JP2011235204A - Hollow fiber membrane - Google Patents

Abstract

PROBLEM TO BE SOLVED: To provide a hollow fiber membrane of high yield strength as well as high porosity, and of excellent capability of removing a protein of a low molecular weight, which can easily be fabricated into a module.SOLUTION: The hollow fiber membrane of an inner diameter of 150 to 250 μm, a membrane thickness of 10 to 30 μm, porosity of 75% or greater, and yield strength of 17 g or greater constituted of an aggregate of particles, is characterized in that the range of 60% of the membrane thickness in the direction from the inner surface to the outer surface thereof is constituted of a structure which is filled with particles of a mean diameter of 50 nm or greater.

Description

  The present invention relates to a hollow fiber membrane that is excellent in strength and elongation even though the porosity is higher than ever. In more detail, by increasing the porosity, it has the performance of type IV to V of the dialyzer function class, but it improves the handling and module assembly of the hollow fiber membrane by improving the strength and slipping. Relates to the hollow fiber membrane.

  In blood purification methods for the treatment of renal failure, natural materials such as cellulose, cellulose diacetate, cellulose triacetate, and synthetic polymers such as polysulfone, Modules such as hemodialyzers, hemofilters or hemodialyzers using dialysis membranes or ultrafiltration membranes using polymers such as ether sulfone, polymethyl methacrylate, polyacrylonitrile, etc. as separation materials are widely used. . Modules using hollow fiber membranes as separation materials are particularly important in the field of blood purification due to advantages such as reduction of circulating blood volume related to extracorporeal circulation, high substance removal efficiency in blood, and productivity of module assembly. High degree.

  Modules using hollow fiber membranes normally flow blood through the hollow part of the hollow fiber membrane, flow dialysate counter-currently to the outer part, and reduce the amount of urea, creatinine, etc. by mass transfer based on diffusion from blood to dialysate. The main goal is to remove molecular weight substances from the blood. Furthermore, with the increase in the number of long-term dialysis patients, dialysis complications have become a problem. In recent years, substances to be removed by dialysis are not only low molecular weight substances such as urea and creatinine, but also have a molecular weight of several thousand to a molecular weight of 1 to 20,000. Blood purification membranes are required to expand to high molecular weight substances and to remove these substances. In particular, β2 microglobulin having a molecular weight of 11700 has been found to be a causative substance of carpal tunnel syndrome and is a removal target. Membranes used for such high molecular weight substance removal treatment are called high performance membranes. In recent years, in Japan, a hollow fiber membrane having an asymmetric structure, in which a synthetic polymer is a main component of a base material, has been used clinically as a high performance membrane.

  In addition, hollow fiber membranes with an asymmetric structure made of synthetic polymers such as polysulfone resins and polyacrylonitrile have sharp fractionation characteristics by having a skin layer on the inner surface that comes into contact with blood. On the other hand, it also has a property that the change with time due to the fact that the fractionation layer is only a thin layer on the inner surface is remarkable (for example, see Non-Patent Document 1).

  As a blood purification film composed of a single component that does not require a hydrophilizing agent, there is a film composed of cellulose acetate. Since cellulose acetate has a structure in which most of the hydroxyl groups that activate the trappings are substituted with acetyl groups, it is a material excellent in blood compatibility without using a hydrophilizing agent. In the blood purification application of cellulose acetate, the issue is to improve the fractionation characteristics and blood compatibility, and the technology to control the particle size of the inner surface in contact with blood, the technology to smooth the inner surface, and the synthetic polymer In order to develop a fractionation characteristic equivalent to that of the structure, a structure having a dense layer on the inner surface has been studied. (For example, see Patent Documents 1, 2, 3, and 4).

  Patent Document 5 discloses a technique relating to a hollow fiber membrane for blood purification that is made of cellulose acetate, has high water permeability, and has excellent performance stability regardless of the patient's condition. A comparative example discloses a hollow fiber membrane having a porosity of 81.4 to 85.6%. However, the yield strength is as low as 7.9 to 12.6 g per single yarn, and there is a problem with the handleability of the hollow fiber membrane.

  Patent Document 6 discloses a technique related to a module having high water permeability and low performance influence on blood system protein concentration and excellent performance stability. And it is described that the porosity of the films obtained in Examples 2 and 4 and Comparative Example 3 is 83.5%, 86.2%, and 85.7%. Only low is obtained.

Renal and dialysis separate volume 63, 195-196 2007 (HDF therapy)

JP 2002-45662 A JP 2006-340977 A JP 2008-178814 A JP-A-10-66725 International Publication No. 2007/102528 Pamphlet JP 2008-284186 A

  An object of the present invention is to provide a hollow fiber membrane that has an excellent yield strength while having a high porosity, not only an excellent removability of low molecular weight proteins, but also an excellent modularity.

  In developing hollow fiber membranes, there was a trade-off between high performance and high elongation. As a result of diligent studies to solve the above problems, the present inventor has secured the high elongation by optimizing the membrane structure while having the performance of the dialyzer function classification IV type to V type by increasing the porosity. At the same time, by optimizing the presence of the hydrophilizing agent on the outer surface of the hollow fiber membrane, a hollow fiber membrane having improved handling properties and module assemblability of the hollow fiber membrane in a subsequent process has been obtained.

The inventor has finally reached the present invention as a result of intensive studies to solve the above problems. That is, the present invention has the following configuration.
(1) A hollow fiber membrane having an inner diameter of 150 to 250 μm, a film thickness of 10 to 30 μm, a porosity of 75% or more, and a yield strength of 17 g or more. A hollow fiber membrane characterized by having a structure filled with particles having an average diameter of 50 nm or more in a range of 60% of the film thickness toward the outer surface.
(2) When the cross section of the hollow fiber membrane is observed with a scanning electron microscope, the macro void is not substantially observed in the membrane cross section in the photograph taken at a magnification of 10,000 times. Hollow fiber membrane.
(3) When the cross section of the hollow fiber membrane is observed using a transmission electron microscope, the outer surface side has a denser structure than the inner surface side. (1) or (2) The hollow fiber membrane as described.
(4) The hollow fiber membrane according to any one of (1) to (3), wherein the hollow fiber membrane is made of a cellulose acetate-based polymer.
(5) A hollow fiber membrane module produced by inserting the hollow fiber membrane according to any one of (1) to (4) into a case so that the end portion filling ratio is 45 to 65%.
(6) The hollow fiber membrane module according to (5), which is used for blood purification.

  The hollow fiber membrane of the present invention imparts high yield strength despite having a high porosity, so it not only excels in removing low molecular weight proteins, but also in impact resistance and handling properties. Good handling and module assembly yield.

The SEM image which shows an example of the cross-sectional structure of the hollow fiber membrane of this invention. 3 is a TEM image showing an example of the structure of the hollow fiber membrane of the present invention. 3 is a TEM image showing an example of the structure of the hollow fiber membrane of the present invention. Schematic which shows a part of manufacturing process of the hollow fiber membrane of this invention. The enlarged view of the glycerol scraping part in the manufacturing process of the hollow fiber membrane of this invention. The microscope picture which shows an example of the droplet adhering to the surface of a hollow fiber membrane.

  Hereinafter, the present invention will be described in detail.

  In order to solve the above problems, the present inventor examined the relationship between the manufacturing process of the hollow fiber membrane, the structure of the hollow fiber membrane, and the performance in blood. In order to improve the removal performance of low molecular weight proteins such as β2 microglobulin in blood, an asymmetric structure with a skin layer on the inner surface is advantageous, and in the market, a blend of a polysulfone polymer and a hydrophilizing agent is used. An asymmetric hollow fiber membrane is the mainstream. However, in such a blend membrane, elution of the hydrophilizing agent from the membrane is unavoidable even in a blood purification treatment of about 4 hours, and the performance change between the start and end of treatment may become remarkable. Moreover, there is a possibility of causing allergic symptoms due to elution of the hydrophilizing agent. In order to obtain a hollow fiber membrane having good module assembly while achieving high performance without using a hydrophilizing agent, the present inventor has a hollow structure with a high porosity and a high elongation, while having a homogeneous structure. In order to obtain a yarn membrane, it was studied earnestly. And it became possible to obtain a hollow fiber membrane excellent in high dialyzability and module assemblability by taking into account the optimization of the basic structure of the membrane, the provision of appropriate stretching in the production process, and the suppression of membrane shrinkage.

  In the present invention, the hollow fiber membrane preferably has an inner diameter of 150 to 250 μm. If the inner diameter is too small, the pressure loss of the blood flowing through the hollow portion of the hollow fiber membrane increases, so that there is a risk of hemolysis. On the other hand, if the inner diameter is too large, the shear rate of blood flowing through the hollow portion of the hollow fiber membrane becomes small, so that proteins in the blood easily accumulate on the inner surface of the membrane over time. The inner diameter at which the pressure loss and shear rate of the blood flowing inside the hollow fiber membrane is in an appropriate range is 160 to 230 μm.

  In the present invention, the average thickness of the hollow fiber membrane is preferably 10 μm or more and 30 μm or less. When the average film thickness is too large, the permeability of the medium to high molecular weight substance may be insufficient even if the water permeability is high. Further, in terms of module design, when the film area is increased, if the film thickness is large, the module becomes large, which is not appropriate. A thinner film thickness is preferred because the material permeability increases, more preferably 25 μm or less, and even more preferably 20 μm or less. If the average film thickness is too thin, it may be difficult to maintain the minimum film strength required for the module in evaluating defects such as burst pressure. Therefore, the average film thickness is more preferably 12 μm or more, and further preferably 13 μm or more. An average film thickness here is an average value when five hollow fiber membranes sampled at random are measured. At this time, the difference between each value and the average value does not exceed 20% of the average value.

  In the present invention, the hollow fiber membrane preferably has a porosity of 75% or more. More preferably, it is 78% or more, More preferably, it is 80% or more. If the porosity is increased, the movement resistance of the substance passing through the film thickness portion is reduced, so that the dialysis performance can be improved accordingly. However, considering the handleability of the hollow fiber membrane, particularly the module assembly property, the porosity of 80% or more has already exceeded the strength limit as a separation membrane. Therefore, the present inventor changed the structure of the hollow fiber membrane from a network structure to a particle-packed structure. The particle-packed structure is easier to control than the network structure to increase the porosity and particle diameter, and is considered suitable for higher performance and strength. However, if the porosity exceeds 87%, the required yield strength cannot be obtained.

  In the present invention, the yield strength of the hollow fiber membrane is preferably 17 g or more per single yarn. 19 g or more is more preferable, and 20 g or more is more preferable. If the yield strength is low, the hollow fiber membrane manufacturing process cannot be scraped off, or the hollow fiber membrane loosens during assembly of the module, causing the hollow fiber membrane bundle to be biased in the module (causing the dialysate to drift). May cause problems.

In the present invention, when the cross section of the hollow fiber membrane is observed using a transmission electron microscope (TEM), a structure in which the outer surface side is denser than the inner surface side is preferable. Observation with TEM is suitable because the distinction between particles and voids becomes clear. A dense structure is a portion that is observed relatively densely when judged by the contrast of the cross section of the film at a magnification at which the cross section of the film can be observed from one side to the outside when viewed with a TEM. Is a dense structure. The cross-sectional sample is observed at a plurality of locations on the sample. In any case, it is confirmed that the cross-sectional contrast has the same tendency, and finally, the presence / absence and position of a dense structure is determined. Here, when observing the film cross-sectional structure, it is not suitable to use partially different images because the density may not be simply compared because of the amount of light when TEM observation is performed. The dense layer is a fractional layer that acts directly on separation, and the fact that the fractional layer is on the outer surface side can be expected to be fractionated by a combination of depth filtration and sieving, which is effective in suppressing performance degradation. There is.
In a dense layer, even if the observation magnification of TEM is increased to 20,000 times, it is difficult to measure the particle size because the particles are close to each other.

In the present invention, it is preferable that the structure is filled with particles having a diameter of 50 nm or more in the region of about 60% of the film thickness from the inner surface to the outer surface. The particle size is more preferably 55 nm or more and 150 nm or less, and further preferably 60 nm or more and 140 nm or less. When particles in this range are evenly packed, proteins in blood, mainly albumin, can be present on the blood contact surface (inner surface) as a reversible layer. Excellent. In the case of an aggregate of particles having a diameter exceeding 150 nm, the strength of the hollow fiber membrane may be weakened.
If there is a dense layer on the inner surface of the hollow fiber membrane, especially a skin layer with a small pore size and a thin structure, a reversible protein adsorption / desorption layer cannot be present on the inner surface of the hollow fiber membrane in contact with blood. Stress is generated between the membrane and blood, which is not suitable.

  In the hollow fiber membrane of the present invention, it is preferable that macrovoids are not substantially observed in the membrane cross section. In the structure having a dense skin layer on the inner surface or outer surface of the film and containing voids in the middle part, the effect of the present invention is hardly obtained because the structural change of the skin layer hardly occurs. In addition, if a macro void exists in the hollow fiber membrane, the distance between the membrane constituent molecules becomes large, and the membrane contraction due to electrostatic attraction between the membrane constituent molecules becomes difficult to work, or the effect of the present invention is hardly obtained. Here, a film in which macrovoids are not substantially observed is a void derived from a void or a structure having a diameter exceeding 0.7 μm when a cross section of the film is observed at a magnification of 10,000 times with a scanning electron microscope. Shows a homogeneous structure where no is observed.

  In the present invention, the base material constituting the hollow fiber membrane is preferably a single polymer base material that is free from worry about the eluate into blood, and cellulose acetate is preferred as a module. In addition, cellulose triacetate having a high degree of substitution of hydroxyl groups is more preferable because it has an effect of suppressing capture activation.

  The hollow fiber membrane of the present invention is suitable for modules used for the treatment of renal failure, such as hemodialysis, hemodiafiltration, and hemofiltration. In addition, despite its high performance, there is no eluate such as hydrophilizing agent from the membrane, and it can be expected to suppress oxidative stress caused by the patient's own blood components. Yes.

The water permeability (UFR) of pure water at 37 ° C. of the hollow fiber membrane in the present invention is preferably in the range of 150 ml / m ² / hr / mmHg to 1500 ml / m ² / hr / mmHg. If the water permeability is less than 150 ml / m ² / hr / mmHg, it cannot be said that the object of the present invention is high water permeability, and generally the amount of protein leak is also low. When the water permeability is too large, the pore diameter becomes large, and the amount of protein leak may increase too much. Therefore, a more preferable range of water permeability is 150 ml / m ² / hr / mmHg to 1200 ml / m ² / hr / mmHg, more preferably 150 ml / m ² / hr / mmHg to 1000 ml / m ² / hr / mmHg. is there.

Using the hollow fiber membrane of the present invention, a module having a membrane area of 1.5 m ^{2 on} the basis of the inner diameter was prepared, and human β 2 MG (molecular weight 11,600) was added to the blood channel side at a concentration of 0.05 to 0.1 mg / l. The ACD (acid-citrate-dextrose) -added bovine plasma kept at 37 ° C was flowed at a flow rate of 200 ml / min, and the dialysate was placed on the dialysate side. When flowing at 500 ml / min and filtered at a filtration flow rate of 15 ml / min, the clearance of β2MG (CLβ15) at 60 minutes after the start of dialysis can reach 60 ml / min or more. It is also possible to exhibit the performance of

  As a method for producing such a hollow fiber membrane, the following conditions are preferable. In order to obtain a particle-packed structure, the polymer concentration of the spinning dope should be lowered, and in order to make the particle diameter in the region near the inner surface 50 nm or more, depending on the type of polymer, etc., in the case of cellulose triacetate 18 mass% or less, more preferably 17 mass% or less. However, since the required film strength may not be obtained even if the polymer concentration in the spinning dope is too low, it is preferably 12% by mass or more, and more preferably 14% by mass or more.

  The spinning solution is preferably filtered immediately before nozzle discharge for the purpose of removing insoluble components and gel. The pore diameter of the filter is preferably small. Specifically, the pore diameter is preferably not more than the thickness of the hollow fiber membrane, and more preferably not more than 1/2 of the thickness of the hollow fiber membrane. When there is no filter or when the pore diameter of the filter exceeds the film thickness of the hollow fiber membrane, a part of the nozzle slit may be clogged, resulting in occurrence of uneven thickness yarn. Furthermore, when there is no filter or when the filter pore diameter exceeds the film thickness of the hollow fiber membrane, partial voids are likely to be caused due to mixing of insoluble components or gels in the spinning dope. In the case of a particle-packed structure, defects in the film such as voids significantly reduce the strength as a blood purification film. Filtration of the stock solution for spinning may be carried out a plurality of times before discharging, which is preferable because the life of the filter can be extended.

  A smaller draft ratio is preferable. Specifically, 1 or more and 10 or less are preferable, 3 or more and 9 or less are more preferable, and 5 or more and 9 or less are more preferable. The draft ratio referred to here is the ratio of the hollow fiber membrane take-off speed at the coagulation bath outlet and the discharge linear speed of the spinning dope discharged from the nozzle (hollow fiber membrane take-off speed / discharge spinning speed of the spinning dope). If the draft ratio is too large, tension is applied during the formation of the film structure, and the deformation and uniformity of the particles may be impaired.

  In order to control the viscosity of the spinning dope in the spinning region, the nozzle temperature when discharging the spinning dope is preferably 50 ° C. or higher and 130 ° C. or lower, more preferably 70 ° C. or higher and 120 ° C. or lower, and more preferably 80 ° C. or higher and 110 ° C. The following is more preferable. If the nozzle temperature is too low, the viscosity of the spinning dope increases, so that the pressure applied to the nozzle increases and the spinning dope may not be discharged stably. On the other hand, if the nozzle temperature is too high, it may affect the film formation by phase separation and the pore size may become too large.

  The discharged spinning solution is immersed in the coagulating liquid through the aerial traveling section. In order to increase the phase separation speed of the outer surface of the membrane, the aerial traveling unit at this time is preferably surrounded by a member (spinning tube) that shields from the outside air, and the relative humidity is preferably increased. Specifically, it is preferable to feed water vapor from the outside and set the relative humidity in the spinning tube to 80 to 100% RH. 90 to 100% RH is more preferable. When the temperature of the supplied steam is drastically lowered in the spinning tube, condensation occurs and the outer surface structure of the membrane becomes non-uniform. Therefore, the temperature of the steam is preferably lower than the temperature in the spinning tube. In order to control the temperature in the spinning tube, a heater for heating the spinning tube from the outside may be installed. The temperature of the water vapor is preferably 15 ° C. or higher and 100 ° C. or lower, more preferably 30 ° C. or higher, and further preferably 40 ° C. or higher. If there is unevenness in the convection of the water vapor in the spinning tube, the phase separation speed will be uneven. Therefore, consideration must be given to feeding the water vapor in the spinning tube so as not to cause unevenness. Specifically, a method of installing a plurality of nozzles for feeding water vapor into the spinning tube is preferable. Although the length of the aerial traveling part depends on the spinning speed, it is preferably 3 to 150 mm, more preferably 5 to 100 mm, and still more preferably 5 to 70 mm. The time for the spinning solution discharged from the nozzle to pass through the spinning tube is preferably 0.0001 seconds to 1.0 seconds, and more preferably 0.001 seconds to 0.1 seconds.

  In the present invention, it is preferable to use a liquid or gas that is inert to the spinning dope as the hollow forming material. Specific examples of such a hollow forming material include liquid paraffin, isopropyl myristate, nitrogen, argon, and the like. Non-solvents such as glycerin, ethylene glycol, triethylene glycol, and polyethylene glycol can be added to these hollow forming materials as necessary.

  The film that has been gelled through the aerial traveling part advances phase separation (grows particles) by passing through a coagulation bath. At this time, the coagulating liquid is preferably an aqueous solution of a solvent used in preparing the spinning dope. When the coagulating liquid is an aqueous solution, the phase separation rate from the outer surface is accelerated, which is preferable. It is the present invention that the two-stage phase separation reaction of passing through an aqueous solution coagulation bath that promotes phase separation from the outer surface in a state where phase separation from the outer surface is promoted by water vapor in the aerial traveling section This is a means for forming a relatively dense layer near the outer surface. The solvent concentration of the coagulation bath is preferably 30% by mass or less, more preferably 27% by mass or less, and further preferably 24% by mass or less. However, if the solvent concentration of the coagulation bath is too low, it is difficult to control the concentration during spinning. Therefore, the lower limit of the solvent concentration is preferably 1% by mass or more, more preferably 5% by mass or more, and further preferably 10% by mass or more. The temperature of the coagulation bath is preferably 5 ° C. or more and 50 ° C. or less for controlling the coagulation rate. 10 degreeC or more and 45 degrees C or less are more preferable. A non-solvent such as glycerin, ethylene glycol, triethylene glycol, or polyethylene glycol, or an additive such as an antioxidant or a lubricant can be added to the coagulation bath as necessary.

  By combining various conditions as described above, it is possible to have a particle packing structure in which the particle size is 50 nm or more in the region of at least 60% of the film thickness from the inner surface to the outer surface of the hollow fiber membrane. It becomes possible.

In order to increase the yield strength of the hollow fiber membrane, the hollow fiber membrane of the present invention is preferably stretched in a coagulation bath. Although the detailed mechanism is unknown by imparting stretching in the coagulation bath, it is considered that the polymers forming the hollow fiber membrane are aligned and the Young's modulus is increased, and the strength against external pressure can be imparted. The stretching here is preferably 5 to 20%, more preferably 10 to 17%. The term “stretching” as used herein refers to the ratio between the second coagulation bath inlet roller speed and the second coagulation bath outlet roller speed.
Stretch ratio (%) = (exit roller speed−inlet roller speed) / inlet roller speed × 100

  The hollow fiber membrane that has passed through the coagulation bath is washed away with unnecessary components such as a solvent through a washing step. The cleaning liquid used at this time is preferably water, and a temperature of 20 ° C. to 80 ° C. is preferable because the cleaning effect is enhanced. If it is less than 20 ° C, the cleaning efficiency is poor, and if it exceeds 80 ° C, the thermal efficiency is poor, and the burden on the hollow fiber membrane is large, which may affect the storage stability and performance. Also, in the process after the structure of the hollow fiber membrane is almost solidified, if a strong force is applied from the outside, the membrane structure, surface shape, and hole shape may be deformed. It is preferable to devise such that resistance is not applied as much as possible. In order to remove unnecessary components such as solvents and additives from the hollow fiber membrane, it is preferable to increase the renewal of the liquid. Conventionally, for example, the hollow fiber membrane is run in the shower of the cleaning liquid, or the flow of the cleaning liquid Cleaning efficiency was improved by making the running of the hollow fiber membrane counter-current. However, when such a cleaning method is adopted, the running resistance of the hollow fiber membrane increases, so that it has been necessary to prevent the hollow fiber membrane from being stretched and loosened or drooped.

  In order to achieve both the suppression of the membrane structure destruction of the hollow fiber membrane and the cleaning performance, it is effective to flow the cleaning liquid and the hollow fiber membrane in parallel flow. As a specific aspect of the washing step, for example, a facility in which the washing bath is inclined and the hollow fiber membrane is lowered is preferable. Specifically, the inclination of the bath is preferably 1 to 3 degrees. If it exceeds 3 degrees, the flow rate of the cleaning liquid becomes too fast, and the running resistance of the hollow fiber membrane may not be suppressed. If it is less than 1 degree, the cleaning failure of the hollow fiber membrane may occur due to the retention of the cleaning liquid. Thus, by suppressing the resistance to the hollow fiber membrane in the cleaning bath, the traveling speed of the hollow fiber membrane at the inlet of the cleaning bath and the traveling speed of the outlet can be made substantially the same. In order to further increase the cleaning efficiency, the cleaning baths are preferably arranged in multiple stages. The number of stages needs to be set appropriately depending on the balance with detergency. For example, if the purpose is to remove the solvent, non-solvent, hydrophilizing agent, etc. used in the present invention, there should be about 3 to 30 stages. That's enough.

  The hollow fiber membrane that has undergone the washing step is subjected to a treatment for filling the pores with glycerin. In this case, the glycerin concentration is preferably 80 to 95% by mass. More preferably, it is 70-90 mass%. If the glycerin concentration is too low, the hollow fiber membrane tends to shrink during drying, and storage stability may deteriorate. On the other hand, if the glycerin concentration is too high, excess glycerin tends to adhere to the hollow fiber membrane, and the adhesiveness at the end of the hollow fiber membrane may deteriorate when assembled into a module. The temperature of the glycerin bath is preferably 50 ° C. or higher and 80 ° C. or lower. More preferably, it is 60 degreeC or more, More preferably, it is 70 degreeC or more. When the temperature of the glycerin bath is too low, the viscosity of the glycerin aqueous solution is high, and there is a possibility that the glycerin aqueous solution does not reach all the pores of the hollow fiber membrane. If the temperature of the glycerin bath is too high, the hollow fiber membrane may be denatured and altered by heat.

  The hollow fiber membrane subjected to the glycerin treatment is one or more provided at the front stage and / or the rear stage of the drying step as shown in FIGS. 4 and 5 in order to remove the excess glycerin aqueous solution adhering to the hollow fiber membrane surface. The glycerin aqueous solution is moved from the surface of the hollow fiber membrane to the surface of the roller in contact with the roller. Since the glycerin aqueous solution adhering to the roller surface is removed by the scraper that contacts the roller, the hollow fiber membrane always comes into contact with the roller whose surface has been renewed. Of course, two or more scrapers may be provided for one roller. The thickness of the glycerin liquid layer on the surface of the hollow fiber membrane is controlled by passing such a process a plurality of times as necessary. At this time, it is preferable that the thickness of the glycerin liquid layer adhering to the surface of the hollow fiber membrane is set so as to exceed the boundary friction and enter the fluid friction region. By forming the glycerin liquid layer to the extent that fluid friction occurs, it becomes possible to improve the slipperiness of the hollow fiber membrane and obtain good module assemblability.

  On the other hand, the hollow fiber membrane of the present invention has a problem that liquid droplets are likely to occur because the glycerin liquid layer is formed on the surface of the hollow fiber membrane as described above. A droplet refers to a liquid agglomerate formed on the surface of a hollow fiber membrane as shown in FIG. As a cause of the generation of droplets, it can be considered that foreign matter (dust) attached to the surface of the hollow fiber membrane serves as a nucleus and absorbs moisture in the atmosphere to form droplets. When droplets are generated, adhesion failure may occur in the assembly of the module, or urethane used for bonding may react with moisture in the droplets to generate an eluting oligomer. Therefore, in the present invention, in order to suppress the generation of droplets, air treated with a dust removal filter is used when the hollow fiber membrane is dried, or humidity control is performed when the hollow fiber membrane is removed.

  Moreover, it is preferable that the humidity of the atmosphere at the time of scraping shall be 30-55% RH. More preferably, it is 35 to 45% RH. If the humidity during winding is too high, excess moisture will adhere to the hollow fiber membrane and droplets will be generated on the surface of the hollow fiber membrane, resulting in poor adhesion at the end of the hollow fiber membrane when assembled into a module. There is. On the other hand, if the humidity is too low, the hollow fiber membrane has no suitable moisture, so that the surface of the hollow fiber membrane is crushed and the scavenging property may be deteriorated. By setting the humidity of the atmosphere at the time of winding to a specific range, good module assemblability can be obtained.

  A hollow fiber membrane thus obtained is bundled into a plurality of bundles and inserted into a module case to produce a module. At this time, the filling rate of the hollow fiber membrane at the module case end is preferably about 45 to 65%. When the filling rate is low, the assembly of the module is improved, but the flow of the dialysate tends to drift, and the performance of the hollow fiber membrane may not be sufficiently exhibited. On the other hand, when the filling rate is high, the hollow fiber membranes are liable to be crushed and deformed, and the gap between the hollow fiber membranes is small, and problems such as poor adhesion are likely to occur. The hollow fiber membrane of the present invention optimizes the adhesion state of the hydrophilizing agent and suppresses the generation of droplets in addition to giving consideration to increasing the strength of the hollow fiber membrane, particularly the yield strength. Therefore, handling and module assembly are good.

  Hereinafter, the effectiveness of the present invention will be described with reference to examples, but the present invention is not limited thereto. In addition, the evaluation method of the hollow fiber membrane in the following this invention is as follows.

(Measurement of breaking strength and yield strength)
The breaking strength and yield strength of the hollow fiber membrane are measured using a tensile tester (Tensilon UTMII manufactured by Toyo Baldwin). A single yarn having a total length of about 15 cm is fixed to a chuck (distance between chucks: 10 cm), and a full-scale 100 g cell connected to the chuck is raised at a speed of 100 mm / min. The breaking elongation and breaking strength at which the hollow fiber membrane is cut from the chart paper are read out to obtain an SS curve. The point where the auxiliary line with an extended initial slope and the auxiliary line with zero inclination at the maximum point intersect is defined as the yield point, the strength at that point is the yield strength, and the elongation is the yield elongation.

(Observation of cross-sectional structure (transmission electron microscope (TEM)))
The hollow fiber membrane to be evaluated is washed with water and then dehydrated with ethanol. After dehydration, ethanol is replaced with 3-methylbutyl acetate, and the membrane is dried using a critical point drying device (manufacturer name, device type). The dried membrane was embedded in resin, and ultrathin sections were prepared using a microtome. The prepared ultrathin slice was dyed in ruthenium tetroxide vapor for 30 minutes and subjected to carbon deposition. Using a transmission electron microscope (JEM2100 manufactured by JEOL Ltd.), the structure of the entire film was observed at an acceleration voltage of 200 kV.

(Section observation (scanning electron microscope (SEM)))
The sample from which the hollow fiber membrane has been lightly washed to remove glycerin is frozen with liquid nitrogen and cut. The obtained sample is fixed to a sample stage so that the cut surface can be observed, and carbon deposition is performed by sputtering. The carbon-deposited sample is observed with a scanning electron microscope (Hitachi S-2500). The acceleration voltage was 10 kV and the magnification was 10,000 times.

(Measurement of hollow fiber membrane inner diameter, outer diameter, film thickness)
In these measurements, the hollow forming material is washed and removed, and then the hollow fiber membrane is dried. The drying method is not limited, but when the form changes remarkably by drying, the hollow forming material is washed and removed, then completely replaced with pure water, and then observed in a wet state. The hollow fiber membrane has an inner diameter, an outer diameter, and a film thickness that are appropriate for the hollow fiber membrane so that the hollow fiber membrane does not fall out into a 3 mm hole in the center of the slide glass, and is cut with a razor on the upper and lower surfaces of the slide glass. Then, after obtaining a hollow fiber membrane cross-section sample, it is obtained by measuring the short diameter and long diameter of the cross section of the hollow fiber membrane using a projector Nikon-V-12A. Measure the short axis and long axis in two directions for each cross section of the hollow fiber membrane, and calculate the arithmetic average value of each of the cross section of the hollow fiber membrane as the inner diameter and outer diameter of one hollow fiber membrane. did. Measurements were similarly made for five cross sections, and the average values were taken as the inner diameter, outer diameter, and film thickness.

(Measurement of porosity)
The porosity of the hollow fiber membrane was measured as follows.
A hollow fiber bundle sufficiently dipped in pure water is centrifuged for 5 minutes at a rotation speed of 900 rpm, and the weight (W) of the hollow fiber in a state where the membrane hole is filled with pure water is measured. Thereafter, it was completely dried in a dryer, the weight (P) of only the hollow fiber was measured, and the porosity (φ) was calculated.
φ (%) = W / (W + P / polymer density) × 100

(Measurement of adhesion rate of membrane pore-type retention agent (glycerin))
The adhesion rate of the membrane pore-type retention agent glycerin to the hollow fiber membrane was measured as follows.
An appropriate amount (about 30 g) of a hollow fiber membrane is prepared. It may be a loop or a bundle. If there is a core material inside the hollow fiber, it is removed if necessary. The hollow fiber membrane is completely dried and the weight W is measured. Thereafter, the hollow fiber membrane is immersed in water at about 40 ° C. and thoroughly washed, and then dried in a dry heat oven at 120 ° C. for 2 hours, and the weight P is measured. Next, the adhesion rate G (wt%) of the membrane pore-shaped holding agent to the hollow fiber membrane was calculated by the following formula.
G (wt%) = (W−P) ÷ W × 100

(Measurement of droplets adhering to the hollow fiber membrane)
The hollow fiber membrane was cut out to a length of about 50 mm, sealed in a Petri dish, and then observed with an optical microscope at a magnification of 40 times. The number and size of droplets present in the field of view were measured. Since very small droplets are unlikely to lead to hollow fiber membrane quality or assembly failure, those having a maximum diameter of about 15 μm or more were measured. When a large amount of droplets are present, the frequency of occurrence of module assembly defects increases.

(Production of hollow fiber membrane module)
A plurality of hollow fiber membranes were bundled, cut into a length of about 30 cm, and wound with a polyethylene film to form a hollow fiber membrane bundle. This hollow fiber membrane bundle was inserted into a cylindrical polycarbonate module case, and both ends were hardened with a urethane potting agent. The end portion was cut to obtain a module in which both ends of the hollow fiber membrane were opened. The number of hollow fiber membranes and the size of the module case were appropriately set so that the end portion filling rate was 55% and the membrane area based on the inner diameter was 1.5 m ² .

(Assembly evaluation of hollow fiber membrane module)
1. Test of adhesion of separation membrane module Fill the hollow part of the separation membrane module and the outer part of the hollow fiber membrane where peeling is not observed at the end adhesion part with pure water, and pressurize the outer part of the module hollow fiber membrane with pressurized air. Feeding and applying 1.5 times the pressure at maximum use for 24 hours with the end sealed. After 24 hours, the end bonded portion was observed to confirm the peeled state. At this time, the state without peeling was regarded as acceptable.
2. Hollow fiber membrane bundle bias The manufactured module was observed from the outside of the case, and a hollow fiber membrane bundle with no bias or cracks was accepted.
3. Adhesion failure Check the adhesion end of the manufactured module visually and by a leak test for adhesive resin filling failure. In the leak test, the module is immersed in water, pressurized air is sent from the dialysate side, and the presence or absence of air leakage is confirmed from the end of the module.

(Measurement of water permeability)
The blood outlet circuit of the module (the outlet side from the pressure measurement point) was sealed with forceps. Purified water kept at 37 ° C is put into a pressurized tank, and while controlling the pressure with a regulator, pure water is sent to the blood flow path side of the module kept at 37 ° C constant temperature bath, and the amount of filtrate flowing out from the dialysate side is measured. did. The transmembrane pressure difference (TMP) is
TMP = (Pi + Po) / 2
And Here, Pi is the dialyzer inlet side pressure, and Po is the dialyzer outlet side pressure. The TMP was changed at four points, the filtration flow rate was measured, and the water permeability (mL / hr / mmHg) was calculated from the slope of the relationship. At this time, the correlation coefficient between TMP and the filtration flow rate must be 0.999 or more. In order to reduce the pressure loss error due to the circuit, TMP is measured in the range of 100 mmHg or less. The water permeability of the hollow fiber membrane is calculated from the membrane area and the water permeability of the module.
UFR (H) = UFR (D) / A
Where UFR (H) is the water permeability of the hollow fiber membrane (mL / m ² / hr / mmHg), UFR (D) is the water permeability of the module (mL / hr / mmHg), and A is the membrane area of the module (m ² ).

(Measurement of β2MG clearance)
The dialysis society magazine 41 (3), p159-167, it implements according to the module performance evaluation criteria shown in 2008. ACD with acid-citrate-dextrose (ACD) added to a module with a membrane area of 1.5 m ² (based on the inner diameter of the hollow fiber membrane) and adjusted to a total protein concentration of 6.5 ± 0.5 g / dl and kept at 37 ° C. Circulate at a blood flow rate of 200 ml / min for 1 hour. Next, human β2MG (genetical recombination product, manufactured by Wako Pure Chemical Industries, Ltd.) was added to a concentration of 0.05 to 0.1 mg / l, and the total protein concentration was adjusted to 6.5 ± 0.5 g / dl. The ACD-added bovine plasma that has been kept warm is flowed to the blood side at a blood flow rate of 200 ml / min, and dialysis is performed with a commercial dialysate at 500 ml / min and a filtration flow rate of 15 ml / min. This clearance evaluation is performed with a single pass. After the start of dialysis, the β2MG concentration of the test solution collected from the blood inlet, outlet, and dialysate outlet at 60 minutes is measured. The clearance is calculated using the following formula.
CLβ15 (ml / min) = 200 × [(200 × CBi) − (185 × CBo)] / (200 × CBi)
Here, CBi: blood inlet concentration, CBo: blood outlet concentration.

Example 1
Cellulose triacetate (Daicel Chemical) 15.5% by mass, N-methyl-2-pyrrolidone (NMP, Mitsubishi Chemical) 59.15% by mass and triethylene glycol (TEG, Mitsui Chemicals) 25.35% % Was heated and dissolved uniformly, and then the resulting film forming solution was defoamed. The obtained film-forming solution was discharged together with liquid paraffin as a hollow forming material from a tube-in orifice nozzle heated to 100 ° C., passed through an aerial traveling section blocked from outside air by a spinning tube, and then immersed in a coagulation bath. Steam at 30 ° C. was blown into the spinning tube, and the humidity in the tube was 80% RH. The length of the aerial traveling section was 20 mm, and the passing time through the spinning tube was 0.02 seconds. Coagulation and phase separation were carried out in a first coagulation bath and a second coagulation bath comprising NMP / TEG / water = 10.5 / 4.5 / 85.0 at 40 ° C. At this time, the draft ratio was 7. The stretching in the second coagulation bath was 10%. The hollow fiber membrane squeezed out from the coagulation bath was washed with a 30 ° C. water-washing bath. At this time, the washing bath was adjusted to have an inclination of 3 degrees so that the washing water gradually descended, and the washing water and the hollow fiber membrane flowed in the same direction. The washing bath was 7 steps. Subsequently, it was immersed in a glycerin bath composed of a 95% by mass aqueous glycerin solution at 90 ° C. The hollow fiber membrane spun out of the glycerin bath was dried with a dryer at 40 ° C. and wound up at a spinning speed of 75 m / min. Dry air used was treated with a HEPA filter. The atmospheric humidity during winding was 30% RH. Before and after the dryer, the hollow fiber membrane was brought into contact with a roller equipped with a silicone scraper to remove excess glycerin. (See FIGS. 4 and 5).

  The resulting hollow fiber membrane had an inner diameter of 200 μm and a film thickness of 15 μm. Table 1 shows the physical properties and performance evaluation results of the hollow fiber membranes obtained in this example.

(Example 2)
Cellulose triacetate (Daicel Chemical) 15.5% by mass, N-methyl-2-pyrrolidone (NMP, Mitsubishi Chemical) 59.15% by mass and triethylene glycol (TEG, Mitsui Chemicals) 25.35% % Was heated and dissolved uniformly, and then the resulting film forming solution was defoamed. The obtained film-forming solution was discharged together with liquid paraffin as a hollow forming material from a tube-in orifice nozzle heated to 110 ° C., passed through an aerial traveling section blocked from outside air by a spinning tube, and then immersed in a coagulation bath. The spinning tube was blown with water vapor at 100 ° C., and the humidity in the tube was 100% RH. The length of the aerial traveling section was 20 mm, and the passing time through the spinning tube was 0.02 seconds. Coagulation and phase separation were carried out in a first coagulation bath and a second coagulation bath comprising NMP / TEG / water = 10.5 / 4.5 / 85.0 at 40 ° C. At this time, the draft ratio was 7. The stretching in the second coagulation bath was 10%. The hollow fiber membrane squeezed out from the coagulation bath was washed with a 30 ° C. water-washing bath. At this time, the washing bath was adjusted to have an inclination of 3 degrees so that the washing water gradually descended, and the washing water and the hollow fiber membrane flowed in the same direction. The washing bath was 7 steps. Subsequently, it was immersed in a glycerin bath composed of a 95% by mass aqueous glycerin solution at 90 ° C. The hollow fiber membrane spun out of the glycerin bath was dried with a dryer at 40 ° C. and wound up at a spinning speed of 75 m / min. Dry air used was treated with a HEPA filter. The atmospheric humidity during winding was 30% RH. In addition, before and after the dryer, the hollow fiber membrane was brought into contact with a roller equipped with a silicone scraper in the same manner as in Example 1 to remove excess glycerin.

  The resulting hollow fiber membrane had an inner diameter of 200 μm and a film thickness of 15 μm. Table 1 shows the physical properties and performance evaluation results of the hollow fiber membranes obtained in this example.

(Example 3)
Cellulose triacetate (Daicel Chemical) 15.5% by mass, N-methyl-2-pyrrolidone (NMP, Mitsubishi Chemical) 59.15% by mass and triethylene glycol (TEG, Mitsui Chemicals) 25.35% % Was heated and dissolved uniformly, and then the resulting film forming solution was defoamed. The obtained film-forming solution was discharged together with liquid paraffin as a hollow forming material from a tube-in orifice nozzle heated to 90 ° C., passed through an aerial traveling section blocked from outside air by a spinning tube, and then immersed in a coagulation bath. Steam at 30 ° C. was blown into the spinning tube, and the humidity in the tube was 80% RH. The length of the aerial traveling section was 20 mm, and the passing time through the spinning tube was 0.02 seconds. Coagulation and phase separation were carried out in a first coagulation bath and a second coagulation bath comprising NMP / TEG / water = 10.5 / 4.5 / 85.0 at 40 ° C. At this time, the draft ratio was 7. The stretching in the second coagulation bath was 20%. The hollow fiber membrane squeezed out from the coagulation bath was washed with a 30 ° C. water-washing bath. At this time, the washing bath was adjusted to have an inclination of 3 degrees so that the washing water gradually descended, and the washing water and the hollow fiber membrane flowed in the same direction. The washing bath was 7 steps. Subsequently, it was immersed in a glycerin bath composed of a 95% by mass aqueous glycerin solution at 90 ° C. The hollow fiber membrane spun out of the glycerin bath was dried with a dryer at 40 ° C. and wound up at a spinning speed of 75 m / min. Dry air used was treated with a HEPA filter. The atmospheric humidity during winding was 30% RH. In addition, before and after the dryer, the hollow fiber membrane was brought into contact with a roller equipped with a silicone scraper in the same manner as in Example 1 to remove excess glycerin.

  The resulting hollow fiber membrane had an inner diameter of 200 μm and a film thickness of 15 μm. Table 1 shows the physical properties and performance evaluation results of the hollow fiber membranes obtained in this example.

Example 4
Cellulose triacetate (Daicel Chemical) 15.5% by mass, N-methyl-2-pyrrolidone (NMP, Mitsubishi Chemical) 59.15% by mass and triethylene glycol (TEG, Mitsui Chemicals) 25.35% % Was heated and dissolved uniformly, and then the resulting film forming solution was defoamed. The obtained film-forming solution was discharged together with liquid paraffin as a hollow forming material from a tube-in orifice nozzle heated to 90 ° C., passed through an aerial traveling section blocked from outside air by a spinning tube, and then immersed in a coagulation bath. Steam at 30 ° C. was blown into the spinning tube, and the humidity in the tube was 80% RH. The length of the aerial traveling section was 20 mm, and the passing time through the spinning tube was 0.02 seconds. Coagulation and phase separation were carried out in a first coagulation bath and a second coagulation bath comprising NMP / TEG / water = 10.5 / 4.5 / 85.0 at 40 ° C. At this time, the draft ratio was 7. The stretching in the second coagulation bath was 10%. The hollow fiber membrane squeezed out from the coagulation bath was washed with a 30 ° C. water-washing bath. At this time, the washing bath was adjusted to have an inclination of 3 degrees so that the washing water gradually descended, and the washing water and the hollow fiber membrane flowed in the same direction. The washing bath was 7 steps. Subsequently, it was immersed in a glycerin bath composed of an aqueous glycerin solution at 90 ° C. and 80 mass%. The hollow fiber membrane spun out of the glycerin bath was dried with a dryer at 40 ° C. and wound up at a spinning speed of 75 m / min. Dry air used was treated with a HEPA filter. The atmospheric humidity during winding was 30% RH. In addition, before and after the dryer, the hollow fiber membrane was brought into contact with a roller equipped with a silicone scraper in the same manner as in Example 1 to remove excess glycerin.

  The resulting hollow fiber membrane had an inner diameter of 200 μm and a film thickness of 15 μm. Table 1 shows the physical properties and performance evaluation results of the hollow fiber membranes obtained in this example.

(Example 5)
Cellulose triacetate (Daicel Chemical) 15.5% by mass, N-methyl-2-pyrrolidone (NMP, Mitsubishi Chemical) 59.15% by mass and triethylene glycol (TEG, Mitsui Chemicals) 25.35% % Was heated and dissolved uniformly, and then the resulting film forming solution was defoamed. The obtained film-forming solution was discharged together with liquid paraffin as a hollow forming material from a tube-in orifice nozzle heated to 90 ° C., passed through an aerial traveling section blocked from outside air by a spinning tube, and then immersed in a coagulation bath. Steam at 30 ° C. was blown into the spinning tube, and the humidity in the tube was 80% RH. The length of the aerial traveling section was 20 mm, and the passing time through the spinning tube was 0.02 seconds. Coagulation and phase separation were carried out in a first coagulation bath and a second coagulation bath comprising NMP / TEG / water = 10.5 / 4.5 / 85.0 at 40 ° C. At this time, the draft ratio was 7. The stretching in the second coagulation bath was 10%. The hollow fiber membrane squeezed out from the coagulation bath was washed with a 30 ° C. water-washing bath. At this time, the washing bath was adjusted to have an inclination of 3 degrees so that the washing water gradually descended, and the washing water and the hollow fiber membrane flowed in the same direction. The washing bath was 7 steps. Subsequently, it was immersed in a glycerin bath composed of a 95% by mass aqueous glycerin solution at 90 ° C. The hollow fiber membrane spun out of the glycerin bath was dried with a dryer at 40 ° C. and wound up at a spinning speed of 75 m / min. Dry air used was treated with a HEPA filter. Further, the atmospheric humidity during winding was 55% RH. In addition, before and after the dryer, the hollow fiber membrane was brought into contact with a roller equipped with a silicone scraper to remove excess glycerin.

  The resulting hollow fiber membrane had an inner diameter of 200 μm and a film thickness of 15 μm. Table 1 shows the physical properties and performance evaluation results of the hollow fiber membranes obtained in this example.

(Example 6)
Cellulose triacetate (Daicel Chemical) 15.5% by mass, N-methyl-2-pyrrolidone (NMP, Mitsubishi Chemical) 59.15% by mass and triethylene glycol (TEG, Mitsui Chemicals) 25.35% % Was heated and dissolved uniformly, and then the resulting film forming solution was defoamed. The obtained film-forming solution was discharged together with liquid paraffin as a hollow forming material from a tube-in orifice nozzle heated to 90 ° C., passed through an aerial traveling section blocked from outside air by a spinning tube, and then immersed in a coagulation bath. The spinning tube was blown with water vapor at 40 ° C., and the humidity in the tube was 90% RH. The length of the aerial traveling section was 20 mm, and the passing time through the spinning tube was 0.02 seconds. Coagulation and phase separation were carried out in a first coagulation bath and a second coagulation bath comprising NMP / TEG / water = 10.5 / 4.5 / 85.0 at 40 ° C. At this time, the draft ratio was 7. Stretching in the second coagulation bath was 15.5%. The hollow fiber membrane squeezed out from the coagulation bath was washed with a 30 ° C. water-washing bath. At this time, the washing bath was adjusted to have an inclination of 3 degrees so that the washing water gradually descended, and the washing water and the hollow fiber membrane flowed in the same direction. The washing bath was 7 steps. Subsequently, it was immersed in a glycerin bath comprising a glycerin aqueous solution at 90 ° C. and 93% by mass. The hollow fiber membrane spun out of the glycerin bath was dried with a dryer at 40 ° C. and wound up at a spinning speed of 75 m / min. Dry air used was treated with a HEPA filter. The atmospheric humidity during winding was 45% RH. In addition, before and after the dryer, the hollow fiber membrane was brought into contact with a roller equipped with a silicone scraper to remove excess glycerin.

  The resulting hollow fiber membrane had an inner diameter of 200 μm and a film thickness of 15 μm. Table 1 shows the physical properties and performance evaluation results of the hollow fiber membranes obtained in this example.

(Comparative Example 1)
Cellulose triacetate (manufactured by Daicel Chemical Industries) 19.0 mass%, N-methyl-2-pyrrolidone (NMP, Mitsubishi Chemical Corporation) 56.7 mass%, and triethylene glycol (TEG, Mitsui Chemicals Co., Ltd.) 24.3 mass% % Was heated and dissolved uniformly, and then the resulting film forming solution was defoamed. The obtained film-forming solution was discharged together with liquid paraffin as a hollow forming material from a tube-in orifice nozzle heated to 100 ° C., passed through an aerial traveling section blocked from outside air by a spinning tube, and then immersed in a coagulation bath. Humidity adjustment in the spinning tube was not performed. The length of the aerial traveling section was 20 mm, and the passing time through the spinning tube was 0.02 seconds. Coagulation and phase separation were carried out in a first coagulation bath and a second coagulation bath comprising NMP / TEG / water = 10.5 / 4.5 / 85.0 at 40 ° C. At this time, the draft ratio was 7. The stretching in the second coagulation bath was 10%. The hollow fiber membrane squeezed out from the coagulation bath was washed with a 30 ° C. water-washing bath. At this time, the washing bath was adjusted to have an inclination of 3 degrees so that the washing water gradually descended, and the washing water and the hollow fiber membrane flowed in the same direction. The washing bath was 7 steps. Subsequently, it was immersed in a glycerin bath composed of a 95% by mass aqueous glycerin solution at 90 ° C. The hollow fiber membrane spun out of the glycerin bath was dried with a dryer at 40 ° C. and wound up at a spinning speed of 75 m / min. Dry air was used without being treated with a HEPA filter. The atmospheric humidity during winding was 30% RH. Before and after the dryer, the hollow fiber membrane was brought into contact with a roller equipped with a silicone scraper to remove excess glycerin.

  The resulting hollow fiber membrane had an inner diameter of 200 μm and a film thickness of 15 μm. Table 1 shows the physical properties and performance evaluation results of the hollow fiber membranes obtained in this example.

  In this comparative example, the particles did not grow sufficiently because the polymer concentration in the film-forming solution was increased and the humidity inside the spinning tube was not adjusted. Therefore, the desired β2MG clearance could not be obtained. Also, because dry air that was not treated with a HEPA filter was used, foreign matter adhered to the surface of the hollow fiber, which became the core, absorbed moisture in the atmosphere to form droplets, and module adhesion deteriorated. Seem.

(Comparative Example 2)
Cellulose triacetate (manufactured by Daicel Chemical Industries) 19.0 mass%, N-methyl-2-pyrrolidone (NMP, Mitsubishi Chemical Corporation) 56.7 mass%, and triethylene glycol (TEG, Mitsui Chemicals Co., Ltd.) 24.3 mass% % Was heated and dissolved uniformly, and then the resulting film forming solution was defoamed. The obtained film-forming solution was discharged together with liquid paraffin as a hollow forming material from a tube-in orifice nozzle heated to 100 ° C., passed through an aerial traveling section blocked from outside air by a spinning tube, and then immersed in a coagulation bath. Humidity adjustment in the spinning tube was not performed. The length of the aerial traveling section was 20 mm, and the passing time through the spinning tube was 0.02 seconds. Coagulation and phase separation were carried out in a first coagulation bath and a second coagulation bath comprising NMP / TEG / water = 10.5 / 4.5 / 85.0 at 40 ° C. At this time, the draft ratio was 7. The stretching in the second coagulation bath was 10%. The hollow fiber membrane squeezed out from the coagulation bath was washed with a 30 ° C. water-washing bath. At this time, the washing bath was adjusted to have an inclination of 3 degrees so that the washing water gradually descended, and the washing water and the hollow fiber membrane flowed in the same direction. The washing bath was 7 steps. Subsequently, it was immersed in a glycerin bath composed of a 95% by mass aqueous glycerin solution at 90 ° C. The hollow fiber membrane spun out of the glycerin bath was dried with a dryer at 40 ° C. and wound up at a spinning speed of 75 m / min. Dry air used was treated with a HEPA filter. The atmospheric humidity during winding was 72% RH. Before and after the dryer, the hollow fiber membrane was brought into contact with a roller equipped with a silicone scraper to remove excess glycerin.

  The resulting hollow fiber membrane had an inner diameter of 200 μm and a film thickness of 15 μm. Table 1 shows the physical properties and performance evaluation results of the hollow fiber membranes obtained in this example.

  In this comparative example, in addition to the problem of Comparative Example 1, since the glycerin is not scraped off, the hollow fiber membranes adhere to each other due to excess glycerin adhering to the outer surface of the hollow fiber membrane, and the module is assembled. Adhesive resin enters between the hollow fiber membranes.

(Comparative Example 3)
Cellulose triacetate (Daicel Chemical) 15.5% by mass, N-methyl-2-pyrrolidone (NMP, Mitsubishi Chemical) 59.15% by mass and triethylene glycol (TEG, Mitsui Chemicals) 25.35% % Was heated and dissolved uniformly, and then the resulting film forming solution was defoamed. The obtained film-forming solution was discharged together with liquid paraffin as a hollow forming material from a tube-in orifice nozzle heated to 100 ° C., passed through an aerial traveling section blocked from outside air by a spinning tube, and then immersed in a coagulation bath. Steam at 30 ° C. was blown into the spinning tube, and the humidity in the tube was 80% RH. The length of the aerial traveling section was 20 mm, and the passing time through the spinning tube was 0.02 seconds. Coagulation and phase separation were carried out in a first coagulation bath and a second coagulation bath comprising NMP / TEG / water = 10.5 / 4.5 / 85.0 at 40 ° C. At this time, the draft ratio was 7. The stretching in the second coagulation bath was 3%. The hollow fiber membrane squeezed out from the coagulation bath was washed with a 30 ° C. water-washing bath. At this time, the washing bath was a countercurrent by a conventional method. The washing bath was 7 steps. Subsequently, it was immersed in a glycerin bath composed of a 95% by mass aqueous glycerin solution at 90 ° C. The hollow fiber membrane spun out of the glycerin bath was dried with a dryer at 40 ° C. and wound up at a spinning speed of 75 m / min. Dry air used was treated with a HEPA filter. The atmospheric humidity during winding was 30% RH. Before and after the dryer, the hollow fiber membrane was brought into contact with a roller equipped with a silicone scraper to remove excess glycerin.

  The resulting hollow fiber membrane had an inner diameter of 200 μm and a film thickness of 15 μm. Table 1 shows the physical properties and performance evaluation results of the hollow fiber membranes obtained in this example.

  In this comparative example, it is considered that the yield strength of the hollow fiber was lowered and the module assemblability was deteriorated because the stretching in the second coagulation bath was low and the washing bath was counterflowed.

  The hollow fiber membrane of the present invention has an advantage that it has excellent yield strength while having a high porosity, and is excellent not only in low-molecular protein removability but also in modularity. Therefore, it greatly contributes to industrial development.

Claims (6)

  A hollow fiber membrane having an inner diameter of 150 to 250 μm, a film thickness of 10 to 30 μm, a porosity of 75% or more, and a yield strength of 17 g or more. The hollow fiber membrane is composed of an aggregate of particles, and is formed from an inner surface to an outer surface. On the other hand, the hollow fiber membrane is characterized in that the range of 60% of the film thickness is a structure filled with particles having an average diameter of 50 nm or more.   The hollow fiber according to claim 1, wherein when the cross section of the hollow fiber membrane is observed with a scanning electron microscope, a macro void is not substantially observed in the cross section of the membrane in a photograph taken at a magnification of 10,000 times. film.   The hollow fiber membrane according to claim 1 or 2, wherein the outer surface side has a denser structure than the inner surface side when a cross section of the hollow fiber membrane is observed using a transmission electron microscope. .   The hollow fiber membrane according to any one of claims 1 to 3, wherein the hollow fiber membrane is made of a cellulose acetate-based polymer.   A hollow fiber membrane module produced by inserting the hollow fiber membrane according to any one of claims 1 to 4 into a case so that an end portion filling rate is 45 to 65%.   The hollow fiber membrane module according to claim 5, which is used for blood purification.