Hollow fibers and blood purifiers

Abstract

To provide a hollow fiber yarn which can achieve both excellent blood compatibility and solute removal performance.SOLUTION: A hollow fiber yarn has a pore in a film thickness part, in which a value of dRa that is arithmetic average roughness on an inner surface in a dry state is 5-21 nm, a value of wRa that is arithmetic average roughness on an inner surface in a wet state is 9-29 nm, and a value of wRa / dRa is 1.05 to 1.49.SELECTED DRAWING: None

Description

[Technical Field]

[0001] The present invention relates to a hollow fiber and a blood purifier. [Background technology]

[0002] Membranes such as hollow fibers built into blood purifiers, such as artificial kidneys, require a high degree of hemocompatibility because they come into direct contact with blood, plasma, etc. In a single treatment, the main issue is to suppress the activation of the coagulation system, such as platelets.However, in long-term treatments such as dialysis, chronic microinflammation is likely to occur, and suppressing the activation of white blood cells, etc., also becomes an important issue.

[0003] Hollow fibers can efficiently remove excess water and solutes from blood, and this removal can be achieved not only by permeation through the fibers but also by adsorption onto the fibers. This adsorption also makes it possible to simultaneously remove large molecular weight proteins that are difficult to remove by permeation. However, hollow fibers are prone to adsorbing proteins, and the adsorbed proteins act as a scaffold for platelets and white blood cells, causing them to adhere to and activate the fibers, resulting in problems such as a decrease in blood cell count, activation of blood cells, and inflammation.

[0004] Known techniques for improving the blood compatibility of hollow fibers include optimizing the membrane surface roughness in a wet state to suppress thrombus formation due to platelet activation (Patent Document 1), and limiting the yield strength of the hollow fiber membrane to a specific range (Patent Document 2). Other known hollow fiber methods include selectively removing small-molecular protein urea substances by heat treatment after production (Patent Document 3), and chemically modifying the inner surface to achieve both adsorption and removal performance and platelet adhesion suppression (Patent Document 4). [Prior art documents] [Patent documents]

[0005] [Patent Document 1] Japanese Patent Application Laid-Open No. 2005-224604 [Patent Document 2] Japanese Patent Application Laid-Open No. 2008-246402 [Patent Document 3] Japanese Patent Application Laid-Open No. 2008-245921 [Patent Document 4] Japanese Patent Application Laid-Open No. 2011-062282 Summary of the Invention [Problem to be solved by the invention]

[0006] However, with conventional techniques, it has been difficult to achieve both sufficient blood compatibility and sufficient solute removal performance, including efficient adsorption and removal of proteins and the like.

[0007] Therefore, an object of the present invention is to provide a hollow fiber that can achieve both excellent blood compatibility and solute removal performance. [Means for solving the problem]

[0008] In order to solve the above problems, the hollow fiber of the present invention has pores in a membrane thickness portion, and is characterized in that the arithmetic mean roughness dRa of the inner surface in a dry state is 5 to 21 nm, the arithmetic mean roughness wRa of the inner surface in a wet state is 9 to 29 nm, and the wRa / dRa value is 1.05 or more. [Effects of the Invention]

[0009] According to the present invention, it is possible to provide a hollow fiber and a blood purifier that are excellent in blood compatibility and solute removal performance. DETAILED DESCRIPTION OF THE INVENTION

[0010] A hollow fiber is a straw-shaped fiber having a hollow portion inside. From the viewpoints of ease of molding and cost, the constituent material of the hollow fiber of the present invention is preferably a polymer, such as polymethyl methacrylate (hereinafter referred to as "PMMA"), polyacrylonitrile, polysulfone, polyethersulfone, polyarylethersulfone, polypropylene, polystyrene, polycarbonate, polylactic acid, polyethylene terephthalate, cellulose, cellulose triacetate, ethylene-vinyl alcohol copolymer, polyvinylidene fluoride, polymethylpentene, or polycaprolactam. Since a polymer with a suitable hydrophobicity can achieve both the adsorption and removal of proteins and the like and blood compatibility, PMMA, polyacrylonitrile, or polystyrene is more preferred.

[0011] The hollow fiber of the present invention has pores in the membrane thickness portion. Here, the membrane thickness portion refers to the thickness portion of the hollow fiber other than the inner and outer surfaces. The presence of pores in the membrane thickness portion reduces the resistance to solute movement inside the hollow fiber, thereby improving permeation and removal performance. In the case of adsorption, solutes can be adsorbed not only on the surface of the hollow fiber but also in the pores due to hydrophobic interactions, thereby improving the adsorption and removal performance per unit volume of the hollow fiber.

[0012] When the inner surface of the hollow fiber of the present invention is in a dry state, the value of dRa, which is the arithmetic mean roughness of the inner surface, must be 5 to 21 nm. The minute irregularities present on the inner surface disrupt the flow of blood in the immediate vicinity of the inner surface and thin the boundary layer with the solute on the inner surface, thereby improving the performance of adsorbing and removing leptin and the like. Therefore, the value of dRa is preferably 6 nm or more, more preferably 7 nm or more, and even more preferably 8 nm or more. On the other hand, the value of dRa is preferably 19 nm or less, more preferably 18 nm or less, and even more preferably 17 nm or less, in order to reduce the frequency of contact, collision, or abrasion between blood cells contained in the blood and the inner surface and thereby suppress damage to blood cells and activation of leukocytes, such as an increase in CD11b.

[0013] The "inner surface" of a hollow fiber refers to the surface of the hollow fiber exposed to the hollow portion inside the fiber. The "dry state" refers to the state in which a hollow fiber that has been thoroughly moistened with pure water is immersed in liquid nitrogen, the water in the pores is instantly frozen with the liquid nitrogen, and the frozen water is then sublimated in a vacuum dryer at 0.1 torr (13.3 Pa) or less.

[0014] When the inner surface of the hollow fiber of the present invention is in a wet state, the arithmetic mean roughness (wRa) of the inner surface must be 9 to 29 nm. For the same reasons as for dRa, the wRa value is preferably 10 nm or more, more preferably 11 nm or more, and even more preferably 12 nm or more. On the other hand, it is preferably 25 nm or less, more preferably 23 nm or less, and even more preferably 21 nm or less.

[0015] The term "wet state" refers to a state in which the hollow fibers are filled with water, the water content of which exceeds the saturation level, and water drips from the hollow fibers.

[0016] The value of wRa / dRa, obtained by dividing wRa by dRa, must be 1.05 to 1.49. When wRa / dRa is 1.05 or more, the molecular chains on the surface of the hollow fiber can form a layer in which they are sufficiently swollen when they come into contact with blood. On the other hand, when wRa / dRa is 1.49 or less, a decrease in blood compatibility due to an increase in eluates from excessively swollen hollow fibers can be suppressed.

[0017] The dRa value can be calculated by fixing a dry hollow fiber to a silicon wafer with double-sided tape, shaving it into a semi-cylindrical shape with a single blade, and observing the exposed inner surface. Specifically, a scanning probe microscope (e.g., NanoScope V Dimension Icon; manufactured by Bruker) is used to observe three randomly selected locations on the inner surface within a 3 μm × 3 μm observation field, measuring the arithmetic mean roughness Ra at each location, and the average of these Ra values ​​can be used as the dRa value. The observation mode is peak force tapping, and the cantilever is a SiN cantilever.

[0018] The wRa value can be determined by performing the same measurements as above on a wet hollow fiber in water using a scanning probe microscope (e.g., NanoScope V Dimension FastScan Bio; manufactured by Bruker), and averaging the measurements to determine the wRa value.

[0019] The pore size of a hollow fiber is evaluated by its peak pore diameter. If the peak pore diameter is too large, the solute adsorption and removal performance per unit volume of the hollow fiber decreases. On the other hand, if the peak pore diameter is too small, it becomes difficult to adsorb substances with large molecular weights, and water permeability also decreases. Therefore, the peak pore diameter is preferably 0.03 μm or more, more preferably 0.05 μm or more, even more preferably 0.07 μm or more, and particularly preferably 0.09 μm or more. On the other hand, it is preferably 2.00 μm or less, more preferably 0.90 μm or less, even more preferably 0.60 μm or less, and particularly preferably 0.30 μm or less.

[0020] The peak pore diameter of the pores can be measured by mercury intrusion porosimetry. Specifically, a measurement sample is placed in a pore size distribution measurement device (e.g., Autopore IV9510, manufactured by Micromeritics), and the pore size distribution is measured under the following measurement conditions. The pore size at which the pore volume peaks in the obtained pore size distribution curve can be determined as the peak pore size.

[0021] The measurement sample can be prepared by thoroughly wetting a hollow fiber with pure water, immersing it in liquid nitrogen to freeze it, and then immediately folding it. The water is removed using a vacuum dryer at 0.1 torr (13.3 Pa) or less, and a thin film of platinum (Pt) or platinum-palladium (Pt-Pd) is then sputtered onto the surface of the dried material. <Measurement conditions> Mercury intrusion pressure: 3 to 400,000 kPa Measurement pore diameter: 4 to 10,000 nm Measurement mode: Pressure increase process Measurement cell volume: 5cm 3 Mercury contact angle: 141.3° Mercury surface tension: 484dyn / cm The surface opening ratio of the inner surface of the hollow fiber of the present invention is preferably 1.0 to 30.0%. To ensure a flow path from the surface of the hollow fiber to the membrane thickness portion and improve adsorption and removal performance, the surface opening ratio of the inner surface is more preferably 1.5% or more, even more preferably 2.0% or more, and particularly preferably 2.5% or more. On the other hand, to smooth the inner surface and reduce physical stimulation to platelets and leukocytes in the blood, thereby inhibiting their activation, the surface opening ratio is more preferably 25% or less, even more preferably 20% or less, and particularly preferably 13% or less. Furthermore, the surface opening diameter of the inner surface of the hollow fiber is preferably 10.0 μm or less, more preferably 6.0 μm or less, even more preferably 3.0 μm or less, and particularly preferably 1.0 μm or less, to inhibit excessive removal of useful substances and blood cells in the blood.

[0022] Samples for measuring the surface open area ratio and surface open area diameter of the inner surface of hollow fiber membranes can be prepared in the same manner as for measuring pore size distribution by mercury intrusion. The inner surface of the sample is exposed and observed at 50,000x magnification using a scanning electron microscope (e.g., S-5500; Hitachi High-Technologies Corporation). Images measuring 640 pixels x 480 pixels are imported into a computer, randomly cropped into 6 μm x 6 μm areas, and analyzed using image processing software. Image analysis involves binarization, where a threshold is set so that the openings appear dark and the rest appear bright, resulting in an image in which bright areas are clearly distinguished as white and dark areas as black. If binarization is not possible due to small differences in contrast within the image, the image can be divided into sections with similar contrast ranges, binarized separately, and then reassembled to restore a single image. Note that the image contains noise; dark areas with five or fewer consecutive pixels are eliminated as noise. These operations are repeated 30 times, and the ratio of the number of pixels in the dark brightness area to the total number of pixels in the 30 analysis images is calculated as a percentage, which is the surface opening rate of the inner surface.The average of the circle equivalent diameters of each dark brightness area in the 30 analysis images can be used as the surface opening diameter of the inner surface.

[0023] The pores of the hollow fiber of the present invention are preferably uniform in the direction perpendicular to the longitudinal direction of the hollow fiber, i.e., have a homogeneous structure. The homogeneous pore structure ensures many adsorption sites by hydrophobic interactions.

[0024] Here, the pores having a homogeneous structure means that the average pore size ratios RI and RO, represented by the following formulas (1) and (2), are both 0.2 to 3.0.

[0025] RI = average pore size in the area near the inner surface / average pore size in the central area (1) RO = average pore size in the area near the outer surface / average pore size in the central area (2) A sample for measuring the average pore size of a hollow fiber can be prepared in the same manner as in the pore size distribution measurement by mercury intrusion porosimetry described above. A cross section perpendicular to the longitudinal direction of the measurement sample is observed using a scanning electron microscope (e.g., S-5500; Hitachi High-Technologies Corporation). Here, the cross section of the hollow fiber, which is the measurement sample, between the inner and outer surfaces is equally divided into five regions. The region closest to the inner surface is designated the inner surface near-region, the central region of the five divisions is designated the central region, and the region closest to the outer surface is designated the outer surface near-region. The circle-equivalent diameters of the pores present in each of the inner surface near-region, central region, and outer surface near-region are determined, and the average pore diameter in each region is calculated. To calculate the average pore diameter in each region, 20 randomly selected areas of 2 μm × 2 μm are photographed at 50,000x magnification using a scanning electron microscope. The circle-equivalent diameters of all pores included in each photograph are determined, and the average of these diameters is used as the average pore diameter. The equivalent circle diameter can be determined by placing a transparent sheet on a printout of the photograph, filling in the pores with black using a black pen or the like, and then copying the transparent sheet onto a blank piece of paper to clearly distinguish the pores as black and the rest as white, and then using image analysis software.

[0026] The hollow fiber of the present invention preferably has longitudinally continuous protrusions on its outer surface. Having longitudinally continuous protrusions on its outer surface is expected to prevent adhesion between hollow fibers when multiple hollow fibers are bundled and incorporated into a blood purifier. Furthermore, since thick and thin membrane portions are formed, water and other substances can quickly pass through the thin membrane portions with low membrane resistance, while the thick membrane portions can provide sufficient adsorption sites for solutes. The number of protrusions is preferably 1 or more, more preferably 2 or more, even more preferably 3 or more, particularly preferably 4 or more, and most preferably 8 or more.

[0027] To increase the contact area with blood, the cross section of the hollow fiber perpendicular to the longitudinal direction may have an irregular shape other than a circle, such as a triangle, a rectangle, a Y-shape, a cross, or a star shape.

[0028] Considering the balance between the strength of the hollow fiber and the adsorption / removal performance per unit volume of the hollow fiber, the membrane thickness of the hollow fiber is preferably 15 to 90 μm, more preferably 20 to 75 μm, and even more preferably 25 to 40 μm.

[0029] If the inner diameter of the hollow fiber is too small, there is a concern that the pressure loss of the blood will increase, while if it is too large, the amount of filling liquid in the blood purifier will increase, which may impose a burden on the patient during extracorporeal circulation. Therefore, the inner diameter is preferably 120 to 260 μm, more preferably 140 to 240 μm, and even more preferably 160 to 220 μm.

[0030] The hollow fiber permeability is 20mL / hr / m to efficiently remove excess water from the blood of patients with renal failure, etc. 2 / mmHg or more is preferred, 31mL / hr / m 2 / mmHg or more is preferable, and 41mL / hr / m 2 On the other hand, if the water permeability is too high, the phenomenon of residual blood remaining inside the hollow fiber after treatment is likely to occur. 2 / mmHg or less is preferred, and 400mL / hr / m2 / mmHg or less is more preferable, and 200mL / hr / m 2 / mmHg or less is more preferable, and 160mL / hr / m 2 / mmHg or less is particularly preferred.

[0031] The water permeability of hollow fibers can be measured using a mini-module. Specifically, 48 hollow fibers are bundled and placed inside a cylindrical plastic tube, both ends of the tube are fixed with potting material, and the ends of the potting material are cut so that the length of the hollow fiber bundle is 10 cm, creating a mini-module with both ends of the hollow fiber membranes open. Water is passed through the hollow fibers inside the mini-module at a hydraulic pressure of 100 mmHg, and the filtration rate, which is the amount of water per unit time that flows out the outer surface of the hollow fibers, is measured. The water permeability (UFR) of the hollow fibers can then be calculated using the following formula (3):

[0032] UFR (mL / hr / m 2 / mmHg)=Qw / (P×T×A) (3) where Qw: filtration volume (mL), T: outflow time (hr), P: pressure (mmHg), A: inner surface area of ​​hollow fiber (m 2 )

[0033] The blood compatibility of hollow fibers is evaluated based on the fluorescence intensity of CD11b, which is expressed on leukocytes when fresh human blood comes into contact with hollow fibers. The lower the CD11b fluorescence intensity, the more suppressed the activation of leukocytes that cause inflammatory reactions in tissues is, and the hollow fibers can be determined to have excellent blood compatibility. The CD11b intensity expressed on leukocytes when fresh human blood comes into contact with hollow fibers is preferably 14.0 or less, more preferably 12.0 or less, even more preferably 10.0 or less, and particularly preferably 9.0 or less. Here, "fresh human blood" refers to venous blood from a healthy individual collected within 30 minutes, to which the anticoagulant heparin sodium injection has been added at 5 U / mL.

[0034] The fluorescence intensity of CD11b when fresh human blood comes into contact with hollow fibers can be measured as follows (steps 1 to 3 below are performed in a clean bench to prevent contamination).

[0035] 1. The total surface area of ​​the hollow fiber is 0.0030 m 2 A mini-module is fabricated in the same manner as in the measurement of water permeability described above, except that the number of hollow fibers is appropriately adjusted so that the mini-module is washed by passing at least 200 mL of physiological saline through it.

[0036] 2. After discarding the saline solution in the mini-module, 6 mL of fresh human blood is circulated for 15 minutes at 37°C at a linear velocity of 1 cm / sec within the hollow fiber, and the blood is then collected.

[0037] 3. A fluorescently labeled CD11b antibody solution (PE anti-human CD11b; BioLegend) was added to the collected blood and allowed to react at room temperature for 15 minutes, after which the blood was fixed with a hemolysis fixative (OptiLyseB; Beckman Coulter) and diluted with pure water as necessary to prepare the evaluation sample. Fresh human blood was also left to stand at 37°C for 15 minutes to prepare the control sample.

[0038] 4. Using a flow cytometer (e.g., FACS Calibur; manufactured by BD), the fluorescence intensity of CD11b of cells present in the granulocyte fraction for each of the evaluation sample and the control sample is quantified, and the value obtained by subtracting the fluorescence intensity of the control sample from the fluorescence intensity of the evaluation sample can be used as the fluorescence intensity of CD11b when fresh human blood comes into contact with the hollow fiber.

[0039] The hollow fiber of the present invention is preferably capable of highly efficiently adsorbing and removing pathogenic substances in the blood, such as cytokines, β2-microglobulin (β2-MG), low-density lipoproteins, very-low-density lipoproteins, and apolipoproteins. The adsorption and removal performance of the hollow fiber can be evaluated using leptin, which is believed to be related to the deterioration of the nutritional status of dialysis patients. The leptin adsorption and removal performance when human serum comes into contact with the hollow fiber is 5 μg / cm or less.3 More than 15 μg / cm is preferable. 3 More preferably, 30 μg / cm 3 More preferably, 55 μg / cm 3 More preferably, 80 μg / cm 3 The above is particularly preferred.

[0040] The leptin adsorption and removal performance when human serum is brought into contact with the hollow fiber can be measured as follows.

[0041] Human leptin (e.g., manufactured by Fujifilm Wako Pure Chemical Industries, Ltd.) was added to human serum (e.g., manufactured by Cosmo Bio Co., Ltd.) to a concentration of 0.10 μg / mL to prepare leptin-added human serum. 6 mL of the prepared leptin-added human serum was placed in a 15 mL centrifuge tube (e.g., manufactured by Greiner), and a hollow fiber was inserted therein to a depth of 0.0142 cm. 3 The mixture was shaken side to side at a rate of 30±1 strokes per minute for 4 hours at 37°C. The human serum containing leptin was sampled before and after shaking, and the leptin concentration was quantified by ELISA. The leptin adsorption and removal performance upon contact between human serum and hollow fibers can be calculated based on the following formula (4).

[0042] Leptin adsorption and removal performance (μg / cm 3 )=(C1-C2)×6 / 0.0142 (4) C1: Leptin concentration before shaking (μg / mL) C2: Leptin concentration after shaking (μg / mL) One example of a hollow fiber spinning method is to use a double-tube annular slit-type hollow fiber spinneret. The spinning dope is passed through the outer tube and discharged, and a liquid or gas is passed through the inner tube to form a hollow section. The hollow fiber then passes through a certain dry air section and reaches a coagulation bath. Here, for example, the membrane thickness of the hollow fiber can be controlled by adjusting the amount of the spinning dope, and the inner diameter of the hollow fiber can be controlled by adjusting the amount of the liquid or gas. Furthermore, the peak pore diameter of the hollow fiber can be controlled by adjusting the temperature of the coagulation bath. For example, when the spinning dope contains PMMA and gas is passed through the inner tube, the temperature of the coagulation bath is preferably 35°C or higher, more preferably 38°C or higher. On the other hand, it is preferably 48°C or lower, more preferably 44°C or lower.

[0043] It is preferable to use a gas to flow through the inner tube, as this makes it easy to set dWa, wRa, surface opening ratio, and surface opening diameter within suitable ranges and the gas does not remain in the hollow portion formed. The dew point of the gas is preferably 5°C or less, more preferably -1°C or less, and even more preferably -9°C or less.

[0044] The spinning solution may be, for example, a solution in which a polymer is dissolved in a solvent. In this case, the polymer concentration is preferably 30% by mass or less, more preferably 27% by mass or less, and even more preferably 24% by mass or less. For example, the peak pore diameter of the hollow fiber pores can be controlled by adjusting the polymer concentration in the spinning solution.

[0045] The solvent adhering to the coagulated hollow fibers can be washed away by, for example, passing the hollow fibers through water. The temperature of the water used for washing can be determined depending on the material of the hollow fibers. For example, when the material of the hollow fibers is PMMA, a temperature of 30 to 50°C is preferred.

[0046] After washing, the hollow fibers may be brought into contact with a moisturizing liquid such as glycerin or an aqueous solution thereof in order to maintain the moisture and shape of the pores.

[0047] After washing or contact with a moisturizing solution, the hollow fibers may be passed through a heat treatment bath filled with a heated moisturizing solution to enhance dimensional stability. The temperature of the moisturizing solution in the heat treatment bath can be determined depending on the material of the hollow fibers. For example, when the hollow fibers are made of PMMA, the temperature is preferably 75°C or higher, more preferably 78°C or higher, and even more preferably 95°C or lower, and particularly preferably 90°C or lower.

[0048] The blood purifier of the present invention has the hollow fiber of the present invention built in. Examples of the blood purifier include a hemodialyzer or a hemofilter, which are generally called artificial kidneys, and a slow hemofilter or hemodiafilter for emergency use. [Example]

[0049] Example 1 A spinning dope was prepared by mixing 31.7 parts by mass of syn-PMMA with a weight-average molecular weight of 400,000, 31.7 parts by mass of syn-PMMA with a weight-average molecular weight of 1.4 million, 16.7 parts by mass of iso-PMMA with a weight-average molecular weight of 500,000, 20 parts by mass of a PMMA copolymer with a molecular weight of 300,000 containing 1.5 mol% sodium p-styrenesulfonate, and 376 parts by mass of dimethyl sulfoxide at 110°C for 8 hours. The resulting spinning dope was extruded into air at a rate of 2.5 g / min through the outer tube of a double-tube annular slit hollow fiber spinneret with an outer diameter / inner diameter of 2.10 / 1.95 mmφ (annular slit section) maintained at 95°C. Air at a temperature of 25°C and a dew point of -9°C was flowed through the 1.30 mm diameter circular tube inside the annular slit section. The dry air section was allowed to run for 50 cm, then introduced into a coagulation bath to produce hollow fibers. The water temperature of the coagulation bath was 43°C. After rinsing the hollow fiber, it was contacted with a 60% by mass aqueous solution of glycerin as a moisturizing liquid and passed through a heat treatment bath at 85°C. After that, a spacer yarn was wound around it and it was taken up at 60 m / min. The inner diameter / membrane thickness of the obtained hollow fiber was 200 / 30 μm. The results of various measurements performed using this hollow fiber are shown in Table 1.

[0050] Example 2 A hollow fiber was obtained in the same manner as in Example 1, except that air at a temperature of 20° C. and a dew point of −5° C. was passed through a circular tube with an inner diameter of 1.30 mm. Various measurements were performed using this hollow fiber, and the results are shown in Table 1.

[0051] Example 3 A hollow fiber was obtained in the same manner as in Example 1, except that air at a temperature of 12° C. and a dew point of −1° C. was passed through a circular tube with an inner diameter of 1.30 mm. Various measurements were performed using this hollow fiber, and the results are shown in Table 1.

[0052] Example 4 A hollow fiber was obtained in the same manner as in Example 1, except that a spinneret with eight 0.3 mm square protrusions evenly spaced around the outer side of the annular slit was used. The cross section of the hollow fiber obtained in the direction perpendicular to the longitudinal direction of the hollow fiber was not circular, but had an irregular shape with eight protrusions, each 20 μm in height and width. Various measurements were performed using this hollow fiber, and the results are shown in Table 1.

[0053] (Comparative Example 1) A hollow fiber was obtained in the same manner as in Example 1, except that air with a temperature of 25° C. and a dew point of 20° C. was passed through the inner tube of the double tube. Various measurements were performed using this hollow fiber, and the results are shown in Table 1.

[0054] (Comparative Example 2) A hollow fiber was obtained in the same manner as in Example 1, except that pure water at a temperature of 25° C. was passed through the inner tube of the double tube. Various measurements were carried out using this hollow fiber, and the results are shown in Table 1.

[0055] From the results in Table 1, it is clear that the hollow fiber of the present invention can achieve excellent blood compatibility and solute removal performance.

[0056] [Table 1]

Claims

1. A composition comprising polymethyl methacrylate, The membrane has pores in the membrane part. the peak pore diameter of the pores is 0.03 to 2.00 μm; The value of dRa, which is the arithmetic mean roughness of the inner surface in a dry state, is 11 to 12 nm; The value of wRa, which is the arithmetic mean roughness of the inner surface in a wet state, is 13 to 14 nm; The value of wRa / dRa is 1.17 to 1.18, A hollow fiber having average pore size ratios RI and RO represented by the following formulas (1) and (2) of 0.2 to 3.0: RI=average pore size in the region near the inner surface / average pore size in the central region (1) RO = average pore size in the region near the outer surface / average pore size in the central region (2)

2. 2. The hollow fiber according to claim 1, wherein the surface opening ratio of the inner surface is 1.0 to 30.0%.

3. 3. The hollow fiber according to claim 1, wherein the diameter of the surface openings on the inner surface is 10.0 μm or less.

4. 4. The hollow fiber according to claim 1, wherein the outer surface has continuous projections extending in the longitudinal direction.

5. Water permeability is 20 mL / mmHg・hr・m ２ The hollow fiber according to any one of claims 1 to 4, wherein

6. 6. The hollow fiber according to claim 1, wherein the fluorescence intensity of CD11b when contacted with fresh human blood is 14.0 or less.

7. The leptin adsorption and removal performance when contacted with human serum was 5 μg / cm ３ The hollow fiber according to any one of claims 1 to 6, wherein

8. A blood purifier incorporating the hollow fiber according to any one of claims 1 to 7.

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