Syringe and tightness test method

Abstract

A syringe (1) comprising a barrel (2), a stopper (3) and a plunger (4). The barrel (2) has a hollow interior, an orifice (21) and an opening (22) opposite the orifice (21). The stopper (3) is arranged in the hollow interior of the barrel (2) thereby defining a sealed chamber (5) in the interior of the barrel (2). The stopper (3) is movable in the interior of the barrel (2) thereby changing the volume of the chamber (5). The plunger (4) extends into the hollow interior of the barrel (2) through the opening (22) of the barrel (2). The plunger (4) has a distal end (41) outside the barrel (2) and a proximal end (42) in the hollow interior of the barrel (2). The stopper (3) has a distal face (31) facing the plunger (4), a proximal face (32) facing the chamber (5) and an internal cavity (33) opening at the distal face (31). The syringe (1) is equipped with a sealing structure to seal the cavity (33) of the stopper (3) such that the cavity (33) of the stopper (3) is sealed against microorganisms.

Description

Technical Field

[0001] This invention relates to a syringe, and more specifically, to a method for testing the seal / tightness between the stop and the plunger of the syringe.

[0002] Such a syringe includes (i) a barrel having a hollow interior, an orifice, and an opening opposite the orifice; (ii) a stop disposed within the hollow interior of the barrel to define a sealed chamber within the barrel, wherein the stop is movable within the barrel to change the volume of the chamber; and (iii) a plunger extending through the opening into the hollow interior of the barrel for delivering a drug substance to a patient. In particular, when the syringe is implemented as a pre-filled syringe, it allows for convenient administration of a predetermined dose of drug substance to a patient. Background Technology

[0003] Many drugs or drug substances are administered in liquid form. For effective administration and efficacy, liquid drug substances are typically delivered parenterally via injection. Therefore, especially for subcutaneous, intramuscular, intradermal, or intravitreal injections, the drug substance is usually provided in a pre-filled syringe (PFS). Such a PFS may have a post or be able to receive a separate connecting needle. In a PFS, the drug substance is provided inside the syringe barrel in the form of a solution, suspension, or other pre-administered liquid. The advantage of a PFS is that the user receives a (quasi-)prepared syringe without the need for preparation work such as filling the syringe with the drug substance, for example, by transferring it from a vial. This reduces the risk of contamination of the drug substance with particles and microorganisms, injury, and / or inappropriate or inconvenient handling during administration. Furthermore, a PFS allows patients to self-administer the medication.

[0004] Typically, a PFS includes a barrel, a rubber stop, a plunger, and a needle or needle adapter, the barrel having an open end and a tip with an orifice substantially opposite the open end, the needle or needle adapter being located at the orifice of the barrel. For example, a particular ophthalmic PFS is described in WO2014 / 005728 A1.

[0005] While PFS (Prepared Filtration for Serving) may be advantageous in terms of use or administration compared to conventional pharmaceutical formulations, manufacturing pharmaceutical substances in PFS is generally more challenging than in other containers such as vials. One aspect that may be particularly important in ophthalmic applications is the external sterilization of the syringe after assembly, combination, and / or packaging.

[0006] In this type of external sterilization, gaseous chemical sterilization is typically used to sterilize the outer surface of the syringe. Therefore, to prevent the medication inside the syringe barrel from being affected, it is important to prevent the sterilizing agent from entering the sealed internal space of the barrel. Specifically, the amount of sterilizing agent entering should be below the limits specified by health authorities or the International Organization for Standardization (ISO), or should not impair the quality of the medication before the expiration of its shelf life. For example, when using ethylene oxide (EO) as a sterilizing agent, the European Medicines Agency (EMEA) specifies limits of 1 µg / mL EO and 50 µg / mL epichlorohydrin (ECH) in guidance EMEA / CVMP / 271 / 01. Alternatively, ISO 10993-7 specifies limits of 0.5 µg EO / IOL / 24 hours and 1.25 µg EO / IOL, which are interpreted as 0.5 µg EO / eye / 24 hours and 1.25 µg EO / eye, and limits of 2.0 µg EO / IOL / 24 hours and 5.0 µg EO / IOL, which are interpreted as 2.0 µg EO / eye / 24 hours and 5.0 µg EO / eye.

[0007] A problem arising from this type of external surface sterilization of syringes is that the sterilizing agent may not adequately reach all parts and sections of the syringe except for the drug substance within the barrel. Space and areas near the plunger connection or abutment stop are often difficult to reach. In particular, when using stops that generally have cavities, the sterilizing agent may struggle to reach the cavity itself. More specifically, the plunger is typically positioned within or abuts the cavity of the stop, thus preventing the sterilizing agent from entering the cavity. This can lead to contaminants such as living organisms residing in the cavity, which may later escape and reduce the safety of using the syringe. Solid stops without cavities may be impractical in some applications, for example, due to machining challenges and / or not being a commercially viable solution. Another issue is that the plunger-to-stop assembly force is limited to prevent stop movement and / or compression of the syringe fluid contents during or after plunger assembly.

[0008] Therefore, there is a need for a system or syringe that can reduce the risk of contamination for users or during drug administration. Summary of the Invention

[0009] This need is addressed by a syringe defined by the features of the present invention and a method defined by the features of the present invention. Preferred embodiments relate to further topics.

[0010] On one hand, the present invention is a syringe comprising a barrel, a stop, and a plunger. The barrel has a hollow interior, an orifice, and an opening opposite the orifice. The stop is disposed within the hollow interior of the barrel, thereby defining a sealed chamber within the barrel. The stop is movable within the barrel, thereby changing the volume of the chamber. In use, the plunger extends through the opening of the barrel into the hollow interior of the barrel. When the plunger moves the stop toward the orifice, the stop can expel liquid through the orifice from the barrel, thereby reducing the volume of the chamber. The plunger has a distal end outside the barrel and a proximal end within the hollow interior of the barrel. The stop has a distal side facing the plunger, a proximal side facing the chamber, and an internal cavity / inner cavity opening at the distal side. The syringe is equipped with a sealing structure to seal the inner cavity / inner cavity of the stop, such that the cavity of the stop is sealed against microorganisms.

[0011] In the context of this invention, the term "syringe" refers to all types of syringes in the literal sense, such as single-chamber syringes, dual-chamber syringes, or multi-chamber syringes. Syringes can be pre-filled, partially filled, or empty. They may also be provided with a post or adapter to which a needle or similar delivery tubing can be attached. In addition to the literal meaning of "syringe," the term "syringe" as used herein also encompasses similar devices or containers, particularly, for example, cartridges.

[0012] As used herein, the term "proximal" refers to the portion, end, or component closest to the drug or drug delivery site when using a syringe, or the direction toward the drug or drug delivery site. Therefore, a proximal direction can be a direction toward the body or person to which the syringe is to be applied. For example, in embodiments of a syringe having a needle intended to penetrate the body or human body and a plunger to be pushed to deliver drug through the needle, the proximal end of the syringe being formed by the tip of the needle. A proximal direction can also be a direction toward the end of the syringe's orifice or the location of the patient's skin where the needle is inserted when delivering a drug or drug substance to a patient.

[0013] Conversely, the term "distal" is used to refer to the end or part of a syringe furthest from the site of drug delivery when using the syringe, or the direction away from that site of drug delivery. Therefore, the distal direction can be a direction away from the body or human body from which the syringe is being used. For example, in use, the distal end of the syringe can be the end of a plunger, which the operator's thumb is placed on to advance the plunger to deliver the drug. Typically, proximal and distal are opposite directions.

[0014] The term "tight" as used with stoppers and plungers can specifically refer to airtightness, or more specifically to tightness against contaminants such as organic deposits (e.g., microorganisms or endotoxins). Advantageously, the tightness is sufficient to prevent potential microorganisms and / or endotoxins from escaping from the stopper cavity.

[0015] Preferably, the liquid is disposed within a chamber of the syringe. Thus, the syringe can be a pre-filled syringe. In a particularly advantageous embodiment, the syringe is an ophthalmic pre-filled syringe, wherein the drug substance is an ophthalmic drug substance.

[0016] The syringe barrel can have a substantially cylindrical main portion. In particular, the main portion can have a hollow cylindrical shape. The barrel can be made of any suitable material, and for most pharmaceutical applications, it is made of a sterile, inert material, such as a suitable rigid plastic or, in particular, glass. Glass barrels may be advantageous for manufacturing, sterility, inertness, and stability reasons. The opening of the barrel can be an opening across the entire diameter of the barrel's interior. The orifice can be realized as a tip or nozzle formed in the end of the barrel opposite the opening. In particular, the orifice can have a channel in the tip, the diameter of which is smaller than the diameter of the internal space of the barrel. The size of the orifice can be determined to allow liquid to drain when the volume of the chamber in the barrel is reduced by advancing a stop via a plunger.

[0017] As used herein, the term "drug" refers to therapeutically active agents, often also called active pharmaceutical ingredients (APIs), and a variety of such therapeutically active substances or combinations thereof. The term also encompasses diagnostic or imaging agents that need to be administered to patients in liquid form, such as contrast agents like MRI contrast agents, tracers like PET tracers, and hormones.

[0018] As used herein, the term "medicinal substance" refers to a drug formulated or reconstituted as described above in a form suitable for administration to a patient. For example, in addition to the drug, a pharmaceutical substance may also include excipients and / or other auxiliary components. In the context of this invention, particularly preferred pharmaceutical substances are drug solutions, especially drug solutions for injection.

[0019] Typically, the liquid within the chamber of a syringe barrel is a drug substance. In the case of a dual-chamber pre-filled syringe, one chamber may contain a drug substance that must be reconstituted with a diluent contained in the second chamber for administration. Alternatively, the first and second chambers may contain two different drug substances that must be mixed before administration. In particular, the syringe may contain a specific dose of drug to be administered at the time of injection.

[0020] As used herein, the term "pharmaceutical product" refers to a finished product comprising one or more pharmaceutical substances. In particular, a pharmaceutical product can be a ready-to-use pharmaceutical product having an appropriate dosage and / or appropriate form for administration. For example, a pharmaceutical product may include a drug delivery device such as a syringe in the form of a pre-filled syringe.

[0021] As used herein, the term "sterilizing agent" refers to any liquid, gaseous, or vaporized substance capable of external or surface sterilization of PFS surfaces. For example, sterilizing agents may be or include ethylene oxide (EO), hydrogen peroxide (H2O2), vapor, evaporated hydrogen peroxide (VHP), evaporated peracetic acid (VPA), or nitrogen dioxide.

[0022] Therefore, the term "sterilization" refers to bringing a structure or component, such as a PFS, to a sterile state. As used herein, the term "sterile" refers to the maximum contamination rate allowed for the PFS or another component to be used in its intended application. For example, it can refer to a PFS state that conforms to the ST67 standard of the American National Standards Institute (ANSI) and the Association for the Advancement of Medical Devices (AAMI) (i.e., conforms to the requirements and guidance of ANSI / AAMI ST67). More specifically, 10 -6 The sterility assurance level (SAL) value can be used for products labeled as sterile according to ANSI / AAMI ST67.

[0023] Therefore, sterilization, or sterilization, can achieve a state where no living organisms are present. Specifically, sterilization can involve an effective process to render a product essentially devoid of living organisms. During such sterilization, the increase in the number of microbial deaths can be described by an exponential function. Therefore, the number of microorganisms surviving during the sterilization process can be expressed probabilistically.

[0024] The stop can be made of an inert and elastically deformable material, such as rubber or silicone. Specifically, it can be implemented as a sealed chamber inside the cylinder containing fluid or a mixture of solids and fluid. Furthermore, it has a proximal side that may face the liquid within the chamber and a distal side that faces the plunger. When installed, the outer circumference of the stop can correspond to the inner circumference of the cylinder. The cavity can be centrally located, thereby receiving the proximal portion of the plunger in a concentrated manner.

[0025] A syringe may have a central axis along which the barrel, stop, and plunger extend. The syringe or some of its parts (such as the barrel) may be rotationally symmetrical about the central axis.

[0026] The sealing structure allows for the closure and sealing of the stop cavity. This ensures that no contaminants, such as living organisms, can escape from the stop cavity at any point during syringe application. Therefore, even if external sterilization fails to completely sterilize the stop cavity, syringe safety is guaranteed regardless, as contaminants ultimately residing in the stop cavity cannot escape due to the tight seal against microorganisms. In this way, the syringe can reduce or even eliminate the risk of contaminants escaping from the stop cavity after terminal sterilization or during syringe use.

[0027] The proximal end of the plunger can form the stop contact portion to allow for a suitable force transmission from the plunger to the stop. For example, the aim is that this transmission can be substantially uniform, thereby preventing variations in the deformation of the stop as it is advanced to expel fluid.

[0028] Therefore, after the plunger and the stop are connected, the component design and materials implemented can ensure that the plunger rod area continuously presses against the corresponding stop area, thereby creating a microbial sealing interface.

[0029] In the preferred first embodiment, the proximal end of the plunger has an abutment surface and a barb extending proximally from the abutment surface. The shape of the cavity of the stop and the barb on the proximal end of the plunger are defined to form a snap-fit, such that the abutment surface of the proximal end of the plunger is adjacent to the distal side of the stop, and the stop is fixed to the plunger.

[0030] In this document, the term "fastening / locking" refers to the connection between the stop and the plunger that is strong enough to prevent them from separating during use of the syringe. This connection allows the stop and plunger to move together or as a single unit. Specifically, an effective mechanical connection is achieved by providing a snap-fit ​​structure realized by barbs and cavities, which allows for the establishment of a shape-fit connection.

[0031] Therefore, in the first embodiment of the syringe, the barb at the proximal end of the plunger preferably has a (distal) neck and a (proximal) head, and the cavity of the stop has a (distal) channel portion and a (proximal) internal chamber portion. A snap-fit ​​engagement between the cavity of the stop and the barb at the proximal end of the plunger is achieved by receiving the neck of the barb at the proximal end of the plunger with the channel portion of the cavity of the stop and receiving the head of the barb at the proximal end of the plunger with the internal chamber portion of the cavity of the stop. When snap-fitted together, this arrangement allows for an effective form-fit connection between the plunger and the stop, and presses the plunger against the stop.

[0032] Therefore, preferably, the neck of the barb at the proximal end of the plunger has a first axial length extending between the abutment surface at the proximal end of the plunger and the head of the barb at the proximal end of the plunger, and the channel portion of the cavity of the stop has a second axial length extending between the distal side of the stop and the internal chamber portion of the cavity of the stop, and when the stop is not engaged with the plunger, the first length of the neck of the barb at the proximal end of the plunger is less than the second length of the channel portion of the cavity of the stop. More specifically, this length difference exists particularly before the stop is connected to the plunger. By determining the dimensions of the first and second lengths in this way, a sealing structure can be achieved, and the stop can be compressed when the plunger is installed onto the stop, such that the cavity is sealed by the plunger, and the connection between the plunger and the stop is tight for microorganisms and generally also airtight. In particular, the distal side of the stop can be pressed against the proximal end of the plunger, such that the stop is compressed and tightly connected to the plunger. This allows for an effective sealing of the cavity. Therefore, the first length of the neck of the barb at the proximal end of the plunger is preferably at least 0.3 mm or about 0.5 mm shorter than the second length of the channel portion of the cavity of the stop. In particular, this difference has proven suitable when it comes to 1 ml or 0.5 ml prefilled syringes, as it ensures, on the one hand, a tight seal of the cavity, and on the other hand, allows for efficient connection or assembly of the plunger and the stop.

[0033] Preferably, the neck of the barb at the proximal end of the plunger has a first compression section, and the channel portion of the cavity of the stop has a second compression section. The first compression section of the neck of the barb at the proximal end of the plunger has a greater degree of taper / contour than the second compression section of the channel portion of the cavity of the stop.

[0034] The term "greater taper / greater taper" associated with compression sections indicates that, along the same length, the first compression section of the neck becomes thinner or its diameter decreases more significantly than the second compression section of the channel portion. Therefore, the angle between the shoulder of the first compression section and the axis of the barb may be greater than the angle between the shoulder of the second compression section and the axis of the channel portion.

[0035] This taper difference between the cavity and the barb allows for an effective sealing structure and a compression stop between the inside and outside, for example, at the beginning of the cavity. This effectively achieves a tight connection between the plunger and the stop, as well as a seal within the cavity.

[0036] Therefore, the first compression section of the neck of the barb near the proximal end of the plunger preferably tapers towards the head of the barb near the proximal end of the plunger. The first compression section can be tapered / tapered. Additionally or alternatively, the second compression section of the passage portion of the stop's cavity preferably tapers towards the inner chamber portion of the stop's cavity. The second compression section can also be tapered / tapered. In particular, when both sections taper, enhanced compression and tightness can be achieved when the stop snaps into the plunger.

[0037] Preferably, the syringe or its sealing structure is achieved by a gasket arranged with barbs around the proximal end of the plunger or an elastomeric component (e.g., an overmolded or co-molded sealing feature structure made of thermoplastic elastomer or similar elastomeric material) attached by physical or chemical methods, wherein the gasket or component is compressed between the abutment surface of the proximal end of the plunger and the distal side of the stop. Such a gasket or component allows for additional or alternative tightness between the plunger and the stop, and allows for a reduction in the risk of stop movement caused by relatively high assembly forces through greater variability in material hardness and dimensional tolerances and lower plunger assembly forces.

[0038] Preferably, the distal side of the stop has a protrusion that extends circumferentially around the cavity of the stop, which opens at the distal side. For a given assembly force, this protrusion allows for a stronger seal.

[0039] On the other hand, the present invention is a method for testing the tightness between a stop and a plunger of a syringe. The stop has a distal side, a proximal side, and an internal cavity opening at the distal side, and the syringe has a barrel having a hollow interior, an orifice, and an opening opposite the orifice. The method includes: (i) for example, without affecting the sealing properties of the stop, piercing the front of the stop with a needle or cannula or cutting the tip of the stop, thereby causing the opening of the cavity of the stop to face the proximal side / making the cavity of the stop open to the proximal side; (ii) arranging the stop into the hollow interior of the barrel through the opening of the barrel such that the distal side of the stop points toward the plunger; (iii) connecting a gas detector to the opening of the syringe barrel; and (iv) supplying gas through the orifice of the barrel.

[0040] The steps of the method according to the invention do not necessarily have to be performed in the listed order (i) to (iv). Other orders of the listed steps are also possible. Additionally, a suitable gas capable of reliable detection may be, for example, helium.

[0041] This method allows for the efficient testing of the seal / tightness between the plunger and the stop. More specifically, when gas is supplied through the orifice, the gas enters the cavity through the proximal side with the opening, placing it inside the cavity. If the gas cannot now exit the cavity through the distal side of the stop, which can be verified by a gas detector, the connection between the stop and the plunger is tight for microorganisms. Furthermore, the tightness can be evaluated by assessing the amount and / or flow rate of gas detected from the distal side of the stop.

[0042] Preferably, the method further includes the step of operating a gas detector to detect gas distal to the stop. This arrangement allows for efficient assessment of the tightness of the connection between the stop and the plunger. Therefore, the gas detector preferably measures the gas concentration distal to the stop. By measuring the concentration, the tightness can be assessed. For example, this allows for comparison of different sealing structures and selection of the most suitable one.

[0043] Preferably, the method involves creating a vacuum on the distal side of the stop. The vacuum can be in the submillibar pressure range. This vacuum allows for an attempt to force gas through the stop. Therefore, tightness can be effectively tested. Attached Figure Description

[0044] The syringe according to the invention and the tightness testing method according to the invention are described in more detail below with reference to exemplary embodiments and the accompanying drawings, in which:

[0045] Figure 1 A schematic cross-sectional side view of a first embodiment of a syringe according to the present invention is shown;

[0046] Figure 2 It shows Figure 1 Detail A;

[0047] Figure 3 A schematic cross-sectional side view of a second embodiment of the syringe according to the present invention is shown;

[0048] Figure 4 It shows Figure 3 Detail B;

[0049] Figure 5 A schematic cross-sectional side view of a third embodiment of the syringe according to the invention is shown; and

[0050] Figure 6 It shows Figure 5 Details C. Detailed Implementation

[0051] In the following description, certain terms are used for convenience and are not intended to limit the invention. The terms “right,” “left,” “up,” “down,” “below,” and “above” refer to directions in the figures. These terms include explicitly stated expressions and their derivatives and expressions with similar meanings. Furthermore, spatially relative terms such as “below,” “below,” “lower,” “above,” “upper,” “near,” and “far” may be used to describe the relationship between one element or feature and another element or feature as shown in the figures. In addition to the positions and orientations shown in the figures, these spatially relative terms are intended to also cover different positions and orientations of the device during use or operation. For example, if the device in the figures is flipped, an element described as “below” or “below” other elements or features will be “above” or “above” other elements or features. Thus, the exemplary term “below” can encompass both above and below positions and orientations. The device may be oriented in other ways (rotated 90 degrees or in other orientations), and the spatially relative descriptions used herein are interpreted accordingly. Similarly, descriptions of movement along and around various axes include various specific device positions and orientations.

[0052] To avoid repetition in the accompanying drawings and descriptions of various aspects and exemplary embodiments, it should be understood that many features are common to multiple aspects and embodiments. The omission of an aspect from the description or drawings does not mean that the aspect is missing from embodiments incorporating that aspect. Rather, the aspect may be omitted for clarity and to avoid lengthy description. In this context, the following applies to the remainder of this specification: if, for clarity, the drawings contain reference numerals not set forth in the directly relevant parts of the specification, reference may be made to those reference numerals in preceding or subsequent descriptive sections. Furthermore, for clarity, if reference numerals are not used for all features of a component in one drawing, reference may be made to other drawings showing the same component. Similar reference numerals in two or more drawings denote the same or similar elements.

[0053] Figure 1 The ophthalmic pre-filled syringe (PFS) 1 shown is a first embodiment of the syringe according to the invention, in an upright / standing position. The PFS 1 includes a barrel 2, a stop 3, and a plunger 4. The barrel 2 is substantially cylindrical, having a hollow interior, an orifice 21, and an opening 22 opposite to the orifice 21. The stop 3 is located within the hollow interior of the barrel 2, defining a sealed chamber 5 within the barrel 2. More specifically, the stop 3 has a top distal side 31 and a bottom proximal side 32, wherein the chamber 5 is located between the proximal side 32 and the orifice 21 of the barrel 2. The orifice 21 has a nozzle whose internal passage is tightly sealed by a sealing cap 8. Around the orifice 21, the PFS 1 is equipped with a Luer lock adapter 9.

[0054] A liquid ophthalmic drug substance 6 is disposed within chamber 5. A stop 3 can move within the cylinder 2, thereby altering the volume of chamber 5. More specifically, by moving the stop 3 downwards or proximally toward the orifice 21, the volume of chamber 5 decreases, allowing the drug substance 6 to be discharged from the orifice 21 after the cap 8 is removed.

[0055] The stop 3 is also designed with an internal cavity 33. The cavity 33 opens upward to the far side 31.

[0056] The plunger 4 has a vertical cylindrical rod portion 43 that extends through the opening 22 of the cylinder 2 into its hollow interior. It has a top distal end 41 and a bottom proximal end 42. The distal end 41 is equipped with a ribbed top finger-pushing surface. The bottom end 42 includes a substantially horizontal abutment surface 421 and a barb 422 extending downward from the abutment surface 421 in a proximal direction. As described in more detail below, the barb 422 is located within the cavity 33 of the stop member 3.

[0057] PFS 1 also features an extended / expanded finger flange 7 that clamps onto the cylinder 2 around the opening 22 of the cylinder 2. The finger flange 7 allows for convenient operation of PFS 1.

[0058] exist Figure 2 The section of PFS 1 surrounding the stop 3 is shown in more detail. Thus, it can be seen that the cavity 33 of the stop 3 has a lower internal chamber portion or proximal internal chamber portion 332 and an upper channel portion or distal channel portion 331 extending from the distal side 31 to the internal chamber portion 332. The barb 422 has a proximal head or lower head 4221 substantially corresponding to the internal chamber portion 332 of the cavity 33 and a distal neck or upper neck 4222 substantially corresponding to the channel portion 331 of the cavity 33. The stop 3 snaps onto the barb 422 of the plunger 4, thereby establishing a shape-fitting connection.

[0059] The neck 4222 of the barb 422 at the proximal end 42 of the plunger 4 has a tapered first compression section 4223, and the channel portion 331 of the cavity 33 of the stop 3 has a cylindrical second compression section positioned around the first compression section 4223. Therefore, the first compression section 4223 of the neck 4222 tapers downwards or proximally more than the second compression section of the channel portion 331, causing the stop material around the first compression section 4223 to be compressed.

[0060] In this way, the first compression section 4223 of the neck 4222 of the barb 422 together with the second compression section of the channel 331 of the cavity 33 establishes a sealing structure to seal the cavity 33 of the stop 3, thereby sealing it against microorganisms.

[0061] To verify the effectiveness of the sealing structure of PFS 1, it can be tested using an embodiment of the method according to the invention for testing the tightness between the stop and the plunger of a syringe. Therefore, this method is applied to an unassembled PFS 1 and includes the following steps: for example, by drilling a hole in the proximal side 32 or by cutting a portion of the proximal side 32, so that the opening of the cavity 33 of the stop 3 faces the proximal side 32; arranging the stop 3 into the hollow interior of the barrel 2 through the opening 22, such that the distal side 31 of the stop 3 points towards the plunger 4; connecting a helium detector to the opening 22 of the barrel 2 and supplying helium through the orifice 21 of the barrel 2 with an overpressure of approximately 5 mbar. The helium detector measures the helium concentration distal to the stop 3. Therefore, if the helium detector does not detect any helium, the sealing structure of PFS 1 hermetically seals the cavity 33. Otherwise, the tightness of the seal is evaluated by the measured helium concentration.

[0062] Figure 3 and Figure 4 The other ophthalmic PFS 10 shown is a second embodiment of the syringe according to the invention, which is in an upright position. PFS 10 and... Figure 1 and Figure 2 The PFS 1 is implemented in a similar manner to a large extent. Specifically, it also includes a cylinder 20, a stop 30, a chamber 50, a drug substance 60, an extended finger flange 70, a cap 80, and a Luer lock adapter 90. The cylinder 20 has an orifice 210 and an opening 220. The stop 30 has a distal side 310, a proximal side 320, and a cavity 330, which has an internal chamber portion 3320 and a cylindrical channel portion 3310.

[0063] The plunger 40 has a vertical cylindrical rod portion 430 that extends through an opening 220 in the cylinder 20 into its hollow interior. It has a top distal end 410 and a bottom proximal end 420. The proximal end 420 includes a substantially horizontal abutment surface 4210 and barbs 4220 extending downward from the abutment surface 4210 in a proximal direction.

[0064] like Figure 4 As shown, the barb 4220 has a lower or proximal head 42210 and a generally cylindrical upper or distal neck 42220. The neck 42220 has a first axial length 42230 extending between the abutment surface 4210 and the head 42210. The first axial length 42230 is less than the second axial length of the channel portion 3310 of the cavity 330 of the stop 30 extending between the distal side 310 of the stop 30 and the internal chamber portion 3320 of the cavity 330. With these different first and second lengths, when the stop 30 is engaged with the barb 4220 of the plunger 40, the stop 30 is compressed against the abutment surface 4210 of the plunger 40.

[0065] In this way, the shorter first axial length 42230 of the neck 42220 of the barb 4220, together with the second axial length of the channel portion 3310 of the cavity 330 of the stop 30, establishes a sealing structure. In particular, through this structure, the distal side 310 of the stop 30 is compressed onto the abutment surface 4210 of the plunger 40, thereby sealing the cavity 330 of the stop 30 against microorganisms.

[0066] Figure 5 and Figure 6 The other ophthalmic PFS 19 shown is a third embodiment of the syringe according to the invention, which is in an upright position. PFS 19 and... Figure 1 and Figure 2 PFS 1 and Figure 3 and Figure 4 The PFS 10 is implemented in a similar manner to a large extent. Specifically, it also includes a cylinder 29, a stop 39, a chamber 59, a drug substance 69, an extended finger flange 79, a cap 89, and a Luer lock adapter 99. The cylinder 29 has an orifice 219 and an opening 229. The stop 39 has a distal side 319, a proximal side 329, and a cavity 339, which has an internal chamber portion 3329 and a cylindrical channel portion 3319.

[0067] The plunger 49 has a vertical cylindrical rod portion 439 that extends through an opening 229 in the cylinder 29 into its hollow interior. It has a top distal end 419 and a bottom proximal end 429. The proximal end 429 includes a substantially horizontal abutment surface 4219 and a barb 4229 extending downward from the abutment surface 4219 in a proximal direction.

[0068] like Figure 6 As best shown, the barb 4229 has a lower or proximal head 42219 and a generally cylindrical upper or distal neck 42229. The barb 4229 of the plunger 49 engages in the cavity 339 of the stop 39, thereby establishing a form-fitting connection between the plunger 49 and the stop 39. Thus, the neck 42229 of the barb 4229 is located in the channel portion 3319 of the cavity 339, and the head 42219 of the barb 4229 is located in the internal chamber portion 3329 of the cavity 339.

[0069] A washer 42239 is arranged between the abutment surface 4219 of the proximal end 429 of the plunger 49 and the distal surface 319 of the stop 39. The washer 42239 is annular and extends around the neck 42229 of the barb 4229. The size and shape of the barb 4229 are determined such that the washer 42239 is compressed. In this way, the washer 42239 and the barb 4229 together establish a sealing structure. Through this sealing structure, the distal surface 310 of the stop 30 is pressed tightly against the proximal end 429 of the plunger 49, so that the cavity 330 of the stop 30 is sealed against microorganisms.

[0070] This specification and accompanying drawings, which illustrate various aspects and embodiments of the invention, should not be construed as limiting the scope of the claims defining the protected invention. In other words, while the invention has been shown and described in detail in the accompanying drawings and the foregoing description, such illustrations and descriptions should be considered illustrative or exemplary rather than restrictive. Various mechanical, compositional, structural, electrical, and operational changes can be made without departing from the spirit and scope of this specification and claims. In some cases, well-known circuits, structures, and techniques have not been shown in detail to avoid obscuring the invention. Therefore, it should be understood that those skilled in the art can make changes and modifications within the scope and spirit of the following claims. In particular, the invention covers other embodiments having any combination of features from the different embodiments described above and below. For example, the invention can be operated in the following manner, wherein:

[0071] Figure 1 and Figure 2 The sealing structure of PFS 1 and Figure 3 and Figure 4 The sealing structure of PFS 10 is combined.

[0072] Figure 1 and Figure 2 The sealing structure of PFS 1 and Figure 5 and Figure 6 The sealing structure of PFS 19 is combined.

[0073] This disclosure also covers all other features shown in the accompanying drawings, although they may not have been described in the preceding or following description. Furthermore, a single alternative to the embodiments described in the drawings and specification, and a single alternative to the features thereof, may be derived from the subject matter of the invention or from the disclosed subject matter. This disclosure includes subject matter consisting of the features defined in the claims or exemplary embodiments, as well as subject matter incorporating said features.

[0074] Furthermore, in the claims, the term "comprising" does not exclude other elements or steps, and the indefinite articles "a" or "an" do not exclude multiple. A single unit or step can perform the function of multiple features recited in the claims. The mere fact that specific measures are recited in mutually different dependent claims does not mean that the combination of these measures cannot be used advantageously. Terms such as "substantially," "about," "approximately," etc., combined with qualifiers or numerical values, in particular also explicitly define the qualifier or the numerical value, respectively. The term "about" in the context of a given numerical value or range refers, for example, to a value or range of 20%, 10%, 5%, or 2% of the given value or range. Components described as "connected" or "linked" may be electrically or mechanically directly connected, or they may be indirectly connected via one or more intermediate components. No reference numerals in the claims should be construed as limiting the scope of protection.

Claims

1. A syringe (1; 10； 19), the syringe comprises: The cylindrical body (2; 20; 29) has a hollow interior, an orifice (21; 210; 219) and an opening (22; 220; 229) opposite to the orifice (21; 210; 219); A stop (3; 30; 39) is arranged within the hollow interior of the cylinder (2; 20; 29) to define a sealed chamber (5; 50; 59) within the cylinder (2; 20; 29), wherein the stop (3; 30; 39) is movable within the cylinder (2; 20; 29), thereby changing the volume of the chamber (5; 50; 59); and A plunger (4; 40; 49) extends through an opening (22; 220; 229) in the cylinder (2; 20; 29) into the hollow interior of the cylinder (2; 20; 29), wherein, The plunger (4; 40; 49) has a distal end (41; 410; 419) outside the barrel (2; 20; 29) and a proximal end (42; 420; 429) inside the hollow interior of the barrel (2; 20; 29). The proximal end (42; 420; 429) of the plunger (4; 40; 49) has an abutment surface (421; 4210; 4219) and barbs (422; 4220; 4229) extending proximally from the abutment surface (421; 4210; 4219). The barbs (422; 4220; 4229) of the proximal end (42; 420; 429) of the plunger (4; 40; 49) have a neck (4222; 42220; 42229) and a head (4221; 42210; 42219). The stop (3; 30; 39) has a distal side (31; 310; 319) facing the plunger (4; 40; 49), a proximal side (32; 320; 329) facing the chamber (5; 50; 59), and an internal cavity (33; 330; 339) opening at the distal side (31; 310; 319). The cavity (33; 330; 339) of the stop (3; 30; 39) has a channel portion (331; 3310; 3319) and an internal chamber portion (332; 3320; 3329). The syringe (1; 10; 19) is equipped with a sealing structure to seal the cavity (33; 330; 339) of the stop (3; 30; 39), thereby sealing the cavity (33; 330; 339) of the stop (3; 30; 39) against microorganisms. The cavities (33; 330; 339) of the stop (3; 30; 39) and the barbs (422; 4220; 4229) of the proximal ends (42; 420; 429) of the plunger (4; 40; 49) are shaped to form a snap-fit, such that the abutment surfaces (421; 4210; 4219) of the proximal ends (42; 420; 429) of the plunger (4; 40; 49) are adjacent to the distal surfaces (31; 310; 319) of the stop (3; 30; 39), thus fixing the stop (3; 30; 39) onto the plunger (4; 40; 49). The neck (4222; 4220; 4229) of the barb (4222; 4220; 4229) of the proximal end (42; 420; 429) of the plunger (4; 40; 49) is received by the passage portion of the cavity (33; 330; 339) of the stop (3; 30; 39) and the internal chamber portion (332; 3320; 33) of the cavity (33; 330; 339) of the stop (3; 30; 39) 29) The head (4221; 42210; 42219) of the barb (422; 4220; 4229) of the proximal end (42; 420; 429) of the plunger (4; 40; 49) is received, thus realizing the snap-fit ​​engagement between the cavity (33; 330; 339) of the stop (3; 30; 39) and the barb (422; 4220; 4229) of the proximal end (42; 420; 429) of the plunger (4; 40; 49). The sealing structure is formed by the neck (4222; 42220; 4229) of the barbs (422; 4220; 4229) at the proximal end (42; 420; 429) of the plunger (4; 40; 49), the neck of the barbs at the proximal end of the plunger having a first axial length (42230), the first axial length extending between the abutment surface (421; 4210; 4219) of the proximal end (42; 420; 429) of the plunger (4; 40; 49) and the head (4221; 42210; 42219) of the barbs (422; 4220; 4229) at the proximal end (42; 420; 429) of the plunger (4; 40; 49). The channel portion of the cavity (33; 330; 339) of the stop (3; 30; 39) has a second axial length, which extends between the distal side (31; 310; 319) of the stop (3; 30; 39) and the internal chamber portion (332; 3320; 3329) of the cavity (33; 330; 339) of the stop (3; 30; 39). When the stop (3; 30; 39) is not engaged with the plunger (4; 40; 49), the first axial length (42230) of the neck (4222; 42220; 42229) of the barb (422; 4220; 4229) at the proximal end (42; 420; 429) of the plunger (4; 40; 49) is less than the second axial length of the channel portion of the cavity (33; 330; 339) of the stop (3; 30; 39), and Due to the relative dimensions of the first axial length and the second axial length, the stop (3; 30; 39) is compressed when the stop (3; 30; 39) engages with the plunger (4; 40; 49).

2. The syringe (1; 10; 19) according to claim 1, wherein, The first axial length (42230) of the neck (4222; 42220; 42229) of the proximal end (42; 420; 429) of the plunger (4; 40; 49) is at least 0.3 mm or 0.5 mm shorter than the second axial length of the channel portion of the cavity (33; 330; 339) of the stop (3; 30; 39).

3. The syringe (1; 10; 19) according to claim 1 or 2, wherein, The neck (4222; 42220; 4229) of the barbs (422; 4220; 4229) at the proximal end (42; 420; 429) of the plunger (4; 40; 49) has a first compression section (4223). The channel portion of the cavity (33; 330; 339) of the stop (3; 30; 39) has a second compression section (331), and The first compression section (4223) of the neck (4222; 42220; 42229) of the proximal end (42; 420; 429) of the plunger (4; 40; 49) is more constricted than the second compression section (331) of the passage portion of the cavity (33; 330; 339) of the stop (3; 30; 39).

4. The syringe (1; 10; 19) according to claim 3, wherein, The first compression section (4223) of the neck (4222; 42220; 42229) of the proximal end (42; 420; 429) of the plunger (4; 40; 49) gradually tapers toward the head (4221; 42210; 42219) of the barb (422; 4220; 4229) of the proximal end (42; 420; 429) of the plunger (4; 40; 49).

5. The syringe (1; 10; 19) according to claim 3, wherein, The second compression section (331) of the channel portion of the cavity (33; 330; 339) of the stop (3; 30; 39) gradually tapers toward the internal chamber portion (332; 3320; 3329) of the cavity (33; 330; 339) of the stop (3; 30; 39).

6. The syringe (1; 10; 19) according to claim 1 or 2, wherein the syringe comprises a washer (42239) arranged around a barb (422; 4220; 4229) at the proximal end (42; 420; 429) of the plunger (4; 40; 49), wherein, The gasket (42239) contacts the abutment surface (421; 4210; 4219) of the proximal end (42; 420; 429) of the plunger (4; 40; 49) and the distal surface (31; 310; 319) of the stop (3; 30; 39).

7. The syringe (1; 10; 19) according to claim 1 or 2, wherein, The far side (31; 310; 319) of the stop (3; 30; 39) has a protrusion that extends circumferentially around a cavity (33; 330; 339) of the stop (3; 30; 39) that opens at the far side (31; 310; 319).

8. The syringe (1; 10; 19) according to claim 1 or 2, wherein, The liquid (6; 60; 69) is arranged in the chamber (5; 50; 59) of the cylinder (2; 20; 29).

9. A method for testing the tightness between a stop (3; 30; 39) and a plunger (4; 40; 49) of a syringe (1; 10; 19), wherein, A stop (3; 30; 39) has a distal side (31; 310; 319), a proximal side (32; 320; 329), and an internal cavity (33; 330; 339) opening at the distal side (31; 310; 319). A syringe (1; 10; 19) has a barrel (2; 20; 29) having a hollow interior, an orifice (21; 210; 219), and an opening (22; 220; 229) opposite to the orifice (21; 210; 219). The syringe (1; 10; 19) is equipped with a sealing structure to seal the cavity (33; 330; 339) of the stop (3; 30; 39), such that the cavity (33; 330; 339) of the stop (3; 30; 39) is sealed against microorganisms. The method includes: The cavity (33; 330; 339) of the stop (3; 30; 39) opens to the proximal side (32; 320; 329). The stop (3; 30; 39) is arranged in the hollow interior of the cylinder (2; 20; 29) through the opening (22; 220; 229) of the cylinder (2; 20; 29), such that the distal side (31; 310; 319) of the stop (3; 30; 39) points towards the plunger (4; 40; 49). Connect the gas detector to the opening (22; 220; 229) of the syringe barrel (2; 20; 29), and Gas is supplied through orifices (21; 210; 219) in the cylinder (2; 20; 29).

10. The method of claim 9, further comprising operating a gas detector to detect gas distal to the stop (3; 30; 39).

11. The method according to claim 10, wherein, The gas detector measures the gas concentration on the far side of the stop (3; 30; 39).

12. The method according to any one of claims 9 to 11, comprising generating a vacuum on the distal side of the stop (3; 30; 39).

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