Abstract:
Methods of sterilizing a hollow fiber filter module, hollow fiber filter modules comprising closures and closures comprising an oxygen absorber are disclosed. A method according to the invention is distinguished in that the interior of the hollow fiber filter module is sealed off by means of the housing associated to the hollow fiber filter module and by means of the closures, and at least one of the closures comprises an oxygen absorber. A hollow fiber filter module according to the invention is characterized by the corresponding closures with or without an oxygen absorber.

Description:
CROSS REFERENCE TO RELATED APPLICATIONS 
       [0001]    This application claims priority to German application DE 10 2014 108 530.2 filed Jun. 17, 2014, the contents of such application being incorporated by reference herein. 
       FIELD OF THE INVENTION 
       [0002]    The present invention relates to a method for sterilization of a hollow fiber filter module. 
         [0003]    In addition, the present invention relates to a hollow fiber filter module which can be used especially in dialysis apparatus for the external purification of blood. A closure, in particular a closure plug for hermetically closing a hollow fiber filter module, also pertains to the subject matter of the invention. 
       BACKGROUND OF THE INVENTION 
       [0004]    Hollow fiber filter modules or dialyzers of common current construction for use in dialysis apparatus for the external purification of blood essentially consist, on the one hand, of a hollow fiber bundle through which blood to be cleaned is conveyed, and on the other hand of a space which surrounds the individual hollow fibers of the hollow fiber bundle and through which the dialysis liquid is conveyed. The direction of flow of the dialysis liquid is opposite to the direction of flow of the blood in most cases. The hollow fibers or the walls of the hollow fibers consist of a semipermeable material which allows, on the one hand, the exchange of water and any substances dissolved therein and on the other hand prevents the exchange of blood cells. 
         [0005]    Various methods are already known for sterilizing hollow fiber filter modules for their intended use in the medical field. 
       DESCRIPTION OF THE RELATED ART 
       [0006]    DE 27 16 178 A1, for instance, describes several methods in each of which a hollow fiber filter module to be sterilized is first packed up in a wrapping, the inner space of the wrapping is subsequently sterilized with a sterilization gas or by irradiation, then evacuated and finally refilled with a controlled gaseous atmosphere. 
         [0007]    If in a method according to DE 27 16 178 A1 the inner space is sterilized gamma radiation, it has to be ensured in general that there is no oxygen in the vicinity of the hollow fibers, because said oxygen would interact or react with the material of the hollow fibers due to the gamma radiation and thus the membrane properties of the hollow fibers would deteriorate. Thus, in order to avoid such deterioration of the membrane properties during a hollow fiber filter module sterilization by irradiation, it has become habitual, as described in EP 0 759 873 B1, to collect the oxygen, which is enclosed together with the hollow fiber filter module in a wrapping, with an oxygen absorber and hence keep it away from the hollow fibers. 
         [0008]    Various oxygen absorbers or corresponding substances and packagings are disclosed, for instance, in US 2001/0023232 A1, EP 0 898 508 B1, EP 0 664 824 B1 and EP 2 009 062 B1. 
         [0009]    A problem with the usual implementation of the sterilization method according to EP 0 759 873 B1 is the fact that the gas-tight packaging requires an expensive welding process, that the volume enclosed by the packaging may vary greatly due to the resiliency of the packaging and therefore the capacity of the oxygen absorber has to be assessed to be unnecessarily large, and that the effort for a safe sterile packaging of a hollow fiber filter module, which packaging meets all transport and storage conditions, is quite considerable. 
       SUMMARY OF THE INVENTION 
       [0010]    Therefore, it is an object of the present invention to reduce the effort for the sterilization of a hollow fiber filter module, meeting the same or even higher safety-related requirements. 
         [0011]    This object is achieved with respect to a sterilization method and with respect to a hollow fiber filter module and a hollow fiber filter closure by the features of the claims. 
         [0012]    Advantageous further developments of the method according to aspects of the invention as well as of the devices according to aspects of the invention are also subject matter of the claims. 
         [0013]    Hollow fiber filter modules or dialyzers which can be used in dialysis apparatus for the external purification of blood and are sterilized by a method according to aspects of the invention with gamma radiation, generically comprise a housing with at least two first ports leading to a first inner zone and at least two second ports leading to a second inner zone. The first ports are provided to introduce fresh dialysis liquid to the first inner zone of the hollow fiber filter module during blood purification and to discharge any used dialysis liquid, which may contain excess water coming from the blood to be cleaned. The second ports are provided to introduce uncleaned blood to the second inner zone and to discharge cleaned blood. 
         [0014]    The sterilization method according to aspects of the invention is distinguished by the manner how the first and second inner zones are tightly closed, in particular in air-tight or hermetical fashion. In contrast to methods known hitherto, this is not realized with the aid of an additional packaging, but on the one hand with the housing and on the other hand with closures. In this context, the closures can be mounted to and dismounted from the corresponding ports of the housing without any tools and are connected to the corresponding ports in a frictional and/or form-fitting manner in the mounted state. By way of example, the ports are closed with closure plugs or closure caps which can be connected to the ports in frictional manner by a press fit or with a thread. It is also possible that the ports are closed with closures which can be connected to the ports in a form-fitting manner such as with a clip connection, or both in a form-fitting and frictional manner. Furthermore, for closing the ports at least once a closure is used which comprises an oxygen absorber with a reactive surface area through which the oxygen absorber receives or absorbs oxygen enclosed in the first and/or in the second inner zone. The oxygen absorber preferably comprises iron powder containing crystal water in order to implement the absorption process. Provided that the requirements with regard to medical applicability are met, other compositions are conceivable, too. The oxygen absorber allows to reduce the fraction of uncombined oxygen in the first and/or in second inner zone by a considerable amount, enabling a damage-free sterilization of the hollow fiber filter module by gamma radiation. 
         [0015]    It is advantageous in the method according to aspects of the invention that the use of individual closures which can be mounted without any tool allows to save an additional packaging and thus a correspondingly required packaging device or packaging machine. Due to the fact that the housing of the hollow fiber filter module is used as a sterile barrier (and not a usually flexible packaging foil), it is not only possible to save the effort for ensuring the tightness and the storage and transport safety of the packaging foil, but also the capacity of the oxygen absorber can be correspondingly matched more precisely with the inner volume of the more stable housing of the hollow fiber filter module. 
         [0016]    As the first and the second inner zones are separated from each other by a semipermeable membrane, the oxygen exchange between two inner zones is possible, but may need a longer time. It is therefore advantageous according to a further aspect of the invention if one port each of the first ports and of the second ports is closed by a closure comprising an oxygen absorber. Thus, it becomes not only unnecessary that the oxygen possibly has to flow or diffuse through the semipermeable membrane in order to reach the oxygen absorber, but it is also possible to adapt the capacities of the at least two oxygen absorbers to the respective volumes of the first and/or second inner zones. 
         [0017]    According to a further aspect of the invention, the first and/or second inner zones can be flushed with a protective gas prior to closing the first and/or second inner zones. This is advantageous because this measure reduces the quantity of enclosed oxygen which has to be absorbed by the oxygen absorber(s). 
         [0018]    Furthermore, it may be of advantage if the increase in volume of the oxygen absorber in the reaction with the oxygen is taken into consideration with respect to the reactive surface area of the oxygen absorber. An oxygen absorber according to aspects of the invention may therefore be distinguished in that the reactive surface area of the oxygen absorber is void of any undercuts which become overgrown by the increase in volume due to the reaction with absorbed oxygen in such a manner that parts of the undercut, which would in fact be able to receive oxygen, are isolated from the oxygen. 
         [0019]    A hollow fiber filter module, according to aspects of the invention, which can be used in dialysis apparatus for the external purification of blood comprises a housing with at least two first ports leading to a first inner zone for supplying and discharging a dialysis liquid and with at least two second ports leading to a second inner zone for supplying and discharging blood. 
         [0020]    A characterizing feature of a hollow fiber filter module according to aspects of the invention is that it comprises closures which each can be mounted to and dismounted from one of the ports of the housing without any tool and can be connected to the respective port in a frictional and/or form-fitting manner. The closures allow to tightly close the first and second inner zones with the housing, in particular in an air-tight or hermetical fashion, without the need of an additional packaging or wrapping. In order to reduce the quantity of enclosed uncombined oxygen in the first and/ or second inner zone and thus prevent detrimental reactions of the uncombined oxygen with the hollow fibers of the hollow fiber filter module during the sterilization by gamma radiation, at least one of the closures comprises an oxygen absorber comprising a reactive surface area with which any oxygen enclosed in the first and/or second inner zone can be received, collected or absorbed at least in part. 
         [0021]    The closures can be mounted to and dismounted from the corresponding ports of the housing without any tools and are connected to the corresponding ports in a frictional and/or form-fitting manner in the mounted state. By way of example, the closures are implemented by closure plugs, closure caps or closure lids which can be connected to the ports in frictional manner by a press fit or with a thread. It is also possible to give the closures such a design that they can be connected to the ports in a form-fitting fashion such as with a clip connection, or both in a form-fitting and frictional manner. 
         [0022]    The oxygen absorber preferably comprises iron powder containing crystal water in order to implement the absorption process. Provided that the requirements with regard to medical applicability are met, other compositions are conceivable as well. 
         [0023]    Advantageously, each one of the closures for the first ports and of the closures for the second ports is provided with an oxygen absorber. Hence, the first and the second inner zones each may have a direct access to one of the oxygen absorbers, allowing to reduce the required waiting period up to the end of which the amount of absorbed oxygen is sufficiently large. 
         [0024]    In order to ensure a safe and/or more ergonomic handling of the closures, it may be advantageous if the outer shape and/or appearance of the closures provided with an oxygen absorber differs from the outer shape and/or appearance of the closures without oxygen absorber. In this context, the term “outer shape and/or appearance” relates in particular to those parts of the closures which are accessible for persons from outside even if the closures are mounted to the hollow fiber filter module of the invention. Such different closures can then be distinguished in visual and/or haptic manner by the staff which is responsible for the hollow fiber filter module. 
         [0025]    As set forth in the description of the method according to aspects of the invention, it may be advantageous if the increase in volume of the oxygen absorber in the reaction with the oxygen is taken into consideration with respect to the reactive surface area of the oxygen absorber. Thus, an oxygen absorber according to aspects of the invention may be distinguished in that the reactive surface area of the oxygen absorber is void of any undercuts which become overgrown by the increase in volume due to the reaction with absorbed oxygen in such a manner that parts of the undercut, which would in fact be able to receive oxygen, are isolated from the oxygen. 
         [0026]    A closure according to aspects of the invention can be mounted to and dismounted from at least one port of a hollow fiber filter module, in particular a hollow fiber filter module according to aspects of the invention, without using a tool and can be connected to the respective port in frictional and/or form-fitting manner. The closure allows to tightly close at least one of the ports, in particular in air-tight or hermetical fashion. 
         [0027]    A characteristic feature of the closure according to aspects of the invention is an oxygen absorber which is located in the closure and whose reactive surface area can absorb at least partially any uncombined oxygen which is enclosed in a first and/or second inner zone. Thus, the oxygen absorber is arranged in the closure in such a manner that the oxygen absorber, on the one hand, is in fluid connection with the first and/or second inner zone to be closed and, on the other hand, is sealed off by parts of the closure from the external atmosphere with respect to the first and/or second inner zones. 
         [0028]    The oxygen absorber preferably comprises iron powder and crystal water. 
         [0029]    Advantageously, the reactive surface area may be designed such that it has no undercuts which—after an increase in volume of the oxygen absorber due to the reaction with absorbed oxygen—would isolate parts of the reactive surface area from any oxygen in the first inner zone and/or in the second inner zone which is still not absorbed. 
     
    
     
       BRIEF DESCRIPTION OF THE DRAWINGS 
         [0030]    The invention is best understood from the following detailed description when read in connection with the accompanying drawings. Included in the drawings are the following figures: 
           [0031]      FIG. 1  is a sectional view of a hollow fiber filter module which for carrying out a sterilization according to the prior art is enclosed in a packaging along with a separate oxygen absorber; 
           [0032]      FIG. 2  is a sectional drawing of a hollow fiber filter module according to aspects of the invention; 
           [0033]      FIG. 3   a  is a sectional view of a closure according to aspects of the invention comprising an oxygen absorber; and 
           [0034]      FIG. 3   b  is a top view of the closure shown in  FIG. 3   a.    
       
    
    
     DETAILED DESCRIPTION OF THE PREFERRED EMBODIMENTS 
       [0035]    A generic hollow fiber filter module  2  as shown in  FIG. 1  comprises a housing  4  which can be subdivided into a lid-shaped blood inlet section  4   a,  a hollow fiber bundle section  4   b - d,  an essentially cylindrical, in particular circularly cylindrical dialysis liquid section  4   e  and a likewise lid-shaped blood outlet section  4 f. 
         [0036]    The hollow fiber bundle section  4   b - d  in turn is formed from a first, in particular round hollow fiber bundle holder  4   b  embedding the ends of hollow fibers  4   c,  a hollow fiber bundle consisting of the hollow fibers  4   c  arranged parallel to one another, and a second, in particular round hollow fiber bundle holder  4   d  embedding the other ends of the hollow fibers  4   c.  Thus, the hollow fiber filter module  2  is sealed at the ends by potting, is mounted by the sealing compound and optionally cut at both ends after the sealing process in order to make any hollow fibers  4   c  again accessible which have been inadvertently closed by the sealing process. 
         [0037]    A dialysis liquid section  4   e  of the housing  4 , the former particularly having the shape of a circular cylinder shell, extends around the space of the hollow fiber bundle section  4   b - d  defined between the two hollow fiber bundle holders  4   b  and  4   d.  The space between the hollow fibers  4   c,  which is enclosed by the two hollow fiber bundle holders  4   b  and  4   c  and the dialysis liquid section  4   e  of the housing  4 , corresponds to a first inner zone  10  of the hollow fiber filter module  2 . 
         [0038]    The lid-shaped blood inlet section  4   a  of the housing  4  is arranged or attached on the first hollow fiber bundle holder  4   b  on its side facing away from the hollow fiber bundle section  4   e  in such a manner that a blood distribution space can be defined between the blood inlet section  4   a  and the first hollow fiber bundle holder  4   b.    
         [0039]    The lid-shaped blood outlet section  4   f  of the housing  4  is arranged or attached on the second hollow fiber bundle holder  4   d  on its side facing away from the hollow fiber bundle section  4   e  in such a manner that a blood collection space can be defined between the blood outlet section  4   f  and the second hollow fiber bundle holder  4 d. 
         [0040]    The blood distribution space, the space within the hollow fibers  4   c  and the blood collection space in combination correspond to a second inner zone  16  of the hollow fiber filter module  2 . 
         [0041]    A port  12  for supplying blood is provided on the blood inlet section  4   a  of the housing  4 , a port  14  for discharging blood is provided on the blood outlet section  4   f  of the housing  4  and, on the dialysis liquid section  4   e  of the housing  4 , a dialysis liquid inlet  6  is provided in the vicinity of the second hollow fiber bundle holder  4   d  and a dialysis liquid outlet  8  is provided in the vicinity of the first hollow fiber bundle holder  4   b.    
         [0042]    As shown in  FIG. 1 , a generic hollow fiber filter module  2  according to the prior art is packed up—prior to a sterilization with gamma radiation—along with a separate oxygen absorber  26  in an especially bag-shaped packaging V made of plastics. In order to close the packaging V so as to be impermeable to gas, the open end is sealed by a weld seam S. 
         [0043]    In comparison,  FIG. 2  shows a sectional drawing, equivalent to  FIG. 1 , of a hollow fiber filter module according to aspects of the invention. In contrast to a conventional hollow fiber filter module, a hollow fiber filter module  2  according to aspects of the invention comprises closures  18 ,  20 ,  22  and  24  in the form of closure plugs which can be attached to the ports  6 ,  8 ,  12  and  14  without any tool in such a manner that the first inner zone  10  and the second inner zone  16  are closed so as to be impermeable to gas. 
         [0044]    As is shown in the  FIGS. 3   a  and  3   b  by the example of the closure  20 , each of the closures  18 ,  20 ,  22  and  24  consists of a circularly cylindrically shaped closure piece  28  which has its outer wall provided with lamellas  30  in circumferential direction, and of a handling piece  32 . Taking the closure  20  as an example, the sealing off of the corresponding port  8  having the shape of a circularly cylindrical shell is effected in that the closure  20  is grasped at its handling piece  32  and the circularly cylindrically shaped closure piece  28  of the closure  20  is moved to the port  8  such that the cylindrical closure piece  28  is inserted in the port  8  (having the shape of a cylinder shell) with a press fit. According to one embodiment, the press fit is established by the elastically deformable design of the entire closure  20 . Embodiments in which either the lamellas  30  or only the closure piece  28  are/is realized so as to be elastically deformable, are also within the meaning of the invention. Any embodiments in which not the closures  18 ,  20 ,  22  and/or  24 , but the corresponding ports  6 ,  8 ,  12  and/or  14  are designed to be completely or partially elastically deformable, are also within the scope of the invention. 
         [0045]    The term “elastically deformable design” means here that the shape of the closure  20  and/or of the port  8  can be changed by a manual application of a compressive force in such a manner that the closure piece  20   a  can be inserted into the corresponding port  8  and that, having finished to exert a compressive force on the closure  20  and/or the port  8 , the shape thereof is again restored in such a manner that the closure piece  28  or the cylindrical outer contour of the closure piece  28  at least partially rests against the port  8  or the cylindrical inner contour of the port  8  and closes the port  8  in a manner so as to be impermeable to gas. The elasticity can be implemented by a suitable selection of the material and/or by a suitable geometrical dimensioning. 
         [0046]    The closure  20  comprises an oxygen absorber  26  on the closure piece  28 , to be more precise on the side of the closure piece  28  which faces the corresponding inner zone  10  if the closure  20  is mounted on the hollow fiber filter module  2 . The oxygen absorber  26  is realized by a porous structure containing iron powder and crystal water. The size of the oxygen absorber  26  is dimensioned to be proportional to the respective inner zones  10  and  16 . 
         [0047]    The closure piece  28  is an essentially round, sleeve-shaped shell which has a round interior in which the round, piston-shaped oxygen absorber  26  is arranged. The oxygen absorber  26  is frictionally connected to the closure piece  28  with a press fit; alternatively or in addition, it may also be cast, glued in situ or bonded by a form-fit connection. The outer cylinder surface of the closure piece  28  may cooperate with a corresponding inner cylinder surface of the port  8  and hence corresponds to the sealing surface. The circumferential lamellas  30  are provided to improve the sealing characteristics. 
         [0048]    The round, sleeve-shaped closure piece  28  is designed to be open to one side such that the oxygen absorber  26  is in fluid connection with the surroundings of the closure  20 . These surroundings correspond to the first or second inner zone  10  of a hollow fiber filter module  2  if the closure  20  is attached to the hollow fiber filter module  2 . In addition, a membrane (not shown in the Figures) can be provided on the open side of the sleeve-shaped closure piece  28 , ensuring on the one hand that any oxygen is able to reach the oxygen absorber  26 , and on the other hand ensuring that parts which break off or separate from the oxygen absorber  26  do not leave the interior of the closure piece  28 , preventing the potential risk of a contamination of the corresponding inner zone  10  of the hollow fiber filter module  2 . 
         [0049]    The other side of the round, sleeve-shaped closure piece  28  is concentrically adjoined by a plate-shaped part of the rotationally symmetrical handling piece  32 . The plate-shaped part of the handling piece  32  is formed in one piece with the closure piece  28 . Alternatively, the plate-shaped part of the handling piece  32  and the closure piece  28  can also have a multi-piece design. The plate-shaped part of the handling piece  32  adjoins the closure piece  28  in such a manner that the interior of the closure piece  28 , in which the oxygen absorber  26  is arranged, corresponds to a blind hole. 
         [0050]    A round, sleeve-shaped edge or an edge in the shape of a circularly cylindrical shell extends at the edge of the plate-shaped, rotationally symmetrical part of the handling piece  32  essentially parallel to the closure piece  28 . The edge of the handling piece  32  has its circumference provided with recessed grips facilitating the gripping and handling of the closure  20 . The edge of the handling piece  32  is arranged on the plate-shaped part of the handling piece  32  in such a manner that it encompasses a tubular part of the port  8  in part, similar to a crown cap, if the closure piece  28  is inserted in the tubular part of the port  8 . Here, the inner surface of the edge of the handling piece  32  may rest against the outer surface of the tubular part of the port  8  and hence be part of the sealing surface. However, it is also possible that a ring-shaped gap remains between the inner surface of the edge of the handling piece  32  and the outer surface of the tubular part of the port  8 . The inner surface of the edge of the handling piece  32  is formed to be slightly conical; alternatively, it may be circularly cylindrical as well. 
         [0051]    As shown in  FIG. 1 , the ports  6 ,  8 ,  12  and  14  and hence the corresponding (not illustrated) closures  18 ,  20 ,  22  and  24  may each have the same size. According to the embodiment shown in  FIG. 2 , it is also possible that only the first ports  6  and  8  and the corresponding closures  18  and  20  or the second ports  12  and  14  and the corresponding closures  22  and  24  have the same size. 
         [0052]    In order to be able to distinguish and generally identify the closures  20  and  22  provided with an oxygen absorber  26  from the equally large closures  18  and  24  without oxygen absorber  26  even in the mounted state, markings  34  in the form of ring-shaped depressions are provided on that side of the handling piece  32  of the closures  20  and  22  which faces away from the corresponding inner zone  10  or  16 , if the closure  20  or  22  is mounted to the hollow fiber filter module  2 . As an alternative to this, it would be possible to use any different reliefs and/or applied graphical information for improving the discriminability between the closures  20  and  22  comprising an oxygen absorber  26  and the equally large closures  18  and  24  without oxygen absorber. 
         [0053]    The closures  20  and  22  are manufactured in the injection molding method from polypropylene. Alternatively, they may also be manufactured from polyoxymethylene, polyether ether ketone, polysulfone or from any other suitable plastics. 
         [0054]    The embodiments of the hollow fiber filter module  2  according to aspects of the invention and of the closure  20  or  22  according to aspects of the invention which are shown in the  FIGS. 2 to 3   b  and described above, only represent possible implementations of the claimed invention. 
         [0055]    By way of example, the closures  18 ,  20 ,  22  and  24  may also be formed in a lid-shaped manner such that there is no closure piece  28  which is inserted in the corresponding port  6 ,  8 ,  12  or  14 , but that the ports  6 ,  8 ,  12  or  14  are each received in a corresponding blind hole in the closure  18 ,  20 ,  22  or  24 . 
         [0056]    In order to connect the closures  18 ,  20 ,  22  and  24  in each case to the corresponding ports  6 ,  8 ,  12  and  14  not only by a frictional fit but also by an interlocking fit, the inner side of the cylinder shell-shaped ports  6 ,  8 ,  12  and  14  may be provided with depressions which are capable of receiving the lamellas  30 .