JP7698534B2 - Blood purifier and its manufacturing method - Google Patents

Description

The present invention relates to a blood purifier in which multiple hollow fiber membranes that are permeable to desired substances are housed in a case, and a method for manufacturing the same.

A blood purifier is applied to, for example, a dialyzer used in hemodialysis, and is constructed by filling a cylindrical case with many hollow fiber membranes. The hollow fiber membrane is made of a thread-like material with many holes called pores, and allows the patient's blood to flow through it, while also allowing specific substances (such as specific proteins) contained in the blood to pass to the outside, purifying it.

As disclosed in Patent Document 1, for example, a conventional blood purifier has a case in which a blood inlet port, a blood outlet port, a dialysate inlet port, and a dialysate outlet port are formed, and a large number of hollow fiber membranes are packed inside the case. A blood circuit for circulating the patient's blood extracorporeally 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 body can be connected to the dialysate inlet port and the dialysate outlet port, respectively.

JP 2002-28233 A

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. In other words, it is usually difficult to maintain a constant permeability of hollow fiber membranes due to variations in the synthesis stage of the raw polymer (molecular weight, etc.) and fluctuations in the manufacturing conditions of the hollow fiber membrane (concentration and temperature of the prepared polymer solution, or concentration and temperature of the coagulation liquid, etc.).

The present invention was made in consideration of these circumstances, and aims to provide a blood purifier and a manufacturing method thereof that can easily and stably maintain constant permeability for the permeation of desired substances.

The invention described in 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, the 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 hollow fiber membranes are those whose permeability is specified in advance by a fractionation curve showing the relationship between the molecular weight and permeability of the substance to be permeated, the hollow fiber membranes having the specified different permeability are housed in the case at a predetermined mixing ratio, and the case is characterized in that a plurality of types of hollow fiber membranes having different permeability and whose fractionation curves are in a relationship in which one fractionation curve overlaps with the other fractionation curve by shifting it left or right, and whose sieving coefficients in the intermediate region between 0 and 1 tend to have the same or similar curve shapes, are housed in the case at a predetermined mixing ratio .

The invention described in claim 2 is a blood purifier in which a case contains a plurality of hollow fiber membranes capable of permeating desired substances, the hollow fiber membranes having different permeability are contained 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 hollow fiber membranes are composed of membranes whose permeability is specified in advance by a fractionation curve showing the relationship between the molecular weight and permeability of the substance to be permeated, the hollow fiber membranes having the specified different permeability are contained in the case at a predetermined mixing ratio, and the case contains a plurality of types of hollow fiber membranes having different permeability and whose fractionation curves tend to have different shapes in the intermediate region between 0 and 1 in the sieving coefficient, in a predetermined mixing ratio .

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

The invention as set forth in claim 4 is the blood purifier as set forth in claim 3 , characterized in that the substance to be permeated is albumin contained in blood, and the permeability of the albumin is adjustable.

The invention described in claim 5 is the blood purifier described in claim 4 , characterized in that it is possible to adjust the permeability of albumin and also to adjust the permeability of blood substances having a larger molecular weight than albumin.

The invention of claim 6 is a combination of the blood purifier of claim 1 or 2 , in which the fractionation curves are significantly different from each other, with one having a molecular weight region with a sieving coefficient of 1 and the other having a sieving coefficient of 0.

The invention described in claim 7 is a method for manufacturing a blood purifier in which a plurality of hollow fiber membranes capable of permeating desired substances are housed in a case, the hollow fiber membranes having different permeability from each other 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 permeability of the hollow fiber membranes is specified in advance by a fractionation curve showing the relationship between the molecular weight and permeability of the substance to be permeated, and the hollow fiber membranes are selected for each specified permeability and housed in the case at a predetermined mixing ratio .

The invention described in claim 8 is characterized in that in the manufacturing method for a blood purifier described in claim 7 , multiple types of hollow fiber membranes having different permeability performances, one of which can be shifted left or right to overlap with the other fractionation curve, and whose fractionation curves tend to have the same or similar curve shapes in the intermediate region between 0 and 1 in terms of sieving coefficient, are contained in the case at a predetermined mixing ratio.

The invention described in claim 9 is characterized in that in the manufacturing method for a blood purifier described in claim 7 , multiple types of hollow fiber membranes having different permeability performances, such that even if one fractionation curve is shifted left or right, it does not overlap with the other fractionation curve, and the fractionation curves have different shapes in the intermediate region between 0 and 1 in terms of sieving coefficient, are contained in the case at a predetermined mixing ratio.

The invention described in claim 10 is characterized in that, in the method for manufacturing a blood purifier described in any one of claims 7 to 9 , the blood purifier comprises a blood purifier in which a patient's blood can flow through the hollow fiber membrane and a dialysis fluid can flow through the case.

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.

The invention described in claim 12 is characterized in that, in the manufacturing method for 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.

The invention described in claim 13 is a combination of the method for manufacturing a blood purifier described in claim 8 or claim 9 , in which the fractionation curves are significantly different from each other, with one having a molecular weight region where the sieving coefficient is 1 and the other having a sieving coefficient of 0.

According to the inventions of claims 1 and 7 , hollow fiber membranes having different permeability are housed in a case in 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.

According to the inventions of claims 1 and 7 , 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 for each 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 predetermined ratio in the case.

According to the inventions of claims 1 and 8 , the case contains a predetermined mixing ratio of multiple types of hollow fiber membranes having different permeability performance but fractionation curves with the same tendency. Therefore, by setting the mixing ratio of multiple types of hollow fiber membranes with fractionation curves with the same tendency, the permeability performance of the substance to be permeated can be easily adjusted.

According to the inventions of claims 2 and 9 , the case contains a predetermined mixing ratio of multiple types of hollow fiber membranes having different permeability performances and fractionation curves with different trends, so that by setting the mixing ratio of the multiple types of hollow fiber membranes having fractionation curves with different trends, the permeability performance of the substance to be permeated can be easily adjusted.

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.

According to the invention 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 satisfactorily.

According to the inventions of claims 5 and 12 , the permeability of the blood albumin, which is the substance to be permeated, can be adjusted, and the permeability of blood substances larger than albumin can be adjusted, so that it is possible to design the removal performance of blood substances with molecular weights larger than albumin, which was not possible with existing blood purifiers, and hemodialysis treatment can be performed well. In addition to albumin, the kidneys of a living body also filter blood substances with larger molecular weights, such as β-globulin (molecular weight 150,000 to 190,000). It was not possible to manufacture a dialyzer that can efficiently remove blood substances with molecular weights larger than albumin while suppressing excessive leakage of albumin using existing technology.

According to the inventions of claims 6 and 13 , the fractionation curves are significantly different from each other, and a combination is provided in which one has a molecular weight region with a sieving coefficient of 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 ingenuity in the manufacturing conditions.

FIG. 1 is a schematic diagram showing a hemodialysis device to which a blood purifier according to a first embodiment of the present invention is applied; A schematic diagram showing the blood purifier (left: exterior, right: interior) A schematic diagram showing the internal structure of the hollow fiber membrane in the blood purifier. Graph showing the fractionation curve of the hollow fiber membrane in the blood purifier Graph showing the fractionation curve of the hollow fiber membrane in the blood purifier according to the second embodiment of the present invention. Table showing typical substances found in blood

Hereinafter, an embodiment of the present invention will be described in detail with reference to the drawings.
The blood purifier according to the embodiment is a blood purifier (dialyzer) in which a plurality of hollow fiber membranes permeable to a desired substance are housed in a case, 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 to have 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.

The 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 dialysis fluid inlet port 2c, and a dialysis fluid outlet port 2d protruding from it. Lid members H are attached to both ends of the case 2, making the inside of the case 2 liquid-tight, and each lid member H has a blood inlet port 2a and a blood outlet port 2b formed therein.

The hollow fiber membrane 3 is made of a thread-like or string-like flexible material that is permeable to desired substances, and as shown in FIG. 3, is configured with pores 3a consisting of multiple openings and flow channels 3b through which liquids such as the patient's blood can flow. 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 liquids such as the patient's blood introduced from the blood introduction port 2a flow through the flow channels 3b and are discharged from the blood discharge port 2b.

In the blood purifier 1 according to this embodiment, during dialysis treatment, as shown in FIG. 1, the blood inlet port 2a and the blood outlet port 2b are connected to the arterial blood circuit 4 and the venous blood circuit 5, respectively, and the dialysate inlet port 2c and the dialysate outlet port 2d are connected to the dialysate inlet line L1 and the dialysate outlet line L2, respectively, which are extended from the dialysis device main body (not shown). Therefore, the dialysis fluid 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.

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 taken from the patient to flow into the flow passage 3b in the hollow fiber membrane 3 of the blood purifier 1. The other end of the arterial blood circuit 4 is made to be able to be attached with an arterial puncture needle a via a connector or the like, and a blood pump 6 is attached midway. The blood pump 6 is made of a squeeze type pump (a configuration in which, when the rotor is driven, the roller squeezes the outer surface of the flexible tube in the longitudinal direction to pump the blood).

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 flow passage 3b in the hollow fiber membrane 3. The other end of the venous blood circuit 5 is connected to a venous puncture needle b via a connector or the like, and an air trap chamber 7 is connected midway.

During hemodialysis treatment, the blood pump 6 is driven to cause the blood collected from the arterial needle a to flow sequentially through the arterial blood circuit 4, the flow passage 3b in the hollow fiber membrane 3 in the blood purifier 1, and the venous blood circuit 5, and then returned to the patient's body via the venous needle b, allowing for extracorporeal circulation.

In addition, when the blood pump 6 is driven, dialysate is introduced into the blood purifier 1 from the dialysate inlet line L1, so that 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 in 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.

Here, 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 and sieving coefficient of the substance to be permeated, and the hollow fiber membranes 3 are selected for each specified permeability and housed in the case 2 at a predetermined mixing ratio.

As shown in Figures 4 and 5, the fractionation curve is a curve represented by a graph in which one axis (horizontal axis in the figures) is the molecular weight of the substance to be permeated (size (kDa) of the substance to be permeated) and the other axis (vertical axis in the figures) is the sieving coefficient, and such fractionation curve can specify the permeation performance of the hollow fiber membrane 3. The sieving coefficient can be calculated by the following formula, 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

Furthermore, blood purifiers such as 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 (filtering all of the liquid), so Cpre can be calculated using the following formula:
Cpre = (inlet concentration of case 1 + outlet concentration of case 1)/2

When the molecular weight of the substance to be permeated is small, it will completely permeate the hollow fiber membrane 3, so there will be no change in concentration before and after filtration and the sieving coefficient will be 1. When the molecular weight of the substance to be permeated is large, it will not be able to permeate 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, so the fractionation curve will also become a graph that slopes downward as the molecular weight increases.

As shown in FIG. 4, in the first embodiment, the blood purifier 1 has 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, housed in a case 2 at a predetermined mixing ratio, and the entire hollow fiber membranes in the case 2 are adjusted to have the permeability performance of fractionation curve C.

The term "fractionation curves with the same trend" refers to a relationship in which fractionation curve A overlaps with fractionation curve B by shifting it to the right, or a relationship in which fractionation curve B overlaps with fractionation curve A by shifting it to the left, as shown in the figure, and refers to a relationship in which the shape of the curve (graph trend) in the intermediate region between the sieving coefficients of 0 and 1 is the same (or similar). For example, the variation in permeability performance for each production lot of hollow fiber membrane 3 often results in fractionation curves with the same trend (fractionation curves shifting left and right).

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 the blood, and the permeability of the albumin can be adjusted. In other words, in hemodialysis treatment, it is necessary to allow albumin to permeate moderately (permeation of about several grams per treatment), but when using a hollow fiber membrane 3 whose permeability varies from production lot to production lot, it becomes difficult to maintain a constant sieving coefficient.

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 at the same time it is necessary to pass through and remove proteins that have accumulated in the body in the high molecular weight range (such as β2-microglobulin with a molecular weight of 18,000). For example, typical substances contained in blood are as shown in Figure 6.

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

For example, as shown in FIG. 4, when the target sieving coefficient for albumin is set to 0.1 (see symbol P in the figure), by storing 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 the case 2 at a predetermined mixing ratio (in the 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), the entire hollow fiber membrane 3 in the case 2 can be adjusted to fractionation curve C. This allows the sieving coefficient for a substance of a predetermined molecular weight (albumin in this embodiment) to be managed at a constant value, and a blood purifier 1 (blood purifier) with stable permeability can be obtained.

As shown in FIG. 5, in the blood purifier 1 in the second embodiment, multiple types (two types in this embodiment) of hollow fiber membranes (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) with different permeability and different tendency of fraction curves A and B are housed in a case 2 at a predetermined mixing ratio, and the entire hollow fiber membrane in the case 2 is adjusted to have the permeability of fraction curve C.

The tendency for the fractionation curves to differ refers to a relationship in which fractionation curve A does not overlap with fractionation curve B even when fractionation curve A is shifted to the right, or a relationship in which fractionation curve B does not overlap with fractionation curve A even when fractionation curve B is 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 manufactured in advance.

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 housing 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 membrane 3 in case 2 can be adjusted to fractionation curve C. In addition, the sieving coefficient for substances with a larger molecular weight than albumin (molecular weight 70 kDa to 80 kDa) can be maintained at approximately 0.1.

When adjusting the spinning conditions to shift the fractionation curve to the right to increase the permeability of substances with a larger molecular weight 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 will be lost during dialysis therapy, which may have adverse effects on the patient. For this reason, with conventional methods, it has not been possible to manufacture a blood purifier that can remove substances with a molecular weight larger than that of albumin.

The method shown in FIG. 5 makes it possible to manufacture a blood purifier that suppresses the permeability of albumin while allowing substances with molecular weights equal to or greater than that of albumin to permeate to a certain extent. The flat portion of the middle region of the 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 a blood purifier manufactured by this method, it is possible to expect therapeutic effects that could not be achieved with conventional blood purifiers. That is, by using a combination in which the fractionation curves A and B are significantly different from each other and one has a molecular weight region with a sieving coefficient of 1 and the other has a sieving coefficient of 0, it is possible to obtain a blood purifier with a step-like fractionation curve that could not be achieved by devising manufacturing conditions.
In addition, the fractionation characteristic C when the first type of hollow fiber membrane 3 of the fractionation curve A and the second type of hollow fiber membrane 3 of the fractionation curve B are mixed at a predetermined mixing ratio can be theoretically calculated.

This allows the sieving coefficient for a substance of a specified molecular weight (albumin in this embodiment) to be controlled at a constant value, making it possible to obtain a blood purifier 1 (blood purifier) with stable permeability, and 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 in plasma components with a molecular weight equal to or greater than that of albumin can be separated. This is because the plasma separation membrane can separate blood cell components and plasma components.

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 adjusted arbitrarily by the mixing ratio, so that the permeability of 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 sieving coefficient of the substance to be permeated, and the hollow fiber membranes 3 are selected for each specified permeability and housed in the case 2 at a predetermined mixing ratio, so that 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.

In addition, in the case 2 according to the first embodiment, multiple types of hollow fiber membranes 3 having different permeability and fraction curves with the same tendency are accommodated in a predetermined mixing ratio, so that the permeability of the substance to be permeated can be easily adjusted by setting the mixing ratio of the multiple types of hollow fiber membranes 3 having the same fraction curves. In addition, in the case 2 according to the second embodiment, multiple types of hollow fiber membranes 3 having different permeability and fraction curves with different tendencies are accommodated in a predetermined mixing ratio, so that the permeability of the substance to be permeated can be easily adjusted by setting the mixing ratio of the multiple types of hollow fiber membranes 3 having different fraction curves. In addition, it has become possible to manufacture a blood purifier that allows substances with molecular weights equal to or greater than albumin to permeate to a certain extent while suppressing the permeability of albumin, which was not possible to manufacture in the past.

Furthermore, since the blood purifier 1 is configured so that the patient's blood can flow through the hollow fiber membrane 3 and the dialysis fluid can flow through the case 2, the permeability of the blood purifier 1 can be easily and stably maintained constant. In addition, 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.

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

However, in a blood purifier that allows substances with molecular weights equal to or greater than that of albumin to pass through to a certain extent while suppressing the permeability of albumin to a certain value, 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 in Figure 5. The characteristics of the blood purifier are dominated by the hollow fiber membranes B, which have a smaller number of membranes. In general, 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 often combined. When blood is circulated extracorporeally using a blood purifier, blood may clot in the header of the blood purifier (urethane cut surface). In that case, blood will not flow through the hollow fiber membranes in the clotted portion. 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 this blood purifier will be lost. Therefore, when combining different hollow fiber membranes, it is better to distribute the hollow fiber membranes evenly. If hollow fiber membranes with a small ratio are placed locally, blood clotting inside the blood purifier may cause a significant change in the performance of the blood purifier. Also, since blood clotting occurs more often on the outside of the hollow fiber membrane bundle, it is better to place hollow fiber membranes with a large ratio on the outside and hollow fiber membranes with a small ratio on the inside.

If hollow fiber membranes with different permeability are housed in the case at a predetermined mixing ratio and the permeability of the substance to be permeated is adjusted as desired by the mixing ratio, the blood purifier and its manufacturing method can also be applied to those with different external shapes or those with added functions.

1. Blood purifier (dialyzer)
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 blood circuit 5 Venous blood circuit 6 Blood pump 7 Air trap chamber A Fraction curve B of first type of hollow fiber membrane Fraction curve C of second type of hollow fiber membrane Fraction curve H of adjusted hollow fiber membrane Lid member F Sealing material L1 Dialysate inlet line L2 Dialysate outlet line a Arterial puncture needle b Venous puncture needle

Claims (13)

A blood purifier in which a plurality of hollow fiber membranes permeable to a desired substance are housed in a case,
The 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 hollow fiber membrane has a permeability that is previously specified by a fractionation curve that shows the relationship between the molecular weight of a substance to be permeated and the permeability, and the hollow fiber membranes having the specified different permeability are accommodated in the case at a predetermined mixing ratio, and
The case is a blood purifier characterized in that it contains, in a predetermined mixing ratio, multiple types of hollow fiber membranes having different permeability performances, one of which can be overlapped with the other by shifting the fractional curve to the left or right, and whose fractional curves tend to have the same or similar curve shapes in the intermediate region between 0 and 1 in terms of sieving coefficient. A blood purifier in which a plurality of hollow fiber membranes permeable to a desired substance are housed in a case,
The 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 hollow fiber membrane has a permeability that is previously specified by a fractionation curve that shows the relationship between the molecular weight of a substance to be permeated and the permeability, and the hollow fiber membranes having the specified different permeability are accommodated in the case at a predetermined mixing ratio, and
The case is a blood purifier characterized in that it contains, in a predetermined mixing ratio, multiple types of hollow fiber membranes having different permeability performances, such that even if one fractionation curve is shifted left or right, it does not overlap with the other fractionation curve, and the fractionation curves have different shapes in the intermediate region between the sieving coefficients of 0 and 1 . 3. The blood purifier according to claim 1 or 2, characterized in that the blood of a patient can flow through the hollow fiber membrane and the dialysis fluid can flow through the case. 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. The blood purifier according to claim 4 , wherein the permeability of albumin is adjustable, and the permeability of blood substances having molecular weights larger than that of albumin is also adjustable. 3. The blood purifier according to claim 1 or 2, wherein the combination has a molecular weight region in which the fractionation curves are significantly different from each other, one having a sieving coefficient of 1 and the other having a sieving coefficient of 0. 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, comprising: housing hollow fiber membranes having different permeability performances in the case at a predetermined mixing ratio; adjusting the permeability performance of a substance to be permeated as desired by the mixing ratio; and selecting the hollow fiber membranes for each of the specified permeability performances and housing them in the case at a predetermined mixing ratio, the permeability performance of each of the hollow fiber membranes being specified in advance based on a fractionation curve showing the relationship between the molecular weight of the substance to be permeated and the permeability. The method for manufacturing a blood purifier as described in claim 7, characterized in that a plurality of types of hollow fiber membranes having different permeability performances, one of which can be made to overlap with the other by shifting the fractionation curve to the left or right, and whose fractionation curves tend to have the same or similar curve shapes in the intermediate region between 0 and 1 in terms of sieving coefficient, are contained in the case in a predetermined mixing ratio. The method for manufacturing a blood purifier as described in claim 7, characterized in that a plurality of types of hollow fiber membranes having different permeability performances, such that even if one fractionation curve is shifted left or right, it does not overlap with the other fractionation curve, and the fractionation curves have different shapes in the intermediate region between sieving coefficients of 0 and 1 , are housed in the case at a predetermined mixing ratio. The method for manufacturing a blood purifier according to any one of claims 7 to 9, characterized in that the blood purifier is configured so that a patient's blood can flow through the hollow fiber membrane and a dialysis fluid can flow through the case. 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. 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. 10. The method for producing a blood purifier according to claim 8 or 9 , wherein the combination has a molecular weight region in which the fractionation curves are significantly different from each other, one having a sieving coefficient of 1 and the other having a sieving coefficient of 0.

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