JP2011024708A - Hollow fiber membrane for blood purification which is excellent in workability for module assembly, and method for manufacturing the same - Google Patents

Abstract

【Task】
Provided is a blood purification hollow fiber membrane having a high yield in module production.
[Solution]
A hollow fiber membrane for blood purification having an inner diameter of 100 to 300 μm, an average film thickness of 10 to 50 μm, and pores filled with glycerin, wherein the hollow fiber membrane is dried in an atomic force microscope The average surface roughness (Ra value) of the outer surface is 10 nm or less.
[Selection figure] None

Description

  The present invention relates to a hollow fiber membrane for blood purification and a method for producing the same, in which, when a module is assembled, the case and the hollow fiber membrane are highly slippery, so that the production yield is good.

  In blood purification methods such as the treatment of renal failure, natural materials such as cellulose, its derivatives cellulose diacetate, cellulose triacetate, synthetic polymers such as polysulfone, and polymethyl are used for the purpose of removing uremic toxins and waste products in the blood. Blood purifiers using dialysis membranes or ultrafiltration membranes made of polymers such as methacrylate and polyacrylonitrile as separation materials are widely used. In particular, a hollow fiber membrane module for blood purification using a hollow fiber membrane as a separation material reduces the amount of circulating blood involved in extracorporeal circulation, high removal efficiency of blood substances, and high production of blood purifier assemblies. It is highly important in the field of blood purification because of its advantages such as sex.

  A hollow fiber membrane module for blood purification using a hollow fiber membrane is obtained by winding a spun hollow fiber membrane into a bundle, inserting the wound hollow fiber membrane bundle into a module case, and then urethane at the end of the case. The hollow fiber membrane bundle and the case are liquid-tightly bonded with a resin such as epoxy or epoxy, and then the bonded portion is cut so that the inner hole is opened.

  At this time, the slipperiness of the hollow fiber membrane greatly affects the yield during module production. For example, when the wound hollow fiber membrane bundle is inserted into the module case, if the difference between the case inner diameter and the hollow fiber membrane bundle diameter is small, the inner surface of the case and the hollow fiber membrane or the hollow fiber membranes are rubbed and thread breakage occurs. It becomes a defective module.

  In order to improve the yield of module production, a method of increasing the strength of the hollow fiber membrane by increasing the polymer concentration at the time of membrane formation or increasing the thickness of the hollow fiber membrane is generally employed. However, since hollow fiber membranes used for blood purification are used for the purpose of removing harmful substances from blood, it is necessary to increase substance permeability, and these methods naturally lead to a disadvantageous tendency to improve performance. There is a limit.

  As a measure for facilitating the insertion of the film bundle into the module case, a method has been proposed in which the outer surface center roughness is set to 15 nm or more and the outer surface open area ratio is controlled to 6 to 20% (Patent Document 1). reference). This method facilitates the filling of the membrane bundle into the module case by controlling the hole ratio and the accompanying surface irregularities when the outer surface of the hollow fiber membrane is open to constant conditions. is there.

  As a physical index, a method of controlling the static friction coefficient and the dynamic friction coefficient of the hollow fiber membrane to the hollow fiber membrane within a certain range has been proposed (see Patent Document 2). These indices are measured according to the measurement standard of chemical fibers, and are an evaluation of the physical characteristics of the hollow fiber membrane.

  In the method of Patent Document 1, in the case of a hollow fiber membrane having an open outer surface, the casing in modularization is facilitated by controlling the unevenness accompanied by the opening, but the pores are filled with glycerin. In the case of a hollow fiber membrane, a parameter called a hole area ratio cannot be used. Further, the method of Patent Document 2 only controls the friction coefficient peculiar to the hollow fiber membrane, and no consideration is given to the friction coefficient between the membrane bundle that is an important friction coefficient in the modular casing process and the case that contacts the membrane bundle. It has not been.

  On the other hand, in the manufacture of industrial yarns, it has long been practiced to improve the slipperiness of yarns using an oil agent. However, for the production of a hollow fiber membrane for blood purification that is in direct contact with blood for medical use, an oil agent cannot be used for safety reasons. As far as the present inventors know, the hollow fiber membrane for blood purification There has never been an example in which an oil agent is used for the purpose of improving thread slippage.

JP 2008-207153 A JP 2008-73134 A

  The present invention was devised in view of the above-described state of the prior art, and its purpose is to apply a hollow fiber membrane and an inner surface of the module case when the bundle of hollow fiber membranes wound in a bundle is inserted into the module case. An object of the present invention is to provide a highly slippery hollow fiber membrane for blood purification that prevents thread breakage due to slipping, and a method for producing the same.

  As a result of intensive studies to achieve the above object, the inventors of the present invention, as a result, in the hollow fiber membrane filled with glycerin in the pores, the average in the dry state of the outer surface of the hollow fiber membrane as measured by an atomic force microscope By reducing the surface roughness (Ra value), the hollow fiber membrane module can be assembled without any damage such as breakage of the hollow fiber membrane due to rubbing between the hollow fiber membrane and the inner surface of the module case, thereby improving the production yield. As a result, the present invention has been completed.

That is, the present invention has the following configuration.
(1) A blood purification hollow fiber membrane having an inner diameter of 100 to 300 μm, an average film thickness of 10 to 50 μm, and pores filled with glycerin, wherein the hollow fiber membrane is atomized in a dry state A hollow fiber membrane for blood purification, wherein the average surface roughness (Ra value) of the outer surface is 10 nm or less as measured by an atomic force microscope.
(2) The load applied when the hollow fiber membrane bundle filled in the polyethylene pipe at a filling rate of 47% is pushed out from the polyethylene pipe is 20 N or less. (1) Hollow fiber membrane for blood purification.
(3) A blood purification hollow fiber membrane module comprising the blood purification hollow fiber membrane according to (1) or (2).

  In the hollow fiber membrane of the present invention, since the average surface roughness of the outer surface of the hollow fiber membrane in which pores are filled with glycerin and the outer surface is not opened is reduced, the yarn on the outer surface of the hollow fiber membrane Good slip. Therefore, when this hollow fiber membrane is wound into a bundle and inserted into a module case, there is almost no thread breakage due to rubbing between the hollow fiber membranes, so there is no defective module, and production of a blood purification hollow fiber membrane module High nature.

  Hereinafter, the hollow fiber membrane for blood purification of the present invention will be described in detail.

  The hollow fiber membrane for blood purification of the present invention is one in which pores are filled with glycerin. When the hollow fiber membrane is measured by an atomic force microscope in a dry state, the average surface roughness (Ra value) of the outer surface. Is 10 nm or less.

  In the hollow fiber membrane in which the pores are filled with glycerin, the inventor rubs the hollow fiber membrane and the inner surface of the module case, that is, the slipperiness is related to the smoothness of the outer surface of the hollow fiber membrane. As a result of investigating the influence of the smoothness of the outer surface of the hollow fiber membrane on the slipperiness, it was found that the slipperiness deteriorates when the smoothness of the outer surface of the hollow fiber is low.

  As a method for evaluating the slipping property, a load applied when a hollow fiber membrane bundle filled in a polyethylene pipe at a constant filling rate was to be pushed out from the polyethylene pipe was measured. It is considered that the smaller the load, the better the slip property of the hollow fiber membrane and the higher the smoothness of the outer surface of the hollow fiber membrane.

  In the hollow fiber membrane of the present invention, it is preferable that a load applied when a hollow fiber membrane bundle filled in a polyethylene pipe at a filling rate of 47% is pushed out of the polyethylene pipe is 20 N or less. More preferably, it is 15 N or less. When the load is applied, the rubbing between the hollow fiber membrane and the inner surface of the module case is small, and the hollow fiber membrane is hardly damaged. On the other hand, if this range is exceeded, the hollow fiber outside the hollow fiber membrane bundle and the polyethylene pipe are strongly rubbed, and the yarn is likely to break or break.

  In addition, the present inventor, the hollow fiber membrane with a small load when trying to push out the hollow fiber membrane bundle filled in the polyethylene pipe from the polyethylene pipe, the average surface of the outer surface of the hollow fiber membrane It was found that the roughness (Ra value) was small and the outer surface was smooth. When the smoothness of the outer surface is high, it is considered that the highly viscous glycerin is not excessively attached to the outer surface, the friction coefficient is reduced, and the slipping property is improved. From such a viewpoint, the average surface roughness (Ra value) of the outer surface of the hollow fiber membrane of the present invention needs to be 10 nm or less when the hollow fiber membrane is measured by an atomic force microscope in a dry state, Furthermore, it is preferable that it is 9 nm or less. When the Ra value exceeds this range, the hollow fiber outside the hollow fiber membrane bundle and the polyethylene pipe are strongly rubbed, and the yarn tends to break or break. The lower limit of the Ra value is practically 0.1 nm in terms of ease of achievement.

  As will be described later, the average surface roughness (Ra value) of the outer surface of the hollow fiber membrane is determined by the temperature at which the spinning dope is discharged from the nozzle (nozzle temperature) and the coagulation bath in the next coagulation step after the discharge. Controls the difference from the temperature immediately before immersion (air travel part temperature), that is, the temperature difference in the air travel part, or the hollow fiber membrane and the cleaning liquid are run in the same direction in the water washing process and are washed. By reducing the tension applied to the hollow fiber membrane as much as possible, it can be suppressed to the above low value.

  The inner diameter of the hollow fiber membrane of the present invention needs to be 100 to 300 μm. If the inner diameter is too small, the pressure loss of the fluid flowing through the hollow portion of the hollow fiber membrane increases, which may cause 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 through the hollow fiber membrane are in an appropriate range is particularly 150 to 250 μm.

  Moreover, the average film thickness of the hollow fiber membrane of this invention needs to be 10-50 micrometers. 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. In addition, in the design of the blood purifier, if the film thickness is large when the membrane area is increased, the size of the blood purifier increases, which is not appropriate. A thinner film thickness is preferred because the material permeability is increased, preferably 45 μm or less, and more preferably 40 μm or less. However, if the average film thickness is too thin, it may be difficult to maintain the minimum film strength necessary for the blood purifier. Therefore, the average film thickness is preferably 12 μm or more, and more preferably 14 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.

  Examples of the material of the hollow fiber membrane in the present invention include cellulose polymers such as regenerated cellulose, cellulose acetate and cellulose triacetate, polysulfone polymers such as polysulfone and polyethersulfone, polyacrylonitrile, polymethyl methacrylate, ethylene vinyl alcohol copolymer Although a coalescence etc. are mentioned, the cellulose type and polysulfone type | system | group which are easy to obtain a highly water-permeable hollow fiber membrane are preferable. In particular, cellulose diacetate or cellulose triacetate is preferable for cellulose, and polysulfone or polyethersulfone is preferable for polysulfone because it is easy to reduce the film thickness.

  The hollow fiber membrane of the present invention has a dense layer on the inner surface by a method as described later, followed by a support layer substantially free of voids, and subsequently a pore diameter larger than the dense layer, A non-uniform structure having an outer surface layer smaller than the support layer is taken. Thereby, the strength of the hollow fiber membrane can be improved while achieving high water permeability.

Next, the manufacturing method of the hollow fiber membrane of this invention is demonstrated. In order to obtain a highly water-permeable hollow fiber membrane of 150 to 1000 ml / m ² / hr / mmHg, the polymer concentration of the spinning solution depends on the type of polymer, but is 26% by mass or less, more preferably 25% by mass. % Or less is preferable. The spinning solution is preferably applied to a filter immediately before nozzle discharge for the purpose of removing insoluble components and gel in the spinning solution. 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, if there is no filter or the filter pore size exceeds the film thickness of the hollow fiber membrane, partial voids due to the insoluble components in the spinning solution or the inclusion of gel, etc., and the texture of the surface structure in units of several tens of μm It tends to cause fineness (such as pulling or partial wrinkling). In hollow fiber membranes having a high porosity, the generation of partial voids can cause a reduction in the physical strength of the membrane. Filtration of the spinning dope may be carried out a plurality of times before discharging, thereby extending the life of the filter.

  The spinning dope treated as described above is discharged using a tube-in-orifice type nozzle having an annular portion on the outside and a hollow forming material discharge hole on the inside. By reducing the variation in the slit width of the nozzle (the width of the annular portion that discharges the spinning dope), uneven thickness of the spun hollow fiber membrane can be reduced. Specifically, the difference between the maximum value and the minimum value of the slit width of the nozzle is preferably 10 μm or less. The slit width of the nozzle varies depending on the viscosity of the spinning dope used, the thickness of the hollow fiber membrane to be obtained, and the type of the hollow forming material. If this variation is large, uneven thickness may be caused, and the thin portion may be torn. Rupture and cause leaks. Moreover, when uneven thickness is remarkable, it becomes a cause by which appropriate intensity | strength as a blood purification film cannot be obtained.

  The temperature of the nozzle when discharging the spinning dope is preferably set to a temperature lower than the general hollow fiber membrane production conditions in order to sufficiently obtain the effect in the aerial traveling portion until entering the coagulation bath in the next step. Specifically, the nozzle discharge temperature of the spinning dope is preferably 50 ° C to 130 ° C, and more preferably 55 ° C to 125 ° C. When the nozzle discharge temperature is too low, the viscosity of the 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, there is a possibility that the pore size becomes too large due to the influence of the phase separation on the membrane structure.

  The discharged spinning solution is immersed in the coagulation bath through the aerial traveling section. At this time, the air travel section is surrounded by a member (spinning tube) that shuts off the outside air, and the temperature difference between the discharge temperature of the spinning stock solution (nozzle temperature) and the temperature immediately before the coagulation bath immersion (air travel section temperature) is 60 to 120 ° C., It is particularly preferable that the temperature is 95 to 120 ° C. The temperature immediately before immersion in the coagulation bath refers to a temperature measured at a height of about 1 cm from the surface of the coagulation bath in the spinning tube, and is substantially the same as the air travel temperature. Specifically, the temperature immediately before immersion in the coagulation bath is preferably 15 ° C. or less, more preferably 10 ° C. or less, and particularly preferably 5 ° C. or less. Examples of the method for controlling the air travel unit at such a low temperature include a method of circulating a refrigerant through the spinning tube and a method of flowing cooled air. The cooling of the refrigerant and the cooling of the wind can be controlled using liquid nitrogen, dry ice, or the like. However, in consideration of workability, the temperature of the aerial traveling section is preferably −20 ° C. or higher. In addition, the atmosphere in the aerial traveling section is desirably kept uniform because it affects the phase separation of the spinning dope, and it is preferable to prevent the temperature and wind speed from becoming uneven by covering with an enclosure or the like. Unevenness in the atmosphere, temperature, and wind speed of the aerial traveling section is not appropriate because it causes variations in the microscopic film structure and causes problems in performance.

  As a method for preventing unevenness in the temperature and wind speed of the aerial traveling part, there is a method of making a hole of an appropriate size in the enclosure of the aerial traveling part so that the cooled wind flows uniformly. The number of holes in the enclosure of the aerial traveling unit is not particularly limited, but it is important to adjust so that the wind is spread over the whole so that the hollow fiber membrane to be spun does not shake. Further, when the nozzle outlet portion is rapidly cooled, gel is likely to be formed in the vicinity of the nozzle outlet, the nozzle may be blocked, and the thickness of the hollow fiber membrane may be increased. In order to avoid such a phenomenon, it can be an effective means to insert a heat insulating material between the nozzle block and the enclosure of the aerial traveling unit. The type of the heat insulating material is not particularly limited as long as it can block heat conduction, and ceramics, plastics, and the like can be used.

  The thickness of the heat insulating material is preferably 5 to 20 mm. If the thickness of the heat insulating material is too thin, the heat is not sufficiently blocked, and the heat insulating effect of the nozzle may not be sufficient. Moreover, when the thickness of a heat insulating material is too thick, there exists a possibility that the effect of the cooling in an aerial travel part may not be reflected in hollow fiber membrane formation. By this method, the possibility that the dope immediately after being discharged from the nozzle closes the nozzle outlet portion is reduced, and a hollow fiber membrane having a high roundness can be stably spun. By making the nozzle temperature appropriately low and keeping the temperature of the aerial traveling part low, the gelation rate in the film forming process can be controlled to be constant. In addition, by setting the aerial running part at a lower temperature than usual, rapid gelation is promoted on the outer surface of the hollow fiber membrane, so the cross-sectional structure of the membrane is compared with the inner part and outer part of the hollow fiber membrane, respectively. A three-layer structure with dense layers can be formed. Taking such a three-layer structure is effective in improving the strength of the hollow fiber membrane.

  The hollow forming material is preferably an inert liquid or gas, although it depends on the spinning dope used. Specific examples of such a hollow forming material include liquid paraffin, isopropyl myristate, nitrogen, argon, and the like. Further, in order to form a dense layer on the inner surface of the hollow fiber membrane, an aqueous solution of solvent used in the preparation of the spinning dope, water or the like can be used. Non-solvents such as glycerin, ethylene glycol, triethylene glycol, and polyethylene glycol, or water can be added to these hollow forming materials as necessary.

  The gelled film is solidified by passing through the coagulation bath through the air running part. The coagulation bath is preferably composed of an aqueous solution of the solvent used when preparing the spinning dope. When the coagulation bath is water, the gelled membrane rapidly solidifies, and a dense layer is formed on the outer surface of the hollow fiber membrane. The surface of the rapidly solidified film does not open, but it is difficult to control the surface roughness. In this case, by making the coagulation bath a mixed solution of a solvent and water, the control of the coagulation time and the surface roughness of the hollow fiber membrane can be easily adjusted appropriately. The solvent concentration of the coagulation bath is preferably 70% by mass or less, and more preferably 50% by mass or less. However, if the solvent concentration is less than 1% by mass, it is difficult to control the concentration during spinning, so the lower limit of the solvent concentration is preferably 1% by mass or more. The temperature of the coagulation bath is preferably 4 to 50 ° C. for controlling the coagulation rate. More preferably, it is 10-45 degreeC. Thus, a hollow fiber membrane having a moderate size, distribution, and number of pores can be obtained by gently forming the hollow fiber membrane with the air running portion and the coagulation bath. 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.

  The hollow fiber membrane that has passed through the coagulation bath is washed away of unnecessary components such as a solvent through a washing step. The cleaning liquid used at this time is preferably water, and the temperature is preferably 20 ° C. to 80 ° C. in terms of the cleaning effect. 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. In addition, the membrane is still active after the coagulation bath process, and if a force is applied from the outside in the washing bath, the membrane structure, surface shape and pore shape may be deformed. It is preferable to prevent resistance 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, 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 is increased, so that it is necessary to prevent the hollow fiber membrane from being pulled or distorted.

  The present inventor has intensively studied to achieve both suppression of deformation of the hollow fiber membrane and cleanability, and as a result, has found that it is effective to flow the cleaning liquid and the hollow fiber membrane in the same direction in parallel flow. As a specific aspect of the washing step, for example, there is an equipment in which the washing bath is inclined and the hollow fiber membrane is lowered. In this case, 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 bath is preferably arranged in multiple stages. The number of stages needs to be set as appropriate 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 needs to be treated with glycerin. For example, in the case of a hollow fiber membrane made of a cellulosic polymer, the hollow fiber membrane is passed through a glycerin bath and then wound through a drying step. In this case, the glycerin concentration is preferably 30 to 80% by mass. If the glycerin concentration is too low, the hollow fiber membrane tends to shrink during drying, and storage stability may deteriorate. Also, 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 blood purifier. The temperature of the glycerin bath is preferably 40 to 80 ° C. 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.

  In the spinning process as a whole, the tension applied to the hollow fiber membrane affects the structure of the membrane. Therefore, it is preferable not to stretch as much as possible in order not to change the membrane structure. This is because the membrane is still active after the coagulation bath process, and when an external force is applied in the washing bath, the membrane structure, surface structure and pore shape are deformed. In particular, the stretching causes the pore shape of the membrane to be deformed from a perfect circle to an ellipse, and therefore has a great influence on the permeation performance. Specifically, the ratio between the traveling speed at the coagulation bath outlet of the hollow fiber membrane and the winding speed at the end of the spinning process is preferably 1 or more and less than 1.2.

  Hereinafter, the effects of the hollow fiber membrane 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 physical property in an Example is as follows.

(Water permeability)
The blood outlet circuit (outlet side from the pressure measurement point) of the dialyzer 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 dialyzer kept at 37 ° C constant temperature bath, and the amount of filtrate flowing out from the dialysate side is measured. It was measured. 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 0.99 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 dialyzer.
UFR (H) = UFR (D) / A
Here, UFR (H) is the water permeability of the hollow fiber membrane (mL / m ² / hr / mmHg), UFR (D) is the water permeability of the dialyzer (mL / hr / mmHg), and A is the membrane area of the dialyzer (mL m ² ).

(Inner diameter, outer diameter, film thickness of hollow fiber membrane)
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. The hollow fiber membrane is cut through a razor on the top and bottom surfaces of the slide glass so that the hollow fiber membrane does not fall out into a hole of φ3 mm in the center of the slide glass. And after obtaining the hollow fiber membrane cross-section sample, it is obtained by measuring the minor axis and major axis of the hollow fiber membrane cross section 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.

(Average surface roughness (Ra value))
A sample in which the outer surface of the hollow fiber membrane to be evaluated was exposed was used. The morphology was observed with an atomic force microscope SPI3800 (manufactured by Seiko Instruments Inc.). The observation mode at this time is the DFM mode, the scanner is FS-20A, the cantilever is DF-3, and the observation field is 3 μm square. Ra value represents the arithmetic average of the unevenness | corrugation of all the measurement points with respect to the reference point at the time of measuring the unevenness | corrugation of the film | membrane surface.

(Extruded load)
The outer periphery of a pipe for measurement in which a hollow fiber membrane bundle is filled in a polyethylene pipe having an inner diameter of 3.4 cm at a filling rate of 47% is fixed so that the shape thereof does not change, the diameter is 2.5 cm, the thickness is 0. Maximum load when trying to push out a hollow fiber membrane bundle from the inside of a pipe using a bar tension gauge (Oba Keiki Seisakusho) with a 5cm Teflon (registered trademark) plate attached to the tip. Was the extrusion load (N). In the present invention, the filling rate is obtained based on the following formula.
Filling rate (%) = (outer diameter reference cross section per hollow fiber membrane × number of hollow fiber membranes) / pipe inner diameter cross section × 100
For example, when the hollow fiber membrane has an inner diameter of 200 × 10 ⁻⁴ cm and a film thickness of 15 × 10 ⁻⁴ cm, ^47/100 × {π × (3.4 / 2) From ² } / [π × {(200 × 10 ⁻⁴ + 15 × 10 ⁻⁴ × 2) / 2} ² ], approximately 10162 to 10379 hollow fiber membranes are required.

(Module production yield)
The hollow fiber membrane bundle is inserted into the polyethylene pipe so that the filling rate is 47%, and this is inserted into the module case. After pulling out the polyethylene pipe, the hollow fiber membrane bundle and the case are liquid-tightly bonded with urethane resin. After the urethane resin is cured, a part of the adhesive part is cut so that the hollow part is opened, thereby producing a module. About 20 modules produced in this way, the contact part of a case and a hollow fiber membrane is observed visually, and module production yield is evaluated by the presence or absence of defective yarn (a broken, a piece, a twist, a crush). As for bending, twisting, and crushing, it is determined that a hollow part that is apparently blocked is a defective thread, and if even one such hollow fiber membrane exists, a defective module is obtained. By applying the present invention, it is possible to achieve a pass rate of 80% or more.

Example 1
Cellulose triacetate (manufactured by Daicel Chemical Industries) 19.0% by mass, N-methyl-2-pyrrolidone (NMP, manufactured by Mitsubishi Chemical Corporation) 56.7% by mass, and triethylene glycol (TEG, manufactured by Mitsui Chemicals) 24.3 The mass% was heated and dissolved uniformly, and then the resulting spinning dope was defoamed. The obtained spinning dope is passed through a two-stage sintered filter having a pore diameter of 10 μm and 5 μm in order, and then simultaneously discharged together with liquid paraffin previously degassed as a hollow forming material from a tube-in orifice nozzle heated to 102 ° C., After passing through a 70 mm dry section that is cut off from the outside air by a spinning tube and adjusted to a uniform atmosphere of 2 ° C., it is solidified in a 20 mass% NMP / TEG (7/3) aqueous solution at 40 ° C. After passing through the water washing bath, it was passed through a glycerin bath at 50 ° C. and 60% by mass, dried with a dryer, and wound up at a spinning speed of 30 m / min. At this time, the discharge amount of the spinning solution was 0.50 ml / min, and the discharge amount of the hollow forming material (liquid paraffin) was 0.96 ml / min. In addition, the washing bath was adjusted to have an inclination of 2.5 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 5 steps. The ratio between the traveling speed of the hollow fiber membrane at the coagulation bath outlet and the winding speed at the end of the spinning process was 1.1.

The resulting hollow fiber membrane had an inner diameter of 200.5 μm and a film thickness of 15.8 μm. Using the obtained hollow fiber membrane, a blood purifier was prepared and evaluated so that the membrane area was 1.5 m ² . The results are shown in Table 1.

(Example 2)
Cellulose triacetate (manufactured by Daicel Chemical Industries) 19.0% by mass, N-methyl-2-pyrrolidone (NMP, manufactured by Mitsubishi Chemical Corporation) 56.7% by mass, and triethylene glycol (TEG, manufactured by Mitsui Chemicals) 24.3 The mass% was heated and dissolved uniformly, and then the resulting spinning dope was defoamed. The obtained spinning dope is passed through a two-stage sintered filter having a pore diameter of 10 μm and 5 μm in order, and then simultaneously discharged together with liquid paraffin previously degassed as a hollow forming material from a tube-in orifice nozzle heated to 102 ° C., After passing through a 70 mm dry section that is cut off from the outside air by a spinning tube and adjusted to a uniform atmosphere of 2 ° C., it is solidified in a 20 mass% NMP / TEG (7/3) aqueous solution at 40 ° C. After passing through the water washing bath, it was passed through a glycerin bath at 50 ° C. and 60% by mass, dried with a dryer, and wound up at a spinning speed of 30 m / min. At this time, the discharging amount of the spinning solution was 0.31 ml / min, and the discharging amount of the hollow forming material (liquid paraffin) was 0.55 ml / min. In addition, the washing bath was adjusted to have an inclination of 2.5 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 5 steps. The ratio between the traveling speed of the hollow fiber membrane at the coagulation bath outlet and the winding speed at the end of the spinning process was 1.1.

The hollow fiber membrane obtained had an inner diameter of 151.2 μm and a film thickness of 12.6 μm. Using the obtained hollow fiber membrane, a blood purifier was prepared and evaluated so that the membrane area was 1.5 m ² . The results are shown in Table 1.

(Example 3)
Cellulose triacetate (manufactured by Daicel Chemical Industries) 19.0% by mass, N-methyl-2-pyrrolidone (NMP, manufactured by Mitsubishi Chemical Corporation) 56.7% by mass, and triethylene glycol (TEG, manufactured by Mitsui Chemicals) 24.3 The mass% was heated and dissolved uniformly, and then the resulting spinning dope was defoamed. The obtained spinning dope is passed through a two-stage sintered filter having a pore diameter of 10 μm and 5 μm in order, and then simultaneously discharged together with liquid paraffin previously degassed as a hollow forming material from a tube-in orifice nozzle heated to 102 ° C., After passing through a 70 mm dry section that is cut off from the outside air by a spinning tube and adjusted to a uniform atmosphere of 2 ° C., it is solidified in a 20 mass% NMP / TEG (7/3) aqueous solution at 40 ° C. After passing through the water washing bath, it was passed through a glycerin bath at 50 ° C. and 60% by mass, dried with a dryer, and wound up at a spinning speed of 30 m / min. At this time, the discharge amount of the spinning solution was 2.00 ml / min, and the discharge amount of the hollow forming material (liquid paraffin) was 1.51 ml / min. In addition, the washing bath was adjusted to have an inclination of 2.5 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 5 steps. The ratio between the traveling speed of the hollow fiber membrane at the coagulation bath outlet and the winding speed at the end of the spinning process was 1.1.

The resulting hollow fiber membrane had an inner diameter of 250.6 μm and a film thickness of 45.3 μm. Using the obtained hollow fiber membrane, a blood purifier was prepared and evaluated so that the membrane area was 1.5 m ² . The results are shown in Table 1.

Example 4
Cellulose triacetate (manufactured by Daicel Chemical Industries, Ltd.) 18.0% by mass, NMP 57.4% by mass, and TEG 24.6% by mass were uniformly dissolved, and then the spinning solution was defoamed. The obtained spinning dope is passed through a two-stage sintered filter having a pore size of 10 μm and 5 μm in order, and then simultaneously discharged together with liquid paraffin previously degassed as a hollow forming material from a tube-in orifice nozzle heated to 120 ° C., After being cut off from the outside air by a spinning tube and passed through a 50 mm dry section adjusted to a uniform atmosphere of 3 ° C., it is solidified in an aqueous solution of 20% by mass NMP / TEG (7/3) at 40 ° C. After passing through the water washing bath, it was passed through a glycerin bath at 50 ° C. and 60% by mass, dried with a dryer, and wound up at a spinning speed of 75 m / min. At this time, the discharge amount of the spinning solution was 1.21 ml / min, and the discharge amount of the hollow forming material (liquid paraffin) was 2.40 ml / min. The washing bath was adjusted so that the inclination was 1 degree and the hollow fiber membrane was gently lowered, and the washing water and the hollow fiber membrane were co-flowed in the same direction. The washing bath was 7 steps. The ratio of the hollow fiber membrane running speed at the coagulation bath outlet to the winding speed at the end of the spinning process was 1.08.

  The resulting hollow fiber membrane had an inner diameter of 199.8 μm and a film thickness of 15.4 μm. Evaluation was conducted in the same manner as in Example 1 using the obtained hollow fiber membrane. The results are shown in Table 1.

(Comparative Example 1)
Cellulose triacetate (manufactured by Daicel Chemical Industries) 19.0 mass%, NMP 56.7 mass%, and TEG 24.3 mass% were heated and dissolved uniformly, and then the spinning dope was defoamed. The obtained spinning dope is passed through a two-stage sintered filter having a pore diameter of 20 μm and 20 μm in order, and then simultaneously discharged together with liquid paraffin previously deaerated as a hollow forming material from a tube-in orifice nozzle heated to 105 ° C., After passing through a 70 mm dry section that was cut off from the outside air by a spinning tube and adjusted to a uniform atmosphere of 48 ° C., it was coagulated in an aqueous solution of 20 mass% NMP / TEG (7/3) at 40 ° C., and 30 ° C. After passing through the water washing bath, it was passed through a glycerin bath at 50 ° C. and 60% by mass, dried with a dryer, and wound up at a spinning speed of 85 m / min. At this time, the discharge amount of the spinning solution was 1.18 ml / min, and the discharge amount of the hollow forming material (liquid paraffin) was 2.40 ml / min. Further, the washing bath was adjusted so that the inclination was 0.5 degree and the hollow fiber membrane was gently raised, and the washing water and the hollow fiber membrane were counterflowed in opposite directions. The washing bath was 7 steps. The ratio of the hollow fiber membrane running speed at the coagulation bath outlet to the winding speed at the end of the spinning process was 1.25.

  The resulting hollow fiber membrane had an inner diameter of 199.8 μm and a film thickness of 15.0 μm. Evaluation was conducted in the same manner as in Example 1 using the obtained hollow fiber membrane. The results are shown in Table 1.

(Comparative Example 2)
Polyethersulfone (Sumitomo Chemical High Polymerization Polyethersulfone 7300P) 16.0% by mass, Polyvinylpyrrolidone (BASF PVP K-90) 6.0% by mass, N-methyl-2-pyrrolidone (NMP, Mitsubishi (Chemical Co., Ltd.) 46.8% by mass and polyethylene glycol (PEG200, manufactured by Daiichi Kogyo Seiyaku Co., Ltd.) 31.2% by mass were heated and dissolved uniformly, and then the spinning solution was defoamed. The obtained spinning dope was passed through a two-stage sintered filter having a pore size of 10 μm and 5 μm in order, and then N-methyl-2-pyrrolidone (NMP, Mitsubishi Chemical) was used as a hollow forming material from a tube-in orifice nozzle heated to 80 ° C. Co., Ltd.) 36% by mass, polyethylene glycol (PEG200, manufactured by Daiichi Kogyo Seiyaku Co., Ltd.) 24% by mass, and water 40% by mass were discharged simultaneously, blocked from the outside by a spinning tube, and adjusted to a uniform atmosphere of 43 ° C. After passing through an 8 mm dry section, it is solidified in a 40% by mass NMP / PEG200 (6/4) aqueous solution at 40 ° C., passed through a 50 ° C. water washing bath, and then passed through a 50 ° C., 60% by mass glycerin bath. And dried with a dryer and wound up at a spinning speed of 30 m / min. At this time, the discharge amount of the spinning solution was 0.65 ml / min, and the discharge amount of the hollow forming material (aqueous system liquid) was 0.97 ml / min. Further, the washing bath was adjusted so that the inclination was 0.5 degree and the hollow fiber membrane was gently raised, and the washing water and the hollow fiber membrane were counterflowed in opposite directions. The washing bath was 7 steps. The ratio of the hollow fiber membrane running speed at the coagulation bath outlet to the winding speed at the end of the spinning process was 1.25.

  The obtained hollow fiber membrane had an inner diameter of 201.2 μm and a film thickness of 20.0 μm. Evaluation was conducted in the same manner as in Example 1 using the obtained hollow fiber membrane. The results are shown in Table 1.

  As is apparent from Table 1, Examples 1 to 4 having an Ra value of 10 nm or less have a low extrusion load and a good module production yield. In particular, the results of Examples 2 and 4 having a low Ra value are very good. On the other hand, Comparative Examples 1 and 2 with an Ra value exceeding 10 nm have a high extrusion load, resulting in a poor module production yield.

  The hollow fiber membrane for blood purification of the present invention can maintain the production yield at the time of module assembly at a high level by reducing the average surface roughness of the outer surface. Therefore, the hollow fiber membrane for blood purification of the present invention has an advantage that it can be produced economically and stably.

Claims (3)

  A hollow fiber membrane for blood purification having an inner diameter of 100 to 300 μm, an average film thickness of 10 to 50 μm, and pores filled with glycerin, wherein the hollow fiber membrane is dried in an atomic force microscope A hollow fiber membrane for blood purification, wherein the average surface roughness (Ra value) of the outer surface is 10 nm or less as measured by   2. The blood purification according to claim 1, wherein the load applied when the hollow fiber membrane bundle filled in the polyethylene pipe at a filling rate of 47% is pushed out of the polyethylene pipe is 20 N or less. Hollow fiber membrane.   A hollow fiber membrane module for blood purification, comprising the hollow fiber membrane for blood purification according to claim 1 or 2.