WO2005000703A2

WO2005000703A2 - Closure for lyophilizing

Info

Publication number: WO2005000703A2
Application number: PCT/EP2004/006527
Authority: WO
Inventors: Albert Louis Victor Jozef Claessens
Original assignee: Helvoet Pharma Belgium N.V.
Priority date: 2003-06-23
Filing date: 2004-06-17
Publication date: 2005-01-06
Also published as: DE102004029119A1; WO2005000703A3

Abstract

The invention relates to a closure (1) for lyophilizing, comprising a sealing part (7). In order to create a structure that is accessible for treatment while being robust during transport, the sealing part (7) is accommodated within a fixing part (6) which is to be placed upon a container (3) in two axially different positions, i.e. a first position in which the sealing part (7) cooperates with the container (3) in a non-sealing manner while an atmospheric connection is provided to the interior (3') of the container, and a second position in which the sealing part (7) cooperates with the container (3) in a sealing fashion.

Description

Lyophilization Nerschluss

The invention relates to a freeze-drying circuit with a sealing part.

A freeze-drying plug is known from EP 0322547 AI. It is only partially inserted into the neck of the container filled with the substance to be treated. This allows a circulation between the inside of the container and its surroundings due to the remaining recesses in the stopper. Vapors can escape during freeze drying. When the treatment is finished, the freeze-drying plug is pushed in completely. There is then a hermetic seal.

A closure for infusion or transfusion containers is known from DE 101 38 191 AI. The has a mounting part with a sealing part accommodated therein. The former can be assigned astride the neck bulge of the container and secured via an axially displaceable ring part.

In addition, the invention is to design a generic freeze-drying closure that is accessible to treatment and robust in transportation.

This object is achieved first and foremost in a freeze-drying closure with the features of claim 1, with the aim being that the sealing part is accommodated in a holding part which is to be applied to a container in two axially different positions, namely in a first Position in which the sealing part does not cooperate in a sealing manner with the container and there is an air connection to the interior of the container, and a second position in which the sealing part cooperates in a sealing manner with the container.

BESTÄTIGU.MGSKOPMε As a result of such an embodiment, a generic freeze-drying closure of increased use value is achieved. There is a highly stable assembly unit in itself. Operationally, this can be assigned to the container in a sufficiently firm manner. One of the two axially different positions is aimed at a gripping stop and the other at a final assembly stop. They can also be switched exactly. Any jumps from freeze-drying closures that occur due to transport are practically impossible. The air connection between the interior of the container and the surroundings is equivalent with regard to the containers, and so is the sealing effect.

The subject matter of the further claims are explained below in relation to the subject matter of claim 1, but may also be of importance in their independent formulation. In this way, the holder part has a clasping section for latching on the neck of the container in the first position. The clasp can be selected tightly, so that even unfavorable tolerance pairings cannot lead to a disadvantage. It is further provided that a ventilation section is formed axially above the clasping section on the holding part. It is closed as soon as the holding part has entered its second position, in which the sealing element interacts accordingly with the container. The sealing element is fixed on the mounting part in the sense of the desired assembly unit, for which purpose the mounting part further has an overlapping section which surrounds the top of the sealing part. Then there is an advantageous feature of the invention that the retaining part is assigned a retaining ring part which, from a first release position secured to the retaining part, in which the retaining part can be moved from the first position into the second position, into a second locking position, which likewise is secured to the bracket part, is displaceable. Such a similar to a hoop Circlip body primarily allows the radial evasion of the bracket portion. It is then moved to the safety position. Such agents replace the classic flaring process. Specifically, an embodiment has been selected with regard to the restraining means in such a way that the holding part has axially directed claws which, assigned to their free end region, in any case have a first holding bead which is formed on the inside and extends in the circumferential direction. This defines the plug seat of the closure that leaves the air connection. Using the radially inward restoring or steering force of the claws, this could already be sufficient, but it is preferred to proceed so that a second mounting bead is formed axially below the first mounting bead, the axial spacing of the mounting beads being adapted to a neck bead of the container is. Its periphery is fully gripped on three sides. Any shaking movements during the transport of the containers have no consequences; the second mounting bead prevents the closure from being loosened upwards. Then an advantageous feature of the invention is that the ventilation section is designed as a circumferential opening between two claws, which circumferential opening in the first position of the holding part provides the air connection to the interior of the container and continues there continuously in the clip section. This design is comparable to a spring-loaded ring of teeth, with a rotationally symmetrical wall design provided further increasing the corresponding spring capacity. In fact, a plurality of circumferential openings are formed between the claws. It is also provided that the holding part and / or the securing part are injection molded parts. The securing part is part of a cap having a cap cover. This opens the access in the required manner, for example for a cannula or an infusion or transfusion set. This is embodied with regard to the cap in the form of a tear-open tab with a predetermined tear line that is generally defined. As for the other ways of assigning the sealing part As far as one is concerned, the sealing part and the holding part are welded. Laser welding can be used here, for example. In this regard, reference is made to the unpublished German patent application with the official file number 103 11 154.9. The content of the disclosure of this patent application is included in full in the present application, also for the purpose of formulating additional claims.

Another economical possibility then arises from the fact that the sealing part is form-fit in the holding part, realized by a locking bead for holding the sealing part under the holding part in the holding part. The sealing part can be easily clipped on. This preferably consists of TPE. It can be manufactured using a two-component spraying process or by means of assembly. However, the use of a known rubber sealing part is also possible. Closing by means of the sealing part takes place in the freeze-drying machine, so it is carried out before it opens again.

The subject matter of the invention is explained in more detail below on the basis of an illustrative exemplary embodiment. It shows:

1 shows a vertical section through a freeze-drying closure, astride a container, in a first position of the holding part, according to a basic version,

2 shows a representation corresponding to FIG. 1, but located in a second position of the holding part and with the circlip part activated, 3 shows the top view of FIG. 2,

4 shows the freeze-drying closure in a cut perspective view in the position according to FIG. 1,

5 shows the same in the position according to FIG. 2,

6 shows a variant of the freeze-drying closure as shown in FIG. 1,

7 is the same in representation as Fig. 2,

8 shows a representation according to FIG. 6, with a rubber plug which is only held in a clamp,

9 the object of FIG. 8 in the position of FIG. 2,

Fig. 10 is an individual representation of the mounting part, as used in the subject of Fig. 8, in a spread form.

The freeze-drying closure shown is constructed in several parts and is designated 1 in its entirety.

The freeze-drying closure 1 can be assigned to the neck 2 of a container 3 in two stages. In the container 3 there can be, for example, a pharmaceutical powder which is dried by freezing using the sublimation effect. This is also called lyophilization. In the open position, the first position of the freeze-drying closure, in a freeze-drying machine, as also described below, sublimation, to expel the moisture, take place in a freeze-drying cabinet enclosed therein. Even within the freeze-drying machine or the freeze-drying cabinet, the closure is moved to the second, closed position by means of a pressure part located therein, as also mentioned below.

Regarding the container 3, it can be a glass vial. The neck 2 ends in a neck bead 4. It points radially outwards. Its accumulation of material leads to an end face 5 which is significantly widened in area compared to the general wall thickness of the container 3.

The longitudinal central axis of the practically cylindrical unit 1, 3 is designated x-x.

The part of the freeze-drying closure 1 which provides the two-stage assignment is an essentially pot-shaped holding part 6. A sealing part 7 is accommodated in this. The latter has an essentially disk-like shape with a centrally located, rudimentary plug 8 which, centering in the first line but also sealingly, can enter the neck opening 9. The ring-shaped environment of the stopper 8 is noticeably jumping back and is matched in width to the end face 5, so that there is a perfect seal there.

The sealing part 7 can consist of rubber. However, TPE is preferably used. The tethering of the sealing part 7 to the holding part 6 can advantageously be achieved by means of a two-component injection molding process. A snap connection is also conceivable. In particular in the snap connection, but also in another connection between the sealing part 7 and the holding part 6 manifests a significant advantage of the arrangement described here. In principle, any sealing part can be used. In particular also one that has already received approval from a certain user, for example in combination with another closure.

A solution is preferred in that the sealing part 7 and the holding part 6 are welded together. This can be achieved particularly advantageously using the so-called laser welding process. For this purpose, the holding part 6 is transparent, at least in the sense of permeability for laser beams.

The variant according to FIGS. 6 and 7 shows that the sealing part 7 is held in a form-fitting manner in the holding part 6. This is achieved by means of a latching bead 10. It is molded on the inside of the holding part 6 and is used to hold the sealing part 7 in the holding part 6 in a manner that grips around the edges, for this purpose the periphery of the sealing part 7 is undercut in a rotationally symmetrical manner.

An already existing radial distance 11 between the inside of the holding part 6 and the corresponding periphery of the sealing part 7 is used to accommodate said latching bead 10. The supporting fastening base for the disk-shaped sealing part 7 is provided by the bottom 12 of the pot-shaped holding part 6, which is located at the top by means of an inverted section.

The bottom 12 leaves a centrally located passage opening 13 for a cannula or the like, which can penetrate the soft body, ie the sealing part 7. Less the described circular passage opening 13, an annular overlap section 14 remains on the holding part 6, which embraces or covers the sealing part 7 on the upper side up to the edge region.

This encirclement or encapsulation by the holding part 6 or also by the optionally provided circlip part, in particular its cap cover 23, also provides the essential advantage that this pressure part does not fall in relation to the displacement of the closure into the second position by a pressure part acting on the top side The sealing part 7 comes into contact. The sealing part 7, in particular if it is made of rubber, in which case there is a corresponding inclination, in particular at the temperatures considered here, cannot adhere to the pressure part, so that it is avoided that, if necessary, by means of the Under certain circumstances, the sealing part then adheres the entire container to the pressure part, which has been raised again.

The fastening measures explained can advantageously be placed in the region of the overlap section 14.

The hole edge of the passage opening 13 diverges away from the relationship. So there is a frustoconical clearance.

In this context, in particular, the general idea that the sealing part 7 is completely free from the container 3, in particular its end face 5, is also important in this context.

The two-stage assignability of the holding part 6 takes into account a captive pre-capturing position relative to the container 3 and a function that provides the seal. This is realized in the form that the holding tion part in two axially different positions is to be applied to the container 3, namely in a first position in which the sealing part 7 does not cooperate in a sealing manner with the container 3 and so there is an air connection to the interior 15 of the container (see FIG. 1), and one second position, in which the sealing part 7 cooperates sealingly with the container 3 (see FIG. 2).

For the correspondingly graduated latching of the holding part 6, this has a U bracket section 15 which interacts with the neck bead 4 of the container 3. This secures the assumed first position of the holding part 6 in such a way that a ventilation section 16 remains on the holding part 6 axially above said clasping section 15, providing the air connection mentioned between the surroundings of the container 3 and the interior 3 ^{1 of} the container.

The environment can be a closed freeze dryer (not shown). In freeze drying, vapors or gases can circulate until the substance to be dried has the desired degree of treatment. Only then does the freeze drying closure 1 close with a corresponding mechanical device in the closed interior of the freeze drying machine.

The clasping section 15 is embodied in the form of axially inwardly directed claws 17 of the holding part 6. The contour of the claws 17 largely follows the peripheral contour of the neck bulge 4; in any case, an exact resting position is achieved.

The claws 17 are formed in a plurality, constituting a circumferential claw ring. The claws 17 leave circumferential openings obtained by cutting free 18, also in a plurality. Correspondingly, the ventilation section 16 is realized as a circumferential opening 18 between two claws 17, which circumferential opening 18 in the first position of the holder part 6 provides the air connection to the interior 3 'of the container and continues into the urine clearing section 15, that is to say continuously there. This results in axially oriented spring fingers cut free up to just before the bottom 15, obtained from the ring wall 19 of the cup-shaped holding part 6. The wall curvature contributes to increasing the resilience or restoring force in the sense of locking.

The axially directed claws 17 have in their. End region of a first mounting bead 20 which extends in the circumferential direction and is formed on the inside of the ring wall 19. It rests on the upper edge of the exposed neck bead 4. The first mounting bead 20 supports the mounting part 6 of the freeze-drying closure 1 in a height-defined manner. There can be no unwanted closing of the ventilation section 16, for example by the holder part 6 sliding down on the neck 2 of the container 3.

The bracket 20 described is interrupted according to the positioning on the claws 17.

The cup-shaped mounting part 6 is also secured against opposing displacement. A corresponding tendency can occur due to rough shaking movements / fine vibrations during the transport of the container 3. However, this is counteracted with simple means. Namely, a second mounting bead 21 is formed axially below the first mounting bead 20. The latter engages under the lower edge of the cantilever neck bead 4. It can be seen that the axial distance between the mounting beads 20, 21 is adapted to the vertical edge thickness of the neck bead 4 of the container 3. There is such a U-shaped receiving space on the claws 17. A comparison e.g. 1 and 2 makes it clear that the first mounting bead 20 can nevertheless be overcome with will, in the sense of the closure of the freeze-drying closure 1. The closing takes place by exerting a vertically downward force, as a result of which the first mounting bead 20 is underneath Digging outward angles of the claws 17 from its active support position, sliding over the outer edge of the neck bead 4 and finally snapping under the lower edge thereof. The second mounting bead 21 finally ends up on the shoulder of the container 3. It can deform in a centering manner thereon, or it can also rest on it without being deformed.

As already indicated above, this second position of the holding part 6 can be secured in the sense of a measure comparable to the flanging. For this purpose, a retaining ring part 22 is assigned to the holding part 6. Its ring acts like an encircling hoop on the ring wall 19. The securing ring part 22 initially releases the latching mobility of the claws 17.

The locking ring part 22 is part of a cap having a cap cover 23. It sits astride the pot-shaped mounting part 6, specifically by means of a stop defined by a stop, which stop position can, however, be overcome with emphasis on the will. The support is achieved by a locking rib 25 seated at the free end of the ring wall 24. It is exposed in the direction of the ring wall 19 of the mounting part 6 and, when preassembled, is inserted in a circumferential locking groove 26 of the mounting part 6.

The retaining ring part 22 is associated with the retaining ring part 22 in such a way that it can be moved from a first release position (FIG. 1) which is secured against locking on the retaining part, in which the retaining part 6 can be moved from the first to the second position. can be axially displaced into a second securing position (see FIG. 2), which is in any case secured to the H-aging part 6. The corresponding axial stroke is ensured by appropriate vertical spacing y of the cap end 23 of the retaining ring part 22 from the bottom 12 of the holding part 6. The locking rib 25 which lifts out overflows the area of the jacket wall occupied by the ventilation section 16 and finally lies below the edge under a rotationally symmetrical wall projection 27 the ring wall 19, forming the crimp-like grip, so that the closure 1 is secured.

In order to reinforce the hold of the locking ring part 22, the inside of the ring wall 24 of the locking ring part 22 and the corresponding outside of the ring wall 19 of the holding part 6 are roughened, preferably horizontally grooved. The grooves 28 and the resulting ribs interlock with one another to prevent sliding. In order to achieve the structural strength required for this, the holding part 6 and / or the locking ring part 22 are created as plastic injection molded parts.

The cap cover 23 provides access to the use of the container 3, specifically in the form of a tear-open flap 29 which is otherwise to be kept in a hole in the cap cover 23. The contour of the latter results from FIG. 3 Pulling part going slightly over the edge of the circlip part 22. This makes it easier to grasp. A first section is cut free to form a gap, the rest is designed as a normal predetermined breaking line, for example in the form of a notch valley following the tab contour.

Further details of the described locking ring part solution can be found in German patent application 101 38 191.3-27. The disclosure content of this Forerunner is fully related to the content of this application, also for the purpose of formulating additional claims.

The central area of the tear-open tab 29 corresponds essentially to the contour of the passage opening 13 of the bottom 12 described above. This area is lowered from the general plane of the cap cover 23 so that it can dip into the said passage opening 13.

With regard to the claws 17, it should also be noted that their root near the ground extends freely up to the radial distance 11. A reduced-thickness joint is formed here. The result is a kind of film hinge.

Axially oriented ribs 30 are located on the inside of the ring wall 24. They can enter the corresponding grooves of the ring wall 19 in a rotationally locking manner.

In the embodiment of FIG. 8, a stopper 8 made of rubber is clamped in the holding part 6. This is done by means of clamping tips 31 protruding on the inside of the holding part 6. A plurality of clamping tips are provided distributed over the circumference. As can be seen, they are formed in the holding part 6 in such a way that they clamp the stopper 8, when the stopper 8 rests on the upper side against the overlap 14, in the edge region, which also sits sealingly on the bottle neck (see also FIG. 9) holders. The plug 8, which is made of natural or synthetic rubber 8, is only held by clamping in the holding part 6. A plurality of clamping tips 31 are formed over the circumference. They have a triangular outline in their area projecting inward beyond the holding part 6. The illustration according to FIG. 8 shows various views offset with respect to the circumference, one view intersecting a clamping tip 31, while the other view passes through an opening 18.

The unfolded version of the holding part 6 can be seen from the illustration in FIG. 10. In more detail than shown in FIG. 8, it can be seen that a total of eight Klernm tips 31 are provided distributed over the circumference in the embodiment.

Otherwise, the mounting part 6 corresponds to the mounting parts 6 described above.

All of the features disclosed are (in themselves) essential to the invention. The disclosure content of the associated / attached priority documents (copy of the prior application) is hereby also included in full in the disclosure of the application, also for the purpose of including features of these documents in claims of the present application.

Claims

EXPECTATIONS

1. Freeze-drying closure (1) with a sealing part (7), characterized in that the sealing part (7) is accommodated in a holding part (6) which is to be applied to a container (3) in two axially different positions, namely in a first position, in which the sealing part (7) does not cooperate in a sealing manner with the container (3) and there is an air connection to the interior of the container (3 ¹ ), and in a second position, in which the sealing part (7) seals with the container (3) works together.

2. Freeze-drying closure according to claim 1 or in particular according thereto, characterized in that the holding part (6) has a clasping section (15) for locking on the neck (2) of the container (3) in the first position.

3. Freeze-drying closure according to one or more of the preceding claims or in particular according thereto, characterized in that a ventilation section (16) is formed axially above the reclamation section (15) on the holding part (6).

4. Freeze-drying closure according to one or more of the preceding claims or in particular according thereto, characterized in that the holding part (6) further has an overlapping section (14) which surrounds the sealing part (7) on the upper side.

5. Freeze-drying closure according to one or more of the preceding claims or in particular according thereto, characterized in that the holding part (6) has a clamping section for holding the sealing part (7) in a clamping position.

6. Freeze-drying closure according to one or more of the preceding claims or in particular according thereto, characterized in that the retaining part (6) is assigned a retaining ring part (22) which, from the first, on the holding part (6) detented release position, in which the Bracket part (6) can be moved from the first to the second position, can be moved to a second securing position, which is also secured to the bracket part (6).

7. Freeze-drying closure according to one or more of the preceding claims or in particular according thereto, characterized in that the holding part (6) has axially directed claws (17) which, assigned to their free end region, in any case have an internally formed, extending in the circumferential direction have the first mounting bead (20).

8. Freeze-drying closure according to one or more of the preceding claims or in particular according thereto, characterized in that a second mounting bead (21) is formed axially below the first mounting bead (20), the axial spacing of the mounting beads (20, 21) is adapted to a neck bulge (4) of the container (3).

9. Freeze-drying closure according to one or more of the preceding claims or in particular according thereto, characterized in that the ventilation section (16) is designed as a peripheral opening (18) between two claws (17), which peripheral opening (18) in the first position of the shark - tion part (6) gives the air connection to the interior of the container (3 ¹ ) and continues there continuously in the clasping section (15).

10. Freeze-drying closure according to one or more of the preceding claims or in particular according thereto, characterized in that a plurality of peripheral openings (18) is formed between the claws (17).

11. Freeze-drying closure according to one or more of the preceding claims or in particular according thereto, characterized in that the holding part (6) and / or the retaining ring part (22) are injection-molded plastic.

12. Freeze-drying closure according to one or more of the preceding claims or in particular according thereto, characterized in that the retaining ring part (22) is part of a cap having a cap cover (23).

13. Freeze-drying closure according to one or more of the preceding claims or in particular according thereto, characterized in that the cap has a tear tab (29).

14. Freeze-drying closure according to one or more of the preceding claims or in particular according thereto, characterized in that the sealing part (7) and the holding part (6) are welded.

15. Freeze-drying closure according to one or more of the preceding claims or in particular according thereto, characterized in that the sealing part (7) in the holder part (6) is positively mounted.

16. Freeze-drying closure according to one or more of the preceding claims or in particular according thereto, characterized by a locking bead (10) for engaging the sealing part (7) in the holding part (6).

17. Freeze-drying closure according to one or more of the preceding claims or in particular according thereto, characterized by clamping tips (31) protruding on the inside in the clamping section.

18. Freeze-drying closure according to one or more of the preceding claims or in particular according thereto, characterized in that a clamping tip (31) is triangular in its outline.

19. Freeze-drying closure according to one or more of the preceding claims or in particular according thereto, characterized in that the sealing part (7) is completely free of the container (3) in the first position.

20. Freeze-drying. Closure according to one or more of the preceding claims or in particular according thereto, characterized in that the sealing part (7) is in any case covered by a hard plastic part to the extent that a pressure part with which the sealing part (7) can be moved into the second position is not comes into contact with the sealing part (7).