Blood purifier and method for manufacturing the same

Abstract

To provide a blood purifier that enables transmissivity for transmitting a desired material to be constant easily and stably, and a manufacturing method thereof.SOLUTION: In a blood purifier in which a plurality of hollow fiber membranes 3 capable of transmitting a desired material are stored in a case 2 (a blood purifier 1 connected to an artery side blood circuit 4 and a vein side blood circuit 5), the hollow fiber membranes 3 having mutually different transmissivities are stored in the case 2 at a predetermined mixing ratio, and the transmissivity for a material to be transmitted is arbitrarily adjusted by the mixing ratio.SELECTED DRAWING: Figure 2

Description

Technical Field

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

Background Art

[0002] A blood purifier is applied to, for example, a dialyzer used for hemodialysis, and is configured by filling a cylindrical case with a large number of hollow fiber membranes. The hollow fiber membrane is composed of a filamentous member in which a large number of holes called pores are formed, and it is possible to circulate the patient's blood inside and to purify by permeating a specific substance (such as a specific protein) contained in the blood to the outside.

[0003] As a conventional blood purifier, for example, as disclosed in Patent Document 1, there is one in which a large number of hollow fiber membranes are filled in a case in which a blood introduction port, a blood discharge port, a dialysate introduction port, and a dialysate discharge port are formed. And a blood circuit for extracorporeal circulation of the patient's blood is connected to the blood introduction port and the blood discharge port, respectively, and a dialysate introduction line and a dialysate discharge line extending from the main body of the dialysis device can be connected to the dialysate introduction port and the dialysate discharge port, respectively.

Prior Art Documents

Patent Documents

[0004]

Patent Document 1

Summary of the Invention

Problems to be Solved by the Invention

[0005] However, in the above-described conventional blood purifier, there has been a problem that the permeation performance for a desired substance (such as albumin contained in blood) varies from product to product, and it is difficult to maintain the permeation performance constant. That is, for a hollow fiber membrane, it is generally difficult to make its permeation performance constant due to variations in the synthesis stage of the polymer as the raw material (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 liquid).

[0006] The present invention has been made in view of such circumstances, and an object thereof is to provide a blood purifier and a method for manufacturing the same that can easily and stably make the permeation performance for a desired substance constant.

Means for Solving the Problems

[0007] The invention according to claim 1 is a blood purifier in which a plurality of hollow fiber membranes capable of permeating a desired substance are housed in a case, and hollow fiber membranes having different permeation performances are housed in the case at a predetermined mixing ratio, and the permeation performance of the substance to be permeated is arbitrarily adjusted by the mixing ratio is such that the hollow fiber membrane is composed of those whose permeation performance has been previously specified by a fractionation curve showing the relationship between the molecular weight and the permeability of the substance to be permeated, and the hollow fiber membranes with the specified and different permeation performances are accommodated in the case at a predetermined mixing ratio, and the case is such that the fractionation curves with different permeation performances are in a relationship where one fractionation curve overlaps the other by shifting it left and right, and a plurality of types of hollow fiber membranes having fractionation curves with a tendency that the shape of the curve in the intermediate region where the sieve coefficient is between 0 and 1 is the same or similar are accommodated at a predetermined mixing ratio characterized in that.

[0008] The invention according to claim 2 is In a blood purifier in which a plurality of hollow fiber membranes capable of permeating a desired substance are accommodated in a case, hollow fiber membranes having different permeation performances are accommodated in the case at a predetermined mixing ratio, and the permeation performance of the substance to be permeated is arbitrarily adjusted by the mixing ratio. The hollow fiber membrane is composed of those whose permeation performance has been previously specified by a fractionation curve showing the relationship between the molecular weight and the permeability of the substance to be permeated, and the hollow fiber membranes with the specified and different permeation performances are accommodated in the case at a predetermined mixing ratio. The case is such that the fractionation curves with different permeation performances are in a relationship where even if one fractionation curve is shifted left and right, it does not overlap the other, and a plurality of types of hollow fiber membranes having fractionation curves with a tendency that the shape of the curve in the intermediate region where the sieve coefficient is between 0 and 1 is different are accommodated at a predetermined mixing ratio, which is characterized in that .

[0011] The invention according to claim 3 is a blood purifier according to claim 1 or Claim 2 characterized in that the blood of the patient can flow through the inside of the hollow fiber membrane, and the blood purifier is configured such that dialysis fluid can flow through the inside of the case.

[0012] The invention according to claim 4 is a blood purifier according to claim 3 characterized in that the substance to be permeated consists of albumin contained in blood, and the permeation performance of the albumin can be adjusted.

[0013] The invention according to claim 5 is a blood purifier according to claim 4In the described blood purifier, it is characterized in that the permeation performance of albumin is adjusted, and the permeation performance of blood substances having a molecular weight larger than albumin can also be adjusted.

[0014] Claim 6 The invention described in claim 1 or Claim 2 In the described blood purifier, it is a combination in which the fractionation curves of each other are greatly different, and there is a molecular weight region where one has a sieve coefficient of 1 and the other has a sieve coefficient of 0.

[0015] Claim 7 In the method for manufacturing a blood purifier in which a plurality of hollow fiber membranes capable of permeating a desired substance are housed in a case, hollow fiber membranes having different permeation performances are housed in the case at a predetermined mixing ratio, and the permeation performance of the substance to be permeated is arbitrarily adjusted by the mixing ratio is such that the permeation performance of the hollow fiber membrane is previously specified by a fractionation curve showing the relationship between the molecular weight and the permeability of the substance to be permeated, and is sorted for each of the specified permeation performances and accommodated in the case at a predetermined mixing ratio Characterized by the above.

[0017] Claim 8 The invention described in claim 7 In the method for manufacturing a blood purifier described in claim, a plurality of types of hollow fiber membranes having different permeation performances, wherein one fractionation curve is shifted left and right to overlap with the other fractionation curve, and the shape of the curve in the intermediate region where the sieve coefficient is between 0 and 1 is the same or similar, are housed in the case at a predetermined mixing ratio.

[0018] Claim 9 The invention described in claim 7 In the method for manufacturing a blood purifier described in claim, a plurality of types of hollow fiber membranes having different permeation performances, wherein one fractionation curve does not overlap with the other fractionation curve even when shifted left and right, and the shape of the curve in the intermediate region where the sieve coefficient is between 0 and 1 is different, are housed in the case at a predetermined mixing ratio.

[0019] Claim 10 The invention described in claim 7~9In the method for manufacturing a blood purifier according to any one of the above, the method is characterized in that it comprises a blood purifier in which the patient's blood can flow through the hollow fiber membrane and dialysis fluid can flow through the case.

[0020] Claim 11 The invention described in claim 10 In the method for manufacturing a blood purifier according to the invention described in claim

[0021] Claim 12 The invention described in claim 11 In the method for manufacturing a blood purifier according to the invention described in claim

[0022] Claim 13 The invention described in claim 8 or Claim 9 In the method for manufacturing a blood purifier according to the invention described in claim

Advantages of the Invention

[0023] According to the invention of claim 1, 7 hollow fiber membranes having different permeation performances are housed in a case at a predetermined mixing ratio, and the permeation performance of the substance to be permeated can be arbitrarily adjusted by the mixing ratio. Therefore, the permeation performance for permeating a desired substance can be easily and stably maintained constantly.

[0024] Claim 1、7 According to the invention of claim

[0025] According to the invention of claim 1、8 , since the case contains a plurality of types of hollow fiber membranes having different permeation performances and fractionation curves with the same tendency at a predetermined mixing ratio, by setting the mixing ratio of the plurality of types of hollow fiber membranes having fractionation curves with the same tendency, the permeation performance of the substance to be permeated can be easily adjusted.

[0026] According to the invention of claim 2、9 , since the case contains a plurality of types of hollow fiber membranes having different permeation performances and fractionation curves with different tendencies at a predetermined mixing ratio, by setting the mixing ratio of the plurality of types of hollow fiber membranes having fractionation curves with different tendencies, the permeation performance of the substance to be permeated can be easily adjusted.

[0027] According to the invention of claim 3、10 , since the blood of the patient can flow through the inside of the hollow fiber membrane and the dialysate can flow through the inside of the case, the permeation performance of the blood purifier can be easily and stably kept constant.

[0028] According to the invention of claim 4、11 , since the substance to be permeated consists of albumin contained in the blood and the permeation performance of the albumin can be adjusted, hemodialysis treatment can be performed well.

[0029] According to the invention of claim 5、12 , since the permeation performance of albumin contained in the blood as the substance to be permeated can be adjusted and the permeation performance of blood substances having a molecular weight greater than albumin can be adjusted, the removal performance of blood substances having a molecular weight greater than albumin, which could not be achieved by existing blood purifiers, can be designed, and hemodialysis treatment can be performed well. The kidneys of a living body filter blood substances in a larger molecular weight range such as β-globulin (molecular weight 150,000 to 190,000) in addition to albumin. A dialyzer that can efficiently remove blood substances having a molecular weight larger than albumin while suppressing excessive leakage of albumin could not be manufactured by existing technologies.

[0030] Claims 6、13 According to the invention of 6、13 , since it is a combination in which the fractionation curves of each other are greatly different and there is a molecular weight region where one has a sieve coefficient of 1 and the other has a sieve coefficient of 0, a blood purifier having a stepped fractionation curve that could not be achieved by devising manufacturing conditions can be obtained.

Brief Description of the Drawings

[0031]

Figure 1

Figure 2

Figure 3

Figure 4

Figure 5

Figure 6

Mode for Carrying Out the Invention

[0032] Hereinafter, embodiments of the present invention will be specifically described with reference to the drawings. The blood purifier according to the embodiment is one in which a plurality of hollow fiber membranes capable of permeating a desired substance are housed in a case, and as shown in FIGS. 1 and 2, it is applied to the blood purifier 1 (dialyzer) used in hemodialysis treatment. Such a blood purifier 1 is configured to have a case 2 and a large number of hollow fiber membranes 3 filled in the case 2, as shown in FIG. 2. Note that FIG. 2 is a cross-sectional view in which the left half shows the appearance (side view) and the right half shows the inside.

[0033] Case 2 is made of a resin member having an accommodation space formed therein, and a blood introduction port 2a, a blood discharge port 2b, a dialysate introduction port 2c, and a dialysate discharge port 2d are respectively formed to protrude. Lid members H are respectively attached to both ends of such a case 2, and the inside of the case 2 can be made liquid-tight. Each lid member H is formed with a blood introduction port 2a and a blood discharge port 2b, respectively.

[0034] The hollow fiber membrane 3 is made of a filamentous or string-like flexible member capable of permeating a desired substance, and as shown in FIG. 3, has a pore 3a composed of a plurality of openings and a flow path 3b through which a liquid such as a patient's blood can flow. Such a hollow fiber membrane 3 is bundled in a large number and accommodated in the case 2, and is fixed and sealed with a sealing material F, so that a liquid such as the patient's blood introduced from the blood introduction port 2a flows through the flow path 3b and is discharged from the blood discharge port 2b.

[0035] During dialysis treatment, as shown in FIG. 1, the blood purification device 1 according to the present embodiment has a blood introduction port 2a and a blood discharge port 2b respectively connected to the arterial side blood circuit 4 and the venous side blood circuit 5, and a dialysate introduction port 2c and a dialysate discharge port 2d are respectively connected to a dialysate introduction line L1 and a dialysate discharge line L2 extending from a dialysis device main body (not shown). Therefore, dialysate can flow through the space between the outer peripheral surface of the hollow fiber membrane 3 and the inner peripheral surface of the case 2 in the case 2.

[0036] The arterial side blood circuit 4 is made of a flexible tube, one end of which is connected to the blood introduction port 2a of the blood purification device 1 to allow the blood collected from the patient to flow into the flow path 3b in the hollow fiber membrane 3 of the blood purification device 1. An arterial side puncture needle a can be attached to the other end of such an arterial side blood circuit 4 via a connector or the like, and a blood pump 6 is attached in the middle. Such a blood pump 6 is a squeezing type pump (a pump configured to squeeze the outer peripheral surface of the flexible tube in the longitudinal direction by driving a rotor to send blood).

[0037] The venous blood circuit 5 is made of a flexible tube like the arterial blood circuit 4. One end thereof is connected to the blood outlet port 2b of the blood purifier 1 to circulate the blood flowing out from the flow path 3b in the hollow fiber membrane 3. A venous puncture needle b can be attached to the other end of such a venous blood circuit 5 via a connector or the like, and an air trap chamber 7 is connected in the middle.

[0038] During hemodialysis treatment, by driving the blood pump 6, the blood collected from the arterial puncture needle a is sequentially flowed through the arterial blood circuit 4, the flow path 3b in the hollow fiber membrane 3 in the blood purifier 1, and the venous blood circuit 5, and can be returned to the patient's body through the venous puncture needle b to perform extracorporeal circulation.

[0039] Also, in a state where the blood pump 6 is driven, by introducing dialysis fluid into the blood purifier 1 from the dialysis fluid introduction line L1, the flow path 3b in the hollow fiber membrane 3 allows the patient's blood to flow, and the dialysis fluid flows through the space between the outer peripheral surface of the hollow fiber membrane 3 and the inner peripheral surface of the case 2 in the case 2. Thereby, during hemodialysis treatment, in the process of extracorporeal circulation of the patient's blood, specific substances contained in the blood can be permeated to the dialysis fluid side through the pores 3a of the hollow fiber membrane 3 and discharged.

[0040] Here, in the blood purifier 1 according to the present embodiment, hollow fiber membranes 3 having different permeation performances are accommodated in the case 2 at a predetermined mixing ratio, and the permeation performance of the substance to be permeated is arbitrarily adjusted by the mixing ratio. Specifically, the permeation performance of the hollow fiber membrane 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 is selected for each of the specified permeation performances and accommodated in the case 2 at a predetermined mixing ratio.

[0041] The fractionation curve is composed of a curve represented by a graph with one axis (the horizontal axis in FIGS. 4 and 5) being 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 same figure) being the sieving coefficient. The permeation performance of the hollow fiber membrane 3 can be specified by such a fractionation curve. The sieving coefficient can be obtained by the following arithmetic formula when the concentration of the substance to be permeated before filtration is Cpre and the concentration of the substance to be permeated after filtration is Cpost. Sieving coefficient = Cpost / Cpre

[0042] In addition, in a blood purifier such as the blood purifier 1, it is not configured to perform total filtration (filter all liquids), but is configured to perform partial filtration (not filter all liquids, and a certain proportion of the liquid is discharged from the case without being filtered). Therefore, Cpre can be obtained by the following arithmetic formula. Cpre = (the inlet concentration of case 1 + the outlet concentration of case 1) / 2

[0043] When the molecular weight of the substance to be permeated is small, since it permeates through the entire hollow fiber membrane 3, there is no change in concentration before and after filtration, and the sieving coefficient becomes 1. When the molecular weight of the substance to be permeated is large, since it cannot permeate through the hollow fiber membrane 3, the concentration after filtration becomes zero, and the sieving coefficient becomes 0. Also, in the intermediate region (the region where the sieving coefficient is between 0 and 1), as the molecular weight (size) of the substance to be permeated increases, the permeation performance gradually decreases. Therefore, the fractionation curve also becomes a graph that decreases as the molecular weight increases.

[0044] As shown in FIG. 4, the blood purifier 1 in the first embodiment contains a plurality of types (two types in this embodiment) of hollow fiber membranes having different permeation performances and fractionation curves A and B with the same tendency (the first type of hollow fiber membrane having the permeation performance of fractionation curve A and the second type of hollow fiber membrane having the permeation performance of fractionation curve B) in the case 2 at a predetermined mixing ratio, and the entire hollow fiber membrane in the case 2 is adjusted to have the permeation performance of fractionation curve C.

[0045] The term "the fractionation curves having the same tendency" refers to a relationship where, as shown in the figure, the fractionation curve A overlaps with the fractionation curve B by shifting the fractionation curve A to the right, or the fractionation curve B overlaps with the fractionation curve A by shifting the fractionation curve B to the left, and the shapes (graph tendencies) of the curves in the intermediate region where the sieve coefficient is between 0 and 1 are the same (or similar). For example, the variation in the permeation performance for each production lot of the hollow fiber membrane 3 often results in the fractionation curves having the same tendency (the fractionation curves shifting left and right).

[0046] Furthermore, in the blood purifier 1 according to the present embodiment, the substance to be permeated consists of albumin (a protein with a molecular weight of 66 kDa) contained in the blood, and the permeation performance of the albumin can be adjusted. That is, in hemodialysis treatment, it is necessary to allow albumin to permeate moderately (about several grams per treatment), but when using a hollow fiber membrane 3 whose permeation performance varies for each production lot, it becomes difficult to keep the sieve coefficient constant.

[0047] In hemodialysis treatment, if a large amount of albumin permeates through the hollow fiber membrane 3 and is lost, there is a risk of developing hypoalbuminemia. Therefore, while it is necessary to suppress excessive permeation, it is also necessary to permeate and remove proteins accumulated in the body in the high molecular weight region (for example, β2-microglobulin with a molecular weight of 18,000). For example, there are representative substances contained in the blood as shown in FIG. 6.

[0048] Therefore, in the present embodiment, the sieve coefficient of albumin in the hollow fiber membrane 3 for each production lot is measured, and by grasping each fractionation curve, the permeation performance is specified in advance. Then, by sorting according to the specified permeation performance and storing them in case 1 at a predetermined mixing ratio, the overall permeation characteristics (fractionation curves) are configured to be adjusted so as to obtain the target sieve coefficient of albumin.

[0049] For example, as shown in FIG. 4, when the target sieving coefficient of albumin is set to 0.1 (see reference symbol P in the figure), 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 placed in case 2 at a predetermined mixing ratio (in this figure, the mixing ratio is 55% for the first type of hollow fiber membrane 3 and 45% for the second type of hollow fiber membrane 3). By doing so, the overall hollow fiber membrane 3 in case 2 can be adjusted to fractionation curve C. As a result, the sieving coefficient for a substance with a predetermined molecular weight (albumin in this embodiment) can be controlled at a constant value, and a blood purifier 1 (blood purifier) with stable permeation performance can be obtained.

[0050] As shown in FIG. 5, the blood purifier 1 in the second embodiment includes a plurality of types (two types in this embodiment) of hollow fiber membranes (the first type of hollow fiber membrane having the permeation performance of fractionation curve A and the second type of hollow fiber membrane having the permeation performance of fractionation curve B) with different permeation performances and different tendencies of fractionation curves A and B, which are accommodated in case 2 at a predetermined mixing ratio, and the overall hollow fiber membrane in case 2 is adjusted to have the permeation performance of fractionation curve C.

[0051] The different tendencies of the fractionation curves refer to, as shown in the figure, a relationship where even if fractionation curve A is shifted to the right, it does not overlap with fractionation curve B, or even if fractionation curve B is shifted to the left, it does not overlap with fractionation curve A, and it means that the shape (graph tendency) of the curve in the intermediate region where the sieving coefficient is between 0 and 1 is different. In this case, the hollow fiber membrane 3 of fractionation curve A and the hollow fiber membrane 3 of fractionation curve B need to be manufactured in advance.

[0052] For example, as shown in FIG. 5, when the target sieving coefficient of albumin is set to 0.1 (see reference symbol P in the figure), by accommodating 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 in case 2 at a predetermined mixing ratio, the overall hollow fiber membrane 3 in case 2 can be adjusted to fractionation curve C. Also, the sieving coefficient of a substance with a molecular weight larger than albumin (molecular weight 70 kDa to 80 kDa) can be maintained at approximately 0.1.

[0053] When using a method of shifting the fractionation curve to the right by adjusting the spinning conditions to enhance the permeability of substances with a molecular weight larger than albumin, it is necessary to tolerate a certain increase in the sieving coefficient of albumin. However, if the permeability of albumin increases, the loss of albumin in dialysis therapy becomes excessive, which may have an adverse effect on patients. Therefore, with the conventional method, it was not possible to manufacture a blood purifier that can remove substances with a molecular weight greater than albumin.

[0054] With the method shown in FIG. 5, it is possible to manufacture a blood purifier that allows a certain degree of permeation of substances with a molecular weight greater than albumin while suppressing the permeability of albumin. The flat portion in the middle region of the fractionation curve C can be freely designed by adjusting the fractionation curves of the hollow fiber membranes to be mixed and the mixing ratio. By accumulating clinical experience with the blood purifier manufactured by this method, it is possible to expect a therapeutic effect that could not be achieved with conventional blood purifiers. That is, according to a combination in which the fractionation curves A and B of each other are significantly different and there is 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 having a stepped fractionation curve that could not be achieved by devising the manufacturing conditions. Note that the fractionation characteristics C when the first type of hollow fiber membrane 3 with fractionation curve A and the second type of hollow fiber membrane 3 with fractionation curve B are mixed at a predetermined mixing ratio can be calculated theoretically.

[0055] Thereby, the sieving coefficient for a substance with a predetermined molecular weight (albumin in this embodiment) can be controlled at a constant value, and a blood purifier 1 (blood purifier) with stable permeation performance can be obtained. By mixing hollow fiber membranes having a plurality of fractionation characteristics at an arbitrary mixing ratio, the fractionation curve can be set arbitrarily. For example, when using a plasma separation membrane as the hollow fiber membrane with fractionation characteristics B, proteins having a molecular weight greater than albumin in the plasma component can be separated. This is because the plasma separation membrane can separate the blood cell component and the plasma component.

[0056] According to the above-described first and second embodiments, hollow fiber membranes having different permeation performances are accommodated in a case at a predetermined mixing ratio, and the permeation performance of the substance to be permeated can be arbitrarily adjusted by the mixing ratio. Therefore, the permeation performance for permeating a desired substance can be easily, stably, and constantly maintained. In particular, the permeation performance of the hollow fiber membrane 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 membrane 3 is selected for each of the specified permeation performances and accommodated in the case 2 at a predetermined mixing ratio. Therefore, the permeation performance can be simply and easily selected based on the fractionation curve, and can be mixed in the case 2 at a predetermined ratio.

[0057] In addition, in the case 2 according to the first embodiment, a plurality of types of hollow fiber membranes 3 having different permeation performances and fractionation curves with the same tendency are accommodated at a predetermined mixing ratio. Therefore, by setting the mixing ratio of the plurality of types of hollow fiber membranes 3 having fractionation curves with the same tendency, the permeation performance of the substance to be permeated can be easily adjusted. Further, in the case 2 according to the second embodiment, a plurality of types of hollow fiber membranes 3 having different permeation performances and fractionation curves with different tendencies are accommodated at a predetermined mixing ratio. Therefore, by setting the mixing ratio of the plurality of types of hollow fiber membranes 3 having fractionation curves with different tendencies, the permeation performance of the substance to be permeated can be easily adjusted. Also, it has become possible to manufacture a blood purifier that can permeate substances having a molecular weight greater than albumin to some extent while suppressing the permeability of albumin, which could not be manufactured conventionally.

[0058] 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, the permeation performance of the blood purifier 1 can be easily, stably, and constantly maintained. Also, since the substance to be permeated is albumin contained in the blood and the permeation performance of the albumin can be adjusted, hemodialysis treatment can be performed well.

[0059] Although the present embodiment has been described above, the present invention is not limited thereto. For example, an index different from the fractionation curve and indicating the permeation performance of a substance may be arbitrarily adjusted. The blood purifier 1 to which the present invention is applied may be either a case in which a liquid is pre-filled in the case 1 (wet type blood purifier) or a case in which no liquid is filled (dry type blood purifier). Further, in the present embodiment, the hollow fiber membranes having two different permeation characteristics are accommodated in the case at a predetermined mixing ratio, but three or more hollow fiber membranes having mutually different permeation characteristics may be accommodated in the case at a predetermined mixing ratio. In addition, in the present embodiment, although it is applied to the blood purifier 1, it may be applied to a blood purifier having a form different from that of the blood purifier 1.

[0060] However, in a blood purifier that allows a substance having a molecular weight greater than albumin to permeate to some extent while suppressing the permeability of albumin to a certain value, for the hollow fiber membrane A and the hollow fiber membrane B in FIG. 5, the number of the hollow fiber membranes A is larger than the number of the hollow fiber membranes B and they will be mixed more. The characteristics of the blood purifier are dominated by the hollow fiber membrane B with a smaller number. Generally, when manufacturing such a bundle of hollow fiber membranes, the bundle of hollow fiber membranes A and the bundle of hollow fiber membranes B are often combined. When extracorporeal circulation is performed in the blood purifier, blood may coagulate in the header (urethane cut surface) of the blood purifier. In that case, blood will no longer flow through the hollow fiber membranes in the coagulated part. If blood coagulation as described above occurs in a hollow fiber membrane bundle in which the hollow fiber membranes A and B are combined, and this coagulum covers only the hollow fiber membrane B, the characteristics of this blood purifier will be lost. Therefore, when combining different hollow fiber membranes, it is better to evenly disperse the respective hollow fiber membranes. If the hollow fiber membrane with a small ratio is locally arranged, the performance of the blood purifier may change greatly due to blood coagulation in the blood purifier. In addition, since blood coagulation occurs more often on the outer side of the hollow fiber membrane bundle, the hollow fiber membrane with a large ratio should be arranged on the outer side and the hollow fiber membrane with a small ratio should be arranged on the inner side.

Industrial Applicability

[0061] If a hollow fiber membrane having different permeation performances is housed in the case at a predetermined mixing ratio, and the permeation performance of the substance to be permeated can be arbitrarily adjusted according to the mixing ratio, it can be applied to those having different external shapes or those with other functions added, etc.

Explanation of Signs

[0062] 1 Hemodialyzer 2 Case 2a Blood inlet port 2b Blood outlet port 2c Dialysate inlet port 2d Dialysate outlet port 3 Hollow fiber membrane 3a Pore 3b Inner flow path 4 Arterial side blood circuit 5 Venous side 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 adjusted hollow fiber membrane H Lid member F Sealing material L1 Dialysate inlet line L2 Dialysate discharge line a Arterial side puncture needle b Venous side puncture needle

Claims

1. In a blood purifier in which a plurality of hollow fiber membranes capable of permeating a desired substance are housed in a case, hollow fiber membranes having different permeation performances are housed in the case at a predetermined mixing ratio, and the permeation performance of the substance to be permeated is arbitrarily adjusted by the mixing ratio, the hollow fiber membranes are composed of those whose permeation performance has been previously specified by a fractionation curve showing the relationship between the molecular weight and the permeability of the substance to be permeated, and the hollow fiber membranes having the specified different permeation performances are housed in the case at a predetermined mixing ratio, and the case is such that hollow fiber membranes having different permeation performances and having a relationship in which one fractionation curve overlaps with the other fractionation curve by shifting the one fractionation curve to the left and right, and having a tendency that the shape of the curve in the intermediate region where the sieve coefficient is between 0 and 1 is the same or similar, are housed at a predetermined mixing ratio. A blood purifier characterized by this.

2. In a blood purifier in which a plurality of hollow fiber membranes capable of permeating a desired substance are housed in a case, hollow fiber membranes having different permeation performances are housed in the case at a predetermined mixing ratio, and the permeation performance of the substance to be permeated is arbitrarily adjusted by the mixing ratio, the hollow fiber membranes are composed of those whose permeation performance has been previously specified by a fractionation curve showing the relationship between the molecular weight and the permeability of the substance to be permeated, and the hollow fiber membranes having the specified different permeation performances are housed in the case at a predetermined mixing ratio, and the case is such that hollow fiber membranes having different permeation performances and having a relationship in which one fractionation curve does not overlap with the other fractionation curve even when shifted to the left and right, and having a tendency that the shape of the curve in the intermediate region where the sieve coefficient is between 0 and 1 is different, are housed at a predetermined mixing ratio. A blood purifier characterized by this.

3. The blood purifier according to claim 1 or claim 2, characterized in that the blood of the patient can flow through the hollow fiber membranes, and the dialysate can flow through the case.

4. The blood purifier according to claim 3, characterized in that the substance to be permeated is albumin contained in the blood, and the permeation performance of the albumin can be adjusted.

5. The blood purifier according to claim 4, characterized in that the permeation performance of albumin can be adjusted, and the permeation performance of blood substances having a molecular weight larger than albumin can also be adjusted.

6. The blood purifier according to claim 1 or 2, which is a combination in which the fractionation curves of each other are significantly different, and there is a molecular weight region where one has a sieve coefficient of 1 and the other has a sieve coefficient of 0.

7. In a method for manufacturing a blood purifier in which a plurality of hollow fiber membranes capable of permeating a desired substance are housed in a case, hollow fiber membranes having different permeation performances are housed in the case at a predetermined mixing ratio, and the permeation performance of the substance to be permeated is arbitrarily adjusted by the mixing ratio. The permeation performance of the hollow fiber membrane is previously specified by a fractionation curve showing the relationship between the molecular weight of the substance to be permeated and the permeability, and the hollow fiber membranes are sorted for each of the specified permeation performances and housed in the case at a predetermined mixing ratio. A method for manufacturing a blood purifier, characterized by the above.

8. A plurality of types of hollow fiber membranes having different permeation performances, wherein one fractionation curve is shifted left and right to overlap with the other fractionation curve, and the shape of the curve in the intermediate region where the sieve coefficient is between 0 and 1 is the same or similar. The method for manufacturing a blood purifier according to claim 7, characterized in that the hollow fiber membranes are housed in the case at a predetermined mixing ratio.

9. A plurality of types of hollow fiber membranes having different permeation performances, wherein one fractionation curve does not overlap with the other fractionation curve even when shifted left and right, and the shape of the curve in the intermediate region where the sieve coefficient is between 0 and 1 is different. The method for manufacturing a blood purifier according to claim 7, characterized in that the hollow fiber membranes are housed in the case at a predetermined mixing ratio.

10. The method for manufacturing a blood purifier according to any one of claims 7 to 9, characterized in that the blood of the patient can flow through the hollow fiber membrane, and the dialysate can flow through the case.

11. The method for manufacturing a blood purifier according to claim 10, characterized in that the substance to be permeated is albumin contained in the blood, and the permeation performance of the albumin can be adjusted.

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

13. The method for manufacturing a blood purifier according to claim 8 or 9, which is a combination in which the fractionation curves of each other are significantly different, and there is a molecular weight region where one has a sieve coefficient of 1 and the other has a sieve coefficient of 0.

Images