JP5044946B2 - Hollow fiber membrane module and method for producing hollow fiber membrane module - Google Patents

Description

  The present invention relates to a semi-dry type hollow fiber membrane module that has a low performance of an eluate (hereinafter simply referred to as an eluate) from a membrane to a liquid to be treated and has high performance.

  Conventionally, hollow fiber membrane modules have been widely used as artificial kidneys, plasma separation, ultrafiltration, water purifiers and the like.

  As the hollow fiber membrane module, in order to prevent drying of the built-in hollow fiber membrane, a wet type module in which a liquid is filled is mainly used. However, filling the liquid increases the weight, which is inconvenient for transportation and handling. In cold regions, the filled liquid may freeze, making it difficult to transport and store. On the other hand, the type not filled with liquid is light in weight by water and has no fear of freezing. As a type not filled with liquid, a dry type hollow fiber membrane module in which the hollow fiber membrane is in a dry state is commercially available, and a method for producing a semi-dry type hollow fiber membrane module in a wet state with water (patent Document 1) and a method for producing a hollow fiber membrane module wetted with glycerin (Patent Document 2) are disclosed.

  On the other hand, when the hollow fiber membrane module is used in a medical device such as an artificial kidney, since the hollow fiber membrane is swollen with water, there is less concern about activating blood immediately after the start of use. In other words, in order to improve biocompatibility, a method such as mixing polyvinyl pyrrolidone, which is a hydrophilic polymer, with a hollow fiber membrane is taken, but the hydrophilic polymer in a dry state has a small particle size due to shrinkage. Therefore, the hydrophilic effect tends to decrease, and the hydrophilic polymer needs a time until swelling, that is, a relaxation time, and therefore may not exhibit the hydrophilic effect when it comes into contact with blood. (See Non-Patent Document 1).

  Therefore, the wet type or semi-dry type hollow fiber membrane module containing water in the hollow fiber membrane is less likely to cause blood activation as described above.

  When processing a liquid with a hollow fiber membrane module, mixing of the eluate in the liquid to be processed may be a problem. For example, in an artificial kidney wetted with glycerin or the like, there is a concern about the elution of glycerin into the blood. Furthermore, since glycerin is washed away by washing the module before use, it is not preferable from the viewpoint of environmental load.

  From the above, the semi-dry type hollow fiber membrane module moistened with water is superior to the wet type in terms of the handleability of the hollow fiber membrane module and compatibility with blood and the environment. However, it was found that in the semi-dry type hollow fiber membrane module, an air lock tends to occur in the first liquid passing space on the inner surface side of the hollow fiber membrane.

  Once an air lock occurs, the air lock is not easily released. Therefore, the liquid to be processed may be difficult to flow in the first liquid passing space of the hollow fiber membrane in which the air lock is generated. That is, the original performance of the hollow fiber membrane module may not be sufficiently exhibited.

That is, in a semi-dry type hollow fiber membrane module that is easy to handle and has little eluate, a high-performance hollow fiber membrane module has not existed so far.
JP 2003-245526 A JP-A-8-168524 Membrane, 30 (4), 185-191 (2005)

  An object of the present invention is to provide a semi-dry type hollow fiber membrane module having a high performance with less eluate and less airlock.

In order to achieve the above object, the present invention has the following configuration.
(1) A first inlet, a first outlet, and a hollow fiber membrane outer surface communicating with a first liquid passing space on the inner surface side of the hollow fiber membrane in a case incorporating a hollow fiber membrane having a membrane inner diameter of 50 to 1000 μm In the hollow fiber membrane module provided with the second inlet and the second outlet communicating with the second fluid passage space on the side, the liquid retention rate of the hollow fiber membrane is 20 to 600% by weight, and When the liquid present in the first liquid passage space or the second liquid passage space is 50% by volume or less of the volume of each space, and when water is further passed through the first liquid passage space at 200 ml / min, The volume of gas discharged from the first outlet from the time when 8 times the amount of water flows out to the time when 60 times the amount of water flows out is 3% of the volume of the first liquid passing space. The water is passed through the first liquid passing space at a flow rate of 100 ml / min, and 200 ml of water is passed through the first liquid passing space. The liquid in the first copies liquid space when flowing out of the outlet, the hollow fiber membrane module UV absorbance at a wavelength 240nm is equal to or more than 1.5.
(2) The hollow fiber membrane module according to (1), wherein the liquid held in the hollow fiber membrane has a viscosity of 0.013 g / (cm · sec) or less.
(3) The hollow fiber membrane module according to (1) or (2), wherein the water content of the liquid held in the hollow fiber membrane is 70% by weight or more.
(4) The hollow fiber membrane module according to any one of (1) to (3), which is used as an artificial kidney.
(5) The hollow fiber membrane module according to any one of (1) to (4), wherein the hollow fiber membrane contains a polysulfone polymer.
(6) The hollow fiber membrane module according to any one of (1) to (5), wherein the internal oxygen concentration after radiation irradiation is 6.1% by volume or less.
(7) viscosity of 0.013 g / (cm · sec) or less, the moisture content is filled liquid is 70 wt% or more, in the hollow fiber membrane module membrane inside diameter Ru 50~1000μm der, second copies After discharging the liquid in the liquid space, the second liquid passing space is set to a pressure higher than that of the first liquid passing space, and then the first liquid is passed through the first liquid passing space at a flow rate of 0.01 to 11 L (Normal) / min. A method for producing a hollow fiber membrane module, wherein the liquid in the liquid space is discharged so that the liquid retention of the hollow fiber membrane is 20 to 600%.
(8) The method for producing a hollow fiber membrane module according to (7), wherein the hollow fiber membrane module is filled with an inert gas and irradiated with radiation.
(9) The method for producing a hollow fiber membrane module according to (7) or (8), wherein the hollow fiber membrane module is any one of an artificial kidney, plasma separation, ultrafiltration, and a water purifier.
(10) The method for producing a hollow fiber membrane module according to any one of (7) to (9), wherein the hollow fiber membrane contains a polysulfone polymer.

  According to the present invention, it is possible to provide a semi-dry type hollow fiber membrane module and a method for manufacturing the same which have a high performance because there are few eluates and air locks are drastically reduced.

  The semi-dry type hollow fiber membrane module referred to in the present invention means that the liquid present in the first liquid passage space or the second liquid passage space is 50% by volume or less of the volume of each space, and the hollow fiber membrane. The liquid retention is 10% by weight or more.

  The hollow fiber membrane module referred to in the present invention will be described with reference to FIGS. 1 and 2. FIG. 1 is an embodiment of a hollow fiber membrane module according to the present invention. A hollow fiber membrane 2 is incorporated in a cylindrical case 1 of the hollow fiber membrane module. The case 1 is provided with a second inlet 5 and a second outlet 6 which are internal spaces of the case 1 and communicate with the outer surface of the hollow fiber membrane. At both ends of the case 1, there are an injection side header 7 having a first injection port 3 and a discharge side header 8 having a first discharge port 4, which are internal spaces of the case 1 and communicated with the inner surface side of the hollow fiber membrane. It is connected. The material of the case and header is not particularly limited, but plastic is used because it is easy to mold. When the hollow fiber membrane module is manufactured by radiation treatment, a radiation-resistant material is required. For example, polycarbonate, polypropylene, or polystyrene is preferable.

  Further, in the case, there are sealing portions 9 at portions closer to the case end than the respective opening positions of the second inlet 5 and the second outlet 6, and the inner surface of the case 1 and the hollow fiber The gap between the outer surface of the membrane 2 and between the hollow fiber membranes 2 is filled. The internal space of the case 1 partitioned by the sealing portion 9 is partitioned by the hollow fiber membrane 2 into a first liquid passing space which is the inner surface side of the hollow fiber membrane and a second liquid passing space which is the outer surface side of the hollow fiber membrane. Is done.

  The first liquid passing space is a space through which the first liquid (liquid to be processed, for example, blood) passes, and the inner space 11 of the hollow fiber membrane 2, the inner space of the injection side header 7, and the inner space of the discharge side header 8. Consists of. The second liquid passing space is a space through which the second liquid (for example, dialysate) is passed, and includes the outer space 12 of the hollow fiber membrane 2. The first liquid passing space communicates with the first inlet 3 and the first outlet 4 and communicates with the outside of the module. The second liquid passing space communicates with the second inlet 5 and the second outlet 6 and communicates with the outside of the module. Note that the “communication” state here does not mean a state of communication through the hole of the hollow fiber membrane.

In the present invention, the liquid retention of the hollow fiber membrane 2 is 20 to 600% by weight. The higher the liquid retention rate of the hollow fiber membrane 2, the heavier the hollow fiber membrane module, the worse the handleability. On the other hand, the smaller the liquid retention rate of the hollow fiber membrane 2, the greater the difference between the state of the surface of the hollow fiber membrane 2 before use and during use. That is, when blood compatibility or the like is required for the hollow fiber membrane 2, the hollow fiber membrane 2 is preferably wetted and swollen with a certain amount of moisture, and further, the hollow fiber membrane module is irradiated with radiation. In some cases, the eluate tends to increase if the liquid retention rate is low. Therefore, in the present invention, the liquid retention of the hollow fiber membrane 2 is 20 to 600% by weight, and more preferably 100 to 350% by weight. The liquid retention rate of the hollow fiber membrane 2 is a value calculated by the following equation (1).
p = (w _w −w _d ) × c ÷ w _d (1)
In the formula (1), p = the liquid retention rate (% by weight) of the hollow fiber membrane 2, w _w = the wet weight (g) of the hollow fiber membrane 2, w _d = the dry weight (g) of the hollow fiber membrane 2, c = Moisture content (%) in the wetting liquid.

  The wet weight here is a weight measured immediately after the hollow fiber membrane 2 is taken out from the hollow fiber membrane module. Further, the dry weight means that the hollow fiber membrane 2 is dried under reduced pressure at 40 ° C. at 1 mmHg or less, and when the weight measurement is performed every 24 hours, the weight change is 1% or less compared to the measurement result 24 hours ago. It is the weight when it becomes.

  In the present invention, as a result of intensive studies, when water was passed through the first liquid passing space of the semi-dry type hollow fiber membrane module at 200 ml / min, and water of 8 times the volume of the first liquid passing space had flowed out. If the volume of the gas discharged from the first discharge port during the period from when the water of 60 times the volume of the first liquid passage flows out to 3% or less of the volume of the first liquid passage space, It has been found that the performance of the hollow fiber membrane module is high because the liquid easily flows into the first liquid passing space. On the contrary, the hollow fiber membrane module in which the gas having a volume larger than 3% of the volume of the first liquid passage space is discharged within the liquid passage time has low performance because the liquid does not easily flow into the first liquid passage space. There are many cases.

  After eight times as much water as the volume of the first fluid passage space has flowed out, the gas is still discharged, which means that there is a hollow fiber membrane 2 in which the liquid flow state is poor or liquid is not flowing, It is considered that the gas cannot be easily discharged by the liquid flow. As factors that influence the flow state of the liquid in the hollow fiber membrane 2, variations in the inner diameter of the hollow fiber membrane, an air lock generated in the inner space 11 of the hollow fiber membrane 2, and the like are conceivable. Even when water of 8 times the volume of the first liquid passing space flows out, if the gas is discharged, there is a high possibility that an air lock has occurred. In addition, it is considered that the gas discharged after the water of 8 times the volume of the first liquid passing space flows out is discharged by the air lock generated in the inner space 11 of the hollow fiber membrane 2. If no gas is discharged after 8 times the amount of water has flowed out and before 60 times as much water as the volume of the first liquid passage space has flowed out, there is a possibility that the airlock will remain. It is considered low.

  As described above, when an air lock occurs, it is not easily released / discharged, so that it is difficult for the liquid to flow into the hollow fiber membrane in which the air lock exists. As a result, a hollow fiber membrane in which no liquid flows is generated. The performance of the hollow fiber membrane module depends on the performance of the hollow fiber membrane itself and the effective membrane area, but since the liquid to be treated does not come into contact with the hollow fiber membrane where the liquid does not flow, It is thought that the performance is lowered because the material is not removed.

  Furthermore, a hollow fiber membrane module in which a gas having a volume larger than 3% of the volume of the first liquid passing space is discharged from the first outlet during the liquid passing time is used for medical applications such as an artificial kidney. In some cases, when blood is flowed, there is a possibility of activation due to contact of blood with gas, or gas mixing into the circuit, which is not preferable.

  Therefore, it is preferable that the volume of the gas coming out of the first outlet 4 within the liquid passing time is 3% or less, more preferably 1.5% or less of the volume of the first liquid passing space.

  In addition, the volume of the gas and liquid here is a value measured at 23 ° C. and 1 atmosphere (absolute pressure). Further, the volume of the first liquid passing space is a value calculated from the following equation (2).

v = S × L × a (2)
In the formula (2), v = volume of the first liquid passing space (ml), S = cross sectional area per hollow fiber of the hollow fiber membrane 2 (cm ² ), L = end surface length of the hollow fiber membrane 2 (cm ), A = the number of yarns of the hollow fiber membrane 2 in the case 1. The cross-sectional area of the hollow fiber membrane 2 can be obtained by observing the end surface of the case portion of the sealing portion 9 with a microscope or the like. When the hollow fiber membrane 2 in the case 1 is formed of the same type and the number of yarns is 100 or more, an arbitrary number of yarns of 100 may be selected and the average value of their cross-sectional areas may be substituted. .

  In the present invention, the first volume of the gas discharged from the first discharge port 4 during the period from when 8 times the amount of water flows out until the amount of 60 times the amount of water flows out. The percentage value with respect to the volume of the liquid space is a value calculated from equation (3).

b = (v _b / v) × 100 (3)
In equation (3), b = percentage (%) of the volume of gas discharged from the first discharge port 4 to the volume of the first liquid passing space, v _b = volume of gas discharged from the first discharge port 4 ( ml), v = volume (ml) of the first liquid passing space. The gas discharged from the first outlet 4 can be collected by connecting a tube to the first outlet 4 and replacing it with water. If the volume of the tube used at this time is large, it takes a long time for the gas discharged from the first discharge port 4 to stay in the tube, causing measurement errors. Therefore, the volume of the tube is preferably 30 ml or less.

  Further, in the present invention, the liquid for wetting the hollow fiber membrane is preferably water for the reasons described later, but it may contain other than water. However, the viscosity of the liquid is preferably 0.013 g / (cm · sec) or less. This is because, in a hollow fiber membrane module that requires a washing operation before use as a product such as an artificial kidney, if the viscosity of the filled liquid is high, the washing efficiency is deteriorated. The viscosity can be measured by, for example, a falling body method.

  Further, the water content in the liquid is preferably 70% by weight or more, and more preferably 90% by weight or more. The moisture content here is a percentage value of the weight of water contained in the liquid with respect to the weight of the liquid. This is because, for the same reason as described above, if there are many components other than water, the cleanability before use as a product is deteriorated, and the effluent from such components also increases.

  With respect to medical hollow fiber membrane modules such as artificial kidneys, the eluate is important in terms of safety. Here, when there are many elution substances, the ultraviolet absorption value in the liquid to be processed will increase. Therefore, the relative amount of the eluate can be easily measured by measuring the ultraviolet absorption value.

  Although the details of the measurement method will be described later, the preferable amount of eluate is the first amount when water is passed through the first liquid passing space at a flow rate of 100 ml / min and 200 ml of water flows out from the first outlet 4. The liquid in the liquid passing space has an ultraviolet absorption value at a wavelength of 240 nm of 1.5 or less, more preferably 1.0 or less, and further preferably 0.3 or less.

  The present invention is suitably used for a blood processing module among hollow fiber membrane modules. The blood processing module referred to in the present invention means a module used for separating and purifying blood-derived components such as blood and plasma, and a module used for extracorporeal blood circulation. Further, the present invention is preferably used for an artificial kidney among blood processing modules.

  Although it does not specifically limit as a raw material of the hollow fiber membrane 2, When using for a medical use, polysulfone polymers, such as a cellulose polymer, polymethylmethacrylate, polyacrylonitrile, polysulfone, and polyethersulfone, etc. are used suitably. Among these, the use of a polysulfone polymer is particularly preferable because a hollow fiber membrane having excellent separation performance can be obtained. The polysulfone polymer referred to in the present invention has an aromatic ring, a sulfonyl group and an ether group in the main chain. For example, polysulfone represented by the chemical formulas of the following formulas (1) and (2) is preferably used. The present invention is not limited to these. N in the formula is an integer such as 50 to 80.

  Specific examples of polysulfone include Udel (registered trademark) Polysulfone P-1700, P-3500 (manufactured by Solvay), Ultrason (registered trademark) S3010, S6010 (manufactured by BASF), Victrex (registered trademark) (Sumitomo Chemical) ), Radel (registered trademark) A (manufactured by Solvay), Ultrasulone (registered trademark) E (manufactured by BASF), and the like. The polysulfone used in the present invention is preferably a polymer composed only of the repeating units represented by the above formulas (1) and / or (2), but other monomers may be used as long as the effects of the present invention are not hindered. It may be copolymerized. Although it does not specifically limit, it is preferable that another copolymerization monomer is 10 weight% or less.

  In the semi-dry type hollow fiber membrane module in the present invention, after discharging the liquid in the second liquid passage space in the hollow fiber membrane module filled with the liquid, the second liquid passage space is set to a pressure higher than that of the first liquid passage space. Thereafter, gas is passed through the first liquid passing space at a flow rate of 0.1 to 11 L (Normal) / min, the liquid in the first liquid passing space is discharged, and the liquid retention rate of the hollow fiber membrane is 20 to 600% by weight. It is obtained by doing. Here, it is most preferable to maintain the second liquid passing space at a pressure higher than that of the first liquid passing space throughout the flow of gas at a flow rate of 0.1 to 11 L (Normal) / min. Even if it is a time for most of the liquid to be discharged from the first liquid passing space, that is, only in the first 10 seconds, preferably only in the first 120 seconds, the effect of the present invention is obtained. May be. Therefore, it is not essential to maintain the second liquid passing space at a pressure higher than that of the first liquid passing space throughout the flow of gas through the first liquid passing space.

  A method for discharging the liquid in the second liquid passing space is not particularly limited, but a method of discharging the liquid from the first liquid passing space through the membrane by pressurizing the second liquid passing space with gas, There is a method of discharging the liquid space from the second liquid passing space in a reduced pressure state. Since the second liquid passing space is set to a pressure higher than that of the first liquid passing space in a later step, it is preferable to use the former method. However, if the pressure at this time is high, the hollow fiber membrane 2 may be crushed and the quality may be affected. Therefore, although not particularly limited, the pressure applied when discharging the liquid in the second liquid passing space is preferably 0.3 MPa or less.

  The reason why the filled liquid is discharged by the above-described method is to suppress the occurrence of gas turbulence in the inner space 11 (first liquid passing space) of the hollow fiber membrane 2. That is, the air lock is considered to occur when a turbulent gas flow occurs, and is intended to prevent the air lock.

  In order to suppress the turbulent flow of gas, it is effective to extrude the liquid in the first liquid passing space at a low flow rate, and therefore, the liquid is extruded with a gas having a flow rate of 11 L (Normal) / min or less. The flow rate is preferably 2.4 L (Normal) / min or less. On the other hand, if the flow rate is too low, it takes time to discharge the liquid, which is not preferable in terms of production efficiency. Therefore, it is preferable to extrude the liquid in the first liquid passing space with a gas having a flow rate of 0.01 L (Normal) / min or more, and more preferably 0.5 L (Normal) / min or more.

  Although the above is a preferable flow rate condition when the first liquid passing space is filled with the liquid, the flow rate condition changes after the liquid is almost discharged. That is, since the first liquid passing space is a gas phase, turbulence is less likely to occur when a gas is flowed than when the first liquid passing space is filled with liquid. Therefore, a preferable flow rate range of the gas flowing into the first liquid passing space after the liquid is almost discharged is 0.01 to 20 L (Normal) / min. In order to set the liquid retention rate of the hollow fiber membrane to 20 to 600%, depending on the specific flow rate in such a flow rate range, it is preferable that the time for passing the gas through the first liquid passing space is at least about 10 seconds, About 120 seconds is often sufficient. However, it takes a long time to bring the hollow fiber membrane retention rate to about 20%, and it may take several days. In consideration of the effect of drying, the time for reducing the liquid retention rate can be shortened by increasing the temperature of the flowing gas.

  At this time, the pressure in the second liquid passage space needs to be higher than the pressure in the first liquid passage space. This is because, for example, when the hollow fiber membrane 2 is a porous membrane, when the pressure of the second fluid passage space is lower than the pressure of the first fluid passage space, the first fluid passage space is directed to the second fluid passage space. This is because a turbulent flow is likely to be formed because pressure is applied. Specifically, it is preferable that the second liquid passing space is in a pressurized state. However, since the hollow fiber membrane 2 may be crushed when the pressurizing pressure is too high, the pressure is preferably 0.3 MPa or less.

  In addition, since the turbulent flow hardly occurs after the liquid is almost discharged as described above, it may not be necessary to make the pressure of the second liquid passing space higher than the pressure of the first liquid passing space.

As a matter of course, if the total flow rate of the gas passing through the first liquid passage space does not reach the volume of the first liquid passage space, a large amount of liquid remains in the first liquid passage space. Therefore, the total flow rate of the gas passing through the first liquid passing space is preferably not less than the volume of the first liquid passing space, and more preferably not less than 400% of the volume of the first liquid passing space.
Here, since the generated air lock is not easily released, after the hollow fiber membrane module filled with the liquid is made a semi-dry type module by the above-described method, a gas may flow into the first liquid passing space. In some cases, it is necessary to prevent air lock from occurring. That is, when a gas is allowed to flow through the first liquid passing space, it is necessary to always use the method described above or a method based thereon.

  Since the airlock is more likely to occur as the hollow fiber membrane has a smaller inner diameter, the effect of the manufacturing method of the present invention is more exhibited. Further, if the inner diameter of the hollow fiber membrane is too small, the pressure inside the membrane when the fluid flows is increased, and the hollow fiber membrane may be damaged. Then, the manufacturing method of this invention is used suitably about the hollow fiber membrane module whose internal diameter of the hollow fiber to incorporate is 50-5000 micrometers. Further, it is more suitably used for a hollow fiber membrane module having an internal diameter of the built-in hollow fiber membrane of 50 to 1000 μm, and more preferably for a hollow fiber membrane module having an internal diameter of the built-in hollow fiber membrane of 50 to 350 μm. In addition, the value of the internal diameter of a hollow fiber membrane is obtained by observing the case part end surface of the sealing part 9 with a microscope.

  Moreover, in the manufacturing method of this invention, although water is preferable as a liquid with which a hollow fiber membrane module is filled, things other than water may be contained. However, as described above, in view of cleaning efficiency before use as a product, the viscosity of the liquid is preferably 0.013 g / (cm · sec) or less, and the water content of the liquid is 70% by weight or more. Further, 90% by weight or more is more preferable.

  The gas used for discharging the liquid filled in the hollow fiber membrane module is not particularly limited, but the hollow fiber membrane 2 is not denatured and even if it remains in the hollow fiber membrane module, the quality is affected. A type having no is suitably selected. Therefore, air, oxygen, nitrogen, argon gas and the like are preferable.

  When the hollow fiber membrane module is used for medical applications such as an artificial kidney, sterilization is necessary. Examples of the sterilization method include radiation sterilization, steam sterilization, and ethylene oxide gas sterilization. In recent years, radiation sterilization methods have been frequently used from the viewpoint of low residual toxicity and simplicity, and γ rays and electron beams are particularly preferably used.

  In the case of a semi-dry type hollow fiber membrane module, radiation sterilization is preferably performed after the hollow fiber membrane module is placed in an inert gas atmosphere. Specific examples of the inert gas include nitrogen, argon, helium, neon, krypton, xenon, and radon. Especially, since nitrogen is cheap, it is used suitably.

  When enclosing an inert gas in the hollow fiber membrane module, it is preferable to employ an inert gas as a gas for discharging the liquid filled in the hollow fiber membrane module described above for simplification of the process. .

  In particular, when oxygen is present, oxygen radicals are generated by radiation irradiation, which causes modification and decomposition of materials such as hollow fiber membranes and cases.

  Furthermore, the oxygen concentration in the hollow fiber membrane module after irradiation is preferably 6.1% by volume or less, more preferably 3.6% by volume or less. In addition, the inside of a hollow fiber membrane module means the inner space of the case 1.

  When the oxygen concentration in the hollow fiber membrane module exceeds 6.1% by volume, water is passed through the first liquid passing space at 200 ml / min with respect to the hollow fiber membrane module after irradiation, and the first liquid passing space is obtained. The volume of gas discharged from the first discharge port is 3 of the volume of the first liquid passing space between the time when 8 times the amount of water is discharged and the time when 60 times the amount of water is discharged. % May not fall below.

  Further, when the oxygen concentration exceeds 6.1%, the performance of the hollow fiber membrane module varies depending on the module, and a high performance module may be obtained. In general, however, the effluent into the liquid being processed tends to increase. The reason for the increase in the eluate is considered to be that the hollow fiber membrane and the like are decomposed by oxygen radicals. On the other hand, the reason why the performance may be high is unknown, but there is a possibility that the film surface is modified by oxygen radicals, affecting the process of airlock generation.

  The method for measuring the oxygen concentration will be described later in detail. With the first inlet 3, the first outlet 4, the second inlet 5, and the second outlet 6 sealed, the air inside the outlet header 8 is removed. Measure with an oximeter. The production method of the present invention is suitably used for the production of a blood processing module among the production of a hollow fiber membrane module. Moreover, it is used suitably for manufacture of an artificial kidney also in the module for blood processing.

  The material of the hollow fiber membrane 2 in the present production method is not particularly limited, but when used for medical purposes, cellulose-based polymers, polymethyl methacrylate, polyacrylonitrile, polysulfone-based polymers such as polysulfone and polyethersulfone, and the like. Preferably used. Among these, the use of a polymer containing a polysulfone polymer is preferable because a hollow fiber membrane having excellent separation performance can be obtained.

EXAMPLES The present invention will be described below with reference to examples, but the present invention is not limited to these examples.
1. Method for producing hollow fiber membrane module Polysulfone (Amoco Udel-P3500) 17% by weight, polyvinylpyrrolidone K30 (International Special Products, hereinafter referred to as ISP) 3.5% by weight, polyvinylpyrrolidone K90 (ISP) 2.5 The film was dissolved by heating at 90 ° C. together with 76% by weight of dimethylacetamide and 1% by weight of water to obtain a film forming stock solution.

  This stock solution was sent to a spinneret part at a temperature of 50 ° C. and discharged from a double slit tube having an inner diameter of 0.35 mm and an inner diameter of 0.25 mm. A solution composed of 60 parts by weight of dimethylacetamide and 40 parts by weight of water was discharged from the inner tube as a core liquid. The discharged stock solution is passed through a 350 mm long space having a dry zone atmosphere adjusted to a temperature of 30 ° C. and a dew point of 39 to 40 ° C., and then solidified at a temperature of 40 ° C. consisting of 25% by weight of dimethylacetamide and 75% by weight of water. A hollow fiber membrane was obtained by passing through a bath. Then, the hollow fiber membrane obtained through the washing process performed for 90 second with 60-75 degreeC water and the drying process performed for 2 minutes at 140 degreeC was passed, and the hollow fiber membrane obtained through the crimping process performed at 160 degreeC was wound up, and it was set as the bundle. Fill the case with the number of hollow fiber membranes that will have an arbitrary surface area inside the membrane, seal the ends with a potting agent made of polyurethane resin, and open the hollow fibers at both ends toward the outside. The potting agent was cut along a direction parallel to the cross section of the case, and headers were attached to both ends of the case after the potting agent was cut to obtain a hollow fiber membrane module. The inner diameter of the hollow fiber at this time was observed with a magnification of 200 times using a microscope (KEYENCE UH-500), and measured with a measuring system (Mitsubishi Kasei MS-3000). The average value of 100 measured was 200 μm. The end face length was 28.5 cm.

  Here, the in-film surface area in the present invention is a value calculated by the equation (4).

S _M = D × π × L × 10 ⁻⁸ × a (4)
In the formula (4), S _M = surface area in membrane (m ² ), D = hollow fiber inner diameter (μm), π = circumferential ratio, L = end surface length (cm) of hollow fiber membrane 2, a = in case 1 Of the hollow fiber membrane 2.
2. As for the hollow fiber membrane module for carrying out the bubble-removability test, the hollow fiber membrane module is once passed through, because the state of the air lock in the first liquid passing space changes. An unused one was used.

  The blood circuit (H-102-KTS Toray Co., Ltd.) was filled with water and connected to the first inlet 3. The empty blood circuit was cut to a length of 9.5 cm and connected to the first outlet 4. The hollow fiber membrane module was fixed with a clamp with the first inlet 3 on the bottom and the first outlet 4 on the top. The liquid level of the chamber of the blood circuit connected to the first inlet 3 and the height of the center of the hollow fiber membrane module were matched.

  The second inlet 5 and the second outlet 6 were closed with stoppers. Using a blood pump (LF-300 MED-TECH), water at 23 ° C. was flowed from the first inlet 3 to the first outlet 4 at a flow rate of 200 ml / min, and passed through the hollow fiber membrane module.

  During the flow of the liquid, the hollow fiber membrane module was kept stationary so as not to give vibration or change in water pressure other than the pump. In addition, liquid passing was not stopped during the test.

  When the flow rate reached 8 times the volume of the first flow space, the circuit outlet was inserted into a graduated cylinder filled with water and with the mouth down. All of the gas discharged from the circuit outlet was collected by water replacement until the flow rate was 60 times the volume of the first flow space.

  The volume of the collected gas was measured at 23 ° C. and 1 atmosphere (absolute pressure). The value of the percentage with respect to the volume of the first liquid passing space of this gas was calculated from the following equation (3).

b = (v _b / v) × 100 (3)
The symbols in the formula (3) are the same as those described above, but b = residual gas ratio (%), v _b = residual gas amount (ml), v = volume of the first liquid passing space (ml), It is calculated | required by (2) Formula mentioned above.
3. Measurement of eluate The blood circuit was filled with distilled water (Otsuka distilled water Otsuka Pharmaceutical), and this was connected to the first inlet 3. An empty blood circuit was connected to the first outlet 4. The hollow fiber membrane module was fixed with a clamp with the first inlet 3 on the bottom and the first outlet 4 on the top. The liquid level of the chamber of the blood circuit connected to the first inlet 3 and the height of the center of the hollow fiber membrane module were matched.

  The second inlet 5 and the second outlet 6 were closed with stoppers. A blood pump (LF-300 MED-TECH) was used to flow from the first inlet 3 to the first outlet 4 at a flow rate of 100 ml / min, and 23 ° C. distilled water was passed through the hollow fiber membrane module.

  5 ml immediately after 200 ml of distilled water passed through the circuit exited from the circuit outlet was taken as a sample. The ultraviolet absorption value at a wavelength of 240 nm for the sample was measured with a spectrophotometer (UV-160 Shimadzu Corporation). At this time, the measurement was performed at 23 ° C.

Separately, a solution obtained by passing distilled water through the blood circuit only in the same manner without passing through the hollow fiber membrane module was collected, and this was used as a blank to measure the ultraviolet absorption value at a wavelength of 240 nm. The value was determined by subtracting from the value.
4). Performance test As a performance of the hollow fiber membrane module, β ₂ -microglobulin clearance was used as an index. The measuring method is shown below.

  The blood circuit was filled with water and connected to the first inlet 3. An empty blood circuit was connected to the first outlet 4. The hollow fiber membrane module was fixed with a clamp with the first inlet 3 on the bottom and the first outlet 4 on the top. The liquid level of the chamber of the blood circuit connected to the first inlet 3, the upper part of the chamber of the blood circuit connected to the first outlet 4, and the height of the center of the hollow fiber membrane module were matched.

  Physiological saline was passed through the hollow fiber membrane module from the first inlet 3 to the first outlet 4 at 200 ml / min for 5 minutes. At that time, the second inlet 5 and the second outlet 6 were closed with caps.

  The plug of the second inlet 5 was removed. The first discharge port 4 was closed with forceps. Saline was passed from the first inlet 3 to the second inlet 5 of the hollow fiber membrane module at 200 ml / min for 5 minutes.

  25 mmol of ethylenediaminetetraacetic acid disodium was added to 50 ml of pure water, and sodium hydroxide was added with sufficient stirring to adjust the pH to 7.4. 10 L of the same lot of bovine blood was collected and stirred. The suspended matter was removed from this solution. About 5 L of this solution, centrifugation at 4 ° C. and 3000 rpm was performed for 30 minutes, and plasma was collected. It is confirmed whether or not the plasma is hemolyzed, and if it is hemolyzed, the above procedure is performed again to obtain plasma.

  Each of bovine blood and bovine plasma was filtered through two layers of gauze. Hematocrit and total protein were measured for the filtered bovine blood and bovine plasma.

  Subsequently, bovine plasma and physiological saline were mixed with bovine blood so that the hematocrit of the bovine blood was 30 ± 3% and the total protein amount was 6.5 ± 0.5 g / dL.

  The bovine blood was heated in a hot water bath to 37 ° C and maintained at 37 ° C.

The bovine blood was then filtered through 4 layers of gauze. To the filtered bovine blood, β ₂ -microglobulin was dissolved in the CAPD waste solution so that the β ₂ -microglobulin concentration was 1 mg / l, and then stirred. The cow blood was divided into 2 L for circulation and 1.5 L for clearance measurement. The adjusted bovine blood was stored at 4 ° C. and used within one week.

  A performance test was conducted using bovine blood prepared by the above method. The following operations were carried out promptly because the freshness of bovine blood would be affected if the interval between operations was greatly increased.

  The circuit was set as shown in FIG. That is, the Bi (Blood Inlet) circuit and the first inlet 3 were connected, and the Bo (Blood Outlet) circuit and the first outlet 4 were connected. At this time, in order to stabilize the pressure in the Bi circuit, a trap was attached between the Bi pump and the Bi chamber, and the circuit was filled with physiological saline to prevent air from entering the hollow fiber membrane module. In addition, the liquid level of the chamber of the Bi circuit and the Di (dialysate inlet) circuit, the upper part of the chamber of the Bo circuit and the Do (dialysate outlet) circuit, and the center of the hollow fiber membrane module are the same. Adjusted to the reference line. Subsequently, the first inlet 3 was down and the first outlet 4 was up and fixed with a clamp. From the Bi circuit, physiological saline was passed through the first inlet toward the first outlet at a flow rate of 100 ml / min for 1 minute. Thereafter, the Bi circuit and the Bo circuit were stopped with forceps, the Di circuit and the second inlet 5 were connected, and the Do circuit and the second outlet were connected.

  As a dialysis machine, TR2000S manufactured by Toray Medical Co., Ltd. was used. TR2000S corresponds to the Bi pump, the F pump, and the dialyzer in FIG.

  Dialysate (Kindaly AF No. 2 Fuso Yakuhin Kogyo Co., Ltd.) A solution and B solution were set in the dialyzer. The filtered tap water was poured from the dialysate side toward the blood side using Tresulfone (registered trademark) (TS-1.6UL Toray Industries, Inc.) in the dialyzer.

  Subsequently, the preparation button of the TR2000S dialysis machine was pressed. When the dialysate concentration is 13 to 15 mS / cm and the temperature is 34 ° C. or higher, preparation is completed. After confirming the completion of preparation, the Di pump was started. At this time, the dialysate side flow rate was set to 500 ml / min.

  The Bi circuit and Bo circuit forceps were removed, the Bi flow rate was set to 200 ml / min, the Bi pump was started, physiological saline was passed through the Bi circuit, and dialysate was passed through the Di circuit for 5 minutes. Thereafter, the Bi pump and the Di pump were stopped.

The water removal rate of the water permeable device was set to 10 ml / (min · m ² ). The Bi pump was started in a state where the Bi circuit inlet was placed in a circulation beaker and the Bo circuit outlet was placed in a disposal container, and 90 seconds of liquid discharged from the Bo circuit outlet was discarded. The liquid flowing out from the Do circuit outlet was discarded. After 90 seconds, the Bo circuit outlet and the Do circuit outlet were immediately put into a circulation beaker to be in a circulating state. The gap between the trap and the Bi chamber was closed with forceps, the liquid level of the trap portion was raised, and then the forceps were removed. Subsequently, the ECU2000 button of the TR2000S dialyzer was started, the F pump was moved, and circulation was performed for 1 hour. The trap and Bi chamber were again closed with forceps, and at the same time, the Bi pump and F pump were stopped.

  Next, the Bi circuit inlet was placed in bovine blood for clearance measurement, and the Bo circuit outlet was placed in an exhaust beaker. The liquid flowing out from the Do circuit outlet was discarded.

  The preparation button on the TR2000S dialysis machine was pressed. After confirming that the preparation was completed at a dialysate concentration of 13 to 15 mS / cm and a temperature of 34 ° C. or higher, the Di pump was started. In addition, the blood pump was started and the forceps between the trap and the Bi chamber were removed.

  After 2 minutes from the start, 10 ml of a sample was collected from bovine blood for clearance measurement, and used as Bi solution. After 4 minutes and 30 seconds from the start, 10 ml of a sample was taken from the Bo circuit outlet and used as Bo solution. These samples were stored in a freezer at −20 ° C. or higher.

  Thereafter, the trap and the Bi chamber were closed with forceps, and at the same time, the Bi pump and the Di pump were stopped.

The clearance was calculated from the concentration of β ₂ -microglobulin in each solution according to the following formula (6). Since the measured values may differ depending on the lot of bovine blood, the same lot of bovine blood was used for comparison data.

Co (ml / min) = (CBi−CBo) × Q _B / CBi (6)
(5) In the formula, _{C O} = beta ₂ - microglobulin clearance (ml / min), CBi = Bi β in solution ₂ - microglobulin concentration, _CB o = β in Bo liquid ₂ - microglobulin _{concentrations,} Q B = Bi Pump flow rate (ml / min).
5. Measurement of oxygen concentration The oxygen concentration was measured by sealing the first inlet 3, the first outlet 4, the second inlet 5, and the second outlet 6 with rubber stoppers.
The oxygen concentration was measured using an oxygen concentration meter (Iijima Electronics Co., Ltd. RO-102). The oxygen concentration meter is a type in which a syringe is integrated, and can measure the oxygen concentration of the gas sent from the needle tip into the oxygen concentration meter.

  Calibration of the oxygen concentration meter was performed by sending a gas having an oxygen concentration of 21% into the sensor unit three times. Calibration was performed once at the beginning of the measurement.

An oximeter needle was inserted into the plug attached to the first discharge port 4, and the gas in the discharge-side header 8 was sent to the sensor unit three times. The value was read in a stable state in which the value of the oximeter did not change by 0.1% within 1 minute, and was taken as the oxygen concentration of the module.

Example 1
1 above. Used a hollow fiber membrane module having an in-membrane surface area of 1.6 m ² . First, the module was filled with pure water. That is, the second inlet 5 and the second outlet 6 were closed with stoppers, and pure water was passed from the first outlet 4 to the first inlet 3. Thereafter, the first inlet 3 and the second inlet 5 were closed, pure water was introduced from the first outlet 4, and pure water was passed through the second outlet 6. At this time, the flow rate of pure water was 500 ml / min, and a flow rate of 500 ml was passed.

  Next, pure water in the module was discharged to obtain a semi-dry type hollow fiber membrane module. That is, the first discharge port 4 and the second discharge port 6 are closed, and compressed air of 23 ° C. is flowed from the second injection port 5 at a flow rate of 20 L (Normal) / min for 15 seconds to push out the filling water in the second liquid passing space. It was. Then, 23 degreeC compressed air was flowed from the 2nd inlet 5, and it closed in the state which made the pressure of the 2nd liquid passage space into the pressurization state of 0.1 MPa. The first discharge port 4 was opened, and compressed air of 23 ° C. was allowed to flow from the first injection port 3 to the first discharge port 4 at a flow rate of 2 L (Normal) / min for 30 seconds to push out the filling water in the first liquid passing space. .

  Subsequently, nitrogen at 23 ° C. was allowed to flow from the first inlet 3 to the first outlet 4 at a flow rate of 2 L (Normal) / min for 15 seconds to enclose the nitrogen. Immediately, the first inlet 3 and the first outlet 4 were plugged and sealed. Thereafter, nitrogen at 23 ° C. was allowed to flow from the second inlet 5 to the second outlet 6 at a flow rate of 2 L (Normal) / min for 15 seconds to enclose the nitrogen. Immediately, the second inlet 5 and the second outlet 6 were plugged and sealed. After nitrogen was sealed, the module was irradiated with γ rays (dose: 25 kGy).

  Make a total of four semi-dry type hollow fiber membrane modules irradiated with γ-rays in the same way, and for each one, perform one of the bubble removal test, eluate measurement, performance test, and oxygen concentration measurement. It was performed once by the above method.

The result was as shown in Table 1. That is, in the hollow fiber membrane module, the volume of the gas discharged from the first discharge port was 1.1% of the volume of the first liquid passing space, and there was little eluate and high performance was exhibited.
(Example 2)
1 above. In Example 1, the hollow fiber membrane module having an in-membrane surface area of 2.1 m ² was discharged after filling with pure water in the same manner as in Example 1, followed by nitrogen encapsulation and γ-ray irradiation.

  Make a total of four semi-dry type hollow fiber membrane modules irradiated with γ-rays in the same way, and for each one, perform one of the bubble removal test, eluate measurement, performance test, and oxygen concentration measurement. It was performed once by the above method.

The result was as shown in Table 1. That is, in the hollow fiber membrane module, the volume of the gas discharged from the first discharge port was 1.7% of the volume of the first liquid passing space, and there was little eluate and high performance was exhibited.
(Example 3)
1 above. In Example 1, the hollow fiber membrane module having an in-membrane surface area of 1.6 m ² was discharged after filling with pure water in the same manner as in Example 1, followed by nitrogen sealing and γ-ray irradiation. However, when discharging the filling water in the first liquid passing space, the flow rate of the compressed air flowing from the first inlet 3 to the first outlet 4 was 1 L (Normal) / min.

  Make a total of four semi-dry type hollow fiber membrane modules irradiated with γ-rays in the same way, and for each one, perform one of the bubble removal test, eluate measurement, performance test, and oxygen concentration measurement. It was performed once by the above method.

The result was as shown in Table 1. That is, in the hollow fiber membrane module, the volume of the gas discharged from the first discharge port was 1.0% of the volume of the first liquid passing space, and there was little eluate and high performance was exhibited. .
Example 4
1 above. In Example 1, the hollow fiber membrane module having an in-membrane surface area of 1.6 m ² was discharged after filling with pure water in the same manner as in Example 1, followed by nitrogen sealing and γ-ray irradiation. However, the flow rate of the compressed air that flowed from the first inlet 3 to the first outlet 4 when discharging the filling water of the first liquid passing space was 4 L (Normal) / min.

  Make a total of four semi-dry type hollow fiber membrane modules irradiated with γ-rays in the same way, and for each one, perform one of the bubble removal test, eluate measurement, performance test, and oxygen concentration measurement. It was performed once by the above method.

The result was as shown in Table 1. That is, in the hollow fiber membrane module, the volume of the gas discharged from the first discharge port was 1.1% of the volume of the first liquid passing space, and there was little eluate and high performance was exhibited.
(Comparative Example 1)
1 above. Then, the hollow fiber membrane module having an in-membrane surface area of 1.6 m ² was discharged after filling with pure water in the same manner as in Example 1, and further filled with nitrogen and irradiated with γ rays (25 kGy). However, when discharging the filling water in the first liquid passing space, the flow rate of the compressed air flowing from the first inlet 3 to the first outlet 4 is 20 L (Normal) / min. Pressurization with compressed air was not performed. Moreover, the flow rate at the time of nitrogen filling was also set to 20 L (Normal) / min.

  Make a total of four semi-dry type hollow fiber membrane modules irradiated with γ-rays in the same way, and for each one, perform one of the bubble removal test, eluate measurement, performance test, and oxygen concentration measurement. It was performed once by the above method.

The result was as shown in Table 1. That is, in the hollow fiber membrane module, the volume of the gas discharged from the first discharge port was 5.2% of the volume of the first liquid passing space, and the eluate was small, but showed low performance. .
(Comparative Example 2)
1 above. In Example 1, the hollow fiber membrane module having an in-membrane surface area of 1.6 m ² was discharged after filling with pure water in the same manner as in Example 1, followed by nitrogen sealing and γ-ray irradiation. However, the flow rate of the compressed air that flowed from the first inlet 3 to the first outlet 4 when discharging the filling water in the first liquid passing space was 20 L (Normal) / min. Moreover, the flow rate at the time of nitrogen filling was also set to 20 L (Normal) / min.

  Make a total of four semi-dry type hollow fiber membrane modules irradiated with γ-rays in the same way, and for each one, perform one of the bubble removal test, eluate measurement, performance test, and oxygen concentration measurement. It was performed once by the above method.

The result was as shown in Table 1. The result was as shown in Table 1. That is, in the hollow fiber membrane module, the volume of the gas coming out from the first outlet is 4.5% of the volume of the first liquid passing space, and the amount of the eluate was small, but low performance was exhibited. It was.
(Comparative Example 3)
1 above. In Example 1, the hollow fiber membrane module having an in-membrane surface area of 1.6 m ² was discharged after filling with pure water in the same manner as in Example 1, followed by nitrogen sealing and γ-ray irradiation. However, the flow rate of the compressed air that flowed from the first inlet 3 to the first outlet 4 when discharging the filling water in the first liquid passing space was 20 L (Normal) / min.

  Make a total of four semi-dry type hollow fiber membrane modules irradiated with γ-rays in the same way, and for each one, perform one of the bubble removal test, eluate measurement, performance test, and oxygen concentration measurement. It was performed once by the above method.

The result was as shown in Table 1. That is, in the hollow fiber membrane module, the volume of the gas coming out from the first outlet is 4.0% of the volume of the first liquid passing space, and the amount of the eluate was small, but low performance was exhibited. It was.
(Comparative Example 4)
1 above. Then, the hollow fiber membrane module having a membrane surface area of 1.6 m ² was discharged after filling with pure water in the same manner as in Example 1, and further irradiated with γ rays. However, nitrogen filling was not performed.

Make a total of four semi-dry type hollow fiber membrane modules irradiated with γ-rays in the same way, and for each one, perform one of the bubble removal test, eluate measurement, performance test, and oxygen concentration measurement. It was performed once by the above method.
The result was as shown in Table 1. That is, in the hollow fiber membrane module, the oxygen concentration is high, the volume of the gas coming out of the first outlet is 3.8% of the volume of the first liquid passing space, and the amount of eluate is slightly higher, Shows low performance.
(Comparative Example 5)
1 above. The hollow fiber membrane module having a membrane surface area of 1.6 m ² was filled in the same manner as in Example 1 and then discharged, followed by nitrogen sealing and γ-ray irradiation. However, 100 parts by weight of glycerin was filled.

  Make a total of four semi-dry type hollow fiber membrane modules irradiated with γ-rays in the same way, and for each one, perform one of the bubble removal test, eluate measurement, performance test, and oxygen concentration measurement. It was performed once by the above method.

  The result was as shown in Table 1. That is, in the hollow fiber membrane module, the volume of the gas coming out from the first discharge port was 0.9% of the volume of the first liquid passing space and showed high performance, but there were many eluates.

The one aspect | mode of the hollow fiber membrane module used for this invention is shown. A part of cross section of the hollow fiber membrane module used for this invention is shown. The circuit diagram in the performance test is shown.

Explanation of symbols

DESCRIPTION OF SYMBOLS 1 Case 2 Hollow fiber membrane 3 1st injection port 4 1st discharge port 5 2nd injection port 6 2nd discharge port 7 Injection side header 8 Discharge side header 9 Sealing part 10 Membrane pressure part of hollow fiber membrane 11 Hollow fiber membrane Inside part 12 Outside part of hollow fiber membrane 13 End face length

Claims (10)

A case in which a hollow fiber membrane having a membrane inner diameter of 50 to 1000 μm is incorporated is a first injection port and a first discharge port communicating with the first liquid passing space on the inner surface side of the hollow fiber membrane, and the outer surface side of the hollow fiber membrane. In the hollow fiber membrane module provided with the second inlet and the second outlet communicating with the second fluid passage space, the liquid retention rate of the hollow fiber membrane is 20 to 600% by weight, and the first fluid passage The liquid existing in the space or the second liquid passing space is 50% by volume or less of the volume of each space, and when water is further passed through the first liquid passing space at 200 ml / min, The volume of gas discharged from the first discharge port between the time when 8 times the volume of water flows out and the time when 60 times the amount of water flows out is 3% or less of the volume of the first liquid passing space. , Water is passed through the first liquid passing space at a flow rate of 100 ml / min, and 200 ml of water is first discharged. The liquid for the one copy liquid space, hollow fiber membrane modules UV absorbance at a wavelength 240nm is equal to or more than 1.5 when flowing out. 2. The hollow fiber membrane module according to claim 1, wherein the liquid contained in the hollow fiber membrane has a viscosity of 0.013 g / (cm · sec) or less. The hollow fiber membrane module according to claim 1 or 2, wherein the water content of the liquid held in the hollow fiber membrane is 70 wt% or more. The hollow fiber membrane module according to any one of claims 1 to 3, wherein the hollow fiber membrane module is used as an artificial kidney. The hollow fiber membrane module according to any one of claims 1 to 4, wherein the hollow fiber membrane contains a polysulfone polymer. The hollow fiber membrane module according to any one of claims 1 to 5, wherein the internal oxygen concentration after radiation irradiation is 6.1% by volume or less. Viscosity of 0.013g / (cm · sec) or less, the liquid water content is 70 wt% or more is filled, membrane inner diameter of the hollow fiber membrane module Ru 50~1000μm der, the second copies liquid space After discharging the liquid, the second liquid passing space is set to a pressure higher than that of the first liquid passing space, and then the gas is passed through the first liquid passing space at a flow rate of 0.01 to 11 L (Normal) / min. A method for producing a hollow fiber membrane module, wherein the liquid is discharged to make the hollow fiber membrane have a liquid retention of 20 to 600%. The method for producing a hollow fiber membrane module according to claim 7, wherein the hollow fiber membrane module is filled with an inert gas and irradiated with radiation. The method for producing a hollow fiber membrane module according to claim 7 or 8, wherein the hollow fiber membrane module is any one of an artificial kidney, plasma separation, ultrafiltration, and a water purifier.   The said hollow fiber membrane contains the polysulfone type polymer, The manufacturing method of the hollow fiber membrane module in any one of Claims 7-9 characterized by the above-mentioned.

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