Syringe stopper with anti-adhesion function

Abstract

A stopper for a syringe including a body having a tail adapted for attachment to a plunger of a syringe, a head, and optionally a plurality of annular ribs and grooves around the circumference of an outer sidewall of the body, the ribs being separated by the grooves. The stopper includes a plurality of projections extending from an outer surface of the tail and / or head and / or a plurality of projections extending outwardly from the outer sidewall from within at least one groove. The projections extending from the outer surface of the tail and / or head are arranged in at least one circle, and the angular distance between two adjacent projections in the circle is less than the angular distance occupied by one projection. Also, a syringe including such a stopper.

Description

[Technical field]

[0001] [CROSS REFERENCE TO RELATED APPLICATIONS] This application claims priority to European Patent Application No. 21212446.5, filed December 6, 2021, the disclosure of which is incorporated herein by reference in its entirety.

[0002] The present invention relates to a stopper for a syringe having an anti-stick feature extending from an exterior surface of the stopper body, and a syringe including such a stopper. [Background technology]

[0003] In the prior art of stoppers for syringes, particularly stoppers made of rubber or rubber-like materials, the surface of a first stopper may adhere to the surface of another, second stopper during storage or assembly. For example, the outer surface of the tail and / or head of one stopper may adhere to the outer surface of the tail, head, or sidewall of another stopper, or the outer sidewalls of two stoppers may adhere to each other. Sticking can occur when stoppers are packaged in plastic bags that are deflated and stacked on pallets during storage or shipping. Sticking can also occur during the manufacture of syringes when stoppers are transported in a vibrating bowl before being assembled into a syringe. Thus, there is a need for a stopper that reduces both the occurrence of sticking in these situations and the adhesive strength of any sticking that does occur.

[0004] In the case of uncoated stoppers, the adhesion of the stoppers to each other is caused by intramolecular forces, such as covalent bonds, which are promoted by gamma sterilization, and / or intermolecular forces, such as van der Waals forces. Covalent bonds are formed between the two surfaces of two different stoppers on the angstrom scale (10 -10m) (Penoccchio et al. Structural properties of carbon-sulfur bonds: A semi-empirical perspective, Can. J. Chem., 2016, Vol. 94 No. 12, pp. 1065-1076). Van der Waals forces vary as the inverse of the sixth power of the distance between the two surfaces on which the force is exerted (Israelachvili, Intermolecular and Surface Forces, 2003). Therefore, very close contact at the interface is required to effectively obtain the interaction between the two surfaces.

[0005] Thus, intimate contact between the surfaces of the stoppers is required for the stoppers to adhere to one another macroscopically.

[0006] Intimate contact between two surfaces of two different stoppers, referred to herein as an apparent contact area, can occur when an external force is applied to the surfaces of the stoppers that are in contact with one another. This force can act on packaged stoppers and can be increased when air is evacuated from bags containing the stoppers to increase the packing density, and when bags of stoppers are packaged into cardboard boxes that are stacked together on a pallet for shipping.

[0007] For elastic materials, such as those used in stoppers, the increase in the apparent contact area can be described using Hertz's theory (Popov, A Rigorous Treatment of Contact Problems - Hertzian Contacts, Contact Mechanics and Friction, 2010; pp. 55-70). It applies to idealized surfaces (half planes / spheres, cylinders / cylinders, etc. with known parameters such as external conditions, Young's modulus, Poisson's ratio, etc.), but the numerical solution of Hertz's equations for more complex geometries, such as stoppers with anti-adhesive properties, is not trivial. If adhesive forces (intramolecular forces) are taken into account (JKR theory, Surface Energy and Contact of Elastic Solids, Proc. R. Soc. London Math. Phys. Sci., 1971, vol. 324, no. 1558, pp. 301-313), the solution for complex geometries becomes even more difficult.

[0008] Furthermore, with the latest developments in contact mechanics (Multicontact mechanics, Persson, Theory of Rubber Friction and Contact Mechanics, J. Chem. Phys., 2001, vol. 115, no. 8, pp. 3840-3861), the concept of apparent contact area is replaced by an effective contact area that depends on the surface roughness and chemical state at different lengths, ranging in size from nanometers to millimeters. This makes the approximation of the effective contact area in this approach feasible only by numerical simulations in combination with well-characterized surfaces.

[0009] With these factors in mind, the stoppers of the present invention were developed with anti-stick features to reduce sticking of the stoppers to each other during assembly and storage. Summary of the Invention

[0010] The present invention relates to a stopper for a syringe, the stopper comprising a proximal tail adapted to be attached to a plunger rod of the syringe, a body having a distal head, and a plurality of protrusions extending from an outer surface of the tail and / or head. The protrusions are arranged in at least one circle on the outer surface of the tail and / or head of the stopper, and an angular distance between two adjacent protrusions in the circle is less than the angular distance occupied by one of the protrusions. The outer surface of the protrusions arranged in the at least one circle defines a polygonal structure. The protrusions can have any shape, including, but not limited to, protrusions having a cross section that is circular, elliptical, square, polygonal, or in the shape of a letter or logo.

[0011] The body of the stopper further includes a cavity adapted to receive and engage at least a portion of the plunger rod of the syringe, with an opening to the cavity provided in the tail of the stopper. The projections may be provided in the tail of the stopper and disposed in at least one circle on the outer surface of the tail of the stopper, extending from an annular ring on the outer surface of the stopper tail defined between the outer periphery of the outer surface and the outer periphery of the cavity. When the projections are cylindrical and form a single circle, the minimum number of projections in a circle is defined as follows:

[0012]

number

[0013] Where:

[0014]

number

[0015] where Dp is the diameter of each projection, Dо is the outer diameter of the outer surface of the tail of the stopper, Dc is the diameter of the periphery of the cavity, and the angular distance between the projections is

[0016]

number

[0017] It is.

[0018] The projections may be arranged in an outer circle along the periphery of the outer surface of the head of the stopper, with the projections inward from the outer circle being centered on the outer surface of the stopper head.

[0019] The protrusions may be arranged in an outer circle along the periphery of the outer surface of the tail and / or head of the stopper, and in an additional concentric circle inward from the outer circle, the angular distance between two adjacent protrusions in each circle being less than the angular distance occupied by one protrusion. A first outer circle of substantially cylindrical protrusions is provided on the tail and / or head of the stopper adjacent the periphery of the outer surface of the tail and / or head of the stopper, and the number of protrusions in the first circle, n1, is

[0020]

number

[0021] where R is the outer diameter of the outer surface of the tail and / or head of the stopper, β is the ratio of the radius r of each projection to the radius R (r / R), and γ is a safety factor for the distance between the circle of projections and the circumference of the end face of the head of the stopper. Additional concentric circles of projections may be provided inward from the first circle of projections, and the number of projections in the i-th circle, ni, is expressed as:

[0022]

number

[0023] where Ri is the inner radius of the (i-1)th circle of the protrusion.

[0024] The projections may be equally spaced along at least one circle, the projections may have any shape, including but not limited to projections having a cross section that is circular, elliptical, square, polygonal, or in the shape of a letter or logo, and / or the outer surface of the head of the stopper may be flat, convex, or conical. A convex outer surface of the head of the stopper is one in which the outer surface of the head of the stopper is curved such that the apex of the curvature extends away from a plane that is perpendicular to the longitudinal axis of the stopper and includes the periphery of the outer surface, i.e., the distance between the apex of the outer surface of the head and said plane is greater than the distance between the portion of the outer surface of the head adjacent the periphery of the outer surface of the head and said plane when the stopper is viewed from the side in a direction perpendicular to the longitudinal axis of the stopper. When the stopper head is convex, a protrusion in a circle adjacent the outer periphery of the outer surface of the stopper head may have a height extending outward from the outer surface of the stopper head that is greater than the height, extending outward from the outer surface of the head, of a protrusion located inside the circle adjacent to the outer surface of the stopper head.

[0025] Where the head of the stopper is conical, a circle of the protrusion may extend from the outer surface of the stopper head having a substantially triangular shape, preferably a substantially isosceles triangular shape, with an apex corresponding to the apex angle of the triangular shape of the protrusion, a base corresponding to the base of the triangular shape of the protrusion, and two sides extending between the apex and the base.

[0026] The invention further relates to a stopper for a syringe comprising a body having a distal tail adapted for attachment to a plunger rod of a syringe, a distal head, a plurality of annular ribs around the circumference of an outer sidewall of the body, and a plurality of grooves around the circumference of the outer sidewall of the body, the ribs being spaced apart from one another by the grooves, and a plurality of projections extending outwardly from the outer sidewall of the body in a radial direction from within at least one of the grooves. The angular spacing of the projections in the at least one groove may be 30° or more, the median angular spacing of the projections in the at least one groove may be between 40° and 60°, and / or the maximum angular spacing of the projections in the at least one groove may be between 60° and 80°. The height of the projections in the radial direction may be 50% or more and less than 100% of the difference between the radius of the rib and the radius of the groove. The projections may be provided in a plurality of grooves with an offset spacing from groove to groove corresponding to half the angular distance between the projections in each groove.

[0027] The present invention further relates to a syringe comprising a syringe body defining a chamber, a plunger rod at least partially received within the chamber, and a stopper as described above attached to an end of the plunger received within the chamber. [Brief description of the drawings]

[0028] [Figure 1] FIG. 1 is a cross-sectional view of a stopper of the present invention within a syringe. [Diagram 2] FIG. 2 is a cross-sectional view of a stopper of the present invention having anti-adhesive projections extending from the exterior surface of the tail. [Diagram 3] FIG. 3 is a bottom view of the stopper of the present invention of FIG. [Figure 4]FIG. 4 illustrates contact between the tails of two of the inventive stoppers of FIG. 2, with the bottom of one inventive stopper shown in solid lines and the bottom of the other inventive stopper shown in dashed lines. [Diagram 5] FIG. 5 is a cross-sectional view of a stopper of the present invention having anti-adhesive projections extending from the outer surface of the head. [Figure 6] FIG. 6 is a top view of the stopper of the present invention of FIG. [Figure 7] FIG. 7 illustrates contact between the heads of two of the inventive stoppers of FIG. 5, with the top of one inventive stopper shown in solid lines and the top of the other inventive stopper shown in dashed lines. [Figure 8] FIG. 8 shows contact between the heads of two stoppers of the present invention that do not have an anti-adhesion protrusion in the center of the outer surface of the head, with the top of one stopper of the present invention shown in solid lines and the top of the other stopper of the present invention shown in dashed lines. [Figure 9] FIG. 9 shows contact between the heads of two stoppers of the present invention having anti-adhesion protrusions in the center of the outer surfaces of the heads, with the top of one stopper of the present invention shown in solid lines and the top of the other stopper of the present invention shown in dashed lines. [Figure 10] FIG. 10 is a top view of a stopper according to the present invention having concentric circles of anti-adhesive projections extending from the exterior surface of the head. [Figure 11] FIG. 11 is a graph showing the relationship between the maximum number nmax of protrusions extending from the outer surface of the head of a stopper according to the present invention and the ratio β of the radius r of the protrusions to the radius R of the outer periphery of the stopper head (r / R). [Figure 12] FIG. 12 is a graph showing the relationship between the maximum number of protrusions in each of the concentric circles of protrusions extending from the head of a stopper according to the present invention and the ratio β of the radius r of the protrusions to the radius R of the outer periphery of the stopper head (r / R). [Figure 13] FIG. 13 is a graph showing the relationship between the effective total contact area and the ratio β(r / R) of the radius r of the projection to the radius R of the outer periphery of the stopper head. [Figure 14]FIG. 14 is a bottom view of a stopper according to the present invention having concentric circles of anti-adhesive projections extending from the outer surface of the tail. [Figure 15] FIG. 15 is a cross-sectional view of a stopper according to the present invention having anti-adhesive projections extending from the outer surface of the convex head. [Figure 16] FIG. 16 is a cross-sectional view of a stopper according to the present invention having anti-adhesive projections extending from the exterior surface of the conical head. [Figure 17] FIG. 17 is a top view of the stopper of the present invention shown in FIG. [Figure 18] FIG. 18 is a cross-sectional view of a stopper according to the present invention having anti-adhesive projections extending from the outer sidewall of the stopper body. [Figure 19] FIG. 19 is a partial cross-sectional view of two prior art stoppers showing the contact between the outer sidewalls of the two stoppers, one of the stoppers shown with cross-hatching and one of the stoppers shown without cross-hatching. [Figure 20] FIG. 20 is a partial cross-sectional view of the two inventive stoppers of FIG. 19 showing contact between the outer sidewalls of the two inventive stoppers, one of the inventive stoppers shown with cross-hatching and one of the inventive stoppers shown without cross-hatching. [Figure 21] FIG. 21 is a graph illustrating the angular spacing of anti-adhesion protrusions extending from the outer sidewall of the stopper body for various stopper configurations. DETAILED DESCRIPTION OF THE PREFERRED EMBODIMENTS

[0029] Unless otherwise stated, all numbers used herein, e.g., representing values, ranges, amounts, or percentages, may be read as being prefaced by the word "in part", even if this term does not appear explicitly. Any numerical ranges described herein are intended to include all subranges contained therein. For example, a range "1-10" is intended to include any and all subranges between and including the recited minimum of 1 and the recited maximum of 10, i.e., all subranges beginning with a minimum value of 1 or more and ending with a maximum value of 10 or less, as well as all subranges between, e.g., 1-6.3, or 5.5-10, or 2.7-6.1. Plurals include the singular and vice versa. When ranges are given, any endpoints of those ranges and / or numbers within those ranges can be combined into the scope of the invention. "Including", "e.g., such as", "for example", and similar terms mean "including / for example / for example", but are not limited thereto.

[0030] For purposes of the following description, the spatial orientation terms used are relative to the referenced embodiment as oriented in the attached drawings, figures, or as described in the detailed description below. However, it should be understood that the embodiments described below may assume many alternative variations and configurations. It should also be understood that the specific components, devices, features, and sequences of operations described in the attached drawings, figures, or in the description herein are merely illustrative and should not be considered limiting. As used herein, "distal" refers to the end of the stopper that includes the head of the syringe or the injection end of the syringe. In a cross-sectional view of the stopper, "distal" refers to the top end of the stopper. Similarly, "distal" refers to the direction toward the head of the stopper or toward the injection end of the syringe. As used herein, "proximal" refers to the end of the stopper that includes the tail or plunger end of the syringe. In a cross-sectional view, "proximal" refers to the bottom end of the stopper. Similarly, "proximal" refers to the direction toward the tail of the stopper or toward the plunger end of the syringe.

[0031] The present invention relates to a stopper 10 for use in a syringe 12. The syringe comprises a syringe body 14 and a plunger 16 to which the stopper 10 is connected.

[0032] As shown in FIG. 1, the syringe body 14 includes a proximal end 18, a distal end 20, and a sidewall 22 extending between the proximal end 18 and the distal end 20. The sidewall 22 defines a chamber 24 adapted to receive a pharmaceutical composition. The chamber 24 is substantially cylindrical. A fitting 26 for attaching the cannula assembly to the syringe 12 extends longitudinally from the distal end 20 of the syringe body 14. The fitting 26 can be a luer lock or a luer slip. The cannula assembly may be permanently attached to the syringe 12, or alternatively, the cannula assembly may be assembled to the syringe 12 immediately prior to use. The syringe body 14 can be made of plastic or glass.

[0033] The plunger 16 may include a plunger rod 28 having a proximal end 30 and a distal end 32, an engagement portion 34 extending from the distal end 32 of the plunger rod 28, and a thumb pad 36 extending radially outward from the proximal end 30 of the plunger rod 28 in a direction substantially perpendicular to the longitudinal axis of the plunger rod 28. At least a portion of the plunger rod 28 and the engagement portion 34 of the plunger rod 28 are contained within the chamber 24 of the syringe body 14. The engagement portion 34 of the plunger rod 28 is adapted to connect to the stopper 10. The plunger 16 is movable relative to the syringe body 14 such that a distal force applied to the plunger 16 while the syringe body 14 is held stationary moves the engagement portion 34 of the plunger rod 28 and the stopper 10 attached thereto distally within the chamber 24 of the syringe body 14, and a proximal force applied to the plunger 16 while the syringe body 14 is held stationary moves the engagement portion 34 of the plunger rod 28 and the stopper 10 attached thereto proximally within the chamber 24 of the syringe body.

[0034] At least a portion of the stopper 10 has a diameter equal to or greater than the inner diameter of the chamber 24 of the syringe body 14 , thereby creating a sealing engagement between the portion of the stopper 10 and the inner surface of the sidewall 22 of the syringe body 14 .

[0035] The stopper 10 of the present invention can be sized for use with any type of syringe, such as a standard 0.5 ml to 20 ml syringe.

[0036] As shown in Figures 2, 3, 5, 6 and 9-17, the stopper 10 includes a body 38 having a proximal tail 40 adapted to connect to the plunger rod 28, a distal head 42, and an anti-adhesive mechanism on at least one of an outer surface 44 of the tail 40 and an outer surface 46 of the head 42. The tail 40 includes an opening 48 to a cavity 50 defined within the body 38. The opening 48 and the cavity 50 are adapted to receive and engage the engagement portion 34 of the plunger rod 28, thereby attaching the stopper 10 to the plunger 16. The opening 48 of the cavity 50 can be a circular opening and has a diameter Dc that is less than the outer diameter Dо of the tail 40 of the stopper 10, such that the outer surface 44 of the tail 40 of the stopper 10 is an annular ring. Although the stopper 10 shown in the figures and described below includes a cavity 50, it should be understood that the cavity 50 is optional and the plunger 16 may be attached to the stopper 10 via other means without requiring a cavity.

[0037] In prior art stoppers, during storage or assembly, the outer surfaces 44, 46 of the tail 40 and / or head 42, respectively, of one stopper may adhere to the outer surface 44, 46 of the tail 40 and / or head 42 of another stopper, or to the side walls of another stopper. The anti-stick feature of the stopper 10 of the present invention is provided to reduce the tendency of the surfaces 44, 46 of the tail 40 and / or head 42 of one stopper 10 to adhere to the surfaces 44, 46 of the tail 40 and / or head 42 of another stopper 10.

[0038] The anti-adhesion feature can be a protrusion 52 extending outwardly from the tail 40 and / or head 42 of the stopper 10. Although the protrusion 52 shown in the figures and described below is substantially cylindrical with a substantially circular cross-section, the protrusion 52 can have any shape so long as the shape and dimensions of the protrusion 52 provide for the prevention of adhesion of the tail 40 and / or head 42 of one stopper 10 to the tail 40 and / or head 42 of another stopper in the manner described below. For example, the protrusion can have a cross-section that is circular, oval, square, polygonal, or in the shape of a letter or logo.

[0039] As shown in Figures 3, 6, 10 and 14, the protrusions 52 are arranged in at least one circle on the outer surface 44, 46 of the tail 40 and / or head 42 of the stopper 10. The arrangement of the protrusions 52 on the circle defines a polygon. For example, three protrusions 52 can be arranged on a circle to define a triangle, four protrusions 52 can be arranged on a circle to define a square or rectangle, five protrusions 52 can be arranged on a circle to define a pentagon, etc.

[0040] The angular distance θs between two adjacent protrusions 52 is less than the angular distance θp occupied by one protrusion 52, i.e., θs<θp. As used herein, the angular distance θs between two adjacent protrusions 52 is the minimum angular distance between the outer surface of the protrusion 52 and the outer surface of the most adjacent protrusion 52. By dimensioning and positioning the protrusions 52 in this manner, the protrusion 52 of one stopper 10 cannot fit between the protrusions 52 of another stopper 10, and the maximum contact area between the outer surfaces 44, 46 of the tails 40 and / or heads 42 of the two stoppers 10 is limited to the maximum total surface area of ​​the protrusions 52 of one stopper 10.

[0041] With respect to the tail 40 of the stopper 10 (FIGS. 2 and 3), a plurality of protrusions 52a may extend proximally outwardly about the outer surface 44 of the tail 40 of the stopper 10. The protrusions 52a are equally spaced around an annular ring on the outer surface 44 of the tail 40.

[0042] The dimension Dp of the projection 52a in the radial direction is equal to or less than the radial width of the annular ring as determined by the difference between the outer diameter D0 of the outer surface 44 of the tail 40 of the stopper 10 and the diameter Dc of the circumference of the opening 48 of the cavity 50. In the case of a cylindrical projection 52a, the diameter of the projection 52a is equal to or less than the radial width of the annular ring as determined by the difference between the outer diameter D0 of the tail 40 of the stopper 10 and the diameter Dc of the circumference of the opening 48 of the cavity 50.

[0043] The angular distance θs between two adjacent protrusions 52 is smaller than the angular distance θp occupied by one protrusion 52, i.e., θs<θp. By dimensioning and positioning the protrusions 52a in this manner, a protrusion 52a on the outer surface 44 of the tail 40 of one stopper 10 cannot fit between protrusions 52a on the outer surface 44 of the tail 40 of another stopper 10 (FIG. 4), and the maximum contact area between the outer surfaces 44 of the tails 40 of the two stoppers 10 is limited to the maximum value of the total surface area of ​​the protrusions 52a of one stopper 10.

[0044] The number of projections 52a can be calculated by giving the diameter Dp of the projections 52a extending around the circumference of the annular ring on the outer surface 44 of the tail 40 of the stopper 10, the outer diameter Do of the tail of the stopper, and the diameter Dc of the opening 48 of the cavity 50.

[0045] When the projection 52a is radially centered within the annular ring of the outer surface 44 of the tail 40 of the stopper 10, i.e., when the projection 52a is at a distance from the common origin of the outer periphery of the tail 40 of the stopper 10 and the opening 48 of the cavity 50, which distance is the sum of the diameter Do of the tail 40 of the stopper 10 and the diameter Dc of the outer periphery of the opening 48 of the cavity 50 divided by four ((Do+Dc) / 4), the angular distance θp occupied by one projection 52a having a dimension (diameter) Dp extending around the annular ring of the outer surface 44 of the tail 40 of the stopper 10 is

[0046]

number

[0047] In the radial direction, the total angular distance occupied by all of the projections 52a is less than π. Therefore, the minimum number of projections nmin is

[0048]

number

[0049] The angular distance θs between the protrusions is:

[0050]

number

[0051] As an example, if the maximum dimension (diameter) Dp extending along the circumference of the annular ring of the outer surface 44 of the tail 40 of the stopper 10 is 1 mm, then the outer diameter Do of the tail of the stopper is 5 mm and the diameter Dc of the cavity opening is 3 mm.

[0052]

number

[0053] In this configuration, the optimum number of protrusions is seven.

[0054] With respect to the head 42 of the stopper 10, a plurality of projections 52b extend distally outward from the outer surface 46 of the head 42, as shown in Figures 5 and 6. The projections 52b are provided in a circular manner in an area corresponding to the annular ring of the tail 40, and are equally spaced along the circumference of the outer surface 46 of the head 42 of the stopper 10 such that the projections define a polygon, specifically, a heptagon, as shown in Figures 5 and 6. In order to minimize contact between the tail 40 and the head 42 between two stoppers 10, the projections 52b on the outer surface 46 of the head 42 may be positioned in a manner corresponding to the projections 52a provided on the outer surface 44 of the tail 40 of the stopper with respect to the circumference of the stopper 10 and the spacing around the circumference of the outer surface 46 of the head 42 of the stopper 10.

[0055] The angular distance θs between two adjacent protrusions 52b is smaller than the angular distance θp occupied by one protrusion 52b, i.e., θs<θp. By dimensioning and positioning the protrusions 52b in this manner, the protrusions 52b on the outer surface 46 of the head 42 of one stopper 10 cannot fit between the protrusions 52b on the outer surface 44 of the head 46 of another stopper 10 (FIG. 7), and the maximum contact area between the outer surfaces 46 of the heads 44 of the two stoppers 10 is limited to the maximum value of the total surface area of ​​the protrusions 52b of one stopper 10.

[0056] While such an arrangement of the projections 52b on the outer surface 46 of the heads 42 of the stoppers 10 reduces the contact area between the heads 42 of one stopper 10 and the tails 40 of another stopper 10, reducing the tendency of the stoppers 10 to stick to each other in the same way that the projections 52a on the outer surface 44 of the tails 40 of the stoppers 10 reduces the contact area between the tails 40 of one stopper 10 and the tails 40 of another stopper 10, reducing the tendency of the tails 40 of the stoppers 10 to stick to each other, the contact area of ​​the heads 42 may not be reduced sufficiently to reduce the possibility of sticking when the contact between the heads 42 occurs as shown in FIG. 8. In the configuration shown in FIG. 8, the two projections located at the intersection of the two stoppers 10 are in direct contact. This situation can be avoided by providing an additional projection 52c at the center of the outer surface 46 of the heads 42 of the stoppers 10, i.e., at the center of the origin of the circumference of the heads 42 of the stoppers 10, as shown in FIG. 9.

[0057] Alternatively or additionally, one or more further concentric circles of projections 52d, 52e may be provided having a diameter smaller than the diameter of the circle of projections 52b provided along the periphery of the outer surface 46 of the head 42 of the stopper 10 (FIG. 10). The number of these projections 52d, 52e and the arrangement of these projections 52d, 52e may be determined by: The outer diameter R of the head 42 of the stopper 10, The maximum allowable direct rigid coverage α, Radius r of protrusions 52d and 52e (half size), a ratio β(r / R) of a radius r of the projections 52d and 52e to a radius R of the outer diameter of the outer surface 46 of the head 42 of the stopper 10; The number n of protrusions 52b, 52d, 52e, 52f on the surface of the head 42 of the stopper 10; a safety factor γ of the distance between the outer circle of the projection 52b and the outer periphery of the outer surface 46 of the head 42 of the stopper 10 and the distance between adjacent circles of the projections 52b, 52d, 52e, 52f; and the angular distance θ occupied by each of the projections, 52b, 52d, 52e, 52f; It can be determined based on the following.

[0058] The maximum allowable direct rigid coverage α is the maximum allowable contact area when the ends of two stoppers 10 are in direct contact with each other. For example, if the ends of the stoppers 10 are perfectly aligned, i.e., all protrusions 52 on one stopper 10 completely overlap the protrusions 52 on the other stopper 10, then α=1 (100%). If α=0.5, then the contact area between the protrusions is 50% of the total contact area of ​​the protrusions 52 of one stopper 10.

[0059] The safety factor γ is the radial spacing between concentric circles to avoid interpenetration of the projections 52 in the radial direction.

[0060] When the outer surfaces 46 of the heads 42 of the two stoppers 10 are perfectly aligned, there is direct outer surface-to-outer surface contact. In order to effectively reduce the adhesion between the two stoppers 10, the protrusions 52b, 52d, 52e, 52f cover a maximum of 50% of the surface area of ​​the outer surfaces 46 of the heads 42 of the stoppers 10, i.e., α=0.5. When the outer diameter R of the heads 42 of the stoppers 10 is set to 1 (arbitrary units), the maximum total number nmax of the protrusions 52b, 52d, 52e, 52f in the stopper 10 at a given ratio β(r / R) of the radius r of the protrusions 52b, 52d, 52e, 52f to the outer diameter R of the heads 42 can be determined using the following formula:

[0061]

number

[0062] As an example, FIG. 11 shows the relationship between the ratio β of 0.025 to 0.5 (2.5 to 50%) and the maximum total number nmax of protrusions 52b, 52d, 52e, and 52f when the maximum allowable direct rigid coverage α is 0.5 (50%) and protrusions 52b, 52d, 52e, and 52f have a radius r of 0.5.

[0063] To further minimize the contact area, the protrusions 52b, 52d, 52e, 52f may be radially spaced from the outer periphery of the stopper 10 at a distance determined by a safety factor γ. In the radial direction, the center of a given protrusion 52b is located at a distance R-γR-r from the center of the stopper 10. The safety factor γ may be set to 0.05 (5%). The angular distance θp occupied by one protrusion is given by:

[0064]

number

[0065] It is.

[0066] To minimize contact between the outer surfaces 46 of the heads 42 of the two stoppers 10 when the heads 42 of the two stoppers 10 are perfectly aligned, the total angular distance occupied by the spaces between the protrusions is less than 180°. The maximum number n1 of protrusions 52b on an outer circle adjacent the periphery of the outer surface 46 of the head 42 of the stopper 10 as a function of the ratio β can be determined as follows:

[0067]

number

[0068] As an example, FIG. 12 shows the relationship between the ratio β of 0.1 to 0.5 (10 to 50%) of protrusions 52b in the outer circle adjacent to the outer periphery of the outer surface 46 of head 42 of stopper 10 and the maximum number n1 when the maximum allowable direct rigid coverage α is 0.5 (50%) and the safety factor γ is 0.05 (5%).

[0069] As a specific example, if the maximum allowable direct rigid coverage ratio α is 0.5 (50%) and the ratio β is 0.125 (12.5%), the maximum total number of protrusions nmax is:

[0070]

number

[0071] In addition, when the radius R of the head 42 of the stopper 10 is 1 (arbitrary unit), the number n1 of the protrusions 52b arranged on the outer circle adjacent to the outer circumference of the outer surface 46 of the head 42 of the stopper 10 is

[0072]

number

[0073] The remaining twenty-one protrusions may be arranged in one or more concentric circles located within an outer circle adjacent the outer periphery of the outer surface 46 of the head 42 of the stopper 10.

[0074] The distance between the concentric circles of the protrusions 52 must be less than twice the diameter Dp of the protrusions 52 such that the space between the outer surfaces of two protrusions 52 on adjacent circles is less than the diameter Dp of the protrusions 52.

[0075] Equation for determining the maximum number n1 of projections 52b on a circle adjacent the circumference of the outer surface 46 of the head 42 of the stopper 10:

[0076]

number

[0077] can be used iteratively to determine the maximum number of protrusions 52d, 52e to place on each concentric circle by replacing R-γR-βR with Rn-γR-βR, where Rn is the radius of the larger outer circle of protrusions adjacent the circle of protrusions for which the maximum number of protrusions is being determined.

[0078] As an example, Figure 12 shows the relationship between the ratio β of 0.1 to 0.5 (10 to 50%) and the maximum number of protrusions on each circle of protrusions when the maximum allowable direct rigid coverage rate α is 0.5 (50%), the safety factor γ is 0.05 (5%), and the stopper radius R is 1 (arbitrary unit).

[0079] As a specific example, when the maximum allowable direct rigid coverage α is 0.5 (50%), the safety factor γ is 0.05 (5%), the ratio β(r / R) is 0.1 (10%), the radius R of the stopper is 1 (arbitrary unit), and the protrusions have a radius r (arbitrary unit) of 0.1, then the number n1 of protrusions 52b arranged on the outer circle of protrusions 52b adjacent to the outer circumference of the outer surface 46 of the head 42 of the stopper 10 is

[0080]

number

[0081] and R1 is 0.75.

[0082] The number n2 of the protrusions 52d arranged in the second concentric circle of the protrusions 52d adjacent to the outer circle of the protrusions 52b is

[0083]

number

[0084] and the R2 is 0.5.

[0085] The number n3 of the protrusions 52e arranged in the third concentric circle of the protrusions 52e adjacent to the second concentric circle of the protrusions 52d is

[0086]

number

[0087] and R3 is 0.25.

[0088] The number n4 of the protrusions 52f arranged in the fourth concentric circle of the protrusions 52f adjacent to the third concentric circle of the protrusions 52e is

[0089]

number

[0090] It is.

[0091] The total effective surface area of ​​the protrusions 52b, 52d, 52e, 52f on the head 42 of the stopper 10 can be calculated by summing the total number of protrusions 52b, 52d, 52e, 52f (n1+n2+n3, etc.) for a given ratio β as shown in FIG. 12 for a given maximum allowable direct rigid coverage α and safety factor γ.

[0092] As an example, Figure 13 shows the effective total contact area for ratios β between 0.1 and 0.5 (10 and 50%) when the maximum allowable direct rigid coverage α is 0.5 (50%) and the safety factor γ is 0.05 (5%).

[0093] As a specific example, when the ratio β is 0.1 (10%), the maximum allowable direct rigid coverage α is 0.5 (50%), the safety factor γ is 0.05 (5%), the radius R of the outer surface 46 of the head 42 of the stopper 10 is 1 (arbitrary unit), and the radius r of the protrusion is 0.1 (arbitrary unit), the total number N of protrusions is calculated as above to be 34, and the effective total contact area is

[0094]

number

[0095] , which is below the maximum allowable direct rigid coverage α of 50%. As can be seen from Fig. 13, when the ratio β(r / R) is less than or equal to 0.3, the effective total contact area is less than or close to 50% of the maximum allowable direct rigid coverage α.

[0096] The above equations for determining the arrangement of the projections 52b, 52d, 52e, 52f on the outer surface 46 of the head 42 of the stopper 10 can also be applied to the projections 52a provided on the outer surface 44 of the tail 40 of the stopper 10, the equation of the outer circle adjacent to the circumference of the outer surface 46 of the head 42 of the stopper 10 being used when the radial width of the annular ring defining the outer surface 44 of the tail 40 of the stopper 10 and the diameter of the projections 52a allow for the provision of only one ring (circle) of the projections 52a. Additional equations can be used for the projections on the outer surface 44 of the tail 40 of the stopper 10 when the radial width of the annular ring defining the outer surface 44 of the tail 40 of the stopper 10 and the diameter of the projections allow for the provision of multiple circles of the projections 52a, 52j (FIG. 14).

[0097] The stopper of the present invention has the following configurations: (1) a single outer circle of protrusions on the outer surface of the head of the stopper adjacent the outer periphery of the outer surface of the head of the stopper, with an additional protrusion at the center of the outer surface of the head of the stopper (FIG. 6); (2) multiple circles of protrusions on the outer surface of the head of the stopper, the circles being concentric, each circle having a different number of protrusions, the closer the circle is to the center of the outer surface of the head of the stopper, the fewer the number of protrusions on the circle (FIG. 10); and (3) multiple circles of protrusions on the outer surface of the head of the stopper, the circles being concentric, each circle having a different number of protrusions, the closer the circle is to the center of the outer surface of the head of the stopper, the fewer the number of protrusions on the circle. (4) a single outer circle of protrusions on the outer surface of the tail of the stopper between the outer periphery of the tail of the stopper and the outer periphery of the opening of the cavity (FIG. 3); (5) multiple circles of protrusions on the outer surface of the end of the stopper between the outer periphery of the tail of the stopper and the outer periphery of the opening of the cavity, the multiple circles being concentric, each circle having a different number of protrusions, the closer the circle is to the outer periphery of the cavity, the fewer the number of protrusions on the ring (FIG. 14); and (6) any combination of any of the head configurations (1-3) and tail configurations (4 and 5). Additionally, for any combination of head configurations (1-3) and any of the tail configurations (4 and 5), the head may have a different total number of protrusions than the tail, and / or the number of protrusions on the outer ring (circle) of protrusions on the head may be different from the number of protrusions on the outer ring of protrusions on the tail, and / or the size of the protrusions on the head may be different from the size of the protrusions on the outer ring of protrusions on the tail. For example, the outer ring of protrusions on the head may include 7 protrusions and the outer ring of protrusions on the tail may include 6 protrusions.

[0098] The outer surface of the head 42 of the stopper 10 may be flat, convex, or conical. A convex outer surface of the head 42 of the stopper 10 is one in which the outer surface of the head of the stopper is curved such that the apex of the curvature extends away from a plane that is perpendicular to the longitudinal axis of the stopper and contains the periphery of the outer surface, i.e., the distance between the apex of the head's outer surface and said plane is greater than the distance between the portion of the head's outer surface adjacent the periphery of the head's outer surface and said plane when the stopper is viewed from the side in a direction perpendicular to the longitudinal axis of the stopper.

[0099] When the outer surface 46a of the head 42a of the stopper 10 is convex (FIG. 15), any additional protrusions 52h disposed inside the outer ring of protrusions 52g adjacent the outer periphery of the outer surface 46a of the head 42a of the stopper 10 may have a height extending outwardly and perpendicularly from the outer surface 46a of the head 42a of the stopper 10 that is less than the height of the outer ring of protrusions 52g adjacent to the outer surface 46a of the head 42a of the stopper 10 in a direction extending outwardly from the outer surface 46a of the protrusions 52g.

[0100] As an alternative to the above projection configuration, if the outer surface 46b of the head 42b of the stopper 10 is conical (FIG. 16), a single ring of projections 52i may be provided.

[0101] The projection 52i may have a substantially triangular shape, preferably having an apex 64 corresponding to an apex angle of the triangular shape of the projection 52i, a base 66 corresponding to the base of the triangular shape of the projection 52i, and two side surfaces 68a, 68b extending between the apex 64 and the base 66. The apex 64 of the projection 52i has a circumferential width that is less than the circumferential width of the base 66 of the projection 52i.

[0102] The apex 64 of each protrusion 52i is adjacent to the center of the outer surface 46 of the head 42 of the stopper 100, i.e., the origin of the outer circumference of the outer surface 46 of the head 42 of the stopper 100, which corresponds to the apex of the cone of the head 42 of the stopper 100, and the base 66 of each protrusion 52i is adjacent to the outer circumference of the outer surface 46 of the head 42 of the stopper 100.

[0103] The base 66 of the projection 52i may be rounded to correspond to the rounded outer periphery of the outer surface 46 of the head 42 of the stopper 100. A space 70 may be provided between the base 66 of the projection 52i and the outer periphery of the head 42 of the stopper 100 such that the projection 52i is spaced from the outer periphery of the outer surface 46 of the head 42 of the stopper 100 such that an annular portion of the outer surface 46 of the head 42 of the stopper 100 directly adjacent the outer periphery of the head 42 of the stopper 100 is not covered by the projection 52i.

[0104] The apex 64 of the projection 52i may be truncated such that a space 72 is provided in the center of the outer surface 46 of the head 42 of the stopper 100. The space 72 may be circular, and the truncated apex 64 of the projection 52i may be curved such that the apex 64 of the projection 52i defines a space 72 in the center of the outer surface 46 of the head 42 of the stopper 100 where it is not covered by the projection 52i.

[0105] The protrusions 52i may be evenly distributed around the circumference of the outer surface 46 of the head 42 of the stopper 100 such that corresponding substantially triangular spaces 74 are provided between adjacent protrusions 52i. Again, as with all of the above-described embodiments, the angular distance θs between two adjacent protrusions is less than or equal to the angular distance θp occupied by one of the protrusions, i.e., θs≦θp.

[0106] Sticking of the outer sidewall of the stopper body can also be an issue, therefore anti-stick features can also be included between the annular ribs on the outer sidewall of the stopper body.

[0107] 18, the substantially cylindrical stopper body 38 may include a plurality of annular ribs 54 along the periphery of an outer sidewall 58 of the stopper body 38. The ribs 54 may be evenly spaced apart from one another by grooves 56. The ribs 54 have a diameter Douter that is greater than a diameter Dinner of the grooves 56.

[0108] When the outer sidewalls 58 of the two stoppers 100 contact each other, the rib 54 of one stopper can be received in the groove 56 of the other stopper 100, and vice versa, resulting in complete contact between the outer sidewalls 58 of the stoppers 100 (FIG. 19).

[0109] To avoid such contact, a number of projections 61 extend radially outward from the outer sidewall 58 of the stopper body 38 within at least one of the grooves 56 (FIG. 20). Locating the projections 61 within the grooves 56 can reduce adhesion without interfering with the function of the ribs 54, which provide a seal with the inner sidewall of the syringe body 14 while reducing the force required to move the stopper 100 within the chamber 24 of the syringe 12.

[0110] The height Hprotrusion of the projection 61 extending radially outward from the groove 56 is set so that the height Hprotrusion is smaller than the diameter Dоuter of the stopper body 38 in the region of the rib 54 minus the diameter Diner of the stopper body in the region of the groove 56 divided by 2, i.e. Hprotrusion<(Dоuter-Diner) / 2. The diameter Dprotrusion of the stopper body 38 in the region of the projection 61 is the sum of the diameter Dinnar of the stopper body in the region of the groove 56 and the height Hprotrusion of the projection. Including a safety factor, it can be ensured that Hprotrusion<(Douter-Dinner) / 2.

[0111] A Monte Carlo simulation using Oracle® CrystalBall software (version 11.1.2.4.600) in Microsoft® Excel was performed to determine the appropriate number (spacing) of protrusions 61 around the periphery of stopper 100 and the height of protrusions 61 to provide the desired anti-stick properties. The following factors were used in the simulation:

[0112] Diameter Douter of the stopper body 38 in the region of the rib 54, Diameter Dinner of the stopper body 38 in the region of the groove 56 the diameter Dprotrusion of the stopper body 38 in the region of the projection 61, the percentage of deformation due to ovalization when the stopper 100 is placed under a force that may cause adhesion; the height Hprotrusion of the protrusion 61, and Safety factor for projection height fp A groove 56 having a diameter Dinner is represented by an ellipse having a major axis ainner and a minor axis binner centered at the origin (0,0) of the Cartesian coordinate system (x,y) as follows:

[0113]

number

[0114] Similarly, rib 54 having diameter Douter is represented by an ellipse with center at ((Dinner+Douter) / 2,0) and major axis aouter and minor axis bouter, as follows:

[0115]

number

[0116] When no external forces are applied (fdeformtion=0), in each of the above, both ellipses are circles, with their minor axes equal to their major axes.

[0117] Switching to polar coordinates with X=rcosθ and x=rsinθ, Equation 1 becomes:

[0118]

number

[0119] Dividing the right hand side of Equation 3 by 1 / ainner gives the equation of the groove ellipse, where ainner=Dinner / 2×(1-fdeformtion / 100) and binner=1 / ainner (constrained isotropic deformation):

[0120]

number

[0121] Similarly, with similar relationships as for the groove ellipse, Equation 2 for the rib ellipse can be switched to polar coordinates to obtain the following, where aouter=Douter / 2×(1−fdeformtion / 100) and bouter=1 / aouter.

[0122]

number

[0123] The positive roots router,1(θ) and router,2(θ) in this equation represent the envelopes of the rib ellipses, and for a given θ, d(θ), the distance between the two ellipses is

[0124]

number

[0125] The minimum angular distance between two protrusions 61 is approximated by the condition that for a given θ, Δθ is the 1° increment used during the simulation.

[0126]

number

[0127] Also,

[0128]

number

[0129] The following rib diameters Douter and groove diameters Dinner were used in the simulation.

[0130] [Table 1]

[0131] The isotropic ovalization parameter fdeformation was varied from 0% (no ovalization) to 10% (extreme ovalization, unlikely in real-world conditions). The protrusion height Hprotrusion was varied from 0.5 × (Douter / 2-Dinner / 2) to (Douter / 2-Dinner / 2), i.e., from 50% of the groove 56 depth to 100% of the groove 56 depth.

[0132] A Monte Carlo simulation was traditionally performed with 10,000 trials for each configuration, and the determined minimum angular distance between protrusions 61 for each stopper is shown in FIG.

[0133] Because the protrusions 61 in the ribs may affect stopper functions such as actuation and sliding forces or container closure integrity if the contact pressure between the barrel and the stopper is altered, a finite element analysis (FEA) was performed to determine the possible effect of the protrusions 61 on the stopper properties.

[0134] A 1 mL barrel (inner diameter 6.35 mm) was assembled with a 1 mL stopper having protrusions of a height equal to approximately 50% of the distance between the inner groove and the outer diameter of the rib. Six protrusions 61 were positioned 60° apart within each groove with a 30° offset between each successive groove. FEA analysis of the system showed that the inner surface of the barrel against the outer surface of the protrusions was clear, therefore no direct contact between the protrusions and the inner surface of the barrel was observed. The contact pressure of the stopper was indeed unaltered, and thus the function of the stopper was not affected by the protrusions.

[0135] 21, the angular spacing of the protrusions 61 is similar regardless of stopper design with a minimum of about 30°, a median of 40°-60°, and a maximum of 60°-80°. Based on the median, there are between 6 and 9 protrusions 61 around the circumference of the stopper to avoid sticking.

[0136] The projections 61 may be provided in multiple grooves with an offset spacing from groove 56 to groove 56 corresponding to half the angular distance between the projections to further minimize the contact area. For example, with six projections per groove 56, a first groove 56 would have projections 61 at 0°, 60°, 120°, 180°, 240°, and 300° around the circumference of the stopper 100, and a second groove 56 would have projections 61 at 30°, 90°, 150°, 210°, 270°, and 330° around the circumference of the stopper 100.

[0137] The height of the protrusion 61 may be 50% to less than 100% of the difference between the rib radius Douter / 2 and the groove radius Dinner / 2.

[0138] The projections 61 may be rounded with a convex outer surface, may have a substantially elliptical cross section, or may have any shape so long as the shape and dimensions of the projections 61 provide for prevention of adhesion of the outer sidewall 58 of one stopper 100 to the outer sidewall 58 of another stopper 100. For example, the projections 61 may have a cross section that is circular, elliptical, square, rectangular, or polygonal, and may have a flat outer surface or a rounded outer surface with straight sides. The rounded convex surface of the projection may be convex in all directions such that the projection has a dome shape.

[0139] The stopper can be made of any suitable material to facilitate movement of the stopper within the syringe barrel while still providing a seal between the stopper and the syringe barrel. Such materials include, but are not limited to, natural rubber, synthetic rubber, and more specifically rubber made from butyl, bromobutyl, chlorobutyl, silicone, nitrile, styrene butadiene, polychloroprene, ethylene propylene diene, fluoroelastomers, thermoplastic elastomers, and combinations and blends thereof, and are preferably made from butyl rubber, such as bromobutyl. The exterior surface of the stopper may optionally be coated with a suitable coating material. Such coating materials include, but are not limited to, coatings that act as a barrier between the stopper material and the pharmaceutical composition occupying the chamber 24 of the syringe 12, allowing for reduced extraction and / or leaching of substances from the stopper material, and reduced penetration of the pharmaceutical composition into the stopper material. For example, polytetrafluoroethylene (PTFE), ethylene tetrafluoroethylene (ETFE), expanded polytetrafluoroethylene (ePTFE), fluorinated ethylene propylene (FEP), polyfluoride, vinyl fluoride, perfluoropropyl vinyl ether, perfluoroalkoxy polymers, tetrafluoroethylene (TFE), parylene, or non-fluoropolymers such as polyethylene, polypropylene, parylene C, and parylene F, and / or a silicone layer for lubricity, reduced stickiness during processing of the vent tube, and / or protection of the stopper.

[0140] While particular embodiments of the invention have been described above for purposes of illustration, it will be apparent to those skilled in the art that many changes in the details of the invention can be made without departing from the invention.

Claims

1. A stopper for a syringe, a body having a proximal tail and a distal head adapted to be attached to a plunger rod of the syringe; a plurality of protrusions extending from an outer surface of the tail and / or the head; Equipped with The protrusions are arranged in at least one circle on the outer surface of the tail and / or the head of the stopper, and the angular distance between two adjacent protrusions in the circle is smaller than the angular distance occupied by one protrusion.

2. 2. The stopper of claim 1, wherein a cavity adapted to receive and engage at least a portion of the plunger rod of the syringe is defined within the body of the stopper, an opening to the cavity is provided in the tail of the stopper, and the protrusions are provided in the tail of the stopper and arranged in at least one circle on the outer surface of the tail of the stopper, extending from an annular ring on the outer surface of the tail of the stopper defined between the outer periphery of the end face of the tail and the outer periphery of the cavity.

3. 3. The stopper according to claim 1 or 2, wherein the protrusions are arranged in an outer circle along the periphery of the outer surface of the tail and / or the head of the stopper, and in at least one additional circle concentric with the outer circle, and the angular distance between two adjacent protrusions in each circle is smaller than the angular distance occupied by one of the protrusions.

4. a first circle of substantially cylindrical protrusions is provided on the tail and / or the head of the stopper adjacent to the outer periphery of the outer surface of the tail and / or the head of the stopper, and the number n1 of the protrusions provided on the first circle is: [Equation 1] wherein R is the outer diameter of the outer surface of the tail and / or the head of the stopper, β is the ratio (r / R) of the radius r of each protrusion to the radius R, and γ is a safety factor of the distance between the circle of the protrusion and the outer periphery of the end face of the head of the stopper.

5. At least one concentric circle of the protrusions is provided inside the first circle of the protrusions, and the number of protrusions provided on the i-th circle is [Equation 2] 5. The stopper according to claim 4, wherein Ri is the inner diameter of the (i-1)th circle of the projection.

6. A single circle of substantially cylindrical projections is provided, the minimum number of projections on said circle being: [Equation 3] where: [Equation 4] where Dp is the diameter of each protrusion, Do is the outer diameter of the periphery of the tail of the stopper, and Dc is the diameter of the periphery of the cavity; wherein the angular distance between the protrusions is: [Equation 5] 3. The stopper according to claim 2, wherein:

7. 3. The stopper according to claim 1, wherein the protrusions are arranged in an outer circle along the outer periphery of the outer surface of the head of the stopper, and the protrusions inside the outer circle are arranged at the center of the outer surface of the head of the stopper.

8. 3. A stopper according to claim 1 or 2, wherein the protrusions are equally spaced along each of the circles, the protrusions are substantially cylindrical, and / or the outer surface of the head of the stopper is flat, convex, or conical.

9. 3. The stopper according to claim 1, wherein the head of the stopper is convex, and a protrusion in a circle adjacent to the outer periphery of the outer surface of the head of the stopper has a height in a direction extending outward from the outer surface of the head of the stopper that is greater than a height in a direction extending outward from the outer surface of the head of the stopper of a protrusion located inside the circle adjacent to the outer periphery of the outer surface of the head of the stopper.

10. 3. A stopper as claimed in claim 1 or 2, wherein the head of the stopper is conical and has a substantially triangular shape, preferably a substantially isosceles triangular shape, with a vertex corresponding to the apex angle of the triangular shape of the protrusion, a base corresponding to the base of the triangular shape of the protrusion, and two sides extending between the vertex and the base, and a circle of the protrusion extending from an outer surface of the head of the stopper.

11. A stopper for a syringe, a body having a proximal tail adapted to be attached to a plunger rod of the syringe, a distal head, a plurality of annular ribs around the circumference of an outer sidewall of the body, and a plurality of grooves around the circumference of the outer sidewall of the body, the ribs being spaced apart from one another by the grooves; Equipped with a plurality of protrusions extending radially outward from the outer sidewall of the body from within at least one of the grooves.

12. 12. The stopper of claim 11, wherein the angular spacing of the protrusions within the at least one groove is 30° or more, the median angular spacing of the protrusions within the at least one groove is 40° to 60°, and / or the maximum angular spacing of the protrusions within the at least one groove is 60° to 80°.

13. 13. A stopper according to claim 11 or 12, wherein the projections are provided in a plurality of grooves with an offset spacing from groove to groove corresponding to half the angular distance between the projections in the respective grooves.

14. 13. The stopper according to claim 11 or 12, wherein the height of the protrusion in the radial direction is less than 50% to 100% of the difference between the radius of the rib and the radius of the groove.

15. A syringe, a syringe body defining a chamber; a plunger rod at least partially received within the chamber; a stopper according to claim 1 or 11 attached to an end of the plunger rod received in the chamber; A syringe equipped with

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