JP4748348B2 - Polysulfone-based permselective hollow fiber membrane bundle - Google Patents

Description

  The present invention relates to a polysulfone-based permselective hollow fiber membrane bundle having high safety and stability in performance, and particularly suitable for blood purifiers and the like.

  In recent years, technology using membranes with selective permeability has made remarkable progress, and so far in a wide range of fields such as gas and liquid separation filters, hemodialyzers in the medical field, blood filters, blood component separation, etc. Practical use is progressing. As the material of the membrane, cellulose resins (regenerated cellulose, cellulose acetate, chemically modified cellulose, etc.), polyacrylonitrile resins, polymethyl methacrylate resins, polysulfone resins, ethylene vinyl alcohol resins, polyamide resins and the like have been used. Among these, the polysulfone resin is a semipermeable membrane material because its blood compatibility is improved by adding a hydrophilizing agent to the film-forming solution in addition to its heat stability, acid resistance, and alkali resistance. As a result, research has been promoted.

  In blood purification therapy for renal failure treatment, etc., hemodialyzer, blood filter or hemodialysis filter using dialysis membrane or ultrafiltration membrane as a separator for the purpose of removing urine toxins and waste products in blood The module is widely used. In particular, modules using hollow fiber membranes as separation materials are important in the dialyzer field due to advantages such as reduction of the amount of blood circulating outside the body, high efficiency of removing substances in the blood, and productivity during module production. high.

  On the other hand, in order to produce a module by bonding the hollow fiber membrane bundle, it is necessary to dry the hollow fiber membrane bundle. However, the porous membrane made of organic polymer, especially dialysis membrane made of hydrophobic resin such as polysulfone In addition, it is known that when the ultrafiltration membrane is dried after the film formation, the water permeability is remarkably reduced as compared with that before drying. Therefore, it was necessary to handle the membrane always in a wet state or in a state immersed in water.

  As a countermeasure against this problem, a conventional method has been to pack a low-volatile organic liquid such as glycerin in the pores in the porous film after film formation and before drying. However, since low-volatile organic liquids generally have high viscosity, it takes time for cleaning and removal, and even after the membrane is molded into a module, a small amount of effluent derived from low-volatile organic liquids (low-volatile organic There was a problem in that various derivatives produced by chemical reaction with liquid were found in the module sealing liquid.

As a method for drying without using a low-volatile organic liquid, a method using an inorganic salt such as calcium chloride in place of the low-volatile organic liquid is disclosed, but the necessity for washing and removing remains unchanged. Moreover, even if it is a trace amount, there is a concern that the remaining inorganic salt may adversely affect the dialysis patient (see Patent Document 1).
JP-A-6-277470

Moreover, as a method for drying the membrane, a method for producing a hollow fiber membrane in which microwave irradiation is performed while performing wet heat treatment with water vapor on the hollow fiber membrane is disclosed (see Patent Document 2). However, there is a drawback of extending the drying time because it is steamed to prevent deformation of the membrane while being dry, and since it is drying after attaching a low volatile organic liquid such as glycerin, The objective of reducing effluent from the membrane is not achieved.
JP 11-332980 A

A hydrophilized film containing polyvinyl pyrrolidone that has been dried without using a low-volatile organic liquid is disclosed (see Patent Documents 3 and 4). These describe the ability to separate plasma components from blood, but it is found that plasma proteins permeate and are not effective as dialysis membranes. In addition, since it is dried at a temperature at which polyvinylpyrrolidone is decomposed and modified, it is an extremely undesirable production method for the purpose of reducing the amount of eluate from the membrane.
JP-A-8-52331 Japanese Patent Publication No.8-9668

In addition, a method for producing a high-performance blood purification membrane by drying a wet membrane having a specific performance at a temperature of 120 ° C. or less without impregnating with a low-volatile organic liquid such as glycerin is disclosed (Patent Document). 5). However, it has been clarified by the same inventors that this method causes a slight difference in performance between the central portion and the outer peripheral portion of the yarn bundle when the yarn bundle is dried.
Japanese Patent No. 3281364

As a measure for solving the problem of the drying method disclosed in Patent Document 5 by the same inventors as Patent Document 5, a method of drying by irradiating microwaves is disclosed (see Patent Documents 6 to 9). These methods are preferable in that they are dried without impregnating the low-volatile organic liquid and can be dried without deteriorating the separation performance of the hollow fiber membrane bundle. However, any of these methods is a method in which gas is blown into the hollow fiber membrane bundle to achieve uniform drying of the center portion and the outer peripheral portion of the yarn bundle. In addition to the microwave irradiation mechanism, this method requires the installation of an auxiliary mechanism for ventilating the gas in the hollow fiber membrane bundle, and has a problem that the structure of the dryer becomes complicated. The method also requires that the hollow fiber membrane bundle to be dried be fixed to an auxiliary mechanism for venting gas into the hollow fiber membrane bundle, the structure of the fixing part becomes complicated, and the hollow fiber membrane bundle is There is a problem that the preparation for drying and the drying operation become complicated, such as setting in the above-mentioned place and controlling the air flow rate.
Another inventor has disclosed a method of drying a hollow fiber membrane bundle by irradiating microwaves while passing air through the hollow fiber membrane bundle under reduced pressure (see Patent Document 10). This method also has the same problem.
JP 2003-175320 A JP 2003-175321 A JP 2003-175322 A JP 2003-284931 A JP-A-9-888

  Moreover, the method of the said patent document lacks consideration with respect to long-term storage stability of a hollow fiber membrane raw material, and the improvement is also required. When a hollow fiber membrane is used as a separation membrane for blood purification therapy, if the elution of the hydrophilic compound increases, the accumulation of the hydrophilic compound as a foreign substance in the human body increases during long-term dialysis, which may cause side effects and complications. In the dialysis-type artificial kidney device manufacturing approval standard, UV (220 to 350 nm) absorbance standards for hollow fiber membrane extracts are set.

  The present inventors have confirmed that the extract extracted by the test method defined by the above-mentioned dialysis artificial kidney device manufacturing approval standard contains hydrogen peroxide that cannot be measured by conventionally known UV absorbance. I found it. It has been found that the presence of the hydrogen peroxide accelerates the oxidative degradation of, for example, polyvinyl pyrrolidone and increases the amount of the polyvinyl pyrrolidone eluted when the hollow fiber membrane bundle is stored. Furthermore, even if hydrogen peroxide is present in a specific part of the hollow fiber membrane bundle, the deterioration reaction of the hollow fiber membrane bundle material starts from that point and propagates to the entire hollow fiber membrane bundle, so it is used as a module. It has been found that the abundance of the hollow fiber membrane bundle in the longitudinal direction needs to ensure a certain amount or less over the entire region. When carried out by the method of the above-mentioned patent document, the amount of the hydrogen peroxide eluted increases, and when the hollow fiber membrane bundle is stored for a long period of time, the oxidative degradation of polyvinylpyrrolidone is promoted, and the UV (220 to 350 nm) absorbance over time. The problem of increasing is generated.

  Further, when carried out by the method of the above-mentioned patent document, ventilation drying is used in combination, and drying can be made uniform between the center portion and the outer peripheral portion of the yarn bundle, but the drying uniformity is rather lowered with respect to the ventilation direction. As a result, the above-mentioned UV (220 to 350 nm) absorbance also has a problem that the longitudinal variation of the hollow fiber membrane bundle is large. This fluctuation leads to a decrease in safety. The fluctuation in UV (220 to 350 nm) absorbance also reflects the surface concentration of polyvinyl pyrrolidone on the outer surface of the hollow fiber membrane bundle, and when the wet hollow fiber membrane bundle is dried, the hollow fiber membrane bundle rises to dryness. This leads to a problem that partial sticking (adhesion) of the hollow fiber membranes occurs in a portion having a high polyvinylpyrrolidone concentration on the surface. If this partial sticking occurs, it will lead to problems such as deterioration of the module assemblability, so improvement is necessary. In the above patent document, no consideration is given to these problems.

  The drying methods described in Patent Documents 5 to 9 describe that the moisture content in the dried film is less than 1% by mass in Examples. In addition, any of the above known methods of irradiating and drying microwaves is a method of irradiating microwaves under normal pressure, and no mention is made of the effect of irradiating microwaves under reduced pressure. Absent. For example, a reduced pressure system is used in the method disclosed in Patent Document 10, but the reduced pressure system in this method is used as a means for allowing air to pass through the hollow fiber membrane bundle, and irradiation is performed under normal pressure. Has been implemented in.

  The present invention is a polysulfone suitable for use in hemodialysis hollow fiber blood purifiers having high performance, high safety, excellent storage stability and module assembly, and particularly high water permeability used for the treatment of chronic renal failure. It is to provide a system permselective hollow fiber membrane bundle.

  In the present invention, the polysulfone-based hollow fiber membrane containing a hydrophilic polymer has a hydrogen peroxide elution amount of 5 ppm or less at all sites obtained by dividing the hollow fiber membrane bundle into 10 pieces in the longitudinal direction. A polysulfone-based permselective hollow fiber membrane bundle having a maximum elution amount range of 5 ppm or less.

  In the polysulfone-based permselective hollow fiber membrane bundle of the present invention, the hydrogen peroxide elution amount is suppressed, and fluctuations in the hydrogen peroxide elution amount in the longitudinal direction of the hollow fiber membrane bundle are suppressed. Deterioration of polyvinyl pyrrolidone and the like when a hollow fiber membrane bundle caused by hydrogen is stored for a long period of time is suppressed, so that UV (220 to 350 nm) absorbance, which is a dialysis-type artificial kidney device manufacturing approval standard, is maintained even after long-term storage. It can be kept below the reference value of 0.10. Further, the polysulfone-based permselective hollow fiber membrane bundle of the present invention has a small variation in the degradation of polyvinylpyrrolidone in the longitudinal direction of the hollow fiber membrane bundle, and is based on the approval standard for dialysis artificial kidney device production in the longitudinal direction of the hollow fiber membrane bundle. When a prescribed test is carried out, UV (220 to 350 nm) absorbance fluctuations in the hollow fiber membrane extract are suppressed, so that partial sticking of the hollow fiber membrane bundle caused by this fluctuation is suppressed, and module assembly is possible. The excellent hollow fiber membrane bundle can be manufactured stably. Moreover, suppression of UV (220 to 350 nm) absorbance fluctuation in the longitudinal direction of the hollow fiber membrane bundle also leads to an improvement in safety when used for blood purification. Therefore, there is an advantage that it is suitable for a blood purifier having high water permeability used for the treatment of chronic renal failure.

で示される繰り返し単位を有するポリスルホン樹脂やポリエーテルスルホン樹脂がポリスルホン系樹脂として広く市販されており、入手も容易なため好ましい。 Hereinafter, the present invention will be described in detail.
The hollow fiber membrane bundle used in the present invention is characterized in that it is composed of a polysulfone resin containing polyvinylpyrrolidone. The polysulfone resin in the present invention is a general term for resins having a sulfone bond and is not particularly limited.

A polysulfone resin or a polyethersulfone resin having a repeating unit represented by is widely available as a polysulfone resin and is preferable because it is easily available.

  As the hydrophilic polymer used in the present invention, those that form a micro phase separation structure with a polysulfone resin are preferably used. Polyethylene glycol, polyvinyl alcohol, carboxymethyl cellulose, polyvinyl pyrrolidone and the like can be mentioned, but it is a preferred embodiment that polyvinyl pyrrolidone is used from the viewpoint of safety and economy. The polyvinyl pyrrolidone is a water-soluble polymer compound obtained by vinyl polymerization of N-vinyl pyrrolidone. The product names are “Collidon” from BASF, “Prasdon” from ISP, and “Pittscall” from Daiichi Kogyo Seiyaku. There are products of various molecular weights. In general, it is preferable to use a low molecular weight (weight average molecular weight of 300,000 or less) in terms of hydrophilic imparting efficiency, and a high molecular weight (weight average molecular weight greater than 300,000) in terms of lowering the elution amount. However, it is appropriately selected according to the required characteristics of the hollow fiber membrane bundle of the final product. Those having a single molecular weight may be used, or two or more products having different molecular weights may be mixed and used. Moreover, you may use what refine | purified a commercial product and sharpened molecular weight distribution, for example.

  In the present invention, it is preferable to produce a selectively permeable hollow fiber membrane using polyvinylpyrrolidone having a hydrogen peroxide content of 300 ppm or less. By setting the hydrogen peroxide content in the polyvinylpyrrolidone used as a raw material to 300 ppm or less, the hydrogen peroxide elution amount of the hollow fiber membrane after film formation can be suppressed to 5 ppm or less, and the hollow fiber membrane bundle of the present invention It is preferable because quality stabilization can be achieved. The hydrogen peroxide content in the polyvinylpyrrolidone used as a raw material is more preferably 250 ppm or less, further preferably 200 ppm or less, and further preferably 150 ppm or less.

  The presence of hydrogen peroxide in the polyvinyl pyrrolidone used as a raw material is considered to trigger the oxidative degradation of polyvinyl pyrrolidone, which increases explosively with the progress of oxidative degradation, and further oxidative degradation of polyvinyl pyrrolidone. It is thought that it promotes. Therefore, setting the hydrogen peroxide content to 300 ppm or less is the first means for suppressing the oxidative degradation of polyvinylpyrrolidone in the process of producing a selectively permeable separation membrane. It is also effective and recommended to take measures to suppress deterioration during transportation and storage of polyvinylpyrrolidone at the raw material stage. For example, it is preferable to use an aluminum foil laminated bag to shield the light and enclose with an inert gas such as nitrogen gas, or enclose and store an oxygen scavenger together. In addition, it is preferable that the measurement and preparation when the package is opened and subdivided be performed after inert gas replacement, and the above-mentioned measures are taken for the storage. Also, in the manufacturing process of the hollow fiber membrane bundle, it is also recommended as a preferred embodiment to take means such as replacing the inside of the supply tank in the raw material supply system with an inert gas. In addition, it is not excluded to use polyvinylpyrrolidone having a reduced hydrogen peroxide content by a recrystallization method or an extraction method.

  The polysulfone-based permselective hollow fiber membrane bundle of the present invention has a hydrogen peroxide elution amount of 5 ppm or less at all sites where the hollow fiber membrane bundle is divided into 10 pieces in the longitudinal direction, and the maximum elution amount difference of hydrogen peroxide Is preferably 5 ppm or less. In addition, when each of the tests defined by the dialysis-type artificial kidney device manufacturing approval standard was performed, the maximum value of UV (220 to 350 nm) absorbance in the hollow fiber membrane extract was less than 0.10, and the same hollow The difference between the maximum and minimum UV (220 to 350 nm) absorbance in the yarn membrane bundle is preferably 0.05 or less.

  The test method defined in the dissolution test method of the dialysis artificial kidney device manufacturing approval standard is that a hollow fiber membrane is arbitrarily taken out of a dry hollow fiber membrane bundle, 1.0 g is weighed, and 100 ml of RO water is added thereto. In addition, the extract obtained by performing extraction at 70 ° C. for 1 hour is quantified. When measuring the hollow fiber membrane of the wet hollow fiber membrane module, physiological saline is passed through the dialysate side channel of the module at 500 mL / min for 5 minutes and then through the blood side channel at 200 mL / min. Then, after passing through the blood side from the blood side to the dialysate side at a rate of 200 mL / min for 3 minutes, the solution was freeze-dried to obtain a dry membrane, which was quantified using the dry membrane.

  The hollow fiber membrane bundle is divided into 10 pieces in the longitudinal direction, and the UV (220 to 350 nm) absorbance measured for each extract obtained by the above method has a bad influence on the fixation of the hollow fiber membrane bundle. It is a parameter | index of polyvinylpyrrolidone content in. Therefore, by suppressing the UV (220 to 350 nm) absorbance fluctuation in the longitudinal direction of the hollow fiber membrane bundle, the fluctuation in the content of polyvinyl pyrrolidone on the hollow fiber membrane surface in the longitudinal direction of the hollow fiber membrane bundle is suppressed, so that The occurrence of partial sticking of the yarn membrane bundle can be reduced. Moreover, since the suppression of the fluctuation leads to keeping the elution amount of polyvinyl pyrrolidone in the entire hollow fiber membrane bundle at a low level, the safety is improved when it is used in a blood purifier. Therefore, the absorbance fluctuation is more preferably 0.04 or less, further preferably 0.03 or less, and further preferably 0.02 or less.

  The difference between the elution amount of hydrogen peroxide and the maximum elution amount is more preferably 4 ppm or less, and further preferably 3 ppm or less. When the elution amount or the maximum elution amount difference of the hydrogen peroxide exceeds 5 ppm, the storage stability deteriorates due to the oxidative degradation of polyvinylpyrrolidone by the hydrogen peroxide as described above. In addition, the amount of polyvinylpyrrolidone eluted may increase. In terms of storage stability, the increase in the amount of polyvinylpyrrolidone eluted is the most prominent phenomenon. In addition, deterioration of the polysulfone-based polymer causes the hollow fiber membrane to become brittle, or polyurethane-based adhesive used for module assembly. This may accelerate the deterioration of the agent and increase the elution amount of deteriorated products such as urethane oligomers, possibly leading to a decrease in safety. The increase in the amount of eluate due to deterioration caused by the oxidizing action of hydrogen peroxide during long-term storage can be evaluated by measuring the UV (220 to 350 nm) absorbance set by the dialysis artificial kidney device manufacturing approval standard. As described above, even if hydrogen peroxide exists in a specific part of the hollow fiber membrane bundle, the deterioration reaction of the hollow fiber membrane material starts from that point and propagates to the entire hollow fiber membrane bundle. It is necessary to ensure a certain amount or less over the entire region in the length direction of the film bundle. That is, the oxidative degradation of polyvinylpyrrolidone initiated by hydrogen peroxide at a specific site spreads throughout the entire hollow fiber membrane bundle, and the amount of hydrogen peroxide further increases due to the degradation. , It becomes easier to elute from the hollow fiber membrane bundle. This deterioration reaction proceeds in a chain. Therefore, when the hollow fiber membrane bundle is stored for a long period of time, the elution amount of hydrogen peroxide and polyvinylpyrrolidone increases, which may lead to a decrease in safety when used as a blood purifier.

  The polysulfone-based permselective hollow fiber membrane bundle of the present invention is obtained by dividing the hollow fiber membrane bundle into 10 pieces in the longitudinal direction after storing the dried hollow fiber membrane bundle in a dry box (atmosphere is air) at room temperature for 3 months. When the test defined by the dialysis-type artificial kidney device manufacturing approval standard is performed, it is preferable that the UV (220 to 350 nm) absorbance in the extract of the hollow fiber membrane is less than 0.10. More preferably, the above properties are maintained even after storage for 5 months or longer. Therefore, the UV (220 to 350 nm) absorbance after storage for 3 months is more preferably 0.08 or less, and further preferably 0.06 or less. In consideration of storing the hollow fiber membrane bundle in a dry state in the manufacturing process of the hollow fiber membrane bundle, transportation, stock storage, and the like, it is preferable to impart the above characteristics.

  The polysulfone-based permselective hollow fiber membrane bundle of the present invention is prepared by storing a wet hollow fiber membrane bundle at room temperature for 1 year, and then dividing the hollow fiber membrane bundle into 10 pieces in the longitudinal direction. When the test defined by the artificial kidney device manufacturing approval standard is performed, the UV (220 to 350 nm) absorbance of each extract is preferably 0.10 or less. It is more preferable that the above characteristics are maintained even after storage for 2 years or more. For this purpose, the UV (220-350 nm) absorbance after storage for 1 year is more preferably 0.08 or less, and further preferably 0.06 or less. Here, the preservation | save in a moist state is applied also to the preservation | save after assembling in a blood purifier, for example. Thus, when the polysulfone-based permselective hollow fiber membrane bundle of the present invention is used in a blood purifier, it is preferable because high safety can be maintained over a long period of time.

  Moreover, it is preferable that the polysulfone-based permselective hollow fiber membrane bundle of the present invention is not partially fixed in the longitudinal direction of the hollow fiber membrane bundle. If there is partial fixation, for example, when assembling the blood purifier, the workability when inserting the hollow fiber membrane bundle into the housing is not preferable.

  Since the polysulfone-based permselective hollow fiber membrane bundle of the present invention satisfies the above characteristics at the same time, it can be suitably used as a blood purifier.

  As a specific production example of the selectively permeable hollow fiber membrane of the present invention, for example, it is preferably produced by a method known in Japanese Patent Application Laid-Open No. 2000-300663. For example, 16 parts by mass of polyethersulfone (4800P, manufactured by Sumitomo Chemical Co., Ltd.) and 5 parts by mass of polyvinyl pyrrolidone (K-90, manufactured by BASF) disclosed in the patent document, 74 parts by mass of dimethylacetamide, 5 parts by mass of water Was dissolved and defoamed as a film-forming solution, and a 50% dimethylacetamide aqueous solution was used as a core solution, and this was simultaneously discharged from the outside and inside of the double-tube orifice, An example is a method in which a hollow fiber membrane is formed in a coagulation bath made of water at 75 ° C., and is washed after washing with water and dried at 60 ° C.

  The content of the polyvinyl pyrrolidone in the membrane relative to the polysulfone polymer in the present invention may be within a range that can provide sufficient hydrophilicity and high wettability to the hollow fiber membrane, and the polysulfone polymer is 99 to 80% by mass. Polyvinylpyrrolidone is preferably 1 to 20% by mass. When the ratio of polyvinyl pyrrolidone relative to the polysulfone-based polymer is too small, the effect of imparting hydrophilicity to the film may be insufficient. Therefore, the content of polyvinyl pyrrolidone is more preferably 1.5% by mass or more. 0 mass% or more is more preferable, and 2.5 mass% or more is further more preferable. On the other hand, if the content is too high, the effect of imparting hydrophilicity is saturated, and the amount of polyvinylpyrrolidone and / or oxidatively deteriorated material eluted from the membrane increases, and the amount of polyvinylpyrrolidone eluted from the membrane described later becomes 10 ppm. May exceed. Therefore, it is more preferably 18% by mass or less, further preferably 15% by mass or less, still more preferably 13% by mass or less, and particularly preferably 10% by mass or less.

  As a specific production method for imparting the above properties to the polysulfone-based permselective hollow fiber membrane bundle of the present invention, in a method of drying a wet hollow fiber membrane bundle by microwave irradiation, the microwave oscillator is directed to the oven. A microwave oscillator having a ratio (Er / Ei) of incident wave energy Ei and reflected wave energy Er reflected from the oven and returning from the oven to the oscillator may be irradiated with microwaves and dried. This is a preferred embodiment. Measurement of the energy Ei of the incident wave from the microwave oscillator to the oven and the energy Er of the reflected wave reflected from the oven and returning from the oven to the oven are performed by installing an energy detector in the waveguide section from the microwave oscillator to the oven. Measured and obtained. When Er / Ei exceeds 0.2, the energy of the microwave hitting the hollow fiber membrane bundle becomes non-uniform, and the effects of the present invention can be fully expressed even if various means for uniform drying described below are taken. You may not be able to. If Er / Ei is large, the magnetron of the oscillator may be destroyed by the reflected wave. Er / Ei is more preferably 0.15 or less, and further preferably 0.10 or less. In the present invention, the method for reducing the above Er / Ei to 0.2 or less is not limited, but it is a preferred embodiment to employ various measures disclosed in Japanese Patent Laid-Open No. 2000-340356. By this correspondence, the intensity distribution of the microwave irradiated to the hollow fiber membrane bundle to be dried is made uniform, the drying of the hollow fiber membrane bundle is made uniform, and the above-mentioned preferred characteristics of the hollow fiber membrane bundle of the present invention should be provided. Can be granted.

  In the present invention, when the wet hollow fiber bundle is dried, the moisture content of the hollow fiber membrane bundle is dried by microwave irradiation until the moisture content is 10 to 20% by mass, and the moisture content is reduced to 10 to 20% by mass. At this point, it is a preferred embodiment to stop the microwave irradiation and subsequently dry under reduced pressure to obtain a dry hollow fiber membrane bundle.

  The final moisture content of the hollow fiber membrane bundle is preferably 1 to 7% by mass, and the moisture content variation rate measured by dividing the dry hollow fiber membrane bundle into 10 in the longitudinal direction is preferably within 10%. The moisture content is more preferably 1.5 to 6% by mass, and the moisture content fluctuation rate is more preferably 8% or less. By setting to the said range, the partial fixation of the hollow fiber membrane bundle by the fluctuation | variation of the content rate of said polyvinylpyrrolidone can be reduced more effectively. That is, when the moisture content is less than 1% by mass, static adhesion is generated. Conversely, when the moisture content exceeds 7% by mass, partial adhesion is promoted by an increase in adhesiveness due to moisture absorption of polyvinylpyrrolidone. Moreover, when the moisture content is reduced to less than 1% by mass, the deterioration of the polyvinylpyrrolidone of the hollow fiber membrane bundle material increases, the elution amount of the deteriorated product increases, and the elution in the longitudinal direction of the hollow fiber membrane bundle. The amount fluctuation becomes large, leading to a decrease in safety when used in a blood purifier, for example. On the other hand, when the moisture content exceeds the saturated moisture content, there is a possibility that bacteria during storage are likely to proliferate, yarn crushing occurs due to the weight of the hollow fiber membrane, and adhesion failure may occur during module assembly.

In addition, fluctuations in the water content cause fluctuations in the elution amount of hydrogen peroxide, leading to a decrease in the storage stability of the hollow fiber membrane and blood purifier.
Although the cause of hydrogen peroxide fluctuation due to this water content fluctuation is not clear, the following inferences are made.
It is considered that the moisture in the hollow fiber membrane has a strong tendency to localize in the portion where polyvinylpyrrolidone exists because of its strong affinity with polyvinylpyrrolidone. This water localization is increased as the moisture content in the hollow fiber membrane decreases, and the absorption of microwaves in the localized portion of this water increases, so the accumulation of thermal energy in this portion increases, The temperature rise in the hollow fiber membrane and the unevenness of the degree of drying are increased. Moreover, since polyvinyl pyrrolidone exists in the vicinity of the water molecule, it is assumed that the polyvinyl pyrrolidone in the portion where the water is localized is deteriorated, leading to an increase in hydrogen peroxide production.

  For the reasons described above, it is preferable that the difference in the maximum elution amount of hydrogen peroxide in the length direction of the hollow fiber membrane bundle is small. Here, the maximum elution amount difference of hydrogen peroxide is the maximum elution amount, the average elution amount of the hydrogen peroxide elution amount obtained by dividing the hollow fiber membrane bundle into 10 pieces in the length direction and measuring each. The difference between the maximum elution amount and the average elution amount and the difference between the average elution amount and the minimum elution amount are obtained from the minimum elution amount, and the larger value is used as the maximum elution amount range. The smaller the maximum elution amount difference of hydrogen peroxide, the less the variation in hydrogen peroxide generation in the length direction of the hollow fiber membrane bundle, and the long-term storage stability in the hollow fiber membrane bundle and hollow fiber membrane module state Will be secured. Therefore, the maximum elution amount difference of hydrogen peroxide is preferably 3 ppm or less, and more preferably 2 ppm or less.

The moisture content referred to in the present invention is the mass (a) of the hollow fiber membrane before drying, the mass (b) of the hollow fiber membrane after drying for 2 hours in a dry heat oven at 120 ° C. (after absolute drying), It can be easily calculated using the following formula.
Moisture content (mass%) = (ab) / b × 100
Here, by setting (a) within the range of 1 to 2 g, a completely dry state (a state in which there is no further mass change) can be obtained after 2 hours.

  It is preferable to dry by microwave irradiation until the moisture content of the hollow fiber membrane bundle becomes 10 to 20% by mass. Microwave drying is a useful method as a method for drying a hollow fiber membrane bundle because it can be efficiently dried, but when drying by microwave irradiation is continued until the final moisture content is 1 to 7% by mass, There is a possibility that the fluctuation of the degree of deterioration of the polyvinyl pyrrolidone and the fluctuation of the moisture content in the longitudinal direction in the hollow fiber membrane will increase, making it impossible to obtain the hollow fiber membrane bundle having the above-mentioned characteristics of the present invention. Therefore, it is preferable to stop the microwave irradiation when the water content in the hollow fiber membrane bundle is reduced to 10 to 20% by mass, and subsequently dry under reduced pressure. It is more preferable to dry by microwave irradiation until it becomes 10-15 mass%. When drying by microwave irradiation until the water content is less than 10% by mass, the degradation of polyvinylpyrrolidone increases, the elution amount of hydrogen peroxide increases, and the storage stability of the hollow fiber membrane bundle may decrease. In addition, the moisture content in the longitudinal direction of the hollow fiber membrane bundle and the variation rate of UV (220 to 350 nm) absorbance increase, and partial fixation of the hollow fiber membrane bundle may occur. On the other hand, if microwave irradiation is stopped at a point of time higher than 20% by mass, the total drying time until drying to the final moisture content becomes longer, and degradation and decomposition of polyvinyl pyrrolidone may proceed due to accumulated energy.

  Furthermore, drying is performed under reduced pressure, so that the efficiency of drying can be improved and the oxygen concentration in the drying environment can be reduced. This is preferable because deterioration of polyvinyl pyrrolidone in the hollow fiber membrane due to oxygen is suppressed. The drying allows the drying to proceed without increasing the degradation of polyvinyl pyrrolidone, and a hollow fiber membrane bundle having the characteristics intended by the present invention can be obtained. The degree of reduced pressure in the drying is not limited, but is preferably 20 kPa or less, and more preferably 15 kPa or less. The drying under reduced pressure may be performed without using a heat source by utilizing preheating by microwave drying. However, from the viewpoint of drying efficiency, for example, the energy is higher than that of microwaves such as hot air and far infrared rays. It is preferable to perform mild drying while heating with a small heat source. In consideration of drying under reduced pressure, drying by far infrared irradiation is particularly preferable.

  Although the cause of the deterioration of polyvinyl pyrrolidone in the longitudinal direction of the hollow fiber membrane and the increase in fluctuation of the moisture content by irradiating microwaves with a low moisture content in the hollow fiber membrane bundle has not been clarified, Drying by water is performed by directly exciting water molecules by microwaves, and as described above, the moisture in the hollow fiber membrane is localized in the portion where polyvinylpyrrolidone exists I guess. On the other hand, for example, drying by far-infrared irradiation has a lower excitation energy than microwaves, and thus it is considered that the occurrence of the above problems is suppressed.

  The water content management method is not limited. Online measurement may be performed by an infrared absorption method or the like, or offline measurement by sampling may be performed.

  In the present invention, as described above, it is important to suppress oxidative degradation of polyvinylpyrrolidone in the drying step. Therefore, it is preferable to carry out the above microwave irradiation in an inert gas atmosphere such as nitrogen gas, but it is economically disadvantageous. On the other hand, a method of performing microwave drying under reduced pressure to suppress oxidative degradation leads to improvement of drying efficiency and is economical and recommended. As a drying condition of the drying method, it is preferable to irradiate microwaves with an output of 0.1 to 100 kW under a reduced pressure of 20 kPa or less. Moreover, the frequency of this microwave is 1,000-5,000 MHz, and it is a preferable embodiment that the highest ultimate temperature of the hollow fiber membrane bundle during a drying process is 90 degrees C or less. If a means of decompression is also provided, the evaporation of moisture is promoted by itself, so there is an advantage that the output of microwave irradiation can be suppressed and the irradiation time can be shortened, but the temperature rise can also be made relatively low. Therefore, the influence on the performance degradation of the hollow fiber membrane bundle is small as a whole. Furthermore, drying accompanied by means of reduced pressure has the advantage that the drying temperature can be relatively lowered, and has a significant point that deterioration and decomposition of the hydrophilic polymer can be remarkably suppressed. An appropriate drying temperature is sufficient from 20 to 80 ° C. More preferably, it is 20-60 degreeC, More preferably, it is 20-50 degreeC, More preferably, it is 30-40 degreeC.

  The fact that the pressure is reduced means that the low pressure acts uniformly on the center portion and the outer peripheral portion of the hollow fiber membrane bundle, the moisture evaporation is promoted uniformly, and the hollow fiber membrane is uniformly dried. Therefore, the failure of the hollow fiber membrane bundle due to non-uniform drying is corrected. In addition, heating by microwaves also acts almost equally on the entire center and outer periphery of the hollow fiber membrane bundle, so it functions synergistically in uniform heating, and is unique in drying the hollow fiber membrane bundle. It will be of significance. The degree of vacuum may be appropriately set according to the output of the microwave, the total moisture content of the hollow fiber membrane bundle, and the number of hollow fiber membrane bundles, but the degree of vacuum is 20 kPa to prevent the temperature of the hollow fiber membrane bundle during drying. Less than, more preferably less than 15 kPa, and even more preferably less than 10 kPa. If it is 20 kPa or more, not only the water evaporation efficiency decreases, but also the temperature of the polymer forming the hollow fiber membrane bundle may increase and deteriorate. Moreover, although the one where a pressure reduction degree is higher is preferable in the meaning which raises temperature rise suppression and drying efficiency, since the cost concerning maintaining the sealing degree of an apparatus becomes high, 0.1 kPa or more is preferable. More preferably, it is 0.25 kPa or more, and further preferably 0.4 kPa or more.

In consideration of shortening the drying time, a higher microwave output is preferable.For example, in hollow fiber membrane bundles containing polyvinylpyrrolidone, degradation or decomposition of polyvinylpyrrolidone occurs due to overdrying or overheating, and wettability decreases during use. It is preferable not to raise the output too much because of problems such as Further, the hollow fiber membrane bundle can be dried even with an output of less than 0.1 kW, but there is a possibility that a problem of reduction in throughput due to an increase in drying time may occur. The optimum value of the combination of the degree of decompression and the microwave output varies depending on the water content of the hollow fiber membrane bundle and the number of processed hollow fiber membrane bundles, and it is preferable to obtain a set value as appropriate through trial and error.
For example, as a temporary guide for carrying out the drying conditions of the present invention, when 20 hollow fiber membrane bundles having a moisture content of 50 g per hollow fiber membrane bundle are dried, the total moisture content is 50 g × 20 fibers = 1,000 g. At this time, it is appropriate that the microwave output is 1.5 kW and the decompression degree is 5 kPa.

  A more preferable microwave output is 0.1 to 80 kW, and a more preferable microwave output is 0.1 to 60 kW. The output of the microwave is determined by, for example, the total number of hollow fiber membranes and the total water content, but when suddenly high-power microwaves are irradiated, drying is completed in a short time, but the hollow fiber membrane is partially denatured. And may cause deformation such as curling. When drying using microwaves, for example, when using something like a water retention agent in the hollow fiber membrane, high power and extreme drying using microwaves will disappear due to scattering of the water retention agent It becomes the cause of. In consideration of the influence on the hollow fiber membrane, especially under conditions under reduced pressure, conventionally, irradiation with microwaves under reduced pressure was not intended. Irradiation of microwaves under reduced pressure according to the present invention means that the evaporation of aqueous liquid is active even in a relatively low temperature state, so that degradation of polyvinylpyrrolidone and deformation of hollow fiber membranes due to high output microwaves and high temperatures Thus, a double effect of preventing damage to the hollow fiber membrane is obtained.

  Although the present invention enables one-stage drying in which the microwave output is constant, i.e., drying by microwaves under reduced pressure, as another embodiment, the microwave output is sequentially changed according to the progress of drying. So-called multi-stage drying, which lowers in stages, is included as a preferred embodiment. Therefore, the significance of multi-stage drying will be described as follows. When drying with microwaves at a relatively low temperature of about 30 to 90 ° C. under reduced pressure, multi-stage drying in which the output of the microwaves is sequentially reduced in accordance with the progress of drying of the hollow fiber membrane bundle. The method is excellent. The degree of pressure reduction, temperature, microwave output, and irradiation time may be determined in consideration of the total amount of hollow fiber membranes to be dried, industrially acceptable drying time, and the like. Multistage drying can be performed in any number of stages, for example, 2 to 6 stages, but it is appropriate to use 2 to 3 stages of drying that is industrially appropriate in consideration of productivity. Depending on the total amount of water contained in the hollow fiber membrane bundle, when relatively large, multistage drying is performed at a temperature of 90 ° C. or lower, for example, at a reduced pressure of about 5 to 20 kPa, and the first stage is 30 to 100 kW. The range can be determined in consideration of the microwave irradiation time such that the second stage is in the range of 10 to 30 kW and the third stage is in the range of 0.1 to 10 kW. When the output of the microwave is large, such as 90 kW in the high part and 0.1 kW in the low part, the number of stages for reducing the output may be increased to 4 to 8 stages, for example. In the case of the present invention, since technical consideration is given to the microwave irradiation called decompression, there is an advantage that the microwave output can be relatively lowered. For example, the first stage is about 10 to 100 minutes by 10 to 20 kW microwave, the second stage is about 3 to 10 kW and about 5 to 80 minutes, and the third stage is about 0.1 to 3 kW and about 1 to 60 minutes. Dry in stages. It is preferable that the microwave output and irradiation time of each stage are lowered in conjunction with the reduction in the total amount of moisture contained in the hollow fiber membrane. This drying method is a very gentle drying method for hollow fiber membrane bundles and cannot be expected in the prior arts of the above-mentioned Patent Documents 8 to 10, and thus makes the effects of the present invention significant.

  To explain another aspect, when the so-called moisture content of the hollow fiber membrane bundle is relatively small, that is, a so-called moisture content of 400% by mass or less, irradiation with a low output microwave of 12 kW or less may be excellent. For example, when the amount of water in the total amount of the hollow fiber membrane bundle is about 1 to 7 kg, the output is 12 kW or less under a reduced pressure of about 3 to 10 kPa at a temperature of 80 ° C. or less, preferably 60 ° C. or less. For example, irradiation with a microwave of about 1 to 5 kW for 10 to 240 minutes, irradiation with a microwave of less than 0.5 to 1 kW for about 3 to 240 minutes, and irradiation with a microwave of less than 0.1 to 0.5 kW for about 1 to 240 minutes If the irradiation output and the irradiation time of the microphone mouth wave are adjusted according to the degree of drying, drying is performed uniformly. The degree of vacuum is set to 0.1 to 20 kPa for each stage, but the first stage having a relatively high moisture content of the hollow fiber membrane is increased to 0.1 to 5 kPa, for example, and the microwave output is increased. The so-called depressurization degree of each stage is such that microwaves are irradiated at a slightly higher pressure than the first stage of 0.1 to 5 kW under a reduced pressure of 5 to 20 kPa in the second stage and the third stage. Appropriate adjustment and change according to the situation can be arbitrarily set in consideration of the transition of the total water content and the moisture content of the hollow fiber membrane bundle. In each stage, the operation of changing the degree of reduced pressure further increases the significance of irradiating microwaves under reduced pressure according to the present invention. Of course, it is necessary to always consider the uniform irradiation and exhaust of the microwave in the microwave irradiation apparatus.

  The maximum temperature reached by the hollow fiber membrane bundle during drying can be measured by applying an irreversible thermolabel to the side of the film that protects the hollow fiber membrane bundle, drying, and checking the display after taking out the drying. . At this time, the maximum reached temperature of the hollow fiber membrane bundle during drying is preferably 90 ° C. or lower, more preferably 80 ° C. or lower. More preferably, it is 70 degrees C or less. If the maximum temperature reaches 90 ° C. or higher, the film structure is likely to change, which may cause performance degradation or oxidative degradation. In particular, in a hollow fiber membrane bundle containing polyvinylpyrrolidone, it is necessary to prevent the temperature rise as much as possible because polyvinylpyrrolidone is easily decomposed by heat. Temperature rise can be prevented by optimizing the degree of decompression and microwave output and irradiating intermittently. Moreover, although the one where a drying temperature is lower is preferable, 30 degreeC or more is preferable from the surface of the maintenance cost of pressure reduction degree, and the shortening of drying time.

  The microwave irradiation frequency is preferably 1,000 to 5,000 MHz in consideration of the suppression of irradiation spots on the hollow fiber membrane bundle and the effect of extruding water in the pores from the pores. More preferably, it is 1,500-4,000 MHz, More preferably, it is 2,000-3,000 MHz.

  In drying by microwave irradiation, it is important to uniformly heat and dry the hollow fiber membrane bundle. In the above-described microwave drying, nonuniform heating due to the reflected wave that occurs accompanying the generation of the microwave occurs, so it is important to take measures to reduce the nonuniform heating due to the reflected wave. The method is not limited and is arbitrary. For example, a method of providing a reflector in an oven disclosed in Japanese Patent Application Laid-Open No. 2000-340356 to reflect reflected waves and uniformize heating is a preferred embodiment. One.

  In the present invention, the above-mentioned microwave drying may be performed only by microwave irradiation, but it is preferable that the microwave drying is performed simultaneously with other heat sources. By this method, the evaporation of water that has been excited by microwave irradiation and moved to the surface of the hollow fiber membrane is accelerated by heating with another heat source, leading to an improvement in drying efficiency. Further, this efficient evaporation of the surface moisture is preferable because the variation in the concentration of polyvinylpyrrolidone on the surface of the hollow fiber membrane induced by the surface moisture is suppressed, and the occurrence of partial sticking is suppressed. As described above, microwave drying is preferably performed under reduced pressure. Therefore, it is particularly preferable to use in combination with far-infrared irradiation capable of efficient heating under reduced pressure. When this method is used, the microwave irradiation is stopped when the moisture content is reached, the far-infrared irradiation is continued while maintaining the reduced pressure state, and the drying can be terminated by continuing further drying. So especially recommended. At this time, after the microwave irradiation is completed, the degree of decompression of the system may be lowered, and after conditioning, the degree of decompression may be raised again to start far-infrared irradiation. Therefore, in this invention, it is a preferable embodiment to dry using a microwave dryer in which a far-infrared heater is attached in a heating oven and an exhaust system in which the heating oven can be decompressed is attached.

  In this invention, it is preferable that the irradiation wavelength of a far infrared ray is 1-30 micrometers. Since water and organic matter have a high absorption rate of far infrared rays having a wavelength of 3 to 12 μm, it is difficult to increase the temperature of the object to be dried even if the wavelength of the far infrared rays is too short or too long. Such costs may increase. Therefore, the wavelength of the far infrared ray to be irradiated is more preferably 1.5 to 26 μm, further preferably 2 to 22 μm, and further preferably 2.5 to 18 μm.

In the present invention, as a radiation medium for irradiating far-infrared rays, a stainless steel medium having a metal oxide film on the surface is preferably used. For example, an austenitic stainless steel powder as described in JP-A-10-5265 is coated with a metal oxide such as Al ₂ O ₃ , Fe ₂ O ₃ , TiO ₂ , CaO, MgO, K ₂ O and Na ₂ O. It is a more preferable embodiment to use a far-infrared radiator coated with, because far-infrared rays can be extracted efficiently at low cost.

  On the other hand, when performing drying by far-infrared irradiation after microwave drying, unlike the case of microwave drying, a discharge phenomenon does not occur even if irradiation is performed under reduced pressure. It can be carried out. From the point of drying efficiency, 5 kPa or less is preferable, 4 kPa or less is more preferable, 3 kPa or less is more preferable, and 2 kPa or less is more preferable. The irradiation energy of the far-infrared irradiation is preferably controlled so as to be 80 ° C. or lower at a temperature detected by a thermocouple provided at the center of the oven. It is more preferable to control at 70 ° C. or lower.

  In the present invention, it is a preferred embodiment that an inert gas such as nitrogen gas is used when the inside of the drying system is returned to normal pressure after drying. Immediately after the drying, the temperature of the hollow fiber membrane bundle is high, so when returning the inside of the drying chamber to atmospheric pressure, when a gas containing oxygen such as air is fed, in the case of a hollow fiber membrane containing polyvinylpyrrolidone, polyvinylpyrrolidone May undergo oxidative degradation due to the effects of oxygen and heat. Therefore, when the inside of the drying chamber is returned to normal pressure after the drying is completed, the oxidative deterioration of the polyvinyl pyrrolidone in the hollow fiber membrane bundle is suppressed by feeding the inert gas.

  For the drying of the hollow fiber membrane bundle, the use of microwaves and far-infrared rays for an unlimited time does not affect the quality. This is because the influence of thermal degradation of the hydrophobic polymer or the hydrophilic polymer material constituting the hollow fiber membrane bundle and environmental degradation such as oxygen, water, and steam can be considered. Therefore, in view of industrial production, it is necessary to consider an appropriate time that is naturally allowed for the drying time. From the viewpoint of protecting the quality of the hollow fiber membrane subjected to relatively harsh drying conditions such as microwaves and far infrared rays, from the viewpoint of industrial productivity, the inventors of the present invention are from the start to the end of drying. The drying time is preferably within 3 hours. More preferably within 2.5 hours, still more preferably within 2 hours.

  The appropriate drying time of the hollow fiber membrane bundle is a value obtained by adding a drying region by far infrared rays to a drying region time by microwave, of course, in this case, a drying means using both of them may be included, The present inventors have analyzed the behavior of whether the switching state between the drying region time by microwaves and the drying region by far infrared rays is most dependent on the technical conditions. If it demonstrates based on FIG. 5, if it dries within the range enclosed by the area | region enclosed with 1 and 2 of a continuous line, it will be said that a product with comparatively favorable quality is easily obtained. For example, if it becomes the area | region of the broken lines (1) and (2) of FIG. 5, it will have a considerable influence on the quality of a hollow fiber membrane bundle. This can be easily understood by taking into account the statistical interpretation shown in FIG.

  Looking closely at such an analysis, as a method of drying a hollow fiber membrane having a relatively high moisture content, microwave drying is optimal in this case, microwave drying under reduced pressure is suitable for it, It can also be said that the drying by far-infrared including conditioning is appropriate drying. As a result of examination by the inventors about this switching, the moisture content of the hollow fiber membrane bundle is 5 to 30% by mass, preferably 8 to 25% by mass, more preferably 10 to 20% by mass by drying with microwaves. The fact that it is most suitable to switch at the stage reached is found.

  For example, when the moisture content of the hollow fiber membrane bundle is relatively high, such as 60 to 400% by mass, it is forcibly reduced to a predetermined moisture content by applying a reduced pressure by a microwave in some cases. The present inventors have found that a technique using infrared rays is most suitable. The appropriate range of 10 to 20% by mass of water content is slightly different depending on the polymer material, structure, etc., but within this range, it can be said that it can be applied to drying of general-purpose hollow fiber membrane bundles.

  FIG. 6 shows an analysis of an example in which the range of 10 to 20% by mass of the drying switching affects the quality of the hollow fiber membrane bundle. Based on Examples and Comparative Examples, several examples are plotted. It can be easily understood that this tendency influences the variation of the hollow fiber membrane bundle, with the water content of the hollow fiber membrane bundle being 10 to 20% by mass as a boundary. The idea of using far-infrared rays in combination with microwaves is based on the knowledge of the present inventors. This is based on the knowledge of the present inventors and is a new idea.

  As a method for controlling the elution amount of hydrogen peroxide within the above-mentioned regulated range, the above-mentioned drying method and the moisture content after drying are important, but the quality of polyvinyl pyrrolidone which is a causative substance of hydrogen peroxide generation is important. And handling are also important factors and need attention. For example, it is preferable to produce using polyvinyl pyrrolidone having a hydrogen peroxide content of 300 ppm or less. By setting the hydrogen peroxide content in the polyvinylpyrrolidone used as a raw material to 300 ppm or less, the hydrogen peroxide elution amount of the hollow fiber membrane bundle after film formation can be suppressed to 5 ppm or less, and the hollow fiber membrane of the present invention It is preferable because the bundle quality can be stabilized. Therefore, the hydrogen peroxide content in the polyvinylpyrrolidone used as a raw material is more preferably 250 ppm or less, further preferably 200 ppm or less, and further preferably 150 ppm or less.

  Regarding the dissolution process of the film-forming solution, for example, when a film-forming solution comprising a polysulfone polymer, polyvinyl pyrrolidone, and a solvent is stirred and dissolved, if polyvinyl pyrrolidone contains hydrogen peroxide, It was found that hydrogen peroxide increased explosively due to the effects of oxygen present and heating during dissolution. Therefore, when charging the raw material into the dissolution tank, it is preferable to input the raw material into the dissolution tank that has been previously replaced with an inert gas. As the inert gas, nitrogen, argon or the like is preferably used. Moreover, although a solvent, and a non-solvent may be added depending on the case, it is also a preferable embodiment that oxygen dissolved in these solvent and non-solvent is replaced with an inert gas.

  In addition, as another method for suppressing the generation of hydrogen peroxide, it is an important requirement to dissolve the film forming solution in a short time. For this purpose, it is usually sufficient to increase the dissolution temperature and / or increase the stirring speed. However, when it does so, degradation and decomposition of polyvinyl pyrrolidone will proceed due to the influence of temperature, stirring linear velocity and shearing force. In fact, according to the study by the inventors, the molecular weight of polyvinylpyrrolidone in the film-forming solution moves in the direction of decomposition (shifts to the low molecular side) as the dissolution temperature increases, or the low molecular side. The appearance of a shoulder that appears to be a decomposition product was observed. From the above, increasing the temperature for the purpose of improving the dissolution rate of the raw material accelerates the degradation and degradation of polyvinylpyrrolidone, and consequently blends the degradation product of polyvinylpyrrolidone into the selectively permeable separation membrane. When the obtained hollow fiber membrane was used for blood purification, degradation products were eluted in the blood, so that it was not excellent in terms of product quality safety. Then, it tried to mix a raw material at low temperature in order to suppress decomposition | disassembly of polyvinylpyrrolidone. Even if it is low-temperature dissolution, it is usually preferable to have a temperature of 5 ° C. or higher and 70 ° C. or lower because it requires a running cost under extreme conditions that are below freezing. 60 degrees C or less is more preferable. However, simply lowering the melting temperature causes degradation of polyvinylpyrrolidone due to the longer melting time, lowering the operability and increasing the size of the equipment, which causes problems in industrial implementation. In particular, when polyvinyl pyrrolidone is dissolved at a low temperature, the polyvinyl pyrrolidone becomes a powdered powder, which makes it difficult to dissolve further, or has a problem that it takes a long time for uniform dissolution.

  As a result of investigating the dissolution conditions for dissolving at low temperature without taking time, the inventors have found that it is preferable to dissolve the components constituting the film-forming solution prior to dissolution, and have reached the present invention. The kneading may be performed by kneading components such as polysulfone polymer, polyvinyl pyrrolidone and a solvent at once, or kneading polyvinyl pyrrolidone and polysulfone polymer separately. As mentioned above, polyvinylpyrrolidone is accelerated by contact with oxygen and leads to the generation of hydrogen peroxide. Therefore, consideration must be given to suppressing contact with oxygen, such as in an atmosphere substituted with an inert gas, even during kneading. It is preferable to carry out in a separate line. A method of supplying only the polyvinyl pyrrolidone and the solvent and supplying the polysulfone polymer directly to the dissolution tank without pre-kneading is also included in the scope of the present invention.

  The kneading may be performed by providing a kneading line separately from the dissolving tank, and the kneaded product may be supplied to the dissolving tank, or both the kneading and dissolving may be performed in a dissolving tank having a kneading function. The type and form of the kneading apparatus in the former separate apparatus are not limited. Either a batch system or a continuous system may be used. A static method such as a static mixer may be used, or a dynamic method such as a kneader or a stirring kneader may be used. The latter is preferred from the efficiency of kneading. The kneading method in the latter case is not limited, and any type such as a pin type, a screw type, and a stirrer type may be used. Screw type is preferred. What is necessary is just to select suitably the shape and rotation speed of a screw from the balance of kneading | mixing efficiency and heat_generation | fever. On the other hand, the type of dissolution tank when using a dissolution tank having a kneading function is not limited. For example, there is a kneading and dissolving machine of a type that expresses a kneading effect by so-called planetary motion in which two frame-type blades rotate and revolve. Recommended. For example, a planetary mixer or a trimix manufactured by Inoue Seisakusho Co., Ltd. corresponds to this method.

  The ratio of the resin component such as polyvinyl pyrrolidone or polysulfone polymer and the solvent during kneading is not limited. A resin / solvent mass ratio of 0.1 to 3 is preferred. 0.5-2 are more preferable.

  As described above, the technical point of the present invention is to suppress the degradation of polyvinyl pyrrolidone and perform efficient dissolution. Therefore, a system in which at least polyvinylpyrrolidone is present is a preferred embodiment in which the system is kneaded and dissolved at a low temperature of 70 ° C. or lower in a nitrogen atmosphere. When the polyvinyl pyrrolidone and the polysulfone polymer are kneaded in separate lines, this requirement may be applied to the polysulfone polymer kneading line. The efficiency of kneading and dissolution and heat generation are two contradictory phenomena. Selection of an apparatus and conditions that avoid the trade-off as much as possible is an important element of the present invention. In this sense, the cooling method in the kneading mechanism is important and needs attention.

Subsequently, the material kneaded by the above method is dissolved. Although the dissolution method is not limited, for example, a dissolution method using a stirring type dissolution apparatus can be applied. In order to dissolve at a low temperature for a short time (within 3 hours), the Froude number (Fr = n ² d / g) is 0.7 to 1.3 and the stirring Reynolds number (Re = nd ² ρ / μ) is It is preferable that they are 50 or more and 250 or less. Here, n is the blade rotation speed (rps), ρ is the density (Kg / m ³ ), μ is the viscosity (Pa · s), g is the gravitational acceleration (= 9.8 m / s ² ), and d is the stirring blade diameter. (M). If the Froude number is too large, the inertial force becomes strong, so that the raw material scattered in the tank adheres to the walls and ceiling, and the desired film-forming solution composition may not be obtained. Therefore, the fluid number is more preferably 1.25 or less, further preferably 1.2 or less, and further preferably 1.15 or less. On the other hand, if the fluid number is too small, the inertial force is weakened, so that the dispersibility of the raw material is lowered, and in particular, polyvinylpyrrolidone becomes a spatter, which makes it difficult to dissolve further or requires a long time for uniform dissolution. Sometimes. Therefore, the fluid number is more preferably 0.75 or more, and further preferably 0.8 or more.

  Since the film-forming solution in the present invention is a so-called low-viscosity fluid, if the stirring Reynolds number is too large, a longer defoaming time or insufficient defoaming occurs due to the entrapment of bubbles in the film-forming solution during stirring. Such problems may occur. Therefore, the stirring Reynolds number is more preferably 240 or less, further preferably 230 or less, and still more preferably 220 or less. On the other hand, when the stirring Reynolds number is too small, the stirring force becomes small, so that dissolution may be easily made nonuniform. Therefore, the stirring Reynolds number is more preferably 35 or more, further preferably 40 or more, still more preferably 55 or more, and particularly preferably 60 or more. Furthermore, when a hollow fiber membrane is formed with such a membrane-forming solution, the operability is deteriorated due to a drop in spinnability due to bubbles, and the quality of the material also becomes a defect due to the inclusion of bubbles in the hollow fiber membrane. It turned out to be a problem by causing a decrease in airtightness and burst pressure. Defoaming the film-forming solution is an effective countermeasure, but it may be accompanied by a change in the composition of the film-forming solution due to viscosity control of the film-forming solution or evaporation of the solvent. .

Furthermore, since polyvinyl pyrrolidone tends to undergo oxidative degradation due to the influence of oxygen in the air, it is preferable to dissolve the film forming solution in an inert gas enclosure. Nitrogen, argon, etc. are raised as the inert gas, but nitrogen is preferably used. At this time, the residual oxygen concentration in the dissolution tank is preferably 3% or less. If the nitrogen sealing pressure is increased, the melting time can be shortened. However, in order to increase the pressure, the equipment cost increases, and from the viewpoint of work safety, it is preferably from atmospheric pressure to 2 kgf / cm ² .

  In addition, as the shape of the stirring blade used for dissolving the low-viscosity film forming solution used in the present invention, a radial turbine blade such as a disk turbine type, a paddle type, a curved blade fan turbine type, an arrow blade turbine type, or a propeller type An axial-flow type wing such as an inclined paddle type or a fiddler type is included, but is not limited thereto.

  By using the low-temperature dissolution method as described above, it is possible to obtain a highly safe hollow fiber membrane in which the degradation degradation of the hydrophilic polymer is suppressed. In addition, it is preferable to use a film-forming solution having a residence time after dissolution of the raw materials within 24 hours for film-forming. This is because thermal energy was accumulated while the film forming solution was kept warm, and a tendency to cause deterioration of the raw material was recognized.

  In addition, as described above, a method of removing hydrogen peroxide mixed from the raw material polyvinylpyrrolidone or generated in the manufacturing process of the hollow fiber membrane bundle by washing is also effective as a method for controlling the above-described characteristic values within a regulated range. is there.

  In the present invention, the amount of polyvinylpyrrolidone eluted and endotoxin, which is an endotoxin, are prevented from penetrating into the blood, and the hollow fiber membrane bundles are prevented from sticking together when the hollow fiber membrane bundles are dried. In order to balance the characteristics, it is preferable that the content of polyvinyl pyrrolidone on the outer surface of the hollow fiber membrane bundle is in a specific range. As a method for satisfying this requirement, it can be achieved, for example, by setting the composition ratio of polyvinylpyrrolidone with respect to the polysulfone polymer to the above-mentioned range or optimizing the film forming conditions of the hollow fiber membrane bundle. It is also an effective method to wash the formed hollow fiber membrane bundle. Film formation conditions include optimization of the humidity at the air gap at the nozzle outlet, stretching conditions, coagulation bath temperature, composition ratio of solvent to non-solvent in the coagulation liquid, and introduction of a cleaning process is also effective. It is.

  As the internal coagulation liquid, a 0 to 80% by mass dimethylacetamide (DMAc) aqueous solution is preferable. More preferably, it is 15-70 mass%, More preferably, it is 25-60 mass%, More preferably, it is 30-50 mass%. If the concentration of the internal coagulation solution is too low, the dense layer of the blood contact surface becomes thick, which may reduce the solute permeability. On the other hand, if the concentration of the internal coagulating liquid is too high, the formation of the dense layer tends to be incomplete, and the fractionation characteristics may be deteriorated. The external coagulation liquid is preferably a 0 to 50% by weight DMAc aqueous solution. If the concentration of the external coagulation solution is too high, the outer surface open area ratio and outer surface average pore area will become too large, which may increase the backflow of endotoxin to the blood side during dialysis and decrease the burst pressure. is there. Therefore, the external coagulation liquid concentration is more preferably 40% by mass or less, further preferably 30% by mass or less, and still more preferably 25% by mass or less. Further, when the external coagulation liquid concentration is too low, it is necessary to use a large amount of water in order to dilute the solvent brought in from the film forming solution, and the cost for waste liquid treatment increases. Therefore, the lower limit of the external coagulation liquid concentration is more preferably 5% by mass or more, further preferably 10% by mass or more, and still more preferably 15% by mass or more.

  In the production of the hollow fiber membrane bundle of the present invention, it is preferable that stretching is not substantially applied before the hollow fiber membrane structure is completely fixed. The fact that the film is not substantially stretched means that the roller speed during the film forming process is controlled so that the film forming solution discharged from the nozzle is not slackened or excessively strained. The discharge linear speed / coagulation bath first roller speed ratio (draft ratio) is preferably in the range of 0.7 to 1.8. If the ratio is less than 0.7, the running hollow fiber membrane bundle may be slack and lead to a decrease in productivity. Therefore, the draft ratio is more preferably 0.8 or more, more preferably 0.9 or more, and 0 .95 or more is even more preferable. When it exceeds 1.8, the membrane structure may be destroyed, for example, the dense layer of the hollow fiber membrane bundle is torn. Therefore, the draft ratio is more preferably 1.7 or less, still more preferably 1.6 or less, still more preferably 1.5 or less, and particularly preferably 1.4 or less. By adjusting the draft ratio to this range, deformation and destruction of the pores can be prevented, clogging of blood protein into the membrane pores can be prevented, and performance stability over time and sharp fractionation characteristics can be expressed. Is possible.

In the present invention, as described above, in the process of producing a hollow fiber membrane bundle, as a means for reducing the elution amount of hydrogen peroxide or bringing the content of polyvinylpyrrolidone on the outer surface of the hollow fiber membrane bundle into a specific range. It is important to introduce a washing step before the drying step. For example, the hollow fiber membrane bundle that has passed through the water-washing bath is wound into a basket in a wet state to form a bundle of 3,000 to 20,000. Next, the obtained hollow fiber membrane bundle is washed to remove excess solvent, polyvinylpyrrolidone. As a method for washing the hollow fiber membrane bundle, in the present invention, it is preferable to treat the hollow fiber membrane bundle by immersing it in hot water at 70 to 130 ° C. or room temperature to 50 ° C. and 10 to 40 vol% ethanol or isopropanol aqueous solution. .
(1) In the case of hot water washing, the hollow fiber membrane bundle is immersed in excess RO water and treated at 70 to 90 ° C. for 15 to 60 minutes, and then the hollow fiber membrane bundle is taken out and subjected to centrifugal dehydration. This operation is repeated several times while updating the RO water to perform the cleaning process.
(2) A method of treating a hollow fiber membrane bundle immersed in excess RO water in a pressurized container at 121 ° C. for about 2 hours may be employed.
(3) When using an ethanol or isopropanol aqueous solution, it is preferable to repeat the same operation as in (1).
(4) It is also a preferable washing method that the hollow fiber membrane bundle is radially arranged in the centrifugal washer, and centrifugal washing is performed for 30 minutes to 5 hours while spraying washing water at 40 ° C. to 90 ° C. from the rotation center in a shower shape. .
Two or more cleaning methods may be combined. In any method, when the processing temperature is too low, it is necessary to increase the number of times of cleaning, which may lead to an increase in cost. On the other hand, if the treatment temperature is too high, the decomposition of polyvinylpyrrolidone is accelerated, and conversely, the cleaning efficiency may be reduced. By performing the above-described cleaning, the content ratio of the outer surface polyvinyl pyrrolidone can be optimized, and it is possible to suppress sticking and reduce the amount of eluate, and also to reduce the hydrogen peroxide elution amount.

When used for a blood purifier, it is preferable that the burst pressure is made of a hollow fiber membrane having a pressure of 0.5 MPa or more, and the water permeability of the blood purifier is 150 ml / m ² / hr / mmHg or more. If the burst pressure is less than 0.5 MPa, there is a possibility that a potential defect leading to a blood leak as described later cannot be detected. Moreover, if the water permeability is less than 150 ml / m ² / hr / mmHg, the dialysis efficiency may decrease. In order to increase the dialysis efficiency, the pore diameter is increased or the number of pores is increased. However, this tends to cause a problem that the membrane strength is reduced or defects are formed. Therefore, it is preferable that the porosity of the support layer portion is optimized by optimizing the pore diameter of the outer surface, and the solute permeation resistance and membrane strength are balanced. A more preferable range of water permeability is 200 ml / m ² / hr / mmHg or more, more preferably 250 ml / m ² / hr / mmHg or more, and still more preferably 300 ml / m ² / hr / mmHg or more. In addition, when the water permeability is too high, it becomes difficult to control water removal during hemodialysis, and therefore, 2000 ml / m ² / hr / mmHg or less is preferable. More preferably 1800ml ^/ m 2 ^/ hr ^/ mmHg or less, more preferably 1500ml ^/ m 2 ^/ hr ^/ mmHg or less, still more preferably not more than ^{1300ml / m 2 / hr / mmHg} .

Usually, a module used for blood purification is subjected to a leak test in which the inside or outside of the hollow fiber is pressurized with air in order to confirm defects of the hollow fiber or the module at the final stage of production. When a leak is detected by the pressurized air, the module is discarded as a defective product or an operation for repairing the defect is performed. The air pressure in this leak test is often several times the guaranteed pressure resistance (usually 500 mmHg) of the hemodialyzer. However, in the case of a hollow fiber type blood purification membrane having a particularly high water permeability, microscopic scratches, crushing, and tearing of the hollow fiber that cannot be detected by a normal pressure leak test are caused by manufacturing processes (mainly sterilization and (Packing), transportation process, or handling in clinical settings (unpacking, priming, etc.) will lead to the occurrence of hollow fiber cutting and pinholes. It is. The trouble can be avoided by setting the burst pressure to the above characteristic.
Further, the uneven thickness of the hollow fiber membrane bundle is effective for suppressing the occurrence of the above-described potential defects.

  The burst pressure in the present invention is an index of the pressure resistance of the hollow fiber membrane bundle after the hollow fiber is made into a module. The inside of the hollow fiber membrane bundle is pressurized with gas, and the pressurized pressure is gradually increased. Is the pressure when bursting without being able to withstand the internal pressure. The higher the burst pressure, the less the cutting of the hollow fiber membrane bundle and the generation of pinholes during use, so 0.5 MPa or more is preferable, 0.55 MPa or more is more preferable, and 0.6 MPa or more is even more preferable. If the burst pressure is less than 0.5 MPa, there may be a potential defect. The higher the burst pressure, the better. However, if the focus is on increasing the burst pressure and the film thickness is increased or the porosity is decreased too much, the desired film performance may not be obtained. Therefore, when finished as a hemodialysis membrane, the burst pressure is preferably less than 2.0 MPa. More preferably, it is less than 1.7 MPa, more preferably less than 1.5 MPa, still more preferably less than 1.3 MPa, and particularly preferably less than 1.0 MPa.

  The uneven thickness in the present invention is a deviation in film thickness when observing 100 cross sections of the hollow fiber membrane bundles in the hollow fiber membrane bundle module, and is represented by a ratio between the maximum value and the minimum value. The minimum thickness deviation of 100 hollow fiber membranes is preferably 0.6 or more. If even one hollow fiber membrane with a thickness deviation of less than 0.6 is included in 100 hollow fiber membranes, the hollow fiber membrane may cause a leak during clinical use. It represents not the value but 100 minimum values. Higher unevenness increases the uniformity of the film, suppresses the appearance of latent defects and improves the burst pressure, more preferably 0.7 or more, more preferably 0.8 or more, still more preferably 0.85 or more. If the uneven thickness is too low, latent defects are likely to be manifested, the burst pressure is lowered, and blood leakage is liable to occur.

  As an achievement means for making the unevenness degree 0.6 or more, for example, it is preferable to make the slit width of the nozzle that is the discharge port of the film forming solution strictly uniform. The hollow fiber membrane bundle film forming nozzle is generally a tube-in-orifice type nozzle having an annular part for discharging a film forming solution and a core liquid discharge hole serving as a hollow forming agent inside thereof. Refers to the width of the outer annular portion that discharges the film-forming solution. By reducing the variation in the slit width, uneven thickness of the formed hollow fiber membrane bundle can be reduced. Specifically, the ratio between the maximum value and the minimum value of the slit width is 1.00 or more and 1.11 or less, and the difference between the maximum value and the minimum value is preferably 10 μm or less, more preferably 7 μm or less, More preferably, it is 5 micrometers or less, More preferably, it is 3 micrometers or less. It is also a preferred embodiment to optimize the nozzle temperature. The nozzle temperature is preferably 20 to 100 ° C. If it is less than 20 ° C., it is easily affected by the room temperature, the nozzle temperature is not stable, and ejection spots of the film forming solution may occur. Therefore, the nozzle temperature is more preferably 30 ° C. or higher, further preferably 35 ° C. or higher, and further preferably 40 ° C. or higher. On the other hand, when the temperature exceeds 100 ° C., the viscosity of the film-forming solution may be too low and ejection may become unstable, and thermal degradation / decomposition of polyvinylpyrrolidone may proceed. Therefore, the nozzle temperature is more preferably 90 ° C. or less, further preferably 80 ° C. or less, and still more preferably 70 ° C. or less.

  Furthermore, as a measure for increasing the burst pressure, it is also an effective method to reduce potential defects by reducing flaws on the surface of the hollow fiber membrane bundle, foreign matters and bubbles. As a method of reducing the occurrence of scratches, the material and surface roughness of rollers and guides in the manufacturing process of the hollow fiber membrane bundle are optimized, and the container and the hollow fiber are inserted when the hollow fiber membrane bundle is inserted into the module container when the module is assembled. It is effective to devise such that contact with the membrane bundle or rubbing between the hollow fiber membrane bundles is reduced. In the present invention, it is preferable to use a roller having a mirror-finished surface in order to prevent the hollow fiber membrane bundle from slipping and scratching the surface of the hollow fiber membrane bundle. In addition, it is preferable to use a guide whose surface is textured or knurled in order to avoid contact resistance with the hollow fiber membrane bundle as much as possible. When inserting the hollow fiber membrane bundle into the module container, the hollow fiber membrane bundle is not directly inserted into the module container. It is preferable to use a method in which the rolled material is inserted into the module container, and after insertion, only the film is extracted from the module container.

  As a method for suppressing the mixing of foreign matter into the hollow fiber membrane bundle, a method using a raw material with little foreign matter, filtering a film-forming solution for film formation, and reducing foreign matter is effective. In the present invention, it is preferable to filter the membrane-forming solution using a filter having a pore size smaller than the thickness of the hollow fiber membrane bundle and then discharge from the nozzle. Specifically, the uniformly-dissolved membrane-forming solution is removed from the dissolution tank. A sintered filter having a pore diameter of 10 to 50 μm provided while being led to the nozzle is passed. The filtration treatment may be performed at least once. However, when the filtration treatment is performed in several stages, it is preferable to reduce the pore size of the filter as it is in the latter stage in order to extend the filtration efficiency and the filter life. The pore size of the filter is more preferably 10 to 45 μm, further preferably 10 to 40 μm. If the filter pore size is too small, the back pressure may increase and the quantitativeness may decrease. Further, as a method for suppressing the mixing of bubbles, it is effective to defoam a polymer solution for film formation. Depending on the viscosity of the film-forming solution, static defoaming or vacuum defoaming can be used. In this case, after the pressure in the dissolution tank is reduced to −100 to −730 mmHg, the tank is sealed and allowed to stand for 5 to 30 minutes. This operation is repeated several times to perform defoaming treatment. If the degree of vacuum is too low, the treatment may take a long time because it is necessary to increase the number of defoaming times. On the other hand, when the degree of vacuum is too high, the cost for increasing the degree of sealing of the system may increase. The total treatment time is preferably 5 minutes to 5 hours. If the treatment time is too long, polyvinylpyrrolidone may be decomposed and deteriorated due to the effect of reduced pressure. If the treatment time is too short, the defoaming effect may be insufficient.

  In this invention, it is preferable that content in the outer surface of the hollow fiber membrane of a hydrophilic polymer is 25-50 mass%. If the content of the hydrophilic polymer on the outer surface is less than 25% by mass, the content of the hydrophilic polymer on the entire membrane, particularly the inner surface of the membrane becomes too low, and blood compatibility and permeation performance may be deteriorated. . In the case of a dry film, wettability may be reduced. When the hemodialyzer is used for blood purification therapy, it is necessary to perform wetting and defoaming by allowing physiological saline or the like to flow inside and outside the hollow fiber membrane of the hemodialyzer. In this priming operation, roundness of the hollow fiber membrane, edge crushing, deformation, hydrophilicity of the membrane material, etc. are thought to affect the priming properties, but it consists of a hydrophobic polymer and a hydrophilic polymer. In the case of a hollow fiber membrane and a dry membrane module, the hydrophilic / hydrophobic balance of the hollow fiber membrane greatly affects the priming property. Therefore, the more preferable content of the hydrophilic polymer is 27% by mass or more, and more preferably 30% by mass or more. If the content of the hydrophilic polymer on the outer surface exceeds 50% by mass, the endotoxin (endotoxin) contained in the dialysate is likely to enter the blood side, leading to side effects such as fever, When the membrane is dried, a hydrophilic polymer existing on the outer surface of the membrane is interposed, and the hollow fiber membranes stick to each other (adhere), which may cause problems such as deterioration in module assembly. Therefore, the more preferable content is 47% by mass or less, and further preferably 45% by mass or less.

  The content of the hydrophilic polymer surface outermost layer of the hydrophilic polymer described above was measured and calculated by the ESCA method as described later, and the outermost layer portion of the hollow fiber membrane surface (depth depth from the surface layer) The absolute value of the content of ˜several tens of liters) is obtained. Normally, the ESCA method (outermost layer) can measure the hydrophilic polymer (PVP) content up to about 10 nm (100 mm) deep from the blood contact surface.

  Moreover, in this invention, it is effective in order to provide an above described property that the porosity of the hollow fiber membrane outer surface is 8 to 25%, and is a preferable embodiment. If the open area ratio is less than 8%, the water permeability may be lowered. Further, when the membrane is dried, the hydrophilic polymer existing on the outer surface of the membrane is interposed, and the hollow fiber membranes are fixed to each other, causing problems such as deterioration in module assemblability. Therefore, the open area ratio is more preferably 9% or more, and further preferably 10% or more. On the other hand, when the open area ratio exceeds 25%, the burst pressure may decrease, or endotoxin may enter from the dialysate side to the blood side during hemodialysis. Therefore, the porosity is more preferably 23% or less, further preferably 20% or less, still more preferably 17% or less, and particularly preferably 15% or less.

  The film thickness of the hollow fiber membrane is preferably 10 μm or more and 60 μm or less. If it exceeds 60 μm, the permeability of medium to high molecular weight substances having a low movement speed may be lowered even if the water permeability is high. The thinner the film thickness, the higher the material permeability. Therefore, the thickness is more preferably 55 μm or less, further preferably 50 μm or less, and still more preferably 47 μm or less. On the other hand, when the film thickness is less than 10 μm, the burst pressure may be lowered even if the film strength is low and the thickness deviation is 0.6 or more. Therefore, the film thickness is more preferably 20 μm or more, further preferably 25 μm or more, still more preferably 30 μm or more, and particularly preferably 35 μm or more.

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

1. Moisture content of hollow fiber membrane bundle The mass (a) of the hollow fiber membrane before drying, the mass (b) of the hollow fiber membrane after drying for 2 hours in a dry heat oven at 120 ° C. (after absolute drying), It can be easily calculated using the following formula.
Moisture content (mass%) = (ab) / b × 100
Here, by setting (a) within the range of 1 to 2 g, a completely dry state (a state in which there is no further mass change) can be obtained after 2 hours.

2. Moisture content fluctuation rate of hollow fiber membrane bundle The hollow fiber membrane bundle was equally divided into 10 pieces of 2.7 cm in the longitudinal direction, and 1 g of dry hollow fiber membrane was weighed from each part, and the moisture content was measured by the above method. Was measured and calculated by the following formula.
Moisture content fluctuation rate (%) = {(maximum moisture content value−minimum moisture content value) / average moisture content value} × 100

3. UV (220-350 nm) absorbance According to the method defined in the dialysis artificial kidney device manufacturing standard, 100 ml of pure water was added to 1 g of hollow fiber membrane, and the extracted solution was extracted at 70 ° C. for 1 hour with a spectrophotometer (Hitachi, Ltd.) The absorbance in the wavelength range of 200 to 350 nm was measured using U-3000), and the maximum absorbance in this wavelength range was determined.
In the measurement, the hollow fiber membrane bundle was equally divided into 10 pieces of 2.7 cm in the longitudinal direction, and 1 g of the hollow fiber membrane bundle in a dry state was weighed from each portion and measured for all samples.
In the case of the wet hollow fiber membrane module, physiological saline was passed through the dialysate side channel of the module at 500 mL / min for 5 minutes, and then passed through the blood side channel at 200 mL / min. Thereafter, the solution was passed through for 3 minutes while filtering from the blood side to the dialysate side at 200 mL / min, and then freeze-dried to obtain a dry membrane, and the above measurement was performed using the dry membrane.

4. Hydrogen peroxide elution amount TiCl ₄ hydrogen chloride solution mixed with 2.6 ml of the extract extracted by the above method in an equimolar ratio with ammonium chloride buffer (pH 8.6) 0.2 ml and 4- (2- Pyridylazo) Resorcinol Na salt aqueous solution prepared in 0.2 mM was added to 0.2 ml of coloring reagent, heated at 50 ° C. for 5 minutes, cooled to room temperature, and the absorbance at 508 nm was measured. It quantified with the analytical curve calculated | required similarly using the sample and calculated | required.
In the measurement, the hollow fiber membrane bundle was equally divided into 10 pieces of 2.7 cm in the longitudinal direction, and 1 g of the hollow fiber membrane bundle in a dry state was weighed from each portion and measured for all samples.
In the case of a wet hollow fiber membrane module, the measurement was performed using a dry membrane obtained by processing in the same manner as the measurement of the amount of polyvinylpyrrolidone eluted.

5. Difference in the maximum elution amount of hydrogen peroxide The difference between the maximum elution amount and the average elution amount from the maximum elution amount, the average elution amount, and the minimum elution amount of hydrogen peroxide obtained by the above measurement of the hydrogen peroxide elution amount. The difference between the average elution amount and the minimum elution amount was determined, and the larger value was taken as the maximum elution amount difference.

6. Partial stickiness of hollow fiber membrane bundle Using a SK cutter to prevent the hollow fiber membrane bundles from being fused by heat generated during cutting of a film-wound dry bundle, cut in 2 cm width in the longitudinal direction of the hollow fiber membrane bundle To do. While neutralizing the ring-shaped hollow fiber membrane bundle (SJ-F020, manufactured by Keyence Corporation), it was slowly dropped onto the paper surface of the desk, and it was visually confirmed whether or not a plurality of lumps were generated. In addition, when visually confirming, the thing which the lump produced by fusion | melting of the cut surface clearly was classified as not partial adhesion. If the fused state is severe, replace the blade to be cut as appropriate.

7. Storage stability of the dried hollow fiber membrane bundle The dried samples used for the measurement of the various elution amounts described above were placed in a dry box (atmosphere: air) conditioned at a humidity of 50% for 3 months at room temperature. After storage, UV (220-350 nm) absorbance was measured by the method described above. Stability was determined by the degree of increase in UV (220-350 nm) absorbance due to the storage. The degree of increase was determined by dividing the hollow fiber membrane bundle into 10 pieces of 2.7 cm in the longitudinal direction, measuring each sample, and determining the average value. Those whose average value did not exceed 0.1, which is the standard value of the dialysis artificial kidney device manufacturing standard, were regarded as acceptable.

8. Storage stability of wet hollow fiber membrane bundle About 10,000 dry hollow fiber membranes obtained in each example and comparative example were inserted into a polyethylene pipe, cut into a predetermined length, and bundled It was. The obtained bundle was filled in a case at a filling rate of 60 vol%, the end part was bonded with urethane resin, the membrane area (hollow fiber membrane inner diameter standard) where the hollow part was opened by cutting the resin was 1.5 m ² It was a module. The module was filled with RO water degassed in advance and irradiated with γ rays at an absorbed dose of 25 kGy for crosslinking. After storing the module after γ-ray irradiation at room temperature for one year, UV (220 to 350 nm) absorbance was measured by the method described above. Stability was determined by the degree of increase in UV (220-350 nm) absorbance due to the storage. The degree of increase was obtained by equally dividing the hollow fiber membrane bundle into 10 pieces in the longitudinal direction, measuring each sample, and determining the average value. Those whose average value did not exceed 0.10, which is the reference value of the dialysis artificial kidney device manufacturing standard, were regarded as acceptable. In the case of a hollow fiber membrane bundle that had been subjected to crosslinking treatment, the crosslinking treatment was canceled and evaluated.

9. Unevenness of thickness The cross section of 100 hollow fibers is observed with a 200 times projector. The thickness of the thickest part and the thinnest part is measured for one yarn cross section having the most difference in film thickness in one field of view.
Thickness unevenness = thinnest part / thickest part thickening degree = 1 so that the film thickness is perfectly uniform.

10. Water permeability The blood outlet circuit of the dialyzer (the outlet side from the pressure measurement point) was sealed with forceps. Purified water kept at 37 ° C is put into a pressurized tank, and while controlling the pressure with a regulator, pure water is sent to the blood flow path side (hollow part) of the dialyzer kept at 37 ° C constant temperature bath and flows out from the dialysate side. The amount of filtrate 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 is changed at four points, the filtration flow rate is measured, and the water permeability (mL / hr / mmHg) is calculated from the slope of the relationship. At this time, the correlation coefficient between TMP and the filtration flow rate must be 0.999 or more. In order to reduce the pressure loss error due to the circuit, TMP is measured in the range of 100 mmHg or less. The water permeability of the hollow fiber membrane bundle 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 bundle (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. (M ² ).

11. Calculation of membrane area The membrane area of the dialyzer is determined as a reference for the inner diameter of the hollow fiber.
A = n × π × d × L
Here, n is the number of hollow fibers in the dialyzer, π is the circumference, d is the inner diameter (m) of the hollow fiber, and L is the effective length (m) of the hollow fiber in the dialyzer.

12. Burst pressure Fill the dialysate side of the module consisting of about 10,000 hollow fiber membrane bundles with water and plug it. Dry air or nitrogen is fed from the blood side at room temperature and pressurized at a rate of 0.5 MPa per minute. The pressure is increased, and the air pressure when the hollow fiber membrane bundle bursts (bursts) with pressurized air and bubbles are generated in the liquid filled on the dialysate side is defined as the burst pressure.

13. Blood Leak Test A 37 ° C. bovine blood to which citric acid is added and coagulation is suppressed is fed to a blood purifier at 200 mL / min, and the blood is filtered at a rate of 20 mL / min. At this time, the filtrate is returned to blood to be a circulatory system. After 60 minutes, the filtrate from the blood purifier is collected, and the red color resulting from red blood cell leakage is visually observed. In this blood leak test, 30 blood purifiers were used in each example and comparative example, and the number of blood leaked modules was examined.

14. Content on the outer surface of the hydrophilic polymer The content of the hydrophilic polymer with respect to the hydrophobic polymer was determined by X-ray photoelectron spectroscopy (ESCA method). A measurement method in the case of using polysulfone-based polymer as the hydrophobic polymer and polyvinylpyrrolidone as the hydrophilic polymer is exemplified.
One hollow fiber membrane was attached to a sample stage, and measurement was performed by X-ray photoelectron spectroscopy (ESCA method). The measurement conditions are as follows.
Measuring device: ULVAC-Phi ESCA5800
Excitation X-ray: MgKα ray X-ray output: 14 kV, 25 mA
Photoelectron escape angle: 45 °
Analysis diameter: 400μmφ
Pass energy: 29.35 eV
Resolution: 0.125 eV / step
Degree of vacuum: about 10 ⁻⁷ Pa or less From the measured value of nitrogen (N) and the measured value of sulfur (S), the PVP content on the surface was calculated by the following formula.
<In case of PVP-added PES (polyethersulfone) membrane>
PVP content (Hpvp) [%]
= 100 × (N × 111) / (N × 111 + S × 232)
<In the case of PVP-added PSf (polysulfone) membrane>
PVP content (Hpvp) [%]
= 100 × (N × 111) / (N × 111 + S × 442)

15. Content of hydrophilic polymer in membrane An example of a measurement method using polyvinyl pyrrolidone (PVP) as the hydrophilic polymer is illustrated. The sample was dried at 80 ° C. for 48 hours using a vacuum dryer, 10 mg of which was analyzed with a CHN coder (manufactured by Yanaco Analytical Co., Ltd., MT-6 type), and the content of PVP was calculated from the nitrogen content according to the following formula: Calculated with
PVP content (mass%) = nitrogen content (mass%) × 111/14

16. Opening ratio of outer surface of hollow fiber membrane The outer surface of the hollow fiber membrane is observed with an electron microscope of 10,000 times and a photograph (SEM photograph) is taken. The image was processed with image analysis processing software to obtain the porosity of the outer surface of the hollow fiber membrane. The image analysis processing software is measured using, for example, Image Pro Plus (Media Cybernetics, Inc.). The emphasis / filtering operation is performed on the captured image so that the hole and the blockage are identified. Thereafter, the holes are counted, and when the lower polymer chain can be seen inside the holes, the holes are combined and counted as one hole. The area (A) of the measurement range and the cumulative area (B) of the pores within the measurement range were calculated and calculated according to the following formula.
Opening ratio (%) = B / A × 100
This was carried out for 10 views and the average was obtained. Scale setting is performed as an initial operation, and holes on the measurement range boundary are not excluded during counting.

17. Membrane thickness of hollow fiber membrane A cross section of the hollow fiber membrane is projected by a projector having a magnification of 200 times. B) is measured, and the film thickness of each hollow fiber membrane is obtained by the following formula,
Film thickness = (B−A) / 2
The average of the film thickness of 90 hollow fiber membranes in 30 fields of view was calculated.

(Example 1)
Polyethersulfone (Sumika Excel (R) 4800P, 18.8% by mass) is added to a kneading and dissolving machine that exhibits a kneading effect by a so-called planetary motion in which two frame-type blades rotate and revolve. Polyvinylpyrrolidone (BASF Koridone (R) K90) (2.7% by mass) and dimethylacetamide (DMAc) (18.8% by mass) were charged and stirred for 2 hours for kneading. Subsequently, a mixed solution of 56.7% by mass of DMAc and RO water of 3.0% by mass was added over 1 hour. Stirring was continued for an additional hour by increasing the number of revolutions of the stirrer and dissolved uniformly. At this time, kneading and dissolution were performed in a nitrogen atmosphere. The temperature during kneading and dissolution was cooled so as not to exceed 40 ° C. The stirring fluid number and stirring Reynolds number at the final dissolution were 1.0 and 100, respectively. The system was then depressurized to -500 mmHg using a vacuum pump, and the system was immediately sealed and allowed to stand for 15 minutes so that the solvent and the like were evaporated and the composition of the film forming solution did not change. This operation was repeated three times to degas the film forming solution. After the defoaming was completed, the inside of the system was again purged with nitrogen and maintained in a weakly pressurized state. The polyvinyl pyrrolidone used was a hydrogen peroxide content of 110 ppm. The obtained film-forming solution was sequentially passed through a two-stage sintered filter of 30 μm and 15 μm, and then degassed at −700 mmHg for 30 minutes in advance as a hollow forming agent from a tube-in orifice nozzle heated to 75 ° C. The solution was discharged together with a 53% by mass DMAc aqueous solution, passed through a 400 mm dry part cut off from the outside air by a film-forming tube, coagulated in a 20% by mass DMAc aqueous solution at 60 ° C., and then rolled up in a wet state. The average nozzle slit width of the tube-in-orifice nozzle used was 60 μm, the maximum was 60.5 μm, the minimum was 59.5 μm, the ratio of the maximum and minimum slit widths was 1.02, and the draft ratio was 1.2. It was. During the film forming process, all the rollers with which the hollow fiber membrane bundle contacts were mirror-finished on the surface, and all the guides with a satin-finished surface were used. A polyethylene film whose surface on the hollow fiber bundle side is textured is wrapped around a bundle of about 10,000 hollow fiber membranes, then cut into 27 cm lengths, and heated in hot water at 80 ° C. for 30 minutes. Washed 4 times for 4 minutes.

  The obtained wet hollow fiber membrane bundle has a structure in which a microwave oscillator is installed on the side wall of the heating oven so that the microwave can oscillate in the horizontal direction and a reflector is installed in the oven for uniform heating. Then, it was introduced into a microwave dryer having an exhaust system for reducing the pressure of the far-infrared heater and the oven, and dried under the following conditions. After heating the hollow fiber membrane bundle under a reduced pressure of 7 kPa at an output of 1.5 kW for 25 minutes, the microwave irradiation was stopped and at the same time the pressure was reduced to 1.5 kPa and maintained for 3 minutes. Subsequently, the degree of vacuum was returned to 7 kPa, the microwave was irradiated and the hollow fiber membrane bundle was heated at an output of 0.5 kW for 8 minutes, and then the microwave was cut to increase the degree of vacuum and maintain 0.7 kPa for 3 minutes. Furthermore, the degree of vacuum was returned to 7 kPa, and microwave irradiation was performed at an output of 0.2 kW for 5 minutes to heat the hollow fiber membrane bundle. After the microwave cutting, the degree of vacuum was increased to 0.5 kPa, and only the far infrared rays were irradiated and maintained for 10 minutes to complete the drying of the hollow fiber membrane bundle. The water content of the hollow fiber membrane bundle after the microwave irradiation was 11% by mass. During drying, the output of the far-infrared heater was adjusted so that the temperature detected by a thermocouple provided at the center of the drying oven was 50 ° C. over the entire period. In addition, the waveguide of the microwave oscillator of the microwave dryer has a structure in which the cross-sectional area gradually increases toward the microwave traveling direction, and a conical reflector is guided at the apex of the cone at the outlet of the waveguide. The Er / Ei of the microwave irradiated with the structure installed in the direction facing the inside of the tube was 0.05. The maximum temperature reached on the surface of the hollow fiber membrane bundle at this time was 65 ° C. The moisture content of the hollow fiber membrane bundle before drying was 330% by mass, and the moisture content after the final drying was 2.0% by mass. The obtained hollow fiber membrane bundle had an inner diameter of 199 μm and a film thickness of 29 μm.

  The obtained dry hollow fiber membrane bundle was equally divided into 10 pieces of 2.7 cm in the longitudinal direction, and 1 g of the dry hollow fiber membrane was weighed out from each part, and the moisture content was measured. Moreover, the extract was obtained according to the dialysis type artificial kidney apparatus manufacture approval reference test, and the hydrogen peroxide elution amount and UV (220-350 nm) absorbance in the extract were measured. Both measurements were stable at low levels at all sites. Moreover, the fluctuation of the moisture content was small. The measurement results are summarized in Tables 1-3.

  Further, the storage stability of the obtained hollow fiber membrane bundle in a dry state is good, and UV (220-350 nm) of the extract obtained from each part obtained by dividing the hollow fiber membrane bundle after storage for 3 months into 10 equal parts. ) The absorbance was 0.03 at the maximum value, and the dialysis type artificial kidney device manufacturing approval reference value of less than 0.10 was maintained. Furthermore, the UV absorbance level of each part was stable at a low level, and the workability of module assembly was good without occurrence of partial sticking.

  Further, as a result of assembling a blood purifier using the obtained hollow fiber membrane bundle and conducting a leak test, no adhesion failure caused by the sticking of the hollow fiber membranes was observed. The blood purifier was preliminarily degassed with RO water and irradiated with γ rays at an absorbed dose of 25 kGy for crosslinking treatment. The storage stability of the hollow fiber membrane bundle obtained in this example is good, and the UV (220-350 nm) absorbance, which is the standard for approval of dialysis-type artificial kidney device production for the hollow fiber membrane bundle after storage for one year, is the maximum value. As a result, it was 0.04, and the dialysis artificial kidney device production approval reference value of 0.10 or less was maintained.

  The blood purifier was filled with pressurized air at a pressure of 0.1 MPa, and a product that passed the leak test with a pressure drop for 10 seconds of 30 mmAq or less was used in subsequent tests. Further, when the hollow fiber membrane bundle was taken out from the blood purifier and the outer surface was observed with a microscope, defects such as scratches were not observed. In addition, citrated fresh cow blood was flowed to the blood purifier at a blood flow rate of 200 mL / min and a filtration rate of 10 mL / min, but no blood cell leak was observed. The results of these analyzes are shown in Table 4.

(Comparative Example 1)
In Example 1, the waveguide of the microwave oscillator of the microwave dryer is irradiated with a structure in which the cross-sectional area is constant and the reflector at the exit of the waveguide is not installed. The microwave is changed to a microwave oscillator whose Er / Ei is 0.3, and the third stage microwave drying time is set to 15 minutes until the moisture content of the hollow fiber membrane bundle becomes 0.2% by mass. A hollow fiber membrane bundle was obtained in the same manner as in Example 1 except that the above changes were made. The water content at the time of switching from microwave drying to far-infrared drying was 3% by mass. Tables 1 to 3 show the water content, the hydrogen peroxide elution amount, and the UV absorbance measured values of the obtained dry hollow fiber membrane bundle. The amount of hydrogen peroxide eluted from the hollow fiber membrane bundle obtained in this comparative example was high, and the amount of hydrogen peroxide eluted in the longitudinal direction of the hollow fiber membrane bundle was greatly varied and the quality was low. In addition, the hollow fiber membrane bundle of this comparative example had a poor storage stability due to the high hydrogen peroxide elution amount. The hollow fiber membrane bundle in the dry state obtained in this comparative example was stored for about 35 days, and the average value of UV (220-350 nm) absorbance exceeded the dialysis-type artificial kidney device production approval reference value of 0.10. Oops. In addition, the UV (220-350 nm) absorbance of the dried hollow fiber membrane bundle varied greatly depending on the sampling site, partial sticking occurred, and the module assembly workability was poor.

  Table 4 shows the characteristic values of the module assembled in the same manner as in Example 1. Further, the storage stability of the hollow fiber membrane bundle obtained in this comparative example in a wet state is not good, and the average value of UV (220-350 nm) absorbance is about 4.5 months, and the dialysis artificial kidney device production approval standard The value has exceeded 0.10.

(Comparative Example 2)
In the method of Comparative Example 1, the hollow fiber membrane bundle was dried by microwave drying at atmospheric pressure at an output of 2.0 kW for 30 minutes, and then at an output of 0.9 kW for 10 minutes, and far infrared rays. The hollow fiber membrane bundle was obtained in the same manner as in Example 1 except that the irradiation was changed to dry for 20 minutes under normal pressure. The water content at the time of switching from microwave drying to far-infrared drying was 34% by mass. The characteristics of the obtained hollow fiber membrane bundle are shown in Tables 1-3. The variation of the moisture content of the hollow fiber membrane bundle obtained in this comparative example was high. Moreover, the hydrogen peroxide elution amount was high, and the hydrogen peroxide elution amount varied greatly depending on the sampling location, resulting in low quality. Furthermore, since the hollow fiber membrane bundle of this comparative example had a high hydrogen peroxide elution amount, the storage stability was inferior. The hollow fiber membrane bundle in the dry state obtained in this comparative example was stored for about 20 days, and the average value of UV (220-350 nm) absorbance exceeded the dialysis artificial kidney device production approval reference value of 0.10. Oops. In addition, the UV (220-350 nm) absorbance of the dried hollow fiber membrane bundle varied greatly depending on the sampling site, partial sticking occurred, and the module assembly workability was poor. Table 4 shows the characteristic values of the module assembled in the same manner as in Example 1. Further, the storage stability of the hollow fiber membrane bundle obtained in this Comparative Example in a wet state is not good, and the average value of UV (220-350 nm) absorbance is about 2.5 months, and the dialysis artificial kidney device manufacturing approval standard The value has exceeded 0.10.

(Example 2)
In the same manner as in Example 1, polyethersulfone (Sumika Chemtex, Sumika Excel (R) 4800P) 18% by mass, polyvinylpyrrolidone (BASF Kollidon (R) K-90) 3.8% by mass, dimethyl A film forming solution consisting of 73.2% by mass of acetamide (DMAc) and 5% by mass of water was obtained. As the polyvinyl pyrrolidone, one having a hydrogen peroxide content of 90 ppm was used. The obtained film-forming solution was passed through a two-stage filter of 15 μm and 15 μm, and then degassed at −700 mmHg for 2 hours in advance from a tube-in orifice nozzle heated to 70 ° C. for 50 mass at 60 ° C. The solution was discharged at the same time as the% DMAc aqueous solution, passed through a 350 mm air gap portion cut off from the outside air by a spinning tube, and then coagulated in water at 60 ° C. The average nozzle slit width of the tube-in-orifice nozzle used was 45 μm, the maximum was 45.5 μm, the minimum was 44.5 μm, the ratio of the maximum and minimum slit widths was 1.02, and the draft ratio was 1.05. It was. The hollow fiber membrane bundle pulled up from the coagulation bath was passed through a water washing tank at 85 ° C. for 45 seconds to remove the solvent and excess polyvinylpyrrolidone, and then wound up. The roller for changing the yarn path during the spinning process was a mirror-finished surface, and the fixing guide was a satin-finished surface.

  A polyethylene film similar to that of Example 1 was wrapped around a bundle of about 10,000 hollow fiber membranes, and then immersed and washed in a 40 vol% isopropanol aqueous solution at 30 ° C. for 30 minutes × 2 times. The hollow fiber membrane bundle having a water content of 2.6% by mass was obtained by drying according to the drying method of Example 1. The resulting hollow fiber membrane had an inner diameter of 199 μm and a film thickness of 27 μm.

  The obtained hollow fiber membrane bundle was equally divided into 10 pieces of 2.7 cm in the longitudinal direction, and 1 g of a dry hollow fiber membrane was weighed from each part, and the moisture content, hydrogen peroxide elution amount and UV (220- 350 nm) absorbance was quantified. The variation of moisture content was small. Further, the elution amount of hydrogen peroxide and the UV (220-350 nm) absorbance were stable at a low level in all sites. These measurement results are summarized in Tables 1 to 3. The hollow fiber membrane bundle thus obtained has good storage stability in the dry state, and the UV (220-350 nm) absorbance, which is the approval standard for dialysis-type artificial kidney device manufacture, of the hollow fiber membrane bundle after storage for 3 months is the maximum value. , It was 0.03, and the dialysis type artificial kidney device manufacturing approval reference value of 0.10 or less was maintained. Moreover, the workability of module assembly was good without occurrence of partial sticking.

  A blood purifier was assembled using the hollow fiber membrane bundle thus obtained, and the blood purifier was filled with RO water. When the outer surface of the hollow fiber membrane bundle taken out from the blood purifier was observed with a microscope, defects such as scratches were not observed, and the burst pressure was excellent. As a result of the leak test, no adhesion failure caused by the sticking of the hollow fibers was found. No blood cell leak was found in the blood leak test using bovine blood. The storage stability of the hollow fiber membrane bundle obtained in this example in a wet state is good, and UV (220-350 nm), which is a dialysis artificial kidney device manufacturing approval standard for the hollow fiber membrane bundle after storage for one year. The absorbance was 0.03 at the maximum value, and the dialysis-type artificial kidney device production approval reference value of 0.10 or less was maintained.

(Comparative Example 3)
In Example 2, polyvinyl pyrrolidone having a hydrogen peroxide content of 500 ppm is used as a raw material, and the dissolution is directly carried out in a dissolution tank having a stirrer without performing kneading, and the raw material supply system and nitrogen gas replacement at the time of dissolution are used. As a tube-in-orifice nozzle, the nozzle slit width is an average of 60 μm, the maximum 65 μm, the minimum 55 μm, the ratio of the maximum and minimum slit width is 1.18, and the hollow fiber membrane bundle is washed. Except that the drying of the hollow fiber membrane bundle is performed by microwave drying for 40 minutes at an output of 2.0 kW at normal pressure and then for 20 minutes at an output of 0.9 kW. A hollow fiber membrane bundle was obtained in the same manner as in Example 2. The moisture content at the time of switching from microwave drying to far-infrared drying was 21% by mass, and the moisture content after drying was 0.8% by mass. The characteristics of the obtained hollow fiber membrane bundle and blood purifier are shown in Tables 1 to 4.

  The amount of elution of hydrogen peroxide in the dry hollow fiber membrane bundle obtained in this comparative example was high, and the amount of elution of hydrogen peroxide varied greatly depending on the sampling location, resulting in low quality. In addition, the hollow fiber membrane bundle of this comparative example had a poor storage stability due to the high hydrogen peroxide elution amount. The hollow fiber membrane bundle obtained in this comparative example is stored in a dry state for about 15 days, and the average value of UV (220-350 nm) absorbance is already maintained at 0.10 or less of the dialysis artificial kidney device manufacturing approval standard value. I can no longer do it. Further, the UV (220-350 nm) absorbance of the dried hollow fiber membrane bundle varied greatly depending on the sampling site, and partial sticking occurred, resulting in poor module assembly workability. Furthermore, since the uneven thickness was low, the burst pressure was low and a blood leak was observed. Further, the storage stability of the hollow fiber membrane bundle obtained in this comparative example in a wet state is not good, and the average value of UV (220-350 nm) absorbance is about 2.0 months, and the dialysis artificial kidney device manufacturing approval standard The value has exceeded 0.10.

(Example 3)
In the same manner as in Example 1, 18% by mass of polysulfone (P-3500 manufactured by Amoco), 9% by mass of polyvinylpyrrolidone (Collidon (R) K-60 manufactured by BASF), 68% by mass of dimethylacetamide (DMAc), water A film forming solution consisting of 5% by mass was obtained. As the polyvinyl pyrrolidone, one having a hydrogen peroxide content of 100 ppm was used. The obtained film-forming solution was passed through a two-stage filter of 15 μm and 15 μm, and simultaneously with a 35 mass% DMAc aqueous solution at 60 ° C. which was degassed in advance as a hollow forming agent from a tube-in orifice nozzle heated to 40 ° C. After discharging and passing through a 600 mm air gap portion cut off from the outside air by a spinning tube, it was solidified in 50 ° C. water. The nozzle slit width of the tube-in-orifice nozzle used was an average of 60 μm, the maximum 61 μm, the minimum 59 μm, the ratio of the maximum and minimum slit widths was 1.03, and the draft ratio was 1.05. The hollow fiber membrane bundle pulled up from the coagulation bath was passed through a water washing tank at 85 ° C. for 45 seconds to remove the solvent and excess polyvinylpyrrolidone, and then wound up. A bundle of about 10,000 hollow fiber membranes was immersed in pure water and washed in an autoclave at 121 ° C. for 1 hour. A polyethylene film similar to that in Example 1 is wrapped around the hollow fiber membrane bundle after washing, and then dried by a method according to the drying method in Example 1, and then dried at a moisture content of 2.2% by mass. A hollow fiber membrane bundle was obtained. The roller for changing the yarn path during the spinning process was a mirror-finished surface, and the fixing guide was a satin-finished surface. The obtained hollow fiber membrane bundle had an inner diameter of 201 μm and a film thickness of 44 μm.

  As is apparent from Tables 1 to 3, the UV (220-350 nm) absorbance of the hollow fiber membrane bundle after storage for 3 months of the dry hollow fiber membrane is 0.04 at the maximum value, which is 0.04. The standard value of 0.10 or less for the type artificial kidney device manufacturing approval was maintained. Moreover, the workability of module assembly was good without occurrence of partial sticking.

  A blood purifier was assembled using the hollow fiber membrane bundle thus obtained. The blood purifier was filled with pressurized air at a pressure of 0.1 MPa, and a product that passed the leak test with a pressure drop for 10 seconds of 30 mmAq or less was used in subsequent tests. Further, when the hollow fiber membrane bundle was taken out from the blood purifier and the outer surface was observed with a microscope, defects such as scratches were not observed. In addition, citrated fresh cow blood was flowed to the blood purifier at a blood flow rate of 200 mL / min and a filtration rate of 10 mL / min, but no blood cell leak was observed. Endotoxin filtered from the outer side of the hollow fiber to the inner side of the hollow fiber was below the detection limit and was at a level with no problem. Further, the storage stability of the hollow fiber membrane bundle obtained in this example in a wet state is good, and the UV (220-350 nm) absorbance of the hollow fiber membrane bundle after storage for 1 year is the maximum value. It was 0.03, and the dialysis-type artificial kidney device manufacturing approval reference value of 0.10 or less was maintained.

Example 4
In the same manner as in Example 1, 17% by mass of polysulfone (Amoco P-1700), 5% by mass of polyvinylpyrrolidone (BASF Kollidon (R) K-60), 68% by mass of dimethylacetamide (DMAc), water A film forming solution consisting of 5% by mass was obtained. As the polyvinyl pyrrolidone, one having a hydrogen peroxide content of 110 ppm was used. The obtained film-forming solution was passed through a two-stage filter of 15 μm and 15 μm, and simultaneously with a 35 mass% DMAc aqueous solution at 65 ° C. degassed as a hollow forming agent from a tube-in orifice nozzle heated to 40 ° C. After discharging and passing through a 600 mm air gap portion cut off from the outside air by a spinning tube, it was solidified in 50 ° C. water. The nozzle slit width of the tube-in-orifice nozzle used was an average of 60 μm, the maximum 61 μm, the minimum 59 μm, the ratio of the maximum and minimum slit widths was 1.03, and the draft ratio was 1.05. The hollow fiber membrane bundle pulled up from the coagulation bath was passed through a water washing tank at 85 ° C. for 45 seconds to remove the solvent and excess polyvinylpyrrolidone, and then wound up. A bundle of about 10,000 hollow fiber membranes was immersed in pure water and washed in an autoclave at 121 ° C. for 1 hour. The roller for changing the yarn path during the spinning process was a mirror-finished surface, and the fixing guide was a satin-finished surface.

  A polyethylene film was wound around the washed hollow fiber membrane bundle, and then dried according to Example 1 so that the water content was 1.5% by mass. The resulting hollow fiber membrane had an inner diameter of 201 μm and a film thickness of 43 μm. As is clear from Tables 1 and 2, the hydrogen peroxide elution amount was stable at a low level in all sites. In addition, the storage stability of the hollow fiber membrane bundle obtained in this example in a dry state is good, and the UV (220-350 nm) absorbance of the hollow fiber membrane bundle after storage for 3 months is the maximum value. It was 0.04, and the dialysis-type artificial kidney device manufacturing approval reference value of 0.10 or less was maintained. Further, the UV (220-350 nm) absorbance of the hollow fiber membrane bundle after drying was stable at a low level in all parts, and the workability of module assembly was good without occurrence of partial sticking.

  A blood purifier was assembled using the hollow fiber membrane bundle thus obtained. The blood purifier was filled with degassed RO water and irradiated with γ rays at an absorbed dose of 25 kGy to carry out a crosslinking treatment.

  The blood purifier was filled with pressurized air at a pressure of 0.1 MPa, and a product that passed the leak test with a pressure drop for 10 seconds of 30 mmAq or less was used in subsequent tests. Further, when the hollow fiber membrane bundle was taken out from the blood purifier and the outer surface was observed with a microscope, defects such as scratches were not observed. In addition, citrated fresh cow blood was flowed to the blood purifier at a blood flow rate of 200 mL / min and a filtration rate of 10 mL / min, but no blood cell leak was observed. Endotoxin filtered from the outer side of the hollow fiber to the inner side of the hollow fiber was below the detection limit and was at a level with no problem. Further, the storage stability of the hollow fiber membrane bundle obtained in this example in a wet state is good, and the UV (220-350 nm) absorbance of the hollow fiber membrane bundle after storage for 1 year is the maximum value. It was 0.04, and the dialysis-type artificial kidney device manufacturing approval reference value of 0.10 or less was maintained.

  Conventionally, no quality control method focusing on the behavior of hydrogen peroxide in a hollow fiber membrane bundle has been known at all. The quality of the hollow fiber membrane bundle can be examined from many points of view. For example, the hollow fiber membrane bundle is cut into 27 cm in the longitudinal direction and is divided into 10 equal intervals of 2.7 cm. Measure the elution amount of hydrogen peroxide at each site. A difference A is determined based on the maximum and minimum elution amounts. And an average elution amount is calculated by averaging it. Further, the maximum value B of the difference between the maximum elution amount or the minimum elution amount and the average elution amount is set as the degree of quality variation. FIG. 1 shows a variation state of the first embodiment. In the case of Comparative Example 1, it can be obtained similarly.

  When the hydrogen peroxide elution amount is particularly about 5 ppm as a boundary, the relationship of the degree of variation in the quality of the hollow fiber membrane bundle is examined as shown in FIG. When the hydrogen peroxide elution amount increases, an unbalance occurs in the hydrogen peroxide elution amount of each part in 10 equal parts of the hollow fiber membrane bundle, so that the difference in the elution amount of each part increases. In that case, the difference in elution of hydrogen peroxide with the same material is unfavorable in terms of quality control because it affects the performance and function of the hollow fiber membrane. It can be understood that the fact that there is no unbalance in each part of the hollow fiber membrane bundle is also excellent in the quality of the hollow fiber membrane. It can be understood that the range of about 5 ppm is a critical range in terms of suppressing variation.

  3 and 4 show a hollow fiber membrane bundle in which the elution amount of hydrogen peroxide from the hollow fiber membrane bundle is suppressed to 5 ppm or less, and the UV absorbance of the extract obtained from the hollow fiber membrane bundle is suppressed to less than 0.1. The behavior of UV absorbance when stored for 3 months in a dry state and when stored for 1 year in a wet state is shown. Those whose hydrogen peroxide elution amount is suppressed to 5 ppm or less can suppress the UV absorbance to 0.1 or less even after long-term storage, so the hydrogen peroxide elution amount in the hollow fiber membrane bundle is 5 ppm or less. It can be said that suppressing it significantly contributes to quality stability.

  In the polysulfone-based permselective hollow fiber membrane bundle of the present invention, the hydrogen peroxide elution amount is suppressed, and fluctuations in the hydrogen peroxide elution amount in the longitudinal direction of the hollow fiber membrane bundle are suppressed. Degradation of polyvinylpyrrolidone and the like when a hollow fiber membrane bundle caused by hydrogen is stored for a long period of time is suppressed, so UV (220 to 350 nm) absorbance, which is a dialysis-type artificial kidney device manufacturing approval standard, even after long-term storage Can be maintained below the reference value of 0.10. In addition, the polysulfone-based permselective hollow fiber membrane bundle of the present invention has a small variation in deterioration of polyvinylpyrrolidone in the longitudinal direction of the hollow fiber membrane bundle, and is defined by the dialysis-type artificial kidney device manufacturing approval criteria in the longitudinal direction of the hollow fiber membrane bundle. When the above test was carried out, the UV (220-350 nm) absorbance fluctuation in the hollow fiber membrane extract was suppressed, so that partial sticking of the hollow fiber membrane bundle caused by this fluctuation was suppressed, and module assembly performance was improved. It has the feature that an excellent hollow fiber membrane bundle can be manufactured stably. Moreover, suppression of UV (220 to 350 nm) absorbance fluctuation in the longitudinal direction of the hollow fiber membrane bundle also leads to an improvement in safety when used for blood purification. Therefore, there is an advantage that it is suitable for a blood purifier having high water permeability used for the treatment of chronic renal failure. Therefore, it is important to contribute to the industry.

The schematic diagram which shows the hydrogen peroxide elution amount of each site | part when a hollow fiber membrane is equally divided into ten. The schematic diagram which shows the variation degree of the quality in a hollow fiber membrane bundle. The schematic diagram which shows the relationship between the storage period of the hollow fiber membrane bundle of a dry state, and UV light absorbency. The schematic diagram which shows the relationship between the storage period of the hollow fiber membrane bundle of a wet state, and UV light absorbency. The schematic diagram which shows the correlation with the drying time and moisture content of a hollow fiber membrane bundle. The schematic diagram which shows the relationship between a dry switching moisture content and the variation degree of quality. The schematic diagram which shows the relationship between the moisture content of a hollow fiber membrane bundle, and the hydrogen peroxide maximum elution amount range.

Claims (5)

In the polysulfone-based hollow fiber membrane containing polyvinylpyrrolidone using polyvinylpyrrolidone having a hydrogen peroxide content of 300 ppm or less as a raw material, the polysulfone-based polymer in the membrane is 99 to 80% by mass, and the polyvinylpyrrolidone is 1 to 20% by mass. The thickness of the hollow fiber membrane is 0.6 or more, the hydrogen peroxide elution amount of all the parts of the hollow fiber membrane bundle divided into 10 in the longitudinal direction is 5 ppm or less, and the maximum elution of hydrogen peroxide A polysulfone-based permselective hollow fiber membrane bundle having a volume difference of 5 ppm or less and a final moisture content of 1 to 7% by mass .   In a polysulfone-based hollow fiber membrane containing a hydrophilic polymer, the hollow fiber membrane bundle was divided into 10 pieces in the longitudinal direction, and each was subjected to a test defined by the dialysis-type artificial kidney device manufacturing approval criteria. The maximum value of UV (220 to 350 nm) absorbance in the yarn membrane extract is less than 0.10, and the difference between the maximum and minimum UV (220 to 350 nm) absorbance in the same hollow fiber membrane bundle is 0.05 or less. The polysulfone-based permselective hollow fiber membrane bundle according to claim 1, wherein   The polysulfone-based permselectivity according to claim 1 or 2, wherein when the hollow fiber membrane bundle in a dry state is divided into 10 pieces in the longitudinal direction and the water content of each is measured, the fluctuation rate of the water content is within 10%. Hollow fiber membrane bundle.   The polysulfone-based permselective hollow fiber membrane bundle according to any one of claims 1 to 3, wherein there is no partial fixation in the longitudinal direction of the hollow fiber membrane bundle. The polysulfone-based permselective hollow fiber membrane bundle according to any one of claims 1 to 4 , which is used for a blood purifier.

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