Closure for pharmaceutical containers and containers equipped with this closure

Abstract

To provide a closure for a medicament container, in general, and a medicament container, particularly a syringe, comprising the closure like this.SOLUTION: The closure is adapted to releasably close an opening at the distal end of a cylindrical medicament container, particularly a syringe, preferably using a Luer lock fastening device. For this purpose, the closure includes a cylindrical closure cap with a cylindrical cavity for receiving and holding a sealing element, and the sealing element, which is recessed relative to the outer edge of the closure cap.SELECTED DRAWING: Figure 2

Description

Technical Field

[0001] The present invention generally relates to a closure for a container for pharmaceuticals and a container for pharmaceuticals, particularly a syringe, provided with this closure.

Background Art

[0002] Containers for pharmaceuticals, particularly syringes, play a major role within the framework of the administration of pharmaceuticals or drugs. These containers, which are generally shaped cylindrically, include a chamber for containing the drug, which is defined at both sides by a proximal end and a distal end. A piston can be inserted into the proximal end, thereby pressing the drug in the distal direction in sliding motion and through an opening at the distal end of the syringe, or drawing the drug into the syringe through this opening in the reverse proximal direction. At this time, the opening at the distal end is often formed by a conical tip.

[0003] To close the opening at the distal end of the container, closures or closing systems have been known for a long time. For example, such closures for closing the opening at the distal end of a syringe are also described in the printed matter US Patent No. 5,624,402 (US 5,624,402) or US Patent No. 6,196,998 (US 6,196,998 B1). Another closing system is described, for example, in the printed matter European Patent No. 1,600,190 (EP 1,600,190 B1).

[0004] These known closures or closing systems have a plurality of drawbacks.

[0005] For example, known closures are often formed from multiple parts and have an inner element made of a flexible material for sealing and an outer element that forms a connection with the container. For this purpose, a threaded connection is often provided. The threading of these multi-part closures causes difficulties when the inner element first comes into contact with the container during joining, as is known from the prior art. At this time, tilting or inclination can occur very easily at the start of the joining process, which prevents the short process time required for installing the closure.

[0006] Furthermore, the inner elements are often manufactured from elastomer materials, which can be contaminated under manufacturing conditions, for example, by silicone oil. Closures are generally stocked and transported as bulk. If this partially contaminated elastomer material of the inner element now comes into contact with the male threads of other closures or containers, this can contaminate the component, which can be critical for both the installation and subsequent release of the closure. This is because the set forces and moments may no longer be reliably maintained, in some cases, thus compromising the reliability of the connection and, consequently, the reliability of the entire product.

[0007] Therefore, there is a need for a closure and a method for attaching this closure to a container that allows for reliable installation without contamination and in a short process time.

[0008] Another drawback lies in the precision and characteristics of the tightening and / or releasing torques for attaching or disengaging the closure in the container. The known wide threads of the closure can sometimes produce a consistently high releasing torque that the user must overcome, especially during disengagement, i.e., when opening the container.

[0009] Therefore, it is desirable to provide a closure that has an opening torque that can accurately provide a set threshold for opening the closure, and at the same time facilitates the subsequent dissociation.

[0010] Another issue lies in the high precision required for the necessary spacing between components needed for sealing at their installed location. In this context, the axial spacing of the sealing elements relative to the opening to be closed in the container is of great importance. Given shape and position tolerances, it may become impossible to maintain the minimum pressure required for sealing, which can raise questions about the reliability of the product.

[0011] Therefore, it is desirable to provide a closure that can reliably guarantee the minimum pressure required to seal the opening of a container.

[0012] Another drawback lies in the color stability of the closure material, which often includes plastic. This color stability is relevant if the closure and / or the container containing the closure can be subjected to sterilization treatments, which can cause color changes or other property changes in the plastic involved.

[0013] Therefore, it is desirable to provide a closure that can be sterilized using conventional methods without causing any visible color change or other changes to the closure. [Overview of the Initiative] [Means for solving the problem]

[0014] The inventor has taken this problem into consideration and, based on one of the independent claims, provides a cylindrical container for pharmaceuticals, in particular a closure for a syringe, and a container for pharmaceuticals, in particular a syringe, equipped with this closure.

[0015] The closure according to the present invention eliminates the drawbacks described above and has several structural improvements compared to known closures or closing systems. Preferred embodiments and variations of the present invention are described in their respective dependent claims.

[0016] A cylindrical container for pharmaceuticals is typically elongated and has a central chamber, a proximal end connected to one side of the chamber into which, for example, a piston can be inserted, and a distal end located on the opposite side, which may include a tip that tapers to a cone shape. The central axis of the container is the longitudinal axis of the configuration described below.

[0017] The distal end is generally formed by a long, tapering cone shape towards the distal end and has an opening formed as a narrow through-hole, through which, when a corresponding piston motion is performed, liquid pharmaceuticals, for example, can be drawn out of the chamber. Conversely, when the piston is moved in the opposite direction, i.e., towards the proximal end, liquid pharmaceuticals can be drawn in. In the field of pharmaceuticals, this cylindrical container is known as a syringe or cannula and can be manufactured from glass or plastic. The closure according to the present invention is basically suitable for both glass and plastic containers. Pharmaceuticals may include liquids, gases, solids, or mixtures thereof.

[0018] In the medical field, a device called a Luer lock has been developed to secure, for example, a needle cannula to the distal end of a container. In plastic containers, this Luer lock device may be formed integrally with the container, for example, as a sleeve or collar, and may at least partially surround the tip of the container. This Luer lock device may include a sleeve with female threads at the distal end of the container.

[0019] Closures are necessary to seal openings at the distal end of a container or to close through-holes at the tip, thereby preventing, for example, contamination of the filled chemical or preventing unintended loss of the chemical. The concept of "seal" or "close" below means to consolidate and / or fluid-tightly close openings at the distal end of a container.

[0020] Therefore, the object of the present invention is a closure for removably closing the opening at the distal end of a cylindrical container for pharmaceuticals, particularly a syringe, preferably using a Luer lock fixing device.

[0021] The closure according to the present invention is particularly well suited for closing an opening at the distal end of a container, which is formed as the tip. The container is preferably made of plastic and includes a sleeve equipped with a Luer lock fastener having female threads.

[0022] The proposed closure is, A cylindrical closing cap having a cylindrical hollow chamber for housing and holding a sealing element, the closing cap including a mounting portion facing the container in the position where it is installed, A sealing element having a sealing portion that is at least partially located inside the mounting portion, and in this case The outer edge of the sealing element is recessed relative to the outer edge of the mounting portion.

[0023] Here, the outer edge of the seal element refers to the outer edge of the seal element facing the container at the mounting position, and similarly, the outer edge of the mounting portion refers to the outer edge of the closure facing the container at the mounting position.

[0024] The closure cap may be formed from one or more parts and, in a preferred embodiment, includes an attachment part that is designed for and attached to the container and faces the container in the attached position, and an operating part that is disposed on the opposite side and enables the user to engage the closure.

[0025] When the container has a luer lock fixing device with an internal thread, the attachment part may preferably include an external thread that engages the luer lock fixing device of the container in the attached position and thus forms a separable joint. In the attached position, the closure cap and the container are coaxially arranged with respect to the longitudinal axis. The closure according to the invention with a seal element inserted into the closure cap is particularly suitable for attachment in a container with a luer lock fixing device, which includes an internal thread for accommodating an external thread that is exactly opposite in fit.

[0026] The operating part may preferably have outer ribs for better handling by the user. The cylindrical hollow chamber of the closure cap may preferably be formed continuously, which enables easy installation and retention of preferably an integral seal element, which may also be formed cylindrically and have an outer geometry that is exactly opposite in fit to the inner geometry of the cylindrical hollow chamber of the closure cap. The seal element is preferably manufactured from an elastomeric material.

[0027] The retraction according to the present invention can significantly improve the mounting process and enhance process reliability surprisingly easily, because it can effectively prevent tilting and toppling during the attachment of the closure to the container. This is due to the fact that centering of the closure is first carried out via the attachment part during joining, and then the sealing element contacts the container, particularly the tip of the container. Exactly, in the case of a fully automated attachment process and a large number of required individual parts, enhancing attachment reliability has great significance for manufacturing efficiency.

[0028] That is, the process reliability is enhanced by the fact that the sealing element is retracted with respect to the outer edge of the attachment part of the closure cap, or in other words, the sealing element is in a deep position with respect to the outer edge on the attachment side of the closure. This is because the centering of the closure during the screwing operation is carried out before the contact of the sealing element with the container has occurred. In contrast, closures existing in the market have a sealing element protruding in the attachment direction from the closure cap. In such a case, during attachment, the first contact occurs between the sealing element and the container, which makes it difficult or even impossible to achieve the desired centering from a process-technical perspective.

[0029] In the present invention, since the first contact for the attachment of the sealing element to the tip of the container is made only after the centering of the closure and the container, a purely axial pushing-in of the sealing element is possible, which reduces the occurrence of errors.

[0030] At the same time, the retraction of the seal element reduces contamination of other closures or containers by manufacturing residues that may accumulate on the surface of the seal element. Such manufacturing residues include, for example, liquids used during the manufacture of the seal element, such as silicone oil that may accumulate on the outside of the seal element. This often happens with seal elements made from elastomer materials.

[0031] Closures equipped with sealing elements are often stocked, transported, and supplied in bulk quantities of thousands within a single package, for example, within a single bag. If the sealing element protrudes from the closure, it may contaminate other closures in the bulk load through contact, if it is contaminated. For example, a silicone-treated sealing element, i.e., contaminated with silicone oil, within the package may come into contact with other non-silicone-treated closures. This contact may contaminate the non-silicone-treated closures with silicone oil.

[0032] If, for example, the male threads of another closure cap become contaminated with silicone oil, this contamination is undesirable during transport or subsequent processes, such as during individualization, gripping, or installation of the closure for attachment to a container in the appropriate machinery. The retraction of the sealing element prevents this undesirable contamination.

[0033] On the product side, contamination of the male threads of the sealing cap can lead to drawbacks, for example, with respect to the tightening torque required for installation and the disengagement or release torque required for subsequent disengagement. For instance, if a contaminated sealing element comes into contact with the male threads, the tightening torque may be significantly reduced or subjected to strong fluctuations.

[0034] With respect to containers, for example, if the risk of manufacturing residues of the sealing element accumulating in the threads during the manufacturing and / or installation process can be reliably eliminated, the risk of contamination can be reduced, thereby increasing the reliability of containers that are closed by the closure.

[0035] For example, experiments have demonstrated that tightening and releasing torques begin to vary significantly due to contamination of the male threads. In other words, the set moment can no longer be maintained. Measured variations in tightening torque in contaminated closures can exceed 0.5 N·cm, 1.0 N·cm, or even 1.5 N·cm. Variations in releasing torque in contaminated closures can range from 2 to 16 N·cm, 2 to 18 N·cm, or even 2 to 20 N·cm. Such large variations are inconvenient for the user.

[0036] Therefore, it is also preferable that the sealing element is set back in this manner relative to the outer edge of the operating part on the side opposite to the closing cap, and this configuration can reduce the risk of contamination.

[0037] Therefore, the present invention contributes not only to improving process reliability but also to manufacturing reliability for pharmaceutical containers. It can provide a closure in which the tightening torque and / or release torque have a small variation of + / - 1.0 N·cm, preferably + / - 0.5 N·cm, from the required or desired torque.

[0038] This is achieved by designing the length of the sealing element such that, in some cases, a contaminated sealing element cannot come into contact with other closing caps. Therefore, it is preferable that the length of the sealing element along the longitudinal axis is shorter than the length of the closing cap. In a preferred embodiment, the ratio of the length of the sealing element to the length of the closing cap is at most 95%, preferably at most 90%, and particularly preferably at most 85%.

[0039] The mounting and removal characteristics of a closure cap are largely determined by the configuration of the male threads of the closure cap. If the container has a Luer lock fastening device, a special configuration of the male threads of the closure cap can enable relatively simple and accurate mounting, thereby also increasing process reliability and manufacturing reliability.

[0040] For this purpose, the male threads of the closing cap can be formed according to the standard ISO 594-2, but according to the present invention, however, the special configuration of the threads is preferably provided with other shapes on the thread sides, thereby creating other engagement of the male threads with the female threads of the Luer lock connector. In a preferred embodiment, the present invention proposes forming the thread sides relatively thin and / or with relatively steep sides. This increases the spacing between the thread sides when the pitch is the same, and consequently reduces the axial play of the closing cap when it is first partially screwed into the Luer lock connector.

[0041] In this case, the male thread is preferably formed as a trapezoidal thread, and preferably has an outer width or thread width of about 0.6 mm ("thread crest width") and a core width of about 1.2 mm ("maximum width of base"). This firstly allows for relatively simple screwing of the closure to the container, based on the relatively small frictional force acting on it. In this case, other structural characteristics of the thread, such as the thread pitch, preferably remain constant.

[0042] In this invention, a suitable thread pitch value is 3 to 5.5 mm, preferably 3.5 to 5.25 mm, and particularly preferably 4 to 5 mm.

[0043] This further allows for the provision of at least one fixed position on the threaded side, preferably a point-shaped protrusion, which protrudes, for example, 0.5 to 1.5 mm from the side. Preferably, at least two protrusions are provided, positioned on opposite sides of the threaded side. Two protrusions positioned on opposite sides can thereby form a so-called protrusion point. Such a pair of protrusions is preferably positioned so that, in the installed position, the pair of protrusions contacts the threaded side of the Luer lock fastener and is preferably somewhat compressed or deformed at this time. With this configuration, an additional force component is applied to the joint between the closure and the container. A pair of protrusions has the advantage that such an additional force component does not act on only one side compared to a single protrusion.

[0044] This force component acts similarly when the closure is released, thereby enabling the precise provision of a set threshold for releasing the closure. In this way, it is possible to provide a more user-friendly and better characteristic for the release torque required to separate the closure from the container.

[0045] For uniform force application, it is preferable to provide more than one pair of raised sections, preferably two, and especially preferably four. This contributes to obtaining a uniform and firm seating of the closure in the container. In this way, it is also facilitated to precisely adjust the torque required for attachment and / or disengagement, and to ensure predetermined force changes during rotational motion.

[0046] In general, when attaching closures to containers used for pharmaceuticals, care must be taken to maintain the specified force precisely, as exceeding or falling below this force can immediately have adverse effects on manufacturing reliability.

[0047] Using the male threads formed as described in the present invention for the closing cap, it is possible to maintain an extremely narrow tightening torque, for example, 18.0 N·cm, with a tolerance of + / - 1.0 N·cm, preferably + / - 0.5 N·cm. This is important because tightening moments greater than about 20 N·cm can cause microcrack formation, especially in plastic Luer lock fasteners. Microcrack formation can lead to malfunction of the container and / or closure, thereby compromising manufacturing reliability. When the tightening torque is less than 16 N·cm, sealing at the tip with a small Luer lock projection can be barely guaranteed.

[0048] The special configuration of the threads further results in a configuration where, when the closure is released for disengagement, a relatively high force component is initially required, after which this force component is reduced to a constant level. This facilitates the opening of the container and the disengagement of the closure for the user. Thus, the torque that must be applied by the user is determined by the opening angle, i.e., by the orientation of the closure relative to the container. After overcoming the initial resistance at the start of disengagement, which arises from the additional force component acting due to the compression of the raised point, the acting force component decreases based on the narrow threads that provide greater free space at the raised point after disengagement, thereby the raised point is compressed only slightly, or preferably no longer compressed at all. In this way, the torque that must be applied for further disengagement is reduced. This makes it possible to produce a precise torque for opening, for example, 16 N·cm with an accuracy of + / - 0.5 N·cm.

[0049] Consequently, the disengagement characteristics of the closure according to the present invention also differ from those of known closures, where the force component that must be applied at the start of disengagement hardly decreases during the closure's disengagement. This is because known closures often have thread curvature for an additional force component, and this curvature acts during the full disengagement operation based on relatively wide threads. For the user, this characteristic of the torque that must be applied for disengagement is rather inconvenient, as it requires applying a relatively high moment for almost full opening.

[0050] According to the present invention, the installation of the closure is further simplified by the fact that the threads are relatively thin on one side, as described above. Such a configuration expands and facilitates the possible angular orientation, that is, the proper angular orientation of the closure and the container relative to each other at the start of installation.

[0051] To further expand this tolerance range for the required angular orientation, in a preferred embodiment, the curvature of the portion of the thread located near the thread entrance is provided to expand the free space from the outer edge to the first thread, thereby further expanding the tolerance range for angular orientation. This curvature is a slight axial misalignment of the thread in the portion described above. Therefore, based on a relatively thin thread, this curvature can also be configured so that no additional force component acts on the joint, preferably.

[0052] This eliminates the need for a narrow tolerance range for the correct angle of insertion and screwing of the closure into the container. Rather, a relatively large angular range is provided within which mounting can be performed. While known closures have a tolerance range that allows for a deviation of less than + / -3° for correct angle mounting, the configuration of the thread entry according to the present invention can extend this angular tolerance to + / -10° or more. Depending on the specific configuration, this angular tolerance according to the present invention can be in the range of + / -5° to + / -15°, preferably + / -8° to + / -12°. This clearly results in preferred mounting characteristics because it reduces the effort required to accurately orient the closure into the container.

[0053] In similarly preferred embodiments, the threads may include additional bevels, or the thread introduction may be formed as a bevel. While known closures have male threads with an obtuse-angled thread introduction, which can cause tilting very quickly during the start of installation, this inclined introduction, or the bevel in the thread introduction, significantly facilitates installation.

[0054] The reliability of a pharmaceutical container equipped with the closure according to the present invention is further influenced by the fitting accuracy of the components that produce the sealing of the container opening. Here, the axial distance between the stopper of the closing cap, which protrudes radially outward and is in contact with the container, particularly the collar of the Luer lock fixing device, at the mounting position, and the inner edge of the sealing portion of the sealing element that seals the opening at the tip, is of critical importance. At this time, the sealing portion of the sealing element is in close contact with and / or surrounds the opening, particularly at the tip, at the mounting position, and attention must be paid to the minimum pressure that can be adjusted with respect to the shape tolerances and position tolerances of the components involved.

[0055] For axial positioning of the sealing element at the opening of the closing cap, the closing cap is preferably formed with an annular shoulder projecting radially inward. The sealing element preferably has an annular notch on its circumferential surface, which is preferably positioned so that the shoulder of the closing cap engages with the notch of the sealing element in the installed position, and this axial stopper creates a locking portion. With this configuration, accurate positioning of the sealing element with respect to the container, and consequently accurate positioning of the inner edge of the sealing element that seals the opening of the container, can be obtained in the installed position.

[0056] For typical containers, and especially for typical syringes, a mounting dimension of 2.85 mm is required, with an extremely small tolerance for the axial distance between the outward-projecting stopper of the closing cap (also called the outer stopper) and the stopper located inside the opening of the closing cap, determined by the shoulder (also called the inner stopper). In this case, the inner stopper acts in the opposite direction with respect to the minimum pressure that must be applied to the sealing element for sealing, thereby determining the sealing force acting on the tip opening.

[0057] Therefore, maintaining extremely small tolerances for these inner and outer stoppers is of great importance for the closure's configuration. According to the present invention, maintaining such tolerances is achieved through a variety of structural measures.

[0058] In one preferred embodiment, the closure cap is designed such that the side walls have a thin and particularly uniform material thickness along the length of the closure cap. Preferably, the wall thickness of the closure cap is at most 2.5 mm, preferably 2.0 mm, at its thickest point. In this case, the wall thickness varies by no more than 0.5 mm, preferably 0.3 mm, over the entire length of the closure cap.

[0059] Maintaining such dimensions is no trivial matter. Closure caps are generally manufactured from thermoplastic plastics using injection molding. This process generates relatively high temperatures during the initial molding, which can lead to dimensional deviations in the closure cap after cooling. A consistent wall thickness ensures uniform cooling and reduces the resulting distortion.

[0060] Furthermore, according to the present invention, the injection molding method is optimized so that an injection point located in the area of ​​the operating part is selected. Particularly preferably, the injection point is located on the outer side of the circumferential surface of the operating part, axially spaced from the outer rib. This further helps to prevent the risk of injury to the user, which may occur in some cases, because the sprue can create sharp edges. In contrast, an injection point on one of the outer ribs is undesirable because it may cause distortion of the thin-walled closing cap.

[0061] The method according to the present invention makes it possible to manufacture a very large number of closing caps with extremely small dimensional errors using injection molding. This is partly due to the thin and uniform wall thickness and the optimized position of the injection point.

[0062] To further maintain the narrow tolerances mentioned above, it is even more helpful to precisely hold the sealing element within the closing cap. In particular, it is necessary to eliminate as much as possible any unintended axial misalignment of the sealing element relative to the closing cap. Such unintended misalignment may occur, for example, based on installation and / or mounting.

[0063] The non-rotatable retention of the sealing element within the continuous opening of the closing cap can be achieved via at least two elongated inner ribs on the inner wall of the opening, preferably axially oriented in its primary orientation within the operating portion area and projecting radially inward. Typically, about 6 to 10 such inner ribs are provided, often eight regularly spaced inner ribs. These inner ribs can preferably be distributed at uniform intervals across the inner circumference for uniform fitting. In other words, these inner ribs serve to prevent rotation of the sealing element within the closing cap during installation or release, and thus act as a rotation-preventing body.

[0064] Based on the manufacturing of the closing cap by injection molding, these inner ribs may have a demolding slope in the longitudinal direction, i.e., axial direction. However, the inclination of the inner ribs may generate a force component acting on the seal element in the axial direction that can cause axial movement of the seal element from its set position. Despite the inner stopper, this movement may cause an undesirable axial displacement of the seal element of 0.3 mm or more relative to the predetermined installation height.

[0065] This misalignment affects the axial distance between the stopper of the closing cap and the inner edge of the sealing portion of the sealing element, as described above, making it impossible to reliably maintain the dimensions set therein. This also means that the minimum pressure between the sealing element and the tip of the container may not be achieved, and as a result, the required sealing performance may not be maintained, and consequently, the required reliability of the container may not be provided. When using screw couplings for pharmaceutical packaging, for example, a minimum requirement is required, which stipulates that the coupling must be able to withstand a pressure of at least 3 bar for 30 seconds.

[0066] On the other hand, in some cases, if the required interval and minimum pressure are not maintained, the required release torque, which is at least 2 N·cm for screw locking devices in the pharmaceutical field, cannot be maintained.

[0067] While known closures often use wide and rather flat inner ribs, the present invention has other configurations for the inner ribs that are relatively narrow, and such configurations, especially when the other number of inner ribs is the same, result in significantly smaller displacement volumes in the sealing element. This greatly reduces the tendency of the sealing element installed in the closure cap to shift axially, thereby allowing the required spacing dimensions to be maintained relatively accurately after the sealing element is installed. In contrast, a large displacement volume results in strong compression of the sealing element, which in turn promotes unwanted axial displacement.

[0068] The axial misalignment of the sealing element within the opening of the closing cap can be 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 configured as in the present invention.

[0069] The inner rib therefore has a width of less than 1 mm, preferably less than 0.9 mm, and particularly preferably less than 0.8 mm. Particularly preferably, the width or cross-section of the inner rib is constant over most of the length of the inner rib, particularly constant over at least 50% of the length of the inner rib, preferably at least 60%, and particularly preferably at least 65%. Such a configuration also significantly reduces the tendency for axial misalignment of the sealing element within the closed cap.

[0070] In this way, the minimum pressure required to close the opening can be maintained. This makes it possible to obtain a closing cap with an axial distance of 2.85 mm between the outer and inner stoppers of the closing cap, and a tolerance of + / - 0.2 mm, preferably + / - 0.1 mm, and particularly preferably + / - 0.05 mm. In this way, the minimum pressure required to seal the opening can be reliably maintained.

[0071] The operating portion may more preferably include at least two elongated outer ribs that are axially positioned in their primary orientation and project radially outward from the circumferential surface, providing the user with a relatively good grip and thereby facilitating twisting and closing. Preferably, there are slender outer ribs that extend substantially along the entire length of the operating portion. In a preferred embodiment, these outer ribs have a length of at least 4.5 mm, preferably at least 5.0 mm, i.e., an axial extension length. The height of these outer ribs, i.e., the radial projection from the circumferential surface, is preferably at least 0.3 mm, so that the user can find a stable gripping surface and, consequently, open the closure relatively well and relatively easily.

[0072] The reliability and usability of pharmaceutical containers equipped with the closure according to the present invention are further determined by the color stability of the container, particularly the color stability of containers equipped with the closure according to the present invention. Since the closures are typically manufactured in large quantities using injection molding, substantially suitable thermoplastics are used as the material for this purpose.

[0073] Color stability is of great importance when closures and / or containers with closures are subjected to sterilization processes, which may cause discoloration or other material changes in the plastics involved. Sterilization helps remove as many contained or attached microorganisms as possible from pharmaceutical packaging, i.e., containers holding pharmaceuticals.

[0074] Various sterilization methods are used, such as sterilization under high-temperature air. These methods are physical sterilization methods that expose heat-stable pharmaceutical products to dry heat. A temperature of at least 180°C is required for at least 30 minutes to remove bacteria, fungi, viruses, or spores from the product.

[0075] Furthermore, autoclaving is known as the most frequently used sterilization method. In this method, for example, steam at a temperature of 120°C at 0.5 bar is used. This allows sensitive products to remain in the autoclave longer than in high-temperature air sterilization.

[0076] Additionally, the water vapor is distributed relatively well across the product surface, which allows for a relatively good sterilization temperature to be achieved throughout the entire product.

[0077] Furthermore, irradiation with electromagnetic beams, such as gamma rays or X-rays, is also known. In so-called gamma sterilization, pharmaceuticals are irradiated, for example, with gamma rays of a determined energy dose. When using gamma rays or X-rays, irradiation is generally carried out with an energy dose in the range of 25-40 kGy.

[0078] Many known sterilization methods limit the selection of materials, such as those for closures, to minimize any definite effects on the material's color or viscosity. In other words, irradiation of closures can alter the polymer structure of the plastics used, which can result in discoloration. Alternatively, certain sensitive thermoplastics may be partially damaged at the required high temperatures, such as by cracking or discoloration.

[0079] While color changes due to sterilization may be desirable for certain application areas, within the framework of this invention, color changes of the closure are undesirable. Regardless of the type of sterilization, that is, when using at least one of the sterilization methods described above, it is desirable that no "color shift," or color change, occurs in the closure as much as possible. In this invention, a color change is considered undesirable if the colored areas of the material after sterilization differ from the colored areas of the material before sterilization by a value ΔE, which is determined as a change in colored areas in the CIE1931 system, and the difference is greater than ΔE = 0.05. In this case, the change in colored areas ΔE is given by the following formula: that is, ΔE = √(x 2 +y 2 ) Therefore, according to the present invention, in a preferred embodiment for the closure, a material is selected that does not change color little or preferably not at all as a result of sterilization.

[0080] This is achieved, quite surprisingly, by selecting specific coloring pigments and antioxidants for the materials used to manufacture the closures. The inventors discovered that a completely specific material composition, including a particular selected pigment that produces the grayish-green color glaze of the closures, has little to no tendency to change color when using at least one of the sterilization methods described above. Instead, the original color is maintained at least almost, and preferably without color shift. This color corresponds to color RAL7009 in the RAL color chart.

[0081] This remarkable color stabilization is achieved by discovering a composition of colored pigments that produces a polymer structure of plastic that remains stable even at elevated temperatures and under the irradiation of electromagnetic rays as described above. The materials for manufacturing the closure are the pigments described below: - Titanium dioxide Kronos(registered trademark) 2233 -Soot PRINTEX(registered trademark) F 85 -6975 Titanium Orange -VYNAMON(registered trademark) Green 600734 It includes as a coloring element, Therefore, closures made from materials containing these pigments for coloring are also suitable for sterilization methods performed by gamma rays or X-rays. Such closures have been found to produce little to no color change, even when irradiated with energy doses in the range of 25-40 kGy, and can therefore be considered color-stable.

[0082] Particularly preferable is that such a material composition produces little to no color change that is imperceptible to the naked eye, even with other sterilization methods such as high-temperature steam sterilization up to 134°C for 10 minutes.

[0083] This is particularly advantageous because it allows for the selection of sterilization methods that can be used to be largely independent of the closure material. Furthermore, the combination of sterilization methods described above does not reduce the sealing performance. In particular, the closure maintains a sealing performance of up to 4 bar for 30 seconds after sterilization and has an opening torque of less than 15 N·cm.

[0084] The present invention also relates, in a final and different aspect, to a method for closing the distal end of a cylindrical container for pharmaceuticals, preferably a syringe, in a way that allows it to be detached without contamination, particularly by the closure described above.

[0085] Next, the present invention will be described in detail with reference to the following preferred embodiments. [Brief explanation of the drawing]

[0086] [Figure 1] This is a longitudinal cross-sectional view showing a closure using conventional technology. [Figure 2] This is a longitudinal cross-sectional view showing the closure according to the present invention. [Figure 3] This is a longitudinal cross-sectional view showing a pharmaceutical container with a Luer lock fastening device, along with a partially attached closure. [Figure 4] This diagram shows the change in torque when the closure according to the present invention is opened to detach from the container. [Figure 5] This diagram shows the change in torque when a closure known from the prior art is opened for disengaging from a container. [Figure 6] This is a plan view showing a part of the closure according to the present invention, which has a curve. [Figure 7] This is a longitudinal cross-sectional view showing a closure according to the present invention equipped with a sealing element. [Figure 8] This is a longitudinal cross-sectional view showing the closure according to the present invention without a sealing element. [Figure 9] This is a perspective view showing the closure according to the present invention. [Modes for carrying out the invention]

[0087] In the detailed description of preferred embodiments below, for clarity, the same reference numerals indicate substantially equivalent parts in the embodiments. However, to further clarify the present invention, preferred embodiments shown in the drawings are not always shown in actual dimensions.

[0088] Figure 1 shows a longitudinal cross-sectional view of a conventional closure 100. This closure 100 includes a cylindrical closing cap 110, which has a cylindrical hollow chamber for housing a sealing element 120, and the closing cap 110 includes a mounting portion 140 facing the container in the installed position and an operating portion 150.

[0089] A seal element 120 having a sealing portion 121 is inserted into the cylindrical hollow chamber of the closing cap 110. Clearly visible, the outer edge 122 of the sealing portion protrudes beyond the outer edge 112 of the closing cap 110. This is inconvenient for automated installation, as tilting and inclination can occur during the initial mounting when the seal element first contacts the container, particularly the tip of the container. This also makes centering the closure during the screw-in operation almost impossible, because the seal element 120 is manufactured from a flexible elastomer material. In a fully automated installation process and with the required number of pieces, installation must be performed particularly slowly given these circumstances, or if it must be repeated, for example after inclination, valuable time can be lost.

[0090] Figure 2 shows a longitudinal cross-sectional view of a closure 1 according to the present invention for detachably closing an opening at the distal end of a cylindrical container (not shown) for pharmaceuticals, particularly for syringes, preferably using a Luer lock fastening device. The closure 1 according to the present invention includes a cylindrical closing cap 10 having a continuous cylindrical hollow chamber 14 for housing a sealing element 20, wherein the closing cap 10 includes a mounting portion 40 facing the container in the installed position and an operating portion 50.

[0091] The mounting portion 40 includes a male thread 41 which, in the mounted position, engages with the female thread of the container's Luer lock fastening device and forms a detachable connection with the container. The operating portion 50 is equipped with an outer rib for handling by the user. The cylindrical hollow chamber 14 of the closing cap 10 is formed continuously to accommodate, for example, an integral seal element 20.

[0092] As can be clearly seen from the drawing, the outer edge 22 of the sealing element 20 is clearly recessed relative to the outer edge 12 of the mounting portion 40 of the closing cap 10.

[0093] The retraction according to the present invention makes it possible to significantly improve the mounting process and increase process reliability with surprising ease. This is because tilting and inclination during mounting of the closure 1 to the container or at the start of the mounting process can be effectively prevented. This is due to the fact that the closure 1 is initially centered through the mounting portion 40 during joining, before the sealing element 20 contacts the container, particularly the front of the container. Indeed, in fully automated mounting processes and with the large number of pieces required, increased mounting reliability has great significance for manufacturing efficiency and can facilitate the saving of valuable time in mounting.

[0094] In other words, the retraction of the seal element 20 relative to the outer edge 12 of the mounting portion 40 of the closing cap 10 enhances process reliability. This is because the centering of the closure 1 during the screwing operation occurs before the seal element 20 makes contact with the container. In this embodiment, the initial contact of the seal element 20 with the tip of the container occurs only after the centering of the closure 1 and the container, allowing for purely axial pushing, which virtually eliminates errors.

[0095] At the same time, the retraction also reduces contamination of other closures or containers by manufacturing residues that may be present on or in contact with the seal element 20. Such manufacturing residues include, for example, liquids used during the manufacture of the seal element, such as silicone oil. This is indeed a common occurrence with seal elements manufactured from elastomer materials, as in this embodiment.

[0096] The setback has a value of approximately 2.5 mm in the embodiment. The risk of contamination can already be reduced when the setback is at least 0.5 mm, preferably at least 1.0 mm, and particularly preferably at least 1.5 mm. In relation to the given tolerance, preferred setbacks are further in the range of 1.5–2.0 mm, 2.0–2.5 mm, or 2.5–3.0 mm.

[0097] As can be seen further in Figure 2, the outer edge 23 of the seal element 20 is also recessed relative to the outer edge 13 of the closing cap 10. This recess is preferably at least 0.5 mm, preferably at least 1.0 mm, and particularly preferably at least 1.5 mm. In an embodiment, the value of the recess is about 2.5 mm, which is approximately the same size as the recess on the opposite side.

[0098] Therefore, the recession of the outer edges 22, 23 of the sealing element 20 relative to the outer edges 12, 13 of the closing cap 10 ensures that the closures, which are positioned side by side within the transport packaging, for example, do not contaminate each other. This is structurally resolved by the reduced length of the sealing element 20 relative to the length of the closing cap 10. In embodiments, the ratio of the length of the sealing element to the length of the closing cap is about 70%. It has been found that the ratio of the length of the sealing element 20 to the length of the closing cap 10 is preferably at most 95%, more preferably at most 90%, and most preferably at most 85%.

[0099] The attachment and removal characteristics of the closure 1 in the container are largely determined by the formation of the male threads on the closing cap 10.

[0100] Figure 3 shows a longitudinal section view of a pharmaceutical container 30 having a Luer lock fastening device, along with a partially attached closure 1. The container 30 includes a sleeve 31 at its distal end, which is formed with female threads 32 and is a Luer lock fastening device. The sleeve 31 surrounds a cone-shaped, tapering tip 33 at the distal end of the container, which has an opening 34 for, for example, discharging pharmaceuticals from a chamber 35.

[0101] The male threads 41 of the mounting portion 40 are formed in the exact opposite direction to the female threads 32 for fitting. The male threads 41 are usually formed according to standard ISO 594-2, in which case, according to the present invention, ribs 42 of a different shape are provided. The ribs 42 according to the present invention are formed with relatively thin and / or relatively steep sides, thereby creating relatively thin threads and, consequently, relatively large spacings between adjacent thread sides. This, firstly, results in relatively easy screwing of the closure 1 into the container 30, because the frictional force acting is relatively small.

[0102] This further allows for the provision of preferably point-shaped protrusions (not shown) at defined positions on the thread surface, preferably at two opposing positions on the thread surface. Two opposing protrusions can thus form a pair of protrusions. In this case, such a pair of protrusions is formed such that, at the mounted position, the points of the protrusions contact the thread surface of the Luer lock fastener and are compressed or deformed to some extent. This results in an additional force component acting on the joint.

[0103] This force component also acts when the closure is released, thereby providing a precisely set threshold for releasing the closure. In this way, a more user-friendly and better characteristic of the release torque can be provided. In this embodiment, the male thread 41 includes a total of four pairs of ridges (not shown).

[0104] In this way, it is further facilitated that the torque required for mounting and / or disengagement can be precisely adjusted, as well as that predetermined force changes during rotational motion are guaranteed.

[0105] Figures 4 and 5 show the change in torque when the closure 1 is opened to detach from the container 30, using an embodiment. Figure 5 shows the characteristics of the opening torque of a conventional closure 100, while Figure 4 shows the characteristics of the opening torque of the closure 1 according to the present invention.

[0106] To ensure clear recognition and to perform dissociation, a relatively high force component must be applied at the start when opening the closure 1 according to the present invention. Once the threshold is exceeded, the force component that must be applied decreases continuously. This facilitates the opening of the container 30 and the dissociation of the closure 1 for the user. Thus, the torque to be applied follows the opening angle. After overcoming the initial resistance at dissociation caused by the protrusion, the force component acting decreases based on the relatively thin threads that provide a relatively large free space, thereby compressing the protrusion only slightly. In this way, it is also possible to adjust the precise torque for opening, for example, 16 N·cm with an accuracy of + / - 0.5 N·cm.

[0107] Therefore, the disengagement characteristics of the closure 1 according to the present invention differ from those of the closure 100 known based on the prior art. In the known closure 100, the force component that must be applied at the start of disengagement hardly decreases during the disengagement of the closure and remains at a high level until completion. This can be clearly seen from the force change in Figure 5. This is due to the fact that the closure 100 has thread curvature for the additional force component, and this curvature acts throughout the entire disengagement. For the user, this characteristic of the torque that must be applied for disengagement is rather inconvenient, because it requires applying a relatively high moment for almost the entire opening.

[0108] According to the present invention, the installation of the closure is further simplified by the fact that the thread 41 is formed relatively thinly on one side, which expands and facilitates the possible angular orientation, i.e., the proper angular orientation of the closure and the container relative to each other at the start of installation. To further expand this tolerance range of the required angular orientation, in a preferred embodiment, the curvature of the portion of the thread located near the thread entrance is provided to increase the free space from the outer edge to the first thread, thereby further expanding the tolerance range of angular orientation.

[0109] Figure 6 shows a plan view of a portion of the closure 1 with a curvature 44. This slight axial displacement of the threads forming the curvature 44 creates additional free space 45 in the portion adjacent to the thread inlet. This expands the tolerance range for angular orientation. In other words, it expands the range over which the required orientation between the closure 1 and the container 30 can be determined before joining. The configuration of the thread inlet according to the present invention in the illustrated embodiment allows this angular tolerance to be expanded to a range of + / -10°. According to the present invention, it is possible to determine the angular tolerance in the range of + / -5° to + / -15°, preferably in the range of + / -8° to + / -12°. This results in significantly better mounting characteristics.

[0110] In a similarly preferred embodiment, the thread entry point 46 is formed with an additional bevel 47 to further facilitate joining.

[0111] The reliability of the container 30 equipped with the closure 1 according to the present invention is further influenced by the fitting accuracy of the components that produce the sealing performance of the opening 34 of the container 30. Here, as can be seen from Figure 3, the axial distance between the stopper 11 of the closing cap 10, which protrudes radially outward and is in contact with the container 30, particularly the collar 36 of the Luer lock fixing device 32, at the mounting position, and the inner edge 24 of the sealing portion 21 of the sealing element 20 that seals the opening 34 at the tip 33, is of critical importance. The sealing portion 21 is in close contact with the tip 33 at the mounting position and surrounds the opening 34, and at this time the inner edge 24 is in contact with the opening 34 at a set minimum pressure.

[0112] For axial positioning of the sealing element 20 in the opening 14 of the closing cap 10, the closing cap 10 is formed with an annular shoulder 15 projecting radially inward. The sealing element 20 has a similarly annular notch 25 on its circumferential surface, which is positioned such that, in the installed position, the shoulder 15 engages with the notch 25 and forms an axial stopper. In this way, precise positioning of the sealing element 20, and consequently precise positioning of the inner edge 24 that seals the opening 34 (not shown) of the container 30, can be achieved.

[0113] Figure 7 illustrates this relationship with a longitudinal cross-sectional view of the closure 1 according to the present invention, which includes a sealing element 20. In the drawing, "S" indicates the so-called installation dimension, that is, the gap between the inner edge 24 of the sealing element 20 and the container 30 at the position where the closure is installed. This gap is important for obtaining the minimum pressure required to seal the opening.

[0114] Figure 8 illustrates this relationship again, in a longitudinal section view of the closure 1 according to the present invention, which in this drawing does not have the seal element 20. To maintain this installation dimension, a fixed gap "A" is required between the outer edge of the outwardly projecting stopper 11 of the closing cap 10, that is, the outer edge that contacts the collar of the container at the installed position, and the stopper 16, which is determined by the shoulder 15 inside the opening 14 of the closing cap 10. In this embodiment, an installation dimension of A = 2.85 mm with a very small tolerance is required. At this time, the inner stopper 16 generates the minimum pressure of the seal element 20 on the opening that must be applied for sealing.

[0115] The closing cap 10 is designed so that, in order to obtain high dimensional accuracy, the side walls have a thin, and especially uniform, material thickness as far as possible along the entire length of the closing cap. Therefore, the wall thickness of the closing cap 10 is a maximum of 2.0 mm at its thickest point. At this time, the wall thickness does not change by more than 0.5 mm, preferably less than 0.3 mm, when viewed along the entire length of the closing cap.

[0116] Furthermore, according to the present invention, the injection molding method is optimized so that an injection point located in the area of ​​the operating portion 50 is selected. Figure 9 shows a perspective view of the closure 1 according to the present invention, in which the injection point for the injection molding method is indicated by the letter "E" in the illustrated embodiment. This ensures that the injection point is located on the outside of the circumferential surface of the operating portion 50, axially spaced from the outer rib 53. This further prevents the risk of injury to the user, which may occur in some cases, because the sprue can create sharp edges that protrude when accessed. In this embodiment, such potential sprue edges are located outside the grip area.

[0117] The non-rotatable retention of the sealing element 20 in the continuous opening 14 of the closing cap is achieved via elongated inner ribs 51 that are axially positioned in their primary orientation and project radially inward, on the inner wall of the opening 14 of the operating portion 50. These inner ribs 51 are distributed at uniform intervals along the inner circumference for uniform fitting. In the illustrated embodiment, a total of eight such inner ribs 51 are provided.

[0118] According to the present invention, the inner rib 51 is provided in a slender configuration, which clearly creates a small displacement volume in the inserted seal element 20. This greatly reduces the tendency of the seal element 20 installed in the closing cap 10 to shift axially, and as a result, the required spacing dimension after the installation of the seal element, i.e., the installation dimension for maintaining the minimum pressure, can be accurately maintained. The axial displacement of the seal element within the opening of the closing 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 configured as in the present invention.

[0119] Therefore, in the illustrated embodiment, the inner rib 51 has a width of about 0.9 mm. Without limitation on the embodiment, a width of less than 1 mm, preferably less than 0.9 mm, and particularly preferably less than 0.8 mm for the inner rib 51 is preferable. For stable installation, furthermore, the width and cross-sectional shape of the inner rib 51 are constant over most of the length of the inner rib 51, as can be clearly seen from, for example, Figure 8. In other words, the cross-section of the rib is constant over its length, except for a small inlet inclined portion 52 for installing the seal element. In embodiments that have proven advantageous, the cross-sectional shape of the inner rib 51 is equal over at least 50% of the length of the inner rib 51, preferably at least 60% of the length, and particularly preferably at least 65% of the length. With this configuration, the tendency for the seal element 20 to later shift axially is significantly reduced.

[0120] In this way, it is possible to maintain the minimum pressure required to close the opening 34. This results in a closing cap 10 with an axial distance of 2.85 mm between the outer stopper 11 and the inner stopper of the closing cap, and a tolerance of + / - 0.2 mm, preferably + / - 0.1 mm, and particularly preferably + / - 0.05 mm. In this way, the minimum pressure required to seal the opening 34 is reliably maintained.

[0121] The operating portion 50 more preferably includes elongated outer ribs 53 that are axially oriented in their primary orientation and project radially outward from the circumferential surface, which provide the user with a relatively good grip and thereby facilitate twisting and closing. In embodiments, the operating portion 50 includes eight such outer ribs 53. These outer ribs 53 extend over substantially the entire length of the operating portion 50. In preferred embodiments, these outer ribs have a length of at least 4.5 mm, preferably at least 5.0 mm, i.e., an axial extension length. In embodiments, this length is approximately 5.3 mm, which already provides a sufficient grip surface.

[0122] The height of these outer ribs 53, i.e., their radial projection relative to the circumferential surface, is at least 0.3 mm, which allows the user to find a stable gripping surface and, consequently, to open the closure relatively well and relatively easily.

[0123] Closure 1 is manufactured from a color-stable plastic. The following pigments are used as coloring elements to color the plastic: - Titanium dioxide Kronos(registered trademark) 2233 -Soot PRINTEX(registered trademark) F 85 -6975 Titanium Orange -VYNAMON(registered trademark) Green 600734 Therefore, closure 1 made of such material is also suitable for sterilization methods that use gamma rays or X-rays. Such closures produce only a color change that is not perceptible to the naked eye when irradiated with energy doses in the range of 25-40 kGy, and can therefore be considered color-stable.

[0124] Such material compositions are also suitable for other sterilization methods, such as high-temperature steam sterilization up to 134°C for 10 minutes, which produce only color changes that are not visible to the naked eye, or are barely perceptible. [Explanation of Symbols]

[0125] 1 Closure 10 Closing caps 11 Stopper 12 Outer edge of the closing cap 13 Outer edge of the closing cap 14 Hollow chamber 15 Shoulder 16 Stopper 20 sealing elements 21 Seal part 22 Outer edge of the seal portion 23 Outer edge of the seal portion 24 Common-law marriage 25 Notches 30 containers 31 sleeves 33 Tip 34 Aperture 35 rooms 36 colors 40 Mounting part 41 Male screw thread 42 Ribs 44 Curvature 45 Free space 46 Thread entrance 47 Slope 50 Operation part 51 Inner Rib 52 Introductory slope 53 Outer Rib 100 closures 110 Closing cap 112 Outer edge of the closing cap 120 sealing element 121 Seal part 122 Outer edge of the seal portion 140 Mounting part 150 Operation part S Installation dimensions A interval E injection point

Claims

1. A closure for detachably closing the opening at the distal end of a cylindrical container for pharmaceuticals using a Luer lock fastening device, wherein the closure is A cylindrical closing cap comprising a cylindrical hollow chamber for housing and holding a sealing element and a stopper projecting radially outward, the cap including a mounting portion facing the container in the mounted position, the mounting portion having male threads, the male threads engaging with a Luer lock fastening device of the container in the mounted position to create a detachable bond, and the stopper contacting the container in the mounted position, the closing cap and A seal element having a sealing portion that is at least partially located inside the mounting portion and closes the opening at the mounted position, It includes, The outer edge of the sealing element is set back relative to the outer edge of the mounting portion. Two raised portions, forming a pair of raised portions, are provided at two mutually opposing positions on the side surface of the male screw thread. A closure in which the two protrusions are arranged such that, in the installed position, the two protrusions contact the side surface of the threads of the luer lock fastening device and are compressed or deformed.

2. The setback of the outer edge of the sealing element relative to the outer edge of the mounting portion is at least 0.5 mm. The closure according to claim 1.

3. The closing cap further includes an operating portion located on the side opposite to the mounting portion, the sealing element being at least partially located inside the operating portion, and the outer edge of the sealing element being recessed relative to the outer edge of the operating portion. The closure according to claim 1 or 2.

4. The ratio of the length of the sealing element to the length of the closing cap is a maximum of 95%. The closure according to any one of claims 1 to 3.

5. The aforementioned sealing element contains an elastomer material. The closure according to any one of claims 1 to 4.

6. A closure according to any one of claims 1 to 5, The aforementioned male threads are formed in accordance with the ISO 594-2 standard. closure.

7. The aforementioned male thread is formed as a trapezoidal thread. The closure according to any one of claims 1 to 6.

8. The portion of the aforementioned male screw thread located near the entrance to the screw thread is provided with an axial curvature. A closure according to any one of claims 1 to 7.

9. The aforementioned male thread includes a slope, The closure according to any one of claims 1 to 8.

10. A closure according to any one of claims 1 to 9, The closing cap has a continuous opening, and the wall thickness of the closing cap is at its thickest point up to 1.5 mm, and / or the wall thickness does not change by more than 0.5 mm over the length of the closing cap. closure.

11. The injection point is located at one position on the circumferential surface of the operating portion of the closing cap, spaced axially from the outer rib. The closure according to claim 3.

12. The axial distance between the outer stopper and the inner stopper of the closing cap is 2.85 mm, with a tolerance of + / - 0.2 mm. The closure according to any one of claims 1 to 11.

13. The continuous opening has at least two elongated inner ribs on its inner wall that are axially oriented in their primary orientation and project radially inward, and the inner ribs have a width of less than 1 mm. The closure according to claim 10.

14. The width or cross-section of the inner rib is constant over most of the length of the inner rib. The closure according to claim 13.

15. The operating portion includes at least two elongated outer ribs that are axially positioned in their primary orientation and project radially outward from the circumferential surface. The closure according to claim 11.

16. A closure according to any one of claims 1 to 15, The closure contains a color-stable plastic. A closure characterized by the following features.

17. The closure color is grayish-green, which corresponds to color tone RAL 7009 according to the RAL color chart. The closure according to claim 16.

18. The material for the closure is the pigment described below: - Titanium dioxide Kronos (registered trademark) 2233 - Soot PRINTEX (registered trademark) F 85 -6975 Titanium Orange - VYNAMON (registered trademark) Green 600734 It includes as a coloring element, The closure according to claim 16 or 17.

19. A method for detachably closing the distal end of a cylindrical container for pharmaceuticals using a Luer lock fastening device, using the closure according to any one of claims 1 to 18, without contamination.

20. The tightening torque and / or release torque have a small variation of only + / - 1.0 N·cm relative to the respective required torques. The method according to claim 19.

21. A method for manufacturing a closure according to any one of claims 1 to 18, The closure includes an operating element having at least two outer ribs, is manufactured using an injection molding method, and an injection point is selected in the region of the operating portion. A method characterized by the following:

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