JP5072063B2 - Carrier module - Google Patents

Description

  The present invention relates to a carrier module used for medical use.

  In recent years, various blood processing columns have been studied. For example, columns for removing leukocytes and granulocytes (Patent Documents 1 and 2), columns for adsorbing cytokines (Patent Documents 3 and 4), leukocytes and Columns (patent document 5) and the like aimed at simultaneously adsorbing toxins have been developed. These usually have a carrier unit for removing and adsorbing a target substance inside the column. Various materials and shapes are used as the carrier unit. When attention is paid to those using a sheet-like carrier having a low bulk density, a flat-type nonwoven fabric filter made of ultrafine fibers, a flat plate A type of nonwoven fabric filter wound in a cylindrical shape is known. Among them, a carrier unit in which a flat nonwoven fabric filter is wound in a cylindrical shape is frequently used because the entire filter device is compact and the operability during blood treatment can be kept good. However, on the other hand, a carrier unit in which a flat nonwoven fabric filter is wound in a cylindrical shape is simply a flat nonwoven fabric filter wound in a cylindrical shape. In addition, in the case of a carrier having a low bulk density, the shape and dimensions are easily changed, and there is a problem that the flow path width in the carrier module tends to be uneven.

When filling a column with a carrier unit in which a nonwoven fabric filter having a low bulk density is wound into a cylindrical shape, a support such as a mesh or a porous sheet is provided between the nonwoven fabric filter and the container, and the nonwoven fabric filter is placed in the container. Has also been proposed to be held stably (Patent Documents 6 and 7). However, in the proposed method, a nonwoven fabric filter wound in a cylindrical shape is further wound around a support such as a mesh, and the nonwoven fabric in the container is accommodated so that there is almost no gap in the container. The filter is simply supported. In other words, it is possible to fix the filter inside the filter container by the force with which the nonwoven fabric filter or the support body tries to spread in the radial direction and the pressing force of the container. Therefore, although it is possible to prevent the nonwoven fabric filter and the support from spreading in the radial direction in the container, the carrier unit itself cannot maintain its shape, the handling property is poor, and the bulk density of the carrier is low. In such a case, there is a problem that the shape and dimensions are easily changed. Further, since a support such as a mesh is interposed between the container and the filter, the pressure loss in the flow path of the processing fluid is increased, and there remains a problem as a carrier module.
JP-A-60-193468 JP-A-5-168706 Japanese Patent Laid-Open No. 10-225515 JP-A-12-237585 JP 2002-113097 A Japanese Patent Laid-Open No. 62-243561 Japanese Patent Publication No.11-058172

  An object of the present invention is to provide a carrier module that is excellent in shape stability and handleability of a carrier unit in view of the problems of the prior art. Another problem is to improve production efficiency during module fabrication.

In order to achieve the above object, the present invention has any one of the following configurations (1) to (8).
(1) A carrier unit having a bulk density of 0.5 g / cm ³ or less, a carrier unit provided with a cylindrical seamless net provided on the outer periphery of the carrier, and a cylindrical container in which the carrier unit is accommodated. Carrier module.
(2) The carrier module according to (1), wherein an opening ratio of the seamless net is 0.1 or more.
(3) The carrier module according to (1) or (2), wherein the carrier includes at least one selected from a woven fabric, a knitted fabric, a nonwoven fabric, and a porous membrane.
(4) The carrier module according to any one of (1) to (3), wherein at least one selected from a woven fabric, a knitted fabric, a nonwoven fabric, and a porous membrane is wound in a cylindrical shape.
(5) The carrier module according to any one of (1) to (4), wherein a clearance is provided between an outer peripheral surface of the carrier unit and an inner wall of the cylindrical container.
(6) The outer diameter of the carrier unit is A, the inner diameter of the cylindrical container is B, and the clearance formed between the outer peripheral surface of the carrier unit and the inner wall of the cylindrical container is (BA) / 2 [mm ], The carrier module according to (5), wherein 0 <(BA) / 2 <10 is satisfied.
(7) Any of the above (1) to (6), wherein the seamless net is provided such that constituent yarns of the seamless net are 5 ° or more and 85 ° or less with respect to the axial direction of the cylindrical container. The carrier module according to claim 1.
(8) The carrier module according to any one of (1) to (7), which is used for a purpose of circulating blood for processing.

According to the present invention, a module using a carrier having a low bulk density is provided by configuring a carrier unit by providing a cylindrical seamless net on the outer periphery of a carrier having a low bulk density of 0.5 g / cm ³ or less. Nevertheless, the stability of the shape of the carrier unit is increased and the handling is excellent. In addition, since the shape stability is increased, a uniform clearance can be secured between the outer peripheral surface of the carrier unit and the inner wall surface of the cylindrical container, the processing liquid can be made to flow uniformly, and the pressure loss can be reduced. Can be suppressed. Further, the assembly operation at the time of module production becomes easy, and efficient carrier module production becomes possible.

The carrier module of the present invention is obtained by, for example, winding a sheet-like carrier having a bulk density of 0.5 g / cm ³ or less into a cylindrical shape, and providing a cylindrical seamless net on the outer periphery of the surrounding body to obtain a carrier unit. The carrier unit is accommodated in a cylindrical container so that a clearance is formed between the cylindrical container and the outer peripheral surface of the carrier unit.

  In the present invention, the “carrier” means a material having a property of directly or indirectly adsorbing or holding a liquid and a solid substance, and a binding substance may be immobilized. For example, examples of suitable carriers for treating blood include fiber materials such as woven fabrics, knitted fabrics, and nonwoven fabrics, and porous membranes such as porous films and sponges, as will be described later.

  The “cylindrical shape” includes a cylindrical shape and a shape similar to the cylindrical shape, and includes a cross-sectional shape of a circle, an ellipse, and a polygon such as a triangle, a rectangle, and a turtle shell. Among them, it is preferable that the distance from the center is substantially uniform and the cross-sectional shape is substantially circular.

  As a method of winding the carrier into a cylindrical shape, it is not particularly realized if it is wound into a roll shape. A sheet-like carrier may be wound around a pipe or a core material to form a cylindrical shape, or the core material may not be used.

  After the carrier is wound, the wound state is maintained by a cylindrical seamless net provided on the outer periphery of the carrier. By using the cylindrical net, the size (outer diameter) of the support wound in a cylindrical shape can be made uniform in the axial direction, and the inner wall surface of the cylindrical container and the carrier unit in the cylindrical container Can be made uniform in the cylinder axis direction. As a result, a medium to be treated such as blood can be supplied uniformly and pressure loss in the module can be reduced. Moreover, individual differences in mass production are reduced, and production can be performed efficiently.

  Furthermore, the cylindrical net in the present invention is seamless. “Seamless” means forming a continuous body in which no lines such as boundaries or seams are observed. Since it is seamless, it is a net with a smooth surface, and there is no possibility of damaging the carrier or peeling off the wound body from seams or discontinuous parts. In addition, since there is no seam or overlap, the thickness of the net is uniform in the circumferential direction, and when the carrier unit is accommodated in the cylindrical container, the clearance generated between the inner wall of the cylindrical container and the cylindrical carrier is circumferential. Can be kept constant. As a result, pressure loss in the module can be further reduced, and a medium to be treated such as blood can be supplied more uniformly over the entire outer periphery of the carrier unit. If blood cannot be supplied uniformly, the blood may stay or drift. In particular, when blood treatment is performed for a long time, the blood coagulation mechanism is activated, which may cause an increase in blood viscosity or a thrombus. An increase in blood viscosity or the occurrence of blood clots is not preferable from the viewpoint of safety because it causes an increase in pressure loss during blood processing.

  Here, the outer diameter of the carrier unit is A [mm], the inner diameter of the cylindrical container is B [mm], and the clearance formed between the outer peripheral surface of the carrier unit and the inner wall of the cylindrical container is (B− When A) / 2 [mm], it is desirable to satisfy 0 <(BA) / 2 <10. A clearance of 0 is not preferable because it is difficult to insert the carrier unit into the cylindrical container and the pressure loss tends to increase. On the other hand, if the clearance exceeds 10 mm, the amount of the carrier filled in the volume of the limited cylindrical container is not preferable.

  The outer diameter of the carrier unit can be measured by the following method. After immersing the carrier unit in water, measure the outer diameter at five locations including the maximum and minimum diameters with a vernier caliper in any cross section of the carrier unit, and calculate the average value of the outer diameter at that location of the carrier unit. And

  When the maximum clearance in the carrier module is C [mm], if the clearance in the cylinder axis direction within the same individual is within the range of C / 2 [mm] to C [mm], the carrier module The clearance is substantially uniform in the cylinder axis direction.

  The cross-sectional shape of the cylindrical seamless net is not particularly limited, and is appropriately selected depending on the shape of the module.

  The seamless net in the present invention is preferably a net having a uniform and regular network structure. By having such a structure, it is possible to evenly distribute the pressure applied to the seamless net when a medium to be processed such as blood passes. The configuration of the net is not particularly limited, and a knot network, a knotless network, a Raschel network, or the like can be used. The constituent yarns of the net can be suitably used because the constituent yarns do not move when the intersecting portions are joined, and the shape retention and handling properties are improved compared to the case where they are not joined. Examples of the bonding method include knots and adhesion by heat. Further, when the constituent yarns of the net are joined together, it is preferable to perform heat fusion that can easily control the thickness and can be performed at low cost.

  Moreover, the shape of the opening part of a seamless net can use polygons, such as a rectangle, a square, a rhombus, and a turtle shell shape, and a circle. Among the polygons, a regular polygon is preferable, and a square or rhombus is particularly preferable from the viewpoint of handling properties.

  The opening of the seamless net is preferably as large as possible, and the opening ratio is preferably 0.1 or more. When the aperture ratio is less than 0.1, the pressure loss due to the seamless net itself increases, which may affect the fluidity of the medium to be treated such as blood. On the other hand, in order to improve the shape stability more reliably, it is more preferable that the aperture ratio is 0.9 or less. Here, the aperture ratio of the seamless net refers to the ratio of the area of the opening existing in the predetermined range to the area of the predetermined range, and is obtained by, for example, the following method. After cutting the seamless net into squares of 2 cm square, the area of the opening when observed from the direction perpendicular to the sheet surface of the seamless net, that is, the total area of the space portion where the seamless net constituent yarn does not exist, The aperture ratio is calculated by the following formula.

Open area ratio = total area of the space part where the net component yarn does not exist / area of the test piece Examples of the material of the seamless net include known polymers such as polyamide, polyester, polyacrylonitrile-based polymer, polyethylene, and polypropylene. Can be selected and used as appropriate. However, when the carrier module of the present invention is used for blood treatment, polypropylene is particularly preferable from the viewpoints of biocompatibility, heat resistance, and chemical resistance.

  In addition, the seamless net preferably has flexibility (softness) and elasticity from the viewpoint of workability to be mounted on the outer periphery of a carrier formed by winding in a cylindrical shape. By using a seamless net having flexibility (flexibility), it becomes possible to easily attach and detach the seamless net to and from the outer periphery of a carrier formed by winding in a cylindrical shape, and use a seamless net having elasticity. Thus, the carrier wound in a cylindrical shape can be prevented from being deformed, and the shape of the carrier can be stably maintained.

  Here, about the diameter of the thread | yarn which comprises a seamless net, in order to improve elasticity, 50 micrometers or more are preferable, 100 micrometers or more are more preferable, and 200 micrometers or more are especially preferable. On the other hand, 2 mm or less is preferable, 1.5 mm or less is more preferable, and 1 mm or less is particularly preferable in order to make the flexibility, softness, and handling properties excellent.

  In addition, when the net structure is formed of multifilaments or spun yarns that are a combination of a plurality of fibers, seamless nets increase pressure loss due to the passage of a medium to be treated such as blood between the combined yarns. There are concerns. Therefore, the constituent yarn is preferably a single yarn (monofilament). If it is a single yarn, it is easy to maintain the mechanical strength per one.

  Further, the thickness of the net is preferably 50 μm or more, more preferably 100 μm or more, and particularly preferably 200 μm or more from the viewpoint of mechanical strength and thickness accuracy. On the other hand, it is preferably 3 mm or less, more preferably 2.5 mm or less, and particularly preferably set to a range of 2 mm or less. By setting the thickness to 50 μm or more, the mechanical strength is increased and the cylindrical carrier can be more reliably held. On the other hand, by setting the thickness to 3 mm or less, the amount of the carrier can be increased in a limited volume filled with the carrier, and the handling property can be improved.

  The diameters of these constituent yarns and the thickness of the net are appropriately selected according to the size of the module. The physical properties and network structure of the polymer having flexibility (softness) and elasticity can be adjusted according to the purpose.

  The seamless net is preferably attached to the cylindrical carrier so that the constituent yarns are 5 ° or more and 85 ° or less with respect to the axial direction of the cylindrical container. By attaching the net so as to be in this range, resistance when passing a medium to be treated such as blood is reduced, and blood can be brought into contact with the carrier more evenly. Also, providing the seamless net so that the constituent yarns are inclined with respect to the axial direction of the module as described above means that the net is more than when the constituent yarns are provided parallel or perpendicular to the axial direction of the module. Since it is possible to effectively utilize the elasticity of the net, it is easy to attach the net to the outer periphery of the carrier.

  When the seamless net is attached, the carrier may be temporarily compressed, but it is preferable that the seamless net is expanded from the viewpoint of handling. Specifically, it is preferable that the net circumference has elasticity that changes to about 1.2 times that before expansion without causing plastic deformation. On the other hand, when the carrier unit is immersed in the liquid, if the carrier swells and the outer diameter of the cylindrical carrier tends to widen, it has rigidity enough to restrain circumferential expansion. It is preferable.

  Next, examples of the carrier used in the present invention will be described. The carrier module of the present invention is suitable for removing leukocytes and cancer cells by adsorption and filtration. Furthermore, it is also suitable for adsorbing and removing physiologically active substances such as cytokines simultaneously with these leukocytes and cancer cells by appropriately selecting the material of the carrier and the fiber diameter.

The bulk density of the carrier in the present invention is 0.5 g / cm ³ or less. The bulk density of the carrier means the weight per fixed volume when the cylindrical container is filled with the carrier. However, if the bulk density is too large, clogging easily occurs during blood circulation, and the medium to be treated such as blood is smooth. The pressure loss may increase. Therefore, in the present invention, the bulk density of the carrier is 0.5 g / cm ³ or less, preferably 0.3 g / cm ³ or less, more preferably 0.15 g / cm ³ or less.

On the other hand, if the bulk density is too small, the strength of the carrier is lowered and the shape retention is deteriorated, which may cause clogging of blood cells in the blood. Depending on how the carrier is filled, drift may occur when a medium to be treated such as blood is passed. If the drift occurs, blood cannot be uniformly contacted with the carrier, which causes a decrease in adsorption or filtration ability. Accordingly, it is preferably 0.01 g / cm ³ or more. Further, it is more preferably 0.02 g / cm ³ or more.

  The bulk density can be measured, for example, by the following method. After the carrier is cut into a 3 cm square, the thickness of the carrier when a 1 mm thick polypropylene plate is placed is measured five times, and the average value is taken as the thickness of the carrier to determine the volume of the small piece. Also, the bulk density is obtained by measuring the weight of the small piece and dividing the weight by the volume. This is carried out with 5 samples and the average value is taken as the bulk density.

  The carrier in the present invention is not particularly limited, but from the viewpoint of processability and pressure loss when used as a blood treatment column, fiber materials such as woven fabric, knitted fabric, and nonwoven fabric, porous films such as porous films and sponges are used. preferable. Moreover, as a carrier material, a known polymer such as polyamide, polyester, polyacrylonitrile-based polymer, polyethylene, polypropylene, or a derivative thereof can be used.

  In the case of a fiber material, it may be a single yarn of the polymer or a core-sheath type, sea-island type, or side-by-side type composite yarn. The cross-sectional shape of the fiber may be a circular cross-section, another irregular cross-section, or a hollow fiber shape. In addition, the diameter of the cross section of the fibers constituting the fiber material (in the case of hollow fibers, the outer diameter of the hollow fibers) should be determined in consideration of the intended adsorption performance. However, for selective removal of granulocytes from blood, it is preferably 4 μm or more, more preferably 5 μm to 10 μm. In addition to this, it is also possible to mix and use thicker fibers at the same time. If a fiber having a cross-sectional diameter of 0.5 to 4 μm is used, it can be suitably used for removing lymphocytes. Furthermore, if fibers less than 0.5 μm are used, it is possible to increase the removal efficiency of the physiologically active substance. The diameter shown here is not only applicable to cylindrical objects, but also applies to, for example, ellipses, rectangles, and polygons, in which case the area of the figure formed by linking the outermost layers is determined, and the area The diameter of the circle corresponding to is obtained and used as the diameter. For example, taking a star shape having five protrusions as an example, a figure connecting the five vertices is considered, its area is calculated, and the diameter of the corresponding circle is the diameter referred to in the present invention.

  The porous film refers to a porous film having a large number of micropores on the surface. The pore size of the micropores is preferably large enough to allow physiologically active substances in blood, that is, proteins, glycoproteins, polysaccharides, proteoglycans, etc., to enter the material. including.

  And when using sheet-like materials, such as a woven fabric, a knitted fabric, a nonwoven fabric, a porous film, as a support | carrier, although it does not limit about the thickness of the sheet-like material, 0.1 mm or more and 10 cm or less are preferable on handling. When incorporated in a radial flow type module, the thickness is preferably 1 cm or less because it is wound around the center pipe. These are determined by the handling method.

  In addition, a substance or a functional group having an adsorbing ability may be introduced into the carrier in order to impart a selective adsorbing ability to a specific substance. Examples of the introduction method include immobilization of a substance or functional group having an adsorption ability by a chemical reaction, and introduction by coating. For example, an amine functional group such as a quaternary ammonium salt and / or a linear amino group is shared. A known technique such as a reaction by radiation irradiation using a hydrophilic monomer and / or a hydrophilic polymer may be used. As the adsorbing material, in order to improve the affinity with an aqueous solution or blood, the surface is preferably hydrophilic, and the material preferably has a hydrophilic coating layer. However, it is not essential to provide a hydrophilic coating layer, since it is possible to improve the affinity also by bringing it into a liquid such as ethanol in advance and then bringing it into contact with an aqueous solution. As a method for enabling the carrier to have a hydrophilic coating layer, the composition of the adsorbing material used is a hydrophilic water-insoluble polymer, and a hydrophilic functional group is covalently bonded to the surface of the water-insoluble polymer. Well-known techniques such as a method of bonding and introducing by a carrier, and a method of coating a carrier material with a hydrophilic water-insoluble polymer can be used.

  The carrier may be combined with a support made of woven fabric, knitted fabric, net or the like to form a laminated structure. Although a two-layer structure of a carrier and a support may be used, it is more preferable to adopt a shape in which a support is sandwiched between carriers, that is, a sandwich structure of carrier-support-carrier. In consideration of the bulk density, it is also possible to make a multilayer structure as long as the pressure loss is not affected.

  As the material for the support, known polymers such as polyamide, polyester, polyacrylonitrile-based polymer, polyethylene, and polypropylene can be used. In the case of subjecting to an organic synthesis reaction for introducing a functional group after being integrated with a carrier, a material may be appropriately selected according to the type of solvent used and the reaction temperature. In particular, polypropylene is particularly preferable from the viewpoint of biocompatibility. By using the support, shape retention can be imparted to the carrier, and a carrier having a stable morphology can be obtained even when the bulk density is small.

  The carrier as described above is generally formed into a hollow cylindrical shape. However, when a sheet-like carrier is used, the sheet-like carrier may be wound around a core material such as a pipe to form a hollow cylindrical shape. However, it may be a hollow cylinder without a core material.

  As a core material, what is necessary is just a shape which has many holes in the surrounding surface of cylindrical members, such as a pipe. Not only a pipe but a cylindrical net may be used. By having a large number of holes in the peripheral surface of the cylindrical member, blood can be passed smoothly.

  The shape of the cylindrical member is not particularly limited as long as the carrier can be wound around the cross section, such as a circle, an ellipse, or a polygon, and the space can be maintained inside. Moreover, what is linear in the axial direction is preferable in order to prevent stagnation of blood.

  The material of the cylindrical member is not particularly limited, but polypropylene, polycarbonate, nylon, polyethylene terephthalate, polyethylene, fluororesin, polyurethane, polysulfone, and the like are preferably used. Note that the size of the cylindrical member and the size of the hole are not particularly limited as long as they are appropriately optimized depending on the size of the carrier, the total amount of blood, the flow rate, and the like.

  When the carrier module is used for the purpose of circulating blood, it is necessary to provide a flow path for guiding blood. For example, a space formed inside the core material is the flow path.

The carrier formed into a hollow cylindrical shape has a cylindrical container having an inlet and an outlet with both ends sealed, and the inlet of the cylindrical container is on the outer periphery of the cylindrical carrier. The outlet of the communicating cylindrical container is stored so as to communicate with the inner peripheral portion of the cylindrical carrier.
When a module using a hollow cylindrical carrier is used for the purpose of removing inflammatory leukocytes in blood, first, most of the inflammatory leukocytes in blood are quickly removed at the outer periphery of the cylindrical carrier, After that, while blood progresses from the outer periphery to the inner periphery of the carrier, the remaining inflammatory leukocytes that could not be removed at the outer periphery of the carrier are also sufficiently removed, so efficient inflammatory leukocyte removal is possible. is there.

  Hereinafter, although the effect of the present invention is shown by an example, the present invention is not limited to these embodiments. In addition, the measurement conditions of each physical property are as follows.

(1) Outer diameter of cylindrical carrier unit The carrier unit is immersed in water, and on one cross section, five outer diameters including the maximum diameter and the minimum diameter are measured using a caliper, and the average value is measured with the carrier. The outer diameter at the location of the unit was used.

(2) Measurement of pressure loss A commercially available blood circuit was connected to the module, and physiological saline was washed at a flow rate of 30 mL / min. Then, heparin (4000 U / L) was added as an anticoagulant and hematocrit adjusted to 40% was flowed at 37 ° C. at a flow rate of 30 mL / min, and the pressure loss of the module was measured. The pressure loss was calculated by connecting a pressure gauge to each of the blood circuits on the inlet side and outlet side of the module and calculating the difference between the inlet side pressure and the outlet side pressure at intervals of 5 minutes. In addition, as a range in which there is no risk of hemolysis or blood coagulation and safety is ensured, a case where blood can be processed without a pressure loss exceeding 100 mmHg was determined to be good.

(3) Preparation of carrier A sea-island composite fiber of 36 islands, in which the islands were further formed by a core-sheath composite, was obtained under the spinning conditions of spinning speed of 800 m / min and draw ratio of 3 times using the following components.

Island core component: Polypropylene Island sheath component: Polystyrene 90wt%, Polypropylene 10wt%
Sea component: Copolymer polyester containing ethylene terephthalate unit as a main repeating unit and 3 wt% of 5-sodiumsulfoisophthalic acid as a copolymer component Composite ratio (weight ratio); Core: sheath: sea = 45: 40: 15
After producing a nonwoven fabric composed of 85 wt% of this fiber and 15 wt% of polypropylene fiber having a diameter of 20 μm, a sheet-like polypropylene net (thickness 0.5 mm, single yarn diameter 0.3 mm, opening 2 mm square) between the two nonwoven fabrics. ) And needle punching to obtain a carrier having a three-layer structure. Next, this nonwoven fabric is treated at 95 ° C. with a 3 wt% sodium hydroxide aqueous solution, and by dissolving polyethylene terephthalate copolymerized with 3 wt% of 5-sodium sulfoisophthalic acid as a sea component, the diameter of the core-sheath fiber is 5 μm. Thus, a nonwoven fabric having a bulk density of 0.02 g / cm ³ was produced.

  Next, 46 wt% of nitrobenzene, 46 wt% of sulfuric acid, 1 wt% of paraformaldehyde, 7 wt% of N-methylol-α-chloroacetamide (hereinafter abbreviated as NMCA) are mixed, stirred and dissolved at 10 ° C or less to prepare an NMCA reaction solution. did. The NMCA conversion reaction solution was brought to 15 ° C., the NMCA conversion reaction solution was added to 1 g of the nonwoven fabric at a solid-liquid ratio of about 40 ml, and the reaction solution was reacted in a water bath for 2 hours while maintaining the reaction solution at 15 to 20 ° C. Thereafter, the nonwoven fabric was taken out from the reaction solution, and immersed in nitrobenzene in the same amount as the NMCA reaction solution and washed. Subsequently, the non-woven fabric was taken out and washed by immersing in methanol to obtain an α-chloroacetamidomethylated polystyrene non-woven fabric (intermediate 1).

  Subsequently, 71 wt% of dimethyl sulfoxide (DMSO), 22 wt% of methanol, 6 wt% of N, N-dimethyloctylamine (DMOA), and 1 wt% of potassium iodide were mixed and dissolved to prepare a DMOA reaction solution. The DMOA reaction solution in the same amount as the NMCA reaction solution was heated to 50 ° C., the intermediate 1 was immersed, and reacted in a 50 ° C. warm bath for 4 hours. The intermediate 1 was taken out from the reaction solution, washed with methanol, then washed with 2 mol / L saline, then washed with water and dried under vacuum to obtain a dimethyloctylammonium non-woven fabric (carrier 1).

[Example 1]
The carrier 1 into which the functional group was introduced was cut into a width of 4.8 cm and a length of 40 cm, and wound around the outer periphery of a polypropylene cylindrical pipe (outer diameter 1 cm) having holes around it. Next, a polypropylene seamless net (thickness: 0.6 mm, single yarn diameter: 0.4 mm, Tokyo polymer (opening) with a rhombus shape and an opening ratio of 0.62 on the outer periphery of the cylindrical carrier. TTX-314PT) manufactured by Co., Ltd. was attached to produce a carrier unit. When the outer diameter of the unit was measured at three locations, it was 34 mm at any location. Further, since the carrier was covered with a cylindrical seamless net, it was not peeled off and the carrier unit itself could maintain its form. Moreover, since the shape of the carrier can be maintained only by the operation of covering the cylindrical seamless net, the workability is also good.

  Subsequently, the carrier unit was housed in a cylindrical polypropylene container having an inner diameter of 36 mm and a length of 50 mm, and a cap having a blood inlet and outlet was fused to both ends of the container to obtain a carrier module. At this time, an end plate is provided at the end of the carrier unit in the axial direction, and the end plate is held by the container main body, so that 1 mm in the axial direction and the circumferential direction is provided between the container and the outer peripheral surface of the carrier unit. Clearance was formed.

  When bovine blood was passed through the carrier module at a flow rate of 30 mL / min for 60 minutes, the maximum pressure loss was 80 mmHg, and blood treatment could be performed satisfactorily.

[Example 2]
Example 1 except that the polypropylene seamless net was changed to a polypropylene seamless net (thickness 0.6 mm, single yarn diameter 0.4 mm) having a rhombus opening and an aperture ratio of 0.54. A carrier unit was prepared by the method described. When the outer diameter of the carrier unit was measured at three locations, it was 34 mm at any location, and the configuration could be maintained by itself without peeling off the carrier. The workability was as good as in Example 1.

  Subsequently, when the carrier module was produced by the method described in Example 1 using the carrier unit, a clearance of 1 mm in the axial direction and the circumferential direction was formed between the outer peripheral surface of the carrier unit and the inner wall of the cylindrical container. Was formed.

  When bovine blood was passed through the carrier module at a flow rate of 30 mL / min for 60 minutes, the maximum pressure loss was 85 mmHg, and blood treatment could be performed satisfactorily.

[Example 3]
Example 1 except that the polypropylene seamless net was changed to a polypropylene seamless net (thickness 0.6 mm, single yarn diameter 0.4 mm) having a square opening and an aperture ratio of 0.44. A carrier unit was prepared by the method described. When the outer diameter of the carrier unit was measured at three locations, it was 33 mm at any location, and the shape of the carrier unit could be maintained by itself without peeling off. The workability was as good as in Example 1.

  Subsequently, a carrier module was produced by the method described in Example 1 using the carrier unit. Between the outer peripheral surface of the carrier unit and the inner wall of the cylindrical container, 1.5 mm in the axial direction and the circumferential direction were provided. Clearance was formed.

  When bovine blood was passed through the carrier module at a flow rate of 30 mL / min for 60 minutes, the maximum pressure loss was 70 mmHg, and blood treatment could be performed satisfactorily.

[Comparative Example 1]
The carrier 1 into which the functional group was introduced was cut into a width of 4.8 cm and a length of 40 cm, and wound around the outer periphery of a polypropylene cylindrical pipe (outer diameter 1 cm) having holes around it. At this time, a sheet-like polypropylene net (thickness 0.6 mm, single yarn diameter 0.4 mm, length 12 cm) having a rhombus shape and an opening ratio of 0.44, a part of the carrier The carrier unit was produced by overlapping and winding so that the outer periphery was covered with the net. When the outer diameter of the unit was measured at three locations, it was 33 mm at any location. Further, the carrier unit is peeled off from the outer peripheral end of the carrier in a free state, and the carrier unit itself cannot maintain its form. Further, compared to Example 1 where the seamless net is covered, the workability is not good because the shape of the carrier unit cannot be fixed simply by overlapping and winding the sheet-like net.

  Subsequently, the carrier unit was placed in a cylindrical polypropylene container having an inner diameter of 36 mm and a length of 50 mm, and a cap having a blood inlet and outlet was fused to both ends of the container to obtain a carrier module. At this time, when the end surface of the carrier unit was observed, a gap was formed between the carrier unit and the inner wall of the container in the vicinity of the end of the winding of the carrier, but the net was in contact with the inner wall of the container except for the part and the clearance. Was almost zero, and the clearance between the inner wall of the container and the outer peripheral surface of the carrier unit was not uniform in the circumferential direction.

  When bovine blood was passed through the carrier module at a flow rate of 30 mL / min, the pressure loss exceeded 100 mmHg during 40-45 minutes from the start of circulation, and blood treatment could not be performed satisfactorily.

[Comparative Example 2]
The carrier 1 was cut into a width of 4.8 cm and a length of 40 cm, and wound around the outer periphery of a polypropylene cylindrical pipe (outer diameter 1 cm) having holes around it. Thereafter, a polypropylene unit having a wire diameter of 125 μm was wound around the outer periphery of the cylindrical carrier at equal intervals at three locations to produce a carrier unit. Compared to Example 1 which covers the seamless net, the yarn is bound with yarn, so that it takes time to produce the carrier unit and the work efficiency is lowered. The outer diameter of the carrier unit was 32 mm when measured at three locations tied with yarn, but it was 35 mm when measured at three locations other than the bound portion, and the size was It was not uniform.

  Subsequently, a carrier module was produced by the method described in Example 1 using the carrier unit. Between the outer peripheral surface of the carrier unit and the inner wall of the cylindrical container, a portion bound with a thread was circumferentially arranged. A clearance of 2 mm was formed, and a clearance of 0.5 mm was formed in the circumferential direction in a portion not bound by the yarn. That is, the clearance was not uniform in the axial direction.

  When bovine blood was passed through the carrier module at a flow rate of 30 mL / min, the pressure loss exceeded 100 mmHg within 55-60 minutes from the start of circulation, and blood treatment could not be performed satisfactorily.

  The carrier module of the present invention can be suitably used as various blood processing modules. It is particularly suitable for removing both leukocytes and cancer cells unnecessary for the human body that are present in excess and physiologically active substances such as cytokines, and is useful for blood treatment and treatment of autoimmune diseases, cancer, allergies, etc. It is.

Claims (7)

A carrier unit including a carrier having a bulk density of 0.5 g / cm ³ or less and a cylindrical seamless net provided on the outer periphery of the carrier; and a cylindrical container in which the carrier unit is accommodated,
The axial end of the carrier unit is provided with an end plate held by the cylindrical container,
A medical carrier module , wherein a clearance is provided between an outer peripheral surface of the carrier unit and an inner wall of the cylindrical container .   The carrier module according to claim 1, wherein an opening ratio of the seamless net is 0.1 or more.   The carrier module according to claim 1 or 2, wherein the carrier includes at least one selected from a woven fabric, a knitted fabric, a nonwoven fabric, and a porous membrane.   The carrier module according to any one of claims 1 to 3, wherein at least one selected from a woven fabric, a knitted fabric, a nonwoven fabric, and a porous membrane is wound in a cylindrical shape. The outer diameter of the carrier unit is A [mm], the inner diameter of the cylindrical container is B [mm], and the clearance formed between the outer peripheral surface of the carrier unit and the inner wall of the cylindrical container is (BA) / when the 2 [mm], 0 <( BA) / 2 satisfies the <10, the carrier module according to claims 1-4. The carrier module according to any one of claims 1 to 5 , wherein the seamless net is provided so that a component thread of the seamless net is 5 ° or more and 85 ° or less with respect to an axial direction of the cylindrical container. . The carrier module according to any one of claims 1 to 6 , which is used for an application in which blood is circulated.