JPH119684A - Hollow fiber membrane type blood dialysis filter, constricted part forming member device jig and hollow fiber membrane bundle inserting jig as well as production of hollow fiber membrane blood dialysis filter - Google Patents

Abstract

PROBLEM TO BE SOLVED: To facilitate manufacture and to improve dialysis membrane efficiency by constituting a constricting part forming member of which the bore in a dry state is expandable and contractable between the outside diameter of a hollow fiber membrane bundle or below and the outside diameter of the hollow fiber membrane bundle or above. SOLUTION: The constricting part 8 is formed by inserting the constricting part forming member between the outer peripheral part of the bundle 4 of the hollow fiber membranes 41 and the inside surface of the cylindrical body 32 of a housing 3. This constricting part forming member is formed to a cylindrical shape and its bore in the dry state is set at the outside diameter of the constricting part 8 or below, for example, about 1 to 10 cm. The bore is made expandable and contractable in a diametral direction up to the bore larger than the outside diameter of the hollow fiber membrane bundle 4 and the expansion and contraction rate thereof is set at 1.01 to 2.00. Mounting is difficult below this range. There is no effect even if the bore is set above this range. The hollow fiber membrane bundle 4 is recommended to have wettability with a dialyzate in order to mount the same without damaging the hollow fiber membranes 41. The hollow fiber membranes are preferably formed of, for example, (crosslinked) polyacrylic acid salt, etc., having a dialyzate contg. rate of about >=10 wt.%. There is no after blood and the damage of the hollow fiber membrane may be prevented by such constitution.

Description

DETAILED DESCRIPTION OF THE INVENTION

[0001]

TECHNICAL FIELD The present invention relates to a hollow fiber membrane type hemodiafiltration filter used in blood purification therapy. More specifically, a hollow fiber membrane bundle is provided in a cylindrical housing, and a stenosis forming member is interposed between the outer peripheral portion of the hollow fiber membrane bundle and the inner surface of the housing to form one of the dialysate flow paths. The present invention relates to a hollow fiber membrane-type hemodiafiltration filter having a stenosis part in a part.

[0002]

2. Description of the Related Art In blood purification therapy, hemodiafiltration, a method for performing a large amount of liquid replacement between blood and dialysate,
Online hemodiafiltration and push-and-pull hemodiafiltration are known. However, it is uneconomical to perform a large amount of liquid replacement by the hemodiafiltration method because a large amount of expensive replacement solution is required. In the online hemodiafiltration method and the push-and-pull hemodiafiltration method, a dedicated There is a drawback in that a device must be added and the circuit configuration becomes complicated.

On the other hand, the inner diameter of the housing is narrowed at the center thereof to be smaller than that of the other portion, and the convergence of the capillary is made denser at the portion than at the other portion, thereby improving the diafiltration efficiency. A dialyzer is known (Japanese Utility Model Publication No. 56-22911). However, the fact that the inner diameter of the cylindrical body is reduced in this way means that the outer peripheral portion of the bundle of the hollow fiber membranes is pressed by a hard cylindrical projection that constitutes the reduced diameter portion. There is a disadvantage that the hollow fiber membrane near the outer periphery of the bundle is distorted and damaged. Also,
Due to the difficulty in inserting the bundle of the hollow fiber membrane into the cylindrical body due to the reduced diameter portion, there is also a disadvantage that assembling operation requires a long time and costs are increased.

On the other hand, in order to solve the problems of the above-mentioned technology, the present inventors have first made the dialysate swellable in the gap between the outer periphery of the hollow fiber membrane bundle and the inner surface of the housing or the gap between the hollow fiber membranes. A stenosis portion is provided in the middle of the dialysate flow path by interposing a stenosis portion forming member having the dialysis solution, so that a pressure difference is generated in the dialysate between the upstream side and the downstream side of the stenosis portion, and diafiltration efficiency is dramatically improved. (JP-A-8-19203)
No. 1). Here, as a method of inserting the constricted portion forming member into a gap or the like between the outer peripheral portion of the hollow fiber membrane bundle and the inner surface of the housing, a method of partially filling the gap with a resin and a method of inserting fibers into the outer periphery of the hollow fiber membrane bundle It shows a method of wrapping around a part or knitting in a gap of a hollow fiber membrane.

[0005]

SUMMARY OF THE INVENTION An object of the present invention is to provide a hollow fiber membrane type hemodiafiltration filter having a constriction in a part of a dialysate flow path. The present invention provides a diafiltration filter which is easy to manufacture and has extremely high diafiltration efficiency.

Another object of the present invention is to provide a means for easily mounting a constriction forming member on the outer periphery of a hollow fiber membrane bundle without damaging the hollow fiber membrane. Still another object of the present invention is to provide a means for easily inserting a hollow fiber membrane bundle on which a stenosis portion forming member is mounted into a housing without damaging the hollow fiber membrane.

[0007]

Means for Solving the Problems In order to solve the above-mentioned problems, the present inventors have conducted further intensive studies on a hollow fiber membrane type hemodiafiltration filter having a constriction in a part of the dialysate flow path. The present invention has been completed.

That is, according to the present invention, there is provided a stenosis portion forming member having a hollow fiber membrane bundle in a cylindrical housing and having a dialysate swelling property in a gap between an outer peripheral portion of the hollow fiber membrane bundle and an inner surface of the housing. In a hollow fiber membrane-type hemodiafiltration filter in which a constriction is formed in a part of the dialysate flow path by interposing, the constriction forming member has a cylindrical shape and is substantially dry. A hollow fiber membrane type hemodiafiltration filter having an inner diameter equal to or less than the outer diameter of the hollow fiber membrane bundle and being expandable and contractible in the radial direction between the inner diameter and an inner diameter larger than the outer diameter of the hollow fiber membrane bundle. It is a vessel.

In the present invention, the constricted portion forming member has a radial expansion / contraction ratio of 1.01 to 2.
00 is the hollow fiber membrane type hemodiafiltration filter.

The present invention further provides the hollow fiber membrane type hemodiafiltration filter, wherein the constricted portion forming member is made of a knitted fabric of a highly water-absorbent resin fiber.

Further, the present invention is a jig for mounting the narrowing portion forming member on the outer peripheral portion of the hollow fiber membrane bundle of the hollow fiber membrane type hemodiafiltration filter, the jig having a smooth outer surface. A cylindrical trunk having an inner diameter larger than the outer diameter of the hollow fiber membrane bundle, and a frusto-conical shape tapering from the outer diameter of the trunk to an outer diameter smaller than the inner diameter of the constriction forming member. A stenosis portion forming member mounting jig comprising a pointed head.

[0012] The present invention is the jig for mounting a stenosis portion forming member, wherein the torso portion and the cusp portion are separable.

Further, the present invention is a jig for inserting the hollow fiber membrane bundle having the constricted portion forming member of the hollow fiber membrane type hemodiafiltration filter attached to an outer peripheral portion into the housing. A hollow fiber membrane bundle having a smooth inner surface, having a cylindrical shape, having a taper, and having an inner diameter larger than an outer diameter of the constricted portion forming member mounted on an outer peripheral portion of the hollow fiber membrane bundle. It is an insertion jig.

The present invention also provides a stenosis portion forming member having a hollow fiber membrane bundle in a cylindrical housing and having a dialysate swelling property in a gap between an outer peripheral portion of the hollow fiber membrane bundle and an inner surface of the housing. The method for producing a hollow fiber membrane-type hemodiafiltration filter in which a constriction is formed in a part of the dialysate flow path by interposing a dialysis fluid, wherein (A) a cylindrical shape and a substantially dry state The inner diameter of the narrowing portion forming member having an inner diameter equal to or less than the outer diameter of the hollow fiber membrane bundle and being expandable and contractible in the radial direction between the inner diameter and the inner diameter larger than the outer diameter of the hollow fiber membrane bundle, Introducing the portion forming member to a predetermined position on the outer peripheral portion of the hollow fiber membrane bundle, and then mounting the narrowed portion forming member on the outer peripheral portion of the hollow fiber membrane bundle by contracting and restoring the inner diameter of the narrowed portion forming member. ,
And (B) inserting the hollow fiber membrane bundle having the stenotic portion forming member attached to the outer periphery into the housing.

The present invention further comprises the step of: (a) covering the outer periphery of the hollow fiber membrane bundle with a protective mesh, and then introducing the constriction forming member. This is a method for manufacturing a filter.

[0016]

DETAILED DESCRIPTION OF THE PREFERRED EMBODIMENTS The present invention will be described below in detail with reference to the drawings.

FIG. 1 is a circuit diagram schematically showing a configuration example of a blood extracorporeal circuit including a hollow fiber membrane type hemodiafiltration filter of the present invention. As shown in FIG. 1, the extracorporeal blood circulation circuit 10 includes a blood removal line 11A, a hemodiafiltration filter 1, a blood return line 11B, and a water removal control unit 17.

The blood removal line 11A is composed of a tube 12, a blood sending pump 13 and a defoaming chamber 14 installed in the middle of the tube 12, and one end of the blood removal line 11A is connected to a needle tube. The other end is connected to the blood inlet 34 of the hemodiafiltration filter 1.

The blood return line 11B is connected to a tube 15
And a defoaming chamber 16 installed in the middle of the tube 15, and one end of the blood return line 11B is connected to a patient's vein via a needle tube.

The water removal control means 17 includes a tube 18 having one end connected to a dialysate inlet 36 of the hemodiafiltration device 1 and a tube 19 having one end connected to a dialysate outlet 37 of the hemodiafiltration device 1. And a double pump 20 for feeding dialysate into the tubes 18 and 19 at the same flow rate and in opposite directions, respectively, and a bypass tube 21 whose both ends are connected to the tube 19 so as to bypass the double pump 20.
And a water removal pump 22 provided in the middle of the bypass tube 21.

As the pump 13, a roller pump is preferably used.

The double pump 20 converts the rotational motion of the motor into a reciprocating motion of the plunger, and alternately receives and discharges dialysate and dialysate drainage by a check valve mechanism.

The water removal pump 22 is configured to convert the rotational movement of the motor into the reciprocating movement of the plunger and to send out the dialysate drainage in the cylinder in a certain direction.

Next, the operation of the extracorporeal blood circulation circuit 10 will be described.

The blood removed from the patient by the operation of the pump 13 flows through the blood removal line 11A, is temporarily stored in the chamber 14 and defoamed, and then enters the hemodiafiltration filter 1 through the blood inlet 34. Inflow. The blood flowing out from the blood outlet 35 flows through the blood return line 11B, is temporarily stored in the chamber 16, is defoamed, and is returned to the patient.

On the other hand, by the operation of the double pump 20, dialysate supplied from a dialysate reservoir (not shown) flows through the tube 18, and flows through the dialysate inlet 36 into the hemodiafiltration device 1.
The dialysis and filtration are performed as described below with the blood through the hollow fiber membranes 41 inside the housing 3 and discharged from the dialysate outlet 37. The discharged dialysate is transferred via the tube 19 and collected. At this time, when the dewatering bomb 22 is operated at a predetermined rotation speed, the amount of dialysate supplied to the hemodiafiltration filter 1 and the amount of dialysate recovered from the dialysate 1 correspond to the discharge amount of the dewatering pump 22. The difference is the amount of water removed from the blood passing through the dialysate 1. Therefore,
By adjusting the rotation speed (discharge amount) of the water removal pump 22, the water removal amount can be adjusted.

FIG. 2 is a longitudinal sectional view showing one embodiment of the hemodiafiltration filter 1 of the present invention. As shown in the figure, the hemodiafiltration filter 1 has a cylindrical main body 31 and covers 38 at both ends thereof.
And a housing 3 comprising headers 32 and 33 which are connected and fixed in a liquid-tight manner by means of and 39 respectively. A blood inlet 34 protrudes from the top of the header 32, and a blood outlet 35 protrudes from the top of the header 33. Also, the header 33 of the tubular main body 31
A dialysis fluid inlet 36 is formed on the side of the cylindrical body 31, and a dialysis fluid outlet 3 is formed on the side of the cylindrical body 31 on the header 32 side.
7 is protruded.

The cylindrical body 31, the headers 32 and 3
3, and the covers 38 and 39 are made of, for example, polyethylene, polypropylene, polycarbonate, polymethyl methacrylate, acrylic resin, hard polyvinyl chloride,
It is made of various hard resins such as styrene-butadiene copolymer resin and polystyrene, and is preferably transparent or translucent to secure the visibility inside. Further, the header 32 and the cover 33 may be colored in different colors in order to easily distinguish between the blood entry side and the blood entry side.

A bundle 4 of hollow fiber membranes 41 is housed in the housing 3 over substantially the entire length thereof. in this case,
The hollow fiber membranes 41 constituting the bundle 4 are, for example, 100 to 70
2,000, and each hollow fiber membrane 41 is
Are arranged in parallel and separated from each other along the longitudinal direction.

Examples of the hollow fiber membrane 41 include regenerated cellulose, cellulose derivatives, polymethyl methacrylate, polyolefins such as polyethylene and polypropylene, polysulfone, polyacrylonitrile, polyamide, polyimide, polyether nylon, silicone and polytetrafluoroethylene. And polyester-based polymer alloys.

The effective membrane area of the entire hollow fiber membrane 41 is not particularly limited, but is preferably from 100 cm ^{2 to} 6.0.
m ² approximately, and more preferably ² about 0.2～2.0M. Both ends of each hollow fiber membrane 41 are liquid-tightly supported and fixed by partitions 51 and 52 at the ends of the tubular main body 31 in a state where the end opening of the hollow fiber membrane 41 is not closed.

The partition walls 51 and 52 are made of a potting material such as polyurethane, silicone, or epoxy resin. In the presence of the bundle 4 of the hollow fiber membranes 41, the liquid potting material is centrifugally injected into the cylindrical main body 31. Is formed by injecting into both ends and curing.

A blood inflow chamber 61 is formed in a space surrounded by the header 32 and the partition 51, and a blood outflow chamber 62 is formed in a space surrounded by the header 33 and the partition 52. A blood flow path 6 is formed in the lumen (hollow portion) of each hollow fiber membrane 41, and both ends of the blood flow path 6 communicate with the blood inflow chamber 61 and the blood outflow chamber 62, respectively. I have.

In a space surrounded by the cylindrical main body 31 of the housing 3 and the partition walls 51 and 52, the gap between the bundle 4 of the hollow fiber membranes 41 and the inner peripheral surface of the cylindrical main body 31 and the adjacent hollow fiber The dialysate dialysate flow path 7 is formed in the gap between the membranes 41. That is, the blood flow path 6 and the dialysate flow path 7 are separated by each hollow fiber membrane 41. The upstream side of the dialysate flow path 7 communicates with the dialysate inlet 36, and the downstream side communicates with the dialysate outlet 37.

With this configuration, the blood flowing into the blood inflow chamber 61 from the blood inflow port 34 flows through the blood flow path 6, is collected in the blood outflow chamber 62, and flows out of the blood outflow port 35. The dialysate flowing from the dialysate inlet 36 flows through the dialysate flow path 7 in a direction opposite to the blood flow (counter flow), and flows out from the dialysate outlet 37.

In the middle of the dialysate flow path 7, there is provided a constriction 8 having a reduced cross-sectional area of the flow path, and a dialysate upstream 71 and a dialysate downstream 72 from the constriction 8 are dialyzed. The pressure of the dialysate flowing through the liquid flow path 7 is configured to have a desired difference.

FIG. 3 is a graph showing the pressure distribution of the blood flowing through the blood channel 6 and the dialysate flowing through the dialysate channel 7. As shown in the figure, the pressure of the blood flowing through the blood flow path 6 decreases almost linearly from the upstream to the downstream, while the pressure of the dialysate flowing through the dialysate flow path 7 is reduced by the constriction. On the upstream side 71 of the dialysate from the stenosis 8, the pressure is higher than the blood pressure at the corresponding portion of the blood flow channel 6, and on the downstream side 72 of the dialysate from the constriction 8, the pressure is lower than the blood pressure at the corresponding portion of the blood flow channel 6. Become.

Accordingly, the blood flowing through the blood flow path 6 is first dialyzed (diffusion of solute) and ultrafiltered (dewatered) through the hollow fiber membranes 41 on the downstream side 72 of the dialysate, and then dialyzed. On the upstream side 71, ultrafiltration (replacement fluid) in the reverse direction from the dialysate side to the blood side is performed via each hollow fiber membrane 41.

As described above, since the replacement fluid is performed on the dialysate upstream side 71, that is, on the downstream side of the blood, the amount of filtration from the blood side to the dialysate side can be increased on the upstream side of the blood. It is possible to replace a large amount of liquid with dialysate. In addition, such a large amount of liquid replacement can be performed with a single hemodiafiltration filter 1 without using a dedicated device or the like separately provided.

In this case, the ultrafiltration rate (pure water filtration coefficient) in the hemodiafiltration filter 1 is 200 ml / water flow rate.
It is preferably at least 20 ml / m ² · hr · mmHg at min and more preferably at least 30 ml / m ² · hr · mmHg at a water flow rate of 300 ml / min.

In the present invention, the constricted portion 8 is formed between the outer peripheral portion of the bundle 4 of the hollow fiber membranes 41 and the cylindrical main body 3 of the housing 3.
It is formed by interposing a stenosis portion forming member 81 between itself and the inner surface of the first member.

The constricted portion forming member 81 used in the present invention has a cylindrical shape and has an inner diameter of 1 to 1 in a substantially dry state.
10 cm, preferably 2-6 cm, length 0.5
８8.0 cm, preferably 3 to 6 cm.

The constriction forming member 81 preferably has a dialysate swelling property so that it can be easily mounted on the hemodiafiltration filter 1 without damaging the hollow fiber membrane. Therefore, the material used for the stenosis portion forming member 81 has a dialysate content of 10% by weight or more, preferably 10 to 2600% by weight,
Particularly preferably, the content is 50 to 2000% by weight. Such materials include (cross-linked) polyacrylates or (cross-linked) acrylic acid-acrylate copolymers, isobutylene-maleic acid copolymers, starch-acrylic acid graft copolymers or saponified products thereof,
Highly water-absorbing resin materials such as a saponified vinyl acetate-acrylate copolymer, carboxymethyl cellulose, and a composite fiber of an acrylonitrile fiber inner core and an acrylate copolymer outer layer, among which sodium polyacrylate Salt (BELLOASIS manufactured by Kanebo Co., Ltd.) and a composite fiber of an acrylonitrile fiber inner core and an outer layer of an acrylate copolymer (LANSEAL manufactured by Toyobo Co., Ltd.) are most preferable.

The tubular constriction forming member 81 has an inner diameter less than the outer diameter of the hollow fiber membrane bundle 4 in a substantially dry state, and is larger than the inner diameter and the outer diameter of the hollow fiber membrane bundle 4. It is necessary to be able to expand and contract in the radial direction between the inner diameter and the inner diameter. That is, the constriction portion forming member 81 preferably has an expansion / contraction ratio defined by an inner diameter at the time of maximum expansion with respect to an inner diameter at a normal time in a substantially dry state, of 1.01 to 2.00,
1.05 to 1.50 are more preferable, and 1.10 to 1.50.
20 is particularly preferred. The expansion and contraction rate of the stenosis portion forming member is 1.
If it is less than 01, it is difficult to attach it to the hollow fiber membrane 4 and
Even if it exceeds, the wearability is not further improved.

As a means for imparting such radial elasticity to the tubular constriction portion forming member, a method of imparting elasticity by knitting the fibrous highly absorbent resin into a knitted material, And a method of knitting the conductive fiber and the highly absorbent resin fiber together to form a knitted fabric so as to have elasticity. In this case, examples of such stretchable fibers include polyurethane (spandex) and polyethylene terephthalate. As a method of knitting these knits, flat knitting, rubber knitting, pearl knitting, single-sided knitting, double-sided knitting, weft insertion knitting, braided knitting, and the like are mentioned. The cylindrical shape is formed by sewing or knitting in a circular knitted fabric.

In the present invention, the stenosis portion forming member 81 is used.
Is inserted into the gap between the outer peripheral portion of the hollow fiber membrane bundle 4 and the inner surface of the tubular main body 31 of the housing 3 by the following steps.

(A) The inner diameter of the narrowed portion forming member 81 is extended, the narrowed portion forming member 81 is introduced into a predetermined position on the outer peripheral portion of the hollow fiber membrane bundle 4, and the inner diameter of the narrowed portion forming member 81 is contracted and restored. (B) Step of inserting the hollow fiber membrane bundle 4 with the stenotic part forming member 81 mounted on the outer periphery into the housing 3 4 is a conceptual diagram showing one embodiment of a step (step (A)) of mounting the constricted portion forming member 81 on the outer peripheral portion of the hollow fiber membrane bundle 4 in the present invention.

In this step, a stenosis portion forming member mounting jig 9 is used. The stenosis portion forming member mounting jig 9 includes:
The trunk 91 is cylindrical and has an inner diameter larger than the outer diameter of the hollow fiber membrane bundle 4.
Is a truncated conical shape, and a narrowing portion forming member 81 is formed from the outer diameter of the body portion 91.
Is tapered to an outer diameter smaller than the inner diameter. Specifically, the inside diameter of the trunk 91 is 1 to 12 cm, preferably 2 to
6 cm, a thickness of 0.05 to 10 mm, preferably 0.2 to 0.8 mm, and a length of 2 to 20 cm, preferably 6 to 15 cm. The tip outer shape of the pointed head 92 is 0.5 to 9 cm, preferably 1 to 5 cm, and the length is 3 to 15 cm. Also, the stenosis portion forming member mounting jig 9
Has a smooth outer surface, such materials as polyacetal, polycarbonate, polyethylene, polypropylene, fluororesin, polyethylene terephthalate,
Synthetic resin such as polystyrene, stainless steel, aluminum, aluminum alloy, nickel, nickel alloy, copper,
Examples include metals such as copper alloys, titanium, and titanium alloys.

In the step (A), first, the distal end of the sharp head 92 of the stenosis part forming member mounting jig 9 having an outer diameter smaller than the inner diameter of the stenosis part formation member 81 is attached.
The inner diameter of the stenosis portion forming member 81 is changed to the outer diameter of the hollow fiber membrane bundle 4 by moving the stenosis portion forming member 81 to the body portion 91 having an inner diameter larger than the outer diameter of the hollow fiber membrane bundle 4. Stretch more. Next, the hollow fiber membrane bundle 4 is passed through the lumen of the trunk portion 91 of the stenosis portion forming member mounting jig 9, and the stenosis portion forming member 81 is moved to a predetermined position on the outer peripheral portion of the hollow fiber membrane bundle 4, thereby constricting the stenosis. The inner diameter of the portion forming member 81 is contracted and restored by releasing the expansion of the inner diameter, and the outer diameter is mounted on the outer periphery of the hollow fiber membrane bundle 4.

FIG. 5 shows a stenosis portion forming member 8 according to the present invention.
It is a conceptual diagram which shows another embodiment of the process (process (A)) of attaching 1 to the outer peripheral part of the hollow fiber membrane bundle 4. In this step, the hollow fiber membrane bundle 4 is attached to the stenosis forming member mounting jig 9.
Before the hollow fiber membrane bundle 4 is inserted into the lumen, the outer periphery of the hollow fiber membrane bundle 4 is covered with a protective mesh 100, and then the stenosis portion forming member mounting jig 9 is attached.
The stenosis forming member 81 is inserted into the lumen of the
00, which can effectively prevent damage to the hollow fiber membrane in the manufacturing process. Examples of the material of the protective mesh 100 include polyester, tetron, glass fiber, rayon, cupra, acetate, acetylated acetate, vinylon, nylon, vinylidene, acrylic, polyurethane (spandex), cotton,
Wool, silk, polyvinyl chloride, polyurea, polyethylene,
Polypropylene and the like are mentioned, but polyester is most preferable from the viewpoint of heat resistance, water permeability and the like.

In this step, as shown in FIG. 6, a stenosis portion forming member mounting jig 9 having a body portion 91 and a pointed head 92 which can be separated is used. By using such a stenosis part forming member mounting jig 9, the posterior cusp is moved from the pointed head 92 side of the stenosis part forming member mounting jig 9 to the trunk part 91 through the stenosis part forming member 81. By removing 92, the hollow fiber membrane bundle 4 can be inserted from the same direction as the stenosis portion forming member 81. For example, the end of the stenosis portion forming member mounting jig 9 on the trunk portion 91 side depending on process conditions. This is convenient when the part is a fixed end.

FIG. 7 shows a stenosis portion forming member 8 according to the present invention.
FIG. 3 is a conceptual diagram showing one embodiment of a step (step (B)) of inserting a hollow fiber membrane bundle 4 equipped with a hollow fiber membrane bundle 1 into a housing 3. In this step, the hollow fiber membrane bundle 4 in which the stenosis portion forming member 81 is mounted on the outer peripheral portion is inserted into the inner cavity of the housing 3.
When inserting the hollow fiber membrane bundle 4, the hollow fiber membrane bundle insertion jig 10
1 is used. As shown in FIG. 8, the hollow fiber membrane bundle insertion jig 101 has an inner diameter larger than the outer diameter of the constricted portion forming member 81 which is cylindrical and has a taper and is mounted on the outer peripheral portion of the hollow fiber membrane bundle 4. Have. Specifically, the maximum inner diameter is 2 to 14 cm,
It is preferably 3 to 6 cm, and the minimum inner diameter is 1.8 to 12 cm.
cm, preferably 2.8-5.8 cm, a thickness of 0.05-10 mm, preferably 0.2-0.8 mm, and a length of 3-10 cm, preferably 5-8 cm. Further, the hollow fiber membrane bundle insertion jig 101 has a smooth outer surface, and examples of such a material include those similar to the above-described stenosis portion forming member mounting jig 9.

In this step, the different diameter housing 102
The hollow fiber membrane bundle insertion jig 101 is mounted on the side of the large inner diameter of the hollow fiber membrane bundle.
The stenosis portion forming member 81 is inserted into the different diameter housing 102 without damaging the hollow fiber membrane and without coming off the hollow fiber membrane bundle 4.

In the hemodiafiltration device of the present invention, when forming the stenotic portion 8, the hollow fiber membrane 41 is further added to the method of interposing the stenotic portion forming member 81 described above.
A method of filling the gap between the superabsorbent resin with the superabsorbent resin, a method of winding the superabsorbent resin fiber around the outer periphery of the bundle 4 or knitting in the gap of the hollow fiber membrane 41 may be used in combination. When filling the gap between the hollow fiber membranes 41 with a highly absorbent resin, the distribution of the constricted portion forming member 81 in the cross-sectional direction of the bundle 4 is uniform or non-uniform (for example, the central portion of the bundle 4 is dense, and the May be coarse or vice versa). As the high-absorbency resin and the high-absorbency resin fiber that can be used in these cases, those similar to those used for the above-described constriction portion forming member 81 can be used.

Thus, in the hemodiafiltration device according to the present invention, the filling rate of the hollow fiber membrane at the constricted portion is 105 to 200%, preferably 120 to 180%, with respect to the filling ratio other than the constricted portion. . If the filling rate in the constricted portion is less than 105%, it is difficult to obtain a liquid replacement effect because the pressure difference between the upstream side and the downstream side of the constricted portion is small.
If it exceeds 200%, the hollow fiber membrane may be crushed.

The average value of the pressure difference (pressure loss) between the dialysate upstream side 71 and the dialysate downstream side 72 through the constriction 8 is preferably about 10 to 120 mmHg, and 30 to 120 mmHg.
About 100 mmHg is more preferable. As a result, the large-volume liquid replacement between the blood and the dialysate as described above is efficiently performed. The constituent material, arrangement density, installation area, and the like of the constricted portion forming member 81 of the constricted portion 8 are appropriately adjusted so as to obtain such a pressure difference.

The position of the constriction 8 in the dialysate flow path is not particularly limited, but the ratio of the flow path length on the dialysate upstream side 71 to the flow path length on the dialysate downstream side 72 is 2: 1 to 1: 2. It is preferred to be on the order of magnitude. As a result, the large-volume liquid replacement between the blood and the dialysate as described above is efficiently performed. In the illustrated configuration example, the stenosis portion 8 is formed at the longitudinal center of the dialysate flow path, and the flow path length on the dialysate upstream side 71 and the flow path length on the dialysate downstream side 72 are set to be substantially equal. .

[0058]

The present invention will be described in more detail with reference to the following examples.

[Example 1] Outer diameter 270 µm and inner diameter 2
A bundle of approximately 10,000 polysulfone hollow fiber membranes (effective membrane area: 1.5 m ² ) and a stenosis portion forming member 4 g (width: 0.04 m) prepared in the same manner as shown in FIG. 6 was prepared. The stenosis forming member was mounted at the center of the hollow fiber membrane bundle using a mounting jig. As the stenosis portion forming member, 8:00
A denier 0 denier sodium acrylate and polyethylene terephthalate spun yarn were woven by braid knitting and used to be able to expand and contract in the radial direction. This hollow fiber membrane bundle is connected to a polycarbonate tapered housing having an effective length of 0. 0 and a dialysate inlet and outlet.
235m, large inner diameter 0.0371m, small inner diameter 0.0352
m) was inserted using a hollow fiber membrane bundle insertion jig.

Next, a polyurethane potting agent is injected into both ends of each hollow fiber membrane inserted into the cylindrical housing and cured to fix each hollow fiber membrane, and both ends are sliced to open each hollow fiber membrane. I let it. At both ends of the cylindrical housing,
Each of the cover with the blood inlet port and the cover with the blood outlet port was fixed in a liquid-tight manner by fusion to obtain a hemodiafiltration filter.

[Example 2] A polyester mesh (70 mesh, wire diameter 120 µm, opening 243 µm, opening ratio 45%, mesh thickness 182 µm) was wound around the same bundle of polysulfone hollow fiber membranes as in Example 1, and the mounting was cured. A stenosis portion forming member 4g (0.04 m width) similar to that in Example 1 was attached to the center of the bundle of hollow fiber membranes using a tool. This bundle of hollow fiber membranes is placed in a polycarbonate tapered housing with a dialysate inlet and an outlet having an effective length of 0.235 m, a large inner diameter of 0.0371 m, and a small inner diameter of 0.3 mm.
0352m) using a hollow fiber membrane bundle insertion jig.
Otherwise, a hemodiafiltration filter was obtained in the same manner as in Example 1.

[Comparative Example 1] The same constricted portion forming member 4g as in Example 1 was added to the same bundle of polysulfone hollow fiber membranes as in Example 1.
Was wound with the same width (0.04 m) as in Example 1. Without using the hollow fiber membrane bundle insertion jig, this bundle of hollow fiber membranes is made of a polycarbonate different-diameter housing (diameter: 0.235 m, large inner diameter: 0.0371 m,
(Small inner diameter: 0.0352 m). Others are Example 1.
A hemodiafiltration filter was obtained in the same manner as described above.

[Test Example 1] Examples 1 and 2 and Comparative Example 1
A hemodiafiltration filter was subjected to a dialysis experiment using cytochrome C based on the criteria for evaluating the performance of an artificial kidney determined by the Japan Society of Artificial Organs. For the solution on the blood side, a dialysate adjusted to a concentration of cytochrome C of 10 mg / dl was used. The filtration flow rate was 15 ml / min. Table 1 shows the results. In Examples 1 and 2 and Test Example 1, no large difference in clearance was observed. Clearance C
The formula for calculating L is shown below.

CL = (Q _Bi × C _Bi −Q _Bo × C _Bo ) / C
_Bi (However, the symbol C is a cytochrome C concentration [mg / d
l], CL represent clearance [ml / min], Q represents flow rate [ml / min], subscript B represents blood side, i represents inlet side, o represents outlet side) [Test Example 2] Example Bovine blood (Ht 30 ± 3%, TP6.0) adjusted with the hemodiafiltration filters of Comparative Examples 1 and 2 and Comparative Example 1
(± 1.0 g / dl), and the number of residual blood when circulating for 4 hours and rinsing with physiological saline for 5 minutes was evaluated. Table 1 shows the results. In Examples 1 and 2, the number of remaining blood was small, suggesting that the hollow fiber membrane was hardly damaged.

[0065]

[Table 1]

[0066]

As described above, the hollow fiber membrane type hemodiafiltration filter of the present invention has a hollow fiber membrane bundle in a cylindrical housing, and has an outer peripheral portion of the hollow fiber membrane bundle and an inner surface of the housing. A hollow fiber membrane type hemodiafiltration filter in which a constriction is formed in a part of the dialysate flow path by inserting a constriction forming member having a swelling property for the dialysate into the gap of the hollow fiber membrane has a cylindrical shape. And the constriction forming member having an inner diameter equal to or less than the outer diameter of the hollow fiber membrane bundle in a substantially dry state and capable of being radially expanded and contracted between the inner diameter and an inner diameter larger than the outer diameter of the hollow fiber membrane bundle. , A diafiltration device that is easy to manufacture and has extremely high diafiltration efficiency can be obtained.

The stenosis portion forming member mounting jig of the present invention has a cylindrical body having a smooth outer surface and an inner diameter larger than the outer diameter of the hollow fiber membrane bundle, and an outer diameter of the body. And a frusto-conical point that tapers to an outer diameter smaller than the inner diameter of the stenotic part forming member, so that the stenotic part forming member damages the hollow fiber membrane at the outer periphery of the hollow fiber membrane bundle. It can be easily mounted without using. Further, by making the body part and the pointed head separable, the stenosis part forming member and the hollow fiber membrane bundle can be inserted into the jig from the same direction. A hemodiafiltration filter can be manufactured without receiving it.

Further, the jig for inserting a hollow fiber membrane bundle according to the present invention
Since the inner diameter is larger than the outer diameter of the constriction forming member mounted on the outer peripheral portion of the hollow fiber membrane bundle having a smooth inner surface and having a tapered shape, the hollow having the constriction forming member mounted thereon The fiber membrane bundle can be easily inserted into the housing without damaging the hollow fiber membrane.

[Brief description of the drawings]

FIG. 1 is a circuit diagram showing an embodiment of an extracorporeal blood circulation circuit including a dialysis filter of the present invention.

FIG. 2 is a longitudinal sectional view showing one embodiment of the hemodiafiltration filter of the present invention.

FIG. 3 is a graph showing a pressure distribution inside a hemodiafiltration filter.

FIG. 4 is a conceptual diagram showing one embodiment of a step (step (A)) of mounting a stenotic portion forming member on the outer peripheral portion of a hollow fiber membrane bundle according to the present invention.

FIG. 5 is a conceptual diagram showing another embodiment of the step (step (A)) of mounting the stenotic portion forming member on the outer peripheral portion of the hollow fiber membrane bundle according to the present invention.

FIG. 6 is a longitudinal sectional view showing one embodiment of a stenosis portion forming member mounting jig of the present invention.

FIG. 7 is a conceptual diagram showing one embodiment of a step (step (B)) of inserting a hollow fiber membrane bundle 4 to which a stenosis portion forming member 81 according to the present invention is attached into a housing 3.

FIG. 8 is a longitudinal sectional view showing one embodiment of the hollow fiber membrane bundle insertion jig of the present invention.

[Explanation of symbols]

 DESCRIPTION OF SYMBOLS 1 ... Hemodiafiltration filter 3 ... Housing 31 ... Cylindrical main body 32, 33 ... Header 34 ... Blood inlet 35 ... Blood outlet 36 ... Dialysate inlet 37 ... Dialysate outlet 38, 39 ... Cover 4 ... Hollow fiber Membrane bundle 41 Hollow fiber membranes 51, 52 Partition wall 6 Blood flow channel 61 Blood inflow chamber 62 Blood outflow chamber 7 Dialysate flow path 71 Dialysate upstream side 72 Dialysate downstream side 8 Stenosis portion 81 ... stenosis part forming member 10 ... extracorporeal blood circulation circuit 11A ... blood removal line 11B ... blood return line 12 ... tube 13 ... pump 14 ... chamber 15 ... tube 16 ... chamber 17 ... water removal control means 18, 19 ... tube 20 ... multiple type Pump 21 ... Bypass tube 22 ... Water removal pump 9 ... Stenosis portion forming member mounting jig 91 ... Torso 92 ... Pointed head 100 ... Protective mesh 101 ... Hollow fiber membrane Insertion jig 102 ... Different diameter housing

Claims (8)

[Claims] 1. A stenosis portion forming member having a dialysate swelling property is inserted into a gap between an outer peripheral portion of the hollow fiber membrane bundle and an inner surface of the housing having a hollow fiber membrane bundle in a cylindrical housing. The hollow fiber membrane-type hemodiafiltration filter having a constriction formed in a part of the dialysate flow path, wherein the constriction forming member has a cylindrical shape and the hollow fiber is substantially dried. A hollow fiber membrane hemodiafiltration filter having an inner diameter equal to or less than the outer diameter of the membrane bundle and being expandable and contractible in the radial direction between the inner diameter and an inner diameter larger than the outer diameter of the hollow fiber membrane bundle. 2. The hollow fiber membrane hemodiafiltration device according to claim 1, wherein the constriction portion forming member has a radial expansion / contraction ratio of 1.01 to 2.00 in a substantially dry state. 3. The hollow fiber membrane type hemodiafiltration device according to claim 1, wherein the constricted portion forming member is made of a knitted fabric of a highly water-absorbent resin fiber. 4. A jig for mounting the constriction forming member on an outer peripheral portion of the hollow fiber membrane bundle of the hollow fiber membrane type hemodiafiltration filter according to claim 1, wherein the outer surface is smooth. A cylindrical body having an inner diameter larger than the outer diameter of the hollow fiber membrane bundle, and a truncated cone tapering from the outer diameter of the body to an outer diameter smaller than the inner diameter of the constriction forming member A stenosis portion forming member mounting jig comprising: a pointed head. 5. The stenosis portion forming member mounting jig according to claim 4, wherein said torso portion and said pointed head are separable. 6. A hollow fiber membrane hemodiafiltration device according to claim 1, wherein said constricted portion forming member is a jig for inserting said hollow fiber membrane bundle mounted on an outer peripheral portion into said housing. A hollow fiber having a smooth inner surface, a cylindrical shape, a tapered shape, and an inner diameter larger than an outer diameter of the constricted portion forming member mounted on an outer peripheral portion of the hollow fiber membrane bundle. Membrane bundle insertion jig. 7. A hollow fiber membrane bundle is provided in a cylindrical housing, and a stenosis portion forming member having swelling property for dialysate is inserted into a gap between an outer peripheral portion of the hollow fiber membrane bundle and an inner surface of the housing. The method for producing a hollow fiber membrane type hemodiafiltration filter in which a constriction is formed in a part of a dialysate flow path by using the hollow fiber in a (A) cylindrical shape and in a substantially dry state The inner diameter of the stenosis portion forming member which has an inner diameter equal to or less than the outer diameter of the membrane bundle and is expandable and contractible in the radial direction between the inner diameter and the inner diameter larger than the outer diameter of the hollow fiber membrane bundle is extended. (B) introducing the stenotic portion forming member to the outer peripheral portion of the hollow fiber membrane bundle by introducing the stenotic portion forming member into a predetermined position on the outer peripheral portion of the hollow fiber membrane bundle, and then contracting and restoring the inner diameter of the stenotic portion forming member; ) Inserting the hollow fiber membrane bundle with the stenosis portion forming member attached to the outer peripheral portion into the housing A method for producing a hollow fiber membrane-type hemodiafiltration filter, comprising the step of: 8. The hollow fiber membrane blood according to claim 7, wherein, in the step (A), the outer peripheral portion of the hollow fiber membrane bundle is covered with a protective mesh, and then the stenotic portion forming member is introduced. A method for manufacturing a dialysis filter.