FIELD OF THE INVENTION

The present invention relates generally to medical devices and more specifically to methods and arrangements for securing safe and sterile fluid access to medical containers. BACKGROUND OF THE INVENTION

Within drug delivery it may be of vital importance to maintain sterility of a product to be administered from its production to its administration. Many drug substances are therefore supplied in sealed containers having penetrable access means, such as rubber septa, which are adapted to be pierced by a person using a suitable tool, e.g. a hollow needle. Some pharmaceutical drugs adapted for parenteral administration are only stable in the ad- ministrable form a relatively short period of time. For convenience reasons and in order to extend the shelf life of such a drug it is sometimes preferred to store individual constituents of the drug separately and to mix them only just before a dose is needed.

Traditionally, a mixing of two substances stored in separate vials is performed using a sy- ringe with a needle to withdraw one substance from one vial and inject it into the other vial containing the other substance. The syringe with the attached needle is then used to withdraw from this vial the desired amount of drug to be injected into the patient. This kind of manual operation is cumbersome and may bring about some uncertainty as to the exact concentration of the resulting drug, because it can be difficult to completely empty a vial by such an approach. Moreover, since the first substance is withdrawn from one vial and transported to another vial via a syringe with a needle, typically including a penetration of two rubber septa in order to establish fluid connection to the respective vial interiors, both sterility and safety may be compromised. To reduce the risk of contamination of the administrable substance it is customary to clean the respective rubber septa with an alcohol swab before needle penetration. This, however, is often considered a hassle by the user, especially if she/he needs to mix the substances and administer the resulting drug quickly to avert a serious situation.

US 5,466,220 (Bioject, Inc.) discloses a drug mixing and transfer device comprising a vial and a syringe co-axially arranged to enable relative motion between them from a fluidly un- connected to a fluidly connected state. During this relative motion a needle on the syringe penetrates a vial seal to allow liquid to be transferred from the syringe into the vial. The device itself is packaged in a flexible protective sterile packaging which is not removed until the vial and the syringe have been pushed together to establish a fluid connection via the needle. While such a device may overcome some of the above mentioned drawbacks of the traditional mixing procedure it appears to entail other inexpediencies. For example, to maintain sterility from acquisition of the device to attainment of an administrable product a user is required to perform the initial operations of the device while it is still in its protective packaging. This introduces a risk of fumbling which can be very stressful in situations where fast mixing and delivery is needed. Furthermore, the particular solution requires a sterilisation of the whole device and thereby also assembly and packaging thereof in a clean room.

WO 97/46203 (Applied Research Systems ARS Holding N.V.) discloses a pre-assembled pack for a drug reconstituting device, which pack comprises a vial co-axially aligned with a cartridge and separated therefrom by a double-ended needle element. The needle element is supported by a two-part needle hub which comprises a protruding portion capable of collapsing within a base portion to cause penetration of a cartridge closure. The cartridge closure engages a sleeve around one end of the double-ended needle element. During use when the protruding portion collapses into the base portion a frangible portion adjoining the two are broken. Thereby, a portion of the needle element becomes exposed to the surround- ing internal environment.

SUMMARY OF THE INVENTION

Having regard to the above, it is an object of the invention to provide an arrangement for securing safe and sterile access to a medical container. Further, it is an object of the invention to provide an arrangement for safe and sterile transfer of media between containers. In particular, it is an object of the invention to provide a simple, intuitive and easy to use arrangement for mixing substances contained in separate containers, which arrangement eliminates the risk of erroneous handling and ensures that sterility of the substances is maintained throughout the mixing procedure.

In the disclosure of the present invention, aspects and embodiments will be described which will address one or more of the above objects and/or which will address objects apparent from the below disclosure as well as from the description of exemplary embodiments. In a first aspect of the invention an assembly for a fluid transfer arrangement is provided. The assembly comprises a first medical container having an outlet opening and defining a general axis, a closure member for sealingly closing the outlet opening, and a connection member comprising a) a transversal base section from which a hollow piercing member pro- trudes in a direction towards the first medical container, and b) a cylindrical sleeve extending axially from the base section. The hollow piercing member is arranged co-axially with the first medical container, and the cylindrical sleeve surrounds the hollow piercing member. The assembly further comprises reception means fluidly connected with the hollow piercing member and structured to receive a second medical container. The closure member com- prises a circumferential lip portion configured for sealing engagement with an inner surface of the cylindrical sleeve, to thereby define a fluid tight chamber. The circumferential lip portion is capable of sliding along the inner surface of the cylindrical sleeve from a first position in which the closure member fluidly separates the hollow piercing member and the first medical container to a second position in which the hollow piercing member has penetrated the closure member and established fluid connection to the first medical container.

Such an assembly enables a fluid transfer arrangement, wherein no separate sterile barriers are needed to maintain an aseptic environment of the drug contacting surfaces. The assembly can be incorporated as part of a pre-assembled device and the sharp piercing member can be completely shielded from the user, thereby avoiding potential stick injuries. The as- sembly can be sterilised before assembly of the device, whereby the need for swabbing of at least one penetrable container closure by the user will be eliminated.

The assembly may further comprise vent means structured to allow air to escape the fluid tight chamber, when the circumferential lip portion slides along the inner surface of the cylindrical sleeve. Thereby, the force required to cause penetration of the closure member can be significantly reduced.

In some embodiments, the vent means comprises a pair of ribs extending axially along an inner surface portion of the cylindrical sleeve and defining, together with the inner surface portion of the cylindrical sleeve, a fluid channel. In other embodiments, the vent means comprises an axially extending groove in an inner surface portion of the cylindrical sleeve. The vent means may extend axially from the base section and terminate within the fluid tight chamber adjacent to the first position of the circumferential lip portion. This will allow the circumferential lip portion to seal the sterilised spike chamber while being in the first position and the vent means to depressurise the chamber shortly after the circumferential lip portion commences the sliding movement along the cylindrical sleeve.

In case the assembly does not include vent means the cylindrical sleeve may be designed to extend axially from the base section a distance which enables the entrapped air in the fluid tight chamber to be compressed to a degree allowing for penetration of the closure member by the hollow piercing member.

The circumferential lip portion may comprise a suitable elastic material, such as e.g. rubber. In particular embodiments, the entire closure member is made of a rubber material.

In a second aspect of the invention a fluid transfer device is provided comprising a first med- ical container having an outlet opening and defining a general axis, a closure member for sealingly closing the outlet opening, a hollow piercing member arranged co-axially with the first medical container and protruding from a transversal base section in a direction towards the first medical container, and a cylindrical sleeve extending axially from the base section and surrounding the hollow piercing member. The fluid transfer device further comprises a second medical container arranged in or for fluid communication with the hollow piercing member. The closure member comprises a circumferential lip portion configured for sealing engagement with an inner surface of the cylindrical sleeve, to thereby define a fluid tight chamber housing the hollow piercing member. The circumferential lip portion is capable of sliding along the inner surface of the cylindrical sleeve from a first position in which the clo- sure member fluidly separates the hollow piercing member and the first medical container to a second position in which the hollow piercing member has penetrated the closure member and established fluid connection to the first medical container.

The fluid transfer device may be used to combine a first medium contained in the first container and a second medium contained in the second container to obtain an administrable drug product. For example, the first medium may be a solvent for reconstitution of a powdered second medium.

In the present specification, reference to a certain aspect or a certain embodiment (e.g. "an aspect", "a first aspect", "one embodiment", "an exemplary embodiment", or the like) signifies that a particular feature, structure, or characteristic described in connection with the re- spective aspect or embodiment is included in, or inherent of, at least that one aspect or embodiment of the invention, but not necessarily in/of all aspects or embodiments of the invention. It is emphasized, however, that any combination of features, structures and/or charac- teristics described in relation to the invention is encompassed by the invention unless expressly stated herein or clearly contradicted by context.

The use of any and all examples, or exemplary language (e.g., such as, etc.), in the text is intended to merely illuminate the invention and does not pose a limitation on the scope of the same, unless otherwise claimed. Further, no language or wording in the specification should be construed as indicating any non-claimed element as essential to the practice of the invention.

BRIEF DESCRIPTION OF THE DRAWINGS

In the following the invention will be further described with references to the drawings, wherein

Fig. 1 shows an exploded view of a drug mixing arrangement employing an assembly according to an embodiment of the invention,

Fig. 2 shows a longitudinal section view of the arrangement of Fig. 1 , in a pre-use state,

Fig. 3 shows a longitudinal section view of the arrangement after fluid connection is estab- lished between the included reservoirs,

Fig. 4 shows a longitudinal section view of the arrangement after removal of the cover,

Fig. 5 shows a close-up perspective view of a mechanical connection between the cover and the syringe holder,

Fig. 6 shows a transverse section view along line A-A of Fig. 3, Fig. 7 shows a close-up longitudinal section view of an assembly according to an embodiment of the invention as employed in the drug mixing arrangement of Fig. 1 , and

Fig. 8 shows a longitudinal section view of an assembly according to another embodiment of the invention.

In the figures like structures are mainly identified by like reference numerals. DESCRIPTION OF EXEMPLARY EMBODIMENTS

When in the following relative expressions, such as "upwards" and "downwards", are used, these refer to the appended figures and not necessarily to an actual situation of use. The shown figures are schematic representations for which reason the configuration of the differ- ent structures as well as their relative dimensions are intended to serve illustrative purposes only.

Fig. 1 is an exploded perspective view of a mixing device 1 for reconstitution of a powdered drug in a vial 20 using a solvent from a syringe 10. The vial 20 comprises a wall 21 having an opening which is sealed by a vial stopper 23 (not visible in this view) and a seal cap 22. The vial 20 is arranged in a vial holder 2 which serves to position and protect the vial 20. A lock ring 3 is fitted over a portion of the vial holder 2 and locked against rotation relative to the vial holder 2 via a longitudinal internal rib (not visible) engaging a longitudinal groove 9 in the outer surface of the vial holder 2. A tower 25 protrudes axially from the seal cap 22 in the direction away from the vial 20. The tower 25 has an inner circumferential sealing rim 26 at its end portion, the purpose of which is explained below.

In the disclosed embodiment the wall 21 is made of glass and the vial holder 2 is made of a transparent plastic. Other suitable materials may, however, be chosen depending on the specific application of the mixing arrangement 1 .

The lock ring 3 is connected to a coupling element 40 via a cam 91 on the interior surface of the lock ring 3 and a cam receiving bayonet groove (not visible) in an exterior surface of the coupling element 40. In the pre-assembled state of the mixing device 1 the cam 91 is positioned at the end of the bayonet groove, whereby the lock ring 3 and the coupling element 40 are prevented from relative translational motion but allowed to undergo a limited relative rotation. The coupling element 40 is a tubular sleeve which further comprises an exterior thread 43 at its distal end portion for engagement with an interior thread 7 (not visible in this view) in the vial holder 2, and an interior thread 41 at its proximal end portion for engagement with an exterior thread 31 of a syringe holder 30. The coupling element 40 also has an exterior thread 42 arranged proximally of the exterior thread 43. The pitch of the interior thread 41 is greater than the pitch of the exterior thread 42. The syringe holder 30 has a proximal portion adapted to receive and hold a portion of the syringe 10, and a distal portion which carries the exterior thread 31 and which is designed to accommodate a connector piece 50 comprising a sleeve body 51 and a distally pointing hollow spike member 52. A number of ratchet arms 32 are arranged equidistantly along the circumference of a central portion of the syringe holder 30. The purpose of these ratchet arms 32 will be clear from the below.

The syringe 10 comprises a barrel 1 1 , the outlet of which is surrounded by a threaded Luer collar 13 and sealed by a syringe stopper 60. A user manipulable piston rod 14 having a push face 15 for easy operation is adapted to drive a piston 19 (not visible in this view) in- side the barrel 1 1. At its proximal end portion the barrel 1 1 holds a flange carrier 80 provided with opposite spreadable wings 81 for offering a more ergonomic grip of the syringe 10.

A cap 4 is adapted to cover the syringe 10 during storage and transportation of the mixing device 1 to prevent operation of the piston rod 14 and thereby to ensure that pressure is not prematurely applied to the contents of the syringe 10. The cap 4 has an interior thread 5 (not visible in this view) adapted to engage with the exterior thread 42 for positioning of the cap 4 relative to the coupling member 40.

Fig. 2 is a longitudinal section view of the mixing device 1 in the assembled state, prior to a first use thereof, showing further details of the arrangement. This state corresponds to the one in which the mixing device 1 is intended to be delivered by the manufacturer. The piston rod 14 is in a retracted position in the barrel 1 1 , thereby defining a syringe interior 18 capable of holding a certain volume of a solvent (not shown). The piston rod 14 is coupled firmly to the piston 19 via a jagged coupling head 16. The cap 4 is fitted snugly around a collar 17 at the proximal end of the syringe 10 and the wings 81 are folded down along the barrel 1 1. This provides a user friendly slender configuration of the mixing device 1 . A Luer 12, defining an outlet of the syringe 10, protrudes into the distal portion of the syringe holder 30 and is retained therein via a screw thread connection between the Luer collar 13 and a threaded inner portion 71 of a stopper fastener 70. A couple of protrusions 72 are provided on the stopper fastener 70 to rotationally lock the stopper fastener 70 with respect to the syringe holder 30. This is described in more detail in connection with Fig. 6. A lock snap 74 on the syringe holder 30 is engagement with the protrusions 72 to provide a bi-directional translational coupling between the stopper fastener 70 and the syringe holder 30. A portion of the syringe stopper 60 is wedged between the Luer 12 and the threaded inner portion 71 and thereby provides a fluid tight engagement with the exterior surface of the Luer 12. The syringe stopper 60 carries a filter 69 for filtering out any impurities of a passing liquid and has a penetrable section 61 allowing for easy rupturing of the syringe sealing by a suitable tool. The connector piece 50 is slidably received in the hollow interior of the distal portion of the syringe holder 30. The sleeve body 51 supports a transverse spike base 54 which carries the distally pointing hollow spike member 52 as well as a proximally pointing hollow spike member 53. In the depicted state of the mixing device 1 the hollow spike member 53 is arranged just distally of the penetrable section 61 and the hollow spike member 52 is arranged just proximally of a penetrable section 24 of the vial stopper 23. The syringe 10 and the vial 20 are therefore fluidly unconnected at this point. The syringe stopper 60 has at its distal end a circumferential sealing lip 62 which is adapted to sealingly engage with an interior portion of the sleeve body 51 to provide a fluid tight compartment 56 for the hollow spike member 53. Similarly, the tower 25 with the sealing rim 26 provides a fluid tight compartment 57 for the hollow spike member 52. This particular construction thus enables the incorporation of a sterilised sub-assembly comprising the syringe stopper 60, the connector piece 50 and the vial stopper 23 during assembly of the mixing device 1 , and further ensures that sterility of the respective hollow spike members 52, 53 is maintained throughout storage, transportation and use of the mixing device 1 with no need for additional sterile barriers. One or more vents 59 are provided in the sleeve body 51 to allow gas, e.g. air, entrapped within the sterile compartment 56 to escape during establishment of fluid connection between the syringe 10 and the vial 20, as will be explained in more detail below.

The coupling element 40 has a number of circumferentially spaced apart catch arms 45 extending downwards from a transversal portion at the end of the interior thread 41 for secur- ing firm attachment of the vial 20. The wall 21 defines a vial interior 28 capable of holding an amount of powdered drug (not shown) to be reconstituted by the solvent from the syringe 10. The wall 21 is flexibly supported by leaf springs 8 in the bottom of the vial holder 2 to account for manufacturing tolerances.

Fig. 3 shows the mixing device 1 after unscrewing of the cap 4 from the exterior thread 42 and an automatically effected establishment of fluid connection between the syringe interior 18 and the vial interior 28. The cap 4 still covers the syringe 10, although now the cap 4 can be easily removed by simply pulling it away from the coupling element 40. Axially extending ribs 6 are arranged on an interior surface of the cap 4 for engagement with the ratchet arms 32, providing for a unidirectional rotational coupling between the cap 4 and the syringe holder 30, ensuring that the cap 4 and the syringe holder 30 are locked against relative rotation during unscrewing of the cap 4 from the exterior thread 42. The exterior thread 42 is a right-hand thread and the interior thread 41 is a left-hand thread, so when the cap 4 is unscrewed from the exterior thread 42, and the cap 4 thereby is moved axially away from the coupling element 40, the exterior thread 31 is screwed further into the interior thread 41 , whereby the syringe holder 30 is moved axially in the opposite direction towards the vial 20, while the ratchet arms 32 slide along the ribs 6. Because the pitch of the interior thread 41 is greater than the pitch of the exterior thread 42 the syringe holder 30, and thereby the syringe 10, moves axially a longer distance towards the vial 20 than the cap 4 moves away from the coupling element 40 during unscrewing of the cap 4 from the exterior thread 42. The pitch difference in the present embodiment is designed to move the exterior thread 31 to the end of the interior thread 41 , and thereby to establish a fluid connection between the syringe 10 and the vial 20, upon less than one full revolution of the cap 4 relative to the coupling element 40.

As can be seen from the figure, in this state of the mixing device 1 the hollow spike member 52 has penetrated the penetrable section 24 and entered partly into the vial interior 28 and the hollow spike member 53 has penetrated the penetrable section 61 and entered partly into a chamber provided in the syringe stopper 60 between the penetrable section 61 and the filter 69. The syringe interior 18 and the vial interior 28 are thereby in fluid communication via a lumen 55 extending through the respective spike members 52, 53 and the spike base 54.

In Fig. 4 the cap 4 has been removed from the coupling element 40 and the piston rod 14 is operable for firstly driving the solvent out of the syringe 10 and into the vial 20 and subsequently withdrawing the reconstituted product from the vial 20 back into the syringe 10.

Fig. 5 is a close-up perspective view of a portion of the mixing device 1 showing the operative coupling between the cap 4 and the syringe 10. For the sake of clarity a portion of the cap 4 has been cut away to reveal the engagement of one of the ratchet arms 32 with one of the ribs 6. This ratchet mechanism will cause the cap 4 to slave the syringe holder 30, and thereby the syringe 10, when turned in the counter-clockwise direction, whereas the ribs 6 will ride over the ratchet arms 32 when the cap 4 is turned in the clockwise direction, ena- bling relative rotational movement between the cap 4 and the syringe holder 30 when the cap 4 is screwed onto the exterior thread 42.

Fig. 6 is a transverse section view along line A-A of Fig. 3, showing more clearly the interaction between the ribs 6 and the ratchet arms 32. It further shows the rotational lock between the syringe holder 30 and the stopper fastener 70. As can be seen the protrusions 72 fit into respective indentations 33 in the central portion of the syringe holder 30, whereby the stopper fastener 70 is forced to follow any rotational motion of the syringe holder 30.

Fig. 7 shows a longitudinal section of an assembly 100 comprising the connector piece 50, the syringe 10, the syringe stopper 60, and the stopper fastener 70, in an initial state corre- sponding to a pre-use condition of the mixing device 1 . The figure shows in greater detail the vents 59, which are provided as channels defined by respective rib pairs 58, each rib pair 58 extending longitudinally from the spike base 54 to a point just below the circumferential sealing lip 62.

When the barrel 1 1 moves towards the vial 20 during dismounting of the cap 4 from the cou- pling element 40 the engagement between the Luer collar 13 and the threaded inner portion 71 together with the engagement between the ridge 73 and the groove 63 force the stopper fastener 70 and the syringe stopper 60 in the same direction. At some point during this movement, depending on the frictional conditions in the mixing device 1 , the syringe stopper 60 will begin to move relative to the connector piece 50. Thereby, the circumferential sealing lip 62 will slide along the inner wall of the sleeve body 51 towards the spike base 54. The respective rib pairs 58 will engage the circumferential sealing lip 62 and deform it locally at the contact areas to allow air entrapped within the compartment 56 to escape through the channels as the syringe stopper 60 continues to advance towards the spike base 54. Thereby, the force needed for collapsing the compartment 56 is comparable to the force needed to overcome the frictional forces between the circumferential sealing lip 62 and the sleeve body 51 , respectively the rib pairs 59.

Fig. 8 is a longitudinal section view of an assembly 200 according to another embodiment of the invention. The assembly 200 comprises a vial 210, containing a powdered drug (not shown), and a connector piece 250, shown in a pre-use position. The connector piece 250 comprises a transversal spike base 254 supporting a spike member 253 through which a lumen 255 extends. The lumen 255 opens distally towards a piercing portion of the spike member 253 and proximally towards a port 252 adapted to receive another container (not shown), such as e.g. a syringe of the Luer type. A sleeve body 251 extends axially from the spike base 254 in the direction of the vial 210 and surrounds the spike member 253.

The vial 210 is sealingly closed by a vial stopper 260, and the connector piece 250 is arranged such that a circumferential sealing lip 262 on the vial stopper 260 engages an inner portion of the sleeve body 251 to provide a fluid tight compartment 256. The circumferential sealing lip 262 is capable of sliding along the inner wall of the sleeve body 251 from the position shown in Fig. 6 to a position in which the spike member 253 has pierced the vial stopper 260 and the distal opening of the lumen 255 is arranged completely within the vial 210. A couple of lock beads 298 on the inner wall of the sleeve body 251 ensure that the connector piece 250 is not easily dismounted from the vial stopper 260.

In use, a sterile barrier foil (not shown) may firstly be removed from the connector piece 250 to uncover the port 252. A syringe containing a solvent for reconstitution of the powdered drug in the vial 210 is then connected to the port 252 and pressed towards the vial 210. Thereby, the connector piece 250 slides towards the vial 210, and the spike member 253 pierces the vial stopper 260 to establish fluid communication between the vial 210 and the syringe via the lumen 255. A transfer of the solvent from the syringe to the vial 210 can now be executed. Subsequently, the reconstituted drug can be transferred to the syringe, which can finally be removed from the port 252 and used as a delivery device.

The respective embodiments of the invention shown in Figs. 7 and 8 represent examples of assemblies for use in different fluid transfer arrangements. These assemblies can be sterilised by the manufacturer and used either as an external individual part of a fluid transfer arrangement or as an internal sub-assembly in a fluid transfer arrangement, while ensuring that the sterile environments surrounding the drug contacting surfaces are maintained.

Operation of the mixing device In the following a situation of use of the mixing device 1 will be described. In order to gain access to the piston rod 14 a subject user grips the lock ring 3 and holds it between two or more fingers of one hand. She or he then grips the cap 4 with the other hand and makes a turning motion to unscrew the interior thread 5 from the exterior thread 42. The cap 4 will be released from the coupling element 40 upon less than one full relative revolution. During the relative rotation of the cap 4 and the coupling element 40 the ribs 6 engage the ratchet arms 32 to thereby slave the syringe holder 30. Due to the interior thread 41 being a left-hand thread and the exterior thread 42 being a right-hand thread, the syringe holder 30 is forced downwards towards the vial 20 as the cap 4 moves upwards away from the lock ring 3. The engagement between the lock snap 74 and the protrusions 72 will cause the stopper fastener 70 to move downwards with the syringe holder 30, and since the syringe 10 is thread- edly coupled with the stopper fastener 70 via the Luer collar 13 and the threaded inner por- tion 71 the syringe 10 will be forced to follow the downward movement of the syringe holder 30.

The connector piece 50 is held in the distal portion of the syringe holder 30 by a friction fit and as the exterior thread 31 travels along the interior thread 41 during the relative rotational motion between the cap 4 and the coupling element 40, and the syringe 10 and the vial 20 are thereby gradually brought closer to one another, the connector piece 50 will move further into the distal portion of the syringe holder 30. During the travel of the exterior thread 31 in the interior thread 41 the hollow spike member 52 will be pressed against the penetrable section 24 and the hollow spike member 53 will be pressed against the penetrable section 61 . Further converging motion of the syringe 10 and the vial 20 will eventually cause the hollow spike member 52 to penetrate the penetrable section 24 and the hollow spike member 53 to penetrate the penetrable section 61 to thereby establish fluid communication between the syringe interior 18 and the vial interior 28. When the exterior thread 31 has travelled to the end of the interior thread 41 the hollow spike member 52 resides within a hollow of the vial stopper 23 distally of the penetrable section 24, and the hollow spike member 53 resides within a space 68 in the syringe stopper 60 delimited by the penetrable section 61 and the filter 69. In the course of entry of the hollow spike member 53 into the space 68 the circumferential sealing lip 62 slides along the interior wall of the sleeve body 51. One or more vents 59 in the form of axially extending ribs on the interior wall of the sleeve body 51 allow the compressed air in the compartment 56 to escape as the syringe stopper 60 is moved into abutment with the spike base 54. The vents 59 extend from the spike base 54 and end just distally of the initial, pre-use position of the syringe stopper 60. Thereby, the compartment 56 can be maintained sterile until use of the mixing device 1 , while the syringe stopper 60 during use can be moved relative to the sleeve body 51 without resistance from entrapped air. The thread engagement between the exterior thread 42 and the interior thread 5 is longer than the thread engagement between the exterior thread 31 and the interior thread 41 , so when the exterior thread 31 has travelled to the end of the interior thread 41 and fluid communication has been established between the syringe interior 18 and the vial interior 28 via the lumen 55 the cap 4 is still not released from the coupling element 40. Hence, the order in which the respective penetrable sections 24, 61 are penetrated is insignificant as the user can not accidentally apply pressure to the syringe interior 18 through operation of the piston rod 14 until fluid communication is properly established between the syringe 10 and the vial 20. During subsequent dismounting movement of the interior thread 5 along the exterior thread 42, the engagement between the ribs 6 and the ratchet arms 32 will still transfer the rotation of the cap 4 to the syringe holder 30. However, as the exterior thread 31 is no longer capable of relative motion with respect to the interior thread 41 , the syringe holder 30 and the coupling element 40 are forced to perform a joint rotational motion relative to the lock ring 3. This is enabled by the cam 91 moving in the bayonet groove in the exterior surface of the coupling element 40. The rotation of the coupling element 40 relative to the lock ring 3 causes a relative rotational motion between the coupling element 40 and the vial holder 2. Because the coupling element 40 is prevented from translational motion relative to the lock ring 3 and because the vial holder 2 is prevented from rotating relative to the lock ring 3 this rela- tive rotational motion between the coupling element 40 and the vial holder 2 causes the interior thread 7 to travel along the exterior thread 43, whereby the vial holder 2 is forced upwards towards the syringe holder 30. Thereby, the connection between the vial 20 and the coupling element 40 is tightened because the vial holder 2 presses the vial 20 against the transversal portion of the coupling element 40. This eliminates the risk of production toler- ances being the cause of a loose connection between the hollow spike member 52 and the vial 20.

The joint rotation of the syringe holder 30 and the coupling element 40 is relatively small as it corresponds to the last part of the rotation of the cap 4 that releases the interior thread 5 from the exterior thread 42. When the cap 4 is released from the exterior thread 42 it can be removed to expose the syringe 10 for operation. At this point the user holds the mixing device 1 such that the syringe 10 faces upwards. By depression of the piston rod 14 the piston 19 is advanced in the barrel 1 1 to force the solvent out through the Luer 12, further through the lumen 55 and into the vial 20, where it mixes with the powdered drug. The mixing device 1 is then turned up-side down and the piston rod 14 is gradually released to allow the built up pressure in the vial 20 to cause or assist a transfer of the mixed product out of the vial 20, through the lumen 55 and into the syringe 10. Alternatively, or additionally, the piston rod 14 is pulled backwards in the barrel 1 1 to cause or assist the transfer of the mixed product from the vial 20. Once the mixed product is fully contained within the syringe 10, the syringe 10 is removed from the rest of the arrangement. This is done by gripping the syringe holder 30 with one hand and the collar 17 with the other hand and then rotating the syringe 10 relative to the syringe holder 30. Because of the locking engagement between the protrusions 72 and the indentations 33 when the syringe 10 is rotated relative to the syringe holder 30 the Luer collar 13 is screwed out of engagement with the threaded inner portion 71. A circumferential groove 63 in the syringe stopper 60 is engaged by a mating ridge 73 on the stopper fastener 70 to lock the syringe stopper 60 against axial movement relative to the stopper fastener 70. Thereby, when the Luer collar 13 is released from the threaded inner portion 71 the syringe 10 can be easily removed from the stopper fastener 70, leaving the syringe stopper 60 in the remaining part of the mixing device 1 . Thus, the syringe 10 is ready for connection with e.g. a cannula or a catheter immediately upon removal from the arrangement, without the user having to manually detach the syringe stopper 60 from the Luer 12 first. This reduces the number of manual steps to be performed even further. The wings 81 can be unfolded to pro- vide for a better grip of the syringe 10 during the following administration.