Abstract:
A medical device ( 1 ) comprising a frame ( 2, 3, 6 ) defining an interior, a barrier element ( 58 ) arranged to fluidly divide at least a portion of the interior, and barrier removal means ( 30 ) connected with the barrier element and operable from an exterior of the frame to remove the barrier element from the interior through an opening ( 99 ) in the frame.

Description:
FIELD OF THE INVENTION 
       [0001]    The present invention relates generally to medical devices and more specifically to such devices incorporating barrier means for fluid division of internal areas. 
       BACKGROUND OF THE INVENTION 
       [0002]    In connection with the administration, of drugs to subjects, particularly drugs that are to be delivered directly into the bloodstream, it may be of vital importance to ensure that the sterility of the drug is maintained until it reaches the intended target. 
         [0003]    Liquid drugs are typically stored in sealed sterile containers and are either administered therefrom or withdrawn therefrom for delivery via an intermediate container. Regardless of which, often a needle element is used to penetrate a sealing septum of the container to enable transfer of the drug out of the container. It is recommended that the exterior surface of the septum is cleaned by the user before needle penetration, e.g. by use of an alcohol swab, to avoid deposition of impurities on the needle. Swabbing is viewed by many as an additional hassle and, accordingly, there is a tendency towards neglecting this step. 
         [0004]    Some pharmaceutical drugs adapted for parenteral administration are only stable in the administrable 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. 
         [0005]    Traditionally, a mixing of two substances stored in separate vials is performed using a syringe with a needle to withdraw the substance from the one vial and inject it into the other vial. 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 may be difficult 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. 
         [0006]    Dedicated mixing devices exist, however, which offer fluid transfer between containers without the user having to handle any sharp objects. 
         [0007]    WO 97/46203 (Applied Research Systems ARS Holding N.V.), for example, 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. In the pre-use state of the device the needle element is shielded at each end by a slidable bung, providing for closed needle chambers. The respective needle elements are adapted to penetrate the bungs before penetrating the vial and cartridge closures. 
         [0008]    WO 2009/014955 (Amylin Pharmaceuticals, Inc.) discloses a pen injection device comprising a dual transfer spike assembly adapted for establishing fluid communication between two cartridges. Various embodiments of pierceable separating members arranged at each end of the dual transfer spike assembly, or about each spike, for the purpose of maintaining sterility of the system are presented. 
         [0009]    Both of the above mentioned disclosures may provide aseptic, closed environments for the individual needle elements until penetration of the respective container closures. However, there are several drawbacks associated with having to penetrate multiple septa in order to establish fluid communication with a given container. First of all, fragments of material may be torn from a septum when it is pierced, so increasing the number of septa to be pierced adds to the risk of carrying septum fragments into the container. Furthermore, each septum the needle has to penetrate may blunt its cutting edge, whereby the force required to advance the needle into the container will increase. 
         [0010]    US 2010/0163439 (Gutierrez Avendano) discloses a mixing device which comprises two containers mechanically joined by a thread interface and fluidly separated by a sheet and a seal. The sheet is removed through an aperture via an exterior pull tab to cause the contents of the two containers to mix. 
         [0011]    The construction of this device requires both filling and assembly of the two containers in an expensive cleanroom environment in order to ensure an acceptable cleanliness of the resulting product. Furthermore, if the sheet is by accident partly or completely pulled out through the aperture the substances of the two containers will mix instantly. This may be an issue if the stability of the mixture is much lower than the stability of each of the substances in isolation. For mixing devices intended for production of an administrable drug it will lead to a shorter time of expiry thereof. 
       SUMMARY OF THE INVENTION 
       [0012]    It is an object of the invention to provide a solution which eliminates, or at least reduces, drawbacks of the prior art. 
         [0013]    In particular, it is an object of the invention to provide a medical device, wherein at least a portion of its interior is fluidly divided to maintain a sterile local environment. 
         [0014]    It is a further object of the invention to provide such a device having access means for establishing fluid connection to a container, wherein the access means and/or a portion of a container closure is housed in a sterile environment until piercing of the container closure, and wherein no other barriers than the container closure needs be pierced by the access means. 
         [0015]    It is an even further object of the invention to provide a medical device, where fluid can be withdrawn from a container without the user having to manually swab the container closure before penetration thereof. 
         [0016]    It is an even further, object of the invention to provide a medical device which is easy to operate and which is suitable for being carried about in e.g. a pocket or a handbag. 
         [0017]    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. 
         [0018]    Thus, in a first aspect of the invention a medical device is provided comprising a frame defining an interior, a barrier element arranged to fluidly divide at least a portion of the interior, and barrier removal means connected with the barrier element and operable from an exterior of the frame to remove the barrier element from the interior through an opening in the frame. 
         [0019]    A construction like this provides for easy removal of internally arranged barrier means in the device such that portions of the device interior may be fluidly separated until the user decides to combine them. The barrier element may e.g. be adapted to separate two gases, or a liquid from a gas. 
         [0020]    Alternatively, or additionally, the barrier element may be adapted to prevent ingress of germs to a particular space within the device. In certain embodiments the barrier element is a sterilisation barrier, allowing the manufacturer to, during manufacturing, sterilise an interior portion of the device, or an element arranged in the interior of the device, separately and subsequently handle the sterilised portion or element outside clean room facilities, e.g. in connection with the assembly of the device. The sterilised interior portion or element may then be kept sterile until a first use of the device, where the barrier element is removed from the device interior and therefore prevented from interfering with any internal operations in the device. 
         [0021]    In the present context, the term “sterilisation barrier” should be understood as a membrane, such as e.g. a foil or paper, capable of allowing passage therethrough of a sterilisation gas, while preventing passage of germs. The sterilisation barrier may be formed from a porous or a non-porous material, e.g. as described in WO 2009/056616 (Novo Nordisk A/S), the entire disclosure of which hereby being incorporated by reference. 
         [0022]    The medical device may be a fluid transfer device capable of transferring a substance from one part of the device to another, e.g. for mixing with another substance. In that case, the medical device may further comprise a first container, e.g. a vial, adapted to hold first contents and access means suitable for establishing fluid communication between the first container and a second container, e.g. holding second contents. The access means may be arranged partially or fully in the interior of the device, and an interior portion of the access means may be fluidly separated from the first container by, at least, the barrier element. Further, the first container and/or the second container may be arranged at least partially in the interior of the device. 
         [0023]    The barrier element may be removably secured to the access means, e.g. covering a penetration tool thereof, whereby the access means may be sealed and handled independently of other device components during manufacturing of the medical device. 
         [0024]    The access means may comprise a single or dual spike construction, e.g. as known from a conventional type vial adaptor. Such a spike construction may comprise a perforated base portion supporting one or two hollow spikes, and one or two cylindrical sleeve members extending from the base portion and encircling the respective spikes. Alternatively, the access means may comprise a single- or double-ended needle mounted in a needle hub. The barrier element may be releasably mounted over the spike (or needle) or peelably secured to a circumferential rim of the sleeve member, in which case the spike (or needle) may be fully contained in a closed space defined by the barrier element, the sleeve member and the base portion (or needle hub). In some embodiments, a respective barrier element is peelably secured to each circumferential rim of the sleeve member, thereby providing a fluid tight local environment for both spike ends. 
         [0025]    The barrier element may alternatively be removably secured to the first container, e.g. covering a penetrable section of a first container closure. Thereby, the exterior surface of the first container closure may be sterilised before assembly of the medical device, eliminating the need for manual swabbing before penetration thereof by the access means. 
         [0026]    The barrier removal means may comprise a support structure removably arranged in the medical device interior and a grip portion connected with the support structure and arranged exteriorly of the frame. The support structure may be adapted to receive at least a portion of the barrier element, and the grip portion may be designed to provide an ergonomic grip, enabling easy extraction of the support structure from the device interior. The at least a portion of the barrier element may be secured to the support structure by welding or gluing, or by other suitable means. 
         [0027]    In a second aspect of the invention a medical device is provided comprising a frame defining an interior, a first barrier element arranged to fluidly separate portions of the interior, a second barrier element arranged to fluidly separate other portions of the interior, and barrier removal means respectively connected with the first barrier element and the second barrier element and operable from an exterior of the frame to remove the first barrier element and the second barrier element from the interior through an opening in the frame. 
         [0028]    The barrier removal means may comprise a support structure removably arranged in the medical device interior and a grip portion connected with the support structure and arranged exteriorly of the frame. At least a portion of the first barrier element may be attached to a first face, e.g. a distally oriented surface, of the support structure, and at least a portion of the second barrier element may be attached to a second face, e.g. a proximally oriented surface, of the support structure. 
         [0029]    In the present context, the term “distally oriented” means facing the distal portion of the device, whereas the term “proximally oriented” means facing the proximal portion of the device. In principle, the terms “distal” and “proximal” normally indicate opposite portions of a device, where a distal portion is further away from the point of user operation than a proximal portion. In this context, however, the terms are merely used to specify two opposite directions. 
         [0030]    The frame may comprise a) a housing structured to at least partially accommodate one or more of the first container, the second container and the access means, and b) a cap removably connectable with the housing via a cap receiving portion. The cap receiving portion may be translationally and rotationally locked with respect to the housing. The housing may be unitary or may comprise a number of interlocked elements. 
         [0031]    The cap may comprise a first helical path and the cap receiving portion may comprise a mating second helical path, whereby the cap is capable of being dismounted from the cap receiving portion by relative rotation of the two. 
         [0032]    The barrier removal means may be structured to prevent or limit cap motion relative to the cap receiving portion when the support structure is positioned in the device interior. For example, the cap may be rotatable about a general axis relative to the cap receiving portion, at least a portion of the opening in the frame may be provided in the cap and may be dimensioned to prevent relative rotation between the cap and the barrier removal means about the general axis when the support structure is positioned in the device interior, and the support structure may be locked against rotation about the general axis relative to the cap receiving portion, e.g. via an engagement with the housing. 
         [0033]    Alternatively, or additionally, the cap may be translatable along the cap receiving portion, the opening in the frame may be provided entirely in the cap and may be dimensioned to limit or prevent relative translation between the cap and the barrier removal means when the support structure is positioned in the device interior, and the support structure may be locked against translation relative to the cap receiving portion, e.g. via an engagement with the housing. 
         [0034]    By preventing the cap from moving relative to the cap receiving portion, or at least limiting its movements relative to the cap receiving portion, when at least a portion of the support structure is arranged in the interior, the barrier removal means may additionally serve as an activation lock for the medical device, ensuring that fluid communication between the first and second containers cannot be established before the user has manually pulled the support structure out through the opening. 
         [0035]    The support structure may extend from the opening into the interior and may be rotationally and/or translationally fixated to the housing at an area opposite the opening to provide a stable arrangement of the barrier removal means. 
         [0036]    In some embodiments the support structure and the grip portion are connected via a flexible portion arranged exteriorly of the opening. Thereby, the grip portion may be placed along or on the exterior frame surface during storage, reducing the transversal dimension of the medical device. 
         [0037]    The fluid transfer device as described in connection with the exemplary embodiments of the present invention is particularly applicable for mixing liquids and for reconstituting a powder using a solvent. Non-exhaustive examples of drugs which may be provided in a powdered form include various factor products for use in the treatment of haemophilia, growth hormone, antibiotics and fertility drugs. 
         [0038]    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 respective 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 characteristics described in relation to the invention is encompassed by the invention unless expressly stated herein or clearly contradicted by context. 
         [0039]    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 
         [0040]    In the following the invention will be further described with references to the drawings, wherein 
           [0041]      FIG. 1  shows a perspective view of a medical device according to an embodiment of the invention, in a pre-use state, 
           [0042]      FIG. 2  shows a longitudinal section view of the device of  FIG. 1 , 
           [0043]      FIG. 3  shows a close-up longitudinal section view of components of the device, 
           [0044]      FIG. 4  shows a longitudinal section view of the device in an in-use state, and 
           [0045]      FIG. 5  shows a perspective transverse section view of the device, detailing a pull tab installed therein. 
       
    
    
       [0046]    In the figures like structures are mainly identified by like reference numerals. 
       DESCRIPTION OF EXEMPLARY EMBODIMENTS 
       [0047]    When in the following relative expressions, such as “downwardly” and “upwardly”, 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 different structures as well as their relative dimensions are intended to serve illustrative purposes only. 
         [0048]      FIG. 1  is a perspective illustration of a medical device  1  according to an exemplary embodiment of the invention. The medical device  1  comprises a housing structure, in the form of a vial holder  2  and a lock ring  6 , which accommodates a vial  20  holding a drug substance (not visible), which may e.g. be a powder or a fluid. The vial  20  is inspectable through a window  80 . A removable cap  3  abuts the lock ring  6  along a circumferential interface, which is only interrupted by a notch in the cap  3 , allowing passage of a pull tab  30  from an interior portion of the medical device  1  to the outside. The pull tab  30  has a grip ring  31 , suited for being operated by a subject user, and a bendable section  32  which enables the grip ring  31  to be placed on a hanger  9  on the cap  3  during storage of the medical device  1 . Thereby, a slender configuration of the packaging in which the medical device  1  is to be offered may be obtained. 
         [0049]    The cap  3  covers a syringe  10  arranged opposite the vial  20 . The syringe  10 , which is inspectable through a window  90 , carries a volume of a substance (not visible) adapted to be mixed with the drug substance in the vial  20 . At its proximal end the cap  3  is provided with a furrowed section  4  which serves as a friction enhanced region offering the user a better grip when removing the cap  3  from the remaining parts of the medical device  1 . 
         [0050]      FIG. 2  is a longitudinal section view of the medical device  1  in a pre-use state, revealing its interior. The figure shows a co-axial alignment of the vial  20 , the syringe  10 , and a connector piece  50 , which carries a hollow spike member  52  for establishment of fluid communication between a vial interior  21  and a syringe interior  11 . The vial  20  is a conventional type of vial having a sealing vial stopper  23  arranged at its opening. The vial stopper  23  is attached to the vial  20  by a seal cap  24  being beaded onto an outwardly extending flange section  22 . A barrier foil  28  covers a portion of the external surface of the vial stopper  23  which is sterilised by the manufacturer, e.g. by steam sterilisation, before assembly of the medical device  1 . Thereby, an aseptic local environment is provided which does not have to be manually cleaned by the user. 
         [0051]    The connector piece  50  is described in more detail below with reference to  FIG. 3 . However, it can be seen from  FIG. 2  that the spike member  52  is accommodated in an internal compartment  56  which is sealed by a barrier foil  58 . 
         [0052]    In the shown pre-use state of the medical device  1  the spike member  52  and the vial stopper  23  are spaced apart a certain axial distance which allows for the inclusion of a transversally extending support bar  33 . The support bar  33  forms part of the pull tab  30  and is physically connected with the grip ring  31  via the bendable section  32 . A flap  29  of the barrier foil  28  is secured to the downwardly oriented surface of the support bar  33 , and a flap  59  of the barrier foil  58  is secured to the upwardly oriented surface of the support bar  33 . 
         [0053]    A coupling element  40  is axially and rotationally fixed to the lock ring  6  and provided with an exterior thread  42  for engagement with an interior thread  5  in the cap  3 . The engagement between the exterior thread  42  and the interior thread  5  secures the cap  3  relative to the lock ring  6  and the vial holder  2 . The coupling element  40  is further provided with an interior thread  41  adapted for engagement with an exterior thread  71  of a syringe holder  70  carrying the syringe  10 . 
         [0054]    The syringe  10  is mechanically coupled with the connector piece  50  via a Luer collar  13  and is fluidly connected with the spike member  52  via an outlet  12 . A piston rod  14  is connected to a piston  15  and operable, after removal of the cap  3  from the coupling element  40 , to pressurise the syringe interior  11 . 
         [0055]    The interior thread  41  and the exterior thread  42  are opposite, and the cap  3  is rotationally coupled with the syringe holder  70 . Thereby, when the cap  3  is rotated in a dismounting direction relative to the coupling element  40  the syringe holder undergoes a rotation in the same direction, but whereas the cap  3  is consequently displaced axially upwards the syringe holder is displaced axially downwards, carrying with it the syringe  10  and the connector piece  50 . 
         [0056]      FIG. 3  is a close-up longitudinal section view of the connector piece  50  and the respective barrier foils  28 ,  58  in a pre-assembly condition where the pull tab  30  has not yet been installed. The connector piece  50  has a transversal spike base  54  carrying the spike member  52  and a threaded coupling piece  53  adapted for mating engagement with the Luer collar  13 . The spike base  54  has a hollow central section which fluidly couples the outlet  12  and a lumen  55  in the spike member  52 . An easily penetrable plug  60  is fitted onto the sharp end of the spike member  52  to prevent leakage therefrom during storage. It is emphasized, however, that an inclusion of such a plug is purely optional as the connector piece  50  and the fluid coupling with the syringe  10  can be designed in such a way that no fluid can leak therefrom before the device is operated in a use situation. A sleeve body  51  extends axially from the spike base  54 , parallel, or substantially parallel, to the spike member  52  and terminates at a circumferential rim  57  to which the barrier foil  58  is attached, e.g. by a suitable adhesive or by welding. It is thereby possible for the manufacturer to sterilise the spike member  52 , e.g. by steam sterilisation, through the seal before general assembly of the medical device  1 . The connector piece  50  can thus be handled more easily, and with the barrier foil  28  being attached to the seal cap  24 , e.g. by a suitable adhesive or by welding, and covering a penetrable section  25  of the vial stopper  23 , the medical device  1  may be assembled outside clean room facilities. 
         [0057]    In  FIG. 3 , the arrow, p, indicates the direction of the pull force that must be applied to the flaps  29 ,  59  in order to remove the barrier foils  28 ,  58  from, respectively, the rim  57  and the seal cap  24 . The respective barrier foils  28 ,  58  may be made of the same material or of different materials. Non-exhaustive examples of suitable materials are e.g. aluminium and paper. 
         [0058]      FIG. 4  is a perspective view of the medical device  1  in an in-use state where the pull tab  30  has been operated to remove the barrier foils  28 ,  58  from the interior of the medical device  1  through an opening  99  in the cap  3 . For the sake of clarity the barrier foil  58  is shown on the support bar  33  in the configuration which it has before being peeled off the rim  57  of the connector piece  50  (and the barrier foil  28  is hidden under the support bar  33 ). 
         [0059]      FIG. 5  is a perspective transverse section view of the cap  3  and the pull tab  30  in a pre-use state of the medical device  1 . The support bar  33  comprises a protrusion  34  which is interposed between two abutment edges  7   a,    7   b  on the lock ring  6  to stabilise the support bar  33  in the interior of the medical device  1 . The engagement between the support bar  33  and the lock ring  6  locks the cap  3  against rotation relative to the lock ring  6 . This serves as a safety feature preventing the cap  3  from being rotated relative to the coupling element  40  until the user removes the pull tab  30 . Accidental rotation of the cap  3  may otherwise advance the spike member  52  towards the vial  20 , due to the aforementioned opposite threads  41 ,  42 , and thereby cause penetration of the barrier foils  58 ,  28  and undesired premature establishment of fluid connection to the vial  20 . 
         [0060]    In the following an operation of the medical device  1  will be described.  FIGS. 1 and 2  display the medical device  1  after the user has lifted the grip ring  31  off the hanger  9 . The rotational locks between the lock ring  6  and the coupling element  40  and between the cap  3  and the lock ring  6 , due to the support bar  33 , prevent the user from dismounting the cap  3  in this state of the medical device  1 . To enable mixing of the contents of the syringe  10  and the vial  20  the user pulls the pull tab  30 , whereby the support bar  33  is withdrawn from the interior of the medical device  1  through the opening  99 . Since the barrier foils  28 ,  58  are secured to the support bar  33  via the respective flaps  29 ,  59  a transversally directed pull force will be exerted on the flaps  29 ,  59  during the withdrawal of the support bar  33  through the opening  99 . This pull force will peel off the barrier foil  58  from the rim  57  and the barrier foil  28  from the seal cap  24 , whereby the plug  60  and the penetrable section  25  will become exposed to one another. 
         [0061]    Following removal of the pull tab  30  the user grabs the cap  3  by the furrowed section  4  and twists it relative to the vial holder  2  and the lock ring  6 . This will cause the interior thread  5  to travel the exterior thread  42  in the upwards direction and the exterior thread  71  to travel the interior thread  41  in the downwards direction, due to the rotational coupling between the cap  3  and the syringe holder  70 . During the downward motion of the syringe holder  70  the connector piece  50  is forced towards the vial  20  as a consequence of the axial connection between the coupling piece  53  and the Luer collar  13 . At some point, the plug  60  will abut the vial stopper  23 , whereafter further downward motion of the syringe holder  70  will force the spike member  52  to penetrate the plug  60  and, subsequently, the penetrable section  25 . The plug  60  is adapted to slide axially along the spike member  52  during entry of the spike member  52  into the vial interior  21 . 
         [0062]    The threaded sections are designed such that when the interior thread  5  moves out of engagement with the exterior thread  42 , and the cap  3  thereby can be removed, the spike member  52  has penetrated the vial stopper  23  and established fluid communication between the syringe interior  11  and the vial interior  21 . 
         [0063]    Upon dismounting of the cap  3  from the coupling element  40  the piston rod  14  is exposed for operation by the user. Pushing the piston rod  14  into the barrel of the syringe  10  will cause the piston  15  to pressurise the substance in the syringe interior  11  and force it out through the outlet  12 , further through the lumen  55  and into the vial  20 , where it will mix with the drug substance. The increased pressure in the vial  20  caused by the introduction of the substance from the syringe  10  exerts a backwards directed force on the piston rod  14  which, upon release of the piston rod  14  by the user, automatically transfers at least a sub-volume of the mixed product through the lumen  55  and into the syringe  10 . The user may have to invert the medical device  1  and pull the piston rod  14  back manually an additional distance to empty the vial  20  (or rather minimise the volume of administrable drug therein). After transfer of the administrable drug product to the syringe  10  the Luer collar  13  is decoupled from the coupling piece  53  and the syringe  10  is ready for receiving a delivery element, such as e.g. a cannula or an infusion set, for administration of the drug. 
         [0064]    The medical device  1  as described in the above removes the need for manual swabbing of external surfaces before mixing of the two substances, and thereby reduces the number of operational steps a user must carry out in order to prepare the drug for delivery, while offering a low effort fluid connection of the two containers.