Blood purifier and manufacturing method for the same

Abstract

To provide a blood purifier and a manufacturing method for the same which are capable of easily and stably stabilizing permeability performance passing desired substance.SOLUTION: In a blood purifier where a plurality of hollow fiber membranes 3 capable of passing a desired substance are housed in a case 2, the hollow fiber membranes with permeability performance different from each other are housed in the case 2 at a prescribed mixture ratio and are composed by the permeability performance of a substance to be passed that is adjusted arbitrarily at a mixture ratio. The hollow fiber membranes 3 considerably vary from each other in a fractionation curve indicating a relation between a molecular mass and the permeability of a substance to be passed, there being a combination of molecular weight areas where one is sieving coefficient of 1 and the other is sieving coefficient of 0.SELECTED DRAWING: Figure 5

Description

[Technical Field]

[0001] The present invention relates to a blood purifier in which a plurality of hollow fiber membranes permeable to a desired substance are housed in a case, and a method for manufacturing the same. [Background technology]

[0002] A blood purifier is used in, for example, a dialyzer used in hemodialysis, and is constructed by filling a cylindrical case with many hollow fiber membranes. The hollow fiber membranes are made of thread-like members with many holes called pores, which allow the patient's blood to flow through them and purify specific substances (such as specific proteins) contained in the blood by allowing them to pass to the outside.

[0003] An example of a conventional blood purifier is one in which a large number of hollow fiber membranes are packed in a case formed with a blood inlet port, a blood outlet port, a dialysate inlet port, and a dialysate outlet port, as disclosed in Patent Document 1. A blood circuit for extracorporeally circulating the patient's blood is connected to the blood inlet port and the blood outlet port, respectively, and a dialysate inlet line and a dialysate outlet line extending from the dialysis device main body can be connected to the dialysate inlet port and the dialysate outlet port, respectively. [Prior art documents] [Patent documents]

[0004] [Patent Document 1] Japanese Patent Application Laid-Open No. 2002-28233 Summary of the Invention [Problem to be solved by the invention]

[0005] However, the conventional blood purifiers described above have a problem in that the permeability of the desired substance (such as albumin contained in blood) varies from product to product, making it difficult to maintain a constant permeability. That is, it is usually difficult to maintain a constant permeability of hollow fiber membranes due to variations in the synthesis stage of the raw polymer (such as molecular weight) and fluctuations in the manufacturing conditions of the hollow fiber membrane (such as the concentration and temperature of the prepared polymer solution or the concentration and temperature of the coagulation solution).

[0006] The present invention has been made in consideration of the above circumstances, and aims to provide a blood purifier and a method for manufacturing the same that can easily and stably maintain constant permeability for permeating desired substances. [Means for solving the problem]

[0007] The invention described in claim 1 is a blood purifier in which a plurality of hollow fiber membranes permeable to desired substances are housed in a case, the hollow fiber membranes having different permeability properties are housed in the case at a predetermined mixing ratio, and the permeability of the substance to be permeated is arbitrarily adjusted by the mixing ratio, and the hollow fiber membranes have a combination of molecular weight ranges in which the fractionation curves showing the relationship between the molecular weight of the substance to be permeated and the permeability are significantly different from each other, with one having a sieving coefficient of 1 and the other having a sieving coefficient of 0.

[0008] The invention described in claim 2 is characterized in that, in the blood purifier described in claim 1, the hollow fiber membranes have permeability performances that are predetermined by the fractionation curve, and the hollow fiber membranes having the specified different permeability performances are housed in the case at a predetermined mixing ratio.

[0009] The invention described in claim 3 is characterized in that, in the blood purifier described in claim 1 or claim 2, the patient's blood can flow through the hollow fiber membrane and the dialysis fluid can flow through the case.

[0010] The invention described in claim 4 is characterized in that, in the blood purifier described in claim 3, the substance to be permeated is albumin contained in blood, and the permeability of the albumin is adjustable.

[0011] The invention described in claim 5 is characterized in that, in the blood purifier described in claim 4, the permeability of albumin can be adjusted and the permeability of blood substances with molecular weights larger than that of albumin can also be adjusted.

[0012] The invention described in claim 6 is characterized in that, in the blood purifier described in any one of claims 1 to 5, the hollow fiber membranes having different fractionation curves are evenly dispersed and housed within the case.

[0013] The invention described in claim 7 is characterized in that, in the blood purifier described in any one of claims 1 to 5, the hollow fiber membranes having different fractionation curves are contained in the case, and those having a higher containment ratio relative to the case are arranged outside the case, and those having a lower containment ratio are arranged inside the case.

[0014] The invention described in claim 8 is a method for manufacturing a blood purifier in which a plurality of hollow fiber membranes permeable to desired substances are housed in a case, wherein hollow fiber membranes having different permeability are housed in the case at a predetermined mixing ratio, and the permeability of the substance to be permeated is arbitrarily adjusted by the mixing ratio, and the hollow fiber membranes have a combination of molecular weight ranges in which the fractionation curves showing the relationship between the molecular weight of the substance to be permeated and the permeability are significantly different from each other, with one having a sieving coefficient of 1 and the other having a sieving coefficient of 0.

[0015] The invention described in claim 9 is characterized in that, in the manufacturing method of the blood purifier described in claim 8, the permeability of the hollow fiber membranes is specified in advance by the fractionation curve, and the hollow fiber membranes are selected according to the specified permeability and stored in the case at a predetermined mixing ratio.

[0016] The invention of claim 10 is characterized in that, in the method for manufacturing a blood purifier of claim 8 or claim 9, the blood purifier is configured so that the patient's blood can flow through the hollow fiber membrane and the dialysis fluid can flow through the case.

[0017] The invention described in claim 11 is characterized in that, in the method for manufacturing a blood purifier described in claim 10, the substance to be permeated is albumin contained in blood, and the permeability of the albumin is adjustable.

[0018] The invention described in claim 12 is characterized in that, in the method for manufacturing a blood purifier described in claim 11, the permeability of albumin contained in blood as the permeation target can be adjusted, and the permeability of blood substances larger than albumin can be adjusted.

[0019] The invention described in claim 13 is characterized in that, in the method for manufacturing a blood purifier described in any one of claims 8 to 12, the hollow fiber membranes having different fractionation curves are evenly dispersed and contained within the case.

[0020] The invention described in claim 14 is characterized in that, in the method for manufacturing a blood purifier described in any one of claims 8 to 12, the hollow fiber membranes having different fractionation curves are contained in the case, and those with a higher containment ratio to the case are placed outside the case, and those with a lower containment ratio are placed inside the case. [Effects of the Invention]

[0021] According to the inventions of claims 1 and 8, hollow fiber membranes having different permeability are housed in a case at a predetermined mixing ratio, and the permeability of the substance to be permeated is adjusted arbitrarily by the mixing ratio, so that the permeability for the desired substance can be easily and stably maintained constant. Furthermore, the fractionation curves are significantly different, with one having a molecular weight range where the sieving coefficient is 1 and the other has a sieving coefficient of 0, making it possible to obtain a blood purifier with a stepped fractionation curve that could not be achieved by tweaking the manufacturing conditions.

[0022] According to the inventions of claims 2 and 9, the permeability performance of the hollow fiber membranes is specified in advance by a fractionation curve showing the relationship between the molecular weight of the substance to be permeated and the permeability (e.g., sieving coefficient), and the membranes are selected according to the specified permeability performance and stored in a case at a predetermined mixing ratio.Therefore, the permeability performance can be simply and easily selected based on the fractionation curve, and the membranes can be mixed in a case at a predetermined ratio.

[0023] According to the inventions of claims 3 and 10, the blood purifier is configured so that the patient's blood can flow through the hollow fiber membrane and the dialysis fluid can flow through the case, so that the permeability of the blood purifier can be easily and stably maintained constant.

[0024] According to the inventions of claims 4 and 11, the substance to be permeated is albumin contained in blood, and the permeability of the albumin can be adjusted, so that hemodialysis treatment can be performed well.

[0025] According to the inventions of claims 5 and 12, the permeability of albumin contained in blood as a permeable substance can be adjusted, and the permeability of blood substances larger than albumin can be adjusted. This makes it possible to design a device that can remove blood substances with molecular weights larger than albumin, which was not possible with existing blood purifiers, and enables successful hemodialysis treatment. In addition to albumin, the kidneys of a living body also filter blood substances with larger molecular weights, such as beta-globulin (molecular weight 150,000 to 190,000). It was not possible to manufacture a dialyzer with existing technology that can efficiently remove blood substances with molecular weights larger than albumin while suppressing excessive albumin leakage. [Brief explanation of the drawings]

[0026] [Figure 1]1 is a schematic diagram showing a hemodialysis machine to which a blood purifier according to a first embodiment of the present invention is applied; [Figure 2] Schematic diagram showing the blood purifier (exterior on the left and interior on the right) [Figure 3] Schematic diagram showing the internal structure of the hollow fiber membrane in the blood purifier [Figure 4] Graph showing the fractionation curve of the hollow fiber membrane in the blood purifier [Figure 5] Graph showing the fractionation curve of the hollow fiber membrane in the blood purifier according to the second embodiment of the present invention. [Figure 6] Table showing typical substances found in blood DETAILED DESCRIPTION OF THE INVENTION

[0027] Hereinafter, an embodiment of the present invention will be described in detail with reference to the drawings. The blood purifier according to the embodiment has a case containing a plurality of hollow fiber membranes that are permeable to a desired substance, and is applied to a blood purifier 1 (dialyzer) used in hemodialysis treatment, as shown in Figures 1 and 2. As shown in Figure 2, the blood purifier 1 is configured with a case 2 and a number of hollow fiber membranes 3 packed in the case 2. Note that the left half of Figure 2 shows the exterior (side view), and the right half is a cross-sectional view showing the interior.

[0028] Case 2 is made of a resin member with an internal storage space, and has a blood inlet port 2a, a blood outlet port 2b, a dialysate inlet port 2c, and a dialysate outlet port 2d protruding therefrom. Cover members H are attached to both ends of case 2, making the interior of case 2 liquid-tight, and each cover member H is formed with a blood inlet port 2a and a blood outlet port 2b.

[0029] The hollow fiber membrane 3 is made of a thread- or string-like flexible member that is permeable to desired substances, and is configured with pores 3a consisting of a plurality of openings and flow paths 3b through which a liquid such as a patient's blood can flow, as shown in Figure 3. A large number of such hollow fiber membranes 3 are bundled together and housed in the case 2, and are fixed and sealed with a sealing material F, so that a liquid such as a patient's blood introduced through the blood inlet port 2a flows through the flow paths 3b and is discharged from the blood outlet port 2b.

[0030] During dialysis treatment, the blood purifier 1 according to this embodiment has a blood inlet port 2a and a blood outlet port 2b connected to an arterial blood circuit 4 and a venous blood circuit 5, respectively, and a dialysate inlet port 2c and a dialysate outlet port 2d connected to a dialysate inlet line L1 and a dialysate outlet line L2, respectively, which extend from a dialysis device main body (not shown), as shown in Fig. 1. Therefore, the dialysate can flow through the space between the outer peripheral surface of the hollow fiber membrane 3 in the case 2 and the inner peripheral surface of the case 2.

[0031] The arterial blood circuit 4 is made of a flexible tube, one end of which is connected to the blood inlet port 2a of the blood purifier 1, and allows blood collected from a patient to flow into the circulation path 3b within the hollow fiber membrane 3 of the blood purifier 1. An arterial puncture needle a can be attached to the other end of the arterial blood circuit 4 via a connector or the like, and a blood pump 6 is attached midway. The blood pump 6 is a peristaltic pump (a pump in which, when the rotor is driven, the rollers squeeze the outer surface of the flexible tube in the longitudinal direction, thereby sending blood).

[0032] The venous blood circuit 5, like the arterial blood circuit 4, is made of a flexible tube, one end of which is connected to the blood outlet port 2b of the blood purifier 1 to circulate blood that has flowed out from the circulation path 3b within the hollow fiber membrane 3. The other end of the venous blood circuit 5 is adapted to be attached with a venous puncture needle b via a connector or the like, and an air trap chamber 7 is connected midway.

[0033] During hemodialysis treatment, by driving the blood pump 6, blood collected from the arterial needle a flows sequentially through the arterial blood circuit 4, the circulation path 3b in the hollow fiber membrane 3 in the blood purifier 1, and the venous blood circuit 5, and is then returned to the patient's body via the venous needle b, thereby enabling extracorporeal circulation.

[0034] Furthermore, when the blood pump 6 is driven, dialysate is introduced into the blood purifier 1 from the dialysate inlet line L1, whereby the patient's blood flows through the flow passage 3b in the hollow fiber membrane 3, and the dialysate flows through the space between the outer peripheral surface of the hollow fiber membrane 3 and the inner peripheral surface of the case 2 within the case 2. As a result, during the process of circulating the patient's blood extracorporeally during hemodialysis treatment, specific substances contained in the blood can be permeated through the pores 3a of the hollow fiber membrane 3 to the dialysate side and discharged.

[0035] In the blood purifier 1 according to this embodiment, hollow fiber membranes 3 having different permeability are housed in a case 2 at a predetermined mixing ratio, and the permeability of the substance to be permeated is adjusted as desired by the mixing ratio. Specifically, the permeability of the hollow fiber membranes 3 is specified in advance by a fractionation curve showing the relationship between the molecular weight of the substance to be permeated and the sieving coefficient, and the hollow fiber membranes 3 are selected for each specified permeability and housed in the case 2 at a predetermined mixing ratio.

[0036] 4 and 5, a fractionation curve is a curve represented by a graph in which one axis (the horizontal axis in the figures) represents the molecular weight of the substance to be permeated (the size (kDa) of the substance to be permeated) and the other axis (the vertical axis in the figures) represents the sieving coefficient, and such a fractionation curve can be used to identify the permeation performance of the hollow fiber membrane 3. The sieving coefficient can be calculated using the following equation, where Cpre is the concentration of the substance to be permeated before filtration and Cpost is the concentration of the substance to be permeated after filtration. Sieving coefficient = Cpost / Cpre

[0037] Furthermore, blood purifiers such as the blood purifier 1 are configured to perform partial filtration (not all of the liquid is filtered, but a certain percentage of the liquid is discharged from the case without being filtered) rather than total filtration (all of the liquid is filtered), so Cpre can be calculated using the following formula: Cpre = (Inlet concentration of Case 1 + Outlet concentration of Case 1) / 2

[0038] If the molecular weight of the substance to be permeated is small, it will completely pass through the hollow fiber membrane 3, so there will be no change in concentration before and after filtration, and the sieving coefficient will be 1. If the molecular weight of the substance to be permeated is large, it will not be able to pass through the hollow fiber membrane 3, so the concentration after filtration will be zero, and the sieving coefficient will be 0. In the intermediate region (the region where the sieving coefficient is between 0 and 1), the permeability will gradually decrease as the molecular weight (size) of the substance to be permeated increases, and the fractionation curve will also become a graph that slopes downward as the molecular weight increases.

[0039] As shown in FIG. 4, the blood purifier 1 in the first embodiment contains, in a case 2, a predetermined mixture ratio of multiple types (two types in this embodiment) of hollow fiber membranes (a first type of hollow fiber membrane having the permeability of fractionation curve A and a second type of hollow fiber membrane having the permeability of fractionation curve B) with different permeability performances but with the same tendency of fractionation curves A and B, respectively. The hollow fiber membranes in the case 2 are all adjusted to have the permeability of fractionation curve C.

[0040] The term "fractionation curves with the same trend" refers to a relationship in which fractionation curve A overlaps with fractionation curve B by shifting the fractionation curve A to the right, or a relationship in which fractionation curve B overlaps with fractionation curve A by shifting the fractionation curve B to the left, as shown in the figure, and refers to a relationship in which the shapes of the curves (graph trends) in the intermediate region between 0 and 1 in sieving coefficient are the same (or similar). For example, fluctuations in permeability between production lots of hollow fiber membranes 3 often result in fractionation curves with the same trend (fractionation curves shifting left or right).

[0041] Furthermore, in the blood purifier 1 according to this embodiment, the substance to be permeated is albumin (a protein with a molecular weight of 66 kDa) contained in blood, and the permeability of the albumin is adjustable. That is, in hemodialysis treatment, it is necessary to allow albumin to permeate appropriately (permeating about several grams per treatment). However, when using hollow fiber membranes 3 whose permeability varies depending on the production lot, it is difficult to maintain a constant sieving coefficient.

[0042] In hemodialysis treatment, if a large amount of albumin passes through the hollow fiber membrane 3 and is lost, there is a risk of hypoalbuminemia, so it is necessary to prevent excessive permeation, while it is also necessary to pass through and remove proteins in the high molecular weight range that have accumulated in the body (for example, β2-microglobulin with a molecular weight of 18,000). For example, typical substances contained in blood are shown in Figure 6.

[0043] Therefore, in this embodiment, the sieving coefficient of albumin in the hollow fiber membranes 3 for each production lot is measured, and the permeability is specified in advance by understanding the respective fractionation curves.The membranes are then selected according to the specified permeability and placed in the case 1 at a predetermined mixing ratio, so that the overall permeability characteristics (fractionation curve) can be adjusted to obtain the target sieving coefficient of albumin.

[0044] For example, as shown in Fig. 4, if the target sieving coefficient for albumin is set to 0.1 (see symbol P in the figure), by placing a first type of hollow fiber membrane 3 with fractionation curve A and a second type of hollow fiber membrane 3 with fractionation curve B in case 2 at a predetermined mixing ratio (in the figure, the mixing ratio is 55% of the first type of hollow fiber membrane 3 and 45% of the second type of hollow fiber membrane 3), all of the hollow fiber membranes 3 in case 2 can be adjusted to fractionation curve C. This makes it possible to maintain the sieving coefficient for a substance with a predetermined molecular weight (albumin in this embodiment) at a constant value, thereby obtaining a blood purifier 1 (blood purifier) with stable permeability.

[0045] As shown in FIG. 5, the blood purifier 1 in the second embodiment has a case 2 containing multiple types (two types in this embodiment) of hollow fiber membranes with different permeability and different tendency fraction curves A and B (a first type of hollow fiber membrane having the permeability of fraction curve A and a second type of hollow fiber membrane having the permeability of fraction curve B) housed in a predetermined mixing ratio, and all of the hollow fiber membranes in the case 2 are adjusted to have the permeability of fraction curve C.

[0046] The tendency of the fractionation curves to differ refers to a relationship in which fractionation curve A does not overlap with fractionation curve B even when shifted to the right, or a relationship in which fractionation curve B does not overlap with fractionation curve A even when shifted to the left, as shown in the figure, and refers to a relationship in which the shape of the curve (graph tendency) is different in the intermediate region between the sieving coefficients of 0 and 1. In this case, hollow fiber membranes 3 with fractionation curve A and hollow fiber membranes 3 with fractionation curve B are produced in advance.

[0047] For example, as shown in Figure 5, if the target sieving coefficient for albumin is set to 0.1 (see symbol P in the figure), by placing a first type of hollow fiber membrane 3 with fractionation curve A and a second type of hollow fiber membrane 3 with fractionation curve B in case 2 at a predetermined mixing ratio, the entire hollow fiber membranes 3 in case 2 can be adjusted to fractionation curve C. In addition, the sieving coefficient for substances with molecular weights larger than that of albumin (molecular weights of 70 kDa to 80 kDa) can be maintained at approximately 0.1.

[0048] When adjusting the spinning conditions to shift the fractionation curve to the right to increase the permeability of substances with molecular weights larger than albumin, it is necessary to allow the sieving coefficient of albumin to increase to a certain extent. However, if the permeability of albumin increases, too much albumin is lost during dialysis therapy, which could have adverse effects on patients. For this reason, conventional methods have not been able to produce blood purifiers that can remove substances with molecular weights larger than albumin.

[0049] The method shown in Figure 5 makes it possible to manufacture a blood purifier that suppresses albumin permeability while allowing substances with molecular weights larger than albumin to pass through to a certain extent. The flat portion of the middle region of fractionation curve C can be freely designed by adjusting the fractionation curve of the hollow fiber membrane to be mixed and the mixing ratio. By accumulating clinical experience with blood purifiers manufactured using this method, it is possible to expect therapeutic effects that could not be achieved with conventional blood purifiers. In other words, by combining fractionation curves A and B that are significantly different from each other and have a molecular weight region where one has a sieving coefficient of 1 and the other has a sieving coefficient of 0, it is possible to obtain a blood purifier with a stepped fractionation curve that could not be achieved by tweaking the manufacturing conditions. The fractionation characteristic C can be theoretically calculated when the first type of hollow fiber membrane 3 of fractionation curve A and the second type of hollow fiber membrane 3 of fractionation curve B are mixed at a predetermined mixing ratio.

[0050] This allows the sieving coefficient for a substance of a predetermined molecular weight (albumin in this embodiment) to be maintained at a constant value, resulting in a blood purifier 1 (blood purifier) with stable permeability. Furthermore, by mixing hollow fiber membranes with multiple fractionation characteristics at any mixing ratio, the fractionation curve can be set as desired. For example, if a plasma separation membrane is used as a hollow fiber membrane with fractionation characteristic B, proteins with molecular weights equal to or greater than albumin in plasma components can be separated. This is because the plasma separation membrane can separate blood cell components from plasma components.

[0051] According to the first and second embodiments described above, hollow fiber membranes having different permeability are housed in a case at a predetermined mixing ratio, and the permeability of the substance to be permeated is arbitrarily adjusted by the mixing ratio, so that the permeability for the desired substance can be easily and stably maintained constant. In particular, the permeability of the hollow fiber membranes 3 is specified in advance by a fractionation curve showing the relationship between the molecular weight and the sieving coefficient of the substance to be permeated, and the hollow fiber membranes are selected for each specified permeability and housed in the case 2 at a predetermined mixing ratio. Therefore, the permeability can be simply and easily selected based on the fractionation curve, and the membranes can be mixed in the case 2 at a predetermined ratio.

[0052] Furthermore, the case 2 according to the first embodiment contains a predetermined mixture ratio of multiple types of hollow fiber membranes 3 with different permeability and fractionation curves that follow the same trend. Therefore, by setting the mixture ratio of the multiple types of hollow fiber membranes 3 with the same fractionation curves, the permeability of the target substance can be easily adjusted. Furthermore, the case 2 according to the second embodiment contains a predetermined mixture ratio of multiple types of hollow fiber membranes 3 with different permeability and fractionation curves that follow different trend. Therefore, by setting the mixture ratio of the multiple types of hollow fiber membranes 3 with the different fractionation curves, the permeability of the target substance can be easily adjusted. Furthermore, it has become possible to manufacture a blood purifier that allows a certain degree of permeation of substances with molecular weights equal to or greater than albumin while suppressing albumin permeability, something that was previously impossible to manufacture.

[0053] Furthermore, since the blood purifier 1 is configured such that the patient's blood can flow through the hollow fiber membrane 3 and the dialysate can flow through the case 2, it is possible to easily and stably maintain constant the permeability of the blood purifier 1. Furthermore, since the substance to be permeated is albumin contained in the blood and the permeability of the albumin can be adjusted, hemodialysis treatment can be performed satisfactorily.

[0054] Although the present embodiment has been described above, the present invention is not limited thereto. For example, an index other than a fractionation curve that indicates the permeability of a substance may be arbitrarily adjusted. The blood purifier 1 to be applied may be either one in which the case 1 is pre-filled with liquid (wet-type blood purifier) or one in which the case is not pre-filled with liquid (dry-type blood purifier). Furthermore, in this embodiment, hollow fiber membranes having two different permeability characteristics are housed in a predetermined mixing ratio in the case, but three or more hollow fiber membranes having different permeability characteristics may also be housed in a predetermined mixing ratio in the case. Although this embodiment is applied to the blood purifier 1, it may also be applied to blood purifiers of a different form than the blood purifier 1.

[0055] However, in a blood purifier that allows substances with molecular weights larger than albumin to pass through to a certain extent while maintaining albumin permeability at a certain level, the number of hollow fiber membranes A is greater than the number of hollow fiber membranes B in the hollow fiber membranes A and B shown in Figure 5. The characteristics of the blood purifier are determined by the number of hollow fiber membranes B, which has the fewer number of membranes. Generally, when manufacturing such a bundle of hollow fiber membranes, a bundle of hollow fiber membranes A and a bundle of hollow fiber membranes B are combined. When blood is circulated extracorporeally using a blood purifier, blood may clot in the header (at the cut surface of the urethane). In this case, blood will not flow through the hollow fiber membranes in the clotted area. If blood clots as described above occur in a hollow fiber membrane bundle that combines hollow fiber membranes A and B and the clot covers only hollow fiber membrane B, the characteristics of the blood purifier will be lost. Therefore, when combining different hollow fiber membranes, it is best to ensure that the hollow fiber membranes are evenly distributed. If hollow fiber membranes with a low ratio are placed locally, blood clotting inside the blood purifier may cause a significant change in the performance of the blood purifier. Furthermore, since blood clotting occurs more frequently on the outside of the hollow fiber membrane bundle, it is better to place hollow fiber membranes with a high ratio on the outside and hollow fiber membranes with a low ratio on the inside. [Industrial Applicability]

[0056] As long as hollow fiber membranes having different permeability are housed in the case at a predetermined mixing ratio and the permeability of the substance to be permeated is arbitrarily adjusted by the mixing ratio, the blood purifier and its manufacturing method can also be applied to blood purifiers with different external shapes or with added functions. [Explanation of symbols]

[0057] 1. Blood purifier (dialyzer) 2 cases 2a Blood introduction port 2b Blood drainage port 2c Dialysis fluid introduction port 2d Dialysis fluid outlet port 3. Hollow fiber membrane 3a Pore 3b Inner flow channel 4 Arterial blood circuit 5 Venous blood circuit 6. Blood Pump 7 Air Trap Chamber A. Fractionation curve of the first type of hollow fiber membrane B. Fractionation curve of the second type of hollow fiber membrane C Fractionation curve of the hollow fiber membrane after adjustment H Cover member F. Encapsulating material L1 Dialysis fluid introduction line L2 Dialysis fluid drain line a Arterial puncture needle b Venous puncture needle

Claims

1. A blood purifier in which a plurality of hollow fiber membranes permeable to a desired substance are housed in a case, A blood purifier in which hollow fiber membranes having different permeability performances are housed in the case at a predetermined mixing ratio, and the permeability performance of the substance to be permeated is arbitrarily adjusted by the mixing ratio, and the hollow fiber membranes have a combination of molecular weight ranges in which the fractionation curves showing the relationship between the molecular weight of the substance to be permeated and the permeability are significantly different from each other, with one having a sieving coefficient of 1 and the other having a sieving coefficient of 0.

2. The blood purifier according to claim 1, characterized in that the hollow fiber membranes have permeability performances that are predetermined based on the fractionation curve, and the hollow fiber membranes having the specified different permeability performances are housed in the case at a predetermined mixing ratio.

3. 3. The blood purifier according to claim 1, wherein the blood of a patient can flow through the hollow fiber membrane and the dialysis fluid can flow through the case.

4. 4. The blood purifier according to claim 3, wherein the substance to be permeated is albumin contained in blood, and the permeability of said albumin is adjustable.

5. 5. The blood purifier according to claim 4, wherein the permeability of albumin can be adjusted and the permeability of blood substances having molecular weights larger than that of albumin can also be adjusted.

6. 6. The blood purifier according to claim 1, wherein the hollow fiber membranes having different fractionation curves are housed in the case in a uniformly dispersed manner.

7. The blood purifier according to any one of claims 1 to 5, characterized in that the hollow fiber membranes having different fractionation curves are accommodated in the case, and those having a higher accommodation ratio to the case are arranged outside the case, and those having a lower accommodation ratio are arranged inside the case.

8. A method for manufacturing a blood purifier in which a plurality of hollow fiber membranes permeable to a desired substance are housed in a case, comprising: A method for manufacturing a blood purifier, characterized in that hollow fiber membranes having different permeability performances are placed in the case at a predetermined mixing ratio, the permeability performance of the substance to be permeated is adjusted as desired by changing the mixing ratio, and the hollow fiber membranes have molecular weight ranges in which the fractionation curves showing the relationship between the molecular weight of the substance to be permeated and the permeability are significantly different from each other, with one having a sieving coefficient of 1 and the other having a sieving coefficient of 0.

9. The method for manufacturing a blood purifier according to claim 8, wherein the permeability of the hollow fiber membranes is specified in advance by the fractionation curve, and the hollow fiber membranes are selected according to the specified permeability and placed in the case at a predetermined mixing ratio.

10. 10. The method for manufacturing a blood purifier according to claim 8 or claim 9, wherein the blood purifier is configured so that the patient's blood can flow through the hollow fiber membrane and the dialysis fluid can flow through the case.

11. 11. The method for manufacturing a blood purifier according to claim 10, wherein the substance to be permeated is albumin contained in blood, and the permeability of said albumin is adjustable.

12. The method for manufacturing a blood purifier according to claim 11, characterized in that the permeability of albumin contained in blood as the permeation target can be adjusted, and the permeability of blood substances larger than albumin can be adjusted.

13. The method for manufacturing a blood purifier according to any one of claims 8 to 12, wherein the hollow fiber membranes having different fractionation curves are contained in the case in an evenly dispersed manner.

14. The method for manufacturing a blood purifier according to any one of claims 8 to 12, characterized in that the hollow fiber membranes having different fractionation curves are accommodated in the case, and the hollow fiber membranes having a higher accommodation ratio to the case are arranged outside the case, and the hollow fiber membranes having a lower accommodation ratio are arranged inside the case.

Images