JP2010148851A - Blood cell removal module and method of manufacturing blood cell removal module - Google Patents

Abstract

<P>PROBLEM TO BE SOLVED: To provide a blood cell removal module and a method of manufacturing the blood cell removal module with no risk of residual blood, and with fewer pressure drop in the blood cell removal compared with absorbents for beads-shaped blood cell removal. <P>SOLUTION: The method of manufacturing the module for the blood cell removal includes the following steps; a step of arranging absorbent 54 for the blood cell removal composed of a plurality of hollow fiber-like or solid fiber-like staples on a net-state cloth 52 through which blood is possible to pass; a subsequent step of fusion-bonding and fixing the net-state cloth 52 using a fusion-bonding device 70 to both the ends of absorbent 54 for the blood cell removal; a step of forming an absorbent integral net-state cloth 60 for the blood cell removal by sealing the end of absorbent 54 for the blood cell removal (S100); a next step of winding up the obtained absorbent integral net-state cloth 60 for the blood cell removal, along a sequence direction of absorbent 54 for the blood cell removal as shown by an arrow mark of white space on a colored background (S110); a step of forming a cylindrical absorbent 50 for the blood cell removal (S112); and a further step of storing the obtained cylindrical absorbent 50 for the blood cell removal in a case 20. <P>COPYRIGHT: (C)2010,JPO&INPIT

Description

  The present invention relates to a blood cell removal module and a method for manufacturing a blood cell removal module.

  In recent years, leukocyte adsorbers have begun to spread as therapeutic devices for inflammatory bowel disease (IBD) and rheumatoid arthritis (RA). In the leukocyte adsorber, the therapeutic effect is exhibited by directly removing leukocytes that cause inflammation from the blood using the principle of adsorption and filtration. The treatment with a leukocyte adsorber is characterized by few side effects unlike the treatment with drugs. For the leukocyte adsorber that has been put into practical use, a method using a carrier having a certain surface roughness and a method using a filter of ultrafine polymer fibers have been proposed.

  For example, Patent Document 1 discloses a granulocyte-adsorbing carrier having an uneven surface having a center line average roughness Ra value of 0.2 μm to 100 μm and an uneven average interval Sm value of 5 μm to 200 μm. Yes.

  Patent Document 2 discloses that at least two polymers having a number average molecular weight of 10,000 or more and different coagulation values are dissolved in a solvent compatible with each polymer, and the polymer solution is in a droplet state. There has been proposed a method for producing a porous bead produced by coagulation in a coagulation liquid containing a non-solvent.

  Furthermore, in Patent Document 3, it is difficult to prevent the fibers made of organic polymer by using a filter such as a non-woven fabric by arranging the fibers of the organic polymer in a highly regular manner, that is, by arranging them substantially in parallel and circulating blood therebetween. A technique for capturing leukocytes on the fiber surface while overcoming problems such as destruction of blood cells and coagulation of blood has been disclosed.

  These methods have been devised to remove mainly white blood cells such as granulocytes and lymphocytes from the blood of cancer patients and patients with abnormal immune systems. However, recent studies have revealed that not only leukocytes but also blood platelets are involved as inflammatory cells, particularly in inflammatory diseases such as autoimmune diseases.

  On the other hand, a blood cell removal module has been proposed in which a blood cell removal adsorbent made of hollow fiber or solid yarn fiber is housed in a case. For example, a plurality of blood cells made of hollow fiber or solid fiber are proposed. After the removal adsorbent is loaded into the case, both ends of the blood cell removal adsorbent made of fiber are bonded and fixed using an adhesive such as polyurethane, and blood is attached to the outer surface of the blood cell removal adsorbent made of fiber. There has been proposed a method in which blood is passed through and brought into contact with the outer surface of a blood cell removing adsorbent made of fibers to reflux. In addition, a blood cell removing module in which both ends of a blood cell removing adsorbent comprising a plurality of fibers are fixed using a fixing means such as a mesh and housed in a case instead of an adhesive has been proposed.

JP-A-5-168706 Japanese Patent Laid-Open No. 62-243561 European Patent No. 1931404

  However, in any of the blood cell removal modules in which the above-described adsorbent for removing blood cells made of hollow fiber or solid fiber is housed in the case, the inter-fiber space except for the end of the adsorbent for removing blood cells made of fiber is used. Is not restrained at all, it is difficult to keep the gap between the fibers of the adsorbent for removing blood cells properly when blood passes through. As a result, there is a possibility that the blood cell adsorption efficiency is lowered and residual blood is generated. Moreover, when fixing the edge part of the adsorbent for blood cell removal using an adhesive agent, a manufacturing process becomes complicated and there is a possibility that the blood and the adhesive agent come into contact with each other. Further, when the blood cell removing adsorbent comprising a hollow fiber is fixed with a mesh, the end surface of the blood cell removing adsorbent remains hollow, so that blood components may flow into the hollow fiber, possibly causing residual blood. In addition, when a bead-shaped adsorbent is used, there is a problem that the pressure loss during blood cell removal increases.

  An object of the present invention is to provide a blood cell removal module and a method for producing the blood cell removal module that are free from residual blood and have less pressure loss during blood cell removal than an adsorbent for removing beaded blood cells.

  As a result of intensive studies to solve the above problems, the present inventors have completed the present invention shown below. The present invention has the following features.

  (I) A blood cell composed of a case provided with an inlet portion into which blood flow before blood cell removal flows and an outlet portion through which blood flow after blood cell removal is discharged, and a plurality of hollow fiber or solid yarn fibers arranged Cylindrical blood cell removal structure comprising a blood cell removing adsorber-integrated mesh cloth fixed at both ends of a removing adsorbent body to a mesh cloth capable of passing blood along the arrangement direction of the blood cell removing adsorbent body And a blood cell removal module.

  (II) The blood cell removal module according to (I), further including a mesh provided inside each of the inlet portion and the outlet portion and holding the blood cell removing adsorbent in the case.

(III) The adsorbent for removing blood cells includes a polyarylate resin having a repeating unit represented by the following chemical formula (1) and a polyethersulfone having a repeating unit represented by the chemical formula (2) or chemical formula (3): The blood cell removal module according to the above (I) or (II), which contains at least one kind of hydrophobic polymer resin.


In the chemical formula (1), R1 and R2 are lower alkyl groups having 1 to 5 carbon atoms, and R1 and R2 may be the same or different.


In the chemical formula (2), R3 and R4 are lower alkyl groups having 1 to 5 carbon atoms, and R3 and R4 may be the same or different.

  (IV) The blood cell removal module according to any one of (I) to (III), which is used for removing white blood cells and platelets in blood.

  (V) Both ends of a blood cell removing adsorbent comprising a plurality of arranged hollow fiber-like or solid yarn-like fibers are fixed to a mesh cloth capable of passing blood to form a blood cell removing adsorbent-integrated mesh cloth. A step of forming a cylindrical blood cell removing adsorbent by winding the blood cell removing adsorber-integrated mesh cloth along the arrangement direction of the blood cell removing adsorbent, and the cylindrical blood cell removing adsorbent, A method of manufacturing a blood cell removal module comprising: an inlet portion into which blood flow before blood cell removal flows and a case provided with an outlet portion from which blood flow after blood cell removal is discharged is provided.

  (VI) In the step of forming the blood cell removing adsorbent-integrated mesh cloth, the blood cell removing adsorbent is a hollow fiber, and the mesh cloth is capable of passing blood through both ends of the blood cell removing adsorbent. In the case of fixing by heat fusion, the method for producing the blood cell removal module according to (V) above, wherein the hollows at both ends of the heat-fusion adsorbent for removing blood cells are sealed.

  According to the present invention, pressure loss at the time of blood cell removal can be reduced as compared with the bead-shaped blood cell removal adsorbent.

  In addition, the mesh cloth functions as a spacer for the blood cell removing adsorbent comprising a plurality of hollow or solid fibers, and the interfiber distance of the stored blood cell removing adsorbent is substantially uniform within the blood cell removing module. In addition, an appropriate gap can be formed. Therefore, stagnation of blood flow in the blood cell removal module is suppressed. This improves blood cell adsorption efficiency, and further eliminates the need to use a mesh for fixing the end of the blood cell removal adsorbent made of conventional fibers, thus reducing the number of parts and simplifying the manufacturing process. It becomes.

  Also, when the adsorbent for removing blood cells is a hollow fiber, the hollows at both end surfaces of the heat-adhered adsorbent for removing blood cells are sealed, so that when removing blood cells, the adsorbent for removing blood cells is inserted into the hollow fiber. It is possible to suppress the occurrence of residual blood due to the inflow of blood.

It is a perspective view of an example of the structure of the module for blood cell removal in embodiment of this invention. It is a disassembled perspective view of an example of the module for blood cell removal in embodiment of this invention. It is a figure explaining an example of the manufacturing method of the module for blood cell removal in embodiment of this invention. It is a figure explaining the structure of the adsorption body for cylindrical blood cell removal in embodiment of this invention, Comprising: It is a figure which shows an example of the cross section along the AA of FIG. It is a figure explaining the structure of the adsorbent for cylindrical blood cell removal in embodiment of this invention, Comprising: It is a figure which shows the other example of the cross section along the AA of FIG.

  The blood cell removal module and the method for manufacturing the blood cell removal module in the embodiment of the present invention will be described below.

  As shown in FIGS. 1 and 2, in the blood cell removal module 10 according to the present embodiment, a cylindrical blood cell removal adsorbent 50 is housed in a case 20. The case 20 includes a case main body 21, headers 40a and 40b each having blood inflow / outflow ports 22 and 24, and a pair of meshes 30a and 30b as necessary.

  On the other hand, as shown in FIGS. 2, 3, and 4, the cylindrical blood cell removing adsorbent 50 has both ends of a blood cell removing adsorbent 54 composed of a plurality of arranged hollow fiber-like or solid fiber-like fibers. A blood cell removing adsorber-integrated mesh cloth 60 fixed to a mesh cloth 52 through which blood can pass is wound in the arrangement direction of the blood cell removing adsorber 54. Here, when both ends of the blood cell removing adsorbent 54 are fixed to the mesh cloth 52 capable of passing blood, both may be fixed using an adhesive, and both ends of the blood cell removing adsorbent 54 may be fixed. May be fused and fixed to a mesh cloth 52 through which blood can pass. When the blood cell removing adsorbent 54 is a hollow fiber-like fiber, fusion (especially heat fusion) is used at the time of fixing, so that both ends of the blood cell removing adsorbent are fixed compared to fixing with an adhesive. The hollow is easily sealed. Therefore, when used as the blood cell removal module 10, inflow of blood components into the hollow fiber is suppressed by a simpler method, and residual blood is prevented.

  Further, a method for manufacturing the cylindrical blood cell removing adsorbent 50 and the blood cell removing module in the present embodiment will be described with reference to FIG. Here, as an example of a method for fixing both end portions of the blood cell removing adsorbent 54 to the mesh cloth 52 that can pass blood, a fusion is taken as an example. As shown in FIG. 3, a blood cell removing adsorbent 54 made of a plurality of hollow fiber-like or solid yarn-like fibers is arranged on a mesh cloth 52 made of mesh or the like that can pass blood, and then adsorbed for removing blood cells. Both ends of the body 54 are fused and fixed to the mesh cloth 52 by using the fusion device 70, and the ends of the blood cell removing adsorbent 54 are sealed (S100), and the blood cell removing adsorber-integrated network is formed. A cloth 60 is formed. Here, the fusion apparatus 70 may use any means of thermal fusion or ultrasonic fusion. As will be described later, the blood cell removing adsorbent 54 is made of resin, while the mesh cloth 52 is also made of resin. Therefore, by using the fusing device 70, both ends of the blood cell removing adsorbent 54 and the mesh cloth 52 can be fixed without using an adhesive, and the end of the blood cell removing adsorbent 54 can be fixed. It can be sealed. Further, the outer end portion of the obtained blood cell removing adsorber-integrated mesh cloth 60 from the fused portion 56 may remain or be cut. Next, the obtained blood cell removing adsorbent body-integrated mesh cloth 60 is rolled up along the arrangement direction of the blood cell removing adsorbent bodies 54 as indicated by white arrows (S110), and the mesh to be used as a spacer is obtained. A cylindrical blood cell removing adsorbent 50 formed of a bundle of blood cell removing adsorbents 54 with a cloth 52 interposed therebetween is formed (S112). Further, by storing the obtained cylindrical blood cell removing adsorbent 50 in the case 20, the blood cell removing module according to the present embodiment is manufactured. Instead of the above-described fusion fixing, the adhesive may be used for fixing, and if necessary, both ends of the blood cell removing adsorbent 54 may be sealed with an adhesive.

  In the obtained cylindrical blood cell removing adsorbent 50, the mesh cloth 52 functions as a spacer of the blood cell removing adsorbent 54 made of a plurality of hollow fiber-like or solid fiber-like fibers. The interfiber distance of the accommodated adsorbent 54 for removing blood cells is substantially uniform in the blood cell removing module, and an appropriate gap is formed. Therefore, the stagnation of blood flow in the blood cell removal module is suppressed, and the blood cell removal module in the present embodiment improves the blood cell adsorption efficiency. Further, as in the prior art, the end portion of the adsorbent for removing blood cells made of fibers is used. Therefore, the number of parts can be reduced and the manufacturing process can be simplified.

  Further, when the blood cell removing adsorbent is a 54 hollow fiber, the hollow ends of both ends of the fused blood cell removing adsorbent 54 are sealed, so that the hollow fiber of the blood cell removing adsorbent 54 is removed when removing the blood cell. It is suppressed that blood flows into the inside and residual blood is generated.

  The cylindrical blood cell removing adsorbent 50 in this embodiment is wound up after arranging not only one layer but also a plurality of layers of blood cell removing adsorbents 54 on the mesh cloth 52 and fusing both ends thereof. Is formed. An example of the configuration of the cylindrical blood cell removing adsorbent 50 in the present embodiment will be described with reference to FIGS. 4 and 5 which are cross-sectional views taken along the line AA of FIG. For example, FIG. 4 shows a cylindrical blood cell in which a blood cell removing adsorbent 54 arranged in a single layer on a mesh cloth 52 and fused and fixed is wound up along the direction of arrangement of the blood cell removing adsorbent 54. A removal adsorbent 50 is shown. FIG. 5 shows a cylindrical shape in which a blood cell removing adsorbent 54 arranged in two layers on a mesh cloth 52 and fused and fixed is wound up in the arrangement direction of the blood cell removing adsorbent 54. A blood cell removing adsorbent 50a is shown. The number of blood cell removing adsorbents 54 arranged and fused on the mesh cloth 52 is appropriately selected according to the diameter and length of the blood cell removing adsorbent 54 and the viscosity of the blood to be passed through.

  Next, the blood cell removing adsorbent 54 made of hollow fiber-like or solid yarn-like fibers used in the blood cell removing module of the present embodiment will be specifically described. The blood cell removing adsorbent 54 is preferably made of a hydrophobic polymer resin. Thereby, since the surface of the adsorbent 54 for removing blood cells becomes hydrophobic, not only granulocytes which are inflammatory cells but also platelets can be efficiently removed by the hydrophobic interaction. Furthermore, inflammatory symptoms derived from autoimmune diseases can be suppressed while suppressing side effects.

  As the hydrophobic polymer resin, polyarylate resin (PAR), polyethersulfone resin (PES), polysulfonic acid resin (PES), or a polymer alloy of these resins is suitable.

  The polyarylate resin is a resin having a repeating unit represented by the following chemical formula (4). The number average molecular weight of the polyarylate resin is preferably 20,000 to 30,000. When the number average molecular weight of the polyarylate resin is larger than 30,000, the surface unevenness becomes too large, and it becomes difficult to form appropriate surface unevenness. On the other hand, when the number average molecular weight of the polyarylate resin is less than 20,000, the strength of the adsorbent for removing blood cells is lowered, and the production yield of the adsorbent for removing blood cells is deteriorated.

  In the chemical formula (4), R1 and R2 are lower alkyl groups having 1 to 5 carbon atoms, and R1 and R2 may be the same or different. Examples of R1 and R2 include a methyl group, an ethyl group, a propyl group, a butyl group, and a pentyl group. Preferred R1 and R2 are methyl groups.

  The polyarylate resin is not particularly limited as long as the repeating unit represented by the chemical formula (4) is a main repeating unit, and may contain other repeating units as long as the object of the present invention is not impaired.

  The polyethersulfone resin is a resin having a repeating unit represented by the following chemical formula (5) or chemical formula (6). The number average molecular weight of the polyethersulfone resin is preferably 15,000 to 30,000. If the number average molecular weight of the polyethersulfone resin is larger than 30,000, the surface unevenness becomes too large, and it becomes difficult to form appropriate surface unevenness. On the other hand, when the number average molecular weight of the polyethersulfone resin is less than 15,000, the strength of the adsorbent for removing blood cells is lowered, and the production yield of the adsorbent for removing blood cells is deteriorated.

  In the chemical formula (5), R3 and R4 are lower alkyl groups having 1 to 5 carbon atoms, and R3 and R4 may be the same or different. Examples of R3 and R4 include a methyl group, an ethyl group, a propyl group, a butyl group, and a pentyl group. Preferred R1 and R2 are methyl groups.

  By setting the Ra on the surface of the adsorbent for removing blood cells to 5 to 100 nm, the adsorptivity of leukocytes and platelets can be further improved. In addition, it is difficult in manufacturing to make Ra of the surface of the adsorbent for removing blood cells smaller than 5. On the other hand, if Ra on the surface of the adsorbent for removing blood cells is larger than 100 nm, contribution to the adsorption of platelets (size 2 to 4 μm) decreases. Ra of the surface of the adsorbent for removing blood cells can be measured by an AFM (atomic force microscope). In the present embodiment, Ra on the surface of the adsorbent for removing blood cells is measured by AFM using “SPA400” manufactured by Seiko Instruments Inc. as an AFM and “DMF SZDF20AL” (manufactured by Seiko Instruments Inc.) as a probe. The area is 10 μm × 10 μm.

  The blood cell removing adsorbent comprising fibers according to the present embodiment is manufactured by a coagulation method described below.

(Method for producing hollow fiber-shaped adsorbent for removing blood cells)
A method for producing a hollow fiber-like adsorbent hollow fiber for removing blood cells in the present embodiment will be described. First, a hydrophobic polymer resin is dissolved in an organic solvent to prepare a spinning dope. The organic solvent is not particularly limited as long as it is a good solvent for the hydrophobic polymer resin, and examples thereof include tetrahydrofuran, dioxane, dimethylformamide, dimethylacetamide, and NMP. Among these, NMP is preferable as the organic solvent.

  Using a double nozzle, the spinning solution is extruded together with the internal coagulation liquid (water-containing organic solvent) and dropped into the external coagulation liquid (water-containing organic solvent) to produce a hollow fiber for removing blood cells. . The temperature when spinning the blood cell removing hollow fiber is preferably about 5 to 15 ° C. By setting the spinning temperature within this range, the stability of the spinning solution is improved and phase separation or the like is less likely to occur. The ratio of the concentration difference between the internal coagulating liquid (core liquid) and the external coagulating liquid is preferably 0.6 to 1.6.

(Method for producing adsorbent for removing blood cells from solid yarn)
A method for producing a solid thread blood cell removing adsorbent in the present embodiment will be described. First, a hydrophobic polymer resin is dissolved in an organic solvent to prepare a spinning dope. The organic solvent is not particularly limited as long as it is a good solvent for the hydrophobic polymer resin, and examples thereof include tetrahydrofuran, dioxane, dimethylformamide, dimethylacetamide, and NMP. Among these, NMP is preferable as the organic solvent.

  By using a normal nozzle (orifice) and dropping the spinning solution together with a coagulation solution (an organic solvent containing water), a solid yarn for removing blood cells can be produced. The temperature for spinning the blood cell removing solid yarn is preferably about 5 to 15 ° C. By setting the spinning temperature within this range, the stability of the spinning solution is improved and phase separation or the like is less likely to occur.

  The outer diameter of the adsorbent for removing blood cells made of fibers in the present embodiment is a hollow fiber or solid thread of 0.1 mm to 5 mm, and the surface of the adsorbent for removing blood cells made of fibers in the present embodiment The average pore diameter is from 50 nm to 300 nm.

  Since the adsorbent for removing blood cells made of fibers in the present embodiment is in a straight thread shape, the patient's blood is highly viscous compared to those using ultra-fine fiber nonwoven fabric (for example, “CELLSOVA” manufactured by Asahi Kasei Kuraray Medical Co., Ltd.). Even if there is a high risk of coagulation in the module case, it can be used.

  The mesh cloth in the present embodiment is preferably, for example, a mesh having a fiber diameter (wire diameter) of 20 μm to 100 μm and a number of fibers per inch of 3 to 80 (3 to 80 mesh), The material of the mesh is selected from polyester, nylon, polyethylene, and polypropylene.

  Unlike the LCAP (Lymphocyte Depletion Therapy), the blood cell removal module in the present embodiment does not remove lymphocytes, so that there is a low risk of removing memory cells involved in immunity. In addition, the cylindrical blood cell removing adsorbent used in the blood cell removing module in the present embodiment is an “adacolumn” of adsorbent made of cellulose diacetate beads used for GCAP (granulocyte removal therapy) (described later). More platelets can be removed compared to JIMRO). As a result, the patient's inflammatory symptoms can be efficiently suppressed. In addition, since the blood cell removal module in the present embodiment can be treated simply by passing whole blood, it is simple and highly safe, and an expensive device such as a centrifuge used in the conventional centrifuge method is used. do not need.

  EXAMPLES Hereinafter, although an Example demonstrates this invention, this invention is not limited to these Examples.

[Example 1]
Polyarylate resin (hereinafter PAR, number average molecular weight 25,000, manufactured by Unitika, trade name: U polymer) and polyethersulfone resin (hereinafter PES, grade 4800P, number average molecular weight 21,000, manufactured by Sumitomo Chemical Co., Ltd., trade name: A polymer stock solution was prepared using Sumika Excel PES) and N-methylpyrrolidone (NMP). The weight mixing ratio of PAR, PES, and NMP was 7.5: 7.5: 85.0. An aqueous solution of N-methylpyrrolidone (mixed 60% of NMP in water) was used as a coagulation liquid and a core liquid. The polymer stock solution described above is discharged into the coagulation liquid together with the core liquid using a double tube spinneret to produce a hollow fiber membrane, which is continuously cut, and has a hollow fiber short shape with an outer diameter of 300 μm, an inner diameter of 200 μm, and a length of 12 mm. An adsorbent for removing blood cells was obtained.

  When the surface roughness of the adsorbent for removing blood cells of this example was measured using AFM (10 μm × 10 μm, SPA400 manufactured by Seiko Instruments Inc., probe: DFM SZDF20AL (Seiko Instruments Inc.)), Ra = 5. It was 2 nm. Moreover, the average pore diameter was 25.4 nm.

About 3,500 hollow fiber-shaped adsorbents for removing blood cells (outer diameter 300 μm, length 70 mm) of this example are arranged in a plane, and a mesh made of polyester resin (70 mesh) as a mesh cloth is formed thereon. In the state where the wire diameter is 71 μm), both ends of the blood cell removing adsorbent and the mesh are fused using a heat sealer, and the end surface of the blood cell removing adsorbent is sealed (adsorption surface area is about 2). , 300 cm ² ). Next, the outer ends of the fused parts are respectively cut off, wound in the arrangement direction of the blood cell removing adsorbents, and formed of a bundle of blood cell removing adsorbents with a spacer mesh interposed therebetween. An adsorbent for removing blood cells was obtained.

  As shown in FIG. 2, the obtained adsorbent 50 for removing cylindrical blood cells is loaded in a polycarbonate case 20 (full length: 70 mm, inner diameter: 27 mm, capacity: 40 mL), and has a blood inlet and a blood outlet. A pair of headers 40a and 40b was attached to produce a blood cell removal module A.

[Comparative Example 1]
A polycarbonate column (total length: 70 mm, inner diameter: 27 mm, volume) similar to that of Example 1 was used for the packing of Adacolumn (manufactured by JIMRO) which is a granulocyte adsorption column (cellulose triacetate beads having a diameter of about 2 mm, Ra = 133 nm). : 40 mL), and a pair of headers having a blood inlet and a blood outlet were attached to prepare a blood cell removal module B.

<Evaluation method>
500 mL of blood is collected from healthy individuals, heparinized, divided into 250 mL blood packs, and each blood is refluxed at 7 mL / min for 30, then granulocyte (neutrophil) count, platelet count, lymphocyte count From these changes, the adsorption rate of each blood cell removal module was calculated. The results are shown in Table 1 below. In addition, this is an average value of the result measured 6 times.

  From Table 1, it can be seen that the blood cell removing module A of Example 1 has a much higher platelet adsorption rate than the blood cell removing module B of Comparative Example 1.

[Example 2]
About 8,000 hollow-fiber adsorbents for blood cell removal (outer diameter 300 μm, length 12 mm) obtained in Example 1 are arranged in a plane, and a mesh cloth made of polyester resin is formed thereon. In a state where the mesh (70 mesh, wire diameter: 100 μm) is overlaid, both ends of the blood cell removing adsorbent and the mesh are fused using a heat sealer to seal the end surface of the blood cell removing adsorbent (adsorption) The surface area is about 0.9 m ² ). Next, the outer ends of the fused parts are respectively cut off, wound in the arrangement direction of the blood cell removing adsorbents, and formed of a bundle of blood cell removing adsorbents with a spacer mesh interposed therebetween. An adsorbent for removing blood cells was obtained.

  As shown in FIG. 2, the obtained cylindrical blood cell removing adsorbent 50 is loaded into a polycarbonate case 20 (total length: 185 mm, inner diameter: 59 mm, capacity: 324 mL), and has a blood inlet and a blood outlet. A pair of headers 40a and 40b was attached to produce a blood cell removal module C.

[Reference example]
Polyarylate resin (hereinafter PAR, number average molecular weight 25,000, manufactured by Unitika, trade name: U polymer) and polyethersulfone resin (hereinafter PES, grade 4800P, number average molecular weight 21,000, manufactured by Sumitomo Chemical Co., Ltd., trade name: A polymer stock solution was prepared using Sumika Excel PES) and N-methylpyrrolidone (NMP). The weight mixing ratio of PAR, PES, and NMP was 7.5: 7.5: 85.0. An aqueous solution of N-methylpyrrolidone (mixed 60% of NMP in water) was used as a coagulation liquid. The polymer solution was dropped from a nozzle having an inner diameter of 0.25 mm from the surface of the coagulation liquid tank at a height of about 20 cm. After sufficiently coagulating in the coagulation solution, the cells were washed with distilled water to obtain blood cell removing beads having a diameter of about 1 mm.

About 300,000 beads (about 290 mL) of the blood cell removal beads obtained in the reference example (adsorption surface area is about 0.9 m ² ) are loaded into a polycarbonate case (total length: 185 mm, inner diameter: 59 mm, capacity: 324 mL). Then, a pair of headers having a blood inlet and a blood outlet were mounted, and a blood cell removal module D was produced.

<Evaluation method>
3L of heparinized bovine blood (hematocrit blood: 32%) was passed through the blood cell removal module in a circulating state at 50 mL / min, 20 minutes later, the inlet pressure of the blood inlet of the blood cell removal module, The outlet pressure at the blood outlet was measured and the pressure loss in the module was calculated. The results are shown in Table 2 below.

  Table 2 shows that the blood cell removal module C of Example 2 has a smaller pressure loss than the bead-filled blood cell removal module D of the reference example. It should be noted that the blood cell removal module C of Example 2 had the same adsorption rate of granulocytes (neutrophils) and platelets as the bead-filled blood cell removal module D of the reference example.

  The present invention is suitable for blood cell removal applications.

  10 Blood Cell Removal Module, 20 Case, 21 Case Body, 22, 24 Blood Inlet / Outlet, 30a, 30b Mesh, 40a, 40b Header, 50, 50a Cylindrical Blood Cell Removal Adsorbent, 52 Mesh Cloth, 54 Blood Cell Removal Adsorption Body, 56 fused portion, 60 blood cell removing adsorbent-integrated mesh cloth, 70 fusion device.

Claims (6)

A case provided with an inlet part into which blood flow before blood cell removal flows and an outlet part through which blood flow after blood cell removal is discharged;
A blood cell removing adsorbent-integrated mesh cloth in which both ends of a blood cell removing adsorbent composed of a plurality of arranged hollow fiber-like or solid thread-like fibers are fixed to a mesh cloth capable of passing blood is used for the blood cell removal. An adsorbent for removing cylindrical blood cells, which is wound along the arrangement direction of the adsorbent;
A blood cell removal module comprising:   2. The blood cell removal module according to claim 1, further comprising a mesh that is provided inside each of the inlet portion and the outlet portion and holds the blood cell removing adsorbent in the case. The adsorbent for removing blood cells includes at least a polyarylate resin having a repeating unit represented by the following chemical formula (1) and a polyethersulfone resin having a repeating unit represented by the following chemical formula (2) or chemical formula (3): The blood cell removal module according to claim 1 or 2, wherein the blood cell removal module contains a kind of hydrophobic polymer resin.


In the chemical formula (1), R1 and R2 are lower alkyl groups having 1 to 5 carbon atoms, and R1 and R2 may be the same or different.


In the chemical formula (2), R3 and R4 are lower alkyl groups having 1 to 5 carbon atoms, and R3 and R4 may be the same or different.
  The blood cell removal module according to any one of claims 1 to 3, wherein the blood cell removal module is used for removing white blood cells and platelets in blood. Fixing both ends of a blood cell removing adsorbent comprising a plurality of arranged hollow fiber-like or solid yarn-like fibers to a mesh cloth capable of passing blood, and forming a blood cell removing adsorbent-integrated mesh cloth;
Wrapping the blood cell removing adsorber-integrated mesh cloth along the array direction of the blood cell removing adsorbent to form a cylindrical blood cell removing adsorbent;
Storing the cylindrical blood cell removing adsorbent in a case provided with an inlet portion into which blood flow before blood cell removal flows and an outlet portion through which blood flow after blood cell removal is discharged;
A method for producing a blood cell removal module, comprising:   In the step of forming the blood cell removing adsorbent-integrated mesh cloth, the blood cell removing adsorbent is a hollow fiber, and both ends of the blood cell removing adsorbent are heat-sealed to a mesh cloth capable of passing blood. 6. The method for producing a blood cell removal module according to claim 5, wherein the hollows at both end portions of the heat-fused adsorbent for removing blood cells are sealed when they are fixed by heat.