JP2006204876A - Method of manufacturing polysulfone-based hollow fiber membrane - Google Patents

Abstract

<P>PROBLEM TO BE SOLVED: To provide a manufacturing method of a polysulfone-based hollow fiber membrane suitable for a blood dialyzing method hollow fiber type blood purifier having high safety and stability of performance, and having high water permeable performance particularly used for a treatment of chronic renal failure. <P>SOLUTION: This invention is a manufacturing method of the polysulfone-based hollow fiber membrane characterized by maintaining at 70°C or less up to supplying a provided spinning solution to a spinning process, by preparing the spinning solution by dissolving at least three components composed of polyvinyl pyrolidone, a polysulfone-based high polymer and a common solvent of these at 70°C or less in an inert gas atmosphere. <P>COPYRIGHT: (C)2006,JPO&NCIPI

Description

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

  In blood purification therapy for the treatment of renal failure, natural materials such as cellulose, cellulose diacetate, cellulose triacetate, and synthetic polymers such as polysulfone and polysulfate are used to remove urine toxins and waste products in the blood. Modules such as hemodialyzers, hemofilters or hemodialyzers using dialysis membranes using polymers such as methyl methacrylate and polyacrylonitrile and ultrafiltration membranes as separation materials are 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.

  Among the above-mentioned membrane materials, polysulfone-based resins having high water permeability are attracting attention as the best match with the progress of dialysis technology. However, when a semi-permeable membrane is made of a single polysulfone, the polysulfone resin is hydrophobic, so it has poor affinity with blood and causes an air lock phenomenon. Can not.

As a method for solving the above-described problems, a method has been proposed in which a hydrophilic polymer is blended with a polysulfone-based resin to form a film, thereby imparting hydrophilicity to the film. For example, a method of blending a polyhydric alcohol such as polyethylene glycol is disclosed (for example, see Patent Documents 1 and 2).
JP-A-61-232860 JP 58-114702 A

Moreover, the method of mix | blending polyvinylpyrrolidone is disclosed (for example, refer patent document 3, 4).
Japanese Patent Publication No. 5-54373 Japanese Examined Patent Publication No. 6-75667

In particular, the latter method using polyvinyl pyrrolidone is attracting attention from the viewpoint of safety and economy, and the above-described problems are solved by this method. However, in the hydrophilization technique by blending a hydrophilic polymer, there arises a problem that the hydrophilic polymer is eluted and mixed into purified blood during dialysis. When elution of the hydrophilic polymer increases, the hydrophilic polymer, which is a foreign substance taken up by the human body, increases in the body during long-term dialysis and may cause side effects and complications. Therefore, the elution amount of the hydrophilic polymer is determined by the dialysis artificial kidney device manufacturing approval standard. In the dialysis artificial kidney device production approval standard, the amount of elution of polyvinylpyrrolidone and the like is quantified by UV absorbance. Techniques have been disclosed for determining the effect of elution control based on the dialysis-type artificial kidney device manufacturing approval criteria (see, for example, Patent Documents 5 to 7). Patent Document 8 discloses a semipermeable membrane for blood treatment in which the elution amount of hydrophilic polymer from the semipermeable membrane is 10 ppm or less. This document discloses a technique for suppressing elution of a hydrophilic polymer from a semipermeable membrane for blood treatment, but it is a process related to deterioration / degradation of the hydrophilic polymer over time, which extends to storage of a hollow fiber membrane. No mention is made of the effects of hydrogen oxide.
Japanese Patent No. 3314861 JP-A-6-165926 JP 2000-350926 A JP 2001-170171 A

  As a result of detailed studies on the elution behavior of the polyvinyl pyrrolidone, the present inventors have found that the extract extracted by the test method defined by the above dialysis-type artificial kidney device manufacturing approval criteria contains a conventionally known UV absorbance. Then, it was found that hydrogen peroxide that cannot be measured was included. When hydrogen peroxide is present in the blood purifier and in the hollow fiber membrane, for example, the oxidative degradation of polyvinyl pyrrolidone is promoted, and the storage stability of the polyvinyl pyrrolidone elution increases when the hollow fiber membrane is stored. I found a thing.

  Furthermore, in the prior art disclosed in Patent Documents 5 to 8 described above, all have been evaluated for specific parts of the hollow fiber membrane. Actually, it has been found that when the treatment such as drying of the hollow fiber membrane is performed in module assembly or the like, the above-described elution amount largely varies in the hollow fiber membrane due to the influence of fluctuations in the drying conditions, etc. Only the evaluation cannot satisfy the high safety requirement. In particular, when hydrogen peroxide as clarified by the present inventors is present in a specific part of the hollow fiber membrane, the deterioration reaction of the hollow fiber membrane material is started from that point and propagates to the entire hollow fiber membrane. It is necessary to ensure that the amount of the hollow fiber membrane used in the module in the longitudinal direction is below a certain amount over the entire region.

Many methods including the above-mentioned Patent Documents 7 and 8 have been disclosed for reducing the amount of polyvinylpyrrolidone eluted by crosslinking treatment of polyvinylpyrrolidone (see, for example, Patent Documents 9 to 18). However, since the crosslinking treatment tends to deteriorate characteristics such as blood compatibility and protein separation selectivity, establishment of a production method in which the elution amount is suppressed after eliminating the crosslinking treatment is desired.
JP-A-6-339620 JP-A-9-70524 JP-A-9-70525 Japanese Patent Laid-Open No. 9-70526 JP-A-9-103664 Japanese Patent Laid-Open No. 10-230148 JP 2001-170167 A JP 2003-201383 A JP 2003-245526 A Japanese Patent No. 3474205

When the polysulfone is molded by the solution method, the polysulfone solution is prevented from becoming clouded due to precipitation of the polysulfone oligomer contained in the polysulfone by maintaining dissolution, liquid feeding, filtration, etc. in the solvent at a temperature of 80 ° C. or higher. A preparation method is disclosed, and a method for producing a hollow fiber membrane in a system containing polyvinylpyrrolidone as a hydrophilic polymer is exemplified (see Patent Document 19).
However, no consideration is given to the deterioration of the components during the production, the generation of hydrogen peroxide as described above, and the long-term stability of the resulting hollow fiber membrane.
Japanese Patent Laid-Open No. 11-60738

In the production of a hollow fiber membrane composed of a polysulfone-based resin and polyvinylpyrrolidone, examples in which dissolution takes place over a long time at a low temperature are described in the examples (see, for example, Patent Documents 20 and 21).
However, no consideration is given to the atmosphere during dissolution. There is no mention of the effect of low-temperature dissolution.
Japanese Patent Laid-Open No. 11-350239 JP 2000-140589 A

  The present invention provides a method for producing a polysulfone-based hollow fiber membrane suitable for use in hemodialysis hollow fiber blood purifiers, etc., which has high safety and stability in performance and has high water permeability especially used for the treatment of chronic renal failure. There is to do.

In the present invention, a spinning solution is prepared by dissolving at least three components comprising polyvinylpyrrolidone, a polysulfone polymer and a common solvent thereof under an inert gas atmosphere at 70 ° C. or less, and the obtained spinning solution is used in a spinning process. It is the manufacturing method of the polysulfone type | system | group hollow fiber membrane characterized by maintaining below 70 degreeC until supply.
In this case, it is preferable that the storage time until the spinning solution is used in the spinning step after dissolution is a maximum of 3 days (72 hours).
Moreover, in this case, it is preferable to dissolve under conditions where the fluid number is 0.7 to 1.3 and the stirring Reynolds number is 50 to 250.
In this case, it is preferable that the supply of the polysulfone polymer and polyvinyl pyrrolidone to the dissolution tank is divided at least twice and the polysulfone polymer and polyvinyl pyrrolidone are alternately supplied and dissolved.
In this case, it is preferable that the components of the hollow fiber membrane are pre-kneaded and then supplied to the dissolution tank for dissolution.
In this case, the spinning solution is preferably prepared in a dissolution tank having a kneading function.
Further, in this case, it is preferable to perform dissolution during preparation of the spinning solution within 10 hours.
In this case, it is preferable that at least the supply of polyvinylpyrrolidone, the kneading, and the storage of the spinning solution are performed in an inert gas atmosphere.
In this case, it is preferable that the oxygen concentration in the system in the dissolving step is 1% by volume or less.
In this case, it is preferable to use polyvinyl pyrrolidone having a hydrogen peroxide content of 300 ppm or less.
In this case, it is preferable that polyvinyl pyrrolidone is not substantially crosslinked.

  The production method of the polysulfone-based hollow fiber membrane of the present invention suppresses the generation of hydrogen peroxide due to the deterioration of the components in the preparation of the spinning solution during the production process and the storage process, in particular, the oxidative degradation of polyvinylpyrrolidone. A hollow fiber membrane with a small amount of hydrogen peroxide elution can be obtained. Therefore, when hollow fiber membranes are stored for a long period of time, degradation of polyvinyl pyrrolidone and the like caused by the hydrogen peroxide is suppressed. The maximum value of UV (220-350 nm) absorbance can be maintained at 0.10 or less, so that there is an advantage that it can be suitably used for blood purifiers used for the treatment of chronic renal failure. Moreover, there exists an advantage that the above-mentioned hollow fiber membrane can be manufactured economically and stably by the manufacturing method of this invention.

Hereinafter, the present invention will be described in detail.
The hollow fiber membrane used in the present invention is characterized by being 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 in terms of hydrophilicity imparting efficiency, while it is preferable to use a high molecular weight in terms of reducing the amount of elution, but depending on the required characteristics of the final hollow fiber membrane, Selected. 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.

  The method for producing the permselective hollow fiber membrane of the present invention is not limited in any way, but a hollow fiber membrane type that can be produced by a method as disclosed in, for example, Japanese Patent Application Laid-Open No. 2000-300663 is preferable. 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 composition ratio of the polyvinyl pyrrolidone in the membrane with respect to the polysulfone polymer in the present invention is not limited as long as it is in a range that can provide sufficient hydrophilicity and high water content to the hollow fiber membrane, and the polysulfone polymer is 99 to 80% by mass. The polyvinyl pyrrolidone content is preferably 1 to 20% by mass. When the proportion of polyvinyl pyrrolidone relative to the polysulfone-based polymer is too small, the effect of imparting hydrophilicity to the membrane may be insufficient. Therefore, the proportion is more preferably 1.5% by mass or more, and 2.0% by mass. The above is more preferable, and 2.5% by mass or more is more preferable. On the other hand, when the ratio is too large, the hydrophilicity-imparting effect 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 exceeds 10 ppm. There is a case. 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.

  The hollow fiber membrane obtained in the present invention preferably has an elution amount of hydrogen peroxide of 5 ppm or less. 4 ppm or less is more preferable, and 3 ppm or less is more preferable. When the elution amount of the hydrogen peroxide exceeds 5 ppm, as described above, the storage stability deteriorates due to the oxidative degradation of the polyvinyl pyrrolidone by the hydrogen peroxide. For example, the elution of the polyvinyl pyrrolidone when stored for a long period of time. The amount 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 caused by deterioration caused by the oxidizing action of hydrogen peroxide during long-term storage can be evaluated by measuring UV (220-350 nm) absorbance set by the dialysis-type artificial kidney device manufacturing approval standard.

  The elution amount of hydrogen peroxide was also quantified using an extract extracted by a method according to the dissolution test method of the dialysis artificial kidney device manufacturing approval standard. That is, the hollow fiber membrane is arbitrarily taken out from the dry hollow fiber membrane, and 1.0 g is weighed. The extract obtained by adding 100 ml of RO water and extracting at 70 ° C. for 1 hour was quantified.

  As described above, even when hydrogen peroxide is present in a specific part of the hollow fiber membrane, the deterioration reaction of the hollow fiber membrane material starts from that point and propagates to the entire hollow fiber membrane, so it is used as a module. The abundance in the length direction of the hollow fiber membrane needs to be secured below a certain amount over the entire region. That is, the oxidative degradation of polyvinyl pyrrolidone initiated by hydrogen peroxide at a specific site spreads throughout the hollow fiber membrane, and the amount of hydrogen peroxide further increases due to the degradation. The degraded polyvinyl pyrrolidone has a molecular weight. Since it falls, it becomes easy to elute from a hollow fiber membrane. This deterioration reaction proceeds in a chain. Accordingly, when the hollow fiber membrane 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 for a blood purifier. Therefore, in the present invention, it is a preferred embodiment that the hydrogen peroxide elution amount is 5 ppm or less at all sites when it is divided into 10 pieces in the longitudinal direction of the hollow fiber membrane and measured for each. 3 ppm or less is more preferable, and 2 ppm or less is more preferable.

  In addition, the polysulfone-based hollow fiber membrane obtained by the method of the present invention is obtained by sterilizing a blood purifier produced using the hollow fiber membrane and storing the hollow fiber membrane in the module in the longitudinal direction after storage at room temperature for 1 year. When the UV (220 to 350 nm) absorbance in the extract of the hollow fiber membrane when the test determined according to the dialysis-type artificial kidney device manufacturing approval criteria was performed, the maximum value when each was measured was 0.00. It is preferable that it is 10 or less. More preferably, it is 0.08 or less. In the case of a module in which a liquid is filled in the module, the filling liquid is first withdrawn, and then pure water is allowed to flow at 500 mL / min for 5 minutes in the dialysate side flow path, and then pure water is similarly applied to the blood side flow path. Flow for 5 minutes at 200 mL / min. Finally, 200 mL / min of pure water is passed through the membrane from the blood side to the dialysate side to finish the washing process. A hollow fiber membrane is taken out from the obtained module and freeze-dried to obtain a measurement sample. In the case of a dry hollow fiber membrane module, the same washing treatment is performed to obtain a measurement sample.

  In the present invention, the amount of polyvinylpyrrolidone eluted from the hollow fiber membrane is preferably 10 ppm or less. When the elution amount exceeds 10 ppm, side effects and complications during long-term dialysis due to the eluted polyvinylpyrrolidone may occur. A method for satisfying the characteristics is optional without limitation, and can be achieved, for example, by setting the composition ratio of polyvinyl pyrrolidone to the polysulfone-based polymer within the above range or optimizing the film forming conditions of the hollow fiber membrane. More preferably, the elution amount of polyvinylpyrrolidone is 9 ppm or less, more preferably 8 ppm or less, and still more preferably 7 ppm or less. In addition, from the viewpoint of safety to living organisms, it is preferable that the amount of polyvinylpyrrolidone eluted is zero, but if the amount of polyvinylpyrrolidone eluted is zero, the degree of hydrophilicity of the blood contact surface decreases and blood compatibility is low. Therefore, it is considered that the elution amount of the hydrophilic polymer is about 0.1 ppm.

  As described above, a method of crosslinking polyvinylpyrrolidone is known as a measure for suppressing the elution amount of polyvinylpyrrolidone from the hollow fiber membrane, but the crosslinking treatment deteriorates characteristics such as blood compatibility and protein separation selectivity. In the present invention, it is preferable to eliminate the crosslinking treatment. Therefore, in the method that excludes the crosslinking treatment, it is necessary to enhance the technique for suppressing the amount of elution.

  The present invention has been completed through intensive studies aimed at establishing a production method capable of economically and stably producing a polysulfone-based hollow fiber membrane satisfying the above characteristics. That is, the present inventor has disclosed a method for producing a hollow fiber membrane in which the generation of hydrogen peroxide which hinders the quality, performance, handling, etc. of the hollow fiber membrane is suppressed to, for example, 10 ppm or less as much as possible. As a result of pursuing a method for solving the problem from the viewpoint, the handling conditions of the spinning solution are involved, that is, the production method of the polysulfone-based hollow fiber membrane in consideration of the spinning solution adjustment process is remarkably effective in solving the problem. It has been found that it is beneficial.

  In the present invention, in the method for producing a hollow fiber membrane consisting essentially of polyvinylpyrrolidone and a polysulfone-based polymer, at least three components comprising polyvinylpyrrolidone, a polysulfone-based polymer and a common solvent thereof under an inert gas atmosphere, The condition of preparing a spinning solution by dissolving at 70 ° C. or lower and maintaining the obtained spinning solution at 70 ° C. or lower until the spinning solution is supplied to the spinning process is preferable in order to obtain a hollow fiber membrane of good quality. The temperature from the melting step to the spinning step after the melting step is more preferably 65 ° C. or lower, and further preferably 60 ° C. or lower. In view of the dissolution time and running cost described later, the dissolution temperature is preferably 5 ° C. or higher, more preferably 10 ° C. or higher.

  When the behavior of how the spinning solution preparation temperature affects the manufactured hollow fiber membrane product is analyzed, as shown in FIG. 1, when the temperature is increased, the generation of hydrogen peroxide is promoted. Become a trend. When polyvinyl pyrrolidone and polysulfone-based polymer materials are dissolved in a common solvent, the time and stirring conditions are also affected, but if only the temperature conditions are considered, the dissolution temperature is, for example, 30 ° C rather than 30 ° C. It is possible that the speed will increase. Furthermore, when the dissolution temperature is 80 ° C., it can be easily assumed that the dissolution rate tends to increase further. However, it cannot be denied that dissolving polyvinyl pyrrolidone under severe conditions such as high temperature and stirring causes the damage and deterioration of polyvinyl pyrrolidone to be accelerated. In addition, the solvent volatility at high temperatures and the working conditions in a high temperature environment are significantly hindered.

  On the other hand, keeping the dissolution temperature as low as 30 ° C., for example, requires much time for dissolving polyvinylpyrrolidone as compared with 80 ° C., for example. Exposing polyvinyl pyrrolidone for a long time in a high temperature environment increases deterioration and damage of polyvinyl pyrrolidone, so that appropriate dissolution conditions are naturally set. FIG. 1 shows such a tendency. FIG. 1 shows that if the spinning solution is prepared at a relatively low temperature, the generation of hydrogen peroxide after a certain time (for example, 2 hours) is less likely to occur. For example, if the preparation time of the spinning solution is set to 2 hours and the behavior is observed, the spinning solution prepared at 30 ° C. lower than 80 ° C. is advantageous from the viewpoint of hydrogen peroxide generation. However, since the dissolution rate is slow at 30 ° C., it takes a long time to dissolve and eventually puts it in an environment where hydrogen peroxide is generated, resulting in a contradictory relationship. As a result of pursuing technical conditions relating to the preparation of the spinning solution from these technical viewpoints, the present inventors have found the optimum requirements. That is, the fact that the dissolution temperature in the preparation of the spinning solution containing polyvinylpyrrolidone is acceptable is 70 ° C. or less with respect to the generation of hydrogen peroxide is investigated. On the other hand, the preparation of a stable spinning solution has also been found out that there is no blur when carried out in an inert gas atmosphere, and that a stable hollow fiber membrane product can be prepared in a reliable and reliable state for quality control. . In an inert gas atmosphere, simply having a mechanism of blocking the direct influence of oxygen present in the atmosphere and suppressing the generation of hydrogen peroxide may be possible. Since the accompanying effect of suppressing the occurrence due to deterioration is also conceivable, it is technically difficult to grasp the details of the detailed mechanism at this stage.

  Then, when the spinning solution is set to about 70 ° C. or lower, the allowable dissolution time is naturally limited. Similarly, the deterioration is affected by the dissolution time and subsequent storage time. Therefore, at the spinning solution preparation temperature of 70 ° C. or less of the present invention, the dissolution time is preferably completed within 10 hours. Within 8 hours is more preferred, and within 6 hours is even more preferred. In addition, the storage time of the spinning solution until it is used for spinning including the filtration step after dissolution is preferably 3 days (72 hours) at maximum. Within 2 days is more preferred, and within 1 day is even more preferred. Longer time is not preferable because deterioration tends to increase. The storage time is somewhat affected by the storage temperature, but the storage time includes the time when the storage time is stored in the dissolution tank after the completion of dissolution. The shorter the storage time, the more oxidative degradation of polyvinylpyrrolidone is suppressed. The analysis of the behavior from the viewpoint of the overall temperature is based on the knowledge of the present inventors, and is also a specific preparation specification focusing on the temperature in the technical field dealing with polyvinylpyrrolidone. The technical considerations from No. 1 contributed significantly to improving the quality of hollow fiber membranes.

  When the maintenance temperature of the process such as storage after the dissolution exceeds 70 ° C., as shown in FIG. 1, the degradation of polyvinyl pyrrolidone, particularly the oxidative degradation, increases the molecular weight of polyvinyl pyrrolidone and the generation of hydrogen peroxide. Increase. According to the study by the inventors, the molecular weight of polyvinylpyrrolidone moves in the direction of decomposition (shifts to the low molecular side) as the dissolution temperature increases, or the shoulder that seems to be a decomposed product on the low molecular side. The phenomenon that appears was observed. Decreasing the molecular weight of polyvinylpyrrolidone blends the degradation product of polyvinylpyrrolidone into the permselective hollow fiber membrane, leading to an increase in the amount of elution from the hollow fiber membrane produced using the spinning solution, and elution of polyvinylpyrrolidone. The UV (220-350 nm) absorbance in the extract of the hollow fiber membrane is deteriorated when the amount is increased or the test defined by the dialysis-type artificial kidney device manufacturing approval standard is carried out. FIG. 2 shows the relationship between the spinning solution preparation temperature (° C.) and the PVP elution amount (ppm) with reference to Examples and Comparative Examples. Similarly, FIG. 3 shows the relationship between the spinning solution preparation temperature (° C.) and the UV absorbance with reference to Examples and Comparative Examples. If the tendency of these FIGS. 1-3 is analyzed, it is very important that the spinning solution preparation temperature is 70 degrees C or less in terms of maintaining the high quality of the hollow fiber membrane, and has a critical technical meaning. This is clearly expressed. Furthermore, if the adverse effect of increasing the production of hydrogen peroxide is described in detail, the long-term stability of the hollow fiber membrane produced using the spinning solution is deteriorated as described above, which is not preferable. Therefore, for example, when the obtained hollow fiber membrane is used for blood purification, a degradation product is eluted in the blood, and it has not been excellent in terms of product quality safety.

  When the maintenance temperature of the process such as storage and the subsequent storage exceeds 70 ° C., the degradation of polyvinyl pyrrolidone, particularly the oxidative degradation increases, and the molecular weight of polyvinyl pyrrolidone decreases and the generation of hydrogen peroxide increases. According to the study by the inventors, the molecular weight of polyvinylpyrrolidone moves in the direction of decomposition (shifts to the low molecular side) as the dissolution temperature increases, or the shoulder that seems to be a decomposed product on the low molecular side. The phenomenon that appears was observed. Decreasing the molecular weight of polyvinylpyrrolidone blends the degradation product of polyvinylpyrrolidone into the permselective hollow fiber membrane, leading to an increase in the amount of elution from the hollow fiber membrane produced using the spinning solution, and elution of polyvinylpyrrolidone. The UV (220-350 nm) absorbance in the extract of the hollow fiber membrane is deteriorated when the amount is increased or the test defined by the dialysis-type artificial kidney device manufacturing approval standard is carried out. On the other hand, when the production of hydrogen peroxide is increased, the long-term stability of the hollow fiber membrane produced using the spinning solution as described above is not preferable. Therefore, for example, when the obtained hollow fiber membrane is used for blood purification, a degradation product is eluted in the blood, and it has not been excellent in terms of product quality safety.

The dissolution method is not limited as long as the above requirements are satisfied. For example, a dissolution method using a stirring type dissolution apparatus can be applied. As the shape of the stirring blade used for dissolving the low-viscosity film forming solution used in the present invention, a radial flow type blade such as a disk turbine type, paddle type, curved blade fan turbine type, arrow blade turbine type, propeller type, inclined type, etc. Examples include, but are not limited to, an axial flow type blade such as a paddle type and a fiddler type. 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 or more and 1.3 or less, 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. 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 long defoaming time or insufficient defoaming occurs due to entrapment of bubbles in the film-forming solution during stirring. 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 55 or more, further preferably 60 or more, still more preferably 65 or more, and particularly preferably 70 or more. Further, when a hollow fiber membrane is formed with such a spinning solution, the operation is deteriorated due to a decrease in spinnability due to bubbles, and in terms of quality, the portion becomes defective due to the entrapment of bubbles in the hollow fiber membrane, and the membrane is not confidential. It has been found that this causes problems such as decreased sex and burst pressure. Defoaming of the spinning solution is an effective countermeasure, but it may involve a change in the composition of the spinning solution due to viscosity control of the spinning solution or evaporation of the solvent.

The dissolution is preferably carried out in an inert gas atmosphere. Nitrogen, argon, etc. are raised as the inert gas, but nitrogen is preferably used. For example, the residual oxygen concentration in the dissolution tank is preferably 1% or less. If the nitrogen filling pressure is increased, the melting time can be shortened. However, in order to increase the pressure, the equipment cost is increased, and from the viewpoint of work safety, atmospheric pressure and 2 kgf / cm ² or less are preferable. By carrying out under the inert gas atmosphere, the polyvinyl pyrrolidone at the time of dissolution is suppressed from coming into contact with oxygen gas, and thus synergistically with the effects of lowering the dissolution temperature and shortening the dissolution time, Oxidation deterioration is suppressed, and the above-described effect is further increased.

  The method for supplying the polysulfone-based polymer or polyvinylpyrrolidone to the dissolution tank at the time of dissolution is also not limited, but it is preferable to divide each into two or more times and alternately supply both to dissolve. When polyvinyl pyrrolidone is dissolved at low temperature, polyvinyl pyrrolidone becomes lumpy and has a problem that it becomes difficult to dissolve further or it takes a long time for uniform dissolution. However, this embodiment can avoid this problem. , Low temperature and short time melting is possible.

  In addition, kneading the components constituting the spinning solution prior to dissolution is also a preferred method for achieving low temperature and short time dissolution and is recommended. 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. The method of kneading only polyvinylpyrrolidone and a 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 carried out by providing a kneading line separately from the dissolving tank and supplied to the dissolving tank, or both 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. 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.

  Regarding the spinning solution dissolving step, for example, when stirring and dissolving a spinning solution comprising a polysulfone polymer, polyvinyl pyrrolidone, and a solvent, if polyvinyl pyrrolidone contains hydrogen peroxide, it is present in the dissolving tank. It was found that hydrogen peroxide increased explosively due to the influence of oxygen to be heated and the influence of 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.

  For the above reasons, in the present invention, it is preferable to produce a hollow fiber membrane using polyvinylpyrrolidone having a hydrogen peroxide content of 300 ppm or less. By making the hydrogen peroxide content in the polyvinyl pyrrolidone used as a raw material 300 ppm or less, it becomes possible to bring the hydrogen peroxide elution amount into the above-mentioned preferable range, and to stabilize the quality of the hollow fiber membrane obtained in the present invention. 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 content of hydrogen peroxide in polyvinyl pyrrolidone used as a raw material is preferably zero, but it is technically and costly difficult to make it completely zero. If the hydrogen peroxide content in the raw material polyvinylpyrrolidone is 50 ppm or less, it is considered acceptable. More preferably, it is 40 ppm or less, More preferably, it is 30 ppm or less, More preferably, it is 20 ppm or less.

  If hydrogen peroxide is present in the polyvinyl pyrrolidone used as the raw material, it is considered that the oxidative deterioration of the polyvinyl pyrrolidone is triggered, and the oxidative deterioration proceeds in a chain manner to promote the oxidative deterioration of the polyvinyl pyrrolidone. 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 it with an inert gas such as nitrogen gas, or to 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. In addition, in the manufacturing process of the hollow fiber membrane, 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. Moreover, it is not excluded to use polyvinylpyrrolidone in which the amount of hydrogen peroxide is reduced by a recrystallization method or an extraction method.

  In the present invention, it is preferable to carry out all the steps in an inert gas atmosphere in the system in which polyvinylpyrrolidone is present, including the steps described above.

  In order to suppress the degradation of polyvinyl pyrrolidone and control the elution amount of hydrogen peroxide within the regulated range, it is important to reduce the contact with oxygen gas even in the drying process of the hollow fiber membrane. For example, drying in an atmosphere substituted with an inert gas can be mentioned, but it is disadvantageous in terms of economy. As an economical drying method, a method of drying by irradiating microwaves under reduced pressure is effective and recommended. In particular, a drying method combining microwave irradiation and far-infrared irradiation is preferable. That is, microwave irradiation drying with high drying efficiency is performed in a region where the moisture content in the hollow fiber membrane is high, and when the moisture content decreases, the hollow fiber membrane is likely to be deteriorated by microwave irradiation drying. A method of completing the drying by switching to the far-infrared irradiation that suppresses the deterioration of the hollow fiber membrane when the water content is reduced is preferable. It is preferable to stop the microwave irradiation when the water content in the hollow fiber membrane is reduced to 10 to 20% by mass, and subsequently dry by far infrared irradiation. 10-15 mass% is more preferable. Drying by microwave irradiation to a moisture content of less than 10% by mass is not preferable because deterioration of polyvinylpyrrolidone increases, the amount of hydrogen peroxide extracted increases, and the storage stability of the hollow fiber membrane decreases. In addition, the moisture content in the longitudinal direction of the hollow fiber membrane and the fluctuation rate of UV (220 to 350 nm) absorbance increase, and the occurrence of partial sticking of the hollow fiber membrane increases, which is not preferable. On the contrary, if microwave irradiation is stopped when it exceeds 20% by mass, the total drying time until drying to the final moisture content becomes longer, which is not preferable.

  Total drying is completed by drying with far-infrared irradiation after the above-described microwave irradiation in the present invention. The water content in the hollow fiber membrane after the drying is preferably 1 to 7% by mass. Moreover, it is preferable that each moisture content fluctuation | variation rate is 10% or less when this dry hollow fiber membrane is divided | segmented into 10 to a longitudinal direction and measured. In addition, when the moisture content exceeds 10% by mass, bacteria may be easily proliferated during storage, the yarn may be crushed due to the weight of the hollow fiber membrane, and adhesion failure of the adhesive may occur during module assembly. Is not preferable.

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.

  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 water content by irradiating with microwaves in a state where the moisture content in the hollow fiber membrane is low has not been clarified, drying by microwave This is because water molecules are directly excited by microwaves and the water in the hollow fiber membrane has a strong affinity for polyvinyl pyrrolidone and is localized in the portion where polyvinyl pyrrolidone exists. It is presumed that That is, this water localization increases as the water content decreases, heat generation at the localized portion of the water increases, leading to non-uniform temperature and dryness of the hollow fiber membrane, and around the water molecules It is presumed that deterioration is promoted due to the presence of polyvinylpyrrolidone. On the other hand, since far-infrared drying and the like have lower excitation energy than microwaves, it is considered that the occurrence of the above problems is suppressed.

  The moisture 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-described microwave irradiation or far-infrared irradiation in an inert gas atmosphere such as nitrogen gas, but it is economically disadvantageous. On the other hand, a method of suppressing oxidation deterioration by performing microwave drying or far-infrared drying under reduced pressure leads to improvement in drying efficiency and is recommended because it is economical. In the most preferred embodiment, both drying operations are performed under reduced pressure. For example, as a drying condition for microwave drying, 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, it is a preferable embodiment that the frequency of the microwave is 1,000 to 5,000 MHz, and the highest temperature reached by the hollow fiber membrane during the drying process is 90 ° C. or less. If a means of decompression is also provided, drying 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 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 central part and the outer peripheral part of the hollow fiber membrane, the evaporation of moisture is promoted uniformly, and the hollow fiber membrane is uniformly dried. Therefore, the failure of the hollow fiber membrane due to nonuniform drying is corrected. In addition, heating by microwaves acts almost equally on the entire center and outer periphery of the hollow fiber membrane, so it functions synergistically in uniform heating, and has a unique significance in drying the hollow fiber membrane. There will be. The degree of vacuum may be set as appropriate depending on the output of the microwave, the total moisture content of the hollow fiber membranes, and the number of hollow fiber membranes, but the degree of vacuum is 20 kPa or less in order to prevent the temperature of the hollow fiber membranes during drying. Preferably it is 15 kPa or less, More preferably, it is 10 kPa or less. If it is 20 kPa or more, not only the water evaporation efficiency is lowered, but also the temperature of the polymer forming the hollow fiber membrane may be increased and deteriorated. Moreover, although the one where a pressure reduction degree is higher is preferable in the meaning which suppresses a temperature rise and raises 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 membranes containing polyvinylpyrrolidone, polyvinylpyrrolidone is deteriorated or decomposed due to overdrying or overheating, and wettability is reduced during use. It is preferable not to raise the output much because there are problems such as occurring. In addition, it is possible to dry the hollow fiber membrane even with an output of less than 0.1 kW, but there is a possibility that a problem of a decrease 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 moisture content of the hollow fiber membrane and the number of processed hollow fiber membranes, 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 membranes having a moisture content of 50 g per hollow fiber membrane 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 degree of decompression 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. A multi-stage drying method in which the output of the microwave is sequentially reduced in accordance with the progress of drying of the hollow fiber membrane when drying with microwaves at a relatively low temperature of about 30 to 90 ° C. under reduced pressure. 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, when relatively large, multi-stage drying is, for example, at a temperature of 90 ° C. or less under a reduced pressure of about 5 to 20 kPa, and the first stage is in the range of 30 to 100 kW. Thus, 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.

  To explain another aspect, when the so-called moisture content is less than 400% by mass, in which the total amount of water in the hollow fiber membrane is relatively small, irradiation with a low-power microwave of 12 kW or less may be excellent. For example, when the water content of the total amount of the hollow fiber membrane is a relatively small amount of 1 to 7 kg, an output of 12 kW or less under a reduced pressure of 3 to 10 kPa at a temperature of 80 ° C. or less, preferably 60 ° C. or less, for example, 10 to 240 minutes with microwaves of 1 to 5 kW, 1 to 240 minutes with microwaves of less than 0.5 to 1 kW, more preferably 3 to 240 minutes, 1 to 240 with microwaves of less than 0.1 to 0.5 kW If the irradiation output of the microphone mouth wave and the irradiation time are adjusted in accordance with the degree of drying, that is, partial irradiation, 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 degree of pressure reduction at each stage, in which the microwave is irradiated at a pressure slightly higher 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. It is possible to arbitrarily set the appropriate adjustment in accordance with the change in consideration of the transition of the total moisture content and the moisture content of the hollow fiber membrane. 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 during drying can be measured by attaching an irreversible thermolabel to the side of the film that protects the hollow fiber membrane, drying, and taking out and confirming the display after drying. At this time, the maximum temperature reached by the hollow fiber membrane 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 hollow fiber membranes containing polyvinyl pyrrolidone, it is necessary to prevent the temperature rise as much as possible because polyvinyl pyrrolidone 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 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. 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, after the moisture content of the hollow fiber membrane is reduced to 10 to 20% by mass, the hollow fiber membrane is preferably dried by irradiation with far infrared rays. Irradiation with microwaves or near infrared rays, or heat drying is preferable in the sense that the material to be dried is dried faster, but in the case of a separation membrane containing polyvinyl pyrrolidone as a hydrophilic polymer, That is, there is a problem that it is susceptible to degradation and degradation due to heat as the moisture content in the hollow fiber membrane decreases. Therefore, in the final stage of drying (low moisture content), it is a preferred embodiment to dry mildly with lower energy. Further, far-infrared rays are a kind of electromagnetic wave and are preferable because they penetrate into the material to be dried as in the case of microwaves, and thus have a characteristic that the material to be dried can be uniformly dried even at low energy.

  In this invention, it is preferable that the irradiation wavelength of a far infrared ray is 1-30 micrometers. If the far-infrared wavelength is too short, the temperature of the object to be dried cannot be increased, and the drying cost may increase, for example, the drying time may be extended. Therefore, the wavelength of the far infrared ray to be irradiated is more preferably 1.5 μm or more, further preferably 2 μm or more, and further preferably 2.5 μm or more. Moreover, when the wavelength of the far infrared rays to irradiate is too long, the temperature of the material to be dried increases too much, so that the degradation and decomposition of the hollow fiber membrane material easily occurs. Therefore, the irradiation wavelength of far infrared rays is more preferably 28 μm or less, further preferably 26 μm or less, and further preferably 24 μm or less.

  In the present invention, ceramic is preferably used as a medium for irradiating far infrared rays. In order to obtain the far-infrared ray of the present invention, for example, a far-infrared irradiation medium made of tungsten, nichrome, stainless steel, silicon carbide, ceramic, or carbon can be cited. Among them, silicon carbide, stainless steel, alumina-based and zirconium-based materials can be used. It is preferable to use a fine ceramic as a medium.

  On the other hand, in the case of drying by far-infrared irradiation performed after the completion of microwave drying, unlike the case of microwave drying, the 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.

  The far-infrared irradiation may be started after the end of microwave irradiation, or may be performed at the time of microwave irradiation, and microwave drying and far-infrared drying may be performed simultaneously. By performing the microwave and far infrared irradiation simultaneously, the evaporation of water that has been excited by the microwave irradiation and moved to the surface of the hollow fiber membrane is accelerated by the far infrared irradiation, leading to an improvement in drying efficiency. Further, this efficient evaporation of surface moisture suppresses the concentration fluctuation of the surface of the hollow fiber membrane of polyvinylpyrrolidone induced by the surface moisture, which is preferable because it leads to suppression of partial sticking. As described above, microwave drying is preferably performed under reduced pressure. Therefore, microwave drying and far-infrared drying are simultaneously performed under reduced pressure, and microwave irradiation is performed when the moisture content is reached. A method of stopping drying by continuing far-infrared irradiation while maintaining a reduced pressure state and continuing further drying is preferable. In this case, 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 the present invention, it is a preferred embodiment that drying is performed using a microwave dryer in which a far-infrared heater is attached in the heating oven and an exhaust system capable of reducing the pressure of the heating oven is attached.

  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. By this measure, oxidative deterioration of polyvinylpyrrolidone in the hollow fiber membrane is suppressed.

  Furthermore, it is preferable that the hollow fiber membrane does not dry out. When it is completely dried, the deterioration of polyvinyl pyrrolidone increases and the production of hydrogen peroxide may be greatly increased. In addition, wettability may be reduced during re-wetting during use, and polyvinyl pyrrolidone may be less likely to absorb water and may be easily eluted from the hollow fiber membrane. The moisture content of the hollow fiber membrane after drying is preferably 1% by mass or more and less than the saturated moisture content. 1.5 mass% or more is more preferable. If the water content of the hollow fiber membrane is too high, bacteria may easily proliferate during storage, and the hollow fiber membrane may crush due to its own weight, or an adhesive failure may occur during assembly of the module. The water content of the hollow fiber membrane is preferably 10% by mass or less, more preferably 7% by mass or less.

  In addition, a method of removing hydrogen peroxide mixed from the raw material polyvinyl pyrrolidone as described above or generated in the manufacturing process of the hollow fiber membrane by washing is also effective as a method of controlling the above-described characteristic value within a restricted range. .

In the present invention, as described above, in the process of producing a hollow fiber membrane as a means for reducing the elution amount of hydrogen peroxide or making the content of polyvinylpyrrolidone on the outer surface of the hollow fiber membrane a specific range, It is important to introduce a washing step before the drying step. For example, a hollow fiber membrane that has passed through a 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 is washed to remove excess solvent, polyvinylpyrrolidone. As a method for washing the hollow fiber membrane, in the present invention, it is preferable to treat the hollow fiber membrane by immersing it in hot water at 70 to 130 ° C., or from 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 is immersed in excess RO water and treated at 70 to 90 ° C. for 15 to 60 minutes, and then the hollow fiber membrane 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 immersed in excess RO water in a pressurized container at 121 ° C. for about 2 hours can also 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 membranes are arranged radially in a 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 washing, it is possible to optimize the abundance ratio of the outer surface polyvinyl pyrrolidone, thereby suppressing sticking and reducing the amount of eluate, and also leading to a reduction in the hydrogen peroxide elution amount.

  The blood purifier of the present invention can be provided with the characteristics that the present invention must have by being modularized using the polysulfone-based hollow fiber membrane. Therefore, the polysulfone-based hollow fiber membrane filled in the blood purifier of the present invention has the above-described polysulfone-based hollow fiber membrane of the present invention such that the elution amount of hydrogen peroxide is more preferably 4 ppm or less, and further preferably 3 ppm or less. It is a preferred embodiment that has the desired characteristics to be possessed. In addition, the polysulfone-based hollow fiber membrane used in the present invention can be stably and economically manufactured by the above-described manufacturing method.

  As a method for suppressing the entry of foreign matter into the hollow fiber membrane, a method using a raw material with little foreign matter, filtering the spinning solution for film formation, and reducing foreign matter is effective. In the present invention, it is preferable to filter the spinning solution using a filter having a pore size smaller than the film thickness of the hollow fiber membrane and then discharge from the nozzle. Specifically, the uniformly dissolved spinning solution is guided from the dissolution tank to the nozzle. A sintered filter having a pore diameter of 5 to 50 μm provided therebetween 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 5 to 45 μm, further preferably 5 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 spinning solution, static defoaming or vacuum defoaming can be used. The pressure in the dissolution tank is reduced to −100 to −750 mmHg, and then the tank is sealed and left 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. Moreover, when the pressure reduction degree is too high, the cost for raising the sealing degree of a system may become high. 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. When returning the degassed system to normal pressure, it is preferable to use an inert gas, particularly nitrogen gas.

  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. Measurement of water permeability The flow is stopped by sandwiching the blood outlet circuit of the dialyzer (the outlet side from the pressure measurement point) with forceps, and total filtration is performed. Purified water kept at 37 ° C is put into a pressurized tank, and the pressure is controlled by a regulator. The pure water is sent to a dialyzer kept warm in a 37 ° C constant temperature bath, and the amount of filtrate flowing out from the dialysate side is measured with a graduated cylinder. To do. 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 is calculated from the membrane area and the water permeability of the dialyzer.
UFR (H) = UFR (D) / A
Here, UFR (H) is the water permeability of the hollow fiber membrane (mL / m ² / hr / mmHg), UFR (D) is the water permeability of the dialyzer (mL / hr / mmHg), and A is the membrane area of the dialyzer (mL m ² ).

2. 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.

3. Elution amount of polyvinyl pyrrolidone Extracted by the method defined in the dialysis artificial kidney device production standard, and the polyvinyl pyrrolidone in the extract was quantified by a colorimetric method.
100 g of pure water is added to 1 g of the dry hollow fiber membrane and extracted at 70 ° C. for 1 hour. The obtained extract (2.5 ml), 0.2 molar aqueous citric acid solution (1.25 ml) and 0.006 normal iodine aqueous solution (0.5 ml) were mixed well and allowed to stand at room temperature for 10 minutes, and the absorbance at 470 nm was measured. Quantification was performed with a calibration curve obtained by measuring according to the above method using a standard polyvinylpyrrolidone.

4. UV (220-350 nm) absorbance The absorbance of the extract extracted by the method described in the method for measuring the amount of polyvinylpyrrolidone eluted is measured using a spectrophotometer (manufactured by Hitachi Ltd., U-3000) in the wavelength range of 200 to 350 nm. The maximum absorbance in this wavelength range was determined.
In this measurement, the hollow fiber membrane was equally divided into 10 pieces of 2.7 cm in the longitudinal direction, and 1 g of a hollow fiber membrane in a dry state was weighed from each part 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 quantification was performed using the dry membrane.

5. Quantitative determination of hydrogen peroxide 2.6 ml of the extract extracted by the above method and 0.2 ml of ammonium chloride buffer (PH 8.6) equimolarly mixed with a molar ratio of TiCl ₄ and 4- (2- A mixed solution of pyridylazo) resorcinol with an aqueous Na salt solution was added, 0.2 ml of a coloring reagent prepared to 0.4 mM was further added, the mixture was heated at 50 ° C. for 5 minutes, cooled to room temperature, and the absorbance at 508 nm was measured. A quantitative value was obtained using a calibration curve obtained by measuring in the same manner using a sample.
In this measurement, the hollow fiber membrane was equally divided into 10 pieces of 2.7 cm in the longitudinal direction, and 1 g of a hollow fiber membrane in a dry state was weighed from each part and measured for all samples.

6. Storage Stability of Hollow Fiber Membrane About 10,000 hollow fiber membranes obtained in each example and comparative example were inserted into a polyethylene pipe and cut into a predetermined length to obtain a bundle. The obtained bundle was filled in the case at a filling rate of 60 vol%, the end was adhered with urethane resin, the resin was cut out, and a blood purifier having a hollow fiber membrane area of 1.5 m ² was obtained. The blood purifier was sterilized by irradiating it with 25 kGy of γ rays in a deoxygenated state. The resulting sterilized blood purifier was stored at room temperature for 1 year. A hollow fiber membrane was cut out from the blood purifier after storage for 1 year, subjected to an eluate test, and 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 obtained by equally dividing the hollow fiber membrane into 10 pieces in the longitudinal direction, measuring each sample, and determining the maximum value. Those whose maximum value did not exceed 0.10 were considered acceptable.

7. Moisture content of hollow fiber membrane The moisture content of the hollow fiber membrane is the mass of the hollow fiber membrane before drying (a), the mass of the hollow fiber membrane after being dried in a 120 ° C dry heat oven for 2 hours (after absolutely dry). (B) was measured and 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.

Example 1
4.02 and 0.16 parts by mass of dimethylacetamide (DMAc) and RO water were charged in a dissolution tank having a disc turbine type stirring blade, respectively, and polyethersulfone (Sumitomo Chemtex, Sumika Excel (registered) was added while stirring. (Trademark) 4800P) 1 part by weight and polyvinyl pyrrolidone (BASF Koridone (registered trademark) K90) 0.144 parts by weight, each divided into three equal parts, polyether sulfone and polyvinyl pyrrolidone are alternately added in this order, and stirred for 2 hours. Then, a spinning solution was obtained by dissolving. At this time, the supply and dissolution of polyethersulfone and polyvinylpyrrolidone were performed in a nitrogen atmosphere. Moreover, it cooled so that the temperature at the time of melt | dissolution might not exceed 65 degreeC. The Froude number and Reynolds number of stirring 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. In addition, the said polyvinyl pyrrolidone used the hydrogen peroxide content 80ppm. The obtained film-forming solution was passed through a two-stage sintered filter of 30 μm and 15 μm in order, and then degassed at −700 mmHg for 30 minutes in advance as a hollow forming agent from a tube-in orifice nozzle heated to 70 ° C. The solution was discharged together with a 46% by weight DMAc aqueous solution, passed through a 400 mm dry section cut off from the outside air by a spinning tube, solidified in a 20% by weight DMAc aqueous solution at 60 ° C., and then rolled up in a wet state. The storage time of the spinning solution from the dissolution of the spinning solution to spinning was 3 days. During this period, the liquid temperature was 35 ° C. and the nitrogen gas substitution state was maintained. During the spinning process, all the rollers with which the hollow fiber membranes contacted were mirror-finished on the surface, and all the guides were textured on the surface.

  A bundle of about 10,000 obtained wet hollow fiber membranes was wrapped with a polyethylene film whose surface contacting with the hollow fiber membrane bundles had a textured finish, and then cut into a length of 27 cm and heated at 80 ° C. Washed in water for 30 minutes x 4 times, installed in a microwave-irradiated dryer equipped with a far-infrared heater that has a structure that allows uniform heating by installing a reflector in the oven. Wave irradiation and far-infrared irradiation were performed simultaneously 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 degree of reduced pressure was increased 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. The water content in the hollow fiber membrane bundle after the microwave irradiation was 11% by mass. After the microwave irradiation is stopped, the degree of decompression is increased to 0.5 kPa, and only the irradiation with far infrared rays is continued. By maintaining for 10 minutes, the drying of the hollow fiber membrane bundle is completed, and nitrogen gas is fed into the drying chamber. Returning to normal pressure, a dried hollow fiber membrane bundle was obtained. 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. The highest temperature reached on the surface of the hollow fiber membrane bundle during this period 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 2.5% by mass. The obtained hollow fiber membrane bundle had an inner diameter of 198 μm and a film thickness of 28 μm. The obtained hollow fiber membrane had an elution amount of polyvinyl pyrrolidone of 5 ppm.

  The obtained hollow fiber membrane 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 from each portion, and hydrogen peroxide was quantified. Hydrogen peroxide was stable at low levels at all sites. The quantitative values are shown in Table 1.

  A blood purifier was assembled using the hollow fiber membrane thus obtained. The blood purifier was sterilized by irradiating it with 25 kGy of γ rays in a deoxygenated state. The resulting sterilized blood purifier was stored at room temperature for 1 year. When the hollow fiber membrane was cut out from the blood purifier after storage for 1 year and subjected to the eluate test, the maximum value of UV (220-350 nm) absorbance, which is the dialysis-type artificial kidney device manufacturing approval standard for the hollow fiber membrane, was 0. 04, and the reference value of 0.10 or less was maintained. The results are shown in Table 2.

(Comparative Example 1)
In Example 1, the stirring blade of the dissolution tank for preparing the spinning solution is a propeller type, and the introduction of polyethersulfone and polyvinylpyrrolidone is conducted all at once without being divided, and the dissolution and storage conditions are shown in Table 2. A hollow fiber membrane and a blood purifier were obtained in the same manner as in Example 1 except for changes. By changing the raw material charging method and the stirring state, polyvinylpyrrolidone spatter was generated and the dissolution time was longer than in Example 1. The results are shown in Tables 1 and 2. The amount of hydrogen peroxide eluted from the hollow fiber membrane obtained in this comparative example was high and low quality. In addition, a blood purifier was assembled using the hollow fiber membrane of this comparative example. The blood purifier was filled with RO water degassed in advance and irradiated with 25 kGy of γ-ray to crosslink PVP. The hollow fiber membrane filled in the blood purifier stored for one year could not maintain the UV (220-350 nm) absorbance of 0.10 or less, which is the dialysis artificial kidney device manufacturing approval standard.

(Comparative Example 2)
In Comparative Example 1, a hollow fiber membrane and a blood purifier were obtained in the same manner as in Comparative Example 1, except that the spinning temperature and the storage temperature of the spinning solution were increased to 90 ° C. and the dissolution and storage were performed in a nitrogen gas atmosphere. . The results are shown in Tables 1 and 2. The hydrogen peroxide elution amount and storage stability of the hollow fiber membrane obtained in this Comparative Example were not satisfactory as in Comparative Example 1.

(Comparative Example 3)
In the method of Comparative Example 1, polyvinyl pyrrolidone having a hydrogen peroxide content of 500 ppm is used as a raw material, the rotational speed of the stirring blade is increased, and the fluid number and Reynolds number at the time of dissolution are 1.5 and 260, respectively. Except for the change, a hollow fiber membrane was obtained in the same manner as in Comparative Example 2. A blood purifier was assembled using the obtained hollow fiber membrane. In this comparative example, since the fluid number and Reynolds number at the time of dissolution of polyvinyl pyrrolidone are too high, undesired phenomena such as dissolution raw material scattering in the tank and adhering to the wall, or entrapment of bubbles in the solution during dissolution There has occurred. The results are shown in Tables 1 and 2. The amount of hydrogen peroxide eluted from the hollow fiber membrane obtained in this comparative example was further increased. Moreover, since the PVP crosslinking treatment was not performed, the storage stability was further deteriorated.

(Comparative Example 4)
In the method of Comparative Example 3, the melting temperature and the storage temperature were set to 90 ° C., and the hollow fiber membrane was changed to dry by irradiating microwaves under normal pressure. A hollow fiber membrane and a blood purifier were obtained in the same manner as in Comparative Example 3 except that the treatment was performed. Microwave irradiation was 2 kW until the moisture content in the hollow fiber membrane reached 65% by mass, and thereafter 0.8KW and dried until the moisture content became 0.5% by mass. Further, from the start of drying to the end of drying, dehumidified air (humidity of 10% RH or less) was passed from the lower part of each yarn bundle to the upper part at a wind speed of 8 m / sec. The maximum temperature reached by the hollow fiber membrane during the drying was 65 ° C. The obtained results are shown in Tables 1 and 2. The amount of hydrogen peroxide eluted from the hollow fiber membrane obtained in this comparative example was further increased. Therefore, the storage stability further deteriorated, and the UV (220-350 nm) absorbance, which is already the dialysis-type artificial kidney device manufacturing approval standard after about 2 months of storage, can no longer maintain an average value of 0.10 or less. .

(Example 2)
Polyethersulfone (Sumitomo Chemtex Co., Ltd., Sumika Excel (registered trademark) 4800P) 1 part by mass is used in a kneading and dissolving machine that exhibits a kneading effect by so-called planetary motion in which two frame-type blades rotate and revolve. 0.144 parts by mass of pyrrolidone (BASF Co., Ltd. Kollidon (registered trademark) K90) and 1 part by mass of dimethylacetamide (DMAc) were charged and kneaded by stirring for 2 hours. Subsequently, a mixed solution of 3.02 parts by mass of DMAc and 0.16 parts by mass of RO water was added over 9 hours. 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 Froude number and Reynolds number of stirring at the time of final dissolution were 1.1 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 having a hydrogen peroxide content of 280 ppm was used. 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 70 ° C. The solution was discharged together with a 46% by mass DMAc aqueous solution and passed through a 400 mm dry part cut off from the outside air by a spinning tube, and then solidified in a 20% by mass DMAc aqueous solution at 60 ° C. 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 1.06. The storage time of the spinning solution from the preparation of the spinning solution to spinning was 2 days. 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 min. This was dried in the same manner as in Example 1 to obtain a hollow fiber membrane and a blood purifier. The results are shown in Tables 1 and 2. The hollow fiber membrane and blood purifier obtained in this example were of high quality, similar to those obtained in the example.

(Example 3)
2 parts by mass of polyethersulfone (Sumika Chemtex Co., Ltd., SUMIKAEXCEL (registered trademark) 4800P), 1 part by mass of polyvinyl pyrrolidone (BASF Koridone (registered trademark) K-90), 2 parts by mass of DMAc It knead | mixed with the screw type kneader of the axis | shaft. The obtained kneaded material was added to a stirring type dissolver charged with 2.57 parts by mass of DMAc and 0.28 parts by mass of water, and dissolved by stirring for 4 hours. The kneading and dissolution were cooled so that the internal temperature did not exceed 65 ° C. Next, after reducing the pressure in the system to −700 mmHg using a vacuum pump, the system was immediately sealed and left for 10 minutes so that the solvent and the like were volatilized and the composition of the film forming solution was not changed. This operation was repeated three times to degas the film forming solution. As the polyvinyl pyrrolidone, one having a hydrogen peroxide content of 130 ppm was used, and the supply tank in the raw material supply system and the dissolution tank were replaced with nitrogen gas. Further, the stirring fluid number and the Reynolds number at the time of dissolution were 1.1 and 100, respectively. The obtained film-forming solution was passed through a two-stage filter of 15 μm and 15 μm, and then degassed in advance at −700 mmHg for 2 hours as a hollow forming agent from a tube-in orifice nozzle heated to 70 ° C. 50 mass at 50 ° 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 hollow fiber membrane 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 polyethylene film similar to that of Example 1 was wrapped around a bundle of about 10,000 hollow fiber membranes, and then washed by immersing twice in a 40 vol% isopropanol aqueous solution at 30 ° C. for 30 minutes. This was dried in the same manner as in Example 1 to obtain a hollow fiber membrane and a blood purifier. The results are shown in Tables 1 and 2. The hollow fiber membrane and blood purifier obtained in this example were of high quality, similar to those obtained in the example.

Example 4
1 part by weight of polyethersulfone (manufactured by Sumika Chemtex, Sumika Excel (registered trademark) 4800P), 0.21 part by weight of polyvinylpyrrolidone (Collidon (registered trademark) K-90, manufactured by BASF), 1.5 parts by weight of DMAc It knead | mixed with the screw type kneader of the axis | shaft. The obtained kneaded material was added to a stirring type dissolver charged with 2.57 parts by mass of DMAc and 0.28 parts by mass of water, and dissolved by stirring for 4 hours. The kneading and dissolution were cooled so that the internal temperature did not exceed 40 ° C. Next, after reducing the pressure in the system to −700 mmHg using a vacuum pump, the system was immediately sealed and left for 10 minutes so that the solvent and the like were volatilized and the composition of the film forming solution was not changed. This operation was repeated three times to degas the film forming solution. As the polyvinyl pyrrolidone, one having a hydrogen peroxide content of 400 ppm was used, and the supply tank in the raw material supply system and the dissolution tank were replaced with nitrogen gas. Further, the stirring fluid number and the Reynolds number at the time of dissolution were 1.1 and 100, respectively. The obtained film-forming solution was passed through a two-stage filter of 15 μm and 15 μm, and then degassed in advance at −700 mmHg for 2 hours as a hollow forming agent from a tube-in orifice nozzle heated to 70 ° C. 50 mass at 50 ° 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 hollow fiber membrane 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 polyethylene film similar to that of Example 1 was wrapped around a bundle of about 10,000 hollow fiber membranes, and then washed by immersing twice in a 40 vol% isopropanol aqueous solution at 30 ° C. for 30 minutes. This was dried in the same manner as in Example 1 to obtain a hollow fiber membrane and a blood purifier. The results are shown in Tables 1 and 2. The hollow fiber membrane and blood purifier obtained in this example were of high quality, similar to those obtained in the example.

  The production method of the polysulfone-based hollow fiber membrane of the present invention suppresses the generation of hydrogen peroxide due to the deterioration of the components in the preparation of the spinning solution during the production process and the storage process, in particular, the oxidative degradation of polyvinylpyrrolidone. A hollow fiber membrane with a small amount of hydrogen peroxide elution can be obtained. Therefore, when hollow fiber membranes are stored for a long period of time, degradation of polyvinyl pyrrolidone and the like caused by the hydrogen peroxide is suppressed. The maximum value of UV (220-350 nm) absorbance can be maintained at 0.10 or less, so that there is an advantage that it can be suitably used for blood purifiers used for the treatment of chronic renal failure. Moreover, there exists an advantage that the above-mentioned hollow fiber membrane can be manufactured economically and stably by the manufacturing method of this invention. Therefore, it is important to contribute to the industry.

It is a schematic diagram which shows the relationship between spinning solution preparation temperature (degreeC) and hydrogen peroxide elution amount (ppm). It is a schematic diagram which shows the relationship between spinning solution preparation temperature (degreeC) and PVP elution amount (ppm). It is a schematic diagram which shows the relationship between spinning solution preparation temperature (degreeC) and UV light absorbency.

Claims (10)

  Preparation of a spinning solution by dissolving at least three components comprising polyvinylpyrrolidone, a polysulfone polymer and a common solvent thereof under an inert gas atmosphere at 70 ° C. or lower, and supplying the obtained spinning solution to the spinning process A method for producing a polysulfone-based hollow fiber membrane, wherein the temperature is maintained at 70 ° C. or less.   The method for producing a polysulfone-based hollow fiber membrane according to claim 1, wherein the storage time until the spinning solution is used in the spinning step after dissolution is a maximum of 3 days.   The method for producing a polysulfone-based hollow fiber membrane according to claim 1 or 2, wherein the dissolution is performed under the conditions of a fluid number of 0.7 to 1.3 and a stirring Reynolds number of 50 to 250.   The supply to the dissolution tank of the polysulfone polymer and polyvinyl pyrrolidone is divided into at least two times, and the polysulfone polymer and polyvinyl pyrrolidone are alternately supplied and dissolved. A process for producing a polysulfone-based hollow fiber membrane as described in 1.   The method for producing a polysulfone-based hollow fiber membrane according to any one of claims 1 to 4, wherein the components of the hollow fiber membrane are pre-kneaded and then supplied to the dissolution tank for dissolution.   The method for producing a polysulfone-based hollow fiber membrane according to any one of claims 1 to 5, wherein the spinning solution is prepared in a dissolution tank having a kneading function.   The method for producing a polysulfone-based hollow fiber membrane according to any one of claims 1 to 6, wherein dissolution during preparation of the spinning solution is performed within 10 hours.   The method for producing a polysulfone-based hollow fiber membrane according to any one of claims 1 to 7, wherein at least supply of polyvinylpyrrolidone, kneading, and storage of the spinning solution are performed in an inert gas atmosphere.   The method for producing a polysulfone-based hollow fiber membrane according to any one of claims 1 to 8, wherein polyvinylpyrrolidone having a hydrogen peroxide content of 300 ppm or less is used. The method for producing a polysulfone-based hollow fiber membrane according to any one of claims 1 to 9, wherein polyvinylpyrrolidone is not substantially cross-linked.