connector is associated with and interlocks and connects to the female end located on a vascular access device (VAD). The Luer connector also has a distal end channel for releasably attaching the Luer connector to the hub of the VAD and a proximal end channel for releasably attaching the Luer connector to the barrel of the syringe.

[0037] As used herein, ISO 80369-7:2016 defines the specifications of a standard Luer connector, including a 6% taper between the distal end and the proximal end. The male standard Luer connector increases from the open distal end towards the proximal end. The female standard Luer connector decreases from the open proximal end towards the distal end. According to ISO 80369-7:2016, the outer cross-sectional diameter of the male standard Luer connector (measured 0.75 mm from the distal end of the tip) is between 3.970 mm and 4.072 mm. The length of the male standard Luer taper is between 7.500 mm and 10.500 mm. The outer cross-sectional diameter (measured 7.500 mm from the distal end of the tip) is between 4.376 mm and 4.476 mm. As used herein, the phrases "male standard Luer connector" and "female standard Luer connector" refer to connectors having the dimensions described in ISO 80369-7, which is hereby incorporated by reference in its entirety.

[0038] As will be readily understood by those skilled in the relevant art, although descriptive terms such as "tip", "hub", "thread", "protrusion / insertion", "tab", "ramp", "wall", "top", "side", "bottom", etc. are used throughout this specification for ease of understanding, they are not intended to limit any components that can be used in combination or separately or that require a specific spatial orientation to implement the various aspects of the embodiments of the present disclosure.

[0039] Before describing several exemplary embodiments of the present disclosure, it should be understood that the present disclosure is not limited to the details of the construction or processing steps set forth in the following description. The present disclosure is capable of having other embodiments and of being practiced or carried out in various ways.

[0040] The situations illustrated in this specification are provided to assist in a comprehensive understanding of the exemplary embodiments of the present disclosure. Accordingly, those of ordinary skill in the art will recognize that various changes and modifications can be made to the embodiments described herein without departing from the scope and spirit of the present disclosure. Additionally, descriptions of well-known functions and constructions are omitted for clarity and brevity.

[0041] In an exemplary implementation of an embodiment of the present disclosure, the barrel of a syringe includes a distal end having a needleless connection. In one or more embodiments, the needleless connection includes at least one thread and other features in all combinations, thereby allowing it to dock with one or more corresponding threads of a corresponding connector.

[0042] In a further exemplary embodiment according to the present disclosure, the configuration of the structural elements that make up the needleless connector includes a collar that protrudes from the distal end of the barrel, the collar including at least one thread for connection to one or more corresponding threads of a corresponding connector.

[0043] In a further exemplary embodiment according to the present disclosure, the collar or the needleless connector may be bent or elastically deformed to allow for better interference fit compliance with the corresponding connector.

[0044] In a further exemplary embodiment according to the present disclosure, the needleless connector may include a female thread whose size and thread pattern will engage with a standard ISO594-2 male fitting type, and / or a male thread whose size and thread pattern will engage with a standard ISO594-2 female fitting type. An example of the ISO594-2 fitting type is the Q-type fitting.

[0045] In one or more embodiments, the female connector may be selected from the group consisting essentially of: a needle-type connector (for direct injection into a patient or insertion into a drug vial for aspirating a drug dose therefrom), a needleless connector, a catheter luer connector, a stopcock, and a hemodialysis connector. In one or more embodiments, the needleless connector is selected from Q-Syte connector, MaxPlus, MaxPlus Clear, MaxZero, UltraSite, Caresite, InVision-Plus, Safeline, OneLink, V-Link, ClearLink, NeutraClear, Clave, MicroClave, MicroClaveClear, Neutron, NanoClave, Kendall, Nexus, InVision, Vadsite, Bionector, etc.

[0046] In one or more embodiments, the male connector may be an intravenous tubing end or a stopcock.

[0047] Referring now to the drawings, a first aspect of the present disclosure is shown in Figures 1 - 7 wherein the syringe 20 includes a substantially cylindrical barrel 22 that defines an open proximal end 24, an inner wall 26, and a distal end 28. In other embodiments, the barrel 22 includes a non-cylindrical profile. The tapered profile distal end 28 of the barrel 22 includes a threaded luer tip or connector 30 that defines an outlet cavity 32 for attachment to and fluid communication with various associated VAD connectors (not shown). A threaded, selectively removable male luer cap 34 seals the outlet cavity from ambient air. Refer to Figure 1 、 2And 4, the primary or drug stopper 36 (which is inserted within the syringe barrel 22) has a proximal axial end that defines a proximal cavity 42, and a tapered distal axial end 42. The tapered profile of the distal axial end 42 mates with the tapered profile of the distal end 28 of the syringe barrel 22 to facilitate complete evacuation of fluid from the syringe. The proximal cavity 40 is in fluid communication with the fan-shaped through-channel 44 and the distal cavity 46 defined within the medical stopper 36. An axially oriented seating surface 47 is defined within the distal cavity 46, surrounding the fan-shaped through-channel 44.

[0048] Reference Figure 1 and 3 , the syringe 20 includes a secondary or saline stopper 48, which is inserted within the barrel inner wall 26. The saline stopper 48 has a tapered distal end 50, which mates with the profile of the proximal axial end 38 of the drug stopper 36. The saline stopper 48 defines a distal end cavity 52 having a radial groove 53. The proximal end 54 of the saline stopper 48 is coupled to the distal end 58 of the push rod 56. The proximal end 60 includes a finger-operated pad.

[0049] Reference Figures 1 - 7 , when the push rod is retracted, the telescoping actuator assembly 60 couples the drug stopper 36, the saline stopper 48, and the push rod 56 under tension. The actuator assembly 60 includes an actuator 64, which has a collet bushing 66. The collet bushing 66 includes an annular bushing edge 68, the proximal face 70 of which is in an opposite orientation to the annular seating surface 47 of the distal cavity 46 of the drug stopper 36. As Figure 2 specifically shown in, when the proximal face 70 of the annular edge 68 of the collet bushing 66 contacts and abuts the annular surface 47 of the drug stopper 36, it isolates the proximal cavity 40 of the drug stopper 36 and any fluid contained therein from the outlet 32 of the syringe 20, since fluid cannot flow through the through-channel 44 into the distal cavity 46.

[0050] Reference Figures 5 - 7 , the collet bushing 66 of the telescoping actuator assembly 62 has a plurality of bushing fingers 72, which respectively define circumferential flanges 74 that frictionally engage in close contact with the cylindrical wall that defines the proximal cavity 40 within the drug stopper 36. The proximal axial ends 76 of the corresponding collet bushing fingers 72 are coupled to and abut against the cross-shaped platform 80 of the actuator shaft 78. The actuator shaft defines a proximal bulbous profile end 82. The nested distal hollow tube 84, intermediate hollow tube 86, and proximal hollow tube 88 of the telescoping actuator assembly 62 couple the saline stopper 48 to the actuator 64, as described below.

[0051] When viewed sequentially from the distal end 28 towards the proximal end 24 of the syringe barrel 22, the drum-shaped profile end 82 of the actuator shaft 78 remains within and in frictional contact with the inner wall surface 90 of the distal telescoping tube 84. The distal telescoping tube 84 defines a through-hole 92 for fluid passage and a circumferential flange 94. The circumferential flange 94 of the telescoping distal tube 84 remains within and in frictional contact with the inner wall surface 96 of the proximal tube 88. The proximal telescoping tube 88 defines a through-hole 98 for fluid passage and a circumferential flange 100. The circumferential flange 100 of the telescoping distal tube 86 remains within and in frictional contact with the inner wall surface 102 of the intermediate tube 88. The proximal telescoping tube 88 defines a through-hole 104 for fluid passage and a circumferential flange 106. The circumferential flange 106 of the telescoping proximal tube 88 remains within the circumferential groove 53 formed within the distal cavity 52 of the saline plug 48. When the telescoping actuator assembly 62 is fully extended ( Figure 5 and 6 ), its axial length is sufficient to extend the actuator 64 away from contact with the corresponding seating surface 47 of the drug plug 36 to effect selective fluid communication between the secondary chamber 108 and the syringe outlet 32. To prevent the telescoping tubes 82, 84, 86 from collapsing during the advancement of the syringe plunger 56, during drug delivery or during aspiration of air from the primary / drug chamber 110, within the telescoping actuator assembly 62, the frictional force generated between any pair of contacts of the drum-shaped profile end 82, the circumferential flanges 94, 100 and their corresponding inner wall surfaces 90, 96, 102 is greater than the combined frictional force generated between the drug plug 36 and the barrel inner wall 22 and the axial force required to advance the collet bushing 66 distal to the seating surface 47 of the drug plug 36. When the external axial force applied to the advancing plunger 56 exceeds the aforementioned combined frictional force generated within the telescoping actuator assembly 62, it will cause the assembly to collapse.

[0052] As Figure 13 shown, when the plunger is fully advanced within the syringe barrel 22, the telescoping distal tube 84, the intermediate tube 86 and the actuator shaft 78 collapse within the proximal telescoping tube 88. The axial lengths of the collapsed nested tubes 82, 84, 88, the actuator shaft 78 and the cross-shaped platform 80 are less than the combined axial length of the distal cavity of the saline plug 48 and the proximal cavity 40 of the drug plug 36 such that the secondary chamber 108 is fully collapsed.

[0053] Although the syringe 20 embodiment includes three nested telescoping tubes 84, 86 and 88 that cooperate with the actuator shaft 78 of the actuator 64, other syringe embodiments have a single tube that cooperates with the actuator shaft. Still other syringe embodiments have two nested tubes that cooperate with the actuator shaft. Additional syringe embodiments include more than three nested telescoping tubes.

[0054] As Figure 1 and 10As shown, syringe 20 is a dual-chamber syringe having serially arranged, axially aligned and oriented, variable-volume secondary chamber 108 and primary chamber 110. Primary chamber 110 is circumferentially defined within barrel inner wall 26 and is axially defined by the distal face 42 of drug stopper 36 and the distal axial end 28 of barrel 22. Secondary chamber 108 is circumferentially defined within barrel inner wall 26 and is axially defined by the distal face 50 of saline stopper 48 and the proximal-distal axial end 38 of drug stopper 36. Telescoping actuator assembly 62 functions as a manually actuated, selective isolation valve that facilitates the expulsion of fluid from secondary chamber 108. Pusher clip 112 (also referred to as a pusher collar) prevents the accidental advancement of pusher 56 and is removed by a healthcare practitioner prior to use of syringe 20 (e.g., see Figure 1 , 8 , 14, and 15). In one or more embodiments, variable-volume primary chamber 110 is pre-filled with the desired drug or is filled with the desired drug at the patient treatment site. In one or more embodiments, variable-volume secondary chamber 108 is pre-filled with the desired amount of saline or other flushing or diluting fluid. In one or more embodiments, during or after the assembly of syringe 20, using a sterile filling method, primary chamber 108 is pre-filled with a liquid or powdered / lyophilized drug, and secondary chamber 110 is pre-filled with saline, other flushing fluid, or other drug diluent. In some embodiments, barrel 22 of syringe 20 includes measurement markings (not shown) to indicate the amount of fluid contained therein.

[0055] Figure 1 , 2 , 8 - 14 depict the functional operation of an embodiment of syringe 20 in which its secondary chamber 108 is pre-filled with a flushing fluid (such as saline) and is packaged for shipment to and use by a healthcare facility. Figure 1 depicts syringe 20 in its shipped state after removal of the outer packaging but prior to removal of male luer cap 34. Pusher clip / pusher collar 112 surrounds pusher 56 between the proximal end 60 of the pusher and the proximal end 24 of syringe barrel 22 to prevent the accidental advancement of the pusher. When shipped, the distal end 42 of drug stopper 36 abuts the distal end 28 of syringe barrel 22 such that primary chamber 108 is fully collapsed and empty. Telescoping actuator assembly 62 isolates the secondary chamber to avoid communication with outlet 32 ( Figure 2 ), preventing the leakage of saline fluid from the syringe. Prior to use, pusher clip / pusher collar 112 and male luer cap 34 are removed from syringe 20.

[0056] Figure 8 and 9Depicts removing air trapped within the pre-filled secondary chamber 108 of the pre-packaged syringe 20 by fully advancing the push rod 56 (arrow A) to separate the proximal face 70 of the bushing edge 68 of the actuator 64 to avoid contact with the placement surface 47 of the drug stopper 36. In this partially advanced state of the push rod 56, the separation of the actuator 64 from the placement surface 47 allows fluid communication between the secondary chamber 108, the proximal chamber 40, the fluid through-channel 44, and the outlet 32 of the Luer tip 30, thereby allowing the trapped air to escape from the secondary chamber 108.

[0057] Figure 10 Depicts aspirating a drug into the main chamber 110 by retracting or withdrawing the push rod 56 (arrow R). Retraction of the push rod 56 tensions the telescoping actuator assembly 62, seating the proximal face 70 of the collet bushing edge 68 against the corresponding placement surface 47 of the drug stopper 36. Retraction of the push rod 56 also creates a negative pressure differential in the main chamber 110 relative to the ambient pressure in the outlet 32; this helps maintain contact between the proximal face 70 and the placement surface 47 (i.e., re-isolating the secondary chamber 108 by closing the valve), while simultaneously aspirating the drug from a drug vial (not shown) into the main chamber.

[0058] Figure 11 Depicts delivering a drug to a patient's VAD (not shown). By advancing the push rod 56 (arrow A) to empty the main chamber, the drug is infused from the main chamber 110 into the previously flushed VAD. The advancement pressure applied to the push rod 56 is sufficient to advance the drug stopper 36 into contact with the distal end 28 of the syringe barrel 22, but not so heavy as to push the actuator 64 out of contact with the placement surface 47 of the drug stopper.

[0059] At Figure 12 and 13 , by advancing the push rod 56 with sufficient pressure to push the actuator 64 out of contact with the placement surface 47 of the drug stopper ( Figure 12 ), the VAD is flushed with a flushing solution (e.g., saline or heparin) pre-packaged in the secondary chamber 108. This opens the valve and delivers the flushing solution from the outlet 32 of the syringe 20 ( Figure 13 ), until the secondary chamber 108 collapses and empties. After the flushing procedure is complete, the syringe 20 is then withdrawn from the VAD.

[0060] Another aspect of the present disclosure is as Figure 14 and 15As shown, the dual-chamber syringe 120 (constructed similarly to syringe 20) facilitates mixing of the pre-filled powdered / lyophilized drug in the primary chamber 110 with the pre-filled diluent (e.g., saline) in the secondary chamber 108. A radially inwardly projecting barrel ring 130 formed on the inner wall 126 of the syringe barrel 122 prevents the drug plug 36 from advancing distally beyond the ring. The advancing pressure required on the plunger 56 to overcome the advancing resistance of the barrel ring 130 is higher than the advancing pressure required to advance the telescoping actuator assembly 62 beyond engagement with the drug plug 36 and allow saline to flow from the secondary chamber 108 into the primary / mixing chamber 110. After removing the plunger clip / collar 112 from the plunger 56 and then advancing the plunger toward the barrel ring 130, the telescoping actuator assembly 62 opens the drug plug fluid passage 44, allowing saline or other diluent to mix with the drug. After shaking or otherwise agitating the drug / diluent mixture, the male Luer cap 34 is removed from the syringe 120, and the syringe plunger 56 is fully advanced to remove trapped air from the primary chamber 108. After connecting the Luer connector 30 to the VAD, the now-mixed drug 120 is delivered. A path seal 132 surrounds the telescoping actuator assembly to prevent backflow or reflux of the diluent / drug mixture from the primary chamber 110 through the drug plug fluid passage 44 into the secondary chamber 110. The outer periphery 134 of the path seal 132 abuts against or is within the proximal cavity 40 in the drug plug 36, while its inner periphery 136 abuts against the respective outer peripheral surfaces of the intermediate telescoping tube 86 and the proximal telescoping tube 88.

[0061] Although separate and alternative syringe embodiments 20 and 120 are shown and described herein, either embodiment can be used for: (a) sequentially administering different pre-filled drugs in their respective primary chambers 110 and secondary chambers 108, or (b) aspirating / administering the drug in their respective primary chambers and then administering another drug from their respective secondary chambers, or (c) aspirating / administering the drug in their respective primary chambers and then flushing the VAD with a pre-filled flush fluid from their respective secondary chambers, or (d) administering the pre-filled drug in their respective primary chambers and then flushing the VAD with a pre-filled flush fluid from their respective secondary chambers, or (e) mixing the pre-filled powdered / lyophilized drug in their respective primary chambers and then flushing the VAD with a pre-filled flush fluid from their respective secondary chambers.

[0062] In the case of a single continuous stroke of the syringe plunger 56, a single syringe 20 facilitates sequential delivery of a pre-filled or freshly aspirated drug within its primary chamber 110 to a patient's VAD, followed by immediate flushing of the VAD with pre-filled saline or other flushing fluid contained within its primary chamber. The syringe 20 does not require manipulation of multiple plungers, non-linear or compound plunger motions, or external valves to sequentially deliver the drug and the flushing fluid. A single syringe 20 performs both the drug delivery and flushing procedures that are typically performed with separate syringes. As previously described, simplifying drug delivery and flushing by using a single syringe 20 reduces the costs associated with purchasing multiple syringes. In some embodiments, a single syringe 20 reduces the risk of patient drug delivery errors because the drug and / or flushing solution is pre-filled in the syringe. In some embodiments, a single syringe 20 reduces the risk of failure to flush a patient's VAD after drug administration due to distraction of the healthcare professional because the flushing solution is pre-filled in the secondary chamber 108. Simply put, a professional is more likely to complete the act of advancing a single plunger 56 with the sequential delivery syringe 20 after they have completed drug administration, without the need to replace the drug syringe with a new and separate flushing syringe. Sequential drug administration and VAD flushing using a single syringe 20 also reduces the risk of infection caused by multiple punctures of the VAD septum by separate syringes. Finally, the syringe 20 with the telescoping actuator assembly 64 does not require piercing of the drug stopper 36 to expel the flushing solution from its secondary chamber 108; this reduces the likelihood of damaged stopper particulate matter infiltrating the VAD or the patient.

[0063] A syringe 120 facilitates mixing of a pre-filled powdered / lyophilized drug within the primary chamber 110 with a pre-filled diluent (e.g., saline) within the secondary chamber, and subsequent delivery of the mixed drug in the case of a single continuous stroke of the syringe plunger 56. The syringe 120 does not require manipulation of multiple plungers, non-linear or compound plunger motions, or external valves to sequentially mix and administer the drug. In some embodiments, a single syringe 120 reduces the risk of patient drug delivery errors because the drug and diluent are pre-filled in the syringe. The syringe 120 with the telescoping actuator assembly 64 does not require piercing of the drug stopper 36 to expel the diluent from its secondary chamber 108 into the primary chamber 110; this reduces the likelihood of damaged stopper particulate matter infiltrating the VAD or the patient.

[0064] The syringe embodiments disclosed herein are constructed of medical grade materials known to those skilled in the art. In some embodiments, the described barrel, plunger, and shaft are made of polypropylene polymer. The seal is made of fiber-filled polytetrafluoroethylene (PTFE) polymer. The stopper is made of polyisoprene polymer.

[0065] Embodiments

[0066] Embodiment (a). A sequential drug delivery syringe comprising: a hollow syringe barrel defining an inner wall, a proximal barrel end, and a distal barrel end, the distal end of the barrel including a connector defining an outlet cavity therethrough, the outlet cavity being in fluid communication with the interior of the barrel, the interior of the barrel being defined by an open proximal end, a distal end, and an inner wall; a plunger disposed with the interior of the barrel having a proximal end extending beyond the proximal end of the barrel and a distal end; a secondary stopper disposed within the interior of the barrel having a proximal axial end coupled to the distal end of the plunger and a distal axial end defining a distal cavity therein; a primary stopper disposed within the interior of the barrel between the secondary stopper and the distal end of the barrel having a proximal axial end defining a proximal cavity, a distal axial end defining a distal cavity having a seating surface, and a through-channel in fluid communication with both its proximal and distal cavities; a telescoping actuator assembly oriented with the respective cavities of the primary and secondary stoppers having: a reciprocable actuator oriented within the through-channel of the primary stopper, the actuator projecting into the proximal and distal cavities of the stopper and having an outer peripheral surface in sliding frictional engagement with the through-channel, and a radially projecting proximal axial face oriented within the corresponding distal cavity of the primary stopper and in an orientation opposite to the seating surface, and a tube having an outer peripheral surface coupled to and within the distal cavity of the secondary stopper and an inner wall surrounding the outer peripheral surface of the actuator and in sliding frictional engagement with the outer peripheral surface of the actuator; a main fluid chamber within the interior of the barrel defined between the distal end surface of the primary stopper and the outlet cavity at the distal end of the barrel, the volume of the main fluid chamber being selectively variable by translation of the plunger; and a secondary fluid chamber within the interior of the barrel defined between the distal end surface of the secondary stopper and the through-channel of the primary stopper, the volume of the secondary fluid chamber being selectively variable by translation of the plunger when the proximal axial face of the actuator is spaced from the seating surface of the primary stopper; wherein when the proximal axial face of the actuator is spaced from the seating surface of the primary stopper, the secondary fluid chamber is in fluid communication with the main fluid chamber and the outlet cavity of the syringe, and when the proximal axial face of the actuator is in abutting contact with the seating surface of the primary stopper, the secondary fluid chamber is isolated from the main fluid chamber; wherein retracting the plunger tensions the telescoping actuator assembly, causing the proximal axial face of the actuator to move back correspondingly into abutting contact with the seating surface of the primary stopper and retracting the stopper;And wherein advancing the push rod alone advances the main plug, causing the proximal axial face of the actuator to move forward accordingly, away from abutting contact with the seating surface of the main plug, advancing the secondary plug, and causing the telescoping actuator assembly to collapse within the corresponding distal cavity of the secondary plug and the proximal cavity of the main plug.;

[0067] Embodiment (b). The syringe according to embodiment (a), wherein the actuator assembly further comprises a plurality of nested tubes that are in sliding frictional engagement with each other, each nested tube having an outer peripheral surface and an inner wall; the outer peripheral surface of the most proximal oriented tube among the nested tubes is coupled to and within the distal cavity of the secondary plug, wherein the inner wall of the most proximal oriented tube is in sliding frictional engagement with the outer peripheral surface of the adjacent tube captured therein; and the inner wall of the most distal oriented tube among the nested tubes surrounds and is in sliding frictional engagement with the outer peripheral surface of the actuator.

[0068] Embodiment (c). The syringe according to embodiment (b), wherein the actuator further comprises a collet bushing having: an annular bushing edge whose radially projecting proximal axial face is in an opposite orientation to the seating surface of the main plug; a plurality of collet bushing fingers projecting away from the proximal axial face of the annular bushing edge and in frictional contact with the surface defining the through-channel, the distal end of each bushing finger projecting into the proximal cavity of the main plug.

[0069] Embodiment (d). The syringe according to embodiment (c), wherein the actuator further comprises: the distal end of the collet bushing finger is coupled to a platform at the distal end of the actuator shaft, the outer surface of the proximal end of the actuator shaft is in sliding frictional engagement with the inner wall of the most distal oriented tube, and the seating surface of the main plug is captured between the collet bushing and the platform.

[0070] Embodiment (e). The syringe according to embodiment (d), wherein at least one of the collet bushing fingers defines a circumferential flange that projects radially outward and is in frictional contact with the surface defining the through-channel.

[0071] Embodiment (f). The syringe according to embodiment (e), wherein the collet bushing comprises four circumferentially evenly spaced collet fingers that are rigidly coupled to a corresponding cruciform platform of the actuator, and the proximal outer surface of the actuator shaft defines a drum-shaped surface profile for frictional engagement with a corresponding inner wall surface of the most distal oriented tube.

[0072] Embodiment (g). The syringe as described in embodiment (f), further comprising three nested tubes, wherein the most proximally oriented tube of the nested tubes defines an outer peripheral flange at its distal end, the outer peripheral flange matingly engaging a corresponding circumferential groove defined within the distal cavity of the secondary stopper, and the inner wall surface of the most distally oriented tube of the nested tubes frictionally engaging the drum-shaped surface of the actuator shaft.

[0073] Embodiment (h). The syringe as described in embodiment (a), wherein the actuator further comprises a collet bushing having: an annular bushing edge with a radially projecting proximal axial face in an opposite orientation to the seating surface of the primary stopper; and a plurality of collet bushing fingers projecting away from the proximal axial face of the annular bushing edge and in frictional contact with the surface defining the through-channel, the distal end of each bushing finger projecting into the proximal cavity of the primary stopper.

[0074] Embodiment (i). The syringe as described in embodiment (h), wherein the actuator further comprises: the distal ends of the collet bushing fingers being coupled to a platform at the distal end of the actuator shaft; the outer surface of the proximal end of the actuator shaft being in sliding frictional engagement with the inner wall of the tube, and the seating surface of the primary stopper being captured between the collet bushing and the platform.

[0075] Embodiment (j). The syringe as described in embodiment (i), wherein at least one of the collet bushing fingers defines a circumferentially projecting circumferential flange that is in frictional contact with the surface defining the through-channel.

[0076] Embodiment (k). The syringe as described in embodiment (j), wherein the collet bushing comprises four circumferentially evenly spaced collet fingers that are rigidly coupled to a corresponding cruciform platform of the actuator, and the proximal outer surface of the actuator shaft defines a drum-shaped surface profile for frictional engagement with a corresponding inner wall surface of the tube.

[0077] Embodiment (l). The syringe as described in embodiment (a), further comprising: an inwardly radially projecting barrel ring formed on the inner wall of the barrel, and a path seal having an inner circumferential surface surrounding the outer surface of the tube of the actuator assembly and an outer circumferential surface in fluid-tight contact with the proximal cavity of the primary stopper, the path seal preventing fluid from flowing back from the primary chamber to the secondary chamber.

[0078] Embodiment (m). The sterile pre-packaged syringe as described in embodiment (l), further comprising a dry or powdered drug in its primary chamber and a drug diluent in its secondary chamber.

[0079] Embodiment (n). A syringe as described in Embodiment (a), wherein the distal end of the main plunger and the distal end of the syringe barrel have corresponding mating profiles that contact each other when the main plunger is fully inserted into the interior of the syringe barrel, such that the volume of the main fluid chamber is minimized.

[0080] Embodiment (o). A syringe as described in Embodiment (a), wherein the proximal end of the main plunger and the distal end of the secondary plunger have corresponding mating profiles that contact each other when the secondary plunger is fully inserted into the interior of the syringe barrel, such that the volume of the secondary fluid chamber is minimized.

[0081] Embodiment (p). A sterile pre-packaged syringe as described in Embodiment (a), further comprising a flushing fluid in its secondary chamber.

[0082] Embodiment (q). A syringe as described in Embodiment (a), wherein advancing the push rod under a first axial pressure advances the main plunger, and advancing the push rod under a second axial pressure greater than the first pressure causes the proximal axial face of the actuator to move forward correspondingly, away from abutting contact with the seating surface of the main plunger, thereby establishing fluid communication between the secondary fluid chamber and the main fluid chamber and the outlet chamber and advancing the secondary plunger.

[0083] Embodiment (r). A sequential drug delivery syringe comprising: a hollow syringe barrel defining an inner wall, a proximal barrel end, and a distal barrel end, the distal end of the barrel including a connector defining an outlet lumen therethrough, the outlet lumen being in fluid communication with the interior of the barrel, the interior of the barrel being defined by an open proximal end, a distal end, and an inner wall; a plunger disposed within the interior of the barrel having a proximal end extending beyond the proximal end of the barrel and a distal end; a secondary stopper disposed within the interior of the barrel having a proximal axial end coupled to the distal end of the plunger and a distal axial end defining a distal cavity therein; a primary stopper disposed within the interior of the barrel between the secondary stopper and the distal end of the barrel having a proximal axial end defining a proximal cavity, a distal axial end defining a distal cavity having a seating surface, and a through-channel in fluid communication with both its proximal and distal cavities; a telescoping actuator assembly oriented with the respective cavities of the primary and secondary stoppers having: a plurality of nested tubes slidingly frictionally engaged with one another, each nested tube having an outer peripheral surface and an inner wall, the outer peripheral surface of the most proximal oriented tube of the nested tubes being coupled to and within the distal cavity of the secondary stopper, wherein the inner wall of the most proximal oriented tube slidingly frictionally engages the outer peripheral surface of an adjacent tube captured therein, and an actuatable actuator oriented within the through-channel of the primary stopper, the actuator including a collet bushing having: an annular bushing edge with a radially projecting proximal axial face oriented opposite a mating annular seating surface of the primary stopper; a plurality of collet bushing fingers projecting away from the proximal axial face of the annular bushing edge and in frictional contact with the surface defining the through-channel, the distal end of each bushing finger projecting into the proximal cavity of the primary stopper, the distal ends of the collet bushing fingers being coupled to a platform oriented on the distal end of an actuator shaft, the outer surface of the proximal end of the actuator shaft slidingly frictionally engaging the inner wall of the most distal oriented tube, the seating surface of the primary stopper being captured between the collet bushing and the platform; a main fluid chamber within the interior of the barrel defined between the distal end surface of the primary stopper and the outlet lumen at the distal end of the barrel, the volume of the main fluid chamber being selectively variable by translation of the plunger; and a secondary fluid chamber within the interior of the barrel defined between the distal end surface of the secondary stopper and the through-channel of the primary stopper, the volume of the secondary fluid chamber being selectively variable by translation of the plunger when the proximal axial face of the annular bushing edge is spaced from the seating surface of the primary stopper;Wherein when the proximal axial surface of the annular bushing edge is spaced apart from the seating surface of the main plug, the secondary fluid chamber is in fluid communication with the main fluid chamber and the outlet chamber of the syringe, and when the proximal axial surface of the annular bushing edge is in abutting contact with the seating surface of the main plug, the secondary fluid chamber is isolated from the main fluid chamber; wherein retracting the push rod tensions the telescopic actuator assembly, causing the proximal axial surface of the annular bushing edge to move correspondingly backward, into abutting contact with the seating surface of the main plug, and retracting the plug; and wherein advancing the push rod alone under a first axial pressure advances the main plug, and advancing the push rod under a second axial pressure greater than the first axial pressure causes the proximal axial surface of the annular bushing edge to move correspondingly forward, away from abutting contact with the seating surface of the main plug, thereby establishing fluid communication between the secondary fluid chamber and the main fluid chamber and the outlet chamber and advancing the secondary plug; and advancing the push rod under a third axial pressure greater than the second axial pressure causes the telescopic actuator assembly to collapse within the corresponding distal cavity of the secondary plug and the proximal cavity of the main plug.;

[0084] Embodiment(s). A method for manufacturing a syringe as described in embodiment (r), comprising:

[0085] Inserting the collet bushing fingers into the through-channel of the main plug such that they project into its proximal cavity; rigidly coupling the platform of the actuator assembly to the ends of the collet bushing fingers, capturing the main plug between the annular edge of the collet bushing and the cross-shaped platform; coupling the most proximal orientation tube of the actuator assembly within the distal cavity of the secondary plug, either before or after coupling the push rod to the secondary plug; and inserting the now-coupled main plug, actuator assembly, secondary plug, and push rod into the interior of the syringe barrel.

[0086] Embodiment (t). A syringe as described in embodiment (s), further comprising: an inwardly radially projecting barrel ring formed on the inner wall of the barrel, and a path seal having an inner circumferential surface and an outer circumferential surface, the inner circumferential surface surrounding the outer surface of the tube of the actuator assembly, the outer circumferential surface being in fluid-tight contact with the proximal cavity of the main plug, the path seal preventing fluid from flowing back from the main chamber to the secondary chamber.

[0087] Throughout this specification, references to "one embodiment", "certain embodiments", "various embodiments", "one or more embodiments", or "an embodiment" mean that a particular feature, structure, material, or characteristic described in connection with the embodiment is included in at least one embodiment of the present disclosure. Thus, the appearances of the phrases "in one or more embodiments", "in certain embodiments", "in various embodiments", "in one embodiment", or "in an embodiment" throughout this specification are not necessarily referring to the same embodiment of the present disclosure. Additionally, in one or more embodiments, the particular features, structures, materials, or characteristics may be combined in any suitable manner. Further, it should be understood that the language and terminology used herein are for the purpose of description and should not be regarded as limiting. As used herein, the terms "comprising", "including", or "having" and their variants are intended to cover the listed items and their equivalents as well as additional items. Unless otherwise specified or limited, the terms "mounted", "connected", "supported", and "coupled" and their variants are construed broadly; they cover direct and indirect mounting, connection, support, and coupling. Additionally, "connected" and "coupled" are not limited to physical, mechanical, or electrical connections or couplings.

[0088] Although the present disclosure provides a description of reference embodiments, it should be understood that these embodiments are merely illustrative of the principles and applications of the present disclosure. It will be apparent to those skilled in the art that various modifications and variations can be made to the present disclosure without departing from the spirit and scope of the present disclosure. Accordingly, the present disclosure is intended to cover modifications and variations that fall within the scope of the appended claims and their equivalents. The appended claims are not limited to the details of the exemplary embodiments of the construction and arrangement of components set forth in the specification or shown in the drawings.

Claims

1. A sequential drug delivery syringe, comprising: A hollow syringe barrel defining an inner wall, a proximal barrel end, and a distal barrel end, the distal end of the barrel including a connector defining an outlet cavity therethrough, the outlet cavity being in fluid communication with the interior of the barrel, the interior of the barrel being defined by an open proximal end, a distal end, and an inner side wall; A plunger disposed within the interior of the barrel, having a proximal end extending beyond the proximal end of the barrel and a distal end; A secondary stopper disposed within the interior of the barrel, having a proximal axial end coupled to the distal end of the plunger and a distal axial end defining a distal cavity therein; A primary stopper disposed within the interior of the barrel, between the secondary stopper and the distal end of the barrel, having a proximal axial end defining a proximal cavity, a distal axial end defining a distal cavity having a seating surface, and a through-channel in fluid communication with both its proximal and distal cavities; A telescoping actuator assembly oriented with respect to the respective cavities of the primary and secondary stoppers, having: A reciprocable actuator oriented within the through-channel of the primary stopper, the actuator projecting into the proximal and distal cavities of the stopper and having an outer peripheral surface in sliding friction engagement with the through-channel, and a radially projecting proximal axial face oriented within the corresponding distal cavity of the primary stopper and opposite in orientation to the seating surface; and A tube having an outer peripheral surface coupled to and within the distal cavity of the secondary stopper and an inner wall surrounding the outer peripheral surface of the actuator and in sliding friction engagement with the outer peripheral surface of the actuator; A main fluid chamber within the interior of the barrel, defined between the distal end surface of the primary stopper and the outlet cavity at the distal end of the barrel, the volume of the main fluid chamber being selectively variable by translation of the plunger; And A secondary fluid chamber within the interior of the barrel, defined between the distal end surface of the secondary stopper and the through-channel of the primary stopper, the volume of the secondary fluid chamber being selectively variable by translation of the plunger when the proximal axial face of the actuator is spaced from the seating surface of the primary stopper; Wherein when the proximal axial face of the actuator is spaced from the seating surface of the primary stopper, the secondary fluid chamber is in fluid communication with the main fluid chamber and the outlet cavity of the syringe, and when the proximal axial face of the actuator is in abutting contact with the seating surface of the primary stopper, the secondary fluid chamber is isolated from the main fluid chamber; Wherein retracting the plunger tensions the telescoping actuator assembly, causing the proximal axial face of the actuator to move correspondingly rearward, into abutting contact with the seating surface of the primary stopper, and retracting the stopper; and Advancing the push rod alone advances the main plug, causing the proximal axial surface of the actuator to move forward accordingly, away from the abutting contact with the seating surface of the main plug, advancing the secondary plug, and causing the telescopic actuator assembly to collapse within the corresponding distal cavity of the secondary plug and the proximal cavity of the main plug.

2. The syringe according to claim 1, wherein the actuator assembly further comprises a plurality of nested tubes that are slidably frictionally engaged with each other, each nested tube having an outer peripheral surface and an inner wall; the outer peripheral surface of the innermost-oriented tube among the nested tubes is coupled to and within the distal cavity of the secondary plug, wherein the inner wall of the innermost-oriented tube is slidably frictionally engaged with the outer peripheral surface of the adjacent tube captured therein; and the inner wall of the outermost-oriented tube among the nested tubes surrounds and is slidably frictionally engaged with the outer peripheral surface of the actuator.

3. The syringe according to claim 2, wherein the actuator further comprises a collet bushing having: an annular bushing edge whose radially projecting proximal axial surface is in an opposite orientation to the seating surface of the main plug; a plurality of collet bushing fingers that project away from the proximal axial surface of the annular bushing edge and are in frictional contact with the surface defining the through-channel, and the distal end of each bushing finger projects into the proximal cavity of the main plug.

4. The syringe according to claim 3, wherein the actuator further comprises: The distal end of the collet bushing finger is coupled to a platform at the distal end of the actuator shaft, the outer surface of the proximal end of the actuator shaft is slidably frictionally engaged with the inner wall of the outermost-oriented tube, and the seating surface of the main plug is captured between the collet bushing and the platform.

5. The syringe according to claim 4, wherein at least one of the collet bushing fingers defines a circumferential flange that projects radially outward, and the circumferential flange is in frictional contact with the surface defining the through-channel.

6. The syringe according to claim 5, wherein the collet bushing comprises four circumferentially evenly spaced collet fingers that are rigidly coupled to a corresponding cruciform platform of the actuator, and the proximal outer surface of the actuator shaft defines a drum-shaped surface profile for frictional engagement with a corresponding inner wall surface of the outermost-oriented tube.

7. The syringe according to claim 6, further comprising three nested tubes, wherein the innermost-oriented tube among the nested tubes defines an outer peripheral flange at its distal end, the outer peripheral flange is matingly engaged with a corresponding circumferential groove defined within the distal cavity of the secondary plug, and the inner wall surface of the outermost-oriented tube among the nested tubes is in frictional engagement with the drum-shaped surface of the actuator shaft.

8. The syringe according to claim 1, wherein the actuator further comprises a collet bushing having: an annular bushing edge with a radially protruding proximal axial face oriented opposite to the seating surface of the main plunger; and a plurality of collet bushing fingers protruding away from the proximal axial face of the annular bushing edge and in frictional contact with the surface defining the through-channel, the distal end of each bushing finger protruding into the proximal cavity of the main plunger.

9. The syringe according to claim 8, wherein the actuator further comprises: The distal end of the collet bushing finger is coupled to a platform at the distal end of the actuator shaft; the outer surface of the proximal end of the actuator shaft is in sliding frictional engagement with the inner wall of the tube, and the seating surface of the main plunger is captured between the collet bushing and the platform.

10. The syringe according to claim 9, wherein at least one of the collet bushing fingers defines a circumferential flange protruding radially outward, the circumferential flange being in frictional contact with the surface defining the through-channel.

11. The syringe according to claim 10, wherein the collet bushing comprises four circumferentially evenly spaced collet fingers rigidly coupled to a corresponding cruciform platform of the actuator, and the proximal outer surface of the actuator shaft defines a drum-shaped surface profile for frictional engagement with a corresponding inner wall surface of the tube.

12. The syringe according to claim 1, further comprising: An inwardly radially protruding barrel ring formed on the inner wall of the barrel, and a path seal having an inner circumferential surface surrounding the outer surface of the tube of the actuator assembly and an outer circumferential surface in fluid-tight contact with the proximal cavity of the main plunger, the path seal preventing fluid from flowing back from the main chamber to the secondary chamber.

13. The sterile pre-packaged syringe according to claim 12, further comprising a dry or powdered drug in its main chamber and a drug diluent in its secondary chamber.

14. The syringe according to claim 1, wherein the distal end of the main plunger and the distal end of the syringe barrel have corresponding mating profiles that contact each other when the main plunger is fully inserted into the interior of the syringe barrel, such that the volume of the main fluid chamber is minimized.

15. The syringe according to claim 1, wherein the proximal end of the main plunger and the distal end of the secondary plunger have corresponding mating profiles that contact each other when the secondary plunger is fully inserted into the interior of the syringe barrel, such that the volume of the secondary fluid chamber is minimized.

16. The sterile pre-packaged syringe according to claim 1, further comprising a flushing fluid in its secondary chamber.

17. The syringe according to claim 1, wherein advancing the push rod under a first axial pressure advances the main plunger, and advancing the push rod under a second axial pressure greater than the first pressure causes the proximal axial face of the actuator to move forward accordingly, away from abutting contact with the seating surface of the main plunger, thereby establishing fluid communication between the secondary fluid chamber and the main fluid chamber and the outlet chamber and advancing the secondary plunger.

18. A sequential drug delivery syringe, comprising: A hollow syringe barrel defining an inner wall, a proximal barrel end, and a distal barrel end, the distal end of the barrel including a connector defining an exit lumen therethrough, the exit lumen being in fluid communication with the interior of the barrel, the interior of the barrel being defined by an open proximal end, a distal end, and an inner wall; A plunger disposed within the interior of the barrel, having a proximal end extending beyond the proximal end of the barrel and a distal end; A secondary stopper disposed within the interior of the barrel, having a proximal axial end coupled to the distal end of the plunger and a distal axial end defining a distal cavity therein; A primary stopper disposed within the interior of the barrel, between the secondary stopper and the distal end of the barrel, having a proximal axial end defining a proximal cavity, a distal axial end defining a distal cavity having a seating surface, and a through-channel in fluid communication with both its proximal and distal cavities; A telescoping actuator assembly oriented with respect to the respective cavities of the primary and secondary stoppers, having: A plurality of nested tubes slidingly frictionally engaging one another, each nested tube having an outer peripheral surface and an inner wall, the outer peripheral surface of the most proximal oriented tube of the nested tubes being coupled to and within the distal cavity of the secondary stopper, wherein the inner wall of the most proximal oriented tube slidingly frictionally engages the outer peripheral surface of an adjacent tube captured therein, and A reciprocable actuator oriented within the through-channel of the primary stopper, the actuator including a collet bushing having: an annular bushing edge, the radially projecting proximal axial face of which is in an opposite orientation to the mating annular seating surface of the primary stopper; a plurality of collet bushing fingers projecting away from the proximal axial face of the annular bushing edge and frictionally contacting the surface defining the through-channel, the distal end of each bushing finger projecting into the proximal cavity of the primary stopper, the distal ends of the collet bushing fingers being coupled to a platform oriented on the distal end of an actuator shaft, the outer surface of the proximal end of the actuator shaft slidingly frictionally engaging the inner wall of the most distal oriented tube, the seating surface of the primary stopper being captured between the collet bushing and the platform; A main fluid chamber within the interior of the barrel, defined between the distal end surface of the primary stopper and the exit lumen at the distal end of the barrel, the volume of the main fluid chamber being selectively variable by translation of the plunger; And A secondary fluid chamber within the interior of the barrel, defined between the distal end surface of the secondary stopper and the through-channel of the primary stopper, the volume of the secondary fluid chamber being selectively variable by translation of the plunger when the proximal axial face of the annular bushing edge is spaced from the seating surface of the primary stopper; Wherein when the proximal axial surface of the annular bushing edge is spaced from the seating surface of the main plug, the secondary fluid chamber is in fluid communication with the main fluid chamber and the outlet chamber of the syringe, and when the proximal axial surface of the annular bushing edge is in abutting contact with the seating surface of the main plug, the secondary fluid chamber is isolated from the main fluid chamber; Wherein withdrawing the push rod tightens the telescopic actuator assembly, causing the proximal axial surface of the annular bushing edge to move correspondingly backward, into abutting contact with the seating surface of the main plug, and withdrawing the plug; And Wherein advancing the push rod alone under a first axial pressure advances the main plug, and advancing the push rod under a second axial pressure greater than the first axial pressure causes the proximal axial surface of the annular bushing edge to move correspondingly forward, away from abutting contact with the seating surface of the main plug, thereby establishing fluid communication between the secondary fluid chamber and the main fluid chamber and the outlet chamber and advancing the secondary plug; and advancing the push rod under a third axial pressure greater than the second axial pressure causes the telescopic actuator assembly to collapse within the corresponding distal cavity of the secondary plug and the proximal cavity of the main plug.

19. A method of manufacturing a syringe as claimed in claim 18, comprising: Inserting the collet bushing fingers into the through-channel of the main plug such that they project into its proximal cavity; Rigidly coupling the platform of the actuator assembly to the ends of the collet bushing fingers, capturing the main plug between the annular edge of the collet bushing and the cruciform platform; Coupling the most proximal orientation tube of the actuator assembly within the distal cavity of the secondary plug, either before or after coupling the push rod to the secondary plug; And Inserting the now-coupled main plug, actuator assembly, secondary plug and push rod into the interior of the syringe barrel.

20. The syringe according to claim 19, further comprising: An inwardly radially projecting barrel ring formed on the inner wall of the barrel, and a path seal having an inner circumferential surface and an outer circumferential surface, the inner circumferential surface surrounding the outer surface of the tube of the actuator assembly, the outer circumferential surface being in fluid sealing contact with the proximal cavity of the main plug, the path seal preventing fluid from flowing back from the main chamber to the secondary chamber.

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