JP6908394B2 - Hollow fiber membrane module and its manufacturing method - Google Patents

Description

The present invention relates to a hollow fiber membrane module and a method for manufacturing the same.

Conventionally, a hollow fiber membrane module has been used for artificial dialysis, blood purification, and the like. In the hollow fiber membrane module, the hollow fiber membrane bundle is housed in a tubular case called a housing. Both ends of the hollow fiber membrane bundle are fixed by an adhesive as a sealing portion that is fixed to the inner wall of the case.

In the hollow fiber membrane module described in Patent Document 1, the hollow fiber membrane bundle is housed inside a tubular housing as a case. Both ends of the housing are covered with two caps. Then, a first introduction port and a first discharge port are formed so as to protrude along the radial direction of the housing on each outer peripheral surface near both ends of the housing. Blood, which is an outer liquid, is introduced into the housing from the first inlet, and the blood flows outside the hollow fiber membrane and is discharged from the first outlet.

A second inlet and a second outlet are formed in each of the two caps, and a dialysate, which is an inner liquid, is introduced into the housing from the second inlet, passes through the inside of the hollow fiber membrane, and is discharged second. It is discharged from the outlet. As a result, waste products in the blood flowing outside the hollow fiber membrane are said to be dialyzed into the dialysate inside through the hollow fiber membrane.

Japanese Unexamined Patent Publication No. 2007-14666

In the hollow fiber membrane module described in Patent Document 1, blood flows outside the hollow fiber membrane. Blood, on the other hand, can coagulate with prolonged stagnation. In the configuration described in Patent Document 1, the flow of dialysate and blood in the housing of the hollow fiber membrane module and the flow of blood in the blood inlet and blood outlet are substantially orthogonal to each other. As a result, the blood that has flowed into the housing from the blood inlet sharply bends and flows, and then sharply bends from the inside of the housing and is discharged to the outside from the blood discharge port. This makes it difficult to achieve uniform blood flow within the hollow fiber membrane module, which can lead to partial blood stagnation. At this time, it is desired to continuously use the hollow fiber membrane module for a long time depending on the medical condition of the patient. In the configuration described in Patent Document 1, blood coagulation may occur due to long-term use, and therefore there is room for improvement in terms of suppressing long-term blood coagulation. In the above, the case where the outer liquid is blood has been described, but the same inconvenience may occur when a liquid having coagulability, which has the property of coagulating with long-term stagnation, is used other than blood.

An object of the present invention is to realize a hollow fiber membrane module capable of suppressing coagulation of a coagulating outer liquid for a long time and a method for producing the same.

The hollow fiber membrane module according to the present invention is formed of a tubular case and a plurality of hollow fiber membranes, is housed in the case, and has two sealing portions fixed to both ends of the inner wall of the case. A hollow fiber membrane bundle fixed at both ends to the case, caps attached to both ends of the case, and inner liquid ports provided on the caps and communicated with each other inside the plurality of hollow fiber membranes. One end is coupled to each of the two sealing portions, and the space inside the case where the hollow fiber membrane bundle is arranged sandwiched between the two sealing portions and outside the plurality of hollow fiber membranes. The outer liquid port comprises an outer liquid port arranged along the axial direction such that one end is open to the outside and the other end is led out through the cap on the corresponding side. , The two sealing portions are arranged on the central axis of the case and open in the central axis direction with respect to the internal space of the case. It is a concave surface that becomes shallower toward the outside in the direction, and blood is introduced from the outer liquid port of one of the two outer liquid ports, passes through the inner space of the case, and is discharged from the other outer liquid port. The dialysate is introduced from one of the two inner liquid ports, passes through the inside of the plurality of hollow fiber membranes, and is discharged from the other inner liquid port .

Further, in the method for manufacturing a hollow fiber membrane module according to the present invention, the hollow fiber membrane bundle is arranged in the case, and port members constituting the outer liquid port are arranged at both ends of the hollow fiber membrane bundle. The hollow fiber membrane bundle arrangement step, the cap attachment step for attaching the adhesive caps to both ends of the case, and the axial direction of the case are aligned in the horizontal direction, and the directions are orthogonal to the axial direction of the case. While rotating the case around the rotation axis, the adhesive in a fluid state is flowed to both ends of the case through the adhesive flow path leading to the adhesive cap, thereby sealing the hollow fiber membrane bundle at both ends. It has a sealing portion fixing step for fixing the stop portion.

According to the hollow fiber membrane module according to the present invention and the method for producing the same, it is possible to realize a hollow fiber membrane module capable of suppressing coagulation of a coagulating outer liquid for a long time.

It is sectional drawing which shows the hollow fiber membrane module which concerns on embodiment of this invention. It is an enlarged view of the lower end portion of FIG. 1A. It is a cross-sectional view of AA of FIG. 1B which is shown by omitting a part. It is a flowchart which shows the manufacturing method of the hollow fiber membrane module shown in FIG. 1A. It is a figure which shows the sealing part fixing step in the manufacturing method of the hollow fiber membrane module shown in FIG. 1A. It is sectional drawing which shows another example of the hollow fiber membrane module which concerns on embodiment of this invention. It is a flowchart which shows the manufacturing method of the hollow fiber membrane module shown in FIG. 3A. It is a figure which shows the concave surface formation step in the manufacturing method of the hollow fiber membrane module shown in FIG. 3A. It is a figure for demonstrating the principle that a concave surface is formed in the concave surface formation step of FIG. It is a figure which shows the relationship of. In FIG. 5, the concave surface when the rotation speed of the first rotation centered on the vertical axis and the rotation speed of the second rotation centered on the case axis (Y axis) are changed by four kinds of combinations and rotated. It is a figure which shows the calculation result. It is a figure which shows the 1st concave surface formation step in another example of the manufacturing method of the hollow fiber membrane module shown in FIG. 3A. It is a figure which shows the 2nd concave surface formation step in another example of the manufacturing method of the hollow fiber membrane module shown in FIG. 3A.

Hereinafter, embodiments of the present invention will be described with reference to the drawings. The shapes, materials, numbers, and numerical values described below are examples for explanation and can be appropriately changed according to the specifications of the hollow fiber membrane module. In the following, the equivalent elements will be described with the same reference numerals in all the drawings. In addition, in the explanation in the text, the codes described earlier shall be used as necessary.

FIG. 1A is a cross-sectional view showing a hollow fiber membrane module according to an embodiment. FIG. 1B is an enlarged view of the lower end portion (left end portion) of FIG. 1A. FIG. 1C is a cross-sectional view taken along the line AA of FIG. 1B, which is shown with a part omitted. In addition, since the lower end portion of FIG. 1A is the left end portion when the vertical direction and the horizontal direction are considered in the state of being viewed along the direction of each symbol in FIG. 1A, it is shown in parentheses. There is. Hereinafter, the same applies to the description of the side or direction in parentheses.

The hollow fiber membrane module 10 includes a case 12, a hollow fiber membrane bundle 14, two caps, an inner liquid introduction side cap 16 and an inner liquid discharge side cap 18, and two outer liquid ports, an outer liquid introduction port 20. And an outer liquid discharge port 22. The hollow fiber membrane module 10 is used to form a blood processor for, for example, hemodialysis, blood filtration, and the like. The hollow fiber membrane module 10 is called an external perfusion type. For example, blood as an outer liquid flows outside the hollow fiber membrane 15 (FIG. 1B) forming the hollow fiber membrane bundle 14, and the hollow fiber membrane 15 has a hollow fiber membrane module 10. It is used so that the dialysate as the inner liquid flows through the inner side.

The case 12 has a tubular shape that accommodates the hollow fiber membrane bundle 14. The case 12 is formed of a cylinder made of a resin material such as polycarbonate or polypropylene.

The inner liquid introduction side cap 16 is attached so as to cover the opening at one end in the axial direction (lower end (left end) of FIG. 1A) of the case 12. The inner liquid discharge side cap 18 is attached so as to cover the opening at the other end in the axial direction (upper end (right end) of FIG. 1A) of the case 12. The inner liquid introduction port 17 is formed in the inner liquid introduction side cap 16 so as to project outward along the axial direction of the case 12 (vertical direction (horizontal direction) in FIG. 1A). The inner liquid introduction port 17 is arranged in a part in the circumferential direction of the outer peripheral portion of the case 12. The inner liquid introduction port 17 is for introducing the inner liquid into the inside of each hollow fiber membrane 15 of the hollow fiber membrane bundle 14 arranged in the case 12.

On the other hand, the inner liquid discharge side cap 18 is formed with an inner liquid discharge port 19 so as to project outward along the axial direction of the case 12. The inner liquid discharge port 19 is arranged in a part in the circumferential direction of the outer peripheral portion of the case 12. The inner liquid discharge port 19 is for discharging the inner liquid from each of the hollow fiber membranes 15 of the hollow fiber membrane bundle 14.

The hollow fiber membrane bundle 14 is formed by a plurality of hollow fiber membranes 15 and is housed in the case 12. Both ends of the hollow fiber membrane bundle 14 are fixed by two sealing portions 24 and 25 fixed to both ends of the inner wall of the case 12.

The hollow fiber membrane 15 is composed of, for example, a thin tube having a circular cross section having a thickness of 5 to 150 μm, an inner diameter of 100 to 500 μm, and an outer diameter of about 110 to 800 μm. The membrane base material of the hollow fiber membrane 15 is not particularly limited as long as it is a material that can impart a predetermined shape and performance. For example, polysulfone, polyethersulfone, polyarylate, polyvinylidene fluoride, polymethylmethacrylate, polyvinylpyrrolidone, polyvinyl alcohol, polyethylene glycol, dextran, cellulose, cellulose derivatives and the like can be used alone or in combination.

For example, a polyether sulfone resin and a polyarylate resin can be used as the hydrophobic membrane base material. The total weight (A + B) of the polyether sulfone resin (A) and the polyarylate resin (B) of the film-forming stock solution for spinning the hydrophobic film base material is 10% by weight to 25% by weight. It may be prepared by dissolving it in an organic solvent. At this time, the mixed weight ratio (A / B) of the polyether sulfone resin (A) and the polyarylate resin (B) is determined in the range of 0.1 to 10.

Further, the hollow fiber membrane 15 is not limited to the case where it is composed of a semipermeable membrane made of a hydrophobic polymer using a polyether sulfone resin and a polyarylate resin as a main film base material, for example, a polyether sulfone resin or a polyarylate. A membrane base material may be formed by a single resin.

Further, the hollow fiber membrane 15 may be provided with a crimp, which is a corrugated crimp and is a crimp. By forming a crimp on the hollow fiber membrane 15, the crimp expands (expands) when the hollow fiber membrane 15 is thermally shrunk in the hollow fiber membrane module 10. This prevents the hollow fiber membrane from being torn due to the shrinkage of the hollow fiber membrane 15 and the sealing portions 24 and 25 from being peeled off. Further, in the hollow fiber membrane bundle 14 in which a plurality of hollow fiber membranes 15 are bundled, it is possible to prevent the adjacent hollow fiber membranes 15 from adhering to each other, whereby the hollow fiber membranes 15 flow outside the plurality of hollow fiber membranes 15. Channeling, which is a drift of the outer liquid, can be suppressed.

The two sealing portions 24, 25 seal the openings at both ends of the case 12 inside the corresponding caps 16, 18. The sealing portions 24 and 25 fill the gaps between the adjacent hollow fiber membranes 15 of the hollow fiber membrane bundle 14 and are fixed to the inner wall surface near the openings at both ends of the case 12 so as to be outside the hollow fiber membrane inside the case 12. Prevents the outer liquid from leaking to the outside through the openings at both ends of the case 12. The sealing portions 24 and 25 also have a function as fixing means for fixing both ends of the hollow fiber membrane bundle 14 to the case 12. The sealing portions 24 and 25 are also called potting materials, and for example, a urethane-based adhesive which is a resin composition is used as the sealing portion. It is preferable to use a two-component adhesive that cures with the passage of time by mixing the main agent and the curing agent.

The openings at both ends of the individual hollow fiber membranes 15 constituting the hollow fiber membrane bundle 14 are open (not filled by the sealing portions 24 and 25), and the inside of the hollow fiber membrane 15 is from the inside of the inner liquid introduction side cap 16. The inner liquid flows into the hollow fiber membrane 15, and the inner liquid is discharged from the inside of the hollow fiber membrane 15 to the inner liquid discharge side cap 18.

The outer liquid introduction port 20 and the outer liquid discharge port 22 are separately arranged along the axial direction of the case 12 on the central axis of the case 12. Specifically, the outer liquid introduction port 20 is on the inner liquid discharge side cap 18 side, and one end at the center of the sealing portion 25 on one of the two sealing portions 24 and 25 (upper side (right side) in FIG. 1A). The portions (lower end portion (left end portion) in FIG. 1A) are arranged in the axial direction so as to be connected. At this time, one end of the outer liquid introduction port 20 opens in the internal space 30 sandwiched between the two sealing portions 24 and 25 and in which the hollow fiber membrane bundle 14 is arranged. Further, the other end of the outer liquid introduction port 20 (the upper end portion (right end portion) of FIG. 1A) penetrates the central portion of the inner liquid discharge side cap 18 which is the corresponding side cap in the axial direction and is led out to the outside. Will be done. As will be described later, the other end of the outer liquid introduction port 20 and the luer lock joint 26 which is a peripheral portion thereof are formed in a luer lock type structure based on the regulation by ISO.

The outer liquid discharge port 22 is on the inner liquid introduction side cap 16 side, and one end portion (FIG. 1A) at the center of the sealing portion 24 on the other side (lower side (left side) of FIG. 1A) of the two sealing portions 24 and 25. The upper end portion (right end portion) of the above is connected and arranged in the axial direction so that one end opens in the internal space 30. Further, the other end of the outer liquid discharge port 22 (the lower end (left end) in FIG. 1A) penetrates the central portion of the inner liquid introduction side cap 16 which is the corresponding cap 16 in the axial direction and is led out to the outside. Will be done. The luer lock joint 26, which is the other end of the outer liquid discharge port 22 and its peripheral portion, is formed in a luer lock type structure based on the regulation by ISO. Specifically, as shown in FIG. 1B, a luer lock joint 26 is fixed around the outer liquid discharge port 22 on the outside of the inner liquid introduction side cap 16. The basic configuration of the luer lock joint 26 at the outer liquid introduction port 20 is the same as that of the luer lock joint 26 at the outer liquid discharge port 22. The luer lock joint 26 has a substantially cylindrical shape with one end closed by a bottom portion 26a and the other end open, and a female screw 26b is formed on the inner peripheral surface. The bottom portion 26a of the luer lock joint 26 is abutted against the outer surface of the inner liquid introduction side cap 16. The bottom portion 26a of the luer lock joint 26 may be fixed to the outer surface of the inner liquid introduction side cap 16. In the outer liquid discharge port 22, a male nozzle 22a is formed inside the luer lock joint 26, and the outer peripheral surface of the male nozzle 22a is a tapered surface inclined so that the diameter decreases toward the tip. The portion of the outer liquid discharge port 22 arranged inside the luer lock joint 26 and the luer lock joint 26 have a luer lock type joint structure defined by ISO 594-2. In the luer lock type joint structure, the male nozzle 22a of the outer liquid discharge port 22 is inserted into the female connector provided at the end of the discharge tube (not shown) for discharging the outer liquid. At this time, a flange portion (not shown) formed on the outer peripheral surface of the female connector is screwed to the female screw 26b of the luer lock joint 26. Similarly, the luer lock joint 26 is fixed around the outer liquid introduction port 20 on the outside of the inner liquid discharge side cap 18 shown in FIG. 1A. The portion of the outer liquid introduction port 20 arranged inside the luer lock joint 26 and the luer lock joint 26 have a luer lock type joint structure defined by ISO 594-2. In the luer lock type joint structure, the male nozzle of the outer liquid introduction port 20 is inserted into the female connector provided at the end of the introduction tube (not shown) for introducing the outer liquid. At this time, the flange portion (not shown) of the female connector is screwed to the female screw of the luer lock joint. The luer lock joint 26 may be integrally formed at the other end of each of the outer liquid discharge port 22 and the outer liquid introduction port 20.

By arranging the outer liquid introduction port 20 on the inner liquid discharge side cap 18 side and the outer liquid discharge port 22 on the inner liquid introduction side cap 16 side in this way, the outer liquid and the inner liquid are reversed in the inner space 30. It can flow in the direction. As a result, mass transfer based on the concentration difference between the outer liquid and the inner liquid in the internal space 30 can be maximized.

As will be described later, the outer liquid introduction port 20 and the outer liquid discharge port 22 may be configured to include two axially separable parts, respectively. For example, the outer liquid introduction port 20 and the outer liquid discharge port 22 are a first port member 23 (see FIG. 2) and a second port member (see FIG. 2), which are held embedded in the sealing portions 24 and 25, respectively. It is configured to include (1) and. The second port member is axially coupled so as to fit inside one end of the first port member 23. The manufacturing method shown in FIG. 2 described later manufactures such a hollow fiber membrane module. At this time, an outer tubular portion is formed on the outer peripheral portion of one end surface of the first port member 23, and the end portion of the second port member is fitted inside the outer tubular portion, whereby the joint portion of each port member is formed. The inner peripheral surface should be flush with each other so that no step is generated. The reason for this is that it does not disturb the flow inside the outer liquid introduction port 20 and the outer liquid discharge port 22. In particular, when blood flows as an outer liquid, blood may stay due to steps on the inner peripheral surfaces of these ports 20 and 22, and blood coagulation may occur.

An outer liquid introduction port 20 and an outer liquid discharge port 22 are arranged at the center of both ends of the hollow fiber membrane bundle 14, and the hollow fiber membrane 15 is arranged except for these portions. In the hollow fiber membrane bundle 14 of the internal space 30, the hollow fiber membranes 15 constituting the hollow fiber membrane bundle 14 are uniformly dispersed in the internal space 30. As a result, a long and wide space in the axial direction is not formed in the central portion of the hollow fiber membrane bundle 14. Therefore, it is possible to prevent blood from channeling and the efficiency of mass transfer through the membrane from being reduced. In FIG. 1C, for the sake of clarity, it is shown that the hollow fiber membranes 15 are arranged on a plurality of circumferences in the hollow fiber membrane bundle 14, but in reality, the plurality of hollow fiber membranes 15 are random. It is distributed and arranged in.

The outer liquid is introduced into the internal space 30 of the case 12 through the outer liquid introduction port 20 and flows to the outside of the hollow fiber membrane 15. As a result, the outer liquid flowing outside the hollow fiber membrane 15 and the solute contained in the inner liquid are exchanged with each other through the hollow fiber membrane 15.

Next, a method of manufacturing the hollow fiber membrane module 10 according to the embodiment will be described. FIG. 1D is a flowchart showing a method of manufacturing the hollow fiber membrane module 10 shown in FIG. 1A. First, as the hollow fiber membrane bundle arrangement step (S10), the hollow fiber membrane bundle 14 is arranged so as to be filled (inserted) in the case 12. At this time, since the excess portions at both ends of the hollow fiber membrane bundle 14 are cut in the cap port attaching step (S13) in the subsequent step, the length of the hollow fiber membrane bundle 14 is set to a length exceeding the total length of the case 12. .. At the same time, the first port member 23 (FIG. 2) is arranged along the axial direction so as to be embedded in the central portion of both ends of the hollow fiber membrane bundle 14.

Next, as the adhesive cap attaching step (S11), the adhesive caps 32 (FIG. 2) are attached to both ends of the case 12 filled with the hollow fiber membrane bundle 14. The adhesive cap 32 has a tubular shape with one end closed, and an adhesive flow path 33 is formed so as to extend outward in a part in the circumferential direction. As a result, the inside of the adhesive cap 32 leads to the adhesive flow path 33. The two adhesive flow paths 33 are bent so that one end of the adhesive flow path 33 faces the two adhesive caps 32 near the axial center portion of the outer peripheral surface of the case 12. At this time, the outer end of the first port member 23 is abutted against the bottom 34 of the adhesive cap 32.

Next, as a sealing portion fixing step (S12), as shown in FIG. 2, one end of the two adhesive flow paths 33 is laid down so that the axial directions of the case 12 coincide with each other in the horizontal direction. The discharge port of the adhesive supply unit 35 is connected to. Then, the case 12 is rotated about the vertical axis O1 which is a vertical axis rotating orthogonal to the axial direction of the case 12 and passing through the axial center of the case 12. Then, while rotating the case 12 in this way, the adhesive 60 in a fluid state is flowed from the adhesive supply unit 35 through the adhesive flow path 33 to both ends of the case 12. In FIG. 2, the adhesive 60 is shown in sand. Further, in FIG. 2, the illustration of the hollow fiber membrane bundle 14 is omitted. At this time, the adhesive 60 is supplied into the adhesive cap 32 so that the adhesive 60 gathers at both ends of the case 12 and inside the adhesive caps 32 on both sides due to the centrifugal force accompanying the rotation of the case 12. In addition, it is brought to both ends. Since the adhesive 60 is solidified by the continuation of this rotation, the sealing portions 24 and 25 (FIG. 1A) can be fixed to both ends of the hollow fiber membrane bundle 14.

When a thermosetting adhesive is used to form the sealing portions 24 and 25, the adhesive may be cured by heating the adhesive when performing the sealing portion fixing step. .. When a thermoplastic resin is used as the adhesive for forming the sealing portions 24 and 25, the heat-melted resin may be filled and then allowed to cool and hardened when the sealing portion fixing step is performed.

Further, as a cap port attaching step (S13) shown in FIG. 1D, the adhesive cap 32 is removed from both ends of the case 12, and the hollow fiber membrane bundles 14 and the sealing portions 24 and 25 project from both ends of the case 12. Cut off the end of the. As a result, the portion of the hollow fiber membrane 15 whose inside of the pipe is filled with the sealing portions 24 and 25 is cut. At this time, the outer end portion of the first port member 23 (FIG. 2) may be cut. Finally, the inner liquid introduction side cap 16 (FIG. 1A) and the inner liquid discharge side cap 18 (FIG. 1A) are attached to both ends of the case 12. At the same time, a second port member (not shown) of the outer liquid discharge port 22 is attached so as to penetrate the inner liquid introduction side cap 16, and the second port member is coupled to the first port member 23 to connect the outer liquid. Form a discharge port. Further, a second port member of the outer liquid introduction port 20 is attached so as to penetrate the inner liquid discharge side cap 18, and the second port member is coupled to the first port member 23 to form an outer liquid introduction port. As a result, the hollow fiber membrane module 10 is formed.

According to the hollow fiber membrane module 10 and the method for manufacturing the same, when the module is used, the outer liquid is introduced from the outer liquid introduction port 20 as one outer liquid port of the two outer liquid ports, and the other outer liquid port is introduced. The outer liquid is discharged from the outer liquid discharge port 22 as. Further, the inner liquid is introduced from the inner liquid introduction port 17 as one inner liquid port of the two inner liquid ports, and the inner liquid is discharged from the inner liquid discharge port 19 as the other inner liquid port. As a result, the outer liquid flows outside the hollow fiber membrane 15 inside the case 12, and the inner liquid flows inside the hollow fiber membrane 15. Therefore, it is possible to suppress the non-uniform flow of the inner liquid, that is, channeling which is a drift. Further, since the outer liquid freely flows on the outside of the hollow fiber membrane 15, the boundary film on the outside of the hollow fiber membrane becomes thin, and the boundary film resistance on the outer liquid side can be reduced. As a result, the resistance when the solute on the outer liquid side is diffused and transported to the inner liquid side via the hollow fiber membrane 15 can be reduced, and the permeation performance can be improved. Further, since the surface area of the outer surface on the side where the outer liquid comes into contact with the surface area of the hollow fiber membrane 15 is larger than the surface area of the inner surface, the permeation performance of the solute on the outer liquid side can be improved. When the hollow thread membrane module 10 is used for blood purification, the pressure loss of the dialysate flow can be increased by increasing the flow rate of the dialysate as the inner liquid, and as a result, the blood side which is the outer liquid can be increased. It is possible to increase the amount of internal filtration and increase the movement of substances by filtration without increasing the pressure loss, that is, without imposing a load on the blood.

Further, according to the embodiment, the outer liquid is introduced from one outer side (upper side (right side) of FIG. 1A) in a direction parallel to the longitudinal direction of the hollow fiber membrane 15, and the outer liquid is introduced from the other outer side (lower side of FIG. 1A). The outer liquid is discharged to the side (left side). As a result, when the hollow fiber membrane bundle 14 is arranged and the outer liquid is sent to the inner space 30 sandwiched between the two sealing portions 24 and 25, most of the outer liquid does not bend significantly and flow. Further, even when the outer liquid is discharged from the internal space 30, most of the outer liquid does not bend significantly and flow. As a result, the flow of the outer liquid in the internal space 30 can be equalized or approached evenly, so that the stagnation of the outer liquid can be suppressed. Therefore, when the hollow fiber membrane module 10 is used for blood purification and blood is flowed as an outer liquid, it can be circulated for a long time without coagulating the blood whose coagulation property is improved by stagnation for a long time.

The configuration shown in FIGS. 1A to 1C is not limited to the case where the outer liquid introduction port and the outer liquid discharge port are manufactured by combining the two parts of the first port member and the second port member, respectively, as described above. .. For example, in the sealing portion fixing step shown in FIG. 2, the outer liquid introduction port and the outer liquid discharge port are composed of only one long port member as shown in FIGS. 1A and 1B, and the adhesive cap 32 is attached to the port member. Hold the port member in a penetrating state. Then, the port member is formed so as to greatly protrude from the outer surface of the sealing portions 24 and 25 in a state where the sealing portions 24 and 25 are fixed to both ends of the hollow fiber membrane bundle 14.

Further, in the above description, the case where the outer liquid introduction port 20 and the outer liquid discharge port 22 are arranged on the central axis of the case 12 has been described, but these ports are located at positions different from the central axis of the case 12, for example, in the case. It may be arranged on the outer peripheral side. On the other hand, when the outer liquid introduction port 20 and the outer liquid discharge port 22 are arranged on the central axis of the case 12, as in the configuration shown in FIGS. 1A to 2, the outer liquid is more evenly distributed in the internal space 30. It can be brought closer and flowed. As a result, the stagnation of the outer liquid can be further suppressed. In the following embodiment, the case where the outer liquid introduction port 20 and the outer liquid discharge port 22 are arranged on the central axis of the case 12 will be described.

Further, in the configuration described above, in each of the two sealing portions 24 and 25, the inner side surface of the hollow fiber membrane bundle 14 facing the center in the axial direction is a substantially planar shape orthogonal to the axial direction. In such a configuration, the outer liquid introduced into the internal space 30 is rapidly expanded in diameter, then rapidly reduced in diameter, and discharged from the internal space 30. As a result, some stagnation of the outer liquid flow may still remain in the internal space 30. The configuration shown in FIG. 3A was invented from such a situation.

FIG. 3A is a cross-sectional view showing another example of the hollow fiber membrane module 10 of the embodiment. In the configuration of this example, in the configurations shown in FIGS. 1A to 2, the inner side surfaces of the two sealing portions 36 and 38 facing the axial center of the hollow fiber membrane bundle 14 are in the radial direction of the case 12 from the center. It is formed on a substantially hemispherical or mortar-shaped concave surface 39 that becomes shallower toward the outside. The concave surface 39 has a depth H (FIG. 3A). With such a configuration, the stagnation of the outer liquid can be further suppressed as described later.

FIG. 3B is a flowchart showing a method of manufacturing the hollow fiber membrane module shown in FIG. 3A. FIG. 4 is a diagram showing a concave surface forming step in the method for manufacturing the hollow fiber membrane module shown in FIG. 3A. In FIG. 3B, another manufacturing method of FIGS. 7 and 8 described later is also shown by broken line arrows and steps in parentheses. In the manufacturing method of this example, in the manufacturing method shown in FIG. 1D, a concave surface forming step (S12B) is performed after the sealing portion fixing step (S12A) and before the cap port mounting step (S13). The sealing portion fixing step (S12A) of FIG. 3B is the same as the sealing portion fixing step (S12) of FIG. 1D. In the concave surface forming step, in the sealing portion fixing step (S12A), a rotating device (FIG.) for rotating the case 12 after the inner side surfaces of the sealing portions 24 and 25 on the internal space 30 side are flattened and cured. The case 12 is installed in (not shown). In this rotating device, the case 12 is arranged in a state where the axial directions are aligned in the horizontal direction. FIG. 4 shows a view seen from above with the case 12 installed in the rotating device. Then, in this state, the case 12 is rotated in one direction (direction of arrow G1 in FIG. 4) about the vertical axis O1 which is a vertical rotation axis orthogonal to the axial direction of the case 12. At the same time, the case 12 is rotated in one direction (in the direction of arrow G2 in FIG. 4) around the case axis O2, which is the central axis of the case 12. The vertical axis O1 passes through the axial center of the case 12. Then, while rotating the case 12 in this way, the liquid in a fluid state is passed through the two first port members 23 constituting the outer liquid introduction port 20 (FIG. 3A) and the outer liquid discharge port 22 (FIG. 3A), respectively. The adhesive 62 is poured over both ends of the case 12. In FIG. 4, the adhesive 62 in the fluid state is shown by a diagonal grid. At this time, the newly introduced adhesive 62 is brought to both ends of the case 12 by the centrifugal force accompanying the first rotation, which is the rotation about the vertical axis O1. At the same time, a large amount of the adhesive 62 is collected near the outer periphery of the case 12 due to the centrifugal force accompanying the second rotation, which is the rotation around the case shaft O2. As a result, as shown in FIG. 3A, the side surface of the hollow fiber membrane bundle 14 facing the axial center is formed on the concave surface 39 in each of the sealing portions 36 and 38. Further, in the concave surface forming step, a required amount of liquid adhesive is flowed to the internal space 30 side through the two first port members 23, and then air is sent to the internal space side through the two first port members 23, respectively. Blow the adhesive inside the first port member. As a result, it is possible to prevent the adhesive from remaining in each first port member 23 and sealing the internal passage, thereby blocking the flow of the outer liquid.

According to the above configuration, the outer liquid introduced into the internal space 30 from the outer liquid introduction port 20 flows through the gradually expanded region along the concave surface 39 on the inlet side (upper side (right side) of FIG. 3A). .. Further, in the vicinity of the outlet of the internal space 30, the outer liquid flows in a region whose diameter is gradually reduced along the concave surface 39 on the outlet side (lower side (left side) of FIG. 3A). As a result, there is no sudden change in the flow path with respect to the blood flow, so that the stagnation of the outer liquid can be further suppressed. Therefore, in the case of a blood purifier that flows blood as an outer liquid, blood coagulation due to stagnation is further suppressed. Other configurations are the same as the configurations shown in FIGS. 1A to 2.

The principle of forming the concave surface 39 (FIG. 3A) will be described in more detail with reference to FIG. FIG. 5 is a diagram for explaining the principle of forming the concave surface 39, in which the distance in the radius r direction from the case axis O2 (Y axis) of the concave surface 39 and the distance in the Y axis direction from the bottom point of the concave surface 39. It is a figure which shows the relationship with Y. For example, when considering the point P on the concave surface, the liquid surface has a centrifugal force RFA due to the first rotation about the vertical axis O1 (FIG. 4) in the direction orthogonal to the case axis O2 (Y axis). , Both the centrifugal force RFB due to the second rotation around the case shaft O2 acts. The respective centrifugal forces RFA and RFB are determined by the ^{number of revolutions per minute (min -1) at the corresponding revolutions in the case 12.} For example, when the first rotation speed of the first rotation around the vertical axis O1 is NA and the second rotation speed of the second rotation around the case axis O2 is NB, the centrifugal forces RFA and RFB at the unit mass are as follows. It is represented by an expression.

RFA = 11.18 × (NA / 1000) ² × 15 ・ ・ ・ (1)
RFB = 11.18 × (NB / 1000) ² × r ・ ・ ・ (2)

Here, the radial distance from the case axis O2 (Y axis) at the point P is r (cm). FIG. 5 shows that the right side of the Y-axis has a positive r and the left side has a negative r. Further, in the equation (1), in order to simplify the differential equation described later, even if the turning radius of the first rotation, which is the distance from the vertical axis O1 to the point P, is different due to the difference in the point P, the first rotation is used. Centrifugal force RFA is invariant. Specifically, in the equation (1), the distance from the vertical axis O1 to the point P is set to a constant value of 15 cm.

Then, from the equations (1) and (2), the isobaric surface equation is applied to the Y and r coordinate systems to obtain the following differential equation.

dY / dr = RFB / RFA = (NB / 1000) ² / (NA / 1000) ² x r / 15 = (NB / NA) ² x r / 15 ... (3)

The following equation can be obtained by solving the differential equation of Eq. (3).

^{Y = (NB / NA) 2} × r 2/30 ··· (4)

As a result, it can be seen that the cross section of the concave surface 39 becomes a parabola, and the concave surface 39 becomes a curved surface formed by rotating the parabola around the Y axis. It can also be seen that the shape of the concave surface 39 is determined by adjusting the first rotation speed NA of the first rotation and the second rotation speed NB of the second rotation.

In FIG. 6, the first rotation speed NA of the first rotation centered on the vertical axis O1 and the second rotation speed NB of the second rotation centered on the case axis O2 (Y axis) are changed by four kinds of combinations. The calculation result of the concave surface 39 when the concave surface 39 is rotated is shown. In FIG. 6, the inner diameter of the case is set to 5 cm. Solid line a, b, c, d, the first rotational speed NA respectively 300 min ^-1, 400 min ^-1, 600 min ^-1, shows a concave 39 when it is 950min ^-1. Further, the second rotation speed NB was set to the same 1500 min ^-1 on the solid lines a, b, c, and d. As the first rotation speed NA decreases, the second rotation centered on the case axis O2 (Y axis) becomes dominant, and the concave surface 39 becomes steeper with respect to the radius r direction of the case 12 and has a depth (for example,). Ha) of the solid line a is large.

The steeper the shape of the concave surface 39, that is, the larger the depth, the less the stagnation of the outer liquid is, and in the case of a blood purifier that allows blood to flow as the outer liquid, it is preferable from the viewpoint that blood is less likely to coagulate. On the other hand, as the depth of the concave surface 39 increases, the amount of adhesive used for manufacturing the hollow fiber membrane module 10 increases, so that the material cost increases and the effective film that can be used for material exchange of the hollow fiber membrane bundle 14 increases. The area will be reduced.

Table 1 below shows the experimental results obtained by changing the conditions in the embodiment and determining the depth H of the concave surface 39 and the time until the blood as the outer liquid coagulates.

In Table 1, the embodiments shown in FIGS. 3A to 6 are shown in Examples 2-1, 2, 2 and 2-3. In Table 1, when the sealing portion fixing step (S12) shown in FIG. 2 is set as the first step, the concave surface forming step shown in FIG. 4 is set as the second step. Further, in the column of "center of vertical axis", the first rotation speed NA of the first rotation centered on the vertical axis O1 is shown. In the column of "Case axis center", the second rotation speed NB of the second rotation centered on the case axis O2 (Y axis) is shown.

In the experiment, an anticoagulant was added to fresh porcine blood, and the ACT (activated whole blood coagulation time) was adjusted to 150 to 180 seconds with the antagonist. Further, the temperature of the blood storage tank was adjusted to about 37 ° C., and blood was circulated in the test module of the hollow fiber membrane module at a blood flow rate of 100 mL / min. Next, filtration was started at a filtration flow rate of 10 mL / min, and the filtrate was returned to the blood storage tank. Further, the inlet pressure of the test module was adjusted to about 70 mmHg by a pressure regulator installed in the circulation circuit, and the test was started. Then, the inlet pressure was measured over time, and the time until reaching 150 mmHg was defined as the lifetime, and that time was defined as the time until blood coagulation.

From the experimental results in Table 1, it was confirmed that the depth H (FIG. 3A) of the concave surface 39 increases as the first rotation speed NA decreases. Further, as the depth H of the concave surface 39 becomes larger, the time until the blood coagulates can be lengthened. For example, in Example 2-1 the depth H of the concave surface 39 was as large as 5 cm, and the time until blood coagulation could be as long as 24 hours.

Table 1 also shows the experimental results of the comparative examples. A comparative example is a configuration in which the outer liquid introduction port and the outer liquid discharge port are connected in the radial direction with respect to the outer peripheral surface of the case of the hollow fiber membrane module, similar to the configuration described in Patent Document 1. Specifically, in the comparative example of the hollow fiber membrane module, in the configuration of the embodiment shown in FIGS. 1A to 2, the outer liquid introduction port and the outer liquid discharge port are set to the inner liquid discharge side cap 18 and the inner liquid introduction side. The configuration is such that it is not attached to the cap 16 in the axial direction. Then, in the comparative example, in the configuration, the outer liquid is passed through one end of the outer liquid introduction port and the outer liquid discharge port extending linearly at two positions near both ends of the cylindrical case, respectively. Secure the inlet port and outer liquid drain port to the case. In this state, the outer liquid introduction port and the outer liquid discharge port extend linearly outward in the radial direction from the outer peripheral surface of the case. In this comparative example, the flow of dialysate and blood in the case of the hollow fiber membrane module and the flow of blood in the outer liquid introduction port and the outer liquid discharge port are substantially orthogonal to each other. In such a comparative example, as can be seen from the experimental results in Table 1, the time to blood coagulation was shortened to 5 hours due to the increase in blood stagnation in the case of the hollow fiber membrane module.

Further, in Table 1, as Example 1, the experimental results of Examples corresponding to the embodiments shown in FIGS. 1A to 2 are also shown. In the first embodiment, there is no step corresponding to the second step. As a result, the depth of the concave surface in Example 1 was 0 cm, and the time until blood coagulation was 8 hours. Therefore, it was confirmed that the time until blood coagulation was shorter than that of Examples 2-1, 2, 2 and 2-3, but could be longer than that of Comparative Example.

FIG. 7 is a diagram showing a first concave surface forming step in another example of the method for manufacturing the hollow fiber membrane module 10 shown in FIG. 3A. FIG. 8 is a diagram showing a second concave surface forming step in another example of the method for manufacturing the hollow fiber membrane module 10 shown in FIG. 3A.

In the manufacturing method of this example, as shown by the broken line arrow and the step in parentheses in FIG. 3B, after the sealing portion fixing step (S12A) and before the cap port mounting step (S13), the first concave surface forming step ( S12B1) and the second concave surface forming step (S12B2) are performed. The first concave surface forming step corresponds to FIG. 7, and the second concave surface forming step corresponds to FIG. As shown in FIG. 7, in the sealing portion fixing step (S12A), as shown in the sand in FIG. 7, the inner side surfaces of the sealing portions 24 and 25 on the internal space 30 side became flat and hardened. Then, after that, in the first concave surface forming step (S12B1), the case 12 is installed in the second rotating device (not shown) that rotates the case 12. In this second rotating device, the case 12 is rotated around the case shaft O2, which is the central axis of the case 12, with the axial directions of the case 12 aligned in the vertical direction. Then, while rotating the case 12 in this way, the case 12 is in a flowing state through the first port member 23 located on the lower side of the two first port members 23 constituting the outer liquid introduction port and the outer liquid discharge port. The adhesive 62 is poured over the lower end of the case 12. In FIG. 7, the adhesive 62 in the fluid state is shown by a diagonal grid. At this time, the newly introduced adhesive 62 gathers on the upper surface of the hardened sealing portion 24 at the lower end due to the action of gravity, and due to the centrifugal force accompanying the rotation around the case shaft O2, the case 12 More gather near the outer circumference. As a result, a new adhesive is cured at the lower end portion, and a concave surface 39 (FIG. 3A) is formed. As a result, in the sealing portion 36 (see FIG. 3A) located on the lower side, the inner side surface of the hollow fiber membrane bundle 14 facing the center in the axial direction is formed on the concave surface 39.

Next, in the second concave surface forming step (S12B2), the lower adhesive 62 (FIG. 7) is cured including the concave surface 39 in the first concave surface forming step, and then the case 12 is shown in FIG. The case 12 is installed in the second rotating device that rotates the case 12 by reversing the upper side and the lower side of the case 12. Then, the case 12 is rotated in the same manner as in the first concave surface forming step. Then, while rotating the case 12 in this way, the fluid state is adhered through the first port member 23 located on the lower side of the two first port members 23 constituting the outer liquid introduction port and the outer liquid discharge port. The agent is poured onto the lower end of the case 12. In FIG. 8, the adhesive 62 in the fluid state is shown by a diagonal grid. At this time, the first port member 23 through which the adhesive 62 flows is the first port member on the opposite side with respect to the axial direction of the case 12 as in the case of the first concave surface forming step. Also in this case, as in the case of the first concave surface forming step, the newly introduced adhesive 62 gathers on the upper surface of the cured sealing portion 25 at the lower end portion. Then, a large amount of the adhesive 62 is collected near the outer periphery of the case 12 due to the centrifugal force accompanying the rotation around the case shaft O2. As a result, the new adhesive is cured and the concave surface 39 (FIG. 3A) is formed. As a result, the inner side surface of the hollow fiber membrane bundle 14 facing the axial center of the sealing portion 38 (see FIG. 3A) located on the lower side is formed on the concave surface 39.

As described above, the configuration of FIG. 3A can also be manufactured by a manufacturing method including the broken line arrow of FIG. 3B and the first concave surface forming step and the second concave surface forming step shown in FIGS. 7 and 8.

In the above, the case where blood is flowed as an outer liquid and dialysate is flowed as an inner liquid in the hollow fiber membrane module has been described. It may be used for the purpose of flowing a certain liquid.

10 Hollow fiber membrane module, 12 cases, 14 Hollow fiber membrane bundle, 15 Hollow fiber membrane, 16 Inner liquid introduction side cap, 17 Inner liquid introduction port, 18 Inner liquid discharge side cap, 19 Inner liquid discharge port, 20 Outer liquid introduction Port, 22 Outer liquid discharge port, 22a male nozzle, 23 1st port member, 24,25 sealing part, 26 luer lock joint, 26a bottom, 26b female screw, 30 internal space, 32 adhesive cap, 33 adhesive flow path , 34 Bottom, 35 Adhesive Supply, 36, 38 Seal, 39 Concave, 60, 62 Adhesive.

Claims (7)

With a tubular case
A hollow fiber membrane bundle formed of a plurality of hollow fiber membranes, housed in the case, and fixed at both ends to the case by two sealing portions fixed to both ends of the inner wall of the case.
Caps attached to both ends of the case
An inner liquid port provided on each of the caps and communicated with the inside of the plurality of hollow fiber membranes,
One end is coupled to each of the two sealing portions, and the space inside the case where the hollow fiber membrane bundle is arranged sandwiched between the two sealing portions and outside the plurality of hollow fiber membranes. An outer liquid port arranged along the axial direction so that one end is open to the outside and the other end is led out through the cap on the corresponding side.
With
The outer liquid port is arranged on the central axis of the case and opens in the central axis direction with respect to the internal space of the case.
Each of the two sealing portions is a concave surface in which the side surface of the hollow fiber membrane bundle facing the center in the axial direction becomes shallower from the center toward the outside in the radial direction.
Blood is introduced from the outer liquid port of one of the two outer liquid ports, the blood is discharged from the other outer liquid port through the case internal space, and the blood is discharged from the other outer liquid port, and one of the two inner liquid ports is said. A hollow filament module used to introduce dialysate from an inner liquid port, pass through the inside of the plurality of hollow filament membranes, and drain the dialysate from the other inner liquid port. The hollow fiber membrane module according to claim 1.
The inner liquid introduction port is a hollow fiber membrane module arranged in a part in the circumferential direction of a portion near the outer periphery of the case. The hollow fiber membrane module according to claim 1 or 2.
The outer liquid port is a hollow fiber membrane module that opens in the central portion of the sealing portion without protruding into the case internal space. The hollow fiber membrane module according to any one of claims 1 to 3.
The outer liquid introduced from the outer liquid port into the case internal space flows in a region gradually expanded along the concave surface on the inlet side, and flows in a region gradually reduced in diameter along the concave surface on the outlet side . Hollow fiber membrane module. The method for manufacturing a hollow fiber membrane module according to claim 1.
A hollow fiber membrane bundle arrangement step in which the hollow fiber membrane bundle is arranged in the case and port members constituting the outer liquid port are arranged at both ends of the hollow fiber membrane bundle.
Cap mounting steps to attach adhesive caps to both ends of the case,
An adhesive flow path leading to the inside of the adhesive cap while rotating the case around a rotation axis in a direction orthogonal to the axial direction of the case in a state where the axial directions of the case are aligned in the horizontal direction. A method for manufacturing a hollow fiber membrane module, which comprises a sealing portion fixing step for fixing the sealing portion to both ends of the hollow fiber membrane bundle by flowing an adhesive in a fluid state through both ends of the case. In the method for manufacturing a hollow fiber membrane module according to claim 5.
After the sealing portion fixing step, the case is rotated about a rotation axis in the vertical direction orthogonal to the axial direction of the case in a state where the axial directions of the case are aligned in the horizontal direction, and the case is rotated. While rotating the case around the central axis of the case, the adhesive in a fluid state is flowed to both ends of the case through the port member, so that the sealing portion faces the center of the hollow fiber membrane bundle in the axial direction. A method of manufacturing a hollow fiber membrane module, comprising a concave surface forming step of forming a side surface into a concave surface that becomes shallower from the center to the outside in the radial direction. In the method for manufacturing a hollow fiber membrane module according to claim 5.
After the sealing portion fixing step, in a state where the axial direction of the case is aligned in the vertical direction, the case is rotated around the central axis of the case and flows through the port member located on the lower side. By flowing the adhesive of the above case to the lower end portion of the case, the side surface of the hollow fiber membrane bundle facing the axial center of the sealing portion located on the lower side becomes a concave surface that becomes shallower from the center toward the outer side in the radial direction. The first concave surface forming step to be formed and
After the first concave surface forming step, the upper side and the lower side of the case are reversed, and the case is rotated in the same manner as in the first concave surface forming step, and the flow conductor is passed through the port member located on the lower side. By flowing the adhesive to the lower end of the case, the side surface of the hollow fiber membrane bundle facing the axial center of the sealing portion located on the lower side is formed into a concave surface that becomes shallower from the center to the outside in the radial direction. A method for manufacturing a hollow fiber membrane module, which comprises a second concave surface forming step.

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