Closure for a container for pharmaceutical preparations and container provided with such closure

Description

[0001] The present invention relates generally to a closure for a container for pharmaceutical preparations and to a container for pharmaceutical preparations, in particular a syringe, provided with this closure. Containers for pharmaceutical preparations, in particular syringes, make a significant contribution to the administration of pharmaceutical preparations or medications. These generally cylindrically shaped containers comprise a chamber for receiving the preparation, which chamber is bounded on both sides by a proximal and a distal end. A piston can be inserted into the proximal end in order to push the preparation in a sliding movement in a distal direction and through an opening at the distal end of the syringe, or in a reverse, proximal movement to draw a preparation through this opening into the syringe. The opening at the distal end is often formed by a conical tip.Closures or closure systems for closing the distal opening of the container have been known for some time. For example, US Pat. Nos. 5,624,402 and 6,196,998 B1 describe such closures for closing the distal opening of a syringe. Further closure systems are described, for example, in EP 1 600 190 B1.

[0002] WO 2012 / 116791 A1 describes another closure for a syringe with a sealing element, wherein the closure has webs and projections that can engage with a syringe flange. EP 1 419 819 A1 describes a tamper-evident closure for a syringe. WO 2013 / 149821 A1 describes a closure system for an application device attachment. EP 3 015 130 A1 describes a protective cap for flow connectors for medical applications. Finally, US Pat. No. 9,821,152 B1 describes another closure assembly for syringes.

[0003] The known closures or closure systems have several disadvantages.

[0004] For example, known closures are often constructed in multiple parts, comprising an inner element made of a flexible material for sealing, and an outer element that connects to the container. A screw connection is often provided for this purpose. Unscrewing these multi-part closures is difficult if, as is known from the prior art, the inner element comes into contact with the container first during joining. This can easily lead to tilting or jamming at the beginning of the joining process, which impedes the required short process times for assembling the closure.

[0005] In addition, the inner element is often made of an elastomeric material, which may be contaminated during production, for example, with silicone oil. The closures are generally stored and transported in bulk. If this partially contaminated elastomeric material of the inner element comes into contact with an external thread of another closure or a container, this component may become contaminated. This can be critical for the assembly of the closure and also for subsequent opening, as specified forces and torques may no longer be reliably maintained, thus jeopardizing the reliability of the connection and thus of the entire product.

[0006] What would be desirable is a closure and a method for mounting this closure on the container that enables contamination-free and safe assembly with short process times.

[0007] Further disadvantages lie in the precision and characteristics of the tightening and / or opening torque required for mounting or releasing the closure on the container. Wide threads on the closure can lead to a consistently high opening torque, which the user must overcome, especially when loosening, i.e., opening the container.

[0008] It would therefore be desirable to provide a closure with an opening torque that allows a predetermined threshold value for opening the closure to be precisely provided, but at the same time simplifies the subsequent release.

[0009] Further problems lie in the high precision of the required spacing of the components required for sealing in the assembled position. Of great importance here is the axial distance between the sealing element and the container opening to be closed. The given shape and position tolerances can lead to a failure to meet the required minimum pressure for sealing, which could compromise the reliability of the product.

[0010] It would therefore be desirable to provide a closure that would allow the required minimum pressure to be reliably ensured to seal the opening of the container.

[0011] Further disadvantages lie in the color stability of the closure material, which is often plastic. This color stability is important because the closure and / or the container with the closure may be subjected to sterilization treatment, which can lead to color changes or other changes in the properties of the plastics involved.

[0012] It would therefore be desirable to provide a closure that allows the usual sterilization methods to be used without any visible change in color or other changes to the closure.

[0013] The inventors have taken up this task and provided a closure for a cylindrical container for pharmaceutical preparations, in particular a syringe, as well as a container for pharmaceutical preparations, in particular a syringe, provided with this closure, according to one of the independent claims.

[0014] The closure according to the invention avoids the above-mentioned disadvantages and therefore features several design improvements compared to known closures or closure systems. Preferred embodiments and further developments of the invention can be found in the respective subclaims.

[0015] Cylindrical containers for pharmaceutical preparations are typically elongated and have a central chamber, a proximal end on one side of the chamber, into which a plunger, for example, can be inserted, and an opposite distal end, which may include a tapered tip. The central axis of the container represents the longitudinal axis of the arrangements described below.

[0016] The distal end is generally elongated, tapering towards the distal end and has an opening in the form of a narrow passage through which, for example, liquid pharmaceutical preparations can be expelled from the chamber, provided the piston is moved accordingly. Conversely, liquid preparations can also be drawn in if the piston is moved in the opposite direction, i.e., towards the proximal end. In the pharmaceutical field, these cylindrical containers are known as syringes or cannulas and can be made of glass or plastic. The closure according to the invention is fundamentally suitable for containers made of both glass and plastic. The pharmaceutical preparations can comprise liquids, gases, solids, or mixtures thereof.

[0017] For attaching a needle cannula, for example, to the distal end of the container, a device known as a Luer-Lock has become established in the medical field. For plastic containers, this Luer-Lock attachment can be integrally formed with the container, such as a cuff or collar, and at least partially surround the tip of the container. This Luer-Lock attachment can comprise a cuff with an internal thread at the distal end of the container.

[0018] A closure is required to seal the opening at the distal end of the container or to close the tip passage, for example, to prevent contamination of the filled preparations or to prevent accidental loss of the preparation. The term "sealing" or "closing" refers to a pressure- and / or fluid-tight closure of the opening at the distal end of the container.

[0019] The present invention therefore relates to a closure for releasably closing an opening at the distal end of a cylindrical container for pharmaceutical preparations, in particular a syringe, preferably by means of a Luer-Lock fastening.

[0020] The closure according to the invention is particularly well suited for closing the opening of a distal end of the container, which is designed as a tip. The container is preferably made of plastic and comprises a sleeve with a Luer-Lock attachment with an internal thread.

[0021] The proposed closure includes: a cylindrical closure cap with a cylindrical cavity for receiving and holding a sealing element, wherein the closure cap comprises a mounting portion which, in the mounted position, points towards the container, a sealing element with a sealing portion which is arranged at least partially within the mounting portion, and wherein the outer edge of the sealing element has a setback relative to the outer edge of the mounting portion.

[0022] The outer edge of the sealing element here means the outer edge of the sealing element facing the container in the assembled position; the outer edge of the assembly section also means the outer edge of the closure facing the container in the assembled position.

[0023] The closure cap can be designed in one or more parts and, in a favorable embodiment, can comprise a mounting portion which is designed for connection to the container and thus points towards the container in the mounted position, and an oppositely arranged actuating portion which enables a user to grip the closure.

[0024] According to the invention, the mounting portion comprises an external thread which, in the assembled position, engages the Luer-Lock attachment of the container, thus creating a detachable connection. In the assembled position, the closure cap and container are arranged coaxially to the longitudinal axis. The closure according to the invention, with a sealing element inserted into the closure cap, is particularly suitable for mounting on a container with a Luer-Lock attachment, which comprises an internal thread for receiving a precisely matching external thread.

[0025] The actuating portion can preferably be equipped with external ribs for improved handling by the user. The cylindrical cavity of the closure cap is designed to be continuous for easy placement and retention of a preferably one-piece sealing element, which can also be cylindrical and have an outer geometry that precisely matches the inner geometry of the cylindrical cavity of the closure cap. The sealing element is preferably made of an elastomeric material.

[0026] The recessed recess according to the invention makes it surprisingly easy to significantly improve the assembly process and increase process reliability, as tilting and jamming during the closure's placement on the container can be effectively prevented. This is due to the fact that during the joining process, the closure is first centered via the assembly section before the sealing element comes into contact with the container, particularly with the container's tip. Increasing assembly reliability is of great importance for manufacturing efficiency, especially in fully automated assembly processes and the high volumes required.

[0027] The recessed sealing element relative to the outer edge of the assembly section of the closure cap—in other words, a recessed sealing element on the assembly side of the closure relative to the outer edge—increases process reliability because the closure is centered during the screwing-in process before the sealing element comes into contact with the container. Existing closures on the market, in contrast, feature a sealing element that protrudes from the closure cap in the assembly direction. During assembly, the initial contact between the sealing element and the container then occurs, making the desired centering difficult or even impossible.

[0028] In this case, the first contact for mounting the sealing element with the tip of the container only occurs after the closure and container have been centered, so that a purely axial sliding of the sealing element is possible, which is less prone to errors.

[0029] At the same time, the recessed sealing element also reduces contamination of other closures or the container itself, for example, from manufacturing residues that can accumulate on the surface of the sealing element. This can include, for example, fluids used in the production of the sealing elements, such as silicone oil, which can accumulate on the outside of the sealing element. This is often the case with sealing elements made of an elastomeric material.

[0030] Closures with the sealing element are often stored, transported, and delivered as bulk goods in several thousand pieces in a package, such as a bag. If the sealing element protrudes from the closure, it can, if contaminated, contaminate other closures in the bulk goods through contact. For example, siliconized sealing elements contaminated with silicone oil in the packaging can come into contact with other, non-siliconized closures. A non-siliconized closure can become contaminated with silicone oil through contact.

[0031] If, for example, an external thread of another closure cap becomes contaminated with silicone oil, this contamination is detrimental during transport or subsequent processes, such as separating, gripping, or placing the closure on the container for assembly on the corresponding machine. This unwanted contamination can be counteracted by setting the sealing element back.

[0032] Contamination of the external thread of the closure cap also has disadvantages on the product side, for example, with regard to the tightening torque required for assembly and the subsequent loosening or opening torque required for removal. For example, if a contaminated sealing element comes into contact with an external thread, the tightening torque can be significantly reduced or subject to significant fluctuations.

[0033] With regard to the container, the reliability of the container closed with the closure can be increased by reducing the risk of contamination if it can be safely ruled out that manufacturing residues of the sealing element can be deposited on a thread, for example during the manufacturing and / or assembly process.

[0034] For example, tests have shown that tightening torque and opening torque begin to vary significantly due to contamination of the external thread. This means that a specified torque can no longer be maintained. The measured variation of the tightening torque for contaminated closures can be more than 0.5 N*cm, more than 1.0 N*cm, or even more than 1.5 N*cm. The variation of the opening torque for contaminated closures can be between 2 and 16 N*cm, between 2 and 18 N*cm, or even between 2 and 20 N*cm. Such large variations are detrimental to the user.

[0035] It is therefore advantageous to provide such a recess of the sealing element relative to the outer edge of the actuating section on the opposite side of the closure cap in order to reduce the risk of contamination.

[0036] According to the invention, therefore, not only a contribution is made to increasing process reliability, but also to the product reliability of containers for pharmaceutical preparations. A closure can be provided in which the tightening torque and / or the opening torque exhibit a small deviation of + / - 1.0 N*cm, preferably + / - 0.5 N*cm, from the required or desired torque.

[0037] This is achieved by designing the length of the sealing element such that the potentially contaminated sealing elements cannot come into contact with other closure caps. The length of the sealing element along the longitudinal axis is thus advantageously shorter than the length of the closure cap. In a preferred embodiment, the length of the sealing element is at most 95%, preferably at most 90%, and particularly preferably at most 85%, of the length of the closure cap.

[0038] The assembly and disassembly behavior of the closure cap is largely determined by the design of the external thread of the closure cap. If the container has a Luer-Lock attachment, a special design of the external thread of the closure cap can enable easier and more precise assembly, which can also increase process safety and product reliability.

[0039] For this purpose, the external thread of the closure cap can be designed according to the current ISO 594-2 standard. However, according to the invention, a special thread design, preferably a different shape of the thread flank, is provided, which results in a different engagement of the external thread with the internal thread of a Luerlock connection. In a preferred embodiment, the invention provides for the thread flank to be narrower and / or with a steeper flank, which, with the same pitch, leads to a greater distance between the thread flanks and thus to less axial play of the closure cap when it is only partially screwed into a Luerlock connection.

[0040] The thread is preferably designed as a trapezoidal thread, preferably with an outer or crest width ("thread crest width") of approximately 0.6 mm and a core width ("maximum width of base") of approximately 1.2 mm. This initially leads to easier screwing of the closure onto the container, as the frictional forces acting are lower. Other design parameters of the thread preferably remain the same, such as the thread pitch.

[0041] An advantageous thread pitch within the meaning of the invention is between 3 and 5.5 mm, preferably between 3.5 and 5.25 mm and particularly preferably between 4 and 5 mm.

[0042] This also makes it possible to provide a protrusion, preferably in the form of a point, on the thread flank at at least one specific position, which protrudes approximately between 0.5 and 1.5 mm from the flank. Preferably, at least two protrusions are provided, arranged at opposite positions on the thread flank. Two protrusions arranged opposite one another can thus form a so-called protrusion pair. Such a protrusion pair is preferably arranged such that, in the assembled position, the protrusion points then rest against the thread flank of the Luer Lock fastening and are preferably slightly compressed or deformed in the process. This introduces an additional force component into the connection between the closure and the container. Compared to a single protrusion, a protrusion pair offers the advantage that this additional force component does not act on one side.

[0043] This force component also acts upon opening the closure, allowing a precise, predefined threshold value for opening the closure. This provides a better, user-friendly characteristic for the opening torque required to release the closure from the container.

[0044] For a uniform force application, it is advantageous to provide more than one pair of protrusions, preferably two, particularly preferably four. This can contribute to a uniform and secure fit of the closure on the container. This further facilitates the precise adjustment of the torque required for assembly and / or release, as well as ensuring a predetermined force distribution during the rotational movement.

[0045] In general, when fitting a closure to containers used for pharmaceutical preparations, it is important to ensure that the prescribed forces are precisely adhered to, as exceeding or falling below these values can quickly have an adverse effect on product safety.

[0046] The external thread of the closure cap designed according to the invention makes it possible to maintain a very tight assembly torque of, for example, 18.0 N*cm with a tolerance of + / - 1.0 N*cm, preferably + / - 0.5 N*cm. This is important because a tightening torque of more than approximately 20 N*cm can lead to microcracking in Luer-Lock fasteners, particularly those made of plastic. This can lead to failure of the container and / or the closure, thereby compromising product reliability. If the tightening torque is less than 16 N*cm, tightness can hardly be guaranteed for tips with a small Luer-Lock projection.

[0047] The special design of the thread also means that when opening the closure, a higher force component must initially be applied to loosen it, after which this force component steadily decreases. This makes it easier for the user to open the container and loosen the closure. The torque required by the user therefore depends on the opening angle, i.e. the orientation of the closure to the container. After overcoming an initial resistance at the start of the loosening process, which occurs as a result of the additional force component due to the compression of the raised points, the applied force component decreases due to the narrower thread turns, which offer the raised points more freedom after loosening, so that the raised points are compressed less or, preferably, no longer. In this way, the torque required for further loosening is reduced.This allows a precise opening torque of, for example, 16 N*cm to be set with an accuracy of + / - 0.5 N*cm.

[0048] Thus, the release behavior of the closure according to the invention also differs from known closures, in which the force component required at the beginning of the release hardly decreases during the release of the closure. This is due to the fact that known closures often provide a bulge in the thread for an additional force component, which then acts throughout the entire release process due to the wider thread. This characteristic of the torque required for release is rather disadvantageous for the user, since a higher torque must be applied for almost the entire opening process.

[0049] According to the invention, the assembly of the closure is further simplified by the fact that the thread is narrower, as explained above, which increases and thus facilitates the possible angular orientation, i.e. the correct angular alignment of the closure and the container to one another at the beginning of the assembly.

[0050] To further expand this tolerance range for the required angular orientation, a preferred embodiment provides a bulge in the thread section adjacent to the thread entry to increase the clearance from the outer edge to the first thread, thereby further increasing the tolerance range for the angular orientation. This bulge thus represents a slight axial offset of the thread in said section. Due to the narrower thread, this bulge can also be advantageously designed in such a way that no additional force component acts on the connection.

[0051] A narrow tolerance range for the correct angular placement and screwing of the closure onto the container is therefore not necessary. Rather, a larger angular range is available within which assembly can take place. While with known closures this tolerance range with regard to correct angular assembly, i.e. a deviation from the ideal orientation during joining, is less than + / - 3°, the inventive design of the thread entry makes it possible to extend this angular tolerance to a range of + / - 10° or even beyond. Depending on the specific design, this inventive angular tolerance can be in a range between + / - 5° and + / - 15°, preferably between + / - 8° and + / - 12°. This leads to significantly more favorable assembly behavior, since the effort required for the exact orientation of the closure in relation to the container can be reduced.

[0052] In a likewise preferred embodiment, the threaded entry can additionally include a chamfer or the threaded entry can be designed as a chamfer. While known closures have an external thread with a blunt thread entry, which can very quickly lead to jamming during the initial assembly, this insertion bevel or chamfer at the thread entry considerably facilitates assembly.

[0053] The reliability of the container for pharmaceutical preparations provided with the closure according to the invention is further influenced by the accuracy of fit of those components that ensure the tightness of the container opening. Of crucial importance here is the axial distance between a radially outwardly projecting stop of the closure cap, which in the assembled position rests against the container, in particular against the collar of the Luer Lock fastening, and the inner edge of a sealing section of the sealing element, which seals the opening of the tip. In the assembled position, the sealing section of the sealing element lies closely against the opening, in particular against the tip, and / or encloses the opening. A minimum pressure must be observed, which can be adjusted via the shape and position tolerances of the components involved.

[0054] For axial positioning of the sealing element in the opening of the closure cap, the latter is preferably formed with a radially inwardly projecting, circumferential shoulder. The sealing element advantageously has a circumferential recess on its outer surface, which is preferably positioned such that, in the assembled position, the shoulder of the closure cap can engage in the recess of the sealing element and cause locking by this axial stop. In this way, precise positioning of the sealing element, and thus of the inner edge of the sealing element, which seals the opening of the container, can be achieved with respect to the container in the assembled position.

[0055] For common containers, especially for common syringes, an assembly dimension of 2.85 mm with a very tight tolerance is required for the axial distance between the outwardly protruding stop of the closure cap, also referred to as the outer stop, and the stop defined by the shoulder within the opening of the closure cap, also referred to as the inner stop. The inner stop acts in the opposite direction to the minimum pressure required for sealing of the sealing element and thus determines the sealing force acting on the opening of the tip.

[0056] Therefore, maintaining a very tight tolerance for this inner and outer stop is of utmost importance for the design of the closure. According to the invention, maintaining this tolerance is achieved through various design measures.

[0057] Firstly, in a preferred embodiment, the closure cap is designed such that the side wall has a thin and, above all, uniform material thickness over the length of the closure cap. Preferably, the wall thickness of the closure cap, i.e., the thickness of the wall, at its thickest point is at most 2.5 mm, preferably at most 2.0 mm. The wall thickness fluctuates by no more than 0.5 mm, preferably by no more than 0.3 mm, over the entire length of the closure cap.

[0058] Maintaining this dimension is no small feat. Caps are generally made of thermoplastics using the injection molding process. This results in higher temperatures during the primary forming process, which can lead to dimensional deviations in the cap after cooling. A consistent wall thickness leads to homogeneous cooling and thus reduces potential warpage.

[0059] Furthermore, according to the invention, the injection molding process is optimized by selecting an injection point located in the region of the actuating section. The injection point is particularly advantageously located on the outside of the lateral surface of the actuating section, axially spaced from an outer rib. This also counteracts a potential risk of injury to a user, as sharp edges can be created by the sprue. However, an injection point on one of the outer ribs is not preferred, as this can lead to warping of the thin-walled closure cap.

[0060] The method according to the invention makes it possible to produce the closure cap by injection molding in very high quantities with a very tight dimensional tolerance, which is partly due to the thin and uniform wall thickness and the optimized position of the injection point.

[0061] To continue to maintain the tight tolerance mentioned above, it is also helpful that the sealing element is precisely held in the closure cap. In particular, unintentional axial movement of the sealing element relative to the closure cap, which could occur during seating and / or assembly, should be avoided as far as possible.

[0062] The sealing element can be secured against rotation in the through-opening of the closure cap by at least two elongated inner ribs, which are arranged axially in their main orientation and project radially inward, on the inner wall of the opening, preferably in the region of the actuating section. Typically, approximately 6 to 10 such inner ribs are provided, and frequently 8 regularly arranged inner ribs. These inner ribs can advantageously be distributed at equal intervals around the inner circumference to ensure uniform pressure. These inner ribs therefore serve to counteract any rotation of the sealing element in the closure cap, for example during assembly or opening, and thus provide an anti-rotation feature.

[0063] Due to the injection-molded nature of the closure cap, these inner ribs may exhibit a draft angle in the longitudinal, i.e., axial, direction. However, this inclination of the inner ribs creates a force component acting axially on the sealing element, which can result in an axial movement of the sealing element from its intended position. Despite the internal stop, this movement can lead to an unwanted axial offset of the sealing element of 0.3 mm or even more relative to the predetermined seating height.

[0064] This offset influences the axial distance described above between the stop of the closure cap and the inner edge of the sealing section of the sealing element, meaning that the specified dimension cannot always be reliably maintained. This can also lead to the minimum pressure between the sealing element and the tip of the container not being achieved, meaning that the required tightness may not be maintained and the required reliability of the container may not be guaranteed. When using screw connections for pharmaceutical packaging, for example, there is a minimum requirement that the connection must withstand a pressure of at least 3 bar for a period of 30 seconds.

[0065] On the other hand, the required opening torque, which is at least 2 N*cm for screw caps in the pharmaceutical sector, may not be met if the required distance and minimum pressure are not observed.

[0066] While known closures often use wide and rather flat inner ribs, the invention provides a different, narrower design of the inner ribs, which results in a significantly smaller displacement volume at the sealing element, especially with an otherwise identical number of inner ribs. This can significantly reduce the tendency of a sealing element mounted in the closure cap to experience axial misalignment, so that the required spacing can be maintained more precisely after the sealing element is installed. A large displacement volume, on the other hand, leads to strong compression of the sealing element and thus promotes undesirable axial misalignment.

[0067] The axial offset of the sealing element in the opening of the closure cap can be limited to less than 0.3 mm, preferably to less than 0.2 mm and particularly preferably to less than 0.15 mm by the inner rib designed according to the invention.

[0068] For this purpose, the inner rib has a width of less than 1 mm, preferably less than 0.9 mm, and particularly preferably less than 0.8 mm. Furthermore, the width or cross-section of the inner rib is particularly advantageously constant over a large part of the length of the inner rib, in particular over a length of at least 50% of the length of the inner rib, preferably over a length of at least 60%, and particularly preferably at least 65%. This also significantly reduces the tendency toward axial displacement of the sealing element in the closure cap.

[0069] This makes it possible to maintain the required minimum compression to seal the opening. A closure cap can be provided in which the axial distance between the outer stop and the inner stop of the closure cap is 2.85 mm with a tolerance of + / - 0.2 mm, preferably + / - 0.1 mm, and particularly preferably + / - 0.05 mm. This ensures that the required minimum compression to seal the opening can be reliably maintained.

[0070] The actuating section can furthermore particularly advantageously comprise at least two elongated outer ribs which are arranged axially in their main orientation and protrude radially outwards from the outer surface, which offer a user a better grip and thus facilitate screwing and unscrewing. Narrow outer ribs are advantageously provided here, which extend over almost the entire length of the actuating section. In a favorable embodiment, these outer ribs have a length, i.e. an extension in the axial direction, of at least 4.5 mm, preferably of at least 5.0 mm. The height of these outer ribs, i.e. the radial projection relative to the outer surface, is advantageously at least 0.3 mm, so that the user finds a stable gripping surface and can therefore open the closure better and more easily.

[0071] The reliability and usability of the container for pharmaceutical preparations provided with the closure according to the invention are further determined by the color stability of the container, and in particular of the container provided with the closure according to the invention. Since closures are typically manufactured in large quantities using injection molding processes, suitable thermoplastics are the materials considered for this purpose.

[0072] Color stability is of great importance because the closure and / or the container with the closure can be subjected to sterilization treatment, which can lead to color changes or other material changes in the plastics involved. Sterilization serves to rid pharmaceutical packaging, for example, containers with pharmaceutical preparations, of as many microorganisms as possible that are contained or adhere to them.

[0073] Various sterilization methods are available, including hot air sterilization. This is a physical sterilization process in which thermostable medical devices are exposed to dry heat. To eliminate germs such as bacteria, fungi, viruses, or spores, temperatures of at least 180°C are required for a period of at least 30 minutes.

[0074] Furthermore, autoclaving is known as the most commonly used sterilization method. It uses steam at temperatures of, for example, 120 °C at 0.5 bar. This allows sensitive products to remain in the autoclave longer than with hot air sterilization.

[0075] In addition, the steam is distributed more effectively over the product surface, which helps to achieve the required sterilization temperature across the entire product.

[0076] Irradiation with electromagnetic radiation, such as gamma rays or X-rays, is also known. In so-called gamma sterilization, pharmaceutical preparations are irradiated with gamma rays at a specific energy dose. When using gamma rays or X-rays, the irradiation is generally carried out with an energy dose in the range of 25-40 kGy.

[0077] Most known sterilization methods restrict the choice of materials, such as the closure material, to minimize certain effects, such as the color or consistency of the material. In other words, irradiation of the closure, for example, can alter the polymer structure of a plastic used, which can subsequently lead to color changes. Certain sensitive thermoplastics can also suffer from the high temperatures sometimes required and, for example, become brittle or change color.

[0078] While a color change as a result of sterilization may be desirable for certain applications, it is assumed within the scope of this invention that a color change of the closure is undesirable. Regardless of the type of sterilization, i.e., when using at least one of the aforementioned sterilization methods, a "color shift," i.e., no color change of the closure, should occur if possible. For the purposes of the present invention, a color change is considered undesirable if the color coordinate of the material after sterilization deviates from that before sterilization by a value ΔE, determined as a color coordinate change in the CIE 1931 system, by more than ΔE = 0.05. The color coordinate change ΔE is given by the following formula: Δ E = x 2 + y 2

[0079] According to the invention, in a preferred embodiment, a material is selected for the closure which hardly or preferably does not change color as a result of sterilization.

[0080] This is achieved, quite surprisingly, by selecting specific color pigments and antioxidants for the material used to manufacture the closure. The inventors have discovered that a very specific material composition, comprising certain selected pigments that impart a gray-green color appearance to the closure, has little or no tendency to change color when using one of the above-mentioned sterilization methods. Instead, the original color is at least virtually retained, and preferably, no color shift occurs. This color corresponds to the color RAL 7009 according to the RAL color system.

[0081] This surprising color-stable effect is achieved by finding a composition of coloring pigments that results in a polymer structure of the plastic that is stable both at elevated temperatures and when exposed to electromagnetic radiation, as described above. A material for manufacturing the closure comprises the following pigments as coloring elements: Titanium dioxide Kronos ®< 2233 Carbon black PRINTEX ®< F 85 6975 Titanium orange VYNAMON ®< Green 600734

[0082] A closure made of a material containing these pigments for coloration is therefore also suitable for sterilization processes that use gamma or X-ray radiation. It has been shown that such closures, when exposed to an energy dose in the range of 25-40 kGy, result in no or barely perceptible color changes to the human eye, and can therefore be considered color-stable.

[0083] It is particularly advantageous that such a material composition also leads to no or hardly perceptible color changes with the human eye when subjected to other sterilization methods, such as hot steam sterilization at up to 134 °C for a period of 10 minutes.

[0084] This is particularly advantageous because the sterilization method to be used can be selected largely independently of the closure material. Even a combination of the above-mentioned sterilization methods does not lead to a reduction in tightness. In particular, after sterilization, the closure maintains a tight seal up to 4 bar for 30 seconds and has an opening torque of less than 15 N*cm.

[0085] Finally, in a further aspect, the invention relates to a method for the contamination-free, releasable closure of a distal end of a cylindrical container for pharmaceutical preparations, preferably a syringe, in particular with a closure as described above.

[0086] The invention is described in more detail below using preferred embodiments and with reference to the attached figures. The drawings show:

[0087] Fig. 1 shows a longitudinal section through a closure according to the prior art, Fig. 2 shows a longitudinal section through a closure according to the invention, Fig. 3 shows a longitudinal section through a container for pharmaceutical preparations which has a Luer-Lock fastening, with a partially mounted closure, Fig. 4 shows a course of the torque when opening a closure according to the invention to release it from the container, Fig. 5 shows a course of the torque when opening a closure known from the prior art to release it from the container, Fig. 6 shows a plan view of a section of a closure according to the invention with a bulge, Fig. 7 shows a longitudinal section through a closure according to the invention with a sealing element, Fig. 8 shows a longitudinal section through a closure according to the invention without a sealing element, Fig. 9 shows an oblique view of a closure according to the invention. Detailed description of preferred embodiments

[0088] In the following detailed description of preferred embodiments, for the sake of clarity, like reference numerals designate substantially like parts in or on these embodiments. However, to better illustrate the invention, the preferred embodiments illustrated in the figures are not always drawn to scale.

[0089] Fig. 1 shows a longitudinal section through a closure 100 according to the prior art. This closure 100 comprises a cylindrical closure cap 110 with a cylindrical cavity for receiving a sealing element 120, wherein the closure cap 110 comprises a mounting portion 140, which in the mounted position faces the container, and an actuating portion 150.

[0090] The sealing element 120, which has a sealing section 121, is inserted into the cylindrical cavity of the closure cap 110. It is clearly visible that the outer edge 122 of the sealing section protrudes beyond the outer edge 112 of the closure cap 110. This is disadvantageous for automated assembly, as it can lead to tilting and jamming during placement at the beginning of assembly when the sealing element first comes into contact with the container, in particular with the tip of the container. Centering of the closure during the screwing-in process is also hardly possible, as the sealing element 120 is made of a flexible elastomeric material. Particularly in fully automated assembly processes and the required high volumes, valuable time can be lost if the assembly must be carried out particularly slowly or, for example, must be repeated after jamming.

[0091] Fig. 2shows a longitudinal section through a closure 1 according to the invention for releasably closing an opening at the distal end of a cylindrical container for pharmaceutical preparations (not shown), in particular a syringe, preferably by means of a Luer lock fastening. The closure 1 according to the invention comprises a cylindrical closure cap 10 with a continuous cylindrical cavity 14 for receiving a sealing element 20, wherein the closure cap 10 comprises a mounting portion 40, which in the mounted position faces the container, and an actuating portion 50.

[0092] The mounting portion 40 includes an external thread 41, which, in the mounted position, engages the external thread of the Luer-Lock attachment of the container and creates a detachable connection therewith. The actuating portion 50 is equipped with external ribs for handling by a user. The cylindrical cavity 14 of the closure cap 10 is formed continuously to accommodate the sealing element 20, which in the example is a one-piece.

[0093] The illustration clearly shows the clear offset of the outer edge 22 of the sealing element 20 compared to the outer edge 12 of the mounting section 40 of the closure cap 10.

[0094] The recess according to the invention makes it surprisingly easy to significantly improve the assembly process and increase process reliability, as tilting and jamming during the placement of the closure 1 onto the container or at the beginning of the assembly process can be effectively prevented. This is due to the fact that during joining, the closure 1 is first centered via the assembly section 40 before the sealing element 20 comes into contact with the container, in particular with the tip of the container. Especially in fully automated assembly processes and the required high volumes, increasing assembly reliability is of great importance for manufacturing efficiency and can help save valuable time during assembly.

[0095] The offset of the sealing element 20 relative to the outer edge 12 of the mounting section 40 of the closure cap 10 thus increases process reliability, since the closure 1 is centered during the screwing-in process before the sealing element 20 comes into contact with the container. In this case, the first contact of the sealing element 20 with the tip of the container occurs only after the closure 10 and the container have been centered, allowing purely axial sliding on, which is less prone to errors.

[0096] At the same time, the recess also reduces the contamination of other closures or the container by manufacturing residues that may be present on or at the sealing element 20. These residues may, for example, be fluids used in the manufacture of the sealing elements, such as silicone oil. This is often the case, especially with sealing elements made of an elastomeric material, as in the present case.

[0097] In this example, the setback is approximately 2.5 mm. The risk of contamination can be reduced if the setback is at least 0.5 mm, preferably at least 1.0 mm, and particularly preferably at least 1.5 mm. In conjunction with the given tolerances, a favorable setback range is also achieved in the range of 1.5 to 2.0 mm, 2.0 to 2.5 mm, or 2.5 to 3.0 mm.

[0098] In the Fig. 2 It can also be seen that a setback of the outer edge 23 of the sealing element 20 relative to the outer edge 13 of the closure cap 10 is also provided. This setback is preferably also at least 0.5 mm, preferably at least 1 mm, and particularly preferably at least 1.5 mm. In the example, the setback is approximately 2.5 mm and is thus approximately the same size as the setback on the opposite side.

[0099] The bilateral offset of the outer edges 22, 23 of the sealing element 20 relative to the outer edges 12, 13 of the closure cap 10 therefore reliably prevents mutual contamination of adjacent closures, for example in transport packaging. This is achieved structurally by a reduced length of the sealing element 20 compared to the length of the closure cap 10. In the example, the ratio of the length of the sealing element to the length of the closure cap is approximately 70%. A ratio of the length of the sealing element 20 to the length of the closure cap 10 of at most 95%, preferably at most 90%, and particularly preferably at most 85% has proven advantageous.

[0100] The assembly and disassembly behavior of the closure 1 on the container is determined to a large extent by the design of the external thread of the closure cap 10.

[0101] Fig. 3shows a longitudinal section of a container 30 for pharmaceutical preparations, which has a Luer-Lock attachment, with a partially assembled closure 1. The container 30 comprises a sleeve 31 at its distal end, which is formed with an internal thread 32 and represents the Luer-Lock attachment. The sleeve 31 encloses a conically tapered tip 33 at the distal end of the container, which has an opening 34, for example for expelling a preparation from the chamber 35.

[0102] The external thread 41 of the mounting section 40 is formed to precisely match the internal thread 32. The external thread 41 is formed according to the current standard ISO 594-2, although the invention provides a different shape for the rib 42. The rib 42 according to the invention is narrower and / or has a steeper flank, which results in a narrower thread pitch and thus a greater distance between the adjacent thread flanks. This initially leads to easier screwing of the closure 1 onto the container 30, since the frictional forces acting are lower.

[0103] This also makes it possible to provide elevations, preferably in the form of points (not shown), at specific positions on the thread flank, preferably arranged at two opposite positions on the thread flank. Two oppositely arranged elevations can thus form a pair of elevations. Such a pair of elevations is designed such that, in the assembled position, the elevation points then rest against the thread flank of the Luer-Lock fastening and are slightly compressed or deformed. This introduces an additional force component into the connection.

[0104] This force component also acts equally when opening the closure, thus making it possible to precisely provide a predefined threshold value for opening the closure. This allows for a better, user-friendly characteristic of the opening torque. In the example, the external thread 41 comprises a total of four pairs of protrusions (not shown).

[0105] This further facilitates the precise adjustment of the torque required for assembly and / or loosening, as well as ensuring a predetermined force distribution during the rotational movement.

[0106] The Figs. 4 and 5 show, using exemplary embodiments, the course of the torque when opening the closure 1 to release it from the container 30. In Fig. 5 a characteristic for the opening torque of a closure 100 according to the prior art is shown, in Fig. 4the characteristic for the opening torque for a closure according to the invention 1.

[0107] It is clearly evident that when opening the closure 1 according to the invention, a higher force component must be applied initially to effect release. If a threshold value is exceeded, the force component to be applied continuously decreases. This makes it easier for the user to open the container 30 and release the closure 1. The torque to be applied therefore depends on the opening angle. After overcoming an initial resistance during release, which occurs as a result of the elevations, the applied force component decreases due to the narrower threads, which offer more clearance, so that the elevations are less compressed. In this way, it is also possible to set a precise torque for opening, for example, 16 N*cm with an accuracy of + / -0.5 N*cm.

[0108] Thus, the release behavior of the closure 1 according to the invention differs from closures 100 known from the prior art, in which the force components required at the beginning of the release hardly decrease during the release of the closure and remain at a high level until the end. Based on the force curve in Fig. 5 This is clearly visible. This is due to the fact that the closure 100 provides a bulge in the thread for an additional force component, which then acts throughout the entire loosening process. This characteristic of the torque required for loosening is rather disadvantageous for the user, since a higher torque must be applied for almost the entire opening process.

[0109] According to the invention, the assembly of the closure is further simplified by the fact that the thread 41 is, on the one hand, narrower, which increases and thus facilitates the possible angular orientation, i.e., the correct angular alignment of the closure and container to one another at the beginning of assembly. To further expand this tolerance range of the required angular orientation, a preferred embodiment provides for a bulge in the section of the thread adjacent to the thread entry to increase the clearance from the outer edge to the first thread, thereby further increasing the tolerance range of the angular orientation.

[0110] Fig. 6shows a plan view of a section of a closure 1 with a bulge 44. This slight axial offset of the thread, which represents the bulge 44, forms an additional free space 45 in a section located adjacent to the thread entry. This increases the tolerance range of the angular orientation. In other words, the range that specifies the required orientation of closure 1 and container 30 prior to joining is expanded. The inventive design of the thread entry in the illustrated embodiment makes it possible to expand this angular tolerance to a range of + / - 10°. According to the invention, it is possible to set the angular tolerance in a range between + / - 5° and + / - 15°, preferably between + / - 8° and + / - 12°. This leads to significantly more favorable assembly behavior.

[0111] In a likewise advantageous embodiment, the thread inlet 46 is additionally formed with a chamfer 47 in order to further facilitate joining.

[0112] The reliability of the container 30 provided with the closure 1 according to the invention is further influenced by the accuracy of fit of those components which ensure the tightness of the opening 34 of the container 30. Of crucial importance here is, as can be seen from the Fig. 3As can be seen, the axial distance between a radially outwardly projecting stop 11 of the closure cap 10, which in the assembled position bears against the container 30, in particular against the collar 36 of the Luer-Lock fastening 32, and the inner edge 24 of a sealing section 21 of the sealing element 20, which seals the opening 34 of the tip 33. In the assembled position, the sealing section 21 lies closely against the tip 33 and encloses the opening 34, with the inner edge 24 bearing against the opening 34 with a predetermined minimum pressure.

[0113] For axial positioning of the sealing element 20 in the opening 14 of the closure cap 10, the closure cap is formed with a radially inwardly projecting, circumferential shoulder 15. The sealing element 20 also has a circumferential recess 25 on its outer surface, which is positioned such that, in the assembled position, the shoulder 15 engages in the recess 25 and creates an axial stop. In this way, precise positioning of the sealing element 20 and thus of the inner edge 24, which seals the opening 34 of the container 30 (not shown), can be achieved.

[0114] Fig. 7shows these relationships using a longitudinal section through a closure 1 according to the invention with a sealing element 20. In the illustration, "S" indicates the so-called settling dimension, i.e., the distance that occurs in the assembled position of the closure between the inner edge 24 of the sealing element 20 and the container 30. This is crucial for achieving the required minimum pressure to seal the opening.

[0115] Fig. 8clarifies these relationships again using a longitudinal section through a closure 1 according to the invention, which in the illustration does not have a sealing element 20. In order to maintain this settling dimension, a specific distance "A" is required between the outer edge of the outwardly projecting stop 11 of the closure cap 10 facing the container, which thus rests on the collar of the container in the assembled position, and a stop 16 defined by the shoulder 15 within the opening 14 of the closure cap 10. In the example, an assembly dimension of A = 2.85 mm with a very small tolerance is required. The inner stop 16 effects the minimum pressure of the sealing element 20 on the opening to be applied for sealing.

[0116] The closure cap 10 is designed to ensure a thin and, above all, uniform material thickness of the side wall over as much of the entire length of the closure cap as possible, in order to achieve high dimensional accuracy. Therefore, the wall thickness of the closure cap 10, i.e., the thickness of the wall, is a maximum of 2.0 mm at its thickest point. The wall thickness fluctuates by no more than 0.5 mm, preferably by no more than 0.3 mm, over the entire length of the closure cap.

[0117] Furthermore, according to the invention, the injection molding process is optimized in that an injection point is selected which lies in the area of the actuating section 50. The Fig. 9shows an oblique view of a closure 1 according to the invention, wherein the injection point for the injection molding process is marked with the letter "E" in the illustrated example. The injection point is thus located on the outside of the lateral surface of the actuating portion 50, axially spaced from an outer rib 53. This can also counteract a potential risk of injury to a user, since the sprue can create sharp edges that protrude when grasped. In this case, these potential sprue edges are located outside the gripping area.

[0118] The rotationally secure retention of the sealing element 20 in the through opening 14 of the closure cap is achieved by elongated inner ribs 51 on the inner wall of the opening 14 of the actuating section 50, which are arranged axially in their main orientation and project radially inward. These ribs are distributed at equal intervals around the inner circumference to ensure uniform pressure. In the example shown, a total of eight such inner ribs 51 are provided.

[0119] According to the invention, a narrow design of the inner ribs 51 is provided, which leads to a significantly smaller displacement volume at an inserted sealing element 20. This greatly reduces the tendency of a sealing element 20 mounted in the closure cap 10 to axially offset, so that the required distance after setting the sealing element, i.e., the setting dimension for maintaining the minimum compression, can be precisely maintained. The axial offset of the sealing element in the opening of the closure cap is limited to less than 0.3 mm, preferably less than 0.2 mm, and particularly preferably less than 0.15 mm by the inner rib designed according to the invention.

[0120] The inner rib 51 therefore has a width of approximately 0.9 mm in the illustrated example. Without limitation to the exemplary embodiment, widths of the inner rib 51 of less than 1 mm, preferably less than 0.9 mm, and particularly preferably less than 0.8 mm are advantageous. Furthermore, for a stable fit, the width and cross-sectional shape of the inner rib 51 are constant over a large part of the length of the inner rib 51, as can be seen, for example, from the Fig. 8 clearly visible. In other words, except for a small insertion bevel 52 for positioning the sealing element, the cross-section of the rib is constant over its length. It has proven advantageous if the cross-sectional shape of the inner rib 51 is the same over a length of at least 50% of the entire length of the inner rib 51, preferably over a length of at least 60%, and particularly preferably at least 65%. This significantly reduces the tendency of the sealing element 20 to later axially offset.

[0121] In this way, it is possible to maintain the required minimum pressure to close the opening 34. This provides a closure cap 10 in which the axial distance between the outer stop 11 and the inner stop of the closure cap is 2.85 mm with a tolerance of + / - 0.2 mm, preferably + / - 0.1 mm, and particularly preferably + / - 0.05 mm. In this way, the required minimum pressure to seal the opening 34 is reliably maintained.

[0122] The actuating section 50 further comprises particularly advantageously elongated outer ribs 53, which are arranged axially in their main orientation and protrude radially outward from the lateral surface, providing a better grip for a user and thus facilitating screwing and unscrewing. In the example, the actuating section 50 comprises eight such outer ribs 53. These outer ribs 53 extend over almost the entire length of the actuating section 50. In a favorable embodiment, these outer ribs have a length, i.e. an extension in the axial direction, of at least 4.5 mm, preferably of at least 5.0 mm. In the example, the length is approximately 5.3 mm, which already leads to a sufficient gripping surface.

[0123] The height of these outer ribs 53, i.e. the radial projection relative to the outer surface, is at least 0.3 mm, so that the user finds a stable gripping surface and can therefore open the closure better and more easily.

[0124] The closure 1 is made of a color-stable plastic. The following pigments are used as coloring elements to color the plastic: Titanium dioxide Kronos ®< 2233 Carbon black PRINTEX ®< F 85 6975 Titanium orange VYNAMON ®< Green 600734

[0125] A closure 1 made of such a material is therefore also suitable for sterilization processes that use gamma or X-ray radiation. It has been shown that such closures, when irradiated with an energy dose in the range of 25-40 kGy, result in no or barely perceptible color changes to the human eye and can therefore be considered color-stable.

[0126] Such a material composition is also suitable for other sterilization methods, such as hot steam sterilization at up to 134 °C for a period of 10 minutes, which results in no or hardly perceptible color changes to the human eye. List of reference symbols:

[0127] 1 Closure 10 Cap 11 Stop 12 Outer edge of the closure cap 13 Outer edge of the closure cap 14 Cavity 15 Shoulder 16 Stop 20 Sealing element 21 Sealing section 22 Outer edge of the sealing section 23 Outer edge of the sealing section 24 Inner edge 25 Recess 30 Container 31 Sleeve 33 Tip 34 Opening 35 Chamber 36 Collar 40 Mounting section 41 External thread 42 Rib 44 Bulge 45 Clearance 46 Thread entry 47 Chamfer 50 Actuating section 51 Inner rib 52 Lead-in chamfer 53 Outer rib 100 Closure 110 Cap 112 Outer edge of the closure cap 120 Sealing element 121 Sealing section 122 Outer edge of the sealing section 140 Mounting section 150Operating section SSettlement ADistance EInjection point

Claims

1. A closure (1) for releasably closing an opening (34) at the distal end of a cylindrical container (30) for pharmaceutical preparations, in particular a syringe, by Luer lock fastening means, comprising a cylindrical closure cap (10) and a sealing element (20), wherein the cylindrical closure cap (10) has a continuous cylindrical cavity (14) for receiving and holding the sealing element (20), and wherein the closure cap (10) comprises a mounting section (40) which, in the mounted position, faces the container, wherein the mounting section (40) has an external thread (41) which, in the mounted position, engages in the Luer lock fastening means of the container (30) and creates a releasable connection; and wherein the sealing element (20) is designed with a sealing section which is arranged at least partially within the mounting section (40) and which, in the mounted position, surrounds the opening, wherein the outer edge of the sealing element (20) is set back relative to the outer edge of the mounting section (40); characterized in that on the flank of the thread turn, at least one pair of protrusions comprising two oppositely arranged protrusions is provided in such a way that, in the mounted position, the protruding points engage on the thread flank of the Luer lock fastening means and are slightly compressed or deformed, so that when opening the closure (1), a higher force component must be applied initially in order to effect the release, wherein the force component to be applied continuously decreases once a threshold value has been exceeded.

2. The closure (1) according to the preceding claim, characterized in that the setback of the outer edge of the sealing element (20) relative to the outer edge of the mounting section (40) is at least 0.5 mm, preferably at least 1 mm and most preferably at least 1.5 mm.

3. The closure (1) according to any one of the preceding claims, characterized in that the closure cap (10) furthermore comprises an actuation section (50) arranged opposite the mounting section (40), wherein the sealing element (20) is arranged at least partially inside the actuation section (50); and wherein the outer edge of the sealing element (20) is set back relative to the outer edge of the actuation section (50) by preferably at least 0.5 mm, more preferably at least 1 mm and most preferably at least 1.5 mm.

4. The closure (1) according to any one of the preceding claims, characterized in that the ratio of the length of the sealing element (20) to the length of the closure cap (10) is at most 95 %, preferably at most 90 % and most preferably at most 85 %.

5. The closure (1) according to any one of the preceding claims, characterized in that the sealing element (20) comprises an elastomeric material.

6. The closure (1) according to any one of the preceding claims, characterized in that the external thread (41) is in the form of a trapezoidal thread, preferably with a modified shape of the thread flank, preferably with an outer width or crest width of 0.6 mm and a root width of 1.2 mm.

7. The closure (1) according to any one of the preceding claims, characterized in that the flank of the thread turn is provided with two pairs of protrusions and preferably with four pairs of protrusions.

8. The closure (1) according to any one of the preceding claims, characterized in that an axial bulge (44) is provided on the portion of the thread turn adjacent to the thread entry (46).

9. The closure (1) according to any one of the preceding claims, characterized in that the thread turn has a chamfer (47).

10. The closure (1) according to any one of the preceding claims, comprising a cylindrical closure cap (10) with a through opening, wherein the wall thickness of the closure cap is at most 1.5 mm at the thickest point, and / or wherein the wall thickness varies over the length of the closure cap by not more than 0.5 mm, preferably by not more than 0.3 mm.

11. The closure (1) according to any one of the preceding claims, characterized in that the injection point is provided at a position on the lateral surface of the actuation section (50) of the closure cap (10) axially spaced apart from an outer rib (53).

12. The closure (1) according to any one of the preceding claims, characterized in that the axial spacing between an outer stop and an inner stop of the closure cap is 2.85 mm with a tolerance of ±0.2 mm, preferably ±0.1 mm and most preferably ±0.05 mm.

13. The closure (1) according to any one of the preceding claims, characterized in that the through opening (14) of the closure cap (10) has at least two elongated inner ribs (51) on the inner wall, which are arranged axially in its main orientation and project inwards, preferably in the area of the actuation section (50), wherein said inner ribs (51) have a width of less than 1 mm, preferably of less than 0.9 mm and most preferably of less than 0.8 mm.

14. The closure (1) according to the preceding claim, characterized in that the width or cross section of the inner rib (51) is consistent over a large part of the length of the inner rib (51), in particular over at least 50 % of the length of the inner rib (51), preferably over at least 60 % of the length and most preferably of at least 65 %.

15. The closure (1) according to any one of the preceding claims, characterized in that the actuation section (50) comprises at least two elongated outer ribs (53), which are arranged axially in their main orientation and project radially outwards from the lateral surface, which preferably have a length of at least 4.5 mm, more preferably of at least 5.0 mm and most preferably of 5.3 mm.

16. The closure (1) according to any one of the preceding claims, characterized in that the closure (1) comprises a colour-stable plastics material.

17. The closure (1) according to the preceding claim, characterized in that the colour of the closure is grey-green and corresponds to the colour RAL 7009 according to the RAL colour system, wherein the closure (1) is preferably colour-stable against effects resulting from treatment with any of the following sterilization methods: hot air, hot steam at up to 134 °C over a duration of 10 minutes, gamma rays or X-rays with an energy dose in the range of 25 - 40 kGy or a combination of these methods.

18. The closure (1) according to any one of the two preceding claims, characterized in that the material for the closure (1) comprises the following pigments as colour-imparting elements: - Titanium dioxide Kronos® 2233 - Carbon black PRINTEX® F 85 - 6975 Titanium Orange - VYNAMON® Green 600734.

19. A method for sealing a distal end of a cylindrical container (30) for pharmaceutical preparations, in particular a syringe, in a contamination-free, releasable manner by Luer lock fastening means using a closure (1) according to any one of the preceding claims.

20. The method for sealing a container (30) according to the preceding claim, characterized in that the tightening torque and / or the opening torque exhibit a small variation of ±1.0 N·cm, preferably ±0.5 N·cm, relative to the respective nominal torque.

21. A method for producing a closure, in particular a closure (1) according to any one of the preceding claims 1 - 18, characterized in that the closure (1) comprises an actuation element with at least two outer ribs (53) and is produced by an injection moulding process, wherein an injection point is selected which lies in the area of the actuation section (50), preferably at a position on the outer lateral surface of the actuation section (50) axially spaced apart from an outer rib (53).