JP2017029712A - Adsorption fiber bundle and body liquid purification column - Google Patents

Abstract

PROBLEM TO BE SOLVED: To provide an adsorption fiber bundle and a column capable of suppressing occurrence of a drift current in the column, and having high adsorption removal performance of a disease cause material, in a body liquid purification column, for solving problems.SOLUTION: An adsorption fiber bundle for body liquid purification comprises, as a center axis, a bar-state substance, the bar-state substance has no channel in which a treated liquid can pass, in its inside, adsorption fibers are wound around the bar-state substance in a spiral-state, and the adsorption fiber bundle is molded into an almost circular column shape.SELECTED DRAWING: Figure 1

Description

  The present invention is directed to removing pathogenic substances in body fluids by adsorption in body fluid purification treatment, and relates to a bundle of fibers capable of adsorbing pathogenic substances and a body fluid purification column incorporating the same.

  Conventionally, the treatment method that removes diseased substances based on the principle of adsorption by circulating the patient's blood extracorporeally and passing it through a body fluid purification column is a high LDL symptom in which the low-density lipoprotein (LDL) concentration in the blood becomes abnormally high In general, it is widely used for sepsis in which the endotoxin concentration in blood is abnormally high.

  These body fluid purification columns are used by passing the body fluid through the column inlet, contacting with the adsorbent in the column, and discharging from the outlet. Thus, the pathogenic substance is adsorbed and removed through a process in which the adsorbent and the body fluid come into contact with each other.

  As the shape of the adsorbent, those using beads or nonwoven fabric are widely used. Moreover, the thing of the form which aligns and fills the thread bundle which aligned the fiber direction of adsorption | suction fiber in the longitudinal direction (usually longitudinal direction) of a cylindrical case is also disclosed.

  For example, Patent Document 1 describes a yarn bundle or rod-shaped porous adsorbent that is aligned in the fiber direction and filled in the longitudinal direction of the cylindrical case. However, Patent Document 1 states that “a gap is formed between the wall surface and the fibrous or rod-shaped porous adsorbent, and when there is a concern about a single flow of body fluid, it is preferable to insert a filler or an adhesive into this gap. When the fibers are filled in a state of being aligned in one direction, the size of the gap formed between the case and the gap between the fibers tends to vary, and the occurrence of drifting is likely to occur. Concerned. When the drift occurs, not only the adsorption performance as a column cannot be exhibited sufficiently, but also stagnation may occur and a thrombus may be formed.

  As other adsorbent forms, Patent Documents 2 and 3 describe inventions in which a case is filled with a blood component adsorbent having a form of beads or fine short fibers to ensure a contact area of the adsorbent.

  In addition, for example, in Patent Documents 4 and 5, a fabric obtained by processing a fiber into a knitted fabric or a nonwoven fabric is continuously wound around the outside of a hollow pipe having a hole in the side so as to be layered when viewed from the pipe cross-sectional direction, A column is disclosed for use in flowing blood from a central pipe to an outer fabric or from an outer fabric to a central pipe.

  In addition, in Patent Document 6, a hollow fiber with a hollow hole on its side surface is wound into a bundle to form a bundle, and the case is filled with blood on either the inside or outside of the hollow fiber, and on the other side. A column is described in which oxygen gas is flowed and gas exchange is performed through contact with a hollow fiber membrane. However, with regard to the flow outside the hollow fiber, the flow direction of the blood from the hole on the side of the hollow pipe toward the spiral hollow fiber bundle is perpendicular to the flow direction of the entire column. There is a possibility that uneven flow may occur by flowing in an oblique direction or staying in the hollow pipe. Therefore, it is necessary to appropriately set the channel resistance by adjusting the case design and the channel diameter and density in the spiral hollow fiber bundle.

JP 60-246765 A JP 2009-254695 A JP 2009-297229 A Japanese Patent Laid-Open No. 9-239022 JP 2002-102332 A JP 11-47268 A

Kazuhiko Ishikiyama et al. JOURNAL OF COLORID AND INTERFACE SCIENCE, 171, 103-111, (1995)

  In the invention according to Patent Document 1, elimination of the drift generated in the above-described column has been a big problem.

  In the inventions according to Patent Documents 2 and 3, it was a problem to uniformly fill the case with the adsorbent in order to bring blood into contact with the adsorbent efficiently.

  Further, in the inventions according to Patent Documents 4 and 5, when the cloth is wound, the step portion when the layers are overlapped from the first layer to the second layer, and the gap between the cloths when the layers are wound are easily generated. As a result, there is a problem that the adsorbing performance cannot be exhibited and the blood stays easily.

  Further, as disclosed in Patent Document 6, when the fiber is spirally wound around the central axis having a flow path through which the liquid to be treated can pass in the central part and the side surface of the rod, the fiber side depends on the part of the central axis. Since there is a difference in the flow rate of the liquid to be processed flowing to the surface, it has been a problem to eliminate the drift.

  In view of the above problems, the problem to be solved by the present invention is to provide an adsorbed fiber bundle and a column with a high pathogenic substance adsorption / removal performance in the body fluid purification column, in which the occurrence of drift in the column is suppressed. It is.

  As a result of intensive studies in order to solve the above problems, the present inventors have found that it is important to improve the adsorption performance by winding the adsorption fibers in a spiral shape to form a substantially cylindrical adsorption fiber bundle. It was. This is because the helical structure can increase the contact area between the adsorbed fiber and blood.

  That is, the adsorbed fiber bundle according to the present invention is shown by the following configuration.

  An adsorbent fiber bundle for body fluid purification, which has a rod-like substance as a central axis, and is formed into a substantially cylindrical shape by adsorbing fibers spirally wound around the rod-like substance.

  Further, according to the findings in the present invention, it is preferable from the viewpoint of uniform flow that there is no flow path in which blood flows in the central portion of the adsorption fiber bundle, that is, there is no hollow space.

  The body fluid purification column according to the present invention is shown by the following configuration.

A casing having each of the body fluid inlet and the body fluid outlet at either end;
An adsorbent fiber bundle housed in the casing,
The adsorbent fiber bundle is a body fluid purification column in which a rod-shaped substance is spirally wound around a central axis and is formed into a substantially cylindrical shape.

  ADVANTAGE OF THE INVENTION According to this invention, the adsorption | suction fiber bundle and purification | cleaning column which can perform the efficient adsorption removal of the pathogenic substance contained in a to-be-processed liquid in which generation | occurrence | production of the drift in a column was suppressed can be provided.

It is the winding shape of the blood component adsorption body which concerns on embodiment of this invention, and adsorption fiber is wound around the rod-shaped substance in the shape of a spiral. It is an expansion | deployment schematic diagram of the blood component adsorption body which concerns on embodiment of this invention, and demonstrates the winding angle when winding helically. It is a figure of the circuit at the time of adsorption | suction performance measurement of a column, and demonstrates the outline of the performance evaluation using blood.

  As the adsorption fiber in the present invention, any material can be used as long as it is a fiber having the ability to capture the target substance from the fluid and reduce the concentration of the target substance in the fluid when it comes into contact with the fluid containing the adsorption target substance. Things can be used. Such a fiber can capture the target substance by a binding or attractive force generated between the fiber and the target substance such as ionic bond, van der Waals force, hydrophobic interaction or specific binding between the ligand and the protein.

  In order to generate an interaction such as bonding or attractive force, the constituent components of the fiber greatly influence. A fiber containing a component that exerts the above-described interaction with the target substance may be used, or a fiber having a ligand or a functional group that causes interaction on the fiber surface is modified even if the fiber does not have the above-described interaction. May be used.

  Generally, it is known that the contact area between the adsorbent and the fluid to be treated greatly contributes to the adsorption efficiency, and the larger the contact area, the more the adsorption is promoted.

  As a means for increasing the contact area, it is effective to reduce the fiber diameter. This is because the surface area per fiber volume can be increased and the entire fiber can be used for adsorption more efficiently. The upper limit of the equivalent circle diameter of the fiber cross section is preferably 300 μm or less, more preferably 240 μm or less, still more preferably 190 μm or less, and particularly preferably 160 μm or less. If the equivalent circle diameter is too large, the amount of yarn packed per unit volume in the column when packed in the column is reduced, which may lead to a decrease in the amount of adsorption. The lower limit of the fiber diameter is preferably 10 μm or more, more preferably 30 μm or more, and particularly preferably 50 μm or more. If the equivalent circle diameter is too small, the strength of the fiber will decrease and it will be easy to cut, so it will lead to destabilization when the fiber is wound around a rod-shaped substance and molded into a substantially cylindrical shape, and impact resistance after commercialization will decrease. There is.

As a method of measuring the equivalent circle diameter, both ends of a yarn to be measured are fixed and cut in a state where a tension of 0.01 to 0.1 g / mm ² is applied. Thereafter, the cut surface is magnified with an optical microscope and photographed. In that case, the scale is also photographed at the same magnification. After digitizing the image, the cross-sectional area S is calculated by tracing the outer circumference of the cross section of the yarn using, for example, the image analysis software “Micro Measurement ver. Calculate the equivalent circle diameter of the opening of. Calculate the average of the 30 measured values and round off to the first decimal place.

Circle equivalent diameter of adsorbed fiber = 2 × (S / π) ^1/2
The cross-sectional shape of the fiber is not limited to a circle, and in order to increase the contact area per unit volume of the fiber, a fiber having at least a part having a different cross-section may be used, or fibers having different cross-sectional shapes may be mixed. May be used.

  In the present invention, the degree of irregularity of the adsorbed fiber is expressed by the ratio of the diameter of the inscribed circle to the circumscribed circle when the yarn cross section is observed, that is, the ratio Do / Di of the diameter Di of the inscribed circle and the diameter Do of the circumscribed circle. .

  Here, the irregular cross-section may be a shape that retains symmetry such as line symmetry and point symmetry, or may be asymmetric, but is generally symmetrical in terms of having uniform fiber properties. It is preferable that When it is determined that the irregular cross-section generally retains line symmetry and point symmetry, the inscribed circle is a circle inscribed in the curve that defines the fiber in the fiber cross section, and the circumscribed circle is a fiber in the fiber cross section. It is a circle that circumscribes the curve that forms the outline of.

  On the other hand, if it is determined that the irregular cross section has a shape that does not retain line symmetry or point symmetry, it is inscribed at least at two points with the curve that forms the outline of the fiber, and exists only inside the fiber. A circle having the maximum radius that can be taken in a range in which the circumference of the tangent circle does not intersect with the curve that forms the outline of the fiber is defined as an inscribed circle. The circumscribed circle is a circle that circumscribes at least two points in the curve showing the contour of the fiber, exists only outside the fiber cross section, and has a minimum radius that can be taken in a range where the circumference of the circumscribed circle and the contour of the fiber do not intersect. A circumscribed circle.

  If the shape of any irregular shape is 1.2 or more, the ability of the fibers to adsorb the substance to be removed can be increased. This is because the degree of profile generally increases the surface area per volume as it increases, so that the adsorption performance can be improved. Therefore, the preferable lower limit of the degree of modification is 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, if the degree of deformity increases too much, another problem can arise. In other words, since the cross-sectional shape is complicated and partially elongated portions are formed, the strength and elongation of the yarn is reduced, the fiber is easily bent or cut, and it is difficult to maintain the fiber shape. Sexuality decreases. In addition, when the spinning dope before being formed as a fiber is quickly cooled using wind or liquid, the complicated shape hinders the flow of wind and liquid into the yarn, resulting in not only the yarn shape but also the surface and the interior. There is a concern that unevenness may occur in the microstructure. Therefore, it is preferable to set a certain upper limit for the degree of deformity, and in the present invention, it is set to 6.6 or less, preferably 4.5 or less, more preferably 3.6 or less.

As a method for measuring the degree of irregularity, both ends of the fiber to be measured are fixed with a tension of 0.1 g / mm ² and cut at random positions. Thereafter, the cut surface is enlarged 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, the diameter Do of the circumscribed circle and the diameter Di of the inscribed circle are measured using, for example, the image analysis software “Micro Measurement ver. 1.04” of SCARA Co., Ltd. . Then, the irregularity degree of each fiber is obtained by the following formula. This measurement is performed at 30 locations, the values are averaged, and the value rounded to the second decimal place is defined as the degree of irregularity.

Deformity = Do / Di
The fiber in the present invention may be either a so-called general hollow fiber or a fiber having no hollow part (solid thread). The upper limit of the ratio of the hollow partial cross-sectional area to the fiber cross-sectional area when using hollow fibers in the present invention is preferably 0.6 or less, more preferably 0.3 or less, particularly preferably 0.1 or less, Preferably it is 0.05 or less. When the ratio of the hollow portion to the fiber cross-sectional area is large, the amount of yarn packed per unit volume in the column when packed in the column is decreased, leading to a decrease in the amount of adsorption as the column, which is not preferable.

  The ratio of the hollow partial cross-sectional area to the fiber cross-sectional area is calculated by analyzing the cross-section of the yarn by the same method as the measurement of the equivalent circle diameter, calculating the fiber cross-sectional area S and the fiber hollow section cross-sectional area Si, calculate.

Ratio of hollow partial cross-sectional area to fiber cross-sectional area = Si / S
In addition, in order to effectively increase the contact area, it is preferable to use a fiber having a porous structure. In particular, those having pores inside are preferred. The lower limit of the average pore radius of the internal pores is preferably 0.5 nm or more, more preferably 1.5 nm or more, particularly preferably 2.0 nm or more, while the upper limit is preferably 100 nm or less, More preferably, it is 40 nm or less, Especially preferably, it is 25 nm or less. Even if it has pores inside, if the average pore diameter is too small, the adsorbed substance may not enter the pores, and the adsorption efficiency may decrease. On the other hand, even if the pore diameter is too large, the adsorbed substance is not adsorbed in the void portion, so that the adsorption efficiency may decrease. Within the above pore diameter range, there is an optimum pore diameter depending on the size of the adsorbed substance to be removed, and if the pore diameter is selected incorrectly, the adsorbed substance may not be sufficiently adsorbed.

  The average pore radius of the porous fiber is determined by measuring the degree of freezing point by capillary aggregation of water in the pores by differential scanning calorimetry (DSC) measurement using a differential scanning calorimeter (DSC). Calculated as radius. The adsorbent material was rapidly cooled to −55 ° C., heated up to 5 ° C. at a rate of 0.3 ° C./min, and the peak top temperature of the obtained curve was taken as the melting point. Calculate the radius.

Primary average pore radius [nm] = (33.30-0.3181 × melting point drop [° C.]) / Melting point drop [° C.]
In the measurement / calculation method, the THEORY formula (2) and the material of the MATERIAL AND METHOD described in Non-Patent Document 1 described above are referred to.

  The material for the porous fiber in the present invention is not particularly limited, but an organic material is preferably used from the viewpoint of easiness of molding and cost, for example, polymethyl methacrylate (hereinafter referred to as PMMA), poly Acrylonitrile (hereinafter referred to as PAN), polysulfone, polyethersulfone, polyarylethersulfone, polypropylene, polystyrene, polycarbonate, cellulose, cellulose triacetate, ethylene-vinyl alcohol copolymer and the like are used. Among them, it is preferable to include a hydrophobic polymer that is an amorphous polymer and has a property of adsorbing protein, and examples thereof include PMMA and PAN. PMMA and PAN are also representative examples of fibers having a uniform structure in the thickness direction, and are preferable because a structure having a uniform structure and a sharp pore size distribution can be easily obtained. Among them, polymethacrylate-based materials are more preferable. Particularly, PMMA is excellent in molding processability and cost, and has high transparency. Therefore, the internal state of the fiber is relatively easy to observe, and the fouling state is evaluated. It is easy and preferable.

  The substantially columnar adsorbed fiber bundle in the present invention indicates a helical fiber bundle 1 when adsorbed fibers 3 are spirally wound around a center rod 2 which is a rod-shaped substance that becomes the center of a column as illustrated in FIG. It is.

  Note that the substantially cylindrical adsorption fiber bundle includes a bundle having a bundle whose cross-sectional diameter is not constant, and may have a shape in which the diameter of the other end is changed with respect to the diameter of one end, for example. Moreover, you may give a constriction in the middle of a substantially cylindrical shape, or may give a bulge conversely.

  The rod-shaped substance in the present invention does not have a flow path through which the liquid to be treated can pass, that is, is solid. Moreover, it plays an extremely important role in stability when winding the adsorbed fiber, strength maintenance after fiber bundle production, and shape maintenance.

  The cross-section of the rod-shaped substance may be an irregular cross section such as a polygon, but a circular cross section is preferred. Using a rod-shaped material with a deformed cross-section, fiber breakage due to force applied at the apex in the deformed shape, fiber deflection between the apexes, and non-uniform flow of liquid to be treated due to the space between the side surfaces of the rod-shaped material There is a risk of conversion.

  The lower limit of the cross-sectional diameter of the rod-shaped substance is preferably 1 mm or more, more preferably 2 mm or more, and particularly preferably 3 mm or more as the equivalent circle diameter. If the cross-sectional diameter of the rod-shaped substance is too small, deformation and destruction of the rod-shaped substance due to fiber tension at the time of winding, and deformation of the fiber bundle after fiber bundle production are likely to occur.

  In addition, the upper limit of the ratio (Rb / Rf) of the cross-sectional diameter (Rb) of the rod-like substance to the outer diameter (Rf) of a cylinder (hereinafter referred to as a fiber cylinder) made of the prepared fibers is preferably 0.7 or less, and more preferably Is 0.6 or less, particularly preferably 0.5 or less, and further preferably 0.3 or less. The lower limit is preferably 0.03 or more, more preferably 0.05 or more, and particularly preferably 0.1 or more. If this ratio is too high, the flow of liquid to be treated in the fiber bundle may be uneven, and the column size may increase. On the other hand, if it is too low, the shape maintenance after the cylinder is produced becomes unstable, and there is a possibility that the yarn arrangement in the cylinder is displaced or distorted, and the fiber breaks due to deformation or twist after insertion into the casing. When the outer diameter of the cylinder is not constant, Rb / Rf calculated using the minimum value of Rf, that is, the maximum value of Rb / Rf is below the above-described preferable upper limit, and Rb / Rf calculated using the maximum value of Rf It is preferable that Rf, that is, the minimum value of Rb / Rf exceeds the preferable lower limit. Similarly, when the cross-sectional diameter of the rod-shaped substance is not constant, the determination may be made using the maximum value of Rb / Rf and the minimum value of Rb / Rf.

  The rod-shaped substance is preferably an instrument made of plastic, metal, or the like. In the case of plastic, for example, a thermoplastic resin excellent in mechanical strength and thermal stability is used. Specific examples of such thermoplastic resins include polycarbonate resins, polyvinyl alcohol resins, cellulose resins, polyester resins, polyarylate resins, polyimide resins, cyclic polyolefin resins, polysulfone resins, polyether sulfones. Resin, polyolefin resin, polystyrene resin, polyvinyl alcohol resin, and mixtures thereof. Among these, resins excellent in moldability and radiation resistance are preferable. This is because a resin excellent in radiation resistance is preferable in the case of radioactive irradiation during sterilization. The resin is manufactured by injection molding using a mold or by cutting a material. Among these, plastic is preferably used from the viewpoints of cost, moldability, weight, blood compatibility and the like. Among these, polypropylene, polystyrene, polycarbonate, and derivatives thereof are preferable in terms of moldability and radiation resistance.

  The fiber occupation ratio in the fiber cylinder of the present invention is extremely important for the adsorption performance of the column. The fiber occupation ratio in the fiber cylinder is preferably 10 to 80%, more preferably 15 to 70%, and particularly preferably 20 to 60%. The range may be any combination of the above upper limit and lower limit. Even if the fiber occupation ratio is too small, the amount of adsorbed fibers packed in the column is small, the adsorption capacity becomes small, and the adsorption performance may be insufficient for use. On the other hand, if it is too large, the flow area of the liquid to be treated is reduced and complicated, and the fluidity is deteriorated.

  The fiber occupation ratio in the fiber cylinder is obtained by removing the rod-like substance volume (Vb) calculated from the cross-sectional area of the rod-like substance and the rod-like substance effective length from the fiber cylinder volume (Vc) calculated from the cross-sectional area and length of the fiber cylinder. It is the ratio of the volume to the fiber volume (Vf) calculated from the fiber cross-sectional area, the number of fibers and the fiber length, and is determined as follows.

Vc = Cylinder cross-sectional area × Fiber cylinder length Vb = Cross-sectional area of rod-shaped substance × Effective length of rod-shaped substance Vf = Fiber cross-sectional area × Number of fibers × Fiber occupancy in long fiber cylinder = Vf × 100 / (Vc−Vb)
When Vc and Vb are obtained, if the cross-sectional diameter is not constant, the volume obtained by appropriately dividing in the length direction can be obtained by adding up the volumes. Moreover, about the effective length of a rod-shaped substance, when the whole length of a rod-shaped substance penetrates the inside of a casing and is longer than casing effective length, a casing effective length is made into a rod-shaped substance effective length. Here, the effective length is the length of the portion where the adsorption works effectively when a body fluid is passed, excluding the portion where the fiber is covered with a potting material or the like in the column.

  The adsorbed fiber bundle in the present invention may be produced by winding one fiber around a rod-shaped substance, or may be produced by simultaneously winding a plurality of fibers arranged at equal intervals. It is preferable that one fiber or a plurality of fibers are continuously wound.

  In the present invention, the continuous winding of the fiber refers to winding without interruption over at least the cylindrical length of the adsorbent (longitudinal axial length of the column), and similarly, winding without interrupting the fiber. It is preferable to overlap. By continuously winding the fibers in this way, it is possible to efficiently wind the fibers, and it is easy to treat the ends of the fibers, and there is a risk that the fibers will unwind inside the case and the shape of the adsorbent may collapse. And the adsorbent can keep its shape inside the case.

  As shown in FIG. 4, the adsorbed fiber 10 has a length (L) 5 of the cylindrical fiber bundle on the outer side of the rod-like substance and an outermost surface circumferential length ( 2πr) 7 is spirally wound with an arbitrary angle θ. This θ is managed as a traverse angle (θ) 8. The upper limit (θ ′) 9 of the traverse angle is a rectangular diagonal line composed of the length (L) 5 of the cylindrical fiber bundle and the semicircular length (πr) 6 at the time of winding the fiber, and the fiber It is managed as an angle between the outermost semicircular circumference (πr) 6 at the time of winding.

  In the present invention, the term “spiral” refers to a thread wound several times with a traverse angle θ with respect to the radial direction of the rod-like substance.

  As a method of winding the yarn, the traverse angle θ is added by rotating the rod-shaped material that has started winding the yarn while moving the thread guide closest to the rod-shaped material in parallel with the axial direction of the rod-shaped material. It can be wound. The yarn path guide that regulates the yarn path may be translated, or the rotating rod-shaped substance may be translated relative to the fixed thread path guide.

  Is wound to one end of the rod-shaped substance, the yarn is wound in the opposite direction toward the other end by reversing the direction of the parallel movement. By continuously repeating this reciprocating operation, the yarn is gradually wound up and wound up to form a cylindrical adsorbent fiber body.

  The traverse angle θ may be changed as the yarn gets thicker or may be constant. The traverse angle θ is expressed by a traverse speed Vt, which is a speed at which the rod-like substance and the yarn path move relatively in parallel, and a yarn winding speed Vr, and can be calculated by the following equation.

θ = tan ⁻¹ (Vt / Vr) (Formula 1)
The traverse angle θ is also maintained in the fiber cylinder after winding.

  The traverse angle θ is an acute angle among the angles formed by the straight line parallel to the bottom surface of the cylinder after winding and the winding yarn, that is, an angle greater than 0 ° and less than 90 °.

  That is, even when the direction of rotation of the rod-like substance is reversed when winding the yarn while maintaining the same traverse angle, the obtuse angle (of the angle formed by the straight line parallel to the bottom of the cylinder and the wound yarn ( 90 ° to 180 °), and more than 0 ° and less than 90 ° are read as θ.

  In the present invention, the traverse angle θ has been found to be extremely important for the shape stability of the fiber cylinder and the fluidity of the liquid to be treated in the fiber. The lower limit of the traverse angle θ is from 0.01 °. It is preferably larger, more preferably greater than 0.1 °, even more preferably greater than 1 °, particularly preferably greater than 5 °, even more preferably 10 ° or more, particularly preferably 20 ° or more. is there. The upper limit θ ′ of the traverse angle θ is preferably an angle satisfying the following formula at any point inside or outside the cylindrical fiber bundle, more preferably less than 50 °, and further preferably less than 40 °.

tanθ ′ = L / πr and 0.01 ° <θ ′ <65 °
In the above formula, L represents the length in the longitudinal direction of the cylindrical fiber bundle, r represents the cross-sectional radius of the cylindrical fiber bundle at the arbitrary point, and π represents the circumferential ratio. For example, θ at a certain point inside the outermost periphery of the cylindrical fiber bundle can be obtained by unwinding the wound yarn until the cross-sectional radius of the target point is reached, and then reading θ. When the outer radius is not constant, the upper limit θ ′ of the traverse angle θ can be obtained by substituting the maximum and minimum average values of the outer radius of the outermost surface of the fiber bundle as r. When the traverse angle is too small, the contact between the fibers becomes too dense, the fluidity of the liquid to be treated is deteriorated, and sufficient adsorption performance may not be exhibited. Further, when the traverse angle is larger than θ ′ represented by the above formula, as shown in FIG. 2, when the fiber is wound around the rod-shaped material, the circumferential direction of the rod-shaped material while the yarn moves from one end to the other end of the rod-shaped material. On the other hand, the length of the wound fiber is not sufficient, and the tension of the yarn may be difficult to be transmitted to the rod-like substance, so that it may be difficult to stably wind the fiber.

  The porous fiber in the present invention can be used as a purification column by being incorporated in a casing having a body fluid inlet and outlet.

  As the shape of the casing, both ends are open ends, and examples thereof include a rectangular cylinder and a cylindrical body such as a square cylindrical body and a hexagonal cylindrical body. Among these, a cylindrical body, particularly a cylindrical body having a perfect circular section is preferable. This is because the body does not have corners so that the body fluid does not stay at the corners. Moreover, by making both sides open, it is difficult for the flow of body fluid to be turbulent, and pressure loss can be minimized. Moreover, it is preferable that a casing is an instrument comprised with a plastic, a metal, etc. In the case of plastic, for example, a thermoplastic resin excellent in mechanical strength and thermal stability is used. Specific examples of such thermoplastic resins include polycarbonate resins, polyvinyl alcohol resins, cellulose resins, polyester resins, polyarylate resins, polyimide resins, cyclic polyolefin resins, polysulfone resins, polyether sulfones. Resin, polyolefin resin, polystyrene resin, polyvinyl alcohol resin, and mixtures thereof. Among these, polypropylene, polystyrene, polycarbonate, and derivatives thereof are preferable in terms of moldability, transparency, and radiation resistance required for the casing. This is because a resin having excellent transparency is convenient for ensuring safety because an internal state can be confirmed during perfusion of blood or the like, and a resin having excellent radiation resistance is preferable when irradiating with radiation during sterilization. The resin is manufactured by injection molding using a mold or by cutting a material. Among these, plastic is preferably used from the viewpoints of cost, moldability, weight, blood compatibility and the like.

  As a method for sealing the end of the purification column, there are a method of arranging a mesh and a method of providing a through hole that is fixed with resin and penetrates the partition wall to communicate the inside and outside of the casing. Here, a through-hole is an opening part penetrating in the porous fiber longitudinal direction of a partition part. In other words, it is a hole that exists in and penetrates the partition wall and communicates the inside and outside of the casing. Among these, the method of arranging the mesh is more preferable because the process is easier than the method of forming the partition walls and the dispersibility of the liquid in the column is high. Also, in order to further increase the dispersibility of the liquid to be treated in the column, a mesh with a larger pressure loss than others is provided on a part of the mesh or a plate called a baffle that blocks the flow is added. Also good.

  In the present invention, it is preferable to provide a porous fiber in which a substance to be adsorbed enters the fiber and is adsorbed. Therefore, it is preferable that the column has a shape and a structure such that the protein can easily move to the inside of the fiber bundle. The movement of fluid in the column can be controlled by the filling rate of fibers into the column, the casing inner diameter, the fiber diameter, the number of fibers, and the like. In the present invention, the upper limit of the fiber filling rate (case filling rate) with respect to the volume of the space excluding the portion occupied by the rod-shaped substance from the casing is preferably 70% or less, more preferably 65%, particularly preferably 62% or less. It is. The lower limit of the case filling rate is 10% or more, more preferably 15% or more, and particularly preferably 20% or more. If the packing rate is too high, the insertability into the case may be deteriorated, and if it is too low, the yarn in the case is biased and the flow in the column may be uneven.

  The calculation method of the case filling rate will be described below. The volume obtained by removing the rod-like substance volume (Vb) calculated from the cross-sectional area of the rod-like substance and the casing length from the casing volume (Vm) calculated from the sectional area and the length of the casing. And the ratio between the fiber cross-sectional area, the casing length, and the fiber volume (Vf) calculated from the number of fibers, is obtained as follows.

Vm = Cross sectional area of casing body × Case effective length Vb = Cross sectional area of rod-shaped substance × Effective length of rod-shaped substance Vf = Fiber sectional area × Number of fibers × Fiber length Case filling rate = Vf / (Vm−Vf) × 100 (% )
In addition, about the cross-sectional area of a casing trunk | drum, when a casing has a taper, it is set as the cross-sectional area in a casing center. Further, when Vc and Vb are obtained, if the cross-sectional diameter is not constant, it can be obtained by appropriately summing the volumes obtained by appropriately dividing in the length direction.

  Regarding the effective length of the rod-shaped material, when the entire length of the rod-shaped material is longer than the casing effective length, such as penetrating the inside of the casing, the casing effective length is set as the rod-shaped material effective length. Here, the effective length is the length of the portion where the adsorption works effectively when a body fluid is passed, excluding the portion where the fiber is covered with a potting material or the like in the column.

  In addition, Vm here does not include the volume of a member portion that does not contain fibers, for example, a member that can serve as an inlet / outlet port of a liquid to be processed, such as a header or a header cap.

  In addition, when a fiber cylinder is inserted into the casing, if a large gap is formed between the casing and the fiber cylinder, the liquid to be treated is short-passed, causing flow unevenness and adsorption removal failure. Therefore, it is preferable that the gap is as small as possible. In order to reduce the gap after inserting the fiber cylinder, the entire inner wall of the case may be filled with potting material, etc., or a mesh or cloth may be further wound around the fiber cylinder to adjust the cylinder diameter and then inserted into the casing. good. The difference (ΔR) in the fiber cylinder cross-sectional diameter (Rf) after insertion with respect to the casing inner diameter (Rc) in the casing cross-section at an arbitrary position after fiber cylinder insertion is preferably 0 mm or more and 5 mm or less, more preferably 0 mm or more and 3 mm or less, Especially preferably, they are 0 mm or more and 1 mm or less. The casing inner diameter (Rc) includes the thickness of the layer when the entire inner wall of the case is filled with a fixing material such as a potting material or an adhesive, but the thickness when the case inner surface is filled with the fixing material or an adsorbent only. Not included. Similarly, the fiber cylinder cross-sectional diameter (Rf) includes the thickness of the layer when a cloth or the like is wound around the fiber cylinder. ΔR = 0 mm substantially means that the side surface of the fiber cylinder is in contact with the casing inner wall or the fixing material.

  The purification column in the present invention can be used mainly for body fluid purification.

  The body fluid to be used by the purification column in the present invention refers to a fluid that is in the living body, such as blood, plasma, lymph, and ascites, and that fills tissues, body cavities, whole-body tubes, circulatory system, and the like.

  In particular, in the case of blood purification applications, there are two methods of treatment: direct perfusion of whole blood and separation of plasma from blood and passage of plasma through the column. The purification column of the present invention is used for both methods. be able to. The removal target is preferably used for pathogenic proteins, bacteria, viruses and the like. In particular, examples of pathogenic proteins include cytokines, β2-microglobulin (β2-MG), IgG, immune complexes, LDL, and the like.

  Moreover, when using as a blood purifier, the method of carrying out adsorption removal on-line by incorporating in an extracorporeal circuit is preferable from the viewpoint of one-time processing amount and ease of operation. In this case, the purification column of the present invention may be used alone or may be used in series with an artificial kidney during dialysis. By using such a technique, it is possible to remove substances that are insufficiently removed only by an artificial kidney simultaneously with dialysis. In particular, the function of the artificial kidney can be complemented by adsorbing and removing large molecular weight substances that are difficult to remove with an artificial kidney using the purification column according to the present invention.

  When used simultaneously with the artificial kidney, it may be connected before the artificial kidney or after the artificial kidney in the circuit. The merit of connecting in front of the artificial kidney is that it is difficult to be affected by dialysis by the artificial kidney, so that the original performance of the purification column is easily exhibited. On the other hand, the merit of connecting after the artificial kidney is that the blood after the water removal by the artificial kidney is processed, so that the solute concentration is high and the adsorption removal efficiency can be expected to increase.

  EXAMPLES Hereinafter, although an Example is given and this invention is demonstrated in detail, this invention is not limited to these.

[Example 1]
<Weight average molecular weight measurement>
The weight average molecular weights of PMMA and PMMA copolymer used for producing porous fibers were determined as follows. First, each PMMA sample was dissolved in 0.1N-lithium chloride.DMF (N, N-dimethylformamide) as a solvent. The relative viscosity at 25.0 ° C. of the sample solution with respect to the solvent was measured using an Ostwald viscometer, and the weight average molecular weight was calculated from the relative viscosity.

<Preparation of porous fiber>
31.7 parts by mass of syn-PMMA having a weight average molecular weight of 400,000, 31.7 parts by mass of syn-PMMA having a weight average molecular weight of 1,400,000, and 16.7 parts by mass of iso-PMMA having a weight average molecular weight of 500,000 Then, 20 parts by mass of a PMMA copolymer having a weight average molecular weight of 300,000 containing 1.5 mol% of parastyrene sulfonic acid soda was mixed with 376 parts by mass of dimethyl sulfoxide and stirred at 110 ° C. for 8 hours to prepare a spinning dope. The obtained spinning dope is discharged into the air at a speed of 1.1 g / min from a base kept at 92 ° C., and the air part is run through 380 mm, then guided to a coagulation bath and passed through the bath. I got a real thread. Water was used for the coagulation bath, and the water temperature (coagulation bath temperature) was 42 ° C. Each fiber was washed with water, guided to a bath composed of an aqueous solution containing 70% by weight of glycerin as a moisturizing agent, passed through a heat treatment bath at a temperature of 84 ° C. to remove excess glycerin, and then wound at 27 m / min. I took it.

  The obtained porous fiber had a circle-equivalent diameter of 111.1 μm, an irregularity of 1.59, and an average pore diameter of 6.6 nm.

<Production of column>
The porous fiber obtained above is wound around a rod-shaped substance made of a polycarbonate cylinder having a length of 20 mm and an inner diameter of 4 mm so that the traverse angle θ is 1 ° until the overall diameter becomes 10 mm to form an adsorption fiber body. did. The adsorption fiber body was built in a polycarbonate cylindrical casing having an inner diameter of 10 mm and an axial length of 20 mm. The case filling rate was 46.4%. Finally, a cap called a header having an inlet and an outlet for the liquid to be treated was attached to the casing end.

<Measurement of column adsorption performance>
As an evaluation of the adsorption performance of the column, the clearance of β2-MG was measured. β2-MG is known to be a causative protein of dialysis amyloidosis, which is a long-term dialysis complication.
Plasma was obtained from bovine blood supplemented with disodium ethylenediaminetetraacetate by centrifugation. The plasma was adjusted so that the total protein amount was 6.5 ± 0.5 g / dL. In addition, bovine plasma was used within 5 days after blood collection. Next, the bovine plasma β2-MG concentration was added to 1 μg / mL and stirred. The bovine plasma was divided into 35 mL for circulation and 50 mL for clearance measurement.

  The circuit was set as shown in FIG. That is, after circulating plasma 15 or clearance measuring plasma 16 kept in a 37 ° C. hot water bath 13 passes through the pump 12 and passes through the purification column 11, one of the branched circuits is for the disposal beaker 14 and the other is for circulation. The structure is connected to plasma 15.

  In the circuit, Bi was taken as the inlet for taking up the liquid to be treated, and Bo as the liquid outlet after the purification column was passed through.

Place Bi in a beaker for circulation containing 35 mL (37 ° C) of bovine plasma prepared above, start the pump at a flow rate of 3.5 mL / min, immediately discard the 90 seconds of liquid discharged from Bo, and immediately Bo was put in a beaker for circulation to obtain a circulation state.
After 1 hour of circulation, the pump was stopped.

  Next, Bi was put in the bovine plasma for clearance measurement adjusted as described above, and Bo was put in a waste beaker.

  The flow rate was 3.5 mL / min. After 2 minutes from the start of the pump, 5 ml of a sample was collected from bovine plasma for clearance measurement (37 ° C.) and used as Bi solution. After 4 minutes and 30 seconds from the start, 5 ml of a sample flowing from Bo was collected and used as Bo solution. These samples were stored in a freezer at -20 ° C or lower.

The clearance was calculated from the β2-MG concentration of each solution according to the following formula I. Since measured values may differ depending on the lot of bovine blood, bovine plasma of the same lot was used for all of the examples and comparative examples.
Co (ml / min) = (CBi−CBo) × QB / CBi (I)
In the formula (I), CO = β2-MG clearance (ml / min), CBi = β2-MG concentration in Bi solution, CBo = β2-MG concentration in Bo solution, QB = Bi pump flow rate (ml / min). .

The amount of β2-MG adsorbed per volume of the adsorbed fiber body was calculated from the concentration of β2-MG in each solution according to the following formula II. Since measured values may differ depending on the lot of bovine blood, bovine plasma of the same lot was used for all of the examples and comparative examples.
Ab (μg / cm ³ ) = (CBs−CBe) × VL / Vf (II)
In the formula (II), Ab is the amount of β2-MG adsorbed per volume of the adsorbed fiber body (μg / cm ³ ), CBs is the β2-MG concentration (μg / mL) of circulating plasma at the start of circulation, and CBe is the end of circulation. Later circulating plasma β2-MG concentration (μg / mL), VL is the circulating plasma volume (mL), and Vf is the fiber volume (cm ³ ).

The β2-MG clearance was 0.33 mL / min, and the β2-MG adsorption amount per volume of the adsorbed fiber body was 26.5 μg / cm ³ .

[Example 2]
Using the same porous fiber and rod-like substance as in Example 1, an adsorption fiber body is formed so that the traverse angle θ is 20 °, and the adsorption fiber body is placed in the same case and header cap column as in Example 1. Built-in. The case filling rate was 27.4%.

The β2-MG clearance measured in the same manner as in Example 1 was 0.20 mL / min, and the β2-MG adsorption amount per volume of the adsorbed fiber body was 42.1 μg / cm ³ .

[Example 3]
Using the same porous fiber and rod-like material as in Example 1, an adsorption fiber body is formed so that the traverse angle θ is 30 °, and the adsorption fiber body is placed in the same case and header cap column as in Example 1. Built-in. Case filling rate was 23.2%.

The β2-MG clearance measured in the same manner as in Example 1 was 0.13 mL / min, and the β2-MG adsorption amount per volume of the adsorbed fiber body was 46.9 μg / cm ³ .

[Example 4]
Using the same porous fiber and rod-like material as in Example 1, an adsorption fiber body is formed so that the traverse angle θ is 40 °, and the adsorption fiber body is placed in the same case and header cap column as in Example 1. Built-in. The case filling rate was 22.1%.

The β2-MG clearance measured in the same manner as in Example 1 was 0.11 mL / min, and the β2-MG adsorption amount per volume of the adsorbed fiber body was 38.4 μg / cm ³ .

[Comparative Example 1]
Using the same porous fiber and rod-like material as in Example 1, after forming an adsorption fiber body so that the traverse angle θ is 30 °, the cylindrical adsorption fiber body from which the rod-like material has been removed is the same as in Example 1. Built in a column consisting of the same case and header cap. The case filling rate was 18.0%.

The β2-MG clearance measured in the same manner as in Example 1 was 0.02 mL / min, and the β2-MG adsorption amount per volume of the adsorbed fiber body was 7.3 μg / cm ³ . The reason why the clearance and the amount of β2-MG adsorbed per volume of the adsorbed fiber body were low was that most plasma did not flow through the adsorbed fiber body but flowed through the central cavity.

  Various numerical data of the above Examples and Comparative Examples are shown together in Table 1.

DESCRIPTION OF SYMBOLS 1 Spiral fiber bundle 2 Center rod 3 Adsorption fiber 4 Outer surface development at the time of fiber winding 5 Length of cylindrical fiber bundle (L)
6 Semi-circumferential length of outermost surface when winding fiber (πr)
7 Circumference of outermost surface (2πr) when winding the fiber
8 Traverse angle (θ)
9 Upper limit of traverse angle (θ ')
DESCRIPTION OF SYMBOLS 10 Adsorption fiber 11 Purification column 12 Pump 13 37 degreeC hot water bath 14 Disposal beaker 15 Circulating plasma 16 Clearance measuring plasma

Claims (12)

Having a rod-like substance as the central axis,
The rod-shaped substance does not have a flow path through which the liquid to be treated can pass,
An adsorbent fiber bundle for purifying body fluid, in which adsorbent fibers are spirally wound around the rod-shaped substance and formed into a substantially cylindrical shape. The adsorption fiber bundle for body fluid purification according to claim 1, wherein the adsorption fibers are continuously wound. The adsorbed fiber bundle according to claim 1 or 2, wherein at least a part of the adsorbed fibers has an irregular shape in cross section. The adsorption fiber bundle according to any one of claims 1 to 3, wherein the adsorption fiber has a porous structure. The adsorption fiber bundle according to any one of claims 1 to 4, wherein a traverse angle θ of the adsorption fibers satisfies a range of 0.01 ° <θ ≦ θ '.
However, θ ′ is tan θ ′ = L / πr and 0.01 ° <θ ′ <65 ° satisfying the following formula at an arbitrary point inside or outside the cylindrical fiber bundle.
L: Length in the longitudinal direction of the cylindrical fiber bundle [m], r: Cross-sectional radius [m] of the cylindrical fiber bundle at the arbitrary point, π: Circumference ratio [−] The adsorption fiber bundle according to any one of claims 1 to 5, wherein a base material of the adsorption fiber is a hydrophobic polymer. The adsorbed fiber bundle according to claim 6, wherein the hydrophobic polymer is polymethacrylate-based. The adsorbed fiber bundle according to any one of claims 1 to 7, wherein the fiber occupation ratio is 10 to 80%. The ratio (Rb / Rf) of the cross-sectional diameter (Rb) of the rod-shaped substance to the outer diameter (Rf) of the adsorption fiber bundle is 0.03 or more and 0.7 or less, according to any one of claims 1 to 8. Adsorption fiber bundle as described. A casing having each of the body fluid inlet and the body fluid outlet at either end;
An adsorbent fiber bundle housed in the casing,
The adsorbent fiber bundle is a body fluid purification column in which a rod-shaped substance is spirally wound around a central axis and is formed into a substantially cylindrical shape. The body fluid purification column according to claim 10, wherein a difference (ΔR) in a substantially cylindrical cross-sectional diameter (Rf) of the adsorption fiber bundle with respect to the casing inner diameter (Rc) is 0 mm or more and 5 mm or less at an arbitrary position of the casing cross section. The body fluid purification column according to claim 10 or 11, wherein a case filling rate which is a filling rate of the fiber with respect to a volume of a space excluding a portion occupied by the rod-like substance from the casing is 10% or more and 70% or less.