JP3284028B2 - Dialysis machine - Google Patents

Description

DETAILED DESCRIPTION OF THE INVENTION

[0001]

[0001] The present invention relates to a dialyzer. More specifically, the present invention relates to a hollow fiber membrane dialyzer used in blood purification therapy, for example.

[0002]

2. Description of the Related Art In blood purification therapy, methods for replacing a large amount of liquid between blood and dialysate include hemodiafiltration and online hemodiafiltration (Henderson, LW et al:
Trans.Am.Soc.Artif.Intern.Organs 24 465-467 (197
8)) and push and pull hemodiafiltration (Usuda,
M. et al: Trans.Am.Soc.Artif.Intern.Organs 28 24-27
(1982)).

[0003] In the hemodiafiltration method, a large amount of replacement liquid requires a large amount of a pyrogen-free replacement liquid in addition to the dialysate. However, preparation of this replacement liquid requires time and effort, and Since the replacement liquid is expensive, the cost is high.

On the other hand, the above-mentioned drawbacks do not occur in the on-line hemodiafiltration method and the push-and-pull hemodiafiltration method because a dialysate is used as a replacement liquid. However, the online hemodiafiltration method requires a special device for removing a part of the dialysate from the dialysate circuit and supplying it to the extracorporeal blood circulation circuit. In order to change the direction of ultrafiltration of blood and dialysate with time, a dialysate supply / recovery line having a forward / reverse pump and a dialysate reservoir is provided in the dialysate circuit. It is necessary to provide a branch. Therefore, in any case, it is necessary to separately add a dedicated device, and there is a disadvantage that the circuit configuration becomes complicated.

On the other hand, a large number of capillaries are stored in a concentrated state by being connected to a blood circulation port inside the cylindrical body, and the inner diameter of the cylindrical body is smaller at the approximate center of the cylindrical body than at other portions. There is known a dialyzer (Japanese Utility Model Publication No. Sho 56-22911) in which a capillary is narrowed and a focused state of a capillary in a cylinder is made denser at a portion where the inner diameter of the cylinder is narrowed to a smaller diameter than at other portions.

However, the fact that the inner diameter of the cylindrical body is reduced as described above means that the outer peripheral portion of the bundle of the hollow fiber membrane is pressed by the ridge of the hard cylindrical body constituting the reduced diameter portion. Therefore, the hollow fiber membrane near the outer periphery of the bundle is distorted, and the filling rate does not change at the core of the bundle, that is,
There is a disadvantage that the gap between the hollow fiber membranes does not change.

[0007] In addition, since it is difficult to insert the bundle of hollow fiber membranes into the cylindrical body due to the reduced diameter portion, the assembling operation requires a long time, resulting in an increase in cost.

[0008]

Accordingly, an object of the present invention is to provide a new dialyzer.

Another object of the present invention is to provide a dialyzer capable of performing hemodialysis with a large amount of liquid replacement with a simple configuration without requiring a dedicated device.

Still another object of the present invention is to provide a dialyzer which is easy to assemble and therefore easy to manufacture.

[0011]

SUMMARY OF THE INVENTION An object of the present invention is to provide a cylindrical housing having a bundle of hollow fiber membranes, and a first flow path and a second flow path separated by the hollow fiber membrane. A dialyzer for performing dialysis and ultrafiltration between a bodily fluid flowing through the first flow path through the hollow fiber membrane and a dialysate flowing through the second flow path, wherein the dialysate has a swelling property. A stenosis portion is provided in the middle of the second flow path by using a material having a dialysis fluid having a pressure difference between the dialysis fluid upstream and downstream of the stenosis portion. Achieved.

In the present invention, the pressure of the dialysate flowing through the second flow path is higher than the pressure of the body fluid flowing through the first flow path upstream of the dialysate in the constriction, and On the downstream side of the dialysate, the dialyzer is configured so that the pressure of the dialysate flowing through the second flow path is set lower than the pressure of the body fluid flowing through the first flow path. The present invention is the dialyzer, wherein the stenosis portion is formed by interposing a stenosis portion forming member between an outer peripheral portion of the hollow fiber membrane bundle and an inner surface of the housing. The present invention is the dialyzer, wherein the stenosis portion is formed by inserting a stenosis portion forming member into a gap between the hollow fiber membranes. The present invention is also the dialyzer wherein the material having swelling property of the dialysate has a dialysate content of 10% or more. The present invention is the dialyzer further comprising water removal control means for adjusting a water removal amount from a body fluid flowing through the first flow path. The present invention is the dialyzer, wherein the stenosis forming member is swellable with a dialysate. The present invention is also the dialyzer, wherein the filling rate of the hollow fiber membrane in the constricted portion is 105 to 200% of the filling ratio in the portion other than the constricted portion.

[0013]

DETAILED DESCRIPTION OF THE PREFERRED EMBODIMENTS A dialyzer according to the present invention will be described below with reference to the drawings.

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

The blood removal line 11A comprises a tube 12, a blood supply pump 13 and a defoaming chamber 14 installed in the tube 12, and one end of the blood removal line 11A is connected to a needle tube. And the other end is connected to the blood inlet 34 of the dialyzer 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 dialyzer 1,
A tube 19 having one end connected to the dialysate outlet 37 of the dialyzer 1, a double pump 20 for feeding dialysate into the tubes 18 and 19 at the same flow rate and in opposite directions, respectively;
Tubes 1 at both ends to bypass double pump 20
9, 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 dual 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 once stored in the chamber 14 and defoamed, and then flows into the dialyzer 1 from the blood inlet 34. . The blood flowing out from the blood outlet 35 flows through the blood return line 11B, is stored in the chamber 16 once, 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 is introduced into the housing 3 of the dialysate 1 through the dialysate inlet 36. As described later, dialysis and filtration are performed with the blood through the hollow fiber membranes 41 in the inside of the filter 3, and the dialysis solution is discharged from the dialysate outlet 37.
The discharged dialysate is transferred via the tube 19 and collected. At this time, when the water removal pump 22 is operated at a predetermined rotation speed, the amount of dialysate supplied to the dialyzer 1 and the amount of dialysate recovered from the dialysate 1 are reduced by the amount corresponding to the discharge amount of the water removal pump 22. This amount 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 dialyzer 1 of the present invention. As shown in the figure, the dialyzer 1 has a cylindrical main body 31 and headers 32 and 3 which are connected and fixed to both ends thereof in a liquid-tight manner by covers 38 and 39, respectively.
3 and a housing 3. Header 32
A blood inflow port 34 protrudes from the top of the header 33, and a blood outflow port 35 protrudes from the top of the header 33. Also, on the side of the cylindrical body 31 on the header 33 side,
A dialysate inflow port 36 is formed so as to protrude, and a dialysate outflow port 37 is formed so as to protrude from the side of the cylindrical body 31 on the header 32 side.

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 7
The number of hollow fiber membranes is about 0000, and the hollow fiber membranes 41 are arranged in parallel and separated from each other along the longitudinal direction of the housing 3.

Examples of the hollow fiber membrane 41 include regenerated cellulose, cellulose derivatives, polyolefins such as polymethyl methacrylate, 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 100 cm 2 to 6.0 m 2.
Degree, more preferably about 0.2 to 2.0 m2. Both ends of each hollow fiber membrane 41 are respectively connected to the cylindrical main body 3.
At one end, the hollow fiber membrane 41 is liquid-tightly supported and fixed by the partition walls 51 and 52 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 wall 51, and a blood outflow chamber 62 is formed in a space surrounded by the header 33 and the partition wall 52. A first flow path (blood flow path) 6 through which blood flows is formed in the inner cavity (hollow portion) of each hollow fiber membrane 41, and both ends of the first flow path 6 are respectively connected to the blood. Inflow chamber 61
And the blood outflow chamber 62.

In the space surrounded by the cylindrical 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 body 31 and the adjacent hollow fiber In the gap between the membranes 41, a second flow path (dialysate flow path) 7 through which the dialysate flows is formed. That is, the first flow path 6 and the second flow path 7 are separated by each hollow fiber membrane 41. The upstream side of the second flow path 7 communicates with the dialysate inlet 36, and the downstream side communicates with the dialysate outlet 37.

With such a configuration, the blood that has flowed into the blood inflow chamber 61 from the blood inflow port 34 flows through the first flow path 6, is collected in the blood outflow chamber 62, and flows out of the blood outflow port 35. On the other hand, the dialysate flowing from the dialysate inlet 36 flows through the second 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 second flow path 7, there is provided a constriction 8 having a reduced cross-sectional area of the flow path, and a dialysate upstream side 71 and a dialysate downstream side 72 from the constriction 8. It is configured to generate a desired difference in the pressure of the dialysate flowing through the second flow path 7.

FIG. 3 is a graph showing the pressure distribution of the blood flowing through the first flow path 6 and the dialysate flowing through the second flow path 7. As shown in the figure, the pressure of the blood flowing through the first flow path 6 decreases almost linearly from upstream to downstream, while the pressure of the dialysate flowing through the second flow path 7 is ,
On the upstream side 71 of the dialysis fluid from the stenosis portion 8, the pressure becomes higher than the blood pressure in the corresponding portion of the first flow path 6,
On the downstream side 72 of the dialysate, the pressure becomes lower than the blood pressure in the corresponding portion of the first flow path 6.

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

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 dialyzer 1 without using a dedicated device or the like separately provided.

In this case, the ultrafiltration rate (pure water filtration coefficient) in the dialyzer 1 is preferably not less than 20 ml / m 2 · hr · mmHg at a water flow rate of 200 ml / min.
More preferably, the pressure is 30 ml / m 2 · hr · mmHg or more when the flow rate is 00 ml / min.

The constricted portion 8 is formed, for example, by inserting a constricted portion forming member 81 between the outer periphery of the bundle 4 of the hollow fiber membranes 41 and the inner surface of the cylindrical body 31 of the housing 3. Alternatively, it is formed by inserting (filling) a constricted portion forming member 81 into a gap between the hollow fiber membranes 41.
Moreover, you may use both of these together.

When the constricted portion forming member 81 is interposed in the gap between the hollow fiber membranes 41, 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 distribution of the bundle 4).
May be dense at the center and rough at the outer periphery, or vice versa.

As the constriction forming member 81 that can be used in these cases, for example, a (crosslinked) polyacrylate or a (crosslinked) acrylic acid-acrylate copolymer (for example, AQUALIC manufactured by Nippon Shokubai Co., Ltd., ARASORB manufactured by Arakawa Chemical Industry Co., Ltd., WO manufactured by Kao Corporation
NDERGEL, AQUAKE manufactured by Iron and Steel Chemical Industry Co., Ltd.
EP, manufactured by Dow Chemical Company. W. A.
L. PARMA manufactured by National Starch
SORB, Stockausen FAVOR, etc.),
Isobutylene-maleic acid copolymer (for example, Kuraray
KI Gel manufactured by Isobutin Co., Ltd., a starch-acrylic acid graft copolymer or a saponified product thereof (for example,
SUNWET, Grain P manufactured by Sanyo Chemical Industries, Ltd.
processing GPC, Henkel SG
P, Magic W manufactured by Super Absorbent
after Gel, LYOGEL manufactured by Uniever
Etc.), saponified vinyl acetate-acrylate copolymer (for example, SUMIKAGE manufactured by Sumitomo Chemical Co., Ltd.)
L), vinyl acetate-unsaturated dicarboxylic acid copolymer (for example, GP manufactured by Nippon Synthetic Chemical Industry), carboxymethylcellulose (for example, Buckeye Cellulose)
CLD, Enka's AKUCELL, etc.), and composite fibers of an acrylonitrile fiber inner core and an acrylate copolymer outer layer (for example, LANSEAL manufactured by Toyobo Co., Ltd.).

Among these, a composite fiber of an inner core of acrylonitrile fiber, which is a super absorbent fiber, and an outer layer of an acrylate copolymer is most preferable. The superabsorbent fiber is disclosed in Toyobo Co., Ltd. catalog "Lanseal F superabsorbent fiber".

When a resin is used as the constricted portion forming member 81, the constricted portion 8 is formed by partially filling the resin between the outer periphery of the bundle 4 and the inner surface of the cylindrical main body 31 and the gap between the hollow fiber membranes 41. When fibers are used as the constricted portion forming member 81, the constricted portions 8 can be formed by winding the fibers or the aggregate thereof around the outer periphery of the bundle 4 or knitting the fibers or the aggregates in the gaps of the hollow fiber membranes 41. Can be formed. The fibers may be further impregnated with a resin and fixed.

Further, the bundle 4 may be divided into a plurality of parts, and the stenotic part forming member 81 may be provided for each of the divided bundles in the same manner as described above to form the stenotic part 8.

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

The stenosis portion forming member 81 includes:
For reasons such as production, it is preferable to use a material having a swelling property of a dialysate (dialysis fluid content), and the dialysate content of these materials is 10% by weight or more, preferably 10 to 2,6.
00% by weight, more preferably 50 to 2,000% by weight. It is the dialysate, not the water, that is absorbed by the dialysate swellable material in the dialyzer. Various types of dialysate are known. Different types of dialysate have different rates of dialysate. Although the dialysate content of the dialysate swellable material is affected by the ionic strength of the solution, the difference between the monovalent and divalent ion concentrations of the commonly used dialysate is so small that the dialysate is replaced by the dialysate. The difference in the rate of weight increase is also small.

The composition of a typical dialysate is shown in Table 1.

The relationship between the amount of the dialysate swellable material used and the dialysate content is expressed by the following equation.

[0048]

(Equation 1)

Where ρ is the density of the dialysate, Dh is the inner diameter of the housing, D0 is the outer diameter of the hollow fiber membrane, N is the number of hollow fiber membranes, ι is the length of the constriction, H is the dialysate-containing rate [(M'-m ') / M'] × 1
00, M 'is the weight of the dialysate swelling material at the time of the dialysate, m'
Is the weight of the dialysate swellable material when dried, and m is the weight of the dialysate swellable material.

The relationship between the length ι of the stenosis part and the effective length L of the module is as follows.

Ι / L ≦ Also, the method of weaving and applying the dialysate swellable material is as follows:
It is as follows. (A) Method of knitting dialysate swellable material The hollow fiber membrane is a warp or a weft of about 1 to several tens bundles, the dialysate swellable fibers are a weft or a warp, and the center of the hollow fiber membrane has a certain width ( (A length of 1/3 or less of the effective length of the hollow fiber membrane). One end of the dialysate swellable fiber in a state where the central part of the hollow fiber membrane is woven in an interdigitated shape is wound inside, and a bundle of hollow fiber membranes is obtained by winding the interdigitated material.

(B) Application method of swelling resin The hollow fiber membrane is made into a bundle of about 1 to several tens, and the bundle of the hollow fiber membranes is expanded in one direction, and a certain width (the hollow fiber membrane) at the center of the hollow fiber membrane is obtained. The dialysate swellable resin is applied to a length less than 1/3 of the effective length). With the dialysate swellable resin dried or cured, one end of the dialysate swellable resin is wrapped around the inside, and the blinds are wrapped around to obtain a bundle of hollow fiber membranes.

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 100 mmHg, and 30 to 70 mmHg.
About mmHg is more preferable. As a result, the large-volume replacement of blood and dialysate as described above is efficiently performed. In order to obtain such a pressure difference, the narrowed portion forming member 81 of the narrowed portion 8 is formed.
The material, arrangement density, installation area, etc. of the above are appropriately adjusted.

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

In the present invention, the configuration, forming method, characteristics, and the like of the stenosis portion 8 are not limited to those described above, and a difference in dialysate pressure occurs between the dialysis solution upstream side and the dialysis solution downstream side of the stenosis portion. Anything may be used as long as it is such.

In the above embodiment, the blood is processed by the dialyzer 1, but the body fluid to be processed may be a blood component such as plasma.

Hereinafter, the dialyzer of the present invention will be described in detail with reference to examples.

[0058]

Example 1 A bundle of about 5,000 polysulfone hollow fiber membranes having an outer diameter of 280 μm and an inner diameter of 200 μm (effective membrane area 0.5
m2), and a dialysate-soluble fiber (LAN manufactured by Toyobo Co., Ltd.) composed of a composite fiber of an acrylonitrile fiber inner layer and an acrylate copolymer outer layer is provided on the outer periphery of the central portion in the longitudinal direction.
SEAL F) (dialysis solution ratio 1,963%) with length 2c
and wound 2 g over m. Then, the bundle of hollow fiber membranes is placed in a polycarbonate cylindrical body having an effective length of 175 mm and an inner diameter of 30 mm and having a dialysate inlet and an outlet, and a gap between the dialysate fluid fiber and the cylindrical body. Inserted so as not to occur.

Next, a polyurethane potting agent is injected into both ends of each hollow fiber membrane inserted into the cylindrical main body and cured to fix each hollow fiber membrane, and both ends are sliced to open each hollow fiber membrane. I let it. A cover with a blood inlet and a cover with a blood outlet were attached to both ends of the cylindrical body, respectively, and these were fixed in a liquid-tight manner by fusion to obtain a dialyzer having a structure shown in FIG.

[0060]

Comparative Example 1 A bundle of about 5,000 polysulfone hollow fiber membranes (effective membrane area: 0.5 m2) similar to that of Example 1 was inserted into a cylindrical body having a dialysate inlet and an outlet. A potting agent was injected into both ends of each hollow fiber membrane inserted into the main body, and cured to fix each hollow fiber membrane. Both ends were sliced to open each hollow fiber membrane. A cover with a blood inlet and a cover with a blood outlet were respectively attached to both ends of the cylindrical main body, and these were fixed in a liquid-tight manner by fusion to obtain a dialyzer.

The effective length and the inner diameter of the cylindrical body are each 1
75 mm and 30 mm.

[0062]

Example 2 A bundle of approximately 11,000 polysulfone hollow fiber membranes (effective membrane area 1.6 m2) similar to that of Example 1 was prepared.
2 g of a dialysis fluid fiber (dialysis solution content: 1,963%) similar to that of Example 1 was wound around the outer periphery of the central portion in the longitudinal direction over a length of 2 cm by 2 cm. The dialysis fluid was inserted into the cylindrical body having an inlet and an outlet so that no gap was formed between the dialysate and the inner surface of the cylindrical body.

Next, a potting agent is injected into both ends of each hollow fiber membrane inserted into the cylindrical main body and cured to fix each hollow fiber membrane, and both ends are sliced to open each hollow fiber membrane. Was. A cover with a blood inlet and a cover with a blood outlet were attached to both ends of the cylindrical body, respectively, and these were fixed in a liquid-tight manner by fusion to obtain a dialyzer having a structure shown in FIG.

The effective length and the inner diameter of the cylindrical main body were 235 mm and 39 mm, respectively.

[0065]

[Comparative Example 2] Known literature (Kenichi Murayama et al .: Kidney and Dialysis Vo)
l. 34 Separate volume high performance membrane '93.
p117 (1993)), the results of online dialysis therapy (pre-dilution method) were cited. Table 2 shows the results. The effective membrane area of the dialyzer was the same as in Example 2.
6m2.

The molecular weight of β2 microglobulin as the solute removed in Comparative Example 2 was 11,800, which was close to the molecular weight of cytochrome C of 12,400. Is considered to indicate the clearance value.

[0067]

Embodiment 3 A bundle of about 4,000 polyamide hollow fiber membranes having an outer diameter of 335 μm and an inner diameter of 215 μm (effective membrane area 0.4 m
2) is prepared, and 2 g of the same hemodialysable liquid fiber (dialysis liquid content: 1,963%) as in Example 1 is wound around 2 cm over the length of 2 cm on the outer periphery of the central portion in the longitudinal direction. The dialysis fluid was inserted into a tubular body having an inlet and an outlet so that no gap was formed between the dialysate fiber and the inner surface of the tubular body.

Next, a potting agent is injected into both ends of each hollow fiber membrane inserted into the cylindrical main body and cured to fix each hollow fiber membrane, and both ends are sliced to open each hollow fiber membrane. Was. A cover with a blood inlet and a cover with a blood outlet were attached to both ends of the cylindrical body, respectively, and these were fixed in a liquid-tight manner by fusion to obtain a dialyzer having a structure shown in FIG.

The effective length and the inner diameter of the cylindrical main body were 175 mm and 30 mm, respectively.

[0070]

Comparative Example 3 A bundle of about 4,000 polyamide hollow fiber membranes (effective membrane area: 0.4 m2) was inserted into a cylindrical body having a dialysate inlet and an outlet, and then inserted into the cylindrical body. A potting agent was injected into both ends of each hollow fiber membrane thus cured, and each hollow fiber membrane was fixed by fixing, and both ends were sliced to open each hollow fiber membrane. At each end of the tubular body,
A cover with a blood inlet and a cover with a blood outlet were attached, and these were fixed in a liquid-tight manner by fusion to obtain a dialyzer.

The effective length and the inner diameter of the cylindrical body are each 1
75 mm and 30 mm.

[0072]

Example 4 A bundle of about 6,000 polyamide hollow fiber membranes (effective membrane area 0.7 m2) similar to that of Example 3 was prepared, and a cellulose resin (dialysis solution ratio of 50 %) Over 1.5 cm width and dried,
This bundle of hollow fiber membranes was inserted into a cylindrical body having a dialysate inlet and an outlet.

Next, a potting agent is injected into both ends of each hollow fiber membrane inserted into the cylindrical main body and cured to fix each hollow fiber membrane, and both ends are sliced to open each hollow fiber membrane. Was. A cover with a blood inlet and a cover with a blood outlet were attached to both ends of the cylindrical body, respectively, and these were fixed in a liquid-tight manner by fusion to obtain a dialyzer having a structure shown in FIG.

The effective length and the inner diameter of the cylindrical main body were 175 mm and 30 mm, respectively.

[0075]

Comparative Example 4 A bundle of about 6,000 polyamide hollow fiber membranes (effective membrane area: 0.7 m2) was inserted into a cylindrical body having a dialysate inlet and an outlet, and then inserted into the cylindrical body. A potting agent was injected into both ends of each hollow fiber membrane thus cured, and each hollow fiber membrane was fixed by fixing, and both ends were sliced to open each hollow fiber membrane. At each end of the tubular body,
A cover with a blood inlet and a cover with a blood outlet were attached, and these were fixed in a liquid-tight manner by fusion to obtain a dialyzer.

The effective length and the inner diameter of the cylindrical main body were 175 mm and 30 mm, respectively.

[0077]

Example 5 A bundle of about 4,500 polyacrylonitrile hollow fiber membranes (effective membrane area 0.6 m2) having an outer diameter of 305 μm and an inner diameter of 245 μm was prepared, and a urethane resin (dialysis solution) (A ratio of 10%) in a layered form, and 3 g of the same urethane resin was partially filled into the gap between the hollow fiber membranes over 1 cm in the inner portion. This bundle of hollow fiber membranes was inserted into a tubular body with a dialysate inlet and an outlet so that the gap between the urethane resin layer and the inner surface of the tubular body was reduced.

Next, a potting agent is injected into both ends of each hollow fiber membrane inserted into the cylindrical main body and cured to fix each hollow fiber membrane, and both ends are sliced to open each hollow fiber membrane. Was. A cover with a blood inlet and a cover with a blood outlet were attached to both ends of the cylindrical body, respectively, and these were fixed in a liquid-tight manner by fusion to obtain a dialyzer having a structure shown in FIG.

The effective length and the inner diameter of the cylindrical main body were 175 mm and 30 mm, respectively.

[0080]

Comparative Example 5 A bundle of about 4,500 polyacrylonitrile hollow fiber membranes (effective membrane area: 0.6 mm) similar to that in Example 5 was prepared.
Inserting into the cylindrical body with dialysate inlet and outlet, then injecting potting agent at both ends of each hollow fiber membrane inserted into the cylindrical body, curing and fixing each hollow fiber membrane, Both ends were sliced to open each hollow fiber membrane. A cover with a blood inlet and a cover with a blood outlet were respectively attached to both ends of the cylindrical main body, and these were fixed in a liquid-tight manner by fusion to obtain a dialyzer.

The effective length and the inner diameter of the cylindrical main body were 175 mm and 30 mm, respectively.

[0082]

Example 6 The dialyzers of Examples 1 to 5 and Comparative Examples 1 and 3 to 5 were respectively incorporated into the extracorporeal blood circulation circuit shown in FIG. 1, and cytochrome C was evaluated in accordance with the artificial kidney performance evaluation standard defined by the Japanese Society of Artificial Organs. (Molecular weight = 12,400)
Dialysis experiments were performed in an in vitro system.

As the solution on the blood side, a dialysate solution containing 40% glycerin was used. Further, the water removal amount (filtration flow rate) was set to 10 ml / min. Further, as a result of the flow of the dialysate, the liquid-absorbing fiber or the dialysate-swellable material swelled, and a constriction was formed in the dialysate-liquid wrapping portion or the dialysate-swellable material application portion. Table 2 shows the experimental results.

[0084]

[Table 1]

[0085]

[Table 2]

As shown in Table 2, when the dialyzer of Example 1 was used, the clearance value of cytochrome C (the amount of the blood side solution in which the concentration of cytochrome C became 0 in 200 ml of the blood side solution) was a comparative example. 11ml / mim compared to 1
High and significant performance improvements were noted.

As shown in Table 2, when the dialyzer of Example 2 was used, the clearance value was higher than that of Comparative Example 2. Therefore, according to the dialyzer of Example 2, the pre-dilution was required. It was confirmed that dialysis therapy with a high removal performance was possible only by controlling the water removal by the normal dialysis method without using a dedicated device.

As shown in Table 2, when the dialyzer of Example 3 was used, the clearance value of cytochrome C was lower than that of Comparative Example 3.
4 times or more as compared with that of the above, and a remarkable improvement in performance was recognized.

As shown in Table 2, when the dialyzer of Example 4 was used, the clearance value of cytochrome C was lower than that of Comparative Example 4.
This was 4 ml / min higher than that of No. 3 and improvement in performance was recognized.

As shown in Table 2, when the dialyzer of Example 5 was used, the clearance value of cytochrome C was lower than that of Comparative Example 5.
12 ml / min higher than that of No., and a remarkable improvement in performance was recognized.

[0091]

Example 7 Approximately 6,000 polyamide membranes, outer diameter of hollow fiber membrane 335 μm, membrane area 0.7 m 2, UFR = 62.9 ml / m
2 g of a dialysate-swelling fiber having the same dialysis fluid as in Example 1 (dialysis fluid content: 1,953%) was wound around 2 cm over 2 cm over a length of 2 cm, and a dialysate flow having an effective length of 175 mm and an inner diameter of 32 mm was wound. It was inserted into a tubular body with inlet and outlet.

Next, a potting material is injected into both ends of each hollow fiber membrane inserted into the cylindrical main body, cured to fix each hollow fiber membrane, and both ends are sliced to open each hollow fiber membrane. I let it. A cover with a blood inlet and a cover with a blood outlet were attached to both ends of the cylindrical main body, respectively, and these were fixed in a liquid-tight manner by fusion to obtain a dialyzer shown in FIG.

[0093]

Comparative Example 6 The same hollow fiber membrane as in Example 7 was used, and a cylindrical body having a dialysate inlet and an outlet having a constriction in the center (inner diameter of the constriction 29.5 mm, constriction width 2 cm, constriction 2 cm) 32mm inside diameter other than the part, 175mm)
And a dialysate was obtained in the same manner as in Example 7.

[0094]

Example 8 The dialyzers of Example 7 and Comparative Example 6 were incorporated into the extracorporeal blood circulation circuit shown in FIG. 1, respectively, and β2-microglobulin (β2-MG) was used in accordance with the artificial kidney performance evaluation standard set by the Japanese Society of Artificial Organs. , Molecular weight 11,800) using an in vitro system.

As the solution on the blood side, human serum (total protein concentration 6.5 g / dl) was used. Further, the water removal amount (filtration flow rate) was set to 10 ml / min. Table 3 shows the results.

[0096]

[Table 3]

[0097]

Embodiment 9 The same polysulfone membrane as in Embodiment 1 was used.
0000 pieces, hollow fiber membrane outer diameter 280 μm, membrane area 1.5
m2, UFR = 46.0 ml / m2 · hr · mmHg, and the same dialysate-swelling dialysate-swelling fiber as in Example 1 (dialysate content: 1,9
53%) and 2 g over 2 cm, effective length 2
It was inserted into a cylindrical body having a diameter of 35 mm and an inner diameter of 32 mm and having a dialysate inlet and an outlet.

Next, a potting material is injected into both ends of each hollow fiber membrane inserted into the cylindrical main body, and the potting material is cured to fix each hollow fiber membrane, and both ends are sliced to open each hollow fiber membrane. I let it. A cover with a blood inlet and a cover with a blood outlet were attached to both ends of the cylindrical main body, respectively, and these were fixed in a liquid-tight manner by fusion to obtain a dialyzer shown in FIG.

Two dialyzers of Example 9 were prepared. One was incorporated into the countercurrent extracorporeal blood circulation circuit shown in FIG. 1, and the other was incorporated into the extracorporeal blood circulation circuit with dialysate as cocurrent, According to the artificial kidney performance evaluation criteria specified in
2-microglobulin (β2-MG, molecular weight 11,80
The dialysis experiment according to 0) was performed in an in vitro system.

[0100] The solution on the blood side was heparinized bovine blood (hematocrit 30%, total protein concentration 6.5).
g / dl in physiological saline, and β2-MG added). Further, the water removal amount (filtration flow rate) was set to 10 ml / min. Table 4 shows the results.

[0101]

[Table 4]

Approximately the same result was obtained in the co-current flow.

[0103]

As described above, according to the dialyzer of the present invention, a stenosis portion is provided in the middle of the second flow path through which the dialysate flows, and the stenosis portion is provided between the upstream side and the downstream side of the dialysate. With a configuration in which a predetermined difference is generated in the dialysate pressure, a large amount of fluid can be exchanged between the body fluid to be processed and the dialysate with a single dialyzer without using a dedicated device or the like separately provided. Substitution can be performed, and the performance of dialysis and filtration is improved.

In particular, the pressure of the dialysate flowing through the second flow path is higher than the pressure of the body fluid flowing through the first flow path on the upstream side of the dialysate from the stenosis, and the pressure of the dialysate is lower on the downstream side of the dialysate than the stenosis. When the pressure of the dialysate flowing through the second flow path is set to be lower than the pressure of the bodily fluid flowing through the first flow path, the dialysate and the dialysis fluid are connected before and after the stenosis in one dialyzer. Since filtration from one side of the liquid to the other and filtration in the reverse direction are performed, the large amount of liquid replacement is performed efficiently, and dialysis and filtration performance are significantly improved.

Further, when the constricted portion is formed by inserting a constricted portion forming member between the outer periphery of the bundle of hollow fiber membranes and the inner surface of the housing or in the gap between the hollow fiber membranes, the formation is easy. In addition, it is easy to stably obtain the above pressure characteristics.

When the stenosis portion forming member is made of a material having a dialysate swelling property, particularly a material having a dialysate content of 10% or more, the bundle of hollow fiber membranes can be easily inserted into the housing. When the dialysate flows during use, the stenotic portion swells and can be brought into close contact with the housing.

When the water removal control means for adjusting the water removal amount from the body fluid flowing through the first flow path is combined, the above-mentioned pressure characteristics and the water removal amount can be appropriately set according to the encouragement. .

[Brief description of the drawings]

FIG. 1 is a circuit configuration diagram showing a configuration example of a blood extracorporeal circuit including a dialyzer of the present invention.

FIG. 2 is a longitudinal sectional view showing one embodiment of the dialyzer according to the present invention.

FIG. 3 is a graph showing a pressure distribution inside a dialyzer.

[Explanation of symbols]

 DESCRIPTION OF SYMBOLS 1 Dialyzer 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 Bundle 41 Hollow fiber membrane 51, 52 Partition wall 6 1st flow Path 61 Blood inflow chamber 62 Blood outflow chamber 7 Second flow path 71 Dialysate upstream side 72 Dialysate downstream side 8 Stenosis 10 Blood extracorporeal 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 Double pump 21 Bypass tube 22 Water removal pump

──────────────────────────────────────────────────続 き Continuation of the front page (56) References JP-A-52-138071 (JP, A) JP-A-49-110053 (JP, U) JP-A-62-119943 (JP, U) JP-A-51-2 7443 (JP, U) (58) Field surveyed (Int. Cl. ⁷ , DB name) B01D 63/02 A61M 1/14 555 A61M 1/18 510

Claims (8)

(57) [Claims] 1. A tubular housing having a bundle of hollow fiber membranes, a first flow path and a second flow path separated by the hollow fiber membrane, and A dialyzer that performs dialysis and ultrafiltration between a bodily fluid flowing through a first flow path and a dialysate flowing through the second flow path, wherein the second dialysate is formed using a material having a dialysate swelling property. A stenosis portion is provided in the middle of the flow path, and a pressure difference is generated between the dialysis fluid upstream and downstream of the stenosis portion. 2. The pressure of the dialysate flowing through the second flow path is higher than the pressure of the body fluid flowing through the first flow path, and the pressure of the dialysate flowing through the first flow path is downstream of the dialysate. 2. The device according to claim 1, wherein on the side, the pressure of the dialysate flowing through the second flow path is set to be lower than the pressure of the body fluid flowing through the first flow path. Dialyzer. 3. The narrowed portion is formed by inserting a narrowed portion forming member between an outer peripheral portion of the bundle of hollow fiber membranes and an inner surface of the housing. 2. The dialyzer according to claim 1. 4. The dialyzer according to claim 1, wherein the constriction is formed by inserting a constriction forming member into a gap between the hollow fiber membranes. 5. The dialyzer according to claim 1, wherein the dialysate swelling material has a dialysate content of 10% or more. 6. The dialyzer according to claim 1, further comprising water removal control means for adjusting a water removal amount from a body fluid flowing through the first flow path. 7. The dialyzer according to claim 3, wherein the stenosis portion forming member is swellable with a dialysate. 8. The dialyzer according to claim 1, wherein the filling rate of the hollow fiber membrane in the constricted portion is 105 to 200% of the filling ratio in the portion other than the constricted portion.