Hollow fiber membrane filter with improved separation properties

Abstract

The present invention relates to a hollow fiber membrane filter for purifying liquids having improved separation properties, comprising a cylindrical housing and a first inlet or outlet chamber and a second inlet or outlet chamber surrounding a first and second end of the cylindrical housing, respectively, the cylindrical housing being designed in at least one end region to improve liquid inflow to the hollow fiber membranes inside the cylindrical housing.

Description

[Technical field]

[0001] The present invention relates to hollow fiber membrane filters for the purification of liquids, in particular for the purification of blood. [Background technology]

[0002] Hollow fiber membrane filters are used for the purification of liquids. In particular, hollow fiber membrane filters are used in medical technology for the purification and decontamination of water, as well as in the form of dialyzers or hemofilters in the treatment of patients with kidney failure by extracorporeal blood therapy. Hollow fiber membrane filters generally consist of a cylindrical housing and a number of hollow fiber membranes arranged therein, which are potted with a potting compound in a potting zone at their ends in the housing and are hermetically connected to the housing. It is known that such hollow fiber membrane filters are designed for use in so-called dead-end processes or in cross-flow processes with two liquids, in which a mass transfer can take place through the membrane walls of the hollow fiber membranes, so that the desired purification of the liquid or of one of the liquids takes place. For this, the hollow fiber membrane filters are designed in such a way that the lumina of the hollow fiber membranes form a first flow space through which the first liquid flows, and the gaps between the hollow fiber membranes in the housing of the hollow fiber membrane filter form a second flow space through which the second liquid can flow. At one or both end regions of the hollow fiber membrane filter, an inlet or outlet space is disposed having liquid access points for allowing the first and second liquids to flow into and out of the respective flow spaces of the hollow fiber membrane filter.

[0003] There are many hollow fiber membrane filters on the market with different designs, especially with regard to the structure of the end regions and the inflow or outflow spaces connecting to the ends. With regard to the development of hollow fiber membrane filters for extracorporeal blood treatment (dialyzers and hemofilters), attempts are continually being made to modify and improve the design of hollow fiber membrane filters. Among other things, the focus is on ensuring that the geometry of the inflow or outflow space of the hollow fiber membrane filter through which the blood flows allows the blood to flow through the space as gently as possible, so that turbulent or stagnant flows that could damage blood cells are avoided. As is generally customary in extracorporeal blood purification, hollow fiber membrane filters are designed in such a way that the patient's blood is guided through a first flow space, i.e. through the lumina of the hollow fiber membrane.

[0004] Furthermore, there are many designs of hollow fiber membrane filters for extracorporeal blood treatment available on the market that are intended to improve the flow through the hollow fiber membrane in the second flow space. During the therapeutic use of hollow fiber membrane filters for extracorporeal blood treatment, an aqueous, physiologically compatible liquid (dialysis fluid) usually flows through the second flow space. In this case, the removal of harmful metabolites from the patient's blood is achieved by transmembrane mass transfer. Among them, the flow through the hollow fiber membrane in the second flow space is crucial for improving the separation of metabolites.

[0005] Kunikata et al. (Kunikata; ASAIO Journal, 55(3), pp. 231-235 (2009)) evaluate the performance data of various commercially available dialyzers with respect to different designs in the dialysate inlet area. In this publication, various design models are presented that are intended to provide a favorable flow behavior of the dialysate entering the dialyzer. In particular, such a solution is presented in which the dialysate entering through the dialysate connection is intended to flow evenly around the hollow fiber membranes arranged in a cylindrical housing in the end area of ​​the dialyzer, thereby resulting in a uniform flow over the hollow fiber membranes. The Asahi Kasei Kuraray APS-15S and Nipro PES-150S dialyzers are partially provided with a peripheral baffle plate facing the dialysate connection. The Asahi Kasei Kuraray APS-15SA dialyzer has a peripheral baffle plate through which the incoming dialysate flows. The Tory CS-16U dialyzer has a peripheral baffle plate with slots through which the incoming dialysate flows. The Fresenius FPX140 dialyzer exhibits a design in which the hollow fiber membranes in the end regions of the dialyzer are crenellated. Based on the investigation, Kunikata et al. concluded that the dialyzer design shown in the end regions of the dialyzer allows for improved dialysate flow to the hollow fiber membranes, thus improving the performance data of the hollow fiber membrane filters shown.

[0006] Since the embodiment shown by Kunikata has an elaborate housing design, these designs must be considered as disadvantageous in terms of the high level of productivity desired at large scale. Furthermore, the search for methods to simplify and accelerate the production of hollow fiber membrane filters continues. Therefore, there is a particular need for a means to enable the production of hollow fiber membrane filters with streamlined manufacturing steps. [Prior art documents] [Patent documents]

[0007] [Patent Document 1] International Publication No. 01 / 60477(A2) Brochure [Patent Document 2] DE 102016224627(A1) [Non-patent literature]

[0008] [Non-Patent Document 1] Written by Kunikata; ASAIO Journal, 55(3), pages 231-235 (2009) Summary of the Invention [Problem to be solved by the invention]

[0009] It was therefore an object of the present invention to provide a hollow fiber membrane filter which improves flow to the hollow fiber membranes, resulting in improved performance data. [Means for solving the problem]

[0010] This object is achieved by a hollow fiber membrane filter having the features of claim 1. Claims 2 to 12 relate to preferred embodiments. DETAILED DESCRIPTION OF THE PREFERRED EMBODIMENTS

[0011] The present invention provides a cylindrical housing extending longitudinally along a central axis and having a housing interior space, a first end region with a first end, and a second end region with a second end; a plurality of hollow fiber membranes disposed within a cylindrical housing and hermetically embedded in respective potting compounds at potting zones at first and second end regions of the cylindrical housing, the ends of the hollow fiber membranes being open, such that the lumina of the hollow fiber membranes form a first flow space and the interior space of the housing surrounding the hollow fiber membranes forms a second flow space; a first inflow or outflow space, each adjacent to the front ends of the first and second ends of the cylindrical housing and the potting zone, in fluid communication with the first flow space of the hollow fiber membrane filter, each having a first liquid access point for directing liquid into / out of the first inflow or outflow space; a second inlet or outlet space surrounding the first and second end regions of the cylindrical housing, the second inlet or outlet space being in fluid communication with the second flow region and each having a second liquid access point for directing liquid into / out of the second inlet or outlet space; a seal separating the first inlet or outlet space from the second inlet or outlet space; and flow passage openings in the end regions of the cylindrical housing which form a fluid connection between the second inlet and / or outlet space and the second flow space, The present invention relates to a hollow fiber membrane filter, characterized in that in at least one end region of a cylindrical housing, the ratio of the sum of the flow cross-sectional areas of all flow path openings to the flow cross-sectional area of ​​at least one second inflow space or outflow space is 0.5:1 to 7:1, or 0.75:1 to 5:1, or 1:1 to 3:1.

[0012] A hollow fiber membrane filter of the above type has high performance parameters with respect to purification of liquids. According to the above definition, an improved flow of liquid through the hollow fiber membrane can occur in at least one end region of the hollow fiber membrane filter as a result of the liquid flowing through the second connection into the second inlet or outlet space and injecting into the second flow space through the flow opening in the end region of the cylindrical housing. In particular, improved separation performances for the test solutes urea and vitamin B12 were measured for the hollow fiber membrane filter according to the invention. The clearance is determined in accordance with the DIN / EN / ISO 8637:2014 standard.

[0013] In one embodiment, the hollow fiber membrane filter can be embodied as a dialyzer. In the context of this application, the term "dialyzer" is used to describe blood filter devices based on the structure of the hollow fiber membrane filter, such as dialysis filters or hemofilters. In other applications, the hollow fiber membrane filter according to the invention can also be used as a filter for water treatment. The structure of the hollow fiber membrane is essentially known in the prior art.

[0014] The term "end region of a cylindrical housing" should be understood in the context of the present application as a section on the cylindrical housing that extends from the end of the cylindrical housing to the center of the cylindrical housing. By the term "end region" it is indicated that it is a region on the cylindrical housing that occupies only a small area compared to the longitudinal extension of the cylindrical housing. In particular, one of these end regions occupies less than one-fifth, or less than one-eighth, or less than one-tenth, or less than one-fifteenth of the total length of the cylindrical housing.

[0015] The potting zone is located in a part of the end region of the cylindrical housing. In the context of this application, the "potting zone" is the region where the hollow fiber membrane of the hollow fiber membrane filter is embedded in the potting compound. The hollow fiber membrane is embedded in the potting compound so as to be fixed to the end region of the cylindrical housing. The potting compound forms a seal with the end region of the cylindrical housing. In particular, the potting zone is provided so that it occupies less than three-quarters, or less than two-thirds, or less than half of the width of the end region. The potting compound is plate-shaped and is arranged in the cylindrical housing perpendicular to the central axis of the cylindrical housing. The term "central axis" should be understood as the longitudinal axis of the cylindrical housing that passes through the center of the cylindrical housing of the hollow fiber membrane filter. In the context of this application, the term "central axis" is used for the geometric description of the hollow fiber membrane filter.

[0016] The first inflow or outflow space is located at the front side adjacent to the potting zone at the end of the cylindrical housing. In the context of the present application, the term "first inflow or outflow space" is understood to mean a volume area in the hollow fiber membrane filter into which liquid can flow either before the liquid enters the first flow space of the hollow fiber membrane filter or after the liquid leaves the first flow space of the hollow fiber membrane filter. The first inflow and outflow spaces are adjacent to the potting zone in a sealed manner by the wall of the end cap and / or adjacent to the end of the end region of the cylindrical housing. In a particular embodiment, the first inflow or outflow space can be embodied as an end cap. The end cap is located at the end of the cylindrical housing and is connected to the cylindrical housing of the hollow fiber membrane filter in a liquid-tight and secure manner by the wall of the end cap. Each of the first inflow or outflow spaces has a first liquid access point for directing liquid into / out of the first inflow or outflow space. The first inflow or outflow space is therefore in fluid communication with the first flow space of the hollow fiber membrane filter, which is formed by the lumina of the hollow fiber membrane. In the context of this application, "lumina" or "lumen" is understood to mean the cavity of the hollow fiber membrane.

[0017] According to the invention, the hollow fiber membrane filter also has a second inflow or outflow space surrounding the respective end region of the cylindrical housing. In the context of the present application, the term "second inflow or outflow space" is understood to mean a defined volume area in the hollow fiber membrane filter into which a liquid can flow either before the liquid enters the second flow space of the hollow fiber membrane filter or after the liquid leaves the second flow space of the hollow fiber membrane filter. The second inflow or outflow space is each formed by a casing surrounding the end region of the cylindrical housing. The wall of the casing sealingly adjoins the potting zone and / or the end of the end region of the cylindrical housing. The casing can be part of the cylindrical housing and attached to it, in which case the second inflow or outflow space is sealingly enclosed by the casing. Alternatively, the casing can also be formed by a separate sleeve or as part of an end cap surrounding the first inflow or outflow space. In that case, the end cap is designed to seat securely on the end of the cylindrical housing, abutting the housing in a liquid-tight manner, while also forming the casing of a second inlet or outlet space, each of which has a second liquid access point for directing liquid into / out of the second inlet or outlet space, which is in fluid communication with a second flow space of the hollow fiber membrane filter, which second flow space is formed by the interior space of the housing of the hollow fiber membrane filter surrounding the hollow fiber membrane.

[0018] As mentioned above, the first and second inlet or outlet spaces are sealingly adjacent to the potting zone and / or to the end of the end region of the cylindrical housing. Thus, the first and second inlet or outlet spaces are liquid-tightly separated from each other at this location. Some examples of suitable sealing means include O-rings, welded zones, or bonded zones disposed between the end of the end region of the cylindrical housing or the end of the potting compound and the walls of the first and second inlet or outlet spaces.

[0019] A fluid connection is formed between the second inlet or outlet space and the second flow space via the flow openings in the end region of the cylindrical housing. Thus, liquid can enter or leave the second flow space. The number of flow openings in the end region of the cylindrical housing can be at least 5, or 10, or 15, or 20, or 30, or 40, or 60. The number of flow openings is at most 350, or 300, or 250, or 200, or 180, or 150. The number of flow openings in the end region of the cylindrical housing is preferably 10-350, or 10-40, or 15-300, or 20-250, or 30-200, or 40-180, or 60-180.

[0020] The geometric ratio of the sum of the flow cross-sectional areas of all the flow openings to the flow cross-sectional area of ​​the at least one second inlet or outlet space is between 0.5:1 and 7:1, or between 0.75:1 and 5:1, or between 1:1 and 3:1. "The sum of the flow cross-sectional areas of the flow openings" is understood to mean the sum of all surface areas of the individual flow openings in the end region of the cylindrical housing.

[0021] In the context of this application, the "cross-sectional flow area of ​​the second inflow or outflow space" is understood to mean the cross-sectional area of ​​the second inflow or outflow space created by forming a cross section through the hollow fiber membrane filter and passing through the central axis of the cylindrical housing. This cross section is arranged so as not to contact the second liquid access points in the second inflow and outflow spaces. By positioning the two cross-sectional areas of the second inflow or outflow space in the aforementioned cross-sectional view, for example, when the second inflow or outflow space has a rotationally symmetrical geometry, only one of these cross-sectional areas is used to determine the cross-sectional flow area.

[0022] Since the improved flow to the hollow fiber membrane in the second flow space is believed to be the reason for the above effect, it is sufficient that the geometric ratio of the flow cross-sectional area of ​​the flow passage opening to the flow cross-sectional area of ​​at least one second inflow or outflow space is met in only one end region of the cylindrical housing, in which case, as a result of using the hollow fiber membrane filter, the inflow liquid from the second inflow or outflow space flows against the hollow fiber membrane in the second flow space.

[0023] In an advantageous embodiment of the invention, the hollow fiber membrane filter is characterized in that at least one second inlet or outlet space, starting from the second liquid access point, forms a rotationally symmetric circumferential space, in particular an annular gap, relative to the central axis of the cylindrical housing in at least one end region of the cylindrical housing, in which there is a predefined ratio of the sum of the flow cross-sectional areas of all the flow openings to the flow cross-sectional area of ​​the at least one second inlet or outlet space. Thanks to the rotationally symmetric geometry of the second inlet or outlet space, components for hollow fiber membrane filters can be produced in an optimized process, in particular by means of injection molding techniques.

[0024] In another advantageous embodiment of the invention, the hollow fiber membrane filter is characterized in that the two second inlet or outlet spaces form a rotationally symmetric circumferential space, in particular an annular gap, as defined in the claims, and further characterized in that in the end region of the cylindrical housing, the ratio of the sum of the flow cross-sectional areas of all the flow openings to the flow cross-sectional area of ​​at least one second inlet or outlet space is in a predefined range of 0.5:1 to 7:1, or 0.75:1 to 5:1, or 1:1 to 3:1. According to this condition, the hollow fiber membrane filter has a symmetrical structure in the end region of the cylindrical housing. In particular, a symmetrical structure simplifies the production of the hollow fiber membrane filter, since the number of different components is small and no preferred orientation of the components needs to be observed during the manufacturing process. The same applies when the hollow fiber membrane filter is used in filtration applications. Here too, it is advantageous if the hollow fiber membrane filter has a symmetrical structure and no preferred orientation needs to be observed in the application.

[0025] In another embodiment, the hollow fiber membrane filter is characterized in that at least one end region and optionally a second end region are divided into a proximal end region, a distal end region, and a transition region arranged between the proximal end region and the distal end region, one end of the distal end region being the end of a cylindrical housing, and the distal end region has an inner diameter at least 2% larger than the inner diameter of the proximal end region. In an aspect of this embodiment, the proximal end region is close to the center of gravity of the cylindrical housing. The distal end region is therefore arranged distal to this center of gravity of the cylindrical housing, and therefore at the end of the cylindrical housing. Advantageously, the packing density of the hollow fiber membranes arranged in the cylindrical housing of the hollow fiber membrane filter is reduced in the distal end region due to the larger inner diameter of the cylindrical housing in this part of the distal end region. This provides the advantage that fewer defects occur when casting the hollow fiber membranes into the cylindrical housing during the manufacture of the hollow fiber membrane filter. Furthermore, the lower packing density in this distal end region allows the hollow fiber membranes to accommodate dialysate flow.

[0026] In the transition region of the end region 103, the inner diameter of the cylindrical housing increases by 2% or more. Preferably, the inner diameter of the cylindrical housing increases in the transition region by 3% or more, or 4% or more, or 5% or more, at most 10%, or at most 8%, or at most 7%, or at most 6%, in particular by 2-10%, or 3-8%, or 4-7%. The transition region occupies at least 1 / 10, or at least 1 / 12, or at least 1 / 14, or at least 1 / 15, or at least 1 / 17, or at least 1 / 18, or at least 1 / 20, as well as at most 1 / 40, or at most 1 / 35, or at most 1 / 30, or at most 1 / 25, in particular 1 / 10-1 / 40, or 1 / 12-1 / 35, or 1 / 14-1 / 30, or 1 / 15-1 / 25, of the total length of the cylindrical housing in the direction of extension of the central axis of the cylindrical housing.

[0027] In a further embodiment of the above embodiment, the hollow fiber membrane filter is characterized in that the flow opening is arranged in the distal end region. Thus, the dialysate flowing into the second flow space can be passed directly through the portion of the hollow fiber membranes with a low packing density via the flow opening. This results in a circumferentially uniform flow which is favorable for the hollow fiber membranes in the distal end region, and which can also penetrate the array of hollow fiber membranes better due to the low packing density in this portion of the distal end region until the flow of the dialysate enters the portion of the hollow fiber membranes with a high packing density.

[0028] In another advantageous embodiment of the present invention, the hollow fiber membrane filter is characterized in that the flow passage openings are circular, oval or slot shaped.Depending on the different inner diameters of the cylindrical housing provided for different applications, the number and shape of the flow passage openings in the end region of the cylindrical housing can vary.This also depends on the manufacturability of the cylindrical housing, which is preferably manufactured using injection molding technology.Therefore, it is advantageous to arrange a large number of flow passage openings in the end region of the cylindrical housing, which have the shape of a circle, an oval or a slot.

[0029] In another advantageous embodiment of the invention, the hollow fiber membrane filter is characterized in that the flow openings are arranged in isolated and / or opposing compartments or evenly around the circumference of the end region of the cylindrical housing.

[0030] In another advantageous embodiment of the present invention, the hollow fiber membrane filter has a total flow cross-sectional area of ​​all flow passage openings of 10 to 350 mm 2 , or 15~200mm 2 , or 15~150mm 2 , or 20~110mm 2The sum of the flow cross-sectional areas of all the assumed flow path openings depends on the inner diameter of the cylindrical housing of the hollow fiber membrane filter, and further on the number of hollow fiber membranes. In a hollow fiber membrane filter having a large surface area of ​​the hollow fiber membrane and a large number of hollow fiber membranes, the flow volume of the second flow space of the hollow fiber membrane filter needs to be correspondingly large in order to achieve sufficient filtration performance. As an example, when about 10,000 hollow fiber membranes are arranged in the second flow space of the hollow fiber membrane filter, the sum of all the flow cross-sectional areas of the flow path openings is about 90 to 150 mm. 2 The inner diameter of the cylindrical housing can be 28-35 mm. In another embodiment, the inner diameter of the housing can be 20-45 mm, in particular 28-45 mm, more particularly 30-40 mm. By adapting the sum of all the flow cross-sectional areas of the flow passage openings to the inner diameter of the cylindrical housing, the inflow of the liquid into the second flow space is adjusted, and thus an improvement in the flow to the hollow fiber membrane in the second flow space is achieved.

[0031] In another advantageous embodiment of the present invention, the hollow fiber membrane filter has a flow cross-sectional area of ​​one or both of the second inflow space and the outflow space of 20 to 50 mm 2 , 20~40mm 2 , or 25mm 2 Here again, the flow cross-sectional area of ​​the inflow space or outflow space can be adapted to the inner diameter of the cylindrical housing of the hollow fiber membrane filter, and therefore, different values ​​can be adopted for the number of hollow fiber membrane filters. As an example, when about 10,000 hollow fiber membranes are arranged in the second flow space of the hollow fiber membrane filter, the flow cross-sectional area of ​​the inflow space or outflow space is 20 to 30 mm 2 By matching the cross-sectional flow area of ​​the inlet or outlet space to the inner diameter of the cylindrical housing, an efficient distribution of the liquid entering the second inlet or outlet space can be obtained, so that a uniform flow of the liquid to the hollow fiber membranes can be achieved as it enters the second flow space.

[0032] The inner diameter of the hollow fiber membrane filter according to the present invention can be 20 to 455 mm. In particular, since 5,000 to 15,000 hollow fiber membranes can be arranged in the cylindrical housing of the hollow fiber membrane filter, the hollow fiber membrane filter has a diameter of 0.6 to 2.5 mm. 2 The membrane surface area is calculated from the product of the internal surface area of ​​the hollow fiber membrane and the number of hollow fiber membranes arranged in the cylindrical housing of the hollow fiber membrane filter. The internal surface area of ​​the hollow fiber membrane is calculated from the product of the inner diameter of the hollow fiber membrane, the circular constant π, and the actual effective length. According to the present invention, in one embodiment, the actual effective length of the hollow fiber membrane filter in the cylindrical housing is 200-350 mm. In the context of this application, the actual "effective length" of the hollow fiber membrane filter or hollow fiber membrane is understood to be the distance between the potting compounds where an effective exchange of substances takes place through the hollow fiber membrane. In one embodiment, the packing density of the hollow fiber membranes in the hollow fiber membrane filter is 55-65%, in particular 60-65%. In the context of this application, the "packing density" is understood to mean the portion of the housing interior space of the cylindrical housing that is occupied by the hollow fiber membranes. Packing density is the percentage ratio of the sum of the cross-sectional areas of the hollow fiber membranes to the cross-sectional area of ​​the cylindrical housing of the hollow fiber membrane filter, the cross-sectional area of ​​the cylindrical housing being understood to be simply the cross-sectional area designated by the inside diameter.

[0033] To construct the hollow fiber membrane filter according to the present invention, it is preferable to use a hollow fiber membrane made of polysulfone and polyvinylpyrrolidone. In particular, the hollow fiber membrane can have a wavy shape. Such a wavy hollow fiber membrane is described, for example, in WO 01 / 60477(A2). The amplitude of the wavy shape can be 0.03 to 0.8 mm. The wavelength of the wavy shape can be 3 to 30 mm, particularly 5 mm to 12 mm. The diameter of the hollow fiber membrane can be 205 to 330 μm, particularly 170 to 200 μm, and the diameter of the lumina of the hollow fiber membrane can be 165 to 230 μm, particularly 175 to 200 μm.

[0034] The potting compound in which the hollow fiber membranes are embedded and sealed in each end region of the cylindrical housing is preferably made of polyurethane.

[0035] The cylindrical housing and the end caps are preferably made from a polypropylene material.

[0036] In an advantageous embodiment of the invention, the hollow fiber membrane filter is constructed to have an aspect ratio of 8 to 12, specifically 9 to 11, more specifically 9 to 10. In the context of the present application, "aspect ratio" is understood to be the ratio of the actual effective length of the hollow fiber membrane filter to the inner diameter of the cylindrical housing. Thus, the flow through the hollow fiber membranes in the second flow region via the ratio of the sum of the flow cross-sectional areas of all flow openings to the flow cross-sectional area of ​​at least one second inlet or outlet space is further improved by a reduction in the inner diameter of the cylindrical housing with the same packing density and membrane surface area. To meet these conditions, the hollow fiber membrane filter is constructed according to the invention in such a way that for the same membrane surface area and packing density, the number of hollow fiber membranes is reduced, but the actual effective length is increased. This is particularly advantageous for hollow fiber membrane filters with a large membrane surface area.

[0037] In another advantageous embodiment of the invention, the hollow fiber membrane filter is characterized in that the first and second inlet or outlet spaces in the first end region of the cylindrical housing and the first and second inlet or outlet spaces in the second end region of the cylindrical housing are enclosed by the first and second end caps, respectively. The end caps are advantageously molded in one piece. The end caps are designed to form a casing, one wall of which encloses the first inlet or outlet space and another wall of which encloses the second inlet or outlet space. The end caps are geometrically shaped to seat on the end region of the cylindrical housing and to be liquid-tight by the seal. The end caps are advantageously manufactured by injection molding. The manufacture of the hollow fiber membrane filter with the end caps defined here contributes to the optimization of the manufacturing process of the hollow fiber membrane filter. The first and second liquid access points are arranged on the end caps.

[0038] In another advantageous embodiment of the invention, the hollow fiber membrane filter is characterized in that the first end cap can be reliably, particularly liquid-tightly, adjoined to the annular peripheral projection on the first end region of the cylindrical housing. In particular, the second end cap can also be reliably, particularly liquid-tightly, adjoined to the annular peripheral projection on the second end region of the cylindrical housing. In this way, the end cap and the cylindrical housing are connected liquid-tight along the peripheral projection. The seal can be applied by welding or gluing.

[0039] In another advantageous embodiment of the invention, the hollow fiber membrane filter is characterized in that the first end cap can be reliably adjoined to the first end of the cylindrical housing, in particular in a liquid-tight manner along an inner circular line. In particular, the second end cap can also be reliably adjoined to the second end of the cylindrical housing, in particular in a liquid-tight manner along an inner circular line. This inner circular line can be embodied, for example, as a circular bead or protrusion on the inside of the end cap. However, instead, the inside of the wall of the end cap can also be directly connected to the end of the cylindrical housing. By connecting the circular line of the end cap to the end of the cylindrical housing, a liquid seal is created between the first inlet and outlet spaces and the second inlet and outlet spaces by welding, gluing or O-rings.

[0040] In another advantageous embodiment of the present invention, the hollow fiber membrane filter has a volume of 1.5 to 5 cm 3 for one or both of the second inlet space and the outlet space. 3 The defined volume area of ​​the second inlet and / or outlet spaces in particular ensures that the liquid entering the second inlet or outlet space is evenly distributed as a function of the inner diameter of the cylindrical housing, which also prevents flow stagnation in the region of at least one second inlet or outlet space and non-uniform flow relative to the hollow fiber membranes in the second flow region.

[0041] In another advantageous embodiment of the invention, the hollow fiber membrane filter is characterized in that the cylindrical housing and the end caps are made of a thermoplastic material, in particular polypropylene. The cylindrical housing and the end caps can therefore be advantageously manufactured using an optimized injection molding process. Furthermore, the choice of material also provides the advantage that the cylindrical housing and the end caps can be securely and hermetically connected to each other through a welding process. [Brief description of the drawings]

[0042] [Figure 1a] FIG. 1a shows a cross section of a hollow fiber membrane filter according to the invention, taken through the central axis A of the cylindrical housing. [Figure 1b] FIG. 1b shows another cross section of the hollow fiber membrane filter according to the invention, passing through both the central axis A of the cylindrical housing and the central axis B of the second liquid access point. [Figure 2a] FIG. 2a shows a side view of a cylindrical housing of a hollow fiber membrane filter according to the invention, depicting an end region of the cylindrical housing. [Figure 2b] Figure 2b shows a side view of another embodiment of a cylindrical housing of a hollow fiber membrane filter according to the invention, depicting the end region of the cylindrical housing. The illustration according to Figure 2b is provided with dimensions. The dimensional values ​​refer to the unit millimeters (mm). [Diagram 3] FIG. 3 shows a cross-sectional schematic diagram of an FX60 hollow fiber membrane filter available from Fresenius Medical Care Deutschland GmbH, passing through both the central axis A of the cylindrical housing and the central axis B of the second liquid access point. [Figure 4] FIG. 4 shows a side view of the cylindrical housing of the FX60 hollow fiber membrane filter available from Fresenius Medical Care.

[0043] FIG. 1a shows a schematic cross-sectional view of a hollow fiber membrane filter 100 according to the invention along the central axis A of the cylindrical housing. Only a part of the hollow fiber membrane filter is shown in FIG. 1a, which illustrates a first end 104 on a cylindrical housing 101 with a first end region 103. A part of the end region 103 is occupied by a potting zone 106 arranged forward with respect to the longitudinal direction, i.e. perpendicular to the central axis A of the cylindrical housing, which potting compound 105 is embedded in the hollow fiber membranes (not shown in FIG. 1a) in the housing interior space 102 at the first end region 103 and at the second end region (not shown) of the cylindrical housing 101, respectively, to form a seal with the housing 101. Also shown is an end cap 111 with a wall 114 surrounding a first inlet or outlet space 107 and a casing region 115 surrounding a second inlet or outlet space 109. The surface of the flow cross section of the second inlet or outlet space 109 is hatched in Fig. 1a. The liquid access point 108 is also shown. In this illustration, the liquid access point 108 represents a typical detail of the blood connection of a dialyzer. The liquid access point 108 forms a liquid access point to the first inlet or outlet space 107. The end cap 111 shown in Fig. 1 is molded in one piece, so that the wall 114 and the casing 115 are part of the end cap. According to the arrangement shown in Fig. 1a, the spaces of the first and second inlet or outlet spaces (107, 109) are surrounded by the end cap 111, the cylindrical housing 101 and the potting compound 105. The first inlet or outlet space is sealed at the end 104 of the cylindrical housing 101 with a circumferential seal 110. The inner circumference 110a of the end cap 111, which is only shown in cross section in Fig. 1, is used for this purpose. In the embodiment shown in FIG. 1, an inner periphery 110 a of the end cap 111 seats against the end 104 of the cylindrical housing 101 , thereby creating a seal 110 between the end 104 of the cylindrical housing and the end cap 111 .Liquid entering the first inlet or outlet space 107 through liquid access point 108 enters the lumina of the hollow fiber membrane and thus enters the first flow space exclusively through the open ends of the hollow fiber membranes (not shown in FIG. 1 a) in the potting compound 105. Another circumferential liquid seal 112 is created by an annular outer circumferential projection 112a on the cylindrical housing 101 that tightly and liquid-tightly abuts the casing 115 of the end cap 111.

[0044] FIG. 1b shows another cross section of the hollow fiber membrane filter 100 according to the invention, passing through both the central axis A of the cylindrical housing and the central axis B of the second liquid access point. The central axis B passes through the center of the second liquid access point 116 adjacent to the second inlet or outlet space 109. 100-111, 114 and 115 in FIG. 1b show the corresponding details of FIG. 1a. The surface of the flow cross section of the second inlet or outlet space 109 is shown in FIG. 1a with parallel lines. Furthermore, in this cross section, the flow openings 113 can be seen on the side of the cylindrical hollow fiber membrane filter opposite the end region 103. According to FIG. 1b, a fluid connection is created via the flow openings 113 between the second liquid access point 116 of the second inlet or outlet space 109 and the second flow space in the housing interior 102 of the hollow fiber membrane filter 100. In the embodiment shown in FIG. 1b, a number of flow passage openings (only two of which are visible in the cross-sectional view of FIG. 1b) are arranged opposite each other in the end region 103 of a cylindrical hollow fiber membrane filter.

[0045] FIG. 2a shows a schematic diagram of a part of a cylindrical housing 101 of a hollow fiber membrane filter according to the invention in a side view. In the illustration of FIG. 2a, a part with a first end 104 of the cylindrical housing 101 is shown. FIG. 2a also shows an annular peripheral protrusion 112a on the cylindrical housing 101, which is provided for the purpose of creating a seal 112 on the casing 115 of the end cap 111. Reference number 103 denotes the end region of the cylindrical housing 101. Reference number 106 denotes a potting zone of the end region, the potting compound 105 is not shown in FIG. 2a. The central axis A points in the longitudinal direction of the cylindrical housing. In the side view, a number of flow openings 113 are shown, which form the connection between the second inlet or outlet space 109 and the second flow space (neither of which is shown in FIG. 2A) in the hollow fiber membrane filter. In the illustrated illustrations the flow openings are depicted as circular, but they can also have an oval, slot or U-shape. The flow cross-sectional area of ​​the flow openings 113 results from the sum of the flow cross-sectional areas for all the individual flow openings 113. The embodiment shown according to Fig. 2a has 22 flow openings 113 in the end region 103 of the cylindrical housing 101, only half of which - i.e. 11 - are visible in Fig. 2a. The additional 11 flow openings are located on the other side of the end region 103 of the cylindrical housing 101.

[0046] Fig. 2b shows a schematic diagram of an embodiment of a part of a cylindrical housing 101 of a hollow fiber membrane filter according to the invention in a side view. In the illustration of Fig. 2b, a part with a first end 104 of the cylindrical housing 101 is shown. Fig. 2b also shows an annular peripheral protrusion 112a on the cylindrical housing 101, which is provided to create a seal 112 on the casing 115 of the end cap 111. Also shown in Fig. 2b are: 103 - end region of the cylindrical housing 101, central axis A, 113 - circular through opening.

[0047] In the illustrated embodiment, the distance from the center of the flow passage opening 113 to the end 104 of the cylindrical housing 101 is 10 mm. At the end 104 of the cylindrical housing, the diameter of the opening of the cylindrical housing is 34 mm. In the illustrated embodiment, the end region 103 of the cylindrical housing is divided into a proximal end region 103a and a distal end region 103b. In the illustrated embodiment, the proximal end region 103a is disposed adjacent to the annular outer peripheral projection 112a and is therefore closer to the center of gravity of the cylindrical housing in terms of the embodiment shown in FIG. 2b. In the embodiment shown in FIG. 2b, the inner diameter of the distal end region 103b of the cylindrical housing is larger than the inner diameter of the proximal end region 103a. The proximal end region and the distal end region are adjacent to each other via a transition region 103c. At the transition region 103c of the end region 103, the inner diameter of the cylindrical housing increases by more than 3%. In particular, according to the embodiment shown in FIG. 2b, the diameter of the distal end region 103b at the end of the cylindrical housing is 34 mm, whereas the inner diameter of the distal end region 103b at the subsequent transition 103c is 33.5 mm. The inner diameter of the cylindrical housing 101 in the proximal end region is 31.9 mm in the embodiment shown in FIG. 2b. The increase in the inner diameter from the proximal end region 103a to the distal end region 103b is therefore 1.6 mm in the illustrated embodiment. The inner diameter of the cylindrical housing 101 is 31.4 mm in the central region. From the dimensions shown in FIG. 2b, it can be seen that the inner diameter in each of the distal end region 103b and the proximal end region 103a tapers further towards the central part of the cylindrical housing. The conical shape of the inner diameter for the individual regions of the cylindrical housing 101 described according to FIG. 2b arises from the need to be able to demold the cylindrical housing as an injection molded part from an injection molding machine. Such geometries required for injection molded parts are known in the injection molding art. The change in inner diameter at the transition region 103c must be distinguished from these necessary cone-like changes in inner diameter. The transition region 103c occupies an area of ​​less than 2 mm in the direction of extension of the central axis A in the embodiment shown in FIG. 2b, where the inner diameter increases from 31.9 mm in the proximal end region to 33.5 mm in the distal end region. The transition region occupies only about 1 / 15 of the total length of the cylindrical housing.

[0048] In one embodiment of the hollow fiber membrane filter according to the present invention, made according to the details shown in Figures 1a, 1b and 2, the sum of the flow cross-sectional areas of all the flow openings can be, for example, 17 mm2. Furthermore, in this embodiment, the flow cross-sectional area of ​​the second inlet or outlet space can be about 26 mm2. The ratio of the sum of the flow cross-sectional areas of all the flow openings to the flow cross-sectional area of ​​at least one second inlet or outlet space is 0.65:1.

[0049] Figure 3 shows a schematic cross-section of an FX hollow fiber membrane filter available from Fresenius Medical Care Deutschland GmbH, the cross-section passing through the central axis A of the cylindrical housing as well as the central axis B of the second liquid access point. As with the previous figures, Figure 3 shows: 301 Cylindrical case 302 A housing interior space of the cylindrical case for receiving a plurality of hollow fiber membranes (not shown in FIG. 3) 303 End Area of ​​Cylindrical Housing 304 First end of cylindrical housing 305 Potting Compound 306 Potting Zone 307 First inflow or outflow space 308 First liquid access point to the first inlet or outlet space 309 Second inflow or outflow space 310 Circumferential seal embodied as an O-ring 310a Inner circumference of end cap 311 End Cap 312a Annular outer peripheral protrusion 314 End Cap Wall 315 Casing of the end region of the cylindrical housing on the end cap; 316 Secondary liquid access point.

[0050] As can be seen from Figure 3, the hollow fiber membrane filters shown in Figures 1a, 1b and 3 are structurally different in the structure of the second inlet and outlet spaces. The flow channel openings (not shown) connecting the second inlet or outlet spaces to the second flow region of the hollow fiber membrane filter are not visible in Figure 3.

[0051] FIG. 4 shows a schematic side view of a cylindrical housing 401 of an FX hollow fiber membrane filter available from Fresenius Medical Care Deutschland GmbH, which has a potting compound 405 in a potting zone 406. FIG. 4 shows an annular peripheral protrusion 412a. The side view also shows flow passage openings 413 arranged circumferentially on an end region 403 of the housing 401. The FX60 hollow fiber membrane filter described according to FIGS. 3 and 4 has a 26 mm 2 In the same embodiment of the FX hollow fiber membrane filter, the sum of the flow cross-sectional areas of all the flow openings is 392 mm 2 The ratio of the sum of the cross-sectional flow areas of all the flow openings to the cross-sectional flow area of ​​the at least one second inlet or outlet space is 15:1. EXAMPLES

[0052] Clearance Determination The clearance is determined according to the DIN / EN / ISO 8637:2014 standard, in the example a blood flow rate of 300 ml / min and a dialysate flow rate of 500 ml / min are set. As test solutions, an aqueous solution of 16.7 mmol / l urea (Merck) and 36.7 μmol / l vitamin B12 (Biesterfeld, BCD Chemie) is used on the blood side, and distilled water on the dialysate side. The concentration of vitamin B12 is determined photometrically at 361 nm. Urea is measured using a Cobas Integra 400 plus device (Roche Diagnostics, Germany) with UREAL test.

[0053] Example 1: Hollow fiber membrane filter according to the present invention A hollow fiber membrane filter was manufactured with construction details according to Figures 1a and 1b and parameters shown in Table 1. A corrugated polysulfone / polyvinylpyrrolidone hollow fiber membrane was used, which is in particular incorporated in the FX60 filter of Fresenius Medical Care. The hollow fiber membrane filter was manufactured according to methods known in the prior art. The hollow fiber membrane filters according to the invention were sterilized using the steam sterilization method known in the prior art and described in DE 102016224627 A1. The clearance and sieving coefficients were investigated for the sterile as well as for the non-sterile embodiment. The results are shown in Table 2.

[0054] Comparative Example 1: FX60 hollow fiber membrane filter The FX60 hollow fiber membrane filter from Fresenius Medical Care was used as a comparative embodiment. The structural details of the FX60 hollow fiber membrane filter are shown in Figures 3 and 4. The technical parameters of the FX60 filter are shown in Table 1. The FX60 hollow fiber membrane filters were sterilized using the same steam sterilization process used for the hollow fiber membrane filters according to the invention. The clearance determined using the hollow fiber membrane filters was investigated for the sterile as well as the non-sterile embodiment. The results are shown in Table 2. Table 1 JPEG2024517456000002.jpg90150 The hollow fiber membrane filters according to the present invention according to Example 1 and the FX60 hollow fiber membrane filter according to Comparative Example 1 used hollow fiber membranes originating from the same production. These hollow fiber membranes were identical in terms of diameter, wall thickness, pore characteristics, and material composition. The number of hollow fiber membranes in Example 1 and Comparative Example 1 was 1.0 mm, and each hollow fiber membrane filter had the same membrane surface area of ​​1.4 m. 2 The results were adjusted to have the following: Table 2 JPEG2024517456000003.jpg42157The results in Table 2 show that the clearance of urea and vitamin B12 of the sterilized and non-sterilized hollow fiber membrane filters according to Example 1 is higher than that of the FX60 hollow fiber membrane filter of Comparative Example 1. Furthermore, the examples according to the present invention only show a slight decrease in urea clearance after sterilization. [Explanation of symbols]

[0055] 100 Hollow fiber membrane filter 101 Cylindrical housing 102 Housing internal space 103 first end region 104 First end 105 Potting Compound 106 Potting Zone 107 First inflow or outflow space / 108 Liquid Access Points 109 Second inflow or outflow space 110 Circumferential seal 110a Inner circumference of end cap 111 End Cap 112 Another circumferential liquid seal 112a Annular outer peripheral protrusion 113 Flow passage opening 114 Wall 115 Casing Area 116 Secondary Liquid Access Point A Central axis of cylindrical housing B Central axis of second liquid access point

Claims

1. A hollow fiber membrane filter (100), A cylindrical housing (101) extending longitudinally along a central axis (A) and having a housing interior space (102), a first end region (103) with a first end (104), and a second end region (103) with a second end; a plurality of hollow fiber membranes disposed within said cylindrical housing (101) and hermetically embedded in respective potting compounds (105) at potting zones (106) at said first end region (103) and said second end region of said cylindrical housing, said ends of said hollow fiber membranes being open, such that the lumina of said hollow fiber membranes form a first flow space and the housing interior space (102) surrounding said hollow fiber membranes forms a second flow space; a first inflow or outflow space (107), each adjacent to a front end of the first end (104) and the second end of the cylindrical housing (101) and the potting zone (106) and in fluid communication with the first flow space of the hollow fiber membrane filter, each first inflow or outflow space (107) having a first liquid access point (108) for directing liquid into / out of the first inflow or outflow space (107); a second inlet or outlet space (109) surrounding the first and second end regions of the cylindrical housing (101), the second inlet or outlet space (109) being in fluid communication with the second flow region, each second inlet or outlet space (109) having a second liquid access point (116) for directing liquid into / out of the second inlet or outlet space (109); a respective seal (110) separating said first inlet or outlet space (107) from said second inlet or outlet space (109); a flow passage opening (113) in the end region (103) of the cylindrical housing (101) forming a fluid connection between the second inlet and / or outlet space (109) and the second flow space; A hollow fiber membrane filter comprising: The hollow fiber membrane filter (100) is characterized in that in at least one end region of the cylindrical housing, the ratio of the sum of the flow cross-sectional areas of all the flow passage openings (113) to the flow cross-sectional area of ​​the at least one second inlet or outlet space is 0.5:1 to 7:1, or 0.75:1 to 5:1, or 1:1 to 3:

1.

2. 2. The hollow fiber membrane filter (100) according to claim 1, characterized in that in the at least one end region (103) of the cylindrical housing (101), in which the ratio of the sum of the flow cross-sectional areas of all flow openings (113) to the flow cross-sectional area of ​​the at least one second inlet or outlet space (109) exists as defined in claim 1, the at least one second inlet or outlet space (109) starting from the second liquid access point forms a circumferential space, in particular an annular gap, which is rotationally symmetrical with respect to the central axis (A) of the cylindrical housing (101).

3. 3. The hollow fiber membrane filter (100) according to claim 2, characterized in that both the second inlet space or the outlet space (109) form the rotationally symmetric circumferential space, in particular the annular gap, as defined in claim 2.

4. 2. The hollow fiber membrane filter according to claim 1, characterized in that the at least one end region (103) and optionally the second end region are divided into a proximal end region (103a), a distal end region (103b) and a transition region (103c) arranged between the proximal end region and the distal end region, one end of the distal end region (103b) of the first and / or second end region corresponds to a respective end of the cylindrical housing (103b), and the distal end region has an inner diameter that is at least 2% larger than the inner diameter of the proximal end region.

5. The hollow fiber membrane filter (100) according to claim 4, characterized in that the flow passage openings are arranged in the distal end region.

6. 2. The hollow fiber membrane filter (100) according to claim 1, characterized in that the flow openings are circular, oval or slot shaped.

7. 2. The hollow fiber membrane filter (100) according to claim 1, characterized in that the flow passage openings (113) are arranged in isolated and / or opposing compartments or in the circumferential direction in the end region (103) of the cylindrical housing (101).

8. The sum of the flow cross-sectional area of ​​all flow passage openings is 10 to 350 mm 2 , or 15 to 200 mm 2 , or 15 to 150 mm 2 , or 20 to 110 mm 2 The hollow fiber membrane filter (100) according to claim 1, characterized in that

9. The flow cross-sectional area of ​​one or two of the second inflow or outflow spaces (109) is 20 to 50 mm 2 , 20-40 mm 2 , or 20 to 25 mm 2 The hollow fiber membrane filter (100) according to claim 1, characterized in that

10. 2. The hollow fiber membrane filter (100) according to claim 1, characterized in that the first inlet or outlet space (107) and the second inlet or outlet space (109) in the first end region (103) of the cylindrical housing (101) and the first and second inlet or outlet spaces in the second end region of the cylindrical housing are surrounded by first and second end caps (111), respectively.

11. 11. The hollow fiber membrane filter (100) according to claim 10, wherein the first and second end caps (111) adjoin annular peripheral projections (112a) on the first end region (103) and on the second end region of the cylindrical housing (101) reliably, in particular in a liquid-tight manner.

12. 11. The hollow fiber membrane filter (100) according to claim 10, characterized in that the first and second end caps (111) are securely adjacent to the first end (104) and the second end (106), respectively, of the cylindrical housing (101), in a particularly liquid-tight manner along an inner circular line (110a).

13. 2. The hollow fiber membrane filter (100) according to claim 1, characterized in that in the end region (103) near the flow passage opening (113), the housing (101) has an inner diameter of 20 to 45 mm, in particular 28 to 45 mm, more in particular 30 to 40 mm.

14. The hollow fiber membrane filter (100) according to claim 1, characterized in that the aspect ratio of the hollow fiber membrane filter (100) is 8 to 12, specifically 9 to 11, and more specifically 9 to 10.

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