Leak-free stopper for syringe assembly with low opening and retention force

Abstract

A thermoplastic elastomer stopper is provided that meets the desired material properties of a stopper for a syringe assembly. [Solution] The thermoplastic elastomer stopper 16 of the present disclosure has a compression set of 50% or less when held at 70°C for 22 hours under 25% compression. The thermoplastic elastomer stopper of the present disclosure has a hardness of 40 to 70 Shore A. The viscosity of the thermoplastic elastomer stopper of the present disclosure is measured at 205°C using a capillary rheometer (die: round hole length 20 mm / diameter 1 mm / 180-degree inlet, piston: d = 15 mm, and melting time = 7 minutes) at a shear rate of 1,000 s -1 70.0 Pa·s or more, shear rate 10,000 s -1 12.0 Pa·s or more, and a shear rate of 50,000 s -1 The non-lubricated stopper exhibits the required functional performance of a lubricated stopper.

Description

[Technical field]

[0001] The present disclosure relates generally to a stopper for a syringe assembly. More particularly, the present disclosure relates to a thermoplastic elastomer (TPE) stopper that meets desired material properties of a stopper for a syringe assembly. [Background technology]

[0002] Syringe assemblies are well known in the medical field for dispensing fluids, such as medicines. A conventional syringe generally includes a syringe barrel having an opening at one end and a plunger mechanism disposed through the opposite end. The plunger mechanism generally includes a plunger rod extending through the barrel, with a plunger head or stopper disposed at the end of the plunger rod within the syringe barrel and a finger flange at the other end of the plunger rod extending from the syringe barrel. In use, the plunger rod is pulled through the syringe barrel to aspirate and fill the syringe barrel with a fluid, such as medicine, with the plunger rod extending from the rear end of the syringe barrel. To deliver the medicine to a patient, the opening of the syringe barrel is adapted to be in fluid communication with the patient, such as through a hypodermic needle fitted to the front end of the syringe barrel or through a luer type fitting extending from the syringe barrel for attachment to a patient's fluid line. When a user applies force to depress the plunger rod and stopper through the syringe barrel toward the front end of the syringe barrel, it forces the contents of the syringe out of the syringe barrel through an opening at the front end for delivery to a patient. Such operations are well known in the medical field and physicians are well accustomed to using such common fluid delivery procedures through standard syringes.

[0003] Syringe assembly requires the slow, controlled initiation and maintenance of a sliding motion of one surface over the other. It is well known that two stationary surfaces having a sliding relationship often exhibit sufficient resistance to the initiation of motion that gradually increasing pressure applied to one of the surfaces does not cause movement until a threshold pressure is reached, at which point a sudden sliding separation of the surfaces occurs. This sudden separation of the sliding relationship from the stationary surface is referred to herein as a "breakout."

[0004] A less well known but important frictional force is the "breakloose force," which refers to the force required to overcome static friction between the surfaces of a syringe assembly that has been sterilized (including by autoclaving or other processes) and may have slight deformations in one or both of its contacting surfaces, e.g., the syringe barrel. In addition to autoclaving, "parking" the assembly can further increase the breakloose force.

[0005] Breakout and opening forces are particularly troublesome in liquid dispensing devices such as syringes, which are used to dispense small, precisely measured amounts of liquid by smoothly and incrementally advancing one surface over a graduated second surface from line to line. The problem is also encountered in devices that use stopcocks, such as burettes, pipettes, and addition funnels, where careful drop-by-drop control of flow is desired.

[0006] An important performance requirement of a stopper is to achieve high pressure resistance to leak, i.e., the ability of the stopper to maintain a leak-free syringe while maintaining low opening and sustaining forces.

[0007] The problem of excessive breakout and opening forces is related to friction. Friction is generally defined as the resistive force that arises when a surface of one material slides or attempts to slide over an adjacent surface of itself or another material. There can be two types of friction between contacting solid surfaces: (1) resistance that opposes the force required to start one surface moving over the other, conventionally known as static friction, and (2) resistance that opposes the force required to move one surface over the other at a variable, fixed, or predetermined speed, conventionally known as kinetic friction.

[0008] The force required to overcome static friction and induce a breakout is called the "breakout force" and the force required to maintain stable sliding of one surface over another after the breakout or opening is called the "sustaining force". Two major factors contribute to static friction and therefore to the breakout or opening force. The term "sticking" as used herein means the tendency of two surfaces in stationary contact to develop adhesion to one another. The term "inertia" is conventionally defined as a force that tends to resist motion that must be overcome to put a material into motion. In the context of the present invention, inertia is understood to mean that component of the breakout force that does not include adhesion. Summary of the Invention [Problem to be solved by the invention]

[0009] The breakout or opening force, especially the degree of sticking, varies according to the composition of the surface. In general, elastic materials show greater sticking than inelastic materials, especially when the surfaces are of similar composition. The length of time that the surfaces are in static contact with each other also affects the breakout and / or opening force. In syringe technology, the term "standing" refers to storage time, keeping time, or the interval between filling and dispensing. In general, standing increases the breakout or opening force, especially if the syringe is refrigerated during standing.

[0010] The traditional approach to overcoming breakout has been to apply a lubricant to the surface-to-surface interface. Such traditional lubricated stoppers have the disadvantage of being soluble in a variety of fluids, such as those commonly used to dispense medicines. Furthermore, these lubricants are subject to air oxidation, resulting in viscosity changes and the development of unpleasant colors. Moreover, they are particularly susceptible to degradation from the surface-to-surface interface. Such lubricant degradation is generally believed to be responsible for the increase in breakout force over time on storage.

[0011] Additional problems with applying a lubricant to the surface of the stopper are that such a lubrication step requires the cost of the lubricant and lubrication equipment, the time and energy to operate and perform the lubrication step, and the stopper must be removed from the automated assembly process for lubrication.

[0012] For these reasons, there is a need for a better syringe assembly that can overcome the high breakout and opening forces, thereby achieving a smooth transition of the two surfaces from static to sliding contact, and a need exists for a stopper that exhibits the required performance characteristics and does not require an additional lubrication step. [Means for solving the problem]

[0013] The present disclosure provides thermoplastic elastomer stoppers that meet the desired material properties of a stopper for a syringe assembly. These material properties are compression set, hardness, stress at a given strain level, and viscosity at a given shear rate. The thermoplastic elastomer stoppers of the present disclosure can have a compression set of 50% or less when held at 70° C. for 22 hours at 25% compression (ASTM D395-03, Method B). The hardness of the thermoplastic elastomer stoppers of the present disclosure can be in the range of 40 to 70 Shore A (ASTM D2240-05). The stress at the desired strain value should also be optimized for the thermoplastic elastomer stoppers of the present disclosure to obtain good leakage and force performance in the assembled syringe. The viscosity of the thermoplastic elastomer stopper of the present disclosure is measured at 205° C. using a capillary rheometer (die: round hole length 20 mm / diameter 1 mm / 180 degree inlet, piston: d=15 mm, and melt time=7 min) at a shear rate of 1,000 s -1 70.0 Pa s or more, shear rate 10,000 s -1 and a shear rate of 50,000 s -1 In one embodiment, the thermoplastic elastomer stopper of the present disclosure provides stiction-free performance in polypropylene or polypropylene copolymer based syringe barrels. For example, the stopper of the present disclosure includes 30-65% elastomer, such as, but not limited to, 30-65% styrene-ethylene-butylene-styrene (SEBS) copolymer blended with 10-35% medium to high density polyethylene (medium to high density with a melting temperature in the range of 120° C. to 130° C.), 20-35% commonly available mineral oil and commonly available radiation stabilizers, antioxidants, and / or processing aids. The molecular weights of the elastomer and polyethylene are selected to obtain the desired material properties as described above.

[0014] The present disclosure also provides a stopper that maintains a leak-free syringe with low opening and staying forces. In one embodiment, the present disclosure provides a lubricant-free stopper that exhibits the functional performance factors required for syringe assembly. Advantageously, the stopper of the present disclosure provides the required functional performance while eliminating the application of external lubricant to the stopper. In this manner, the negative consequences of external lubricant application to the stopper are eliminated. For example, the lubrication step to the stopper requires the cost of lubricant and lubrication equipment, the time and energy to operate and perform the lubrication step, and the stopper must be removed from the automated assembly process for lubrication. The present disclosure also provides a stopper that allows for a fully automated stopper assembly process. Furthermore, the present disclosure allows for an autoclave-sterilizable lubricant-free stopper for syringe assembly by using a high melt temperature polymer as the hard phase.

[0015] The present invention provides a stopper for a syringe assembly having an exterior surface adapted to sealably engage with an inner surface of a chamber of a medical device. The respective surfaces can be frictionally engaged. When used within a medical device, the stopper of the present invention can reduce the force required to achieve breakout force, opening force, and / or sustaining force, such that the transition of the surfaces from static contact to sliding contact occurs without a sudden surge. When the breakout or opening is complete and the surfaces are in sliding contact, they slide smoothly with very low sustaining force. These advantages are achieved without the use of lubricants applied to the surface of the stopper. The present invention also provides a stopper that achieves high pressure against leaking. In this way, the stopper of the present invention maintains a leak-free syringe with low opening and sustaining forces. The stopper of the present disclosure, and the effects achieved by the method of the present invention, can provide the advantages of low breakout force, low opening force, and sustaining force without leakage throughout the entire standing period. When the stopper of the present disclosure is part of a liquid dispensing device such as a syringe assembly, small, very precise increments of liquid can be repeatedly dispensed without sudden surges. Thus, a syringe assembly including the stopper of the present disclosure can be used to administer medication to a patient without risk of surges, thereby providing precise control of the dose and greatly improved patient safety. This is achieved and maintained after sterilization and over the life of the stopper, e.g., five years.

[0016] According to one embodiment of the present invention, a stopper for a syringe assembly comprises a thermoplastic elastomer, the thermoplastic elastomer having a compression set of 50% or less when held at 70° C. for 22 hours at 25% compression, the thermoplastic elastomer having a hardness of about 40-70 Shore A, and the viscosity of the thermoplastic elastomer having a shear rate of 1,000 s when measured using a capillary rheometer (die: round hole length 20 mm / diameter 1 mm / 180 degree inlet, piston: d=15 mm, and melt time=7 min) at 205° C. -1 70.0 Pa s or more, shear rate 10,000 s -1and a shear rate of 50,000 s -1 and is 3.0 Pa s or more.

[0017] In one configuration, the thermoplastic elastomer has a compression set of 35% or less when held at 70°C for 22 hours under 25% compression. In another configuration, the thermoplastic elastomer has a compression set of about 10% to 35% when held at 70°C for 22 hours under 25% compression. In another configuration, the thermoplastic elastomer has a hardness of about 45 to 65 Shore A. In one configuration, the thermoplastic elastomer has a hardness of about 53 to 63 Shore A. In another configuration, the viscosity of the thermoplastic elastomer is about 10% to 20% at a shear rate of 1,000 sec. -1 In other configurations, the viscosity of the thermoplastic elastomer is between 70.0 Pa·s and 320.0 Pa·s at a shear rate of 1,000 s -1 In one configuration, the viscosity of the thermoplastic elastomer is between 100.0 Pa·s and 170.0 Pa·s at a shear rate of 10,000 s -1 In other configurations, the viscosity of the thermoplastic elastomer ranges from 12.0 Pa·s to 46.0 Pa·s at a shear rate of 10,000 s -1 In other configurations, the viscosity of the thermoplastic elastomer ranges from 16.0 Pa·s to 27.0 Pa·s at a shear rate of 50,000 s -1 In one configuration, the viscosity of the thermoplastic elastomer is between 3.0 Pa·s and 12.0 Pa·s at a shear rate of 50,000 s -1 and the viscosity is 4.5 Pa·s to 7.5 Pa·s.

[0018] In accordance with another embodiment of the present invention, a syringe assembly includes a syringe barrel having a proximal end, a distal end, and a sidewall extending therebetween, defining a chamber having an interior, the syringe barrel formed from a first material, and a stopper slidably disposed within the interior of the syringe barrel chamber, the stopper being sized relative to the interior of the syringe barrel chamber to provide a sealing engagement with the sidewall of the syringe barrel, the stopper being formed from a second material different from the first material, the second material not comprising more than 4% of the first material, more preferably the second material not comprising more than 1.5% of the first material, and even more preferably the second material not comprising more than 1% of the first material. The syringe assembly further includes a plunger rod having a first end engageable with a portion of the stopper.

[0019] In accordance with another embodiment of the present invention, a syringe assembly includes a syringe barrel having a proximal end, a distal end, and a sidewall extending therebetween defining a chamber having an interior, and a stopper slidably disposed within the interior of the syringe barrel chamber, the stopper being sized relative to the interior of the syringe barrel chamber to provide sealing engagement with the sidewall of the syringe barrel and formed from a non-lubricated thermoplastic elastomer. The syringe assembly further includes a plunger rod having a first end engageable with a portion of the stopper.

[0020] In one configuration, the stopper comprises a polyethylene blended with a styrene block copolymer. In another configuration, the stopper comprises an olefin block copolymer containing a polyethylene block. The stopper composition may also include mineral oil, radiation stabilizers, antioxidants, and / or processing aids.

[0021] According to another embodiment of the present invention, a syringe assembly includes a syringe barrel having a proximal end, a distal end, and a sidewall extending therebetween, the syringe barrel defining a chamber having an interior, the syringe assembly further including a stopper comprising a thermoplastic elastomer, the thermoplastic elastomer having a compression set of 50% or less when held at 70° C. for 22 hours at 25% compression, a hardness of the thermoplastic elastomer of about 40-70 Shore A, and a viscosity of the thermoplastic elastomer of about 100% at a shear rate of 1,000 sec -1 70.0 Pa s or more, shear rate 10,000 s -1 and a shear rate of 50,000 s -1 The stopper may have a formulation including an elastomeric phase, such as, but not limited to, a styrene block copolymer, an olefin block copolymer, an SBR rubber, or a polyisoprene, and a hard polymer phase, such as, but not limited to, a polyolefin and other higher melting temperature polymers (above 170° C.), such as, but not limited to, ethylene tetrafluoroethylene and fluorinated ethylene propylene polymers, along with a hydrocarbon liquid, such as mineral oil, and radiation stabilizers and / or other processing aids, the stopper is slidably disposed within an interior of the chamber of the syringe barrel, the stopper is sized relative to an interior of the chamber of the syringe barrel to provide a sealing engagement with a sidewall of the syringe barrel, the stopper being formed from a non-lubricated thermoplastic elastomer. The syringe assembly further includes a plunger rod having a first end engageable with a portion of the stopper, and the formulation of the stopper is different from the barrel material, e.g., the hard phase for the formulation of the stopper should not be polypropylene-based if the barrel material is formed from polypropylene or is a polypropylene-based barrel.

[0022] According to other embodiments of the present invention, the stopper of the present invention provides manufacturing and / or molding advantages. For example, in one embodiment, the stopper of the present invention includes a shear feature, i.e., a thin wall section, at the mold gating point in the mold cavity. The shear feature of the stopper of the present invention adds shear heating at the mold gate point. In this manner, the stopper of the present invention eliminates cold material entering the mold cavity, eliminates flow lines and / or weld lines common to stopper molding, eliminates sink marks, improves gate quality control, improves mold cycle time, and eliminates surface and / or visual imperfections.

[0023] According to another embodiment of the present invention, a stopper for a syringe assembly includes a lower portion, a roof portion having a first thickness, and a shear element disposed adjacent to the roof portion, the shear element having a second thickness, the second thickness of the shear element being less than 52% and greater than 36% of the first thickness of the roof portion.

[0024] In one configuration, the second thickness of the shear portion is about 44% of the first thickness of the roof portion.In another configuration, the stopper includes a catch can portion having a receiving volume.

[0025] According to another embodiment of the present invention, a stopper for a syringe assembly includes a lower portion, a roof portion, a core portion disposed adjacent to the roof portion, the core portion having a semi-elliptical shape, a first sealing rib disposed adjacent to the roof portion, and a second sealing rib disposed adjacent to the lower portion.

[0026] In one configuration, the first sealing rib is configured to provide increased contact pressure at the first sealing rib as fluid pressure increases. In one embodiment, the first rib width provides lower breakout and durability forces with acceptable compression set during shelf life. In another configuration, a slip additive is added to the thermoplastic elastomer.

[0027] In accordance with other embodiments of the present invention, the stoppers of the present disclosure may be used with unlubricated barrels modified with slip agents, which may be a combination of slow crystallizing (blooming) components for long term performance and fast crystallizing (blooming) components to reduce frictional properties more quickly.

[0028] According to another embodiment of the present invention, a stopper for a syringe assembly includes a lower portion, a roof portion having a first thickness, a shear portion disposed adjacent to the roof portion having a second thickness, the second thickness of the shear portion being less than 52% and greater than 36% of the first thickness of the roof portion, and a catch can portion having a receiving volume.

[0029] In accordance with another embodiment of the present invention, a syringe assembly includes a syringe barrel having a proximal end, a distal end, and a sidewall extending therebetween, the syringe barrel having a barrel material formulation defining a chamber having an interior, and a stopper including a thermoplastic elastomer, the thermoplastic elastomer having a compression set of 50% or less when held at 70° C. for 22 hours at 25% compression, the thermoplastic elastomer having a hardness of about 40-70 Shore A, and the thermoplastic elastomer having a viscosity of about 100% at a shear rate of 1,000 sec. -1 70.0 Pa s or more, shear rate 10,000 s -1 and a shear rate of 50,000 s -1 the stopper comprising a formulation having a hard polymer phase having a high melting temperature of greater than 170° C. and a viscosity of 3.0 Pa·s or greater at room temperature; a stopper formed from a non-lubricated thermoplastic elastomer and sized relative to the interior of the chamber of the syringe barrel to provide a sealing engagement with a sidewall of the syringe barrel; and a plunger rod having a first end engageable with a portion of the stopper, wherein the stopper formulation is different from the barrel material formulation. [Brief description of the drawings]

[0030] The above-mentioned 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, by referring to the following description of embodiments of the present disclosure in conjunction with the accompanying drawings.

[0031] [Figure 1] FIG. 2 is an assembled top view of a syringe assembly including a stopper in a first position, according to one embodiment of the present invention. [Figure 2A] 2 is a cross-sectional view of the syringe assembly of FIG. 1 with the stopper in a second position, in accordance with one embodiment of the present invention. [Figure 2B] FIG. 13 is a detailed view of a portion of the stopper that contacts the interior surface of the syringe barrel, according to one embodiment of the present invention. [Diagram 3] FIG. 2 is a plan view of a stopper according to one embodiment of the present invention. [Figure 4] FIG. 4 is a cross-sectional view taken along line 4-4 of FIG. 3, according to one embodiment of the present invention. [Diagram 5] FIG. 5 is a cross-sectional view taken along line 5-5 of FIG. 3, according to one embodiment of the present invention. [Figure 6] FIG. 13 is a plan view of a stopper according to another embodiment of the present invention. [Figure 7] 7 is a cross-sectional view taken along line 7-7 of FIG. 6 according to another embodiment of the present invention. [Figure 8] 8 is a cross-sectional view taken along line 8-8 of FIG. 6 according to another embodiment of the present invention. [Figure 9] 1 is a graph of a conventional stopper exhibiting stiction. [Figure 10] 1 is a graph of a stopper exhibiting no stiction, according to one embodiment of the present invention. [Figure 11] 1 is a table comparing the stress-strain properties of various stoppers according to one embodiment of the present invention. [Figure 12] 1 is a table comparing functional characteristics of various stoppers according to one embodiment of the present invention. [Figure 13] 1 is a table comparing functional characteristics of various stoppers according to one embodiment of the present invention. [Figure 14A]1 is a graph of viscosity and shear rate for various stoppers according to one embodiment of the present invention. [Figure 14B] 1 is a table of manual operation characteristics of various stoppers according to one embodiment of the present invention. [Figure 15] 1 is a table comparing contact pressure values ​​of a conventional stopper with that stopper at a first sealing rib according to an embodiment of the present invention. [Figure 16] 1 is a table of various thermoplastic elastomer stoppers according to one embodiment of the present invention. [Figure 17] 1 is a table of polypropylene (PP) content for various thermoplastic elastomer stoppers according to one embodiment of the present invention. [Figure 18] 1 is a graph of the pump force profile of a thermoplastic elastomer stopper according to one embodiment of the present invention. [Figure 19] 1 is a graph of the pump force profile of a thermoplastic elastomer stopper according to one embodiment of the present invention. [Figure 20] 1 is a table of polypropylene (PP) content, polyethylene (PE) content, compression set, and leakage performance of various thermoplastic elastomer stoppers according to one embodiment of the present invention. [Figure 21] 1 is a table of polypropylene (PP) content, polyethylene (PE) content, compression set, viscosity at specific shear rates, and manual handling for various thermoplastic elastomer stoppers according to one embodiment of the present invention. [Figure 22] 1 is a table of force performance of thermoplastic elastomer stoppers having different levels of erucamide slip agent, according to one embodiment of the present invention. [Figure 23] 1 is a table of leak pressure and durability rankings for thermoplastic elastomer stoppers predicted by FEA simulation, in accordance with one embodiment of the present invention. [Figure 24] 1 is a table of leak pressure and durability rankings for thermoplastic elastomer stoppers according to one embodiment of the present invention. [Diagram 25]1 is a table of material properties for a thermoplastic elastomer stopper according to one embodiment of the present invention. [Figure 26] 1 is a table of manual operation of a thermoplastic elastomer stopper having different levels of erucamide slip agent according to one embodiment of the present invention. [Figure 27] 2 is a cross-sectional view of a thermoplastic elastomer stopper and hot tip portion of a hot runner system in accordance with one embodiment of the present invention. [Figure 28] 2 is a cross-sectional view of a thermoplastic elastomer stopper and hot tip portion of a hot runner system in accordance with one embodiment of the present invention.

[0032] Corresponding reference characters indicate corresponding parts throughout the several views. The illustrations set forth herein illustrate exemplary embodiments of the present disclosure, and such illustrations should not be construed as limiting the scope of the present disclosure in any way. DETAILED DESCRIPTION OF THE PREFERRED EMBODIMENTS

[0033] Except in the working examples or where otherwise indicated, all numbers expressing quantities of components, material properties, and the like used in the specification and claims and figures should be understood in all instances to be modified 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 at least be construed in light of the number of reported significant digits and by applying ordinary rounding techniques.

[0034] Notwithstanding that the numerical ranges and parameters setting forth the broad scope of the invention are approximations, the numerical values ​​set forth within 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 equipment. Furthermore, when numerical ranges varying in scope are set forth herein, it is contemplated that any combination of these values ​​inclusive of the recited values ​​may be used.

[0035] For purposes of the following description, the terms "upper", "lower", "right", "left", "vertical", "horizontal", "top", "bottom", "lateral", "longitudinal", and their derivatives shall refer to the present invention as oriented within the figures of the drawings. It should be understood, however, that the present invention may assume various alternative variations unless expressly specified otherwise. 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 invention. Hence, specific dimensions and other physical characteristics relating to the embodiments disclosed herein are not to be considered as limiting.

[0036] In the following discussion, "distal" refers generally to a direction toward an end of the syringe assembly adapted to contact a patient and / or engage a separate device, such as a needle assembly or an IV connection assembly, and "proximal" refers in the opposite direction to distal, i.e., away from that end of the syringe assembly adapted to engage a separate device. In this disclosure, the above references are used to describe components of a syringe assembly according to the present disclosure.

[0037] The present disclosure provides thermoplastic elastomer stoppers that meet the desired material properties of a stopper for a syringe assembly. These material properties are compression set, hardness, stress at a given strain level, and viscosity at a given shear rate. The compression set of the thermoplastic elastomer stoppers of the present disclosure can be 50% or less when measured at 25% compression (ASTM D395-03, Method B) for 22 hours at 70°C. The hardness of the thermoplastic elastomer stoppers of the present disclosure can be in the range of 40 to 70 Shore A (ASTM D2240-05). The stress at the desired strain value should also be optimized for the thermoplastic elastomer stoppers of the present disclosure to obtain good leakage and force performance in the assembled syringe. The viscosity of the thermoplastic elastomer stopper of the present disclosure is measured at 205° C. using a capillary rheometer (die: round hole length 20 mm / diameter 1 mm / 180 degree inlet, piston: d=15 mm, and melt time=7 min) at a shear rate of 1,000 s -1 70.0 Pa s or more, shear rate 10,000 s -1 and a shear rate of 50,000 s -1 The viscosity of the stopper may be 3.0 Pa·s or greater at 100° C. In one embodiment, the thermoplastic elastomer stopper of the present disclosure provides stiction-free performance in a barrel based on polypropylene or polypropylene copolymer. For example, the stopper of the present disclosure may include 30-65% elastomer, such as, but not limited to, 30-65% styrene-ethylene-butylene-styrene (SEBS) copolymer blended with 10-35% medium to high density polyethylene (medium to high density with a melting temperature in the range of 120° C. to 130° C.), 20-35% commonly available mineral oil, and commonly available radiation stabilizers, antioxidants, and / or processing aids. The molecular weights of the elastomer and polyethylene are selected to obtain the desired material properties as described above.

[0038] The present disclosure also provides a stopper that maintains a leak-free syringe with low opening and staying forces. In one embodiment, the present invention provides a lubricated stopper that exhibits the functional performance factors required for syringe assembly. Advantageously, the stopper of the present disclosure provides the required functional performance while eliminating the application of external lubricant to the stopper. In this manner, the negative consequences of external lubricant application to the stopper are eliminated. For example, the lubrication step to the stopper requires the cost of lubricant and lubrication equipment, the time and energy to operate and perform the lubrication step, and the stopper must be removed from the automated assembly process for lubrication. The present disclosure also provides a stopper that allows for a fully automated stopper assembly process. Furthermore, the present disclosure allows for an autoclavable lubricated stopper for syringe assembly by using a high melt temperature polymer as the hard phase. For example, with reference to FIG. 16, several different formulations of the present disclosure's stopper are provided, which are referenced throughout this disclosure. These formulations include various TPE chemistries such as olefin block copolymers, polyethylene blended with styrene block copolymers, polypropylene blended with styrene block copolymers, and polyethylene blended with EPDM TPV, etc. These TPE formulations may include commonly available radiation stabilizers, antioxidants, and / or processing aids.

[0039] In a first exemplary embodiment, the stopper of the present disclosure is formed from an olefin block copolymer, such as the TPE-1 embodiment. In a second exemplary embodiment, the stopper of the present disclosure is formed from a polyethylene blended with a styrene block copolymer having a first composition, such as the TPE-2 embodiment. In a third exemplary embodiment, the stopper of the present disclosure is formed from a polyethylene blended with a styrene block copolymer having a second composition, such as the TPE-3 embodiment. In a fourth exemplary embodiment, the stopper of the present disclosure is formed from a polypropylene blended with a styrene block copolymer formulation having a lower viscosity than the TPE-1 and TPE-2 embodiments, such as the TPE-4 embodiment. In a fifth exemplary embodiment, the stopper of the present disclosure is formed from a polyethylene blended with a styrene block copolymer having a third composition, such as the TPE-5 embodiment. In other exemplary embodiments, the stopper of the present disclosure is formed from other materials and / or formulations, such as the several different exemplary formulations of the stopper of the present disclosure provided in FIG. 16.

[0040] In accordance with other embodiments of the present invention, the stoppers of the present disclosure may be used with unlubricated barrels modified with slip agents, which may be a combination of slow crystallizing (blooming) components for long term performance and fast crystallizing (blooming) components to reduce frictional properties more quickly.

[0041] 1 and 2A, the syringe assembly 10 includes a syringe barrel 12, a plunger rod 14, and a stopper 16. The syringe assembly 10 may be adapted for dispensing and ejecting fluids and / or collecting fluids. For example, the syringe assembly 10 may be used to inject or infuse fluids, such as medicines. The syringe assembly 10 is contemplated for use with a needle, such as by connecting the syringe assembly 10 to a separate needle assembly (not shown), or for connection to an intravenous (IV) connection assembly (not shown). It should be understood that the present disclosure may be used with any type of syringe assembly. These types of syringes include conventional pre-filled syringe assemblies, metered dose syringes, aspirating syringes for withdrawing fluids from a patient or medicines from a container, and the like.

[0042] 1 and 2A, the syringe barrel 12 generally includes a barrel body or sidewall 30 extending between a first or distal end 32 and a second or proximal end 34. The sidewall 30 defines an elongated opening or interior chamber 36 of the syringe barrel 12. In one embodiment, the interior chamber 36 may span the syringe barrel 12 such that the syringe barrel 12 is cannulated along its entire length. In one embodiment, the syringe barrel 12 may be in the general form of an elongated cylindrical barrel known in the art in the general shape of a hypodermic syringe. In alternative embodiments, the syringe barrel 12 may be in other forms for containing a fluid for expulsion, such as, for example, in the general form of an elongated rectangular barrel. The syringe barrel 12 may be formed from glass or may be injection molded from a thermoplastic material, such as, for example, polypropylene, polyethylene, cycloaliphatic polyolefins, polyester, or polycarbonate, according to techniques known to those of skill in the art, although the syringe barrel 12 may be made from other suitable materials and according to other applicable techniques. In some configurations, the syringe barrel 12 may include a flange 40 extending outwardly around at least a portion of the proximal end 34. The flange 40 may be configured to be easily grasped by a physician.

[0043] The distal end 32 of the syringe barrel 12 includes an exit opening 38 in fluid communication with the chamber 36. The exit opening 38 may be sized and adapted to engage a separate device, such as a needle assembly or an IV connection assembly, and therefore may include a mechanism for such engagement as is known in the art. For example, the distal end 32 may include a generally tapered luer tip 42 for engagement with an optional separate tapered luer structure of a separate device (not shown) for attachment therewith. In one configuration, the tapered luer tip 42 and the separate tapered luer structure may both comprise the syringe assembly 10. In such a configuration, the separate tapered luer structure may be fitted with an attachment mechanism, such as a threaded engagement, for corresponding engagement with the separate device (not shown). In another configuration, the tapered luer tip 42 may be provided for direct engagement with the separate device (not shown). Additionally, a mechanism for locking engagement therebetween, such as a luer collar or luer lock including an internal thread, may also be provided with at least one of the tapered luer tip 42 and / or a separate tapered luer structure. Such luer connections and luer locking mechanisms are well known in the art.

[0044] The proximal end 34 of the syringe barrel 12 is generally open ended, but is intended to be closed to the external environment as discussed herein. The syringe barrel 12 may include markings 44, such as graduations located on the sidewall 30, to indicate as to the level or amount of fluid contained within the interior chamber 36 of the syringe barrel 12. Such markings 44 may be provided on the exterior surface of the sidewall 30, the interior surface of the sidewall 30, or may be integrally or otherwise formed within the sidewall 30 of the syringe barrel 12. In other embodiments, alternatively or additionally, the markings 44 may provide a description of the contents of the syringe or other identifying information as may be known in the art, such as maximum and / or minimum fill lines.

[0045] The syringe assembly 10 may be useful as a pre-filled syringe and thus may be provided for end use of a fluid, such as a medicine or drug, contained within the internal chamber 36 of the syringe barrel 12, pre-filled by the manufacturer. In this manner, the syringe assembly 10 may be manufactured, pre-filled with a medicine, and sterilized for dispensing, storage, and use by an end user without the end user having to fill the syringe with a medicine from a separate vial prior to use. In such an embodiment, the syringe assembly 10 may include a cap or sealing member disposed at the distal end 32 of the syringe barrel 12 to seal the fluid, such as a medicine, within the internal chamber 36 of the syringe barrel 12.

[0046] 1-2B, the syringe assembly 10 includes a stopper 16 movably or slidably disposed within the interior chamber 36 and in sealing contact with the inner surface of the sidewall 30 of the syringe barrel 12. The stopper 16 is sized relative to the interior of the syringe barrel 12 to provide a sealing engagement with the inner surface of the sidewall 30 of the syringe barrel 12. In a prefilled syringe assembly, the stopper 16 also provides a seal to prevent liquid or pharmaceutical from leaking out of the syringe barrel 12. Additionally, in one embodiment, the stopper 16 may include one or more annular ribs extending around the periphery of the stopper 16 to increase the sealing engagement between the stopper 16 and the inner surface of the sidewall 30 of the syringe barrel 12. In an alternative embodiment, a single O-ring or multiple O-rings may be circumferentially disposed around the stopper 16 to increase the sealing engagement with the inner surface of the sidewall 30.

[0047] 1 and 2A, the syringe assembly 10 further includes a plunger rod 14 that provides a mechanism for dispensing fluid contained within the internal chamber 36 of the syringe barrel 12 through an exit opening 38. The plunger rod 14 is adapted to advance the stopper 16. In one embodiment, the plunger rod 14 is sized for movement within the internal chamber 36 of the syringe barrel 12 and generally includes a first or distal end 60 engageable with a portion of the stopper 16, a second or proximal end 62, a plunger rod body 64 extending between the first end 60 and the second end 62, and a flange 66 disposed adjacent the second end 62, as discussed in more detail below.

[0048] 1 and 2A, the plunger rod 14 includes a distal end 60 that is engageable with a portion of the stopper 16. In one embodiment, the plunger rod 14 and the stopper 16 may include engagement portions for securing the plunger rod 14 to the stopper 16. For example, these engagement portions may include corresponding threaded portions for securing the plunger rod 14 to the stopper 16. In other embodiments, these engagement portions may include snap-fit ​​features, press-fit features, ball detents, locking tabs, spring-loaded locking features, latches, adhesives, or other similar features. In other embodiments, the plunger rod 14 and the stopper 16 may be formed simultaneously, such as by coextrusion. In this manner, the plunger rod 14 is locked to the stopper 16. That is, significant relative movement between the plunger rod 14 and the stopper 16 is prevented, and the movement of the plunger rod 14 is transferred to the stopper 16, allowing the stopper 16 to slide between positions within the syringe barrel 12. In other embodiments, the plunger rod 14 and the stopper 16 may be integrally formed as a plunger assembly.

[0049] All of the components of the syringe assembly 10 may be constructed from any known material, and are preferably constructed from medical grade polymers.

[0050] The stopper 16 of the present disclosure has construction features that provide the stopper with greater resistance to leakage, reduced syringe forces such as pump and opening forces, and better demolding, which is achieved and maintained after sterilization and over the life of the syringe, e.g., five years.

[0051] 2A and 2B, in one embodiment, the stopper 16 of the present disclosure includes a supported stopper design. For example, the stopper 16 includes a first sealing rib 56A adjacent to the stopper roof portion 70A. In one embodiment, the first sealing rib 56A of the stopper 16 is sandwiched between an inner wall surface of the barrel sidewall 30 and a tip 68 of the distal end 60 of the plunger rod 14, as shown in FIG. 2B. In one embodiment, the stopper 16 of the present disclosure is a supported 10 ml syringe stopper design.

[0052] In other embodiments, the stopper 16 of the present disclosure includes an unsupported stopper design. For example, the first sealing rib 56A of the stopper 16 is not sandwiched between the syringe barrel 12 and the plunger rod 14.

[0053] 3-5, in one embodiment, the stopper 16 includes an upper portion 50, a lower portion 52, and a middle portion 54 between the upper portion 50 and the lower portion 52. The stopper 16 includes a first sealing rib 56 located adjacent the upper portion 50 and a second sealing rib 58 located adjacent the lower portion 52. The stopper 16 also includes a roof portion 70 and a core portion 72 disposed adjacent the roof portion 70. The embodiment of the stopper 16 shown in FIGS. 3-5 includes a shear portion 74 and a catch can portion 76 that allow the thermoplastic elastomer stopper to be molded in an open gate system. In one embodiment, the catch can portion 76 is configured to fit within the constraints of other features of the molded part, with the shear portion 74 allowing for easy part release. The volume of the catch can portion 76 may vary based on the attributes of the particular molding machine and tooling design. The catch can portion 76 has a receiving volume that is at least that volume of residual material left from a previous shot during molding application.

[0054] 4 and 5, the first sealing rib 56 is sized and shaped to provide an active sealing rib that provides greater resistance to leakage. For example, with reference to FIG. 2B, the stopper of the present disclosure includes a first sealing rib 56A that provides a first contact area 96 with the interior surface of the sidewall 30 of the syringe barrel 12, and a second sealing rib 58 that provides a second contact area 98 with the interior surface of the sidewall 30 of the syringe barrel 12.

[0055] Referring to FIG. 15, the contact pressure of the first sealing rib of the stopper indicates resistance to fluid leakage. Higher first sealing rib contact pressure leads to higher resistance to leakage. With the active sealing rib, i.e., first sealing rib 56 design of the present disclosure, as the fluid pressure increases, the contact pressure at the stopper sealing rib increases. Thus, the stopper of the present disclosure provides higher resistance to leakage. FIG. 15 shows the stopper of the present disclosure, which provides higher resistance to leakage than conventional stoppers due to the above sealing rib design.

[0056] 4 and 5, second sealing rib 58 has a reduced thickness. Thus, referring to FIG. 2B, second contact area 98, i.e., the contact area between second sealing rib 58 and the interior surface of sidewall 30 of syringe barrel 12, is reduced. Such reduced second contact area 98 results in reduced forces to operate the syringe, such as pumping and opening forces.

[0057] 4 and 5, the roof portion 70 includes an increased roof thickness that results in improved leak performance. For example, the increased roof thickness of the stopper 16 of the present disclosure results in a 20% increase in leak pressure. The roof portion 70 of the stopper 16 helps contribute to a higher contact pressure when fluid pressure is applied, which leads to a higher resistance to leaking, as shown in FIG.

[0058] 4 and 5, the core portion 72 includes a semi-elliptical shape that provides better demolding of the stopper 16. The angled design of the core portion 72 prevents breakage of the stopper and increases the mechanical strength of the core pin.

[0059] 6-8, in one embodiment, the stopper 16B includes an upper portion 80, a lower portion 82, and an intermediate portion 84 between the upper portion 80 and the lower portion 82. The stopper 16B includes a first sealing rib 86 located adjacent the upper portion 80 and a second sealing rib 88 located adjacent the lower portion 82. The stopper 16B also includes a roof portion 90 and a core portion 92. The stopper 16B may be moldable onto a valve gate system.

[0060] 8, the first sealing rib 86 is sized and shaped to provide an active sealing rib that provides greater resistance to leakage. For example, with reference to FIG. 2B, the stopper of the present disclosure includes a first sealing rib 86 that provides a first contact area 96B with the inner surface of the sidewall 30 of the syringe barrel 12, and a second sealing rib 88 that provides a second contact area 98B with the inner surface of the sidewall 30 of the syringe barrel 12.

[0061] As discussed above, the higher first sealing rib contact pressure of the stopper of the present disclosure leads to a higher resistance to leakage. With the active sealing rib, i.e., first sealing rib 86 design of the present disclosure, as the fluid pressure increases, the contact pressure at the stopper sealing rib increases. Thus, the stopper of the present disclosure provides a higher resistance to leakage. Figure 15 shows the stopper of the present disclosure, which provides a higher resistance to leakage than conventional stoppers due to the above sealing rib design.

[0062] 8, second sealing rib 88 includes a reduced thickness. Thus, referring to FIG. 2B, second contact area 98B, i.e., the contact area between second sealing rib 88 and the interior surface of sidewall 30 of syringe barrel 12, is reduced. Such reduced second contact area 98B results in reduced forces that move the syringe, such as pumping and opening forces.

[0063] With reference to Figure 8, roof portion 90 includes an increased roof thickness that provides improved leak performance. For example, stopper 16B of the present disclosure provides a 20% increase in leak pressure. With reference to Figure 8, core portion 92 includes a rectangular shape. In other embodiments, it is contemplated that core portion 92 may have other shapes. For example, core portion 92 may have an elliptical shape to aid in demolding during injection molding of the stopper.

[0064] In one embodiment, the stopper 16 of the exemplary embodiment is made of a material that provides the required functional properties of the stopper without requiring the outer surface of the stopper to be lubricated. For example, the stopper 16 may be formed from a thermoplastic elastomer. In one embodiment, the stopper 16 includes a polyethylene-based thermoplastic elastomer. In one embodiment, to reduce stiction of the syringe assembly 10 with the syringe barrel 12, the stopper 16 includes a polyethylene-based thermoplastic elastomer that includes at least 20% polyethylene with optimized material properties, such as hardness, compression set, stress, and strain.

[0065] In one embodiment, such as the TPE-2 embodiment, the stopper 16 may be formed from a polyethylene blended with a thermoplastic elastomer, such as a styrene block copolymer. In other embodiments, the stopper 16 may be formed from an olefin block copolymer blended with a polyethylene block. Polyethylene, or an embodiment having a similar structure, such as, but not limited to, an olefin block copolymer, also reduces stiction of the syringe assembly 10 with the syringe barrel 12.

[0066] The stopper 16 of the present disclosure provides a thermoplastic elastomer with reduced stiction with the syringe barrel of the syringe assembly. Additionally, the stopper 16 of the present disclosure provides low syringe forces, such as opening force, breakout force, and sustaining force, and acceptable leakage performance during shelf life, i.e., the period between the product manufacturing date and expiration date. The stopper 16 of the present disclosure provides low syringe forces along with low compression set, such that the stopper 16 does not require the outer surface of the stopper to be lubricated.

[0067] In an exemplary embodiment of the present disclosure, the thermoplastic elastomer composition will include 30 to 65 wt. % thermoplastic elastomer, 10 to 35 wt. % polyolefin or other high melting temperature polymer, and 20 to 35 wt. % other additives such as a hydrocarbon liquid, e.g., mineral oil. In other embodiments, the other additives may include other hydrophobic liquids with high boiling temperatures to ensure that the required amount is present on and inside the stopper. In other embodiments, an olefin block copolymer with a polyethylene hard phase (40 to 80%) may replace the thermoplastic elastomer and polyolefin or high melting temperature polymer.

[0068] The stopper 16 of the present disclosure does not require the outer surface of the stopper to be lubricated due to segregation of the hydrocarbon liquid, such as mineral oil, on the stopper surface. In this manner, the segregated hydrocarbon liquid on the stopper surface acts as a lubricant, replacing the need and reducing the operating force of the syringe. Segregation of the high hydrocarbon liquid surface is determined by the competition between the energy and the entropy of mixing. By making the stopper of the present disclosure more viscous or increasing the molecular weight of the thermoplastic elastomer, the degree of mixing of the hydrocarbon liquid in the formulation is reduced and a greater amount of the hydrocarbon liquid segregates on the stopper surface. In this manner, the segregated hydrocarbon liquid on the surface acts as a lubricant, replacing the need and reducing the operating force of the syringe to the level observed with an externally lubricated stopper. Thus, the stopper of the present disclosure provides a stopper that has the required functional properties of the stopper without the need for the outer surface of the stopper to be lubricated, thereby eliminating the problems associated with applying a lubricant to the surface of the stopper. Problems with such lubrication steps include the required cost of lubricant and lubrication equipment, the time and energy to operate and perform the lubrication step, and the requirement for the stopper to be removed from the automated assembly process to be lubricated. The stopper of the present disclosure allows for full automation of the stopper during assembly by eliminating the external lubrication step during assembly of the stopper.

[0069] In one embodiment, the presence of polyethylene on the surface of the stopper, combined with the surface energy of the stopper, enables the stopper to have the required functional properties without the need for the outer surface of the stopper to be lubricated, thereby eliminating the problems associated with applying a lubricant to the surface of the stopper. For example, polystyrene in a blend of polyethylene and styrene block copolymer (approximately 41 mJ / m 2 ) compared to the lower surface energy of polyethylene (approximately 35 mJ / m 2) can result in selective segregation of polyethylene to the surface, reduced interaction between the stopper and barrel material, and stiction-free performance. In a TPE-2 embodiment, the stopper 16 may be formed of polyethylene blended with a styrene block copolymer. The hard phase of the styrene block copolymer is chemically bonded to the soft phase so that the polyethylene is selectively segregated to the surface. Polypropylene is less desirable than polyolefins in stoppers in syringes with polypropylene or polypropylene copolymer barrels due to increased interaction between the stopper and barrel polypropylene that can result in stiction.

[0070] Furthermore, stoppers with increased thermoplastic elastomer molecular weight to achieve the viscosity requirements also solve the high compression set problem encountered with many previous stoppers for syringe assembly applications. The addition of low viscosity hydrocarbon liquids, such as mineral oil, to the stoppers of the present disclosure also improves the flow properties of the stopper blend composition at the thermoplastic elastomer processing temperature. In one embodiment, the thermal expansion coefficient of the syringe stopper can be reduced by the addition of inorganic fillers, such as silica or calcium carbonate, due to the low thermal expansion coefficients of such inorganic fillers and their effect on the crystalline architecture of the TPE matrix. In this way, the addition of inorganic fillers compensates for the high thermal expansion coefficient of the thermoplastic elastomer.

[0071] As noted above, the stopper 16 may be formed from an unlubricated thermoplastic elastomer. Such stoppers 16 provide low compression set. For example, unlubricated thermoplastic elastomer stoppers 16 provide a compression set of 35% or less at 25% compression at 70° C. for 22 hours. The stoppers of the present disclosure provide the required compression set through the use of high molecular weight components.

[0072] In one embodiment of the present disclosure, a stopper for a syringe assembly comprises a thermoplastic elastomer having a compression set of 50% or less when measured at 25% compression for 22 hours at 70° C. In another embodiment, the compression set of the thermoplastic elastomer is about 35% or less when held at 70° C. for 22 hours at 25% compression. In another embodiment, the compression set of the thermoplastic elastomer is about 10%-35% when held at 70° C. for 22 hours at 25% compression.

[0073] Low compression set is desirable for syringe stopper applications because the stopper's interface with the barrel determines both the syringe application force and the leakage performance. With high compression set, the syringe leakage and force performance will be satisfactory after assembly, but the leakage performance will be compromised during syringe storage life as shown in Figure 20. Figure 20 shows that TPE stopper materials with compression set levels above 50% (ASTM D395-03, Method B, 22 hours at 70°C) have poor leakage performance during syringe storage life.

[0074] Additionally, the stopper 16 of the present disclosure provides a better hand feel for syringes with multiple different fluids. For example, the manual handling of filling a syringe with fluid without a needle attached is improved, and using the stopper 16 of the present disclosure with a syringe assembly provides good control at the droplet level, for example when placing a drop of blood on a slide for evaluation. By improving the manual handling of the syringe assembly, the clinician can smoothly dispense the fluid to the patient, thereby reducing patient discomfort. Furthermore, by improving the manual handling of the syringe assembly, fluid spurting leading to contamination is eliminated. The stopper of the present disclosure provides improved manual handling characteristics through the use of high molecular weight components. Additionally, the stopper of the present disclosure uses a higher viscosity of the TPE to provide a stopper that provides the above functional performance factors for the syringe assembly while eliminating an external lubricant on the stopper. For example, a stopper formed with a lower viscosity than the TPE-2 embodiment of the present disclosure may have poor control with spurting of isopropanol and blood. Thus, the higher viscosity of the TPE-2 embodiments of the present disclosure is an important factor for good maneuverability.

[0075] Referring to FIG. 14B, a table is provided showing the improved hand-operability characteristics of stoppers of the present disclosure formed from olefin block copolymers, such as TPE-1 embodiments, and stoppers of the present disclosure formed from polyethylene blended with styrene block copolymers, such as TPE-2 embodiments. An embodiment of TPE-4, which is a polypropylene blended with a styrene block copolymer formulation having a lower viscosity than the embodiments of TPE-1 and TPE-2, shows poor liquid control with blowing (FIG. 14A). An embodiment of TPE-5 (such as that shown in FIG. 14A), which is also based on polyethylene blended with a styrene block copolymer similar to TPE-2 but with a lower viscosity, also shows poor liquid control with blowing. The minimum viscosity of the TPE formulation recorded for the embodiments in the present disclosure is required for good hand-operability of the stopper formulation used in syringe applications.

[0076] Referring to FIG. 14B, the stopper of the present disclosure is formed from a TPE having high viscosity, which provides additional advantages such as no external lubricant on the stopper and improved manual operation over conventional stoppers. The stopper of the present disclosure provides improved and / or favorable maintenance of manual operation of the syringe with fluid and / or limited excipient interaction. The stopper of the present disclosure formed from a highly viscous TPE helps achieve better manual operation with different fluids. The stopper of the present disclosure formed from a highly viscous TPE provides improved and / or favorable excipient interaction or manual operation of the syringe with fluid. Various manual operation of the fluid may be observed, such as good control at droplet level (best control), good control but non-droplet fluid flow at the beginning of the plunger movement, good control at droplet level at the beginning but spurting in the middle of the fluid injection, starting with spurting but improving control later, and starting with spurting and not being controlled during the fluid injection or poor control with spurting (worst control).

[0077] Slip additives are commonly added to TPE formulations to reduce the coefficient of friction. An unexpected effect was observed on syringe hand-operation by the presence of slip additives in the TPE stopper formulation (with the effect of formulation viscosity on this performance shown in FIG. 14A). By adding slip additives such as but not limited to erucamide, oleamide, or behenamide at concentrations less than 1%, hand-operation improves significantly above the critical concentration of slip additive as shown in FIG. 26. The presence of slip additives in the TPE stopper formulation also affects the syringe force as predicted by the reduction in the coefficient of friction shown in FIG. 22.

[0078] With reference to FIG. 21, the stopper of the present disclosure is formed from a high viscosity TPE. Viscosity below a critical level leads to poor excipient handling with fluid spurting during injection. In one embodiment of the present disclosure, the viscosity of the thermoplastic elastomer is measured using a capillary rheometer (die: round hole length 20 mm / diameter 1 mm / 180 degree inlet, piston: d=15 mm, and melt time=7 min) at a shear rate of 1,000 sec. -1 70.0 Pa s or more, shear rate 10,000 s -1 and a shear rate of 50,000 s -1 In one embodiment, the viscosity of the thermoplastic elastomer is greater than or equal to 3.0 Pa·s at a shear rate of 1,000 s -1 In another embodiment, the viscosity of the thermoplastic elastomer is from 70.0 Pa·s to 320.0 Pa·s at a shear rate of 1,000 s -1 In another embodiment, the viscosity of the thermoplastic elastomer is from 100.0 Pa·s to 170.0 Pa·s at a shear rate of 10,000 s -1 In another embodiment, the viscosity of the thermoplastic elastomer is from 120.0 Pa·s to 46.0 Pa·s at a shear rate of 10,000 s -1 In another embodiment, the viscosity of the thermoplastic elastomer is from 16.0 Pa·s to 27.0 Pa·s at a shear rate of 50,000 s -1 In one embodiment, the viscosity of the thermoplastic elastomer is from 3.0 Pa·s to 12.0 Pa·s at a shear rate of 50,000 s -1 and 4.5 Pa s to 7.5 Pa s.

[0079] A stress-strain curve is a material property that characterizes the behavior of a particular material. The linear portion of the stress-strain curve is governed by a relationship known as Hooke's Law. For stoppers, this stress-strain relationship is translated into an appropriate material model as one of the inputs to FEA (Finite Element Analysis) during the design process.

[0080] In one embodiment, the stress at the desired strain value is also optimized for the thermoplastic elastomer stoppers of the present disclosure to obtain good leak and force performance in the assembled syringe. Referring to Figure 11, a table with desired stress values ​​is provided.

[0081] 11-14B, in one embodiment, such as the TPE-1 embodiment, the stopper 16 may be formed from an olefin block copolymer. In other embodiments, such as the TPE-2 embodiment, the TPE-3 embodiment, or the TPE-5 embodiment, the stopper 16 may be formed from a polyethylene blended with a styrene block copolymer. In other embodiments, such as the TPE-4 embodiment, the stopper 16 may be formed from a polypropylene blended with a styrene block copolymer. Conventional based stoppers may be formed from styrene-based or polyisoprene-based materials.

[0082] The present disclosure provides a thermoplastic elastomer stopper that meets the desired material properties and design of the stopper for a syringe assembly. With reference to FIG. 12 and FIG. 13, a table is provided that demonstrates the importance of the design and desired physical properties for the material of the stopper of the present disclosure. It is noted herein that the test method "IT" shown in FIG. 12 adheres to ISO standard 7886-1:1993. In one embodiment, the material properties may include compression set, hardness, stress at a given strain level, and viscosity at a given shear rate. In one embodiment, the thermoplastic elastomer stopper of the present disclosure may have a compression set of 50% or less when held at 70° C. for 22 hours at 25% compression (ASTM D395-03, Method B). In one embodiment, the hardness of the thermoplastic elastomer of the present disclosure should be within the range of 40 to 70 Shore A (ASTM D2240-05). The stress at the desired strain value should also be optimized for the thermoplastic elastomer stopper of the present disclosure to obtain good leakage and force performance in the assembled syringe. In one embodiment, the viscosity of the thermoplastic elastomer stopper of the present disclosure is 0.01 to 0.15 at a shear rate of 1,000 sec.-1 70.0 Pa s or more, shear rate 10,000 s -1 and a shear rate of 50,000 s -1 In one embodiment, the thermoplastic elastomer stopper of the present disclosure provides stiction-free performance in a barrel based on polypropylene or polypropylene copolymer. For example, the stopper of the present disclosure includes 30-65% thermoplastic elastomer such as 30-65% styrene-ethylene-butylene-styrene (SEBS) copolymer blended with 10-35% polyolefin or a higher melting temperature polymer such as, but not limited to, 10-35% medium to high density polyethylene (medium to high density with a melting temperature of 120° C. to 130° C.), excluding polypropylene, and 20-35% commonly available mineral oil and commonly available radiation stabilizers, antioxidants, and / or processing aids. The molecular weights of the SEBS and polyethylene are selected to obtain the desired material properties as described above.

[0083] An important characteristic of the material used to make the stopper 16 is that it is made of a material that provides the required functional characteristics of the stopper without requiring the outer surface of the stopper to be lubricated, along with a design for low force. The stopper 16 of the exemplary embodiment may have the following material characteristics: In one embodiment, it is contemplated that the stopper 16 has a stopper material hardness of about 45 Shore A to about 65 Shore A. In some embodiments, it is contemplated that the stopper 16 has a stopper material hardness of about 53 Shore A to about 63 Shore A.

[0084] The present disclosure provides a thermoplastic elastomer stopper that meets the desired material properties of a stopper for a syringe assembly. These material properties include hardness and compression set. These properties, below a defined critical concentration of barrel material and high viscosity resin used in the stopper formulation, result in improved performance of the stopper, such as better syringe control during manual injection and pump use. The desired range for the hardness of the stopper of the present disclosure is reflected by the desired stress value at a given strain level, as shown in FIG. 11. A syringe stopper has two competing requirements, good leakage performance and low operating force, which are met by a stopper material of the required hardness. A stopper material with a low hardness will have poor leakage performance, and a stopper material with a high hardness will have high (undesirable) force performance that will result in leakage of fluid in the barrel through the stopper ribs.

[0085] The stoppers of the present disclosure also provide a stiction-free syringe stopper manufactured from the compositions of the present disclosure. Autoclavable syringes are obtained with the use of high melt temperature polymers in the formulation.

[0086] Conventional autoclavable stoppers are generally formed from a thermosetting resin coated with a lubricant, however, the manufacture of such conventional autoclavable stoppers requires multiple processing steps and generates increased and excessive waste.

[0087] Conventionally, thermoplastic elastomer stoppers based on polypropylene blends can also be used in autoclave sterilizable syringes. The autoclave sterilizability of such syringes is obtained by adding many inorganic fillers in the stopper formulation to provide structural integrity at autoclave sterilization temperatures. The use of inorganic fillers damages the surface of the mold, resulting in reduced efficiency and high operating costs. The presence of inorganic fillers in the composition also leads to problems with extractables and leachables during use and storage of the syringes. Thus, there is a need for a thermoplastic elastomer composition for producing autoclave sterilizable syringe stoppers that does not require inorganic fillers.

[0088] As discussed above, the stoppers of the present disclosure are made of a material that provides the required functional properties of the stopper without requiring the outer surface of the stopper to be lubricated. For example, the stoppers of the present disclosure may be formed from a thermoplastic elastomer. In this manner, the stoppers of the present disclosure also enable autoclave sterilizable stoppers for syringe assemblies.

[0089] In one embodiment, the thermoplastic elastomer composition of the stopper of the present disclosure is based on a high melt temperature polymer, for example a melt temperature of 170° C. or higher is required for autoclavable syringes.

[0090] As previously discussed, in one embodiment, the stopper of the present disclosure may be formed from a thermoplastic elastomer composition comprising a blend of injection moldable elastomers including block copolymers and high transition temperature polymers. In some embodiments, the elastomers may include butyl rubber blended with styrene block copolymers, olefin block copolymers, polyisoprene, and high transition temperature polymers, which may include ethylene tetrafluoroethylene (ETFE) and fluorinated ethylene propylene (FEP) polymers.

[0091] In one embodiment, the stopper composition of the present disclosure includes 30 to 65 wt. % elastomer, such as, but not limited to, styrene block copolymers and olefin block copolymers, 10 to 35 wt. % high transition temperature polymer, such as, but not limited to, ethylene tetrafluoroethylene, and 20-35 wt. % other additives, such as mineral oil, to meet desired processing requirements and material properties, such as hardness, tensile, viscosity, and compression set properties for stoppers for syringe assembly applications. In other embodiments, the stopper composition of the present disclosure includes radiation stabilizers, antioxidants, and / or processing aids.

[0092] The stopper of the present disclosure overcomes the shortcomings of conventional stoppers by providing an injection moldable thermoplastic syringe stopper in which stiction-free performance is created by migration of a hydrocarbon liquid, such as mineral oil, to the surface incorporated within the composition of the stopper. High temperature stable polymers at levels of at least 10 to 35% by weight in the composition provide structural integrity during autoclave sterilization and any other exposure to high temperature conditions. For example, high transition temperature polymers may include ethylene tetrafluoroethylene (ETFE) and fluorinated ethylene propylene (FEP) polymers. As discussed above, the thermoplastic elastomer composition of the stopper of the present disclosure is based on high melt temperature polymers. For example, melt temperatures of 170° C. or higher are required for autoclave sterilizable syringes. In this manner, the stopper of the present disclosure provides a lubricant-free, stiction-free, autoclave sterilizable, injection moldable stopper while eliminating the step of external lubrication on the stopper.

[0093] The stoppers of the present disclosure also provide additional manufacturing and / or molding advantages. For example, in one embodiment, the stoppers of the present disclosure include a shear feature, i.e., a thin wall section, at the mold gating point in the mold cavity. The shear feature of the stoppers of the present disclosure adds shear heating at the mold gate point. In this manner, the stoppers of the present disclosure eliminate cold material entering the mold cavity, eliminate flow lines and / or weld lines common to stopper molding, eliminate sink marks, improve gate quality control, improve mold cycle times, and eliminate surface and / or visual imperfections.

[0094] As noted above, the embodiment of the stopper 16 shown in Figures 3-5 includes a shear portion 74 and a catch can portion 76 that allow for molding the thermoplastic elastomer stopper in an open gate system. An open gate system may also be referred to as a hot tip system. In one embodiment, the shear portion 74 has a thickness that is less than 52% and greater than 36% of the thickness of the roof portion 70 of the stopper 16. In one embodiment, the shear portion 74 has a thickness that is about 44% of the thickness of the roof portion 70 of the stopper 16. In one embodiment, the shear portion 74 is about 50% of the typical wall thickness at the gate location. In one embodiment, the shear portion 74 has a thickness of 0.012 inches (0.305 mm). In one embodiment, the shear portion 74 has a thickness of 0.018 inches (0.457 mm). In one embodiment, the shear portion 74 has a thickness of 0.023 inches (0.584 mm).

[0095] Conventional open gate hot runner systems fail to close the gate, causing residual heat and residual heat that leaves a small amount of unmelted and / or slightly melted residual resin from the previous shot. This material is then forced into and incorporated into the stopper or other molded part during the next shot. Furthermore, this residual material can go anywhere within the molded part. If the residual material reaches the surface of the stopper, it will compromise the aesthetic quality of the part and, depending on the location, can cause functional performance issues. For example, if the residual unmelted material reaches the surface of the stopper ribs, it will prevent the stopper from sealing against the barrel wall, resulting in leaks and product failure. This residual material compromises the quality and performance of the molded part and increases scrap rates and therefore costs.

[0096] 4 and 5, the catch can portion 76 is designed to allow for easy part release. The catch can portion 76 is designed to fit within the constraints of other features of the molded part, allowing for shear features, and optimizing for easy part release. The catch can portion 76 is also designed to fit within the constraints of other features of the molded part, such as allowing for shear features 74. The catch can portion 76 includes a receiving volume that depends on the attributes of the molding machine and tooling design. In one embodiment, the catch can portion 76 has a volume that is at least the volume of residual material left from the previous shot. In one embodiment, the catch can portion 76 needs to be of sufficient volume that is determined by the hot runner drop and located opposite the gate.

[0097] 27, catch can portion 76 and hot tip portion 200 of a hot runner system are shown. In one embodiment, a gate portion 204 adjacent to the stopper 16 is allowed to move slowly into the catch can portion 76. In this manner, residual material can be captured within the catch can portion 76 so that it does not flow into the molded area of ​​the stopper 16 causing flow lines and / or knit lines within a portion of the stopper 16.

[0098] 28, a cold slug 210 of TPE solidifies at the end of the hot tip 212 at the end of the molding cycle and is then injected into the cavity in the subsequent cycle. This cooled material does not remelt back into the flow path for new material and can get stuck in the sealing ribs of the stopper 16, causing a leak path. The catch can section 76 needs to be of a size large enough to capture the cold slug 210, and the gap in the shear section 74 needs to be small enough to keep the cold slug 210 from passing through with the good TPE, similar to a strainer. The geometry of the catch can section 76 and shear section 74 is determined by the size of the gate slug created by the hot tip hot runner system, not the size of the stopper being molded.

[0099] 5, the core section 72 includes a shape that provides better demolding of the stopper 16. The angular position of the core section 72 prevents breakage of the stopper and increases the mechanical strength of the core pin.

[0100] 2B, the core portion 72 includes a semi-elliptical shape 79 having a radius that aids in distributing the plastic within the cavity. The semi-elliptical shape 79 also adds strength to the stopper 16 and improves the central protrusion of the stopper 16.

[0101] 3 and 6, the stopper of the present disclosure also includes umbrella arm elements 78, 94. The umbrella arm elements 78, 94 allow the stopper roof to be fully supported by the plunger rod without requiring full contact over the entire under-stopper surface area. The umbrella arm elements 78, 94 reduce cycle time and reduce the amount of resin used per shot. In this manner, the umbrella arm elements 78, 94 provide cost savings in production output and in raw materials. The umbrella arm elements 78, 94 also provide an environmentally friendly advantage by providing a system that requires less raw materials.

[0102] As discussed above, the problem of excessive breakout and opening forces is related to friction. Friction is generally defined as the resistive force that arises when a surface of one material slides or attempts to slide over an adjacent surface of itself or another material. There can be two types of friction between contacting solid surfaces: (1) resistance that opposes the force required to start one surface moving over the other, conventionally known as static friction, and (2) resistance that opposes the force required to move one surface over the other at a variable, fixed, or predetermined speed, conventionally known as kinetic friction.

[0103] The force required to overcome static friction and induce a breakout is called the "breakout force" and the force required to maintain stable sliding of one surface over another after the breakout or opening is called the "sustaining force". Two major factors contribute to static friction and therefore to the breakout or opening force. The term "sticking" as used herein means the tendency of two surfaces in stationary contact to develop adhesion to one another. The term "inertia" is conventionally defined as a force that tends to resist motion that must be overcome to put a material into motion. In the context of the present invention, inertia is understood to mean that component of the breakout force that does not include adhesion.

[0104] The breakout or opening force, especially the degree of sticking, varies according to the composition of the surface. In general, elastic materials show greater sticking than inelastic materials, especially when the surfaces are of similar composition. The length of time that the surfaces are in static contact with each other also affects the breakout and / or opening force. In syringe technology, the term "standing" refers to storage time, storage time, or the interval between filling and dispensing. In general, standing increases the breakout or opening force, especially if the syringe is refrigerated during standing.

[0105] As discussed, conventional stoppers require a lubricant to be applied to the surface of the stopper. The present disclosure provides stoppers that are made of materials that provide the required functional properties of the stopper without requiring that the outer surface of the stopper be lubricated.

[0106] 9, a thermoplastic elastomer stopper based on a styrene block copolymer blended with polypropylene combined with a polypropylene barrel exhibits stiction; that is, in the rest position, the stopper develops adhesion against the inner surface of the syringe barrel and requires an opening force to overcome the friction between the stopper and the inner surface of the polypropylene syringe barrel. The stiction between the stopper and barrel makes it difficult to provide a smooth incremental line-to-line advancement of the stopper within the syringe barrel.

[0107] 10, stoppers of the present disclosure based on styrene block copolymers blended with polyethylene do not require lubrication of the outer surface of the stopper due to segregation of a hydrocarbon liquid such as mineral oil on the stopper surface, and provide smooth incremental line-to-line advancement of the stopper without stiction within the syringe barrel. This allows fluid to be dispensed from the syringe assembly in precisely controlled amounts. In other embodiments, stoppers of the present disclosure formed from olefin block copolymers exhibit stiction-free performance similar to that shown in FIG. 10.

[0108] In one embodiment, the syringe barrel 12 is formed from a first material and the stopper 16 is formed from a second material different from the first material, the second material not containing more than 4% of the first material, more preferably the second material not containing more than 1.5% of the first material, and even more preferably the second material not containing more than 1% of the first material. For example, the stopper 16 may be formed from a polyethylene-based thermoplastic elastomer and the syringe barrel 12 may be formed from polypropylene. In other embodiments, the stopper 16 may be formed from a polyisoprene or SBR material and the syringe barrel 12 may be formed from a glass, cycloaliphatic polyolefin, polyester, or polycarbonate material. In this manner, the degree of adhesion that the stopper develops against the inner surface of the syringe barrel is reduced. For example, chemical interactions between the stopper and the syringe barrel are mitigated, the stopper and the syringe barrel do not exhibit stiction, and the syringe assembly provides a smoothly incremental line-to-line advancement of the stopper within the syringe barrel, which allows fluid to be dispensed from the syringe assembly in precisely controlled amounts.

[0109] The tests, studies, and experiments of this disclosure were conducted on stopper stick-slip motion at low speeds (0.1 ml / hr for a 10 ml syringe configuration) with polypropylene (PP) barrels and PP content in the TPE stopper shown in FIG. 17. For continuous drug delivery at low speeds, smooth stopper motion is desirable. As can be noticed in FIG. 17, at PP concentrations of 1% or less, there is no stick-slip stopper motion. In contrast, the occurrence of stick-slip motion increases above this critical PP concentration, as shown by all syringes at PP concentrations of 5.7% and above. These results would translate similarly to barrels of alternative resin composition, where the same resin is also incorporated into the stopper formulation.

[0110] The composition of the thermoplastic stopper resin should not have the same material as in the barrel to avoid stiction. For example, for a barrel based on polypropylene or polypropylene copolymer, the stopper formulation should not be based on polypropylene. Thermoplastic elastomers with a formulation based on a hard phase with lower surface tension also help to reduce stiction. For example, polyethylene (surface tension about 35 mJ / m 2 ) or ETFE (approx. 23 mJ / m 2 ) mixed with styrene block copolymer (polystyrene surface tension approx. 41 mJ / m 2 ) results in selective surface segregation of the hard phase and reduced interaction with the barrel.

[0111] In a syringe assembly including a stopper and a syringe barrel formed from the same material, the chemical interaction between the stopper and the syringe barrel is increased, resulting in stiction between the stopper and the syringe barrel. For example, while in a resting position, the stopper develops adhesion to the inner surface of the barrel, requiring an opening force (generally higher than the sustaining force) which is the force required to overcome the static friction between the surface of the stopper and the syringe barrel. In extreme cases, with slower motion, adhesion forces may develop between the barrel and the stopper, making it difficult to provide a smooth incremental line-to-line advancement of the stopper in the syringe barrel. For a syringe for pump application with such a stopper, the drug delivery will be less smooth and therefore undesirable. For a barrel based on polypropylene (PP), for smooth or no stick-slip motion during pump use, the formulation should not have more than a critical level of PP as shown in FIG. 17. The PP content in these formulations was calculated using the energy of melting from DSC corresponding to PP, the energy of melting of 100% crystalline PP as 293 J / g, and assuming 50% PP crystallinity in the stopper material. The DSC peak associated with PP melting was not discernible in TPE-1, TPE-2 (all slip agent levels), TPE-3, TPE-5, and TPE-6, indicating that the PP content in these TPEs was less than 1%. Figure 17 shows that formulations TPE-4, TPE-10, TPE-11, TPE-12, TPE-13, TPE-14, and TPE-15 have PP content greater than 1% and do not meet the stick-slip performance requirements. An example of a syringe pump force profile for TPE-2-S0.6 and TPE-4 (lubricated with silicone lubricant) is shown in Figures 9 and 10. Although TPE-6 has a PP content less than 1%, TPE-6 fails to meet the stiction performance. This is due to the minimum amount of polyethylene required for the styrene block copolymer stopper system.

[0112] Based on the research and experimentation of the present disclosure, stick-slip motion of the stopper relative to the plunger rod is avoided when the syringe barrel 12 is formed from a first material and the stopper 16 is formed from a second material different from the first material, where the second material does not contain more than 4% of the first material, more preferably the second material does not contain more than 1.5% of the first material, and even more preferably the second material does not contain more than 1% of the first material. For example, as described above, the stopper 16 may be formed from a polyethylene-based thermoplastic elastomer and the syringe barrel 12 may be formed from polypropylene. In other embodiments, the stopper 16 may be formed from a polyisoprene or SBR material and the syringe barrel 12 may be formed from a glass, alicyclic polyolefin, polyester, or polycarbonate material. In this manner, the degree of adhesion that the stopper develops against the inner surface of the syringe barrel is reduced, as described above. For example, chemical interactions between the stopper and the syringe barrel are mitigated, the stopper and the syringe barrel do not exhibit stiction, and the syringe assembly provides smooth incremental line-to-line advancement of the stopper within the syringe barrel, which allows fluid to be dispensed from the syringe assembly in precisely controlled amounts.

[0113] The breakout or opening force, especially the degree of sticking, varies according to the composition of the surface. In general, elastic materials show greater sticking than inelastic materials, especially when the surfaces are of similar composition. The length of time that the surfaces are in static contact with each other also affects the breakout and / or opening force. In syringe technology, the term "standing" refers to storage time, storage time, or the interval between filling and dispensing. In general, standing increases the breakout or opening force, especially if the syringe is refrigerated during standing.

[0114] As known in the art, conventional stoppers require a lubricant to be applied to the surface of the stopper. The present disclosure provides a stopper made of a material that provides the required functional properties of the stopper without requiring the outer surface of the stopper to be lubricated. The stopper of the present disclosure includes a stopper material with sufficiently high viscosity enabled by the high molecular weight of the elastomer and / or the hard phase of the formulation. The mineral oil incorporated in the formulation segregates to the stopper surface due to the low entropy of mixing, fulfilling the role played by the externally applied silicone lubricant on the conventional syringe stopper surface.

[0115] Figure 13 demonstrates hand forces for lubricated and non-lubricated TPE stoppers in a 10 ml embodiment after gamma sterilization. The hand forces of the syringes are similar for syringes with lubricated and non-lubricated stoppers.

[0116] In one embodiment, the stopper of the present disclosure is formed from a TPE based on polyethylene blended with a styrene block copolymer. In such an embodiment, the propensity of polyethylene for the surface of the stopper, and the surface energy of the stopper, allows for a lubricated stopper that has the required functional properties of the stopper without the need for the external surface of the stopper to be lubricated, thereby eliminating the extra step of applying lubricant on the syringe stopper surface. In this way, the negative consequences of applying lubricant externally to the stopper are eliminated. For example, a lubrication step on the stopper requires the cost of lubricant and lubrication equipment, time, and energy to operate and perform the lubrication step, and the stopper must be removed from the automated assembly process and assembled. The lubricated stopper of the present disclosure also provides a stopper that allows for a fully automated stopper assembly process. The polystyrene (about 41 mJ / m) in the blend of polyethylene and styrene block copolymers. 2 ) compared to the lower surface energy of polyethylene (approximately 35 mJ / m 2) can result in selective segregation of polyethylene to the surface, reduced interaction between the stopper and barrel material, and stiction-free performance. This is also supported by atomic force microscopy (AFM) measurements on the TPE-2-S0.6 embodiment, where the hard phase is selectively segregated towards the surface. Since the hard phase of the styrene block copolymer is chemically bonded to the soft phase, this suggests that the polyethylene is selectively segregated to the surface. To determine the critical concentration of polyethylene required within the styrene block copolymer, two TPE stopper formulations with polyethylene content of 8% (TPE-6) and 25% (TPE-2 and TPE-5 with total slip agent levels) were investigated in 10 ml embodiments with polypropylene barrels and plunger rods. For example, pump force profiles for TPE-2-S0.6 and TPE-6 are given in Figures 18 and 19. Stiction was observed at a pump rate of 0.1 ml / hr for the formulation with 8% polyethylene content, but was absent for the 25% polyethylene content, indicating that the critical polyethylene concentration lies in the range of 8% to 25%.

[0117] Syringe stoppers are constantly under stress in the syringe assembly and undergo compression set over time. Syringe functional performance, hand force, and leak performance are dependent on stopper dimensions and are competing requirements. As the stopper diameter (OD) increases, the hand force of the syringe increases or worsens and the pressure to leak increases or gets better. Since the stopper diameter is largest immediately after assembly, hand force is the most necessary operation for a freshly assembled syringe. In contrast, the pressure to leak decreases or gets worse over time. In one embodiment, the design and dimensions of the stopper are designed to achieve an acceptable hand force at T=0 while at the same time meeting the leak performance during the entire shelf life. Compression set measurements (ASTM D395-03, Method B, 25% strain for 22 hours at 70° C.) provide a good indication of the magnitude of the stopper diameter over time. As shown in Figure 20, the leakage performance for the different TPE stopper embodiments suggests that leakage performance was not met by TPE formulations having a compression set of greater than 50%. Formulations with acceptable leakage performance have a compression set of 35% or less.

[0118] As discussed above, non-lubricated stoppers with high TPE viscosity are not only useful in that they are non-lubricated stoppers, but also provide good operability in the ability to dispense filled liquid from a syringe. The ability to dispense blood droplets without spurting or jetting is important for use of syringes in applications where blood is placed on a glass slide for droplet analysis. Jetting of blood would result in contamination of the work area during such activities and potential infection for medical personnel, which is undesirable. Furthermore, such syringes are capable of repeatedly dispensing small, very precise increments of liquid without sudden surges. Thus, syringe assemblies including the stoppers of the present disclosure can be used to administer medication to patients without risk of surges, thereby providing precise control of the dose and greatly improved patient safety.

[0119] Attaching a needle to the syringe creates back pressure and improves the maneuverability. Therefore, all of the tests, studies, and experiments in this disclosure were conducted in the worst case conditions of the syringe without an attached needle. Tests for the ability to control blood dispensing at the droplet level were conducted in a 10 ml, E-beam sterilized syringe using sheep blood, as shown in FIG. 21. FIG. 21 also demonstrates the viscosity at different shear rates measured using a capillary rheometer (die: round hole length 20 mm / diameter 1 mm / 180 degree inlet, piston: d=15 mm, and melt time=7 min) at 205°C. TPE-1-S0.6 and TPE-2 (with full slip agent level) with high compounding viscosity show good maneuverability, but low viscosity. TPE-3 (based on polypropylene blended with styrene block copolymer) and TPE-5 (polyethylene blended with styrene block copolymer) show poor maneuverability with blood.

[0120] The amount of slip agent (such as, but not limited to, erucamide, oleamide, and behenamide) present within the TPE formulation also affects the manual operability of the syringe with different fill fluids. For example, the tests, studies, and experiments of this disclosure include manual operation tests for isopropanol dispensed at droplet level for TPE-2 based on polypropylene blended with styrene block copolymer with different levels of slip agent, erucamide, in a 10 ml stopper (Design 5). A critical level of slip agent between 0.2-0.3% is required for good manual operation. For such formulations, the stopper strain in the assembled syringe should be optimized to eliminate visual defects due to selective segregation of slip agent on the stopper surface. Such visual defects may cause a foreign body perception to the end user. The presence of slip agent within the formulation also reduces or improves the syringe force without affecting the leakage performance, since the leakage performance of the syringe is mainly dependent on the interference between the syringe components. FIG. 22 demonstrates the force change on TPE-2 stoppers and E-beam sterilized syringes with different slip agent levels in 10 ml Design 5.

[0121] The TPE stopper in the syringe assembly undergoes complex compression and tension modes during use, and the TPE material properties in tension and compression affect the functional performance (hand force and leak performance) of the syringe. Stress-strain curves are material properties that characterize the behavior of a particular material. The testing, research, and experimentation of the present disclosure includes using FEA (Finite Element Analysis) simulations to predict the desired stress at a given strain level that will result in the best functional performance. With reference to FIG. 11, the stress values ​​for the desired curves are given for TPE-1-S0.6, TPE-2-S0.6, and TPE-3. The testing, research, and experimentation of the present disclosure includes using FEA simulations to assign relative rankings for pressure and persistence against syringe leakage for these three TPE formulations (FIG. 23), which were consistent with the experimental data (FIG. 24). Leak pressure and persistence tests were performed on 10ml Design 4 in non-sterile conditions (aging at 60° C. for one week). TPE-3 had the lowest or worst leakage performance. The staying power of TPE-1-S0.6, TPE-2-S0.6 was higher than TPE-3, but it was acceptable. Since the leakage performance worsens with time, TPE-1-S0.6, TPE-2-S0.3, and TPE-2-S0.6 can be selected as the final TPE formulations with acceptable syringe force and leakage performance with no stiction and the possibility of being used without externally applied silicone lubricant.

[0122] The TPE stress at a given strain is also reflected by the hardness of the formulation. TPE1-S0.6, TPE-2 (with 0.3% and 0.6% erucamide) that meet the stress at a given strain level have hardness of 53 Shore A and 63 Shore A. Therefore, the most preferred hardness range for the TPE stopper formulation of the present disclosure is 53-63 Shore A.

[0123] Based on the data presented above, the final TPE selection table for the syringe stopper is presented in Figure 25. TPE-1-S0.6, TPE-2-S0.3, and TPE-2-S0.6 meet all the requirements for the syringe stopper application and can be used unlubricated.

[0124] When using syringes with TPE stoppers with a higher coefficient of thermal expansion than the barrel material, unexpected exposure to high temperatures (such as 60°C) for extended periods of time leads to expansion of the barrel. This is due to increased stress on the barrel at high temperatures due to the mismatch in coefficients of thermal expansion, leading to irreversible creep of the barrel and expansion of the stopper in the resting position. The coefficient of thermal expansion of the syringe stopper can be reduced by the addition of inorganic fillers such as silica or calcium carbonate due to the low coefficient of thermal expansion of such inorganic fillers and their effect on the crystalline architecture of the TPE matrix. In this way, the addition of inorganic fillers compensates for the high coefficient of thermal expansion of the thermoplastic elastomer, resulting in an acceptable level of creep of the barrel material.

[0125] Autoclave sterilizable syringes can also be obtained using high melt temperature polymers in the formulation. Conventional autoclave sterilizable stoppers are generally formed from thermosetting resins coated with lubricants. However, the manufacture of such conventional autoclave sterilizable syringes requires multiple steps and generates a lot of waste. Conventionally, thermoplastic elastomer stoppers based on polypropylene blends can also be used in autoclave sterilizable syringes. The autoclave sterilizability of such syringes is obtained by adding many inorganic fillers in the stopper formulation to provide structural integrity at autoclave sterilization temperatures. The use of inorganic fillers damages the surface of the mold, resulting in reduced efficiency and high operating costs. The presence of inorganic fillers in the composition also leads to problems with extractables and leachables during use and storage of the syringes. Thus, there is a need for a thermoplastic elastomer composition for producing syringe stoppers that can be autoclave sterilized without the need for inorganic fillers.

[0126] As discussed above, the stopper of the present disclosure is made of a material that provides the required functional properties of the stopper without requiring the outer surface of the stopper to be lubricated. For example, the stopper of the present disclosure may be formed from a thermoplastic elastomer. In this manner, the stopper of the present disclosure also allows for an autoclave sterilizable stopper for a syringe assembly. In one embodiment, the thermoplastic elastomer composition of the stopper of the present disclosure is based on a high melting temperature polymer. For example, a melting temperature of 170° C. or higher is required for an autoclave sterilizable syringe. As discussed above, in one embodiment, the stopper of the present disclosure may be formed from a thermoplastic elastomer composition that includes a blend of injection moldable elastomers including block copolymers and high transition temperature polymers. In some embodiments, the elastomer may include styrene block copolymers, olefin block copolymers, polyisoprene, and butyl rubber blended with high transition temperature polymers that may include ethylene tetrafluoroethylene (ETFE) and fluorinated ethylene propylene (FEP) polymers. In one embodiment, the stopper composition of the present disclosure includes 30 to 65 wt. % elastomer, such as, but not limited to, styrene block copolymers and olefin block copolymers, 10 to 35 wt. % high transition temperature polymer, such as, but not limited to, ethylene tetrafluoroethylene, and 20-35 wt. % other additives, such as mineral oil, to meet desired processing requirements and material properties, such as hardness, tensile, viscosity, and compression set properties for a stopper for syringe assembly applications. In another embodiment, the stopper composition of the present disclosure includes radiation stabilizers, antioxidants, and / or processing aids. The stopper of the present disclosure overcomes the shortcomings of conventional stoppers by providing an injection moldable thermoplastic syringe stopper in which stiction-free performance is created by migration of a hydrocarbon liquid, such as mineral oil, to the surface incorporated within the stopper composition. High temperature stable polymers at levels of at least 10 to 35 wt. % in the composition provide structural integrity during autoclave sterilization processing and any other exposure to high temperature conditions.For example, high transition temperature polymers may include ethylene tetrafluoroethylene (ETFE) and fluorinated ethylene propylene (FEP) polymers. As discussed above, the thermoplastic elastomer composition of the stopper of the present disclosure is based on a high melt temperature polymer. For example, a melt temperature of 170° C. or higher is required for an autoclave sterilizable syringe. In this manner, the stopper of the present disclosure provides a lubricant-free, stiction-free, autoclave sterilizable, injection moldable stopper, eliminating the step of external lubrication to the stopper.

[0127] Syringe assembly 10 may be used to fill syringe barrel 12 with medication from a separate vial prior to use. For example, syringe assembly 10 may be used with non-preloaded medication kits, such as diabetes medication kits.

[0128] 1, the use of syringe assembly 10 to fill syringe barrel 12 with a medicinal product from a separate vial prior to use will now be described. With syringe assembly 10 in the position shown in FIG. 1, and with the needle assembly locked to distal end 32 of syringe barrel 12 and in communication with a vial containing the fluid, when it is desired to aspirate or draw a fluid, such as a medicinal product, into chamber 36 of syringe barrel 12, a user moves plunger rod 14 in a direction generally along arrow A until a desired amount of fluid has been drawn into chamber 36 of syringe barrel 12. In this manner, a vacuum is created within chamber 36 of syringe barrel 12 by moving stopper 16 via plunger rod 14 in a direction generally along arrow A. As the user moves stopper 16 via plunger rod 14 in a direction generally along arrow A, the user actively increases the volume within chamber 36 of syringe barrel 12. Because the stopper is sized relative to the syringe barrel 12 to provide a sealing engagement with the interior wall of the syringe barrel 12 as described above, and because the needle assembly locked to the distal end 32 of the syringe barrel 12 is disposed within a vial containing a fluid, air cannot enter the chamber 36 of the syringe barrel 12, and therefore, as a user actively increases the volume within the chamber 36, an equal number of air molecules are located within the chamber 36. This reduces the pressure within the chamber 36 of the syringe barrel 12 relative to the air pressure outside the syringe barrel 12. Thus, a vacuum, i.e., a space of lower air pressure, is created, drawing fluid, such as a medication, into the chamber 36 of the syringe barrel 12.

[0129] The syringe assembly 10 may also be used in pre-filled syringe assemblies and / or injectable syringe assemblies. In this way, the user does not need to fill the device before injection, thereby saving time and maintaining a constant volume for delivery. The syringe assembly 10 in a pre-filled syringe application may be provided for end use of a fluid, such as a medicine, contained within the chamber 36 of the syringe barrel 12, pre-filled by the manufacturer. In this way, the syringe assembly 10 can be manufactured, pre-filled with a medicine, sterilized, and packaged in suitable packaging for delivery, storage, and use by an end user without the end user having to fill the syringe with a medicine from a separate vial prior to use. In such an embodiment, the syringe assembly 10 may include a cap or sealing member disposed at the distal end 32 of the syringe barrel 12 to seal the fluid, such as a medicine, within the chamber 36 of the syringe barrel 12.

[0130] 1 and 2A, the use of the syringe assembly 10 to expel a fluid, such as a pharmaceutical agent, contained within the chamber 36 of the syringe barrel 12 will now be described. In such an embodiment, the fluid is contained within the chamber 36 of the syringe barrel 12, and the stopper 16 is disposed adjacent the proximal end 34 of the syringe barrel 12, as shown in FIG. 2A. In a pre-filled syringe application, the user may first remove the cap or sealing member from the distal end 32 of the syringe barrel 12. The user may then attach the tip 42 of the syringe barrel 12 to a separate needle assembly or IV connection assembly and lockably engage the needle assembly or IV connection assembly to the tip 42 of the syringe barrel 12 in a known manner. Prior to dispensing the pharmaceutical agent, any air trapped within the chamber 36 of the syringe barrel 12 may be expelled in a known manner.

[0131] When it is desired to expel or dispense the medication contained within the syringe barrel 12, the syringe assembly 10 is grasped with the user's thumb on the flange 66 of the plunger rod 14 and with the user's fingers extending around the flange 40 of the syringe barrel 12. In this manner, the syringe assembly 10 is grasped by the user in a known and well-accepted manner. The user then performs a pushing motion between the thumb on the flange 66 of the plunger rod 14 and the four fingers gripping the flange 40 of the syringe barrel 12, thereby moving the stopper 16 through the plunger rod 14 in a direction generally along arrow B (FIG. 1). In this manner, the movement of the stopper 16 through the plunger rod 14 in a direction generally along arrow B forces the fluid contained within the chamber 36 of the syringe barrel 12 out of the outlet opening 38. The fluid may be expelled from the syringe barrel 12 through the outlet opening 38 into a separate needle assembly or an IV assembly and into a patient.

[0132] While the present disclosure has been described as having an exemplary design, the present disclosure may be further modified within the spirit and scope of the present disclosure. Accordingly, this application is intended to cover any variations, uses, or adaptations of the present disclosure that employ its general principles. Further, this application is intended to cover departures from the present disclosure that come within known or customary practice in the art to which the present disclosure pertains and that fall within the limits of the appended claims.

Claims

1. A stopper for a syringe assembly, the stopper comprising an elastomeric body, the elastomeric body having a compression set of 50% or less when held at 70° C. for 22 hours under a compression of 25%, the elastomeric body having a hardness of 40 to 70 Shore A, and a viscosity of the elastomeric body at 205° C. at a shear rate of 1,000 sec -1 100 to 170.0 Pa·s, shear rate 10,000 s -1 16.0 to 29.1 Pa·s, and a shear rate of 50,000 s -1 4.5 to 7.5 Pa·s at 25° C., and said elastomeric body comprises an olefin block copolymer.

2. 2. The stopper of claim 1, wherein the elastomeric body has a hardness of 53 to 63 Shore A.

3. The viscosity of the elastomer body is increased at a shear rate of 1,000 s -1 2. The stopper of claim 1, having a viscosity of 163.9 Pa·s at 100°C.

4. The viscosity of the elastomeric body is measured at a shear rate of 10,000 s -1 2. The stopper of claim 1, having a viscosity of 29.1 Pa·s at 100°C.

5. The viscosity of the elastomeric body is measured at a shear rate of 50,000 s -1 2. The stopper of claim 1, having a viscosity of 7.1 Pa·s at 100°C.

6. a syringe barrel having a proximal end, a distal end and a sidewall extending therebetween and defining a chamber having an interior; A stopper disposed inside the syringe barrel, the stopper comprising an elastomer body, the compression set of the elastomer body being 50% or less when held at 70° C. for 22 hours under a compression of 25%, and the viscosity of the elastomer body at 205° C. being 50% or less at a shear rate of 1,000 s -1 100 to 170.0 Pa·s, shear rate 10,000 s -1 16.0 to 29.1 Pa·s, and a shear rate of 50,000 s -1 a stopper having a viscosity of 4.5 to 7.5 Pa·s at room temperature, the elastomeric body comprising an olefin block copolymer; a plunger rod having a first end engageable with a portion of the stopper; A syringe assembly comprising:

7. 7. The syringe assembly of claim 6, wherein the elastomeric body has a hardness of 53 to 63 Shore A.

8. The viscosity of the elastomer body is increased at a shear rate of 1,000 s -1 7. The syringe assembly of claim 6, having a viscosity of 163.9 Pa·s at 25°C.

9. The viscosity of the elastomeric body is measured at a shear rate of 10,000 s -1 7. The syringe assembly of claim 6, having a viscosity of 29.1 Pa·s at 20°C.

10. The viscosity of the elastomeric body is measured at a shear rate of 50,000 s -1 7. The syringe assembly of claim 6, having a viscosity of 7.1 Pa·s at 25°C.

Images