JP6834677B2 - Adsorption column - Google Patents

Description

The present invention relates to an adsorption column, and is suitably used for adsorbing a substance to be adsorbed from a treatment liquid such as blood or blood components. Extracorporeal circulation to remove specific diseases for which certain substances to be adsorbed must be removed, such as β ₂ -microglobulin, which is a protein, cytokines, autoimmune antibodies, and low-density lipoprotein, which is a lipid-protein complex. Suitable for columns.

In addition to artificial dialysis, blood purification therapy called apheresis is widely used as a treatment in which a treatment solution such as blood is taken out of the body, pathogenic substances in the treatment solution are removed by an adsorption column, purified, and then returned. Apheresis therapy mainly includes simple plasma exchange therapy, double-filtered plasma exchange therapy, plasma adsorption therapy that removes harmful substances from plasma after separating plasma from blood, and blood adsorption therapy that removes harmful substances from whole blood. is there.

In plasma adsorption therapy and blood adsorption therapy, attempts have been made to immobilize a ligand that interacts with a specific substance on an adsorption carrier in order to adsorb and remove a specific substance (Patent Documents 1 and 2).

In fact, in plasma adsorption therapy, "Imusova" (registered trademark) (Asahi Kasei Clare Medical Co., Ltd.) that adsorbs and removes autoantibodies and "Liposova" (registered trademark) (registered trademark) that adsorbs and removes low-density lipoproteins ) And other adsorption columns have been put into practical use. In the blood apheresis, endotoxin adsorption removal "Toremikishin" (registered trademark) (Toray Industries, Inc.) and, beta ₂ - microglobulin (hereinafter, beta ₂ -MG) to adsorb and remove "Rikuseru" (registered trademark) ( Adsorption columns such as Kaneka Co., Ltd. have been put into practical use. In each of these, a ligand that interacts with the substance to be removed is immobilized on the adsorption carrier.

Beads are used in all of the above products, except that "Tremixin" uses ordinary yarn as the knitted fabric as the form of the adsorption carrier. The reason for this is that since the bead-shaped adsorption carrier can be uniformly filled in the adsorption column, there is little bias in the flow of the liquid to be treated, and there is an advantage that the column can be easily designed.

On the other hand, in order to improve the adsorption performance of the substance to be adsorbed on the adsorption column, it is generally considered to increase the volume of the adsorption column and the amount of the adsorption carrier, but the amount of extracorporeal circulation treatment liquid (treatment liquid capacity) ) Increases, and if the treatment solution is blood, it causes side effects such as lowering blood pressure and anemia, which is not a preferable solution. As another means for improving the adsorption performance, increasing the surface area per volume of the adsorption carrier can be mentioned. However, when the adsorption carrier is bead-shaped, if the bead diameter is reduced in order to increase the surface area, each The gap between the beads becomes narrower, the flow path resistance becomes higher, and the pressure loss increases, which makes it difficult to flow the treatment liquid.

Examples of forms other than beads include knitted fabrics and hollow fiber membranes. However, in the case of knitted fabric, although it is possible to design the fiber with suppressed flow path resistance, it is not easy in manufacturing to make the fiber porous for providing suction holes.

When the adsorption carrier is a hollow fiber membrane, the adsorption performance is enhanced by adopting a structure in which the treatment liquid flows both inside and outside the membrane. Further, unlike beads, the treatment liquid flow path is clearly divided inside and outside, and the blood flow is better than that of beads. Patent Document 3 describes that in the use of hemodialysis membranes, _{the removal performance of β 2-} MG is improved by controlling the pore radius of the hollow fiber membrane. However, in hemodialysis treatment, filtration is performed from the inside to the outside of the hollow fiber, and water is removed from the blood by the combined effect of filtration and diffusion, and the efficiency of removing uremic substances is also improved. Is designed on the assumption that the pore radius is filtered.

Further, Patent Document 4 also describes a hollow fiber as an adsorbent for removing blood cells. A structure in which both ends of a hollow fiber bundle loaded in a casing are pressed with a mesh to attach a header, and blood flows both inside and outside the hollow fiber. It is described as. However, here, it is only described that the unevenness of the surface is controlled for the purpose of adsorbing leukocytes and platelets on the surface of the hollow fiber, and in a specific embodiment, the phase separation is intentionally performed at the stage of manufacturing the hollow fiber membrane. There is no idea about the control of the porous structure by utilizing the pore formation by the phase separation inside the hollow fiber, and there is no description about the pores in the first place.

Patent Document 5 describes that the porous support is composed of solid fibers as an adsorbent for adsorbing components in the body fluid, and the average pore diameter of the pores of the solid fibers is 0.01 μm or more. It is described as 10 μm or less.

JP-A-59-17355 Japanese Unexamined Patent Publication No. 2004-129975 Japanese Unexamined Patent Publication No. 63-109871 JP-A-2009-254695 Japanese Unexamined Patent Publication No. 6-296860

Regarding the invention described in Patent Document 3, first, unlike the blood dialyzer, the adsorption column does not filter, so that the movement of the substance to be adsorbed from the surface of the hollow fiber membrane to the inside of the hollow fiber membrane is controlled only by diffusion. Therefore, the pore radius on the yarn surface must be designed differently. Further, in a hemodialyzer, the arrangement of the hollow fibers and the shape and dimensions of the case are designed so that the dialysate efficiently flows outside the hollow fiber membrane, but in the design of the adsorption column that does not allow the dialysate to flow. in the case of designing them in the same design concept, it is impossible to adsorb adsorbates such as proteins, including beta ₂ -MG efficiently.

Regarding the inventions described in Patent Documents 3 and 4, in order to efficiently adsorb the substance to be adsorbed both inside and outside the hollow fiber, the distribution ratio of the blood flow rate flowing inside and outside the hollow fiber membrane should be adjusted. The design of is important, but their ideas are not described.

As described above, the pore radius when the protein is adsorbed into the hollow fiber membrane only by diffusion, the structure control including not only the inner surface of the hollow fiber membrane but also the outer surface, and further, the inner and outer surfaces of the hollow fiber membrane. Regarding the control of the distribution ratio of the flow rate of the treatment liquid in the above, it has been difficult to realize an adsorption column having high adsorption performance only by combining the above-mentioned conventional techniques.

Further, in Patent Document 5, for the purpose of increasing the chance that the body fluid containing the adsorbent comes into contact with the adsorbent, the body fluid determined not only by the shape of the case and the simple case shape but also by the filling rate of the solid fiber and the like. There is no description as to how much it is appropriate to secure the flow path area of.

In the prior art, for example, when the adsorption carrier is a porous bead, the surface area per volume is small because it is spherical. Therefore, there is a problem that the treatment liquid component is deposited on the surface of the porous beads to close the pores, and the adsorption site cannot be effectively utilized even if the pores inside the beads have an adsorption capacity. In the case of a hollow fiber membrane, it is difficult to design the surface inside and outside the hollow fiber membrane and control the distribution ratio of the treatment liquid flow rate inside and outside the hollow fiber membrane. When solid yarn was used, no consideration was given to the optimization of the column case.

An object of the present invention is to improve the defects found in the prior art using the beads, the hollow fiber membrane, the solid yarn, and the like.

According to the present invention, it is possible to provide an adsorption column in which the residue of the liquid to be treated (residual blood in the case of blood) is suppressed and the adsorption performance of the substance to be adsorbed is excellent.

As a result of diligent studies to achieve the above problems, the present inventors have found that an adsorption column having improved adsorption performance of a substance to be adsorbed can be achieved by the following configuration.
(1) Porous solid yarns are arranged substantially parallel to the longitudinal direction of the tubular column case.
(A) The average pore radius of the porous solid yarn is 5 nm to 100 nm.
(B) The equivalent diameter of the cross section of the flow path is 10 μm or more and 250 μm or less. (C) An adsorption column having a pressure loss of 2 kPa to 30 kPa when bovine blood is flowed at a flow rate of 200 mL / min.
(2) The adsorption column according to (1) above, wherein the equivalent diameter of the porous solid yarn is 1 μm to 1000 μm.
(3) The adsorption column according to (1) or (2) above, wherein the effective length of the porous solid yarn is 5 cm to 50 cm.
(4) The adsorption column according to any one of (1) to (3) above, wherein the pore size of the porous solid yarn is 1% to 40%.
(5) The adsorption column according to any one of (1) to (4) above, wherein the porosity of the porous solid yarn is 150% to 1000%.
(6) Any of the above (1) to (5), wherein the porous solid yarn is one or more selected from polysulfone-based polymers, ester group-containing polymers, polystyrene, polypropylene, polyacrylonitrile, polyurethane and derivatives thereof. The adsorption column described in Crab.
(7) When the blood contact area with the solid yarn is 3 m ² _{, the clearance of β 2} -microglobulin after 1 hour of circulation is 40 mL / min or more when the blood flow rate is 200 mL / min. ) To (6).

The adsorption column in the present invention can take out the treatment liquid from the body, efficiently remove the causative protein, purify it, and then return it to the body, and the treatment liquid remaining on the adsorption column after treatment (in the case of blood, the residue). (Called blood) can also be reduced. Any adsorption column that removes β _2- MG can be suitably used for dialysis amyloid treatment. Further, any column that adsorbs an antibody can be suitably used for the treatment of autoimmune diseases.

An aspect of the adsorption column used in the present invention is shown. An aspect of a solid yarn cross section for explaining an inscribed circle and a circumscribed circle is shown. The circuit in β _2- MG clearance measurement is shown. _{The β 2-} MG clearance measurement circuit diagram of the artificial kidney module is shown. Deformed cross section The discharge shape of the spinneret of solid yarn is shown.

In the present invention, attention was paid to a porous solid yarn as an adsorption carrier in an adsorption column. Furthermore, by combining the method of arranging the porous solid yarn on the column, the shape of the porous solid yarn, and the porous structure, the adsorption performance of the target substance to be adsorbed is remarkably improved, and the blood return property (subject). This has led to the invention of an excellent adsorption column (when the treatment liquid is blood).

The solid yarn according to the present invention is arranged in a column case, and the column case has a tubular shape and has outlets and inlets for the liquid to be treated, preferably both ends are opened to serve as outlets and inlets, respectively.

First, as a method of arranging the porous solid yarn on the column, the solid yarn bundle is inserted and arranged substantially parallel to the longitudinal direction of the column case. Approximately parallel means that it is preferably parallel to the longitudinal direction of the column case, but may include threads having an inclination of up to 45 degrees. Here, the longitudinal direction of the column case is the direction of the cylinder axis. The advantage of this is that it has excellent blood return properties.

Further, when considering the phenomenon of adsorption, the substance to be adsorbed must come into contact with the solid yarn and be adsorbed while the blood passes through the column. Therefore, in order to maximize the adsorption performance of the solid yarn, it is important that the protein in contact with the solid yarn is rapidly diffused into the solid yarn. When the solid yarn bundle is inserted and arranged substantially parallel to the longitudinal direction of the column case, the liquid to be treated flows along the longitudinal direction of the solid yarn, so that turbulence is unlikely to occur.

Further, in the present invention, it has been found that the equivalent diameter of the cross section of the flow path is important in order to increase the chance that the substance to be adsorbed comes into contact with the solid yarn while the liquid to be treated passes through the column. Here, the flow path is a space through which the liquid to be treated can flow between the solid yarns arranged substantially parallel to the column longitudinal direction, and the flow path cross section is a cross section perpendicular to the case longitudinal direction of the flow path. is there. Further, the equivalent diameter represents the diameter when the cross section of the flow path is regarded as a circle, and specifically, it indicates the width of the flow path obtained by the following equation (1). That is, when the corresponding diameter of the cross section of the flow path is large, the chance that the substance to be adsorbed comes into contact with the surface of the solid yarn is reduced. Therefore, the equivalent diameter of the cross section of the flow path is 250 μm or less, preferably 200 μm or less, and more preferably 150 μm or less. On the other hand, if the cross-sectional area of the flow path is too small, the pressure loss of the column becomes large. Further, as will be described later, an appropriate pressure loss is necessary, but if it is too high, it activates blood, which is not preferable. Therefore, the equivalent diameter of the cross section of the flow path is 10 μm or more, more preferably 30 μm or more.

_{The equivalent diameter (D p} ) of the cross section of the flow path is obtained by the following equation (1).
D _p = ((D _case / 2) ^2- (D _fiber / 2) ² x N) x 2 / (D _case + D _fiber x N) ... (1)
D _case : Inner diameter of column case, D _fiber : Equivalent diameter of solid yarn, N: Number of solid yarns In the present invention, since the solid yarn is porous, proteins enter the inside of the solid yarn and are adsorbed. To. Therefore, it is necessary to have a solid yarn shape and a porous structure so that proteins can easily move to the inside of the solid yarn. Furthermore, in the present invention, it has been found that increasing the pressure loss of the column facilitates the movement of proteins into the solid yarn. On the other hand, if the pressure loss is too large, it will activate the blood. That is, the pressure loss when bovine blood is flowed through the column at a flow rate of 200 mL / min is 2 kPa or more, preferably 3 kPa or more, more preferably 4 kPa or more, while the upper limit is 30 kPa or less and 20 kPa or less. It is preferable, more preferably 12 kPa or less, and particularly preferably 8 kPa or less. The pressure loss can be controlled by adjusting the filling rate of the solid yarn in the column, the inner diameter of the case, the diameter of the solid yarn, the number of solid yarns, and the like. The method for measuring the pressure loss will be described later.

In the present invention, the filling rate of the yarn in the case is preferably 35% or more, more preferably 45% or more, still more preferably 48% or more. On the other hand, 70% or less is preferable, 65% or less is more preferable, and 58% or less is further preferable. When the filling rate is 35% or more, uneven flow is less likely to occur and blood return property is improved, so that residual blood is less likely to occur. The inner diameter of the case is preferably 2 cm or more, more preferably 3 cm or more, and even more preferably 4 cm or more. On the other hand, 15 cm or less is preferable, 10 cm or less is more preferable, and 8 cm or less is further preferable.
The equivalent diameter of the solid yarn is preferably 1 μm or more, more preferably 30 μm or more, still more preferably 50 μm or more. On the other hand, 1000 μm or less is preferable, 300 μm or less is more preferable, and 200 μm or less is further preferable. When the equivalent diameter of the solid yarn is 1 μm or more, the spinnability is improved and platelets and leukocytes are less likely to adhere. On the other hand, when the equivalent diameter of the solid yarn is 1000 μm or less, the substance to be adsorbed such as protein easily enters the inside of the solid yarn by diffusion, and the adsorption performance of the solid yarn is improved.
In addition, in order to enhance the adsorption performance of proteins and the like, a ligand may be introduced into the solid yarn or the adsorbent may be kneaded. As the ligand, it may be immobilized to the inside of the porous structure or may be immobilized on the surface of the solid yarn. Further, in order to suppress the adhesion of platelets and leukocytes, an antithrombotic polymer may be coated on the surface of the solid yarn.

The filling factor is the ratio of the case volume (Vc) calculated from the cross-sectional area and length of the case to the solid yarn volume (Vf) calculated from the cross-sectional area and case length of each solid yarn and the number of solid yarns. It is obtained from the following equations (2) to (4).
Vc = cross-sectional area of case body x effective length ... (2)
Vf = solid thread cross-sectional area x number of solid threads x effective length ... (3)
Vf / Vc × 100 (%) ・ ・ ・ (4)
The cross-sectional shape of the solid yarn may be circular, but is preferably irregular. The equivalent diameter of the porous solid yarn used in the present invention is a value of the diameter obtained from the cross-sectional area of the solid yarn, and is a diameter calculated when the solid yarn cross section is regarded as a circle.

The degree of deformation is expressed by the ratio of the diameters of the inscribed circle and the circumscribed circle when observing the thread cross section, that is, the ratio Do / Di of the diameter Di of the inscribed circle and the diameter Do of the circumscribed circle. Here, the deformed cross section may have a shape that maintains symmetry such as line symmetry and point symmetry, or may be asymmetric, but it is generally symmetric in that it has a uniform solid yarn. It is preferable that the shape has a shape. When it is judged that the irregular cross section maintains line symmetry and point symmetry, the inscribed circle is the circle inscribed in the curve forming the contour of the solid thread in the cross section of the solid thread, and the circumscribed circle is the middle. It is a circle circumscribing the curve forming the outline of the solid thread in the cross section of the actual thread. FIG. 2 shows the circumscribed circle, the inscribed circle, and the diameters Do and Di in the case of a solid yarn having a modified cross section having 3 fins. On the other hand, when it is judged that the deformed cross section has a shape that does not maintain line symmetry or point symmetry at all, it is inscribed at at least two points with the curve forming the contour of the solid thread, and only inside the solid thread. The inscribed circle is a circle having the maximum radius that can be taken in the range where the circumference of the inscribed circle and the curve forming the contour of the solid thread do not intersect. The circumscribed circle is circumscribed at at least two points on the curve showing the contour of the solid thread, exists only outside the cross section of the solid thread, and is the minimum possible within the range where the circumference of the circumscribed circle and the contour of the solid thread do not intersect. Let the circle having the radius of be the circumscribed circle.

When the degree of deformation is 1.2 or more, the ability of the solid yarn to adsorb the substance to be removed can be increased. This is because the degree of deformation generally increases as the surface area per volume increases, so that the adsorption performance can be improved. Therefore, the lower limit of the degree of deformation is preferably 1.2 or more, more preferably 1.5 or more, still more preferably 1.8 or more, and particularly preferably 2.0 or more. On the other hand, when the degree of deformation is kept below a certain level, the central portion of the cross section of the yarn and the fin portion become elongated, and the strength and elongation of the yarn decrease, which prevents bending of the fin and cutting of the fin. It enhances spinning stability and makes it possible to maintain the shape of solid yarn. In addition, even when the case is inserted by bundling the threads, the fins are unlikely to be chipped. From this, it is preferable to set a certain upper limit for the degree of deformation, and in the present invention, 6.6 or less is a preferable range, more preferably 4.5 or less, still more preferably 3.6 or less. It is preferable that the column contains solid yarn having 3 or more fins and 10 or less fins.
When two or more types of solid yarn having a degree of deformation and an equivalent diameter are built in the case, the average degree of deformation and the average equivalent diameter are used.

As a method for measuring the degree of deformation, both ends of the solid yarn to be measured are ^{fixed with a tension of 0.1 g / mm 2} and cut at a random position. Then, the cut surface is magnified and photographed with an optical microscope, for example, DIGITAL MICROSCOPE DG-2 manufactured by SCARA. When shooting, the scale is also shot at the same magnification. After digitizing the image, for example, using the image analysis software "Micro Measure ver. 1.04" of SCARA Co., Ltd., measure the diameter Do of the circumscribed circle and the diameter Di of the inscribed circle in the cross section of the fiber. .. Then, the degree of deformation of each fiber is obtained by the above formula. This measurement is performed at 30 points, the values are averaged, and the value rounded to the first decimal place is taken as the degree of deformation.

When a deformed solid yarn is contained in the column, the blood contact area per volume of the solid yarn increases, which has the advantage of improving the adsorption performance. However, unlike the circular solid yarn, it has anisotropy, which will be described later. If the quality of the yarn bundle is not adjusted appropriately, uneven blood flow is likely to occur, and the original adsorption performance of the solid yarn cannot be exhibited.

Regarding the effective length of the solid yarn (the length of the part that is not covered with resin and can come into contact with the liquid to be treated), if it is too short or too long, the protein adsorption performance will be low. 5.5 cm or more is preferable, 3.5 cm or more is more preferable, and 4.5 cm or more is further preferable. On the other hand, 50 cm or less is preferable, 30 cm or less is more preferable, and 10 cm or less is further preferable. The effective length is preferably 0.25 times or more and 10 times or less, more preferably 0.5 times or more and 3 times or less, and 0.7 times or more and 1 times or less with respect to the inner diameter of the case. Is even more preferable.

The adsorption column according to the present invention preferably has header portions at the outlet and inlet of the case, and when the header portions of the column are connected to both end faces of the case, it is preferable that the liquid to be treated can flow between the inlet and outlet. Since the solid yarns are arranged in a bundle in the longitudinal direction of the case, blood is introduced into the end face portion of the solid yarns and is drawn out from the other end face portion. As a result, blood tends to flow between the solid threads. Therefore, uneven flow is less likely to occur, residual blood is low, and adsorption performance can be improved.

Further, when the solid yarn is arranged in a bundle in the longitudinal direction of the case and blood flows from the end of the solid yarn, the quality of the solid yarn bundle affects the flow unevenness. Here, poor quality of the solid yarn bundle means that the bundle inserted in the case collapses into an elliptical shape, the bundle is split in two, or the inside of the solid yarn bundle. It means that the unevenness of density is large. From the viewpoint of improving the quality of the yarn bundle, it is not preferable to insert a plurality of yarn bundles together into the case, and the tension at the time of winding the yarn at the time of spinning is preferably 0.5 gf / piece to 10 gf / piece. Further, when the solid yarn is moistened with a highly viscous liquid such as an aqueous glycerin solution, the yarn bundle quality can be maintained. The concentration of the glycerin aqueous solution is preferably 30 to 90% by mass. Furthermore, the preferred yarn filling rate for the case is as described above. Flow unevenness can be quantified by a pulse test. The details of the measurement will be described later, but the space time of the peak top obtained from the pulse test is preferably 0.85 or more and 1 or less, and more preferably 0.9 or more and 1 or less.

The porous structure of the solid yarn is an important factor that affects the adsorption rate of the substance to be adsorbed. If the average pore radius is small, it becomes difficult for the substance to be adsorbed to enter the inside of the pores due to diffusion, and the adsorption efficiency is lowered. On the other hand, if the pore radius is too large, the substance to be adsorbed is not adsorbed in the void portion of the pore, so that the adsorption efficiency is conversely lowered. That is, the optimum pore size exists according to the size of the substance to be adsorbed to be removed, and if the pore size is selected incorrectly, the substance to be adsorbed cannot be sufficiently adsorbed. From these facts, the average pore radius of the solid yarn is preferably in the range of 5 to 100 nm, and in this range, substances such as low molecular weight substances and proteins / lipid aggregates such as proteins and low-density lipoproteins. Can be adsorbed. The average pore radius at the time of adsorbing and removing the protein is preferably 5 nm or more and 100 nm or less, and more preferably 7 nm or more and 50 nm or less. The molecular weight of from 10,000 to 30,000 about protein, causing dialysis amyloidosis beta ₂ - Micro glycidyl Brin (β ₂ -MG) and cytokines that cause multiple organ failure acute, such as interleukin-l [beta], interleukin 6. High mobility group box 1 (HMGB1) and the like are present, and removal of these proteins is a preferable mode. In order to adsorb the protein in this molecular weight region, it is preferably 10 nm or more and 30 nm or less. In addition, proteins having a molecular weight of 100,000 or more include autoantibodies that cause rheumatoid arthritis and the like. In order to adsorb the protein in this molecular weight region, it is preferably 15 nm or more and 50 nm or less.

In the present invention, β _2- MG is particularly targeted for adsorption removal, and a high adsorption rate can be obtained by appropriately setting the above range. The _{method for measuring the adsorption performance of β 2-} MG will be described later, but in ^{a column having a blood contact area of 3 m 2} with the solid yarn, the clearance after 1 hour of circulation is 40 mL / min when the blood flow rate is 200 mL / min. The above is preferable, 50 mL / min or more is more preferable, and 60 mL / min or more is further preferable. The blood volume of the column at this time (header volume + case internal volume-solid thread volume (π x solid thread radius ² x effective length x number of threads)) is preferably 170 mL or less, preferably 130 mL or less. More preferably. Incidentally, the blood contact area is sometimes difficult columns Preparation of 3m ^2, if between 1m ² ~6m 2, may be converted from the overall mass transfer coefficient 3m ² value.

The details of the measurement method for the average pore radius of the solid yarn will be described later in Examples, but it is obtained by measuring the degree of freezing point drop due to the aggregation of water capillaries in the pores by differential scanning calorimetry (DSC). ..

The surface structure of the solid yarn is also an important factor because it affects the movement of the substance to be adsorbed inside the membrane. When the aperture ratio on the surface is small, the protein tends to be difficult to move inside the membrane. On the other hand, if the aperture ratio is too large, the unevenness of the surface becomes large, so that blood is easily activated. In particular, platelets and leukocytes are activated and tend to induce adhesion. Therefore, the aperture ratios of the inner and outer surfaces of the film are preferably 1% or more, more preferably 2% or more, still more preferably 4% or more. On the other hand, 40% or less is preferable, 30% or less is more preferable, and 20% or less is further preferable.

Regarding the average pore diameter on the surface of the solid yarn, this is the diameter of the two-dimensional pores that can be confirmed on the yarn surface, but if this is too small, the protein is difficult to diffuse inside the membrane, and if it is too large, it activates blood. Cheap. Therefore, the average pore diameter (diameter) of the surface is preferably 0.01 μm or more, more preferably 0.1 μm or more. On the other hand, 10 μm or less is preferable, and 1 μm or less is more preferable. Here, when the hole diameter on the surface is not circular, a corresponding equivalent diameter obtained by a circle having the same area as the area surrounded by the outer circumference of the hole can be used. Further, as the shape of the holes on the surface, an elliptical shape or a slit shape is preferable because the aperture ratio can be increased. Specifically, the length of the major axis portion of the hole (the longest radius in the hole) is preferably 1.5 times or more the length of the minor axis portion (the shortest radius in the hole), and is twice or more. Is more preferable. On the other hand, if the ratio of the major axis is too large, the yarn strength may decrease. Therefore, the length of the major axis portion is preferably 10 times or less, more preferably 5 times or less the length of the minor axis portion.

It is preferable that the average pore diameter (diameter) of the surface is larger than the average pore diameter. The reason for this is that when the pore diameter on the surface is larger than the pore radius, the protein easily enters the inside of the solid yarn, and the adsorption efficiency is increased.

The details of the measurement method for the aperture ratio and the average pore diameter will be described later, but it is calculated by taking an electron microscope image of the surface of the hollow fiber membrane and performing image processing.

It is preferable that the specific surface area inside the solid yarn is large because the adsorption capacity increases. On the other hand, in order to maintain the strength of the solid yarn, it is preferable to keep the specific surface area below a certain level. Therefore, the specific surface area is preferably at least ^{10 m} 2 / g, more preferably at least 100 m ² / g, while the 10000m is preferably from ² / g, more preferably at most 1000 m ² / g.

Further, as the composition of the solid yarn, it is preferable to have a hydrophobic polymer because an adsorption effect of a hydrophobic substance such as a protein can be expected by a hydrophobic interaction. On the other hand, it is preferable to keep the hydrophobicity below a certain level in order to prevent the protein from being adsorbed and deposited on the membrane surface without diffusing into the membrane, blocking the pores, and adsorbing a large amount of albumin. Therefore, as the hydrophobicity, when the polymer is formed into a film, the contact angle is preferably 40 ° or more, more preferably 50 ° or more, further preferably 60 ° or more, and preferably 110 ° or less. It is more preferably 100 ° or less, and even more preferably 90 ° or less. Examples of the hydrophobic polymer include polysulfone-based polymers, polyarylates, polycarbonates, ester group-containing polymers such as polymethylmethacrylate and cellulose acetate-based polymers, polystyrene, polypropylene, polyacrylonitrile and derivatives thereof. Examples of the polysulfone-based polymer include polysulfone, polyethersulfone, and polyallyl ethersulfone, examples of the ester group-containing polymer include polyester-based polymer and polymethylmethacrylate, and examples of cellulose acetate-based polymer include cellulose diacetate and cellulose triacetate. In addition, examples of the derivative include a copolymer and a modified product into which a functional group has been introduced. As the copolymer, it is preferable to add other monomers in the range of 10 mol% or less per repeating monomer to the above polymer, and more preferably in the range of 5 mol% or less. Further, as the amount of the functional group introduced, it is preferable to introduce the functional group in the range of 20 mol% or less per repeating monomer, and more preferably in the range of 10 mol% or less. In particular, the ionic group and the hydrophilic group can impart appropriate hydrophilicity to the polymer, and have an effect of preventing adhesion to the surface of the solid yarn from closing the pores.

As a method for controlling the surface structure and pore radius of the solid yarn, a method using phase separation of a polymer solution is used. Methods using phase separation can be broadly divided into heat-induced phase separation methods and non-solvent-induced phase separation methods, and which method is suitable depends on the type of polymer and the range of desirable pore size.

The liquid holding rate of the solid yarn depends on the porosity and the material of the solid yarn. Since the space where water can enter inside the solid yarn becomes a porous part that contributes to adsorption, the liquid holding rate is an index for adsorption. That is, when the liquid holding rate is low, the porosity rate is low, so that the adsorption performance is low. Further, when the solid yarn has a high hydrophobicity, it is difficult for water to enter the fine pores, so that the liquid holding ratio is lower than the actual pore ratio. Therefore, even in this case, the adsorption performance is lowered. Further, when the liquid holding rate is high, the porosity rate is high or the hydrophilicity of the solid yarn is high. On the other hand, if the hydrophilicity of the solid yarn is too high, it is difficult for the protein to be adsorbed even if it enters the pores. From the above, the liquid holding ratio of the solid yarn is preferably in the range of 150% or more and 1000% or less, and more preferably in the range of 180% or more and 700% or less. The liquid holding ratio (%) is determined by the membrane mass in the saturated water content state / the dry membrane mass × 100.

The rough manufacturing process of the solid yarn according to the present invention is as follows, but is not necessarily limited to the following. First, a spinning stock solution in which a polymer is dissolved in a solvent is prepared. Next, the spinning stock solution is discharged from the mouthpiece. After discharging from the mouthpiece, it is passed through an aerial part (dry part) controlled to a constant atmosphere and then led to a coagulation bath. By the steps up to this point, the surface structure and the internal porous structure of the solid yarn are almost determined. Then, after undergoing a washing step, the yarn is wound to obtain a yarn bundle. If the film performance changes due to drying, there may be a step of applying a moisturizer such as glycerin.

In order to achieve the porous structure of the present invention, among the above hydrophobic polymers, an ester group-containing polymer, particularly a polymer having an ester group in the side chain is preferably used. In particular, polymethylmethacrylate and polymethylmethacrylate derivatives are preferably used. If the hydrophobicity is too strong, the substance to be adsorbed such as protein may be adsorbed on the surface before being diffused into the membrane to form a fouling layer, and the inside of the membrane may not be effectively utilized for adsorption. Therefore, a certain degree of hydrophilicity is also important as a material for the film, and the polar group of the ester group is effective for imparting such a hydrophilic-hydrophobic balance to the film surface. Further, a polymer having a molecular weight of 110 as a repeating unit and having one ester group, such as polymethylmethacrylate, is suitable because it has a good balance between hydrophilicity and hydrophobicity. The ester group is preferably located in the polymer side chain rather than the polymer main chain. When a solid yarn is produced using polymethylmethacrylate as a film material, it is preferably dissolved in a good solvent such as dimethyl sulfoxide so that the polymer concentration is 15 to 30% by mass. This solution is discharged from the annular spinneret, passed through a dry part, and then led to a coagulation bath. A cooling gas is sprayed on the dry part. At this time, the cooling gas preferably has a dry-bulb temperature of 5 to 20 ° C, more preferably 8 to 17 ° C. The dew point, which is a measure of the water content, is preferably 0 to 20 ° C, more preferably 5 to 15 ° C. The atmosphere of the dry part has a great influence on the surface structure. It is preferable to apply cold air from the direction perpendicular to the yarn. Further, the cold air flow velocity is preferably 3 to 10 m / sec, more preferably 6 to 8 m / sec.

The time for the discharged yarn to pass through the dry portion is preferably 0.01 to 2 seconds, more preferably 0.1 to 1 second.

Regarding the draft rate at the time of discharge, this is a parameter defined as the ratio of the speed at which the undiluted spinning solution comes out of the spinneret and the take-up speed of the produced solid yarn. When this draft ratio is large, the pores of the yarn become It is stretched into an elliptical shape, and the surface area per space is smaller than that of spherical pores. If the draft rate is too small or too large, the spinning stability will deteriorate. From the above, the draft rate is preferably 1.5 to 30, more preferably 3 to 20.

Then, it is led to a coagulation bath mainly composed of water to solidify and desolvate. By increasing the coagulation bath temperature, the pore radius can be increased. Although the exact mechanism is not clear, it is considered that the competitive reaction between the desolvation from the stock solution and the coagulation shrinkage causes the desolvation to be rapid in the high temperature bath and is solidified and fixed before the shrinkage. However, if the coagulation bath temperature becomes too high, the pore radius becomes too large as described above. Therefore, the coagulation bath temperature is preferably 40 ° C. or higher, more preferably 42 ° C. or higher, and preferably 55 ° C. or lower. 48 ° C. or lower is more preferable. Further, by adding a small amount of a solvent good for the thread-forming polymer such as dimethyl sulfoxide in addition to water, the size of the pore radius can be uniformly controlled. However, if the amount is too large, the spinning stability deteriorates, so the concentration of a good solvent other than water is preferably 1 to 40% by mass, more preferably 10 to 30% by mass. The longer the yarn is immersed in the coagulation bath, the more uniformly the size of the pores can be controlled. On the other hand, if it is too long, the spinning stability will be poor. From the above, the time during which the yarn is immersed in the coagulation bath is preferably 0.01 to 2 seconds, more preferably 0.1 to 1 second. It is also effective to insert a drawing step after spinning and stretch it.

Next, the solvent adhering to the solidified solid yarn is washed. The means for washing the solid yarn is not particularly limited, but a method in which the solid yarn is passed through a bath filled with water in multiple stages (water washing bath) is preferably used. The temperature of the water in the water washing bath is preferably 30 to 50 ° C. from the viewpoint of washing efficiency.

Further, in order to maintain the pore size of the solid yarn, there may be a step of applying a moisturizing component, which is preferably performed after the water washing step. Typical examples of moisturizing ingredients include glycerin and its aqueous solution.

Further, in order to improve the dimensional stability of the highly shrinkable solid yarn, it is possible to pass the step of a bath (heat treatment bath) filled with an aqueous solution of a heated moisturizing component, and preferably the above-mentioned washing step, Performed after the moisturizing process. The heat treatment bath is filled with an aqueous solution of a heated moisturizing component, and when the solid yarn passes through this heat treatment bath, it shrinks due to the thermal action, and it becomes difficult to shrink in the subsequent steps, resulting in a film structure. Can be stabilized. The heat treatment temperature at this time is preferably 75 ° C. or higher, more preferably 83 ° C. or higher. On the other hand, 90 ° C. or lower is preferable, and 86 ° C. or lower is set as a more preferable temperature. When the yarn is stretched during this heat treatment step, the aperture ratio of the film surface can be efficiently improved and the pores on the surface can be made elliptical.

The obtained solid yarn is wound up into a yarn bundle, and then inserted into a column. First, the solid yarn is cut to a required length, the required number of yarns are bundled, and then the solid yarn is inserted into a plastic case which is a tubular portion of the adsorption column. Arrange so that the longitudinal direction of the solid yarn is substantially parallel to the longitudinal direction of the case. There are two methods for retaining the solid yarn inside the column case. The first is a method of arranging a mesh on the end face of the yarn bundle. The second method is to fix the yarn bundle at the end face portion of the yarn bundle with a potting portion (pot layer) composed of a case and a resin layer. At this time, the potting portion needs a communication hole for communicating the inside of the case in which the solid yarn is arranged and the outside of the case, that is, the header portion. In order to form the communication hole, a method of inserting a small pin-shaped cylinder into the end face of the yarn bundle and then flowing the resin near the end face to perform potting can be mentioned. After the resin has solidified, both ends are cut with a cutter or the like to remove the portion where the solid thread is blocked by the resin, and if the pin-shaped cylinder is removed, an opening of a communication hole is opened at the end of the pot layer. Is formed.

After that, the treatment liquid inlet and outlet ports called headers can be attached to both ends of the case to obtain an adsorption column.

Here, when the liquid to be treated is blood, the phenomenon that blood remains in the column remains when the operation of returning the blood in the column or circuit to the body using physiological saline after the extracorporeal circulation treatment is performed. Called blood. Causes of residual blood include cases where blood remains due to poor flow of physiological saline in the column, and cases where the blood coagulation system is activated and blood viscosity increases and remains. In the present invention, it is preferable to consider the blood return property of the adsorption column. In particular, solid yarn is often damaged during spinning, winding, and inserting a yarn bundle. If the surface of the solid thread is scratched and uneven, blood is activated and blood cell components adhere to the site, which may cause residual blood. That is, it is preferable to reduce the roughness of the portion in contact with the yarn, such as a roller or a guide for guiding the yarn.

Further, in the present invention, the solid yarns are arranged substantially parallel to the longitudinal direction of the case, but if the yarn bundle contains a large number of solid yarns, all the yarns are substantially parallel when the case is inserted. It may not be possible to insert it in, especially if the thread is twisted and inserted, resulting in poor blood return. From the above, when the column longitudinal direction is set to 0 °, it is preferable that the number of threads having an insertion angle of 10 ° or more for the solid yarn with respect to the column longitudinal direction is 10% or less of the number of threads on the outer peripheral portion. More preferably, it is 5% or less. The thread on the outer peripheral portion referred to here refers to a thread that can be visually confirmed from the side surface of the column. On the other hand, even if the surface of the solid yarn is too flat, the contact area with the blood cell component becomes large, and the adhesion of platelets and leukocytes increases. Therefore, as the surface irregularities, the average roughness (Ra) of the center line of the surface is preferably 0.1 μm or more, more preferably 0.2 μm or more, while 5 μm or less is preferable, and 2 μm or less is more preferable.

The details of the blood return test will be described later, but the amount of residual blood in the column at the time of the test is preferably 5 mL or less, more preferably 1 mL or less.

For all the items specified in the above-mentioned numerical range in the present specification, any numerical value such as an upper limit, a preferable upper limit, a more preferable upper limit, etc. in each item, and a lower limit, a preferable lower limit, a more preferable lower limit, etc. It may be any numerical range in combination with any numerical value.

Hereinafter, the present invention will be described with reference to Examples and Comparative Examples, but the present invention is not limited to these examples.

1. 1. Preparation of adsorption column 1. (1) Preparation of PMMA solid yarn 3.5 parts by mass of isotactic polymethyl methacrylate (iso-PMMA) having a mass average molecular weight of 510,000 and syndiotactic polymethyl methacrylate (syn-) having a mass average molecular weight of 890,000. PMMA) 13.3 parts by mass and 4.2 parts by mass of copolymerized syndiotactic polymethyl methacrylate (syn-PMMA) containing 1.5 mol% of sodium parastyrene sulfonate and having a molecular weight of 300,000 are mixed with 79 parts by mass of dimethyl sulfoxide. Then, the mixture was stirred at 110 ° C. for 8 hours to prepare a spinning stock solution.

The obtained spinning stock solution was discharged into the air from an annular mouthpiece having a diameter of 0.3 mm kept at 96 ° C. The spun yarn was then run through a dry portion set to a length of 38 cm and then led to a coagulation bath. As the atmosphere of the dry part, cold air having a temperature of 15 ° C. and a dew point of 12 ° C. was applied perpendicularly to the yarn at a speed of 7 m / sec. Further, a mixed aqueous solution of 85% by mass of water and 15% by mass of dimethyl sulfoxide was put into the coagulation bath and used. The yarn diameter and bath temperature of the solid yarn were carried out under various conditions as shown in each of the examples and comparative examples described later.

After passing through the coagulation bath, it is led to a washing bath, glycerin is added as a 63% by mass aqueous solution as a moisturizer, and after a heat treatment step at 83 ° C., excess glycerin is removed with a scraper and wound to obtain a solid yarn. It was.

1. 1. (2) Column formation The adsorption column shown in FIG. 1 was prepared for the obtained solid yarn or hollow fiber. That is, the yarn bundle was inserted into the case of the column and arranged substantially parallel to the longitudinal direction of the case. Furthermore, meshes, O-rings, and headers were attached to both ends of the case to form columns. The inner diameter of the column case, the number of threads, and the effective length were as shown in Examples and Comparative Examples described later. The glycerin remaining on the yarn after column formation was washed with water, the inside of the column was filled with water, and then sterilized by irradiating with γ-rays of 25 kGy.

2. 2. Measuring method As shown below, measuring instruments such as average pore radius, equivalent diameter of solid yarn, and surface aperture ratio were specified. However, if the measurement accuracy is equal to or higher than that, the measurement may be performed using another device.

2. 2. (1) Measurement of average pore radius of solid yarn The average pore radius of solid yarn was determined by differential scanning calorimetry (DSC). The melting point of ice confined in nano-sized pores is lower than that of ordinary bulk ice (melting point: 0 ° C.). Utilizing this phenomenon, the pore radius distribution can be calculated and the average pore radius can be obtained by combining the Laplace equation and the Gibbs-Duhem equation from the melting point distribution of the DSC curve.

Specifically, the degree of decrease in melting point ΔT increases as the pore radius R decreases, and ΔT and R are expressed by the following equations.

Here, α is a constant (nmK) as a function of temperature, which is 56.36ΔT-0.90 for the freezing process and 33.30ΔT-0.32 for the thawing process. Α / ΔT in the first term of the formula indicates the diameter of water in the freezing pores. Β in the second term of the formula indicates the thickness of non-freezing pore water adsorbed on the pore surface.

Further, the shape of the DSC curve reflects the pore distribution curve of the porous body, and the pore distribution curve (dV / dR) can be calculated from the DSC curve (dq / dt).

Here, V: cumulative pore volume, m: mass of porous body (solid yarn), ΔH (T): heat of fusion at temperature T, ρ (T): density of pore water at temperature T, z: Pore shape factor (cylindrical 2.0, spherical 3.0).

As a measuring method, after removing the adhering water on the surface of the solid yarn sample immersed in water, dozens of pieces having a length of about 5 mm were packed in a closed pan, weighed, and subjected to DSC. The sample was cooled to −55 ° C. and then heated at a heating rate of 0.3 ° C./min for measurement. A DSC Q100 manufactured by TA Instruments was used as the DSC device.

2. 2. (2) Measurement of equivalent diameter of solid yarn 20 of the solid yarns filled in the column are arbitrarily extracted, washed with pure water, and the inside of the yarn is replaced with pure water. After that, the solid yarn was sandwiched between the slide glass and the cover glass, and the measurement was performed using a projector (V-10A manufactured by Nikon Corporation) to obtain the average value of 20 yarns and rounded off to the nearest whole number.

2. 2. (3) Measurement of pressure loss in bovine blood 2. (6) In the β _2- MG clearance (β _2- MG CL) measurement, the pressure difference between the blood side inlet (Bi) and the blood side outlet (Bo) 5 minutes after the start of circulation is measured, and the pressure difference between Bi and Bo is measured. The pressure was lost.

2. 2. (4) Measurement of surface aperture ratio The solid yarn was sputtered to form a thin film of Pt-Pd on the surface of the solid yarn, which was used as a sample. This sample was observed with a field emission scanning electron microscope (S800 manufactured by Hitachi, Ltd.) at a magnification of 10000 times. At this time, the automatic functions of the device were used for the brightness and contrast of the image. Next, the hole portion was painted black using "Microsoft Paint" (registered trademark) (Microsoft Ltd.). After binarization, image processing is performed to invert the holes white and the other parts black using "Matrox Inspector 2.2" (registered trademark) (Matrox Electrical Systems Ltd.), and the number of white holes. The diameter of the opening and the total opening area of the white hole were obtained, and the opening ratio was calculated. In addition, even if the entire hole is not shown and the edges are cut off, the part shown in the image is included in the calculation. For these measurement operations, images were taken at 5 random locations for each of the 3 threads, the average value for a total of 15 images was calculated, and the hole diameter was rounded to the first decimal place. The aperture ratio was calculated as a value rounded off to the nearest whole number.

When the shape of the hole was not a circle, the diameter corresponding to the circle having the same area as the area of the hole was calculated and used as the hole diameter. Further, those having a pore diameter of less than 0.2 μm were regarded as noise and were not counted.

2. 2. (5) Pulse test A circuit was connected to the adsorption column, and 1 L of ultrapure water was flowed through the circuit and the adsorption column at 200 mL / min for washing. 1 mL of ink diluted 110 times with ultrapure water was injected with a syringe from the port portion of the circuit within 2 seconds.

The time when the ink injection was started was set to 0 seconds, and 3 mL of sampling was performed every 1 second from 3 seconds later (total 100 seconds, 98 samples). A spectrophotometer (U-2000 manufactured by Hitachi, Ltd.) was used to measure the concentration of ink, and a calibration curve was prepared at a wavelength of 600 nm, and then the sample was measured.

From the obtained data, create a scatter plot with the X-axis as the spatial time (φ) and the Y-axis as the dimensionless concentration (E), and peak the spatial time (φ) of the sample with the highest dimensionless concentration (E). It was the top. Here, φ and E are represented by the following equations (5) and (6), respectively.
φ = t / TI = t / (VI / v) ・ ・ ・ (5)
TI: Column theory transit time t: Sampling time (the start of ink injection is 0 sec)
VI: Theoretical column volume v: Flow velocity (200 ml / sec)
E = C / C0 ・ ・ ・ (6)
C: Concentration of ink in each sampling solution C0: Initial concentration of ink 2. (6) as a performance evaluation of beta ₂ -MG clearance (beta ₂ -MG CL) measurement adsorption column was measured clearance beta ₂ -MG. beta ₂ -MG is known to be a cause protein dialysis amyloidosis is a long-term dialysis complications.

Bovine blood supplemented with disodium ethylenediaminetetraacetate was adjusted so that hematocrit was 30 ± 3% and total protein content was 6.5 ± 0.5 g / dL. Bovine blood was used within 5 days after blood collection.

Next, β _2- MG concentration was added to 1 mg / L, and the mixture was stirred. For such bovine blood, 2 L thereof was divided for circulation and 1.5 L for clearance measurement.

The circuit was set as shown in FIG. The Bi circuit inlet is placed in a circulation beaker containing 2 L (37 ° C) of bovine blood adjusted above, the Bi pump 11 is started at a flow rate of 200 mL / min, and the liquid discharged from the Bo circuit outlet is discharged for 90 seconds. Immediately after discarding the minutes, the Bo circuit outlet was inserted into the circulation beaker to put it in a circulating state.
The pump was stopped after 1 hour of circulation.

Next, the Bi circuit inlet was placed in the bovine blood for clearance measurement adjusted above, and the Bo circuit outlet was placed in the disposal beaker.

The flow velocity was set to 200 mL / min, and 10 ml of a sample was collected from bovine blood (37 ° C.) for clearance measurement 2 minutes after the start of the pump to prepare a Bi solution. After 4 minutes and 30 seconds had passed from the start, 10 ml of a sample flowing from the outlet of the Bo circuit was collected and used as a Bo solution. These samples were stored in a freezer below -20 ° C.

The clearance was calculated from the concentration of β _{2-MG of each solution by the following formula I.} Since the measured values may differ depending on the lot of bovine blood, the same lot of bovine blood was used for all the examples and comparative examples. When different blood lots are used, it is preferable to use an average value of 2 or more lots.
Co (ml / minute) = (CBi-CBo) × Q B / CBi (I)
In equation (I), _CO = β _2- MG clearance (ml / min), CBi _{= β 2- MG concentration in Bi solution, CB o = β 2-} MG concentration in Bo solution _{, Q B} = Bi pump flow rate ( ml / min).

2. 2. (7) Blood-returning test The adsorption column was washed with a physiological saline solution by flowing 700 mL from bottom to top at a flow rate of 200 mL / min. At this time, no defoaming operation such as giving vibration to the adsorption column was performed.

Then, bovine blood was conducted from below at a flow rate of 200 mL / min. Heparin was added to bovine blood to adjust the hematocrit to 30% and the total protein content to 6.5 g / dL. After confirming that bovine blood appeared in the upper header of the adsorption column, the adsorption column was turned upside down to allow blood to flow from top to bottom. It was circulated for 1 hour in this state.

For blood return, physiological saline was used in an amount of 2 to 3 times the blood volume of the column, and the blood was flowed from top to bottom at a one-pass flow rate of 100 mL / min. The returned blood flowing out from under the column is sampled over time, and the final 100 mL of returned blood (if the blood volume of the column is 100 mL, the solution during 200 to 300 mL of physiological saline) is 2 with pure water. The amount of hemoglobin contained in the liquid was calculated by diluting it twice and hemolyzing it, and measuring the absorbance at a wavelength of 414 nm with an ultraviolet-visible spectrophotometer (UV-160 manufactured by Shimadzu) to obtain it as the amount of residual blood in the column. It was. The calibration curve was prepared using bovine blood adjusted so that hematocrit was 30% and the total protein amount was 6.5 g / dL.

[Example 1]
Above 1. In (1), spinning was performed at a coagulation bath temperature of 48 ° C. to obtain a solid yarn having an equivalent diameter of 113 μm. An adsorption column was prepared by inserting 60,000 solid yarns having an effective length of 140 mm into a case having an inner diameter of 46 mm. The various results are shown in Table 1, and high β _2- MG clearance and good residual blood (small residual blood volume) were obtained. As a result of the pulse test, the peak top was 0.77, which was a good flow [Example 2].
Using the same yarn and case as in Example 1, an adsorption column was prepared in the same manner except that 82,000 solid yarns were inserted. The various results are shown in Table 1, and high β _2- MG clearance and good residual blood (small residual blood volume) were obtained. Since the pressure loss is higher than that of Example 1, _{it is considered that the β 2-} MG clearance is also higher than that of Example 1.

[Example 3]
Above 1. In (1), a solid yarn having an equivalent diameter of 280 μm was obtained. An adsorption column was prepared by inserting 13500 solid yarns having an effective length of 140 mm into a case having an inner diameter of 46 mm. The various results are shown in Table 1, and high β _2- MG clearance and good residual blood (small residual blood volume) were obtained.

[Example 4]
Above 1. In (1), spinning was performed at a coagulation bath temperature of 50 ° C. to obtain a solid yarn having an equivalent diameter of 127 μm. An adsorption column was prepared by inserting 69000 solid yarns having an effective length of 140 mm into a case having an inner diameter of 46 mm. The various results are shown in Table 1, and high β _2- MG clearance and good residual blood (small residual blood volume) were obtained. Since the pressure loss was slightly higher than that of Example 2, the surface aperture ratio and the average pore diameter (diameter) of the surface were high, it _{is considered that the β 2-} MG clearance was also higher than that of Example 2.

[Example 5]
Above 1. In (1), spinning was performed at a coagulation bath temperature of 50 ° C. to obtain a solid yarn having an equivalent diameter of 102 μm. An adsorption column was prepared by inserting 166,200 solid yarns having an effective length of 47.8 mm into a case having an inner diameter of 58 mm. The various results are shown in Table 1, and high β _2- MG clearance and good residual blood (small residual blood volume) were obtained. Although the pressure loss was lower than that of Example 2, the surface aperture ratio and the average pore diameter (diameter) of the surface were high, so _{that it is considered that the β 2-} MG clearance was about the same as that of Example 2.

[Comparative Example 1]
Using the same yarn and case as in Example 1, an adsorption column was prepared in the same manner except that 40,000 solid yarns were inserted. As various results shown in Table 1, beta ₂ -MG clearance, poor results were obtained in comparison with Example 1 the residual ischemic both. Since the pressure loss was low, the β _2- MG clearance was low, and the filling rate was low, so it is probable that the residual blood volume was also high. Moreover, as a result of the pulse test, the peak top was 0.28, and the flow was not so uniform.

[Comparative Example 2]
Using the same yarn and case as in Example 3, an adsorption column was prepared in the same manner except that 8500 solid yarns having an effective length of 350 mm were inserted. The various results are shown in Table 1, and the β _2- MG clearance was low. It is probable that the corresponding diameter of the cross section of the flow path was large [Comparative Example 3].
Spinning was performed at a coagulation bath temperature of 40 ° C. to obtain a solid yarn having a yarn diameter of 165 μm. An adsorption column was prepared by inserting 42,000 solid yarns into a case having an inner diameter of 46 mm with an effective length of 140 mm. The various results are shown in Table 1, and the β _2- MG clearance was low. It is considered that the average pore radius of the solid yarn was small.

[Comparative Example 4]
A solid yarn of the same level as in Example 1 was shredded to about 20 mm to prepare about 4200000 yarns and randomly inserted into a case having an inner diameter of 46 mm to prepare an adsorption column. The various results are shown in Table 1, and the β _2- MG clearance was low and the residual blood volume was high.

Adsorption column according to the present invention, the processing liquid blood can be suitably used in applications for adsorbing and removing proteins such as beta ₂ -MG using as, not limited to blood, proteins contained biological fluid, the drainage It can also be used for adsorption and removal of. Further, by appropriately designing the average pore radius of the solid yarn, it can be widely used not only for adsorbing and removing proteins but also for adsorbing and removing substances to be adsorbed.

1 Solid thread 2 Case 3 Potting agent 4 Blood side entrance (Bi)
5 Blood side outlet (Bo)
6 Dialysate side inlet (Di)
7 Dialysate side outlet (Do)
8 Reference line 9 Dialysis device 10 Hollow fiber membrane module 11 Bi pump 12 F pump 13 Disposal container 14 Circulation bovine blood 15 Clearance measurement bovine blood 16 Bi circuit 17 Bo circuit 18 Di circuit 19 Do circuit 20 Hot water tank 21 Mesh 22 Header 23 O-ring

Claims (7)

A bundle of porous solid yarns is arranged substantially parallel to the longitudinal direction of the tubular column case.
(A) The average pore radius of the porous solid yarn is 5 nm to 100 nm.
(B) The equivalent diameter of the cross section of the flow path is 10 μm or more, 250 μm or less ,
(C) The pressure loss when bovine blood was flowed at a flow rate of 200 mL / min was 2 kPa to 30 kPa ,
(2) The degree of deformation, which is the ratio of the diameters of the inscribed circle and the circumscribed circle when observing the cross section of the porous solid yarn, is 1.2 or more and 6.6 or less.
(E) The filling rate of the porous solid yarn with respect to the column case is 35% or more.
(F) When the longitudinal direction of the column case is 0 °, the porous solid yarn having an insertion angle of 10 ° or more with respect to the longitudinal direction is 10% or less of the porous solid yarn on the outer peripheral portion. Is an adsorption column. The adsorption column according to claim 1, wherein the equivalent diameter of the porous solid yarn is 1 μm to 1000 μm. The adsorption column according to claim 1 or 2, wherein the effective length of the porous solid yarn is 5 cm to 50 cm. The adsorption column according to any one of claims 1 to 3, wherein the pore size of the porous solid yarn is 1% to 40%. The adsorption column according to any one of claims 1 to 4, wherein the porosity of the porous solid yarn is 150% to 1000%. The adsorption according to any one of claims 1 to 5, wherein the porous solid yarn is one or more selected from polysulfone-based polymers, ester group-containing polymers, polystyrene, polypropylene, polyacrylonitrile, polyurethane and derivatives thereof. column. Any of claims 1 to 6, wherein when the blood contact area with the solid yarn is 3 m ² , the clearance of β2-microglobulin after 1 hour of circulation is 40 mL / min or more when the blood flow rate is 200 mL / min. The adsorption column according to one item.