JP3659256B1 - Polysulfone-based permselective hollow fiber membrane bundle and drying method thereof - Google Patents

Polysulfone-based permselective hollow fiber membrane bundle and drying method thereof Download PDF

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JP3659256B1
JP3659256B1 JP2004085428A JP2004085428A JP3659256B1 JP 3659256 B1 JP3659256 B1 JP 3659256B1 JP 2004085428 A JP2004085428 A JP 2004085428A JP 2004085428 A JP2004085428 A JP 2004085428A JP 3659256 B1 JP3659256 B1 JP 3659256B1
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hollow fiber
fiber membrane
membrane bundle
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polysulfone
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公洋 馬淵
英之 横田
勝朗 久世
憲幸 玉村
仁 大野
典子 門田
典昭 加藤
博史 柴野
克彦 野瀬
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Toyobo Co Ltd
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Abstract

【課題】乾燥工程における中空糸膜の性能低下や中空糸膜成分の劣化を低減し、高性能で、安全性が高く、かつ保存安定性やモジュール組み立て性の優れた中空糸膜束およびその乾燥方法を提供する。
【解決手段】本発明は、ポリビニルピロリドンを含むポリスルホン系樹脂よりなる湿潤状態のポリスルホン系選択透過性中空糸膜束を乾燥するにあたり、中空糸膜束中の水分率を１質量％以上飽和含水率未満の範囲で乾燥を終了することを特徴とするポリスルホン系選択透過性中空糸膜束の乾燥方法。また、乾燥中空糸膜束を長手方向に１０個に分割し、各々を透析型人工腎臓装置製造承認基準により定められた試験を実施したとき、中空糸膜の抽出液における１０個に分割したすべの部位で抽出液中の過酸化水素濃度が５ｐｐｍ以下あることを特徴とするポリスルホン系選択透過性中空糸膜束。
【選択図】なし
[PROBLEMS] To reduce hollow fiber membrane performance and degradation of hollow fiber membrane components in a drying process, and to provide a high-performance, high-safety hollow fiber membrane bundle excellent in storage stability and module assembly and its drying. Provide a method.
The present invention provides a moisture-containing polysulfone-based selectively permeable hollow fiber membrane bundle comprising a polysulfone-based resin containing polyvinylpyrrolidone, wherein the moisture content in the hollow fiber membrane bundle is 1% by mass or more. A method for drying a polysulfone-based permselective hollow fiber membrane bundle, characterized in that drying is completed within a range of less than. Moreover, when the dry hollow fiber membrane bundle is divided into 10 pieces in the longitudinal direction and each of them is subjected to the test defined by the dialysis-type artificial kidney device manufacturing approval criteria, all of the dry hollow fiber membrane bundles are divided into 10 pieces in the hollow fiber membrane extract. A polysulfone-based permselective hollow fiber membrane bundle having a hydrogen peroxide concentration in the extract of 5 ppm or less at the site of
[Selection figure] None

Description

本発明は、湿潤状態の中空糸膜束の乾燥方法および中空糸膜束に関するものである。さらに詳しくは、湿潤状態の中空糸膜束の乾燥方法に関し、乾燥工程における中空糸膜の性能低下や中空糸膜成分の劣化を低減し高性能で、安全性が高く、かつ保存安定性やモジュール組み立て性に優れた中空糸膜束が製造できる中空糸膜束の乾燥方法および安全性や性能の安定性が高く、特に血液浄化器用に適したポリスルホン系選択透過性中空糸膜束に関する。   The present invention relates to a method for drying a wet hollow fiber membrane bundle and a hollow fiber membrane bundle. More specifically, the present invention relates to a method for drying a wet bundle of hollow fiber membranes, reducing the performance of the hollow fiber membranes in the drying process and the deterioration of the components of the hollow fiber membranes, providing high performance, high safety, storage stability and modules. The present invention relates to a drying method of a hollow fiber membrane bundle that can produce a hollow fiber membrane bundle excellent in assemblability, and a polysulfone-based selectively permeable hollow fiber membrane bundle that is highly stable in safety and performance and particularly suitable for use in a blood purifier.

近年、選択的な透過性を有する膜を利用する技術がめざましく進歩し、これまでに気体や液体の分離フィルター、医療分野における血液透析器、血液濾過器、血液成分選択分離フィルター等の広範な分野での実用化が進んでいる。該膜の材料としては、セルロース系（再生セルロース系、酢酸セルロース系、化学変性セルロース系等）、ポリアクリロニトリル系、ポリメチルメタクリレート系、ポリスルホン系、ポリエチレンビニルアルコール系、ポリアミド系等の樹脂が用いられてきた。このうちポリスルホン系樹脂は、その熱安定性、耐酸、耐アルカリ性に加え、製膜溶液に親水化剤を添加して製膜することにより、血液適合性が向上することから、半透膜素材として注目され研究が進められてきた。   In recent years, technologies using selective permeable membranes have made remarkable progress, and so far a wide range of fields such as gas and liquid separation filters, hemodialyzers in the medical field, blood filters, blood component selective separation filters, etc. Practical use in is progressing. As the material of the membrane, resins such as cellulose (regenerated cellulose, cellulose acetate, chemically modified cellulose, etc.), polyacrylonitrile, polymethyl methacrylate, polysulfone, polyethylene vinyl alcohol, and polyamide are used. I came. Of these, the polysulfone-based resin, in addition to its thermal stability, acid resistance, and alkali resistance, improves the blood compatibility by adding a hydrophilizing agent to the film-forming solution, so that it can be used as a semipermeable membrane material. Attention has been paid to research.

腎不全治療などにおける血液浄化療法では、血液中の尿毒素、老廃物を除去する目的で、透析膜や限外ろ過膜を分離材として用いた血液透析器、血液ろ過器あるいは血液透析ろ過器などのモジュールが広く使用されている。特に中空糸型の膜を分離材として用いたモジュールは体外循環血液量の低減、血中の物質除去効率の高さ、さらにモジュール生産時の生産性などの利点から透析器分野での重要度が高い。 In blood purification therapy for renal failure treatment, etc., hemodialyzer, blood filter or hemodialysis filter using dialysis membrane or ultrafiltration membrane as a separator for the purpose of removing urine toxins and waste products in blood The module is widely used. In particular, modules using hollow fiber membranes as separation materials are important in the dialyzer field due to advantages such as reduction of the amount of blood circulating outside the body, high efficiency of removing substances in the blood, and productivity during module production. high.

一方、中空糸膜束を接着してモジュールを作製するためには中空糸膜束を乾燥させる必要があるが、有機高分子よりなる多孔膜、なかでもポリスルホン系等の疎水性樹脂からなる透析膜、限外ろ過膜は、製膜後に乾燥させると乾燥前に比べ著しく透水量が低下することが知られている。そのため膜は常に湿潤状態か、水に浸漬させた状態で取り扱う必要があった。   On the other hand, in order to produce a module by bonding the hollow fiber membrane bundle, it is necessary to dry the hollow fiber membrane bundle. However, the porous membrane made of organic polymer, especially dialysis membrane made of hydrophobic resin such as polysulfone In addition, it is known that when the ultrafiltration membrane is dried after the film formation, the water permeability is remarkably reduced as compared with that before drying. Therefore, it was necessary to handle the membrane always in a wet state or in a state immersed in water.

この対策として従来よりとられてきた方法は、製膜後、乾燥前にグリセリン等の低揮発性有機液体を多孔膜中の空孔部分に詰めておくことであった。しかしながら、低揮発性有機液体は、一般に高粘度なため、洗浄除去に時間がかかり、膜をモジュール成型して洗浄後も微量ではあるが低揮発性有機液体由来の溶出物等（低揮発性有機液体と化学反応して生成した様々な誘導体）がモジュール封入液中にみられることに問題があった。   As a countermeasure against this problem, a conventional method has been to pack a low-volatile organic liquid such as glycerin in the pores in the porous film after film formation and before drying. However, since low-volatile organic liquids generally have high viscosity, it takes time for cleaning and removal, and even after the membrane is molded into a module, a small amount of effluent derived from low-volatile organic liquids (low-volatile organic liquids). There was a problem in that various derivatives produced by chemical reaction with liquid were found in the module sealing liquid.

低揮発性有機液体を用いずに乾燥させる方法として、低揮発性有機液体の代わりに塩化カルシウム等の無機塩を用いる方法が開示されているが、洗浄除去する必要性に変わりはない。また、微量であるとしても残存した無機塩が透析患者に与える悪影響が危惧される
（特許文献１参照）。
特開平６−２７７４７０号公報 As a method for drying without using a low-volatile organic liquid, a method using an inorganic salt such as calcium chloride in place of the low-volatile organic liquid is disclosed, but the necessity for washing and removing remains unchanged. Moreover, even if it is a trace amount, there is a concern that the remaining inorganic salt may adversely affect the dialysis patient (see Patent Document 1).
JP-A-6-277470

また、膜の乾燥方法として、中空糸膜に対し水蒸気による湿熱処理を行いながらマイクロ波を照射する中空糸膜の製造方法が開示されている（特許文献２参照）。しかし、乾燥でありながら膜の変形を防ぐために水蒸気処理していることから乾燥時間を長くする欠点があり、さらに、グリセリン等の低揮発性有機液体を付着させてからの乾燥であることから、膜からの溶出物を低減させるという目的は達成されない。
特開平１１−３３２９８０号公報 Moreover, as a method for drying the membrane, a method for producing a hollow fiber membrane in which microwave irradiation is performed while performing wet heat treatment with water vapor on the hollow fiber membrane is disclosed (see Patent Document 2). However, there is a drawback of extending the drying time because it is steamed to prevent deformation of the membrane while being dry, and since it is drying after attaching a low volatile organic liquid such as glycerin, The objective of reducing effluent from the membrane is not achieved.
JP 11-332980 A

低揮発性有機液体を用いずに乾燥処理をしたポリビニルピロリドンを含む親水化膜が開示されている（特許文献３および４参照）。これらには、血液から血しょう成分を分離する性能が記載されているが、血しょうタンパクが透過することから透析膜としては有効でないことが分かる。また、ポリビニルピロリドンを分解・変性させる温度で乾燥していることから、膜からの溶出物を低減させるという目的においては極めて好ましくない製法である。
特開平８−５２３３１号公報 特公平８−９６６８号公報 A hydrophilized film containing polyvinyl pyrrolidone that has been dried without using a low-volatile organic liquid is disclosed (see Patent Documents 3 and 4). These describe the ability to separate plasma components from blood, but the plasma proteins permeate, indicating that they are not effective as dialysis membranes. In addition, since it is dried at a temperature at which polyvinylpyrrolidone is decomposed and modified, it is an extremely undesirable production method for the purpose of reducing the amount of eluate from the membrane.
JP-A-8-52331 Japanese Patent Publication No.8-9668

また、特定の性能を有する湿潤膜をグリセリン等の低揮発性有機液体に含浸せずに１２０℃以下の温度で乾燥して高性能な血液浄化膜を製造する方法が開示されている（特許文献５参照）。しかし、この方法は、糸束状にして乾燥した場合には、糸束の中心部と外周部の膜とでは若干の性能差が生じることが同一発明者等により明らかにされている。
特許第３２８１３６４号公報 In addition, a method for producing a high-performance blood purification membrane by drying a wet membrane having a specific performance at a temperature of 120 ° C. or less without impregnating with a low-volatile organic liquid such as glycerin is disclosed (Patent Document). 5). However, it has been clarified by the same inventors that when this method is dried in the form of a yarn bundle, there is a slight difference in performance between the central portion and the outer peripheral portion of the yarn bundle.
Japanese Patent No. 3281364

特許文献５と同一発明者らにより特許文献５に開示されている乾燥方法の課題解決の方策として、マイクロ波を照射して乾燥する方法が開示されている（特許文献６〜８参照）。これらの方法は低揮発性有機液体に含浸せず乾燥する方法であり、かつ中空糸膜束の分離性能を低下させずに乾燥できる点では好ましい方法であるが、該方法は中空糸膜素材の長期保存安定性に対する配慮が不足しておりその改善が必要である。中空糸膜を血液浄化療法用の分離膜として使用する場合は、親水性化合物の溶出が多くなると人体に取り異物である親水化合物の長期透析時の体内蓄積が増え副作用や合併症等を引き起こす可能性があり透析型人工腎臓装置製造承認基準において中空糸膜の抽出液におけるＵＶ（２２０〜３５０ｎｍ）吸光度の基準が設定されている。   As methods for solving the problems of the drying method disclosed in Patent Document 5 by the same inventors as Patent Document 5, a method of drying by irradiating microwaves is disclosed (see Patent Documents 6 to 8). These methods are a method of drying without impregnating with a low-volatile organic liquid, and are preferable in that they can be dried without deteriorating the separation performance of the hollow fiber membrane bundle. There is a lack of consideration for long-term storage stability and improvement is necessary. When a hollow fiber membrane is used as a separation membrane for blood purification therapy, if the elution of the hydrophilic compound increases, the accumulation of the hydrophilic compound as a foreign substance in the human body increases during long-term dialysis, which may cause side effects and complications. In the dialysis-type artificial kidney device manufacturing approval standard, UV (220 to 350 nm) absorbance standards for hollow fiber membrane extracts are set.

本発明者等は、上記の透析型人工腎臓装置製造承認基準により定められた試験法で抽出された抽出液中には、従来公知のＵＶ吸光度では測定できない過酸化水素が含まれていることを見出した。該過酸化水素が存在すると、例えばポリビニルピロリドンの酸化劣化を促進し、中空糸膜束を保存した時に該ポリビニルピロリドンの溶出量が増加する事を見出した。さらに、過酸化水素は中空糸膜束の特定部位に存在しても、その個所より中空糸膜束素材の劣化反応が開始され中空糸膜束の全体に伝播していくため、モジュールと用いられる中空糸膜束の長手方向の存在量が全領域にわたり、一定量以下を確保する必要がある事を見出した。上記特許文献の方法で実施した場合は、該過酸化水素の溶出量が多くなり該中空糸膜束を長期保存した場合にポリビニルピロリドンの酸化劣化が促進され、経時によりＵＶ（２２０〜３５０ｎｍ）吸光度が増加という課題が発生する。   The present inventors have confirmed that the extract extracted by the test method defined by the above-mentioned dialysis artificial kidney device manufacturing approval standard contains hydrogen peroxide that cannot be measured by conventionally known UV absorbance. I found it. It has been found that the presence of the hydrogen peroxide accelerates the oxidative degradation of, for example, polyvinyl pyrrolidone and increases the amount of the polyvinyl pyrrolidone eluted when the hollow fiber membrane bundle is stored. Furthermore, even if hydrogen peroxide is present in a specific part of the hollow fiber membrane bundle, the deterioration reaction of the hollow fiber membrane bundle material starts from that point and propagates to the entire hollow fiber membrane bundle, so it is used as a module. It has been found that the abundance of the hollow fiber membrane bundle in the longitudinal direction needs to ensure a certain amount or less over the entire region. When carried out by the method of the above-mentioned patent document, the elution amount of the hydrogen peroxide increases, and when the hollow fiber membrane bundle is stored for a long period of time, the oxidative deterioration of polyvinylpyrrolidone is promoted, and the UV (220-350 nm) absorbance over time. The problem of increasing is generated.

また、上記特許文献の方法で実施した場合は、前述のＵＶ（２２０〜３５０ｎｍ）吸光度についても中空糸膜束の長手方向の変動が大きいという課題が発生する。該変動は安全性の低下につながる。また、ＵＶ（２２０〜３５０ｎｍ）吸光度の変動は中空糸膜束外表面のポリビニルピロリドンの表面濃度をも反映しており、湿潤状態の中空糸膜束を乾燥した場合に乾燥上がりに中空糸膜束表面のポリビニルピロリドン濃度の高い部分で部分的な中空糸膜同士のくっつき（固着）が発生するという課題につながる。該部分的な固着が発生するとモジュール組み立て性が悪化する等の問題につながるので改善が必要である。上記特許文献においては、これらの課題に対する配慮が全くなされていない。
特開２００３−１７５３２０号公報 特開２００３−１７５３２１号公報 特開２００３−１７５３２２号公報 Moreover, when it implements by the method of the said patent document, the subject that the fluctuation | variation of the longitudinal direction of a hollow fiber membrane bundle is large also generate | occur | produces about the above-mentioned UV (220-350 nm) absorbance. This fluctuation leads to a decrease in safety. The fluctuation in UV (220 to 350 nm) absorbance also reflects the surface concentration of polyvinyl pyrrolidone on the outer surface of the hollow fiber membrane bundle, and when the wet hollow fiber membrane bundle is dried, the hollow fiber membrane bundle rises to dryness. This leads to a problem that partial sticking (adhesion) of the hollow fiber membranes occurs in a portion having a high polyvinylpyrrolidone concentration on the surface. If this partial sticking occurs, it will lead to problems such as deterioration of the module assemblability, so improvement is necessary. In the above patent document, no consideration is given to these problems.
JP 2003-175320 A JP 2003-175321 A JP 2003-175322 A

上記した特許文献５〜８の乾燥方法は乾燥膜中の水分率を１質量％未満にすることが実施例において記載されている。また、特許文献２および６〜８の乾燥方法においてマイクロ波を照射して乾燥する方法が開示されているが、何れもが常圧状態でマイクロ波を照射する方法であり、減圧下でマイクロ波を照射することの効果に関しては全く言及されていない。   The drying methods described in Patent Documents 5 to 8 describe that the moisture content in the dried film is less than 1% by mass in Examples. Moreover, although the method of irradiating a microwave and drying in the drying method of patent document 2 and 6-8 is disclosed, all are the methods of irradiating a microwave in a normal-pressure state, and are microwaves under pressure reduction. No mention is made of the effect of irradiation.

乾燥工程における中空糸膜の性能低下や中空糸膜成分の劣化を低減し、高性能で、安全性が高く、かつ保存安定性やモジュール組み立て性の優れた中空糸膜束およびその乾燥方法を提供することにある。   Provided a high-performance, high-safety hollow fiber membrane bundle with excellent storage stability and module assembly, and a method for drying the same, with reduced performance of hollow fiber membranes and deterioration of hollow fiber membrane components in the drying process There is to do.

本発明は、ポリビニルピロリドンを含むポリスルホン系樹脂よりなる湿潤状態のポリスルホン系選択透過性中空糸膜束を乾燥するに当たり、ポリビニルピロリドンを含むポリスルホン系樹脂よりなる湿潤状態のポリスルホン系選択透過性中空糸膜束を乾燥するに当たり、中空糸膜束の含水率の低下に伴い、マイクロ波の照射出力を段階的に下げながら中空糸膜束の含水率を１重量％以上飽和含水率未満（または１．５〜１０質量％または２．０〜７質量％）の範囲で乾燥を終了することにより、又はポリビニルピロリドンを含むポリスルホン系樹脂よりなる湿潤状態のポリスルホン系選択透過性中空糸膜束を乾燥するに当たり、中空糸膜束の含水率の低下に伴い、通風向きを交互に逆転するか、または通風温度を段階的に下げながら中空糸膜束の含水率を１重量％以上飽和含水率未満（または１．５〜１０質量％または２．０〜７質量％）の範囲で乾燥を終了することにより、乾燥中空糸膜束を室温で３ヶ月保存した後の中空糸膜束を長手方向に１０個に分割し、各々を透析型人工腎臓装置製造承認基準により定められた試験を実施したとき、全ての抽出液におけるＵＶ（２２０〜３５０ｎｍ）吸光度の最大値を０．１０以下とすることを特徴とするポリスルホン系選択透過性中空糸膜束の乾燥方法とすることにより達しえたものである。
The present invention relates to a wet polysulfone-based selectively permeable hollow fiber membrane made of a polysulfone-based resin containing polyvinylpyrrolidone in drying a wet polysulfone-based selectively permeable hollow fiber membrane bundle made of a polysulfone-based resin containing polyvinylpyrrolidone. In drying the bundle, as the moisture content of the hollow fiber membrane bundle decreases, the moisture content of the hollow fiber membrane bundle is decreased by 1% by weight or more and less than the saturated moisture content (or 1.5%) while gradually reducing the microwave irradiation output. 10% by mass or 2.0-7% by mass), or when drying a wet polysulfone-based selectively permeable hollow fiber membrane bundle made of a polysulfone-based resin containing polyvinylpyrrolidone, with decreasing water content of the hollow fiber membrane bundle, the hollow fiber membranes or reversing the ventilation direction alternately, or with the ventilation temperature stepped down 3 months moisture content by ending the drying in a range of less than 1% by weight or more saturated water content (or 1.5 to 10 wt%, or from 2.0 to 7 wt%), a dry hollow fiber membrane bundle at room temperature When the hollow fiber membrane bundle after storage is divided into 10 pieces in the longitudinal direction and each is subjected to the test defined by the dialysis-type artificial kidney device manufacturing approval criteria, the UV (220-350 nm) absorbance in all the extracts This can be achieved by a method for drying a polysulfone-based permselective hollow fiber membrane bundle, characterized in that the maximum value of is 0.10 or less .

本発明の中空糸膜束の乾燥方法は、乾燥工程における中空糸膜の性能低下や中空糸膜成分、特にポリビニルピロリドンの劣化が低減され、該劣化により生成する過酸化水素溶出量が抑制されており、該過酸化水素により引き起される中空糸膜束を長期にわたり保存した場合のポリビニルピロリドン等の劣化が抑制されるので、長期保存をしても透析型人工腎臓装置製造承認基準であるＵＶ（２２０−３５０ｎｍ）吸光度を０．１０以下に維持するができる利点がある。また、中空糸膜束の長手方向におけるポリビニルピロリドンの劣化の変動が小さく、中空糸膜束の長手方向における上記のＵＶ（２２０−３５０ｎｍ）吸光度変動が抑制されるので、この変動により引き起こされる中空糸膜束の部分固着が抑制され、モジュール組み立て性の優れた中空糸膜束が安定して製造できるという特徴を有する。また、該中空糸膜束の長手方向におけるＵＶ（２２０−３５０ｎｍ）吸光度変動の抑制は、血液浄化用に使用した場合の安全性の向上にもつながる。従って、慢性腎不全の治療に用いる高透水性を有する血液透析法中空糸型血液浄化器用等に用いられる中空糸膜束の乾燥方法として好適であるいう利点がある。また、本発明の中空糸膜束は上記の特徴を有するので、血液浄化器用等に好適に使用することができる。   The drying method of the hollow fiber membrane bundle of the present invention reduces the performance degradation of the hollow fiber membrane in the drying step and the degradation of the hollow fiber membrane component, particularly polyvinylpyrrolidone, and suppresses the elution amount of hydrogen peroxide generated by the degradation. Since the degradation of polyvinyl pyrrolidone and the like when the hollow fiber membrane bundle caused by the hydrogen peroxide is stored for a long time is suppressed, UV, which is a dialysis-type artificial kidney device manufacturing approval standard even if stored for a long time (220-350 nm) There is an advantage that the absorbance can be maintained at 0.10 or less. Moreover, since the fluctuation | variation of the deterioration of polyvinylpyrrolidone in the longitudinal direction of a hollow fiber membrane bundle is small and said UV (220-350 nm) absorbance fluctuation | variation in the longitudinal direction of a hollow fiber membrane bundle is suppressed, the hollow fiber caused by this fluctuation | variation This is characterized in that partial fixation of the membrane bundle is suppressed and a hollow fiber membrane bundle excellent in module assemblability can be manufactured stably. Moreover, suppression of UV (220-350 nm) absorbance fluctuations in the longitudinal direction of the hollow fiber membrane bundle also leads to an improvement in safety when used for blood purification. Therefore, there is an advantage that it is suitable as a method for drying a hollow fiber membrane bundle used for hemodialysis hollow fiber blood purifiers having high water permeability used for the treatment of chronic renal failure. Moreover, since the hollow fiber membrane bundle of the present invention has the above characteristics, it can be suitably used for blood purifiers and the like.

以下、本発明を詳細に説明する。
本発明におけるポリスルホン系選択透過性中空糸膜束は、ポリビニルピロリドンを含むポリスルホン系樹脂より構成されてなる。ポリスルホン系樹脂とは、スルホン結合を有する樹脂の総称であり特に限定されないが、例を挙げると化１、化２で示される繰り返し単位をもつポリスルホン樹脂やポリエーテルスルホン樹脂がポリスルホン系樹脂として広く市販されており、入手も容易なため好ましい。

Figure 0003659256
Figure 0003659256
 Hereinafter, the present invention will be described in detail.
The polysulfone-based selectively permeable hollow fiber membrane bundle in the present invention is composed of a polysulfone-based resin containing polyvinylpyrrolidone. Polysulfone resin is a generic term for resins having a sulfone bond, and is not particularly limited. For example, polysulfone resins and polyethersulfone resins having repeating units represented by chemical formulas 1 and 2 are widely available as polysulfone resins. It is preferable because it is easily available.
Figure 0003659256
Figure 0003659256

ポリビニルピロリドンは、Ｎ−ビニルピロリドンをビニル重合させた水溶性の高分子化合物であり、ＢＡＳＦ社より「ルビテック」、ＩＳＰ社より「プラスドン」、第一工業製薬社より「ピッツコール」の商品名で市販されており、それぞれ各種の分子量の製品がある。一般には、親水性の付与効率では低分子量のものが、一方、溶出量を低くする点では高分子量のものを用いるのが好適であるが、最終製品の中空糸膜束の要求特性に合わせて適宜選択される。単一の分子量のものを用いても良いし、分子量の異なる製品を２種以上混合して用いても良い。また、市販の製品を精製し、例えば分子量分布をシャープにしたものを用いても良い。ポリビニルピロリドンの分子量としては質量平均分子量１０，０００〜１，５００，０００のものを用いることができる。具体的には、例えばＢＡＳＦ社より市販されている分子量９，０００のもの（Ｋ１７）、以下同様に４５，０００（Ｋ３０）、４５０，０００（Ｋ６０）、９００，０００（Ｋ８０）、１，２００，０００（Ｋ９０）を用いるのが好ましく、目的とする用途、特性、構造を得るために、それぞれ単独で用いてもよく、適宜２種以上を組み合わせて用いても良い。   Polyvinyl pyrrolidone is a water-soluble polymer compound obtained by vinyl polymerization of N-vinyl pyrrolidone. The product names are “Lubitec” from BASF, “Prasdon” from ISP, and “Pittscall” from Daiichi Kogyo Seiyaku. There are products of various molecular weights that are commercially available. In general, it is preferable to use a low molecular weight in terms of imparting hydrophilicity, while a high molecular weight is preferable in terms of reducing the amount of elution, but in accordance with the required characteristics of the hollow fiber membrane bundle of the final product. It is selected appropriately. 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. As the molecular weight of polyvinylpyrrolidone, those having a mass average molecular weight of 10,000 to 1,500,000 can be used. Specifically, for example, those having a molecular weight of 9,000 (K17) commercially available from BASF, and the same below, 45,000 (K30), 450,000 (K60), 900,000 (K80), 1,200 000 (K90) is preferable, and in order to obtain the intended use, characteristics, and structure, they may be used alone or in combination of two or more.

本発明におけるポリスルホン系樹脂に対するポリビニルピロリドンの膜中の構成割合は、中空糸膜に十分な親水性や、高い含水率を付与できる範囲であれば特に限定されず任意に設定することができるが、ポリスルホン系樹脂に対するポリビニルピロリドンの質量割合で１〜２０質量％が好ましく、３〜１５質量％がより好ましい。１質量％未満では、膜の親水性付与効果が不足する可能性がある。一方、２０質量％を超えると、親水性付与効果が飽和し、かつ親水性高分子の膜からの溶出量が増大し安全性が低下する可能性がある。   The composition ratio in the film of polyvinylpyrrolidone with respect to the polysulfone resin in the present invention is not particularly limited as long as it is a range that can impart sufficient hydrophilicity and high water content to the hollow fiber membrane, but can be arbitrarily set, The mass ratio of polyvinylpyrrolidone to the polysulfone resin is preferably 1 to 20 mass%, more preferably 3 to 15 mass%. If it is less than 1% by mass, the hydrophilicity-imparting effect of the film may be insufficient. On the other hand, if it exceeds 20% by mass, the effect of imparting hydrophilicity is saturated, and the elution amount of the hydrophilic polymer from the membrane may increase and the safety may decrease.

本発明における中空糸膜束の製造方法は何ら限定されるものではないが、例えば特開２０００−３００６６３公報で知られるような方法が例示される。例えば、ポリエーテルスルホン（４８００Ｐ、住友化学社製）１６質量％とポリビニルピロリドン（Ｋ−９０、ＢＡＳＦ社製）５質量％、ジメチルアセトアミド７４質量％、水５質量％を混合溶解し、脱泡したものを紡糸溶液として、５０％ジメチルアセトアミド水溶液を芯液として使用し、これを２重管オリフィスの外側、内側より同時に吐出し、５０ｃｍの空走部を経て、７５℃、水の凝固浴中に導き中空糸膜束を形成し、水洗後まきとり、約１００００本束ねたところで筒状ポリプロピレン製フィルムに充填して２７ｃｍの長手にカットし、湿潤状態の中空糸膜束を製造することができる。   Although the manufacturing method of the hollow fiber membrane bundle in this invention is not limited at all, For example, the method known by Unexamined-Japanese-Patent No. 2000-300663 is illustrated. For example, 16% by mass of polyethersulfone (4800P, manufactured by Sumitomo Chemical Co., Ltd.), 5% by mass of polyvinylpyrrolidone (K-90, manufactured by BASF), 74% by mass of dimethylacetamide and 5% by mass of water were mixed and dissolved, and defoamed. As a spinning solution, 50% dimethylacetamide aqueous solution is used as the core solution, and this is simultaneously discharged from the outside and inside of the double tube orifice. A hollow fiber membrane bundle can be produced by forming a guide hollow fiber membrane bundle, scraping it after washing with water, and bundling about 10,000 bundles, filling a cylindrical polypropylene film and cutting it into a length of 27 cm.

本発明における乾燥方法は、例えば上記方法等により得られた湿潤状態の中空糸膜束に適用するのが好ましい実施態様である。   The drying method in the present invention is a preferred embodiment that is applied to a wet hollow fiber membrane bundle obtained by the above method, for example.

本発明においては、中空糸膜束中の含水率が１質量％以上飽和含水率未満の範囲で乾燥を終了することが好ましい。１．５〜１０質量％がより好ましく、２．０〜７質量％がさらに好ましい。７質量％を超えると該中空糸膜束を用いてモジュールを組み立てる際の中空糸膜束をモジュールのハウジングに固定する接着工程において、接着不良が発生する危険性がある。   In the present invention, it is preferable to finish the drying in the range where the moisture content in the hollow fiber membrane bundle is 1% by mass or more and less than the saturated moisture content. 1.5-10 mass% is more preferable, and 2.0-7 mass% is further more preferable. If it exceeds 7% by mass, there is a risk of poor adhesion in the bonding step of fixing the hollow fiber membrane bundle to the module housing when the module is assembled using the hollow fiber membrane bundle.

本発明の含水率（％）とは、乾燥前の中空糸膜の重量（ａ）、乾燥後の中空糸膜束の質量（ｂ）を測定し、含水率（％）＝（ａ−ｂ）×１００／ｂにより容易に算定できる。   The moisture content (%) of the present invention means the weight (a) of the hollow fiber membrane before drying, the mass (b) of the hollow fiber membrane bundle after drying, and the moisture content (%) = (ab). It can be easily calculated by × 100 / b.

なお、飽和含水率とは、水膨潤状態にある膜の微細構造の空孔部分を十分完全に水で充満されている状態であり、選択透過性分離膜を水中に十分浸漬して水分を飽和させた状態で水中より取り出し、表面付着水を取り除いた状態での含水率のことである。該飽和含水率は選択透過性分離膜の素材や構造により変化するが、一般的には４０〜６０質量％である。   The saturated moisture content is a state in which the pores of the fine structure of the membrane in a water-swelled state are sufficiently filled with water, and the selectively permeable separation membrane is sufficiently immersed in water to saturate the water. It is the water content in the state where it is taken out from the water in a state of being removed and the surface adhering water is removed. The saturated water content varies depending on the material and structure of the selectively permeable separation membrane, but is generally 40 to 60% by mass.

含水率が１質量％未満になるよう乾燥すると、中空糸膜束素材のポリビニルピロリドンの劣化が増大し、該劣化物の溶出量が増大し、かつ、中空糸膜束の長手方向の該溶出量変動が大きくなり、例えば血液浄化器用に用いる場合の安全性の低下につながる。また、中空糸膜束の長手方向での中空糸膜束の外表面における該劣化物等親水性化合物の表面濃度の変動が大きくなり、中空糸膜束の親水性化合物の表面濃度の高い部分で部分的な固着が発生するという課題につながる。該部分的な固着が発生するとモジュール組み立て性が悪化する等の問題につながる。さらに、過酸化水素の溶出量が増大し、かつ中空糸膜束の長手方向の該溶出量の変動が大きくなる。過酸化水素が存在すると、例えばポリビニルピロリドンの酸化劣化を促進し、中空糸膜束を保存した時に該ポリビニルピロリドンの溶出量が増加する。すなわち、保存安定性が悪化する。過酸化水素は中空糸膜束の特定部位に存在しても、その個所より中空糸膜束素材の劣化反応が開始され中空糸膜束の全体に伝播していくため、モジュールと用いられる中空糸膜束の長手方向の存在量が全領域にわたり、一定量以下を確保する必要がある。従って、過酸化水素溶出量が増大することは例え局部的といえども安全性の低下につながる。一方、含水率が飽和含水率を超えた場合は、保存時菌が増殖しやすくなったり、中空糸膜の自重により糸潰れが発生したり、モジュール組み立て時に接着剤の接着障害が発生する可能性がある。   When dried so that the water content is less than 1% by mass, the degradation of the polyvinylpyrrolidone of the hollow fiber membrane bundle material increases, the elution amount of the degraded product increases, and the elution amount in the longitudinal direction of the hollow fiber membrane bundle Fluctuations increase, leading to a reduction in safety when used for blood purifiers, for example. In addition, the variation in the surface concentration of the hydrophilic compound such as the deteriorated product on the outer surface of the hollow fiber membrane bundle in the longitudinal direction of the hollow fiber membrane bundle becomes large, and the surface concentration of the hydrophilic compound in the hollow fiber membrane bundle is high. This leads to the problem of partial sticking. If the partial fixing occurs, it leads to problems such as deterioration of the module assembly. Furthermore, the elution amount of hydrogen peroxide increases, and the variation of the elution amount in the longitudinal direction of the hollow fiber membrane bundle increases. In the presence of hydrogen peroxide, for example, the oxidative degradation of polyvinyl pyrrolidone is promoted, and the amount of the polyvinyl pyrrolidone eluted increases when the hollow fiber membrane bundle is stored. That is, storage stability deteriorates. Even if hydrogen peroxide is present in a specific part of the hollow fiber membrane bundle, the degradation reaction of the hollow fiber membrane bundle material starts from that location and propagates to the entire hollow fiber membrane bundle. It is necessary to secure a certain amount or less of the film bundle in the longitudinal direction over the entire region. Therefore, an increase in the elution amount of hydrogen peroxide leads to a decrease in safety even if it is localized. On the other hand, if the moisture content exceeds the saturated moisture content, the bacteria may be easily proliferated during storage, the yarn may be crushed due to the weight of the hollow fiber membrane, or adhesive failure may occur during assembly of the module. There is.

上記の乾燥終了時の含水率管理方法は限定されない。赤外線吸収法等によりオンライン計測をしても良いし、サンプリングによるオフライン計測で行っても良い。   The water content management method at the end of the drying is not limited. Online measurement may be performed by an infrared absorption method or the like, or offline measurement by sampling may be performed.

本発明の乾燥方法における熱源は限定なく、熱風、遠赤外線、マイクロ波等が挙げられる。これらの熱源は単独で用いても良いし、２種以上を併用しても良い。以下に好ましい実施態様を例示する。   The heat source in the drying method of the present invention is not limited, and examples thereof include hot air, far infrared rays, and microwaves. These heat sources may be used independently and may use 2 or more types together. Preferred embodiments are illustrated below.

乾燥工程に関しては従来技術では、例えば特開２０００−３００６６３号公報に開示されているように６０℃のエアを中空糸膜束の長手方向に、一方向から２０時間通風することにより中空糸膜束を乾燥させていた。しかし、この方法では過酸化水素溶出の中空糸膜束の長手方向での変動が大きく好ましい範囲を超える部分が多発し、本発明を満足することができなかった。この理由についてはよくわからないが、エアを一定方向から通風して中空糸膜束の乾燥を行うと、中空糸膜束のエア入口部より出口部に向かって順次乾燥が進行するため、エア入口部では速く乾燥が終了し、エア出口部で遅れて乾燥が終了する。すなわち、エア入口部では中空糸膜束が過乾燥になることによって、中空糸膜束素材の分解劣下が進行し、結果として入口部は該中空糸膜束の構成材料、特に、ポリビニルピロリドンの酸化劣化が増大することにより引き起こされたのではないかと推測する。そこで本発明者ら、中空糸膜束の部分的な過乾燥を防ぎ、均等に乾燥させることを目的とし、乾燥時のエアの向きを定時毎（例えば、１時間毎や３０分毎）に１８０度反転しながら中空糸膜束の乾燥処理を行った。また、他の目的として、乾燥時の熱による酸化反応速度を抑制するために、乾燥器内温度および乾燥エアの温度を従来の６０℃から４０℃に低下させることによって本発明の中空糸膜束を得ることができた。上記のごとく、酸化劣化が変動要因になっていると推定されることより、乾燥時の雰囲気を窒素ガス等の不活性ガスに置換して実施する方法も有効である。   With respect to the drying process, in the prior art, for example, as disclosed in Japanese Patent Application Laid-Open No. 2000-300663, a hollow fiber membrane bundle is obtained by passing air at 60 ° C. in the longitudinal direction of the hollow fiber membrane bundle for 20 hours from one direction. Was dried. However, in this method, fluctuations in the longitudinal direction of the hollow fiber membrane bundle eluted with hydrogen peroxide are large, and many portions exceeding the preferred range occur, and the present invention cannot be satisfied. I do not know the reason for this well, but when air is ventilated from a certain direction and the hollow fiber membrane bundle is dried, the air inlet portion of the hollow fiber membrane bundle is sequentially dried from the air inlet portion to the outlet portion. Then, the drying is completed quickly, and the drying is completed with a delay at the air outlet. That is, the hollow fiber membrane bundle becomes excessively dried at the air inlet portion, so that degradation of the hollow fiber membrane bundle material proceeds.As a result, the inlet portion is made of the constituent material of the hollow fiber membrane bundle, particularly polyvinylpyrrolidone. It is presumed that it was caused by an increase in oxidative degradation. Therefore, the present inventors aim to prevent partial overdrying of the hollow fiber membrane bundle and to dry it uniformly, and the direction of air during drying is set to 180 at regular intervals (for example, every hour or every 30 minutes). The hollow fiber membrane bundle was dried while being inverted. As another object, the hollow fiber membrane bundle of the present invention is reduced by reducing the temperature in the dryer and the temperature of the drying air from the conventional 60 ° C. to 40 ° C. in order to suppress the oxidation reaction rate due to heat during drying. Could get. As described above, it is estimated that oxidation deterioration is a fluctuation factor. Therefore, it is also effective to perform the method by substituting the atmosphere during drying with an inert gas such as nitrogen gas.

乾燥器内の風量および風速は、中空糸膜束の量、総含水量に応じて通風乾燥器を調整すればよいが、通常は風量が０．０１〜５Ｌ／ｓｅｃ（中空糸膜束１本）程度で足りる。通風媒体としては不活性ガスを用いるのが好ましいが、通常の空気を使用する場合には、除湿したものを使用するのが好ましい。乾燥温度は２０〜８０℃であればよいが、温度を高くすると、中空糸膜束の損傷を大きくし、乾燥が部分的にアンバランスになりがちであるから、比較的常温から最高６０℃程度までにするのが好ましい。例えば、含水率２００〜１０００質量％のように含水率が高い状態では、６０〜８０℃と比較的高い温度で乾燥可能であるが、乾燥が進行し、例えば含水率が１〜５０質量％程度に低下に伴い比較的温度の低い常温から最高６０℃程度の範囲において乾燥するのが好ましい。乾燥は、中空糸膜の中心部分および外周部分は勿論のこと、それを束ねた中空糸膜束の中心部分および外周部分の水分含有率に較差がないのが理想的である。実際には中空糸膜、中空糸膜束の、中心部および外周部の含水率に若干の差がある。したがって、ここでいう中空糸膜束の「含水率」とは、中空糸膜束の中心部、中間部および外周部などの何点かの含水率を算定の根拠にして、それら何点かの含水率の平均値を求めた平均含水率のことである。勿論それほどの精度を期待しない場合には、中空糸膜束の水分総量を算定の根拠にすることも可能であるが、精度が下がるという弊害がある。そして、中空糸膜束の中心部、中間部および外周部などの含水率の較差が小さいということは、品質のよい製品を造るための好ましい実施態様であるから、それを製造する乾燥方法に技術的な配慮をする必要がある。通風媒体として、例えば、窒素ガス、アルゴンガスなどの不活性ガスを使用する場合には、実質的に無酸素状態での乾燥であるため親水性高分子の劣化分解が起こりにくく、乾燥温度を高めることが可能である。   The air volume and speed in the dryer may be adjusted by the ventilation dryer according to the amount of the hollow fiber membrane bundle and the total water content. Usually, the air volume is 0.01 to 5 L / sec (one hollow fiber membrane bundle). ) Is enough. As the ventilation medium, it is preferable to use an inert gas. However, when normal air is used, it is preferable to use a dehumidified medium. The drying temperature may be 20 to 80 ° C. However, if the temperature is increased, damage to the hollow fiber membrane bundle is increased, and drying tends to become partially unbalanced. It is preferable that For example, in a state where the moisture content is high, such as a moisture content of 200 to 1000% by mass, drying is possible at a relatively high temperature of 60 to 80 ° C., but the drying proceeds, for example, the moisture content is about 1 to 50% by mass. As the temperature decreases, it is preferable to dry in a range from a relatively low temperature of room temperature to a maximum of about 60 ° C. Ideally, there is no difference in the moisture content of the central portion and the outer peripheral portion of the hollow fiber membrane bundle in which the drying is performed as well as the central portion and the outer peripheral portion of the hollow fiber membrane. Actually, there is a slight difference in the moisture content of the center portion and the outer peripheral portion of the hollow fiber membrane and the hollow fiber membrane bundle. Therefore, the “moisture content” of the hollow fiber membrane bundle here refers to the water content at several points such as the center, middle, and outer periphery of the hollow fiber membrane bundle, based on the calculation. It is the average moisture content which calculated | required the average value of the moisture content. Of course, when not so much accuracy is expected, the total amount of water in the hollow fiber membrane bundle can be used as a basis for calculation, but there is an adverse effect that the accuracy is lowered. And since it is a preferable embodiment for producing a good quality product that the difference in moisture content of the hollow fiber membrane bundle such as the central part, the intermediate part and the outer peripheral part is small, it is technical to the drying method for producing it. It is necessary to give special consideration. For example, when an inert gas such as nitrogen gas or argon gas is used as the ventilation medium, since the drying is performed in a substantially oxygen-free state, the degradation and decomposition of the hydrophilic polymer hardly occur, and the drying temperature is increased. It is possible.

風量および乾燥温度は、中空糸膜束に含まれる水分総量により決まる。含水率が高い場合に風量を例えば０．１〜５Ｌ／ｓｅｃ（中空糸膜束１本）という比較的高く設定し、温度も５０〜８０℃と比較的高く設定する。乾燥が進行し、中空糸膜束の水分含有量が低くなったら、風量を、例えば０．１Ｌ／ｓｅｃ（中空糸膜束１本）以下に徐々に下げるという風量を調整し、一方で、温度もそれに連動させ徐々に常温に近づける乾燥方法を採用することが乾燥の工夫の一つである。中空糸膜束の中心部、中間部および外周部などの含水率の較差が小さいということは、各部の乾燥が同時に均一に進行させることでもある。このため、中空糸膜束を通風乾燥するときに送風向きを交互に逆転させるということは、通風乾燥機における中空糸膜束に対する送風の向きを１８０度変えた方向から交互に変えて送風することである。勿論、その送風方向の反転は内容物である中空糸膜束それ自体を通風方向に対して１８０度交互に回転させるというように装置を工夫する場合もある。又、乾燥のための中空糸膜束を固定し、送風装置に工夫して通風方向を交互に１８０度程度変えた方向から送風する方法もあるが、送風手段に関しては特に限定する必要はない。特に循環型送風乾燥機の場合には、内容物の中空糸膜束それ自体を交互に１８０度反転させるような装置が設計上は勿論のこと、運転上も合理的に機能する。この一見ありふれたような、反転を含む本発明の乾燥方法は、特に中空糸膜束という、特殊な材料において、一束の部分固着を防ぐという品質管理において、汎用の材料の乾燥には見られない、予期しえぬ成果をあげることができたというものである。   The air volume and the drying temperature are determined by the total amount of water contained in the hollow fiber membrane bundle. When the moisture content is high, the air volume is set to a relatively high value of, for example, 0.1 to 5 L / sec (one hollow fiber membrane bundle), and the temperature is also set to a relatively high value of 50 to 80 ° C. When drying progresses and the moisture content of the hollow fiber membrane bundle becomes low, the air volume is adjusted to gradually reduce the air volume to, for example, 0.1 L / sec (one hollow fiber membrane bundle) or less. One of the ideas of drying is to adopt a drying method that gradually moves it to room temperature in conjunction with it. The small difference in the moisture content of the hollow fiber membrane bundle such as the central part, the intermediate part, and the outer peripheral part means that the drying of each part proceeds simultaneously and uniformly. For this reason, when the hollow fiber membrane bundle is air-dried, the air blowing direction is alternately reversed. This means that the air blowing direction with respect to the hollow fiber membrane bundle in the air dryer is alternately changed from the direction changed by 180 degrees. It is. Of course, the device may be devised such that the reversal of the air blowing direction causes the hollow fiber membrane bundle itself, which is the contents, to rotate 180 degrees alternately with respect to the air flow direction. Further, there is a method in which a hollow fiber membrane bundle for drying is fixed, and a blower is devised to blow air from the direction in which the ventilation direction is alternately changed by about 180 degrees. However, the blower means is not particularly limited. In particular, in the case of a circulation type blower / dryer, an apparatus that alternately inverts the hollow fiber membrane bundle of the contents itself by 180 degrees functions not only in design but also in operation. The drying method of the present invention including reversal, which is common at first glance, is found in the drying of general-purpose materials, particularly in the quality control of preventing a bundle of partial sticking in a special material such as a bundle of hollow fiber membranes. There was no unexpected result.

乾燥における、通風の交互反転時間は、乾燥するための中空糸膜束の水分総量および風速、風量、乾燥温度、空気の除湿程度などの要因により変わる性格のものであるが、均一乾燥を求めるなら、送風方向をこまめに反転させることが好ましい。工業的に実用上設定される風向反転時間は乾燥開始後の含水率にも影響するが、例えば６０〜８０℃程度の高温で、例えば６５℃で１〜４時間、２５〜６０℃において、例えば３０℃程度において１〜２０時間乾燥するという、総乾燥時間が２４時間という長い時間を設定した場合に、３０〜６０分程度の間隔で機械的に風向を反転させることができる。水分総量が多い、初期の乾燥段階において、例えば６０〜８０℃程度の高温において、０．１〜５Ｌ／ｓｅｃ（中空糸膜束１本）程度の比較的風量が多い条件で乾燥する場合には、最初に風の直接当たる部分の乾燥が比較的早いから、１０〜１２０分程度の間隔で風向の反転を、１〜５時間程度繰り返す。特に、最初の段階は１０〜４０分間隔で風向を反転させることが好ましい。中空糸膜束の中心部および外周部の含水率の較差が少なくなり、安定してきたら、乾燥温度も徐々に３０℃程度の常温に近づけ、反転時間も３０〜９０分程度の間隔で風向の反転を繰り返し、比較的長い１〜２４時間程度その風向の反転を繰り返せばよい。その際の風量および温度の切り換えは、中空糸膜束の含水率を考慮して任意に決めることができる。それを定量的に示せば、中空糸膜束の中心部および外周部の水分含有量を算定の根拠にした、含水率が５０〜１００質量％程度以下になったら、乾燥の状況を観察しながら適宜変更することができる。乾燥ということであるから、固定した時間間隔で機械的に風向反転時間を設定して行うことができる。一方で、乾燥の進行の程度を観察しながら風向反転時間、総乾燥時間を決めるという、状況判断や経験則に頼るような要素もある。なお、本発明の含水率（％）とは、乾燥前の中空糸膜束の質量（ａ）乾燥後の中空糸膜束の質量（ｂ）を測定し、含水率（％）＝（ａ−ｂ）×１００／ｂにより容易に算定できる。   The alternate inversion time of ventilation in the drying is of a character that varies depending on factors such as the total moisture content of the hollow fiber membrane bundle for drying and the wind speed, air volume, drying temperature, degree of dehumidification of the air, etc. It is preferable to frequently reverse the blowing direction. The wind direction reversal time that is practically set industrially affects the moisture content after the start of drying, for example, at a high temperature of about 60 to 80 ° C., for example, at 65 ° C. for 1 to 4 hours, at 25 to 60 ° C., for example, When the total drying time of 24 hours is set at about 30 ° C. for 1 to 20 hours, the wind direction can be mechanically reversed at intervals of about 30 to 60 minutes. In the initial drying stage where the total amount of moisture is large, for example, when drying at a high temperature of about 60 to 80 ° C. under conditions of relatively large air volume of about 0.1 to 5 L / sec (one hollow fiber membrane bundle) First, since the portion directly exposed to the wind is relatively dry, the reversal of the wind direction is repeated for about 1 to 5 hours at intervals of about 10 to 120 minutes. In particular, in the first stage, it is preferable to reverse the wind direction at intervals of 10 to 40 minutes. When the difference in moisture content at the center and the outer periphery of the hollow fiber membrane bundle decreases and becomes stable, the drying temperature gradually approaches the room temperature of about 30 ° C., and the reversal time is reversed at intervals of about 30 to 90 minutes. And the inversion of the wind direction may be repeated for a relatively long 1 to 24 hours. The switching of the air volume and temperature at that time can be arbitrarily determined in consideration of the moisture content of the hollow fiber membrane bundle. If it shows quantitatively, based on the moisture content of the center part and the outer peripheral part of the hollow fiber membrane bundle, when the water content is about 50 to 100% by mass or less, while observing the drying situation It can be changed as appropriate. Since it is drying, it can be performed by mechanically setting the wind direction inversion time at fixed time intervals. On the other hand, there are factors that rely on situational judgment and empirical rules, such as deciding the wind direction inversion time and total drying time while observing the degree of progress of drying. The moisture content (%) of the present invention means the mass of the hollow fiber membrane bundle before drying (a) the mass (b) of the hollow fiber membrane bundle after drying, and the moisture content (%) = (a− b) It can be easily calculated by x100 / b.

また、減圧下でマイクロ波を照射して乾燥するのも有効な手段の一つである。該乾燥方法の乾燥条件としては、２０ＫＰａ以下の減圧下で出力０．１〜１００ＫＷのマイクロ波を照射することが好ましい実施態様である。また、該マイクロ波の周波数は１，０００〜５，０００ＭＨｚであり、乾燥処理中の中空糸膜束の最高到達温度が９０℃以下であることが好ましい実施態様である。減圧という手段を併設すれば、それだけで水分の乾燥が促進されるので、マイクロ波の照射の出力を低く抑え、照射時間も短縮できる利点もあるが、温度の上昇も比較的低くすることができるので、全体的には中空糸膜束の性能低下に与える影響が少ない。さらに、減圧という手段を伴う乾燥は、乾燥温度を比較的下げることができるという利点があり、特に親水性高分子の劣化分解を著しく抑えることができるという有意な点がある。適正な乾燥温度は２０〜８０℃で十分足りるということになる。より好ましくは２０〜６０℃、さらに好ましくは２０〜５０℃、よりさらに好ましくは３０〜４０℃である。   Moreover, it is one of effective means to dry by irradiating microwaves under reduced pressure. As a drying condition of the drying method, it is preferable to irradiate microwaves having an output of 0.1 to 100 kW under a reduced pressure of 20 KPa or less. Moreover, the frequency of this microwave is 1,000-5,000 MHz, and it is a preferable embodiment that the highest ultimate temperature of the hollow fiber membrane bundle during a drying process is 90 degrees C or less. If a means of decompression is additionally 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 bundle is small as a whole. Furthermore, drying accompanied by means of reduced pressure has the advantage that the drying temperature can be relatively lowered, and has a significant point that deterioration and decomposition of the hydrophilic polymer can be remarkably suppressed. An appropriate drying temperature is sufficient from 20 to 80 ° C. More preferably, it is 20-60 degreeC, More preferably, it is 20-50 degreeC, More preferably, it is 30-40 degreeC.

減圧を伴うということは、中空糸膜束の中心部および外周部に均等に低圧が作用することになり、水分の蒸発が均一に促進されることになり、中空糸膜の乾燥が均一になされるために、乾燥の不均一に起因する中空糸膜束の障害を是正することになる。それに、マイクロ波による加熱も、中空糸膜束の中心および外周全体にほぼ等しく作用することになるから、均一な加熱において、相乗的に機能することになり、中空糸膜束の乾燥において、特有の意義があることになる。減圧度についてはマイクロ波の出力、中空糸膜束の有する総水分含量および中空糸膜束の本数により適宜設定すれば良いが、乾燥中の中空糸膜束の温度上昇を防ぐため減圧度は２０ｋＰａ以下、より好ましくは１５ｋＰａ以下、さらに好ましくは１０ｋＰａ以下で行う。２０ｋＰａ以上では水分蒸発効率が低下するばかりでなく、中空糸膜束を形成するポリマーの温度が上昇してしまい劣下してしまう可能性がある。また、減圧度は高い方が温度上昇抑制と乾燥効率を高める意味で好ましいが、装置の密閉度を維持するためにかかるコストが高くなるので０．１ｋＰａ以上が好ましい。より好ましくは０．２５ｋＰａ以上、さらに好ましくは０．４ｋＰａ以上である。   The fact that the pressure is reduced means that the low pressure acts uniformly on the center portion and the outer peripheral portion of the hollow fiber membrane bundle, the moisture evaporation is promoted uniformly, and the hollow fiber membrane is uniformly dried. Therefore, the failure of the hollow fiber membrane bundle due to non-uniform drying is corrected. In addition, heating by microwaves also acts almost equally on the entire center and outer periphery of the hollow fiber membrane bundle, so it functions synergistically in uniform heating, and is unique in drying the hollow fiber membrane bundle. It will be of significance. The degree of vacuum may be appropriately set according to the output of the microwave, the total moisture content of the hollow fiber membrane bundle, and the number of hollow fiber membrane bundles, but the degree of vacuum is 20 kPa to prevent the temperature of the hollow fiber membrane bundle during drying. Hereinafter, it is performed more preferably at 15 kPa or less, and further preferably at 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 bundle 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.

乾燥時間短縮を考慮するとマイクロ波の出力は高いほうが好ましいが、例えばポリビニルピロリドンを含有する中空糸膜束では過乾燥や過過熱によるポリビニルピロリドンの劣化、分解が起こったり、使用時の濡れ性低下が起こるなどの問題があるため、出力はあまり上げないのが好ましい。また０．１ｋＷ未満の出力でも中空糸膜束を乾燥することは可能であるが、乾燥時間が伸びることによる処理量低下の問題が起こる可能性がある。減圧度とマイクロ波出力の組合せの最適値は、中空糸膜束の保有水分量および中空糸膜束の処理本数により異なるものであって、試行錯誤のうえ適宜設定値を求めるのが好ましい。
例えば、本発明の乾燥条件を実施する一応の目安として、中空糸膜束１本当たり５０ｇの水分を有する中空糸膜束を２０本乾燥した場合、総水分含量は５０ｇ×２０本＝１，０００ｇとなり、この時のマイクロ波の出力は１．５ｋＷ、減圧度は５ｋＰａが適当である。 In consideration of shortening the drying time, a higher microwave output is preferable, but for example, a hollow fiber membrane bundle containing polyvinylpyrrolidone deteriorates or decomposes polyvinylpyrrolidone due to overdrying or overheating, and decreases wettability during use. It is preferable not to raise the output much because there are problems such as occurring. Further, the hollow fiber membrane bundle can be dried even with an output of less than 0.1 kW, but there is a possibility that a problem of reduction in throughput due to an increase in drying time may occur. The optimum value of the combination of the degree of decompression and the microwave output varies depending on the water content of the hollow fiber membrane bundle and the number of processed hollow fiber membrane bundles, and it is preferable to obtain a set value as appropriate through trial and error.
For example, as a temporary guide for carrying out the drying conditions of the present invention, when 20 hollow fiber membrane bundles having a moisture content of 50 g per hollow fiber membrane bundle are dried, the total moisture content is 50 g × 20 fibers = 1,000 g. At this time, it is appropriate that the microwave output is 1.5 kW and the decompression degree is 5 kPa.

より好ましいマイクロ波出力は０．１〜８０ｋＷ、さらに好ましいマイクロ波出力は０．１〜６０ｋＷである。マイクロ波の出力は、例えば、中空糸膜の総数と総含水量により決まるが、いきなり高出力のマイクロ波を照射すると、短時間で乾燥が終了するが、中空糸膜が部分的に変性することがあり、縮れのような変形を起こすことがある。マイクロ波を使用して乾燥するという場合に、例えば、中空糸膜に保水剤のようなものを用いた場合に、高出力やマイクロ波を用いて過激に乾燥することは保水剤の飛散による消失の原因にもなる。それに特に減圧下の条件をともなうと中空糸膜への影響を考えれば、従来においては減圧下でマイクロ波を照射することは意図していなかった。本発明の減圧下でマイクロ波を照射するということは、水性液体の蒸発が比較的温度が低い状態においても活発になるため、高出力マイクロ波および高温によるポリビニルピロリドンの劣化や中空糸膜の変形等の中空糸膜の損傷を防ぐという二重の効果を奏することになる。   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 moisture content. 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. Considering the influence on the hollow fiber membrane especially when the conditions under reduced pressure are considered, conventionally, it was not intended to irradiate microwaves under reduced pressure. Irradiation of microwaves under reduced pressure of the present invention means that the evaporation of aqueous liquid becomes active even in a relatively low temperature state. Thus, a double effect of preventing damage to the hollow fiber membrane is obtained.

本発明は、減圧下におけるマイクロ波により乾燥をするという、マイクロ波の出力を一定にした一段乾燥を可能としているが、別の実施態様として、乾燥の進行に応じて、マイクロ波の出力を順次段階的に下げる、いわゆる多段乾燥を好ましい態様として包含している。そこで、多段乾燥の意義を説明すると次のようになる。減圧下で、しかも３０〜９０℃程度の比較的低い温度で、マイクロ波で乾燥する場合に、中空糸膜束の乾燥の進み具合に合わせて、マイクロ波の出力を順次下げていくという多段乾燥方法が優れている。乾燥をする中空糸膜の総量、工業的に許容できる適正な乾燥時間などを考慮して、減圧の程度、温度、マイクロ波の出力および照射時間を決めればよい。多段乾燥は、例えば、２〜６段という任意に何段も可能であるが、生産性を考慮して工業的に適正と許容できるのは、２〜３段乾燥にするのが適当である。中空糸膜束に含まれる水分の総量にもよるが、比較的多い場合に、多段乾燥は、例えば、９０℃以下の温度における、５〜２０ｋＰａ程度の減圧下で、一段目は３０〜１００ｋＷの範囲で、二段目は１０〜３０ｋＷの範囲で、三段目は０．１〜１０ｋＷというように、マイクロ波照射時間を加味して決めることができる。マイクロ波の出力を、例えば、高い部分で９０ｋＷ、低い部分で０．１ｋＷのように、出力の較差が大きい場合には、その出力を下げる段数を例えば４〜８段と多くすればよい。本発明の場合に、減圧というマイクロ波照射に技術的な配慮をしているから、比較的マイクロ波の出力を下げた状態でもできるという有利な点がある。例えば、一段目は１０〜２０ｋＷのマイクロ波により１０〜１００分程度、二段目は３〜１０ｋＷ程度で５〜８０分程度、三段目は０．１〜３ｋＷ程度で１〜６０分程度という段階で乾燥する。各段のマイクロ波の出力および照射時間は、中空糸膜に含まれる水分の総量の減り具合に連動して下げていくことが好ましい。この乾燥方法は、中空糸膜束に非常に温和な乾燥方法であり、前掲の特許文献８〜１０の先行技術においては期待できないことから、本発明の作用効果を有意にしている。   Although the present invention enables one-stage drying in which the microwave output is constant, i.e., drying by microwaves under reduced pressure, as another embodiment, the microwave output is sequentially changed according to the progress of drying. So-called multi-stage drying, which lowers in stages, is included as a preferred embodiment. Therefore, the significance of multi-stage drying will be described as follows. When drying with microwaves at a relatively low temperature of about 30 to 90 ° C. under reduced pressure, multi-stage drying in which the output of the microwaves is sequentially reduced in accordance with the progress of drying of the hollow fiber membrane bundle. The method is excellent. The degree of pressure reduction, temperature, microwave output and irradiation time may be determined in consideration of the total amount of hollow fiber membranes to be dried and the industrially acceptable drying time. Multistage drying can be performed in any number of stages, for example, 2 to 6 stages, but it is appropriate to use 2 to 3 stages of drying that is industrially appropriate in consideration of productivity. Depending on the total amount of water contained in the hollow fiber membrane bundle, when relatively large, multistage drying is performed at a temperature of 90 ° C. or lower, for example, at a reduced pressure of about 5 to 20 kPa, and the first stage is 30 to 100 kW. The range can be determined in consideration of the microwave irradiation time such that the second stage is in the range of 10 to 30 kW and the third stage is in the range of 0.1 to 10 kW. When the output of the microwave is large, such as 90 kW in the high part and 0.1 kW in the low part, the number of stages for reducing the output may be increased to 4 to 8 stages, for example. In the case of the present invention, since technical consideration is given to the microwave irradiation called decompression, there is an advantage that the microwave output can be relatively lowered. For example, the first stage is about 10 to 100 minutes by 10 to 20 kW microwave, the second stage is about 3 to 10 kW and about 5 to 80 minutes, and the third stage is about 0.1 to 3 kW and about 1 to 60 minutes. Dry in stages. It is preferable that the microwave output and irradiation time of each stage are lowered in conjunction with the reduction in the total amount of moisture contained in the hollow fiber membrane. This drying method is a very gentle drying method for hollow fiber membrane bundles and cannot be expected in the prior arts of the above-mentioned Patent Documents 8 to 10, and thus makes the effects of the present invention significant.

別の態様を説明すると、中空糸膜束の水分総量が比較的少ないという、いわゆる含水率が４００質量％以下の場合には、１２ｋＷ以下の低出力マイクロ波による照射が優れている場合がある。例えば、中空糸膜束総量の水分量が１〜７ｋｇ程度と比較的少量の場合には、８０℃以下、好ましくは６０℃以下の温度における、３〜１０ｋＰａ程度の減圧下において、１２ｋＷ以下の出力の、例えば１〜５ｋＷ程度のマイクロ波で１０〜２４０分、０．５〜１ｋＷ未満のマイクロ波で１〜２４０分程度、好ましくは３〜２４０分、０．１〜０．５ｋＷ未満のマイクロ波で１〜２４０分程度照射するという、乾燥の程度に応じてマイク口波の照射出力および照射時間を調整すれば乾燥が均一に行われる。減圧度は各段において、一応０．１〜２０ｋＰａという条件を設定しているが、中空糸膜の水分含量の比較的多い一段目を例えば０．１〜５ｋＰａと減圧を高め、マイクロ波の出力を１０〜３０ｋＷと高める、二段目、三段目を５〜２０ｋＰａの減圧下で０．１〜５ｋＷによる一段よりやや高い圧力下でマイクロ波を照射するという、いわゆる各段の減圧度を状況に応じて適正に調整して変えることなどは、中空糸膜束の水分総量および含水率の低下の推移を考慮して任意に設定することが可能である。各段において、減圧度を変える操作は、本発明の減圧下でマイクロ波を照射するという意義をさらに大きくする。勿論、マイクロ波照射装置内におけるマイクロ波の均一な照射および排気には常時配慮する必要がある。   To explain another aspect, when the so-called moisture content of the hollow fiber membrane bundle is relatively small, that is, a so-called moisture content of 400% by mass or less, irradiation with a low output microwave of 12 kW or less may be excellent. For example, when the amount of water in the total amount of the hollow fiber membrane bundle is about 1 to 7 kg, the output is 12 kW or less under a reduced pressure of about 3 to 10 kPa at a temperature of 80 ° C. or less, preferably 60 ° C. or less. For example, microwaves of about 1 to 5 kW for 10 to 240 minutes, microwaves of less than 0.5 to 1 kW for about 1 to 240 minutes, preferably 3 to 240 minutes, microwaves of less than 0.1 to 0.5 kW If the irradiation output and the irradiation time of the microphone mouth wave are adjusted according to the degree of drying, ie, irradiation for about 1 to 240 minutes, the 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 decompression at each stage, in which microwaves are 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 bundle. In each stage, the operation of changing the degree of reduced pressure further increases the significance of irradiating microwaves under reduced pressure according to the present invention. Of course, it is necessary to always consider the uniform irradiation and exhaust of the microwave in the microwave irradiation apparatus.

中空糸膜束の乾燥を、減圧下でマイクロ波を照射して乾燥することと、通風向きを交互に逆転する乾燥方法を併用することも乾燥において工程が煩雑にはなるが、有効な乾燥方法である。マイクロ波照射方法および通風交互逆転方法も、一長一短があり、高度の品質が求められる場合に、これらを併用することができる。最初の段階で、通風交互逆転方法を採用して、平均含水量が２０〜６０質量％程度に進行したら、次の段階で減圧下でマイクロ波を照射して乾燥することができる。この場合に、比較的マイクロ波を照射して乾燥してから、次に通風向きを交互に逆転する乾燥方法を併用することもできる。これらは、乾燥により製造される中空糸膜の品質、特に中空糸膜における長さ方向において部分固着がないポリスルホン系選択透過性中空糸膜束の品質を考慮して決めることができる。これらの乾燥方法を同時に行うこともできるが、装置の煩雑さ、複雑さ、価格の高騰などの不利な点があるため実用的ではない。しかし、遠赤外線等の有効な加熱方法を併用することは本発明の乾燥方法の範囲からは排除しない。   The drying of the hollow fiber membrane bundle is performed by irradiating with microwaves under reduced pressure, and using a drying method that alternately reverses the direction of ventilation also makes the process complicated in drying, but an effective drying method It is. The microwave irradiation method and the alternating ventilation reverse method also have merits and demerits, and these can be used in combination when high quality is required. In the first stage, when the average alternating water content proceeds to about 20 to 60% by mass by adopting a ventilation alternating reversal method, it can be dried by irradiating microwaves under reduced pressure in the next stage. In this case, after drying by relatively irradiating microwaves, a drying method that alternately reverses the direction of ventilation can be used in combination. These can be determined in consideration of the quality of the hollow fiber membrane produced by drying, in particular, the quality of the polysulfone-based permselective hollow fiber membrane bundle having no partial fixation in the length direction of the hollow fiber membrane. These drying methods can be performed simultaneously, but are not practical because of disadvantages such as the complexity and complexity of the apparatus and the price increase. However, the combined use of an effective heating method such as far infrared rays is not excluded from the scope of the drying method of the present invention.

乾燥中の中空糸膜束の最高到達温度は、不可逆性のサーモラベルを中空糸膜束を保護するフィルム側面に貼り付けて乾燥を行い、乾燥後に取り出し表示を確認することで測定することができる。この時、乾燥中の中空糸膜束の最高到達温度は９０℃以下が好ましく、より好ましくは８０℃以下に抑える。さらに好ましくは７０℃以下である。最高到達温度が９０℃以上になると、膜構造が変化しやすくなり性能低下や酸化劣化を起こしてしまう場合がある。特にポリビニルピロリドンを含有する中空糸膜束では、熱によるポリビニルピロリドンの分解等が起こりやすいので温度上昇をできるだけ防ぐ必要がある。減圧度とマイクロ波出力の最適化と断続的に照射することで温度上昇を防ぐことができる。また、乾燥温度は低い方が好ましいが、減圧度の維持コスト、乾燥時間短縮の面より３０℃以上が好ましい。   The maximum temperature reached by the hollow fiber membrane bundle during drying can be measured by applying an irreversible thermolabel to the side of the film that protects the hollow fiber membrane bundle, drying, and checking the display after taking out the drying. . At this time, the maximum reached temperature of the hollow fiber membrane bundle during drying is preferably 90 ° C. or lower, more preferably 80 ° C. or lower. More preferably, it is 70 degrees C or less. If the maximum temperature reaches 90 ° C. or higher, the film structure is likely to change, which may cause performance degradation or oxidative degradation. In particular, in a hollow fiber membrane bundle containing polyvinylpyrrolidone, it is necessary to prevent the temperature rise as much as possible because polyvinylpyrrolidone is easily decomposed by heat. Temperature rise can be prevented by optimizing the degree of decompression and microwave output and irradiating intermittently. Moreover, although the one where a drying temperature is lower is preferable, 30 degreeC or more is preferable from the surface of the maintenance cost of pressure reduction degree, and the shortening of drying time.

マイクロ波の照射周波数は、中空糸膜束への照射斑の抑制や、細孔内の水を細孔より押出す効果などを考慮すると１，０００〜５，０００ＭＨｚが好ましい。より好ましくは１，５００〜４，０００ＭＨｚ、さらに好ましくは２，０００〜３，０００ＭＨｚである。   The microwave irradiation frequency is preferably 1,000 to 5,000 MHz in consideration of the suppression of irradiation spots on the hollow fiber membrane bundle and the effect of extruding water in the pores from the pores. More preferably, it is 1,500-4,000 MHz, More preferably, it is 2,000-3,000 MHz.

該マイクロ波照射による乾燥は中空糸膜束を均一に加熱し乾燥することが重要である。上記したマイクロ波乾燥においては、マイクロ波の発生時に付随発生する反射波による不均一加熱が生じるので、該反射波による不均一加熱を低減する手段を取る事が重要である。該方策は限定されず任意であるが、例えば、特開２０００−３４０３５６号公報において開示されているオーブン中に反射板を設けて反射波を反射させ加熱の均一化を行う方法が好ましい実施態様の一つである。   In drying by microwave irradiation, it is important to uniformly heat and dry the hollow fiber membrane bundle. In the above-described microwave drying, nonuniform heating due to the reflected wave 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.

本発明における中空糸膜束は、乾燥中空糸膜束を長手方向に１０個に分割し、各々を透析型人工腎臓装置製造承認基準により定められた試験を実施したとき、１０個に分割したすべの部位で抽出液中の過酸化水素濃度が５ｐｐｍ以下であることが好ましい。ここで、透析型人工腎臓装置製造承認基準の溶出試験は、該分割した中空糸膜束から１ｇをはかりとる。これに１００ｍｌのＲＯ水を加え、７０℃１時間抽出を行いＵＶ（２２０−３５０ｎｍ）吸光度を測定するものであるが、該抽出液中の過酸化水素を定量することにより求めたものである。   The hollow fiber membrane bundle according to the present invention is divided into 10 when the dry hollow fiber membrane bundle is divided into 10 pieces in the longitudinal direction and each is subjected to a test defined by the dialysis-type artificial kidney device manufacturing approval criteria. It is preferable that the hydrogen peroxide concentration in the extract is 5 ppm or less. Here, the elution test of the dialysis-type artificial kidney device manufacturing approval standard measures 1 g from the divided hollow fiber membrane bundle. 100 ml of RO water was added to this, and extraction was carried out at 70 ° C. for 1 hour to measure UV (220-350 nm) absorbance, which was determined by quantifying hydrogen peroxide in the extract.

該過酸化水素溶出量は、４ｐｐｍ以下がより好ましく、３ｐｐｍ以下がさらに好ましい。該過酸化水素の溶出量が５ｐｐｍを超えた場合は、過酸化水素による酸化劣化等で前記の保存安定性が悪化し、例えば、長期保存した場合にポリビニルピロリドンの溶出量が増大することがある。保存安定性としては、該ポリビニルピロリドンの溶出量の増加が最も顕著な現象であるが、その他、ポリスルホン系高分子の劣化が引き起こされて中空糸膜束がもろくなるとか、モジュール組み立てに用いるポリウレタン系接着剤の劣化を促進し該劣化物の溶出量が増加し安全性の低下につながる可能性がある。該長期保存における過酸化水素の酸化作用により引き起こされる劣化起因の溶出量の増加は透析型人工腎臓装置製造承認基準により設定されているＵＶ（２２０−３５０ｎｍ）吸光度の測定により評価できる。   The hydrogen peroxide elution amount is more preferably 4 ppm or less, and further preferably 3 ppm or less. When the elution amount of the hydrogen peroxide exceeds 5 ppm, the storage stability is deteriorated due to oxidative degradation caused by hydrogen peroxide, for example, the elution amount of polyvinylpyrrolidone may increase when stored for a long period of time. . In terms of storage stability, the increase in the amount of polyvinylpyrrolidone eluted is the most prominent phenomenon. In addition, deterioration of the polysulfone polymer causes the hollow fiber membrane bundle to become brittle, or the polyurethane system used for module assembly. There is a possibility that the deterioration of the adhesive is promoted, the amount of elution of the deteriorated product is increased, and the safety is lowered. The increase in the amount of elution due to deterioration caused by the oxidizing action of hydrogen peroxide in the long-term storage can be evaluated by measuring UV (220-350 nm) absorbance set by the dialysis artificial kidney device manufacturing approval standard.

さらに、本発明においては乾燥中空糸膜束をドライボックス中（雰囲気は空気）に室温で３ヶ月保存した後の中空糸膜束透析型人工腎臓装置製造承認基準により定められた試験を実施したとき、中空糸膜の抽出液におけるＵＶ（２２０〜３５０ｎｍ）吸光度が０．１０以下であることが好ましい。５ヶ月以上保存しても上記特性が維持されるのがより好ましい。そのためには、３ヶ月保存後のＵＶ（２２０〜３５０ｎｍ）吸光度が０．０８以下であることがより好ましく、０．０６以下であることがさらに好ましい。中空糸膜束の製造工程、輸送および在庫用の保管等で乾燥状態の中空糸膜束を保管することを考慮すると上記特性の付与が好ましい。なお、該３ヶ月保存後のＵＶ（２２０〜３５０ｎｍ）吸光度は中空糸膜束を長手方向に１０個に分割し、各々について測定した時の平均値で評価したものである。   Furthermore, in the present invention, when a test defined by the approval criteria for manufacturing a hollow fiber membrane bundle dialysis artificial kidney device is performed after the dried hollow fiber membrane bundle is stored in a dry box (atmosphere is air) at room temperature for 3 months. The UV (220 to 350 nm) absorbance in the hollow fiber membrane extract is preferably 0.10 or less. More preferably, the above properties are maintained even after storage for 5 months or longer. Therefore, the UV (220 to 350 nm) absorbance after storage for 3 months is more preferably 0.08 or less, and further preferably 0.06 or less. In consideration of storing the hollow fiber membrane bundle in a dry state in the manufacturing process of the hollow fiber membrane bundle, transportation and storage for inventory, etc., it is preferable to give the above characteristics. The UV (220-350 nm) absorbance after storage for 3 months is evaluated by the average value when the hollow fiber membrane bundle is divided into 10 pieces in the longitudinal direction and measured for each.

上記特性は、前記の乾燥中空糸膜束を長手方向に１０個に分割し、各々を透析型人工腎臓装置製造承認基準により定められた試験を実施したとき、１０個に分割したすべの部位で抽出液中の過酸化水素濃度が５ｐｐｍ以下であるという特性を満足することにより達成することができる。また、上記特性は、本発明において開示する製造方法の実施により達成することができる。   The above-mentioned characteristics are that the dry hollow fiber membrane bundle is divided into 10 pieces in the longitudinal direction, and each of the parts divided into 10 pieces is subjected to the test defined by the dialysis type artificial kidney device manufacturing approval standard. This can be achieved by satisfying the characteristic that the hydrogen peroxide concentration in the extract is 5 ppm or less. Further, the above characteristics can be achieved by carrying out the manufacturing method disclosed in the present invention.

透析型人工腎臓装置製造承認基準を満たすためにはＵＶ（２２０−３５０ｎｍ）吸光度は０．１０未満が必須であり本発明においても必要要件であるが、従来技術で明らかにされていなかった前記の要件を満たすことにより始めて中空糸膜束を長期にわたり保存しても、該透析型人工腎臓装置製造承認基準であるＵＶ（２２０−３５０ｎｍ）吸光度を０．１０以下に維持することができることを見出したことが本発明の大きな特徴である。すなわち、図１に示す概念図により本発明の意図する中空糸膜束の長期安定性が確保できることになる。   In order to satisfy the dialysis-type artificial kidney device manufacturing approval standard, the UV (220-350 nm) absorbance must be less than 0.10, which is a necessary requirement in the present invention. It was found that UV (220-350 nm) absorbance, which is the dialysis-type artificial kidney device manufacturing approval standard, can be maintained at 0.10 or less even if the hollow fiber membrane bundle is stored for a long time for the first time by satisfying the requirements. This is a major feature of the present invention. That is, the conceptual diagram shown in FIG. 1 can ensure the long-term stability of the hollow fiber membrane bundle intended by the present invention.

上記の過酸化水素の溶出量を達成するためには、前述の乾燥上がりの含水率や乾燥方法が重要であるが、過酸化水素の生成の原因物質であるポリビニルピロリドンの品質や取り扱い等も重要な要因であり配慮が必要である。例えば、ポリビニルピロリドンとして過酸化水素含有量が３００ｐｐｍ以下のものを用いて製造することが好ましい。原料として用いるポリビニルピロリドン中の該過酸化水素含有量を３００ｐｐｍ以下にすることで、製膜後の中空糸膜束の過酸化水素溶出量を５ｐｐｍ以下に抑えることができ、本発明の中空糸膜束の品質安定化が達成できるので好ましい。したがって、原料として用いるポリビニルピロリドン中の過酸化水素含有量は２５０ｐｐｍ以下がより好ましく、２００ｐｐｍ以下がさらに好ましく、１５０ｐｐｍ以下がよりさらに好ましい。   In order to achieve the above elution amount of hydrogen peroxide, the water content after drying and the drying method are important, but the quality and handling of polyvinyl pyrrolidone, which is the causative agent of hydrogen peroxide generation, are also important. This is a major factor and needs attention. For example, it is preferable to produce using polyvinyl pyrrolidone having a hydrogen peroxide content of 300 ppm or less. By setting the hydrogen peroxide content in the polyvinylpyrrolidone used as a raw material to 300 ppm or less, the hydrogen peroxide elution amount of the hollow fiber membrane bundle after film formation can be suppressed to 5 ppm or less, and the hollow fiber membrane of the present invention It is preferable because the bundle quality can be stabilized. Therefore, the hydrogen peroxide content in the polyvinylpyrrolidone used as a raw material is more preferably 250 ppm or less, further preferably 200 ppm or less, and further preferably 150 ppm or less.

該原料として用いるポリビニルピロリドン中に含有される過酸化水素は、ポリビニルピロリドンの酸化劣化の過程で発生すると推定される。従って、過酸化水素含有量を３００ｐｐｍ以下にするには、ポリビニルピロリドンの製造工程でポリビニルピロリドンの酸化劣化を抑える方策をとることが有効である。また、ポリビニルピロリドンの搬送や保存時の劣化を抑える手段を取る事も有効であり推奨される。例えば、アルミ箔ラミネート袋を用いて、遮光し、かつ窒素ガス等の不活性ガスで封入するとか、脱酸素剤を併せて封入し保存することが好ましい実施態様である。また、該包装体を開封し小分けする場合の計量や仕込みは、不活性ガス置換をして行い、かつその保存についても上記の対策を取るのが好ましい。また、中空糸膜束の製造工程においても、原料供給系での供給タンク等を不活性ガス置換する等の手段をとることも好ましい実施態様として推奨される。また、再結晶法や抽出法で過酸化水素量を低下させる方法をとることも排除されない。   It is estimated that hydrogen peroxide contained in polyvinylpyrrolidone used as the raw material is generated in the process of oxidative degradation of polyvinylpyrrolidone. Therefore, to reduce the hydrogen peroxide content to 300 ppm or less, it is effective to take measures to suppress the oxidative degradation of polyvinylpyrrolidone in the production process of polyvinylpyrrolidone. It is also effective and recommended to take measures to suppress deterioration during transportation and storage of polyvinylpyrrolidone. 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. Also, in the manufacturing process of the hollow fiber membrane bundle, it is also recommended as a preferred embodiment to take a means such as replacing the supply tank or the like in the raw material supply system with an inert gas. In addition, it is not excluded to take a method of reducing the amount of hydrogen peroxide by a recrystallization method or an extraction method.

また、ポリスルホン系樹脂、ポリビニルピロリドン、溶媒からなる紡糸溶液を撹拌、溶解する際、ポリビニルピロリドン中に過酸化水素が含まれていると、溶解タンク内に存在する酸素の影響および溶解時の加熱の影響により、過酸化水素が爆発的に増加することがわかった。したがって、溶解タンクに原料を投入する際には、予め不活性ガスにて置換された溶解タンク内に原料を投入するのが好ましい。不活性ガスとしては、窒素、アルゴンなどが好適に用いられる。また、溶媒、場合によっては非溶媒を添加することもあるが、これら溶媒、非溶媒中に溶存している酸素を不活性ガスで置換して用いるのも好適な実施態様である。   Also, when stirring and dissolving a spinning solution composed of a polysulfone resin, polyvinyl pyrrolidone, and a solvent, if hydrogen peroxide is contained in the polyvinyl pyrrolidone, the influence of oxygen present in the dissolution tank and the heating during dissolution It was found that hydrogen peroxide increased explosively due to the influence. 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.

該過酸化水素溶出量を上記の規制された範囲に制御する方法としては、例えば、前述したごとく原料として用いるポリビニルピロリドン中の過酸化水素量を３００ｐｐｍ以下にすることが有効な方法であるが、該過酸化水素は上記した中空糸膜の製造過程でも生成するので、該中空糸膜の製造条件を厳密に制御する必要がある。特に、該中空糸膜を製造する際の乾燥工程での生成の寄与が大きいので、乾燥条件の最適化が重要である。特に、この乾燥条件の最適化は、過酸化水素の生成抑制に大きく寄与するので重要である。さらに、該乾燥条件の最適化は、中空糸膜の長手方向の溶出量変動を小さくすることに関して有効な手段となる。   As a method for controlling the elution amount of hydrogen peroxide to the above regulated range, for example, as described above, it is effective to make the amount of hydrogen peroxide in polyvinylpyrrolidone used as a raw material 300 ppm or less. Since the hydrogen peroxide is also produced during the manufacturing process of the hollow fiber membrane described above, it is necessary to strictly control the manufacturing conditions of the hollow fiber membrane. In particular, since the contribution of the production in the drying process when producing the hollow fiber membrane is large, it is important to optimize the drying conditions. In particular, the optimization of the drying conditions is important because it greatly contributes to the suppression of hydrogen peroxide production. Furthermore, the optimization of the drying conditions is an effective means for reducing the fluctuation in the elution amount in the longitudinal direction of the hollow fiber membrane.

また、過酸化水素の発生を抑制する他の方法として、製膜溶液を溶解する際、短時間に溶解することも重要な要件である。そのためには、通常、溶解温度を高くすることおよび／または撹拌速度を上げればよい。しかしながら、そうすると温度および撹拌線速度、せん断力の影響によりポリビニルピロリドンの劣化・分解が進行してしまう。事実、発明者らの検討によれば、製膜溶液中のポリビニルピロリドンの分子量は溶解温度の上昇に従い、分子量のピークトップが分解方向に移動（低分子側にシフト）したり、または低分子側に分解物と思われるショルダーが現れる現象が認められた。以上より原料の溶解速度を向上させる目的で温度を上昇させることは、ポリビニルピロリドンの劣化分解を促進し、ひいては選択透過性分離膜中にポリビニルピロリドンの分解物をブレンドしてしまうことから、例えば、得られた中空糸膜を血液浄化に使用する場合、血液中に分解物が溶出するなど、製品の品質安全上、優れたものとはならなかった。そこで、ポリビニルピロリドンの分解を抑制する目的で低温で原料を混合することを試みた。低温溶解とはいっても氷点下となるような極端な条件にするとランニングコストもかかるため、通常５℃以上７０℃以下が好ましい。６０℃以下がより好ましい。しかし、単純に溶解温度を下げると溶解時間の長時間化によるポリビニルピロリドン劣化分解、操業性の低下や設備の大型化を招くことになり工業的に実施する上では問題がある。   In addition, as another method for suppressing the generation of hydrogen peroxide, it is an important requirement to dissolve the film forming solution in a short time. For this purpose, it is usually sufficient to increase the dissolution temperature and / or increase the stirring speed. However, when it does so, degradation and decomposition of polyvinyl pyrrolidone will proceed due to the influence of temperature, stirring linear velocity and shearing force. In fact, according to the study by the inventors, the molecular weight of polyvinylpyrrolidone in the film-forming solution moves in the direction of decomposition (shifts to the low molecular side) as the dissolution temperature increases, or the low molecular side. The appearance of a shoulder that appears to be a decomposition product was observed. From the above, increasing the temperature for the purpose of improving the dissolution rate of the raw material promotes the degradation and decomposition of polyvinylpyrrolidone, and eventually blends the degradation product of polyvinylpyrrolidone into the selectively permeable separation membrane. When the obtained hollow fiber membrane is used for blood purification, the degradation product is eluted in the blood, and it has not been excellent in terms of product quality safety. Then, it tried to mix a raw material at low temperature in order to suppress decomposition | disassembly of polyvinylpyrrolidone. Even if it is low-temperature dissolution, it is usually preferable to have a temperature of 5 ° C. or higher and 70 ° C. or lower because it requires a running cost under extreme conditions that are below freezing. 60 degrees C or less is more preferable. However, simply lowering the melting temperature causes degradation of polyvinylpyrrolidone due to the longer melting time, lowering the operability and increasing the size of the equipment, which causes problems in industrial implementation.

低温で時間をかけずに溶解するための溶解条件について検討を行った結果、溶解に先立ち紡糸溶液を構成する成分を混練した後に溶解させることが好ましいことを見出し本発明に到達した。該混練はポリスルホン系高分子、ポリビニルピロリドンおよび溶媒等の構成成分を一括して混練しても良いし、ポリビニルピロリドンとポリスルホン系高分子とを別個に混練しても良い。前述のごとくポリビニルピロリドンは酸素との接触により劣化が促進され過酸化水素の発生につながるので、該混練時においても不活性ガスで置換した雰囲気で行う等、酸素との接触を抑制する配慮が必要であり別ラインで行うのが好ましい。混練はポリビニルピロリドンと溶媒のみとしてポリスルホン系高分子は予備混練をせずに直接溶解タンクに供給する方法も本発明の範ちゅうに含まれる。   As a result of examining the dissolution conditions for dissolving at low temperature without taking time, it was found that it is preferable to knead the components constituting the spinning solution prior to dissolution, and the present invention was reached. The kneading may be performed by kneading components such as polysulfone polymer, polyvinyl pyrrolidone and a solvent at once, or kneading polyvinyl pyrrolidone and polysulfone polymer separately. As mentioned above, polyvinylpyrrolidone is accelerated by contact with oxygen and leads to the generation of hydrogen peroxide. Therefore, consideration must be given to suppressing contact with oxygen, such as in an atmosphere substituted with an inert gas, even during kneading. It is preferable to carry out in a separate line. A method of supplying only the polyvinyl pyrrolidone and the solvent and supplying the polysulfone polymer directly to the dissolution tank without pre-kneading is also included in the scope of the present invention.

該混練は溶解タンクと別に混練ラインを設けて実施し混練したものを溶解タンクに供給してもよいし、混練機能を有する溶解タンクで混練と溶解の両方を実施しても良い。前者の別個の装置で実施する場合の、混練装置の種類や形式は問わない。回分式、連続式のいずれであっても構わない。スタティックミキサー等のスタティックな方法であっても良いし、ニーダーや撹拌式混練機等のダイナミックな方法であっても良い。混練の効率より後者が好ましい。後者の場合の混練方法も限定なく、ピンタイプ、スクリュータイプ、撹拌器タイプ等いずれの形式でもよい。スクリュータイプが好ましい。スクリューの形状や回転数も混練効率と発熱とのバランスより適宜選択すれば良い。一方、混練機能を有する溶解タンクを用いる場合の溶解タンクの形式も限定されないが、例えば、２本の枠型ブレードが自転、公転するいわゆるプラネタリー運動により混練効果を発現する形式の混練溶解機が推奨される。例えば、井上製作所社製のプラネタリュームミキサーやトリミックス等が本方式に該当する。   The kneading may be performed by providing a kneading line separately from the dissolving tank, and the kneaded product may be supplied to the dissolving tank, or both the kneading and dissolving may be performed in a dissolving tank having a kneading function. The type and form of the kneading apparatus in the former separate apparatus are not limited. Either a batch system or a continuous system may be used. A static method such as a static mixer may be used, or a dynamic method such as a kneader or a stirring kneader may be used. The latter is preferred from the efficiency of kneading. The kneading method in the latter case is not limited, and any type such as a pin type, a screw type, and a stirrer type may be used. Screw type is preferred. What is necessary is just to select suitably the shape and rotation speed of a screw from the balance of kneading | mixing efficiency and heat_generation | fever. On the other hand, the type of dissolution tank when using a dissolution tank having a kneading function is not limited. Recommended. For example, a planetary mixer or a trimix manufactured by Inoue Seisakusho Co., Ltd. corresponds to this method.

混練時のポリビニルピロリドンやポリスルホン系高分子等の樹脂成分と溶媒との比率も限定されない。樹脂／溶媒の質量比で０．１〜３が好ましい。０．５〜２がより好ましい。   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.

前述のごとくポリビニルピロリドンの劣化を抑制し、かつ効率的な溶解を行うことが本発明の技術ポイントである。従って、請求項８に記載のごとく少なくともポリビニルピロリドンが存在する系は窒素雰囲気下、７０℃以下の低温で混練および溶解することが好ましい実施態様である。ポリビニルピロリドンとポリスルホン系高分子を別ラインで混練する場合にポリスルホン系高分子の混練ラインに本要件を適用してもよい。混練や溶解の効率と発熱とは二律背反現象である。該二律背反をできるだけ回避した装置や条件の選択が本発明の重要な要素となる。そういう意味で混練機構における冷却方法が重要であり配慮が必要である。   As described above, the technical point of the present invention is to suppress the degradation of polyvinyl pyrrolidone and perform efficient dissolution. Accordingly, it is a preferred embodiment that the system in which at least polyvinylpyrrolidone is present as described in claim 8 is kneaded and dissolved in a nitrogen atmosphere at a low temperature of 70 ° C. or lower. 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.

引き続き前記方法で混練されたものの溶解を行う。該溶解方法も限定されないが、例えば、撹拌式の溶解装置による溶解方法が適用できる。低温・短時間（３時間以内）で溶解するためには、フルード数（Ｆｒ＝ｎ２ｄ／ｇ）が０．７以上１．３以下、撹拌レイノルズ数（Ｒｅ＝ｎｄ２ρ／μ）が５０以上２５０以下であることが好ましい。ここでｎは翼の回転数（ｒｐｓ）、ρは密度（Ｋｇ／ｍ３）、μは粘度（Ｐａ・ｓ）、ｇは重力加速度（＝９．８ｍ／ｓ２）、ｄは撹拌翼径（ｍ）である。フルード数が大きすぎると、慣性力が強くなるためタンク内で飛散した原料が壁や天井に付着し、所期の製膜溶液組成が得られないことがある。したがって、フルード数は１．２５以下がより好ましく、１．２以下がさらに好ましく、１．１５以下がよりさらに好ましい。また、フルード数が小さすぎると、慣性力が弱まるために原料の分散性が低下し、特にポリビニルピロリドンが継粉になり、それ以上溶解することが困難となったり、均一溶解に長時間を要することがある。したがって、フルード数は０．７５以上がより好ましく、０．８以上がさらに好ましい。 Subsequently, the material kneaded by the above method is dissolved. Although the dissolution method is not limited, for example, a dissolution method using a stirring type dissolution apparatus can be applied. In order to dissolve at a low temperature for a short time (within 3 hours), the Froude number (Fr = n 2 d / g) is 0.7 to 1.3 and the stirring Reynolds number (Re = nd 2 ρ / μ) is It is preferable that they are 50 or more and 250 or less. Here, n is the blade rotation speed (rps), ρ is the density (Kg / m 3 ), μ is the viscosity (Pa · s), g is the gravitational acceleration (= 9.8 m / s 2 ), and d is the stirring blade diameter. (M). If the Froude number is too large, the inertial force becomes strong, so that the raw material scattered in the tank adheres to the walls and ceiling, and the desired film-forming solution composition may not be obtained. Therefore, the fluid number is more preferably 1.25 or less, further preferably 1.2 or less, and further preferably 1.15 or less. On the other hand, if the fluid number is too small, the inertial force is weakened, so that the dispersibility of the raw material is lowered, and in particular, polyvinylpyrrolidone becomes a spatter, which makes it difficult to dissolve further or requires a long time for uniform dissolution. Sometimes. Therefore, the fluid number is more preferably 0.75 or more, and further preferably 0.8 or more.

本願発明における製膜溶液はいわゆる低粘性流体であるため、撹拌レイノルズ数が大きすぎると、撹拌時、製膜溶液中への気泡のかみこみによる脱泡時間の長時間化や脱泡不足が起こるなどの問題が生ずることがある。そのため、撹拌レイノルズ数はより好ましくは２４０以下、さらに好ましくは２３０以下、よりさらに好ましくは２２０以下である。また、撹拌レイノルズ数が小さすぎると、撹拌力が小さくなるため溶解の不均一化が起こりやすくなることがある。したがって、撹拌レイノルズ数は、３５以上がより好ましく、４０以上がさらに好ましく、５５以上がよりさらに好ましく、６０以上が特に好ましい。さらに、このような紡糸溶液で中空糸膜を製膜すると気泡による曳糸性の低下による操業性の低下や品質面でも中空糸膜への気泡のかみ込みによりその部位が欠陥となり、膜の機密性やバースト圧の低下などを引き起こして問題となることがわかった。紡糸溶液の脱泡は効果的な対処策だが、紡糸溶液の粘度コントロールや溶剤の蒸発による紡糸溶液の組成変化を伴うこともありうるので、行う場合には慎重な対応が必要となる。   Since the film-forming solution in the present invention is a so-called low-viscosity fluid, if the stirring Reynolds number is too large, the defoaming time becomes long due to the entrapment of bubbles in the film-forming solution during stirring, or the defoaming is insufficient. 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, if the stirring Reynolds number is too small, the stirring force becomes small, so that the dissolution may become uneven. Therefore, the stirring Reynolds number is more preferably 35 or more, further preferably 40 or more, still more preferably 55 or more, and particularly preferably 60 or more. Furthermore, when a hollow fiber membrane is formed with such a spinning solution, the operability 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 confidentiality of the membrane 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 be accompanied by a change in the composition of the spinning solution due to viscosity control of the spinning solution or evaporation of the solvent.

さらに、ポリビニルピロリドンは空気中の酸素の影響により酸化分解を起こす傾向にあることから、紡糸溶液の溶解は不活性気体封入下で行うのが好ましい。不活性気体としては、窒素、アルゴンなどが上げられるが、窒素を用いるのが好ましい。このとき、溶解タンク内の残存酸素濃度は３％以下であることが好ましい。窒素封入圧力を高めてやれば溶解時間短縮が望めるが、高圧にするには設備費用がかさむ点と、作業安全性の面から大気圧以上２ｋｇｆ／ｃｍ２以下が好ましい。 Furthermore, since polyvinylpyrrolidone tends to undergo oxidative degradation due to the influence of oxygen in the air, it is preferable to dissolve the spinning solution in an inert gas enclosure. Nitrogen, argon, etc. are raised as the inert gas, but nitrogen is preferably used. At this time, the residual oxygen concentration in the dissolution tank is preferably 3% or less. If the nitrogen 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, the pressure is preferably from atmospheric pressure to 2 kgf / cm 2 .

その他、本願発明に用いるような低粘性製膜溶液の溶解に用いられる撹拌翼形状としては、ディスクタービン型、パドル型、湾曲羽根ファンタービン型、矢羽根タービン型などの放射流型翼、プロペラ型、傾斜パドル型、ファウドラー型などの軸流型翼が挙げられるが、これらに限定されるものではない。   In addition, as the shape of the stirring blade used for dissolving the low-viscosity film forming solution used in the present invention, a radial turbine blade such as a disk turbine type, a paddle type, a curved blade fan turbine type, an arrow blade turbine type, or a propeller type An axial-flow type wing such as an inclined paddle type or a fiddler type is included, but is not limited thereto.

以上のような低温溶解方法を用いることにより、親水性高分子の劣化分解が抑制された安全性の高い中空糸膜を得ることが可能となる。さらに付言すれば、製膜には原料溶解後の滞留時間が２４時間以内の紡糸溶液を使用することが好ましい。なぜなら製膜溶液が保温されている間に熱エネルギーを蓄積し、原料劣化を起こす傾向が認められたためである。   By using the low-temperature dissolution method as described above, it is possible to obtain a highly safe hollow fiber membrane in which the degradation degradation of the hydrophilic polymer is suppressed. In addition, it is preferable to use a spinning solution having a residence time of 24 hours or less after dissolution of the raw material for film formation. This is because thermal energy was accumulated while the film forming solution was kept warm, and a tendency to cause deterioration of the raw material was recognized.

本発明における中空糸膜束のその他の特性は限定されないが、例えば、ポリビニルピロリドンの中空糸膜束の外表面における存在割合が２５〜５０質量％であるのが好ましい。２７〜４５質量％がより好ましく、３０〜４５質量％がさらに好ましい。外表面のポリビニルピロリドンの存在割合が２５質量％未満では膜全体、特に膜内表面のポリビニルピロリドンの存在割合が低くなりすぎ、血液適合性や透過性能の低下が起こる可能性がある。また本発明の乾燥方法を適用しても、プライミング性が低下することがある。血液透析器を血液浄化療法に使用する時には、生理食塩水などを血液透析器の中空糸膜束内外部に流すことにより、湿潤化および泡抜きを行う必要がある。このプライミング操作において、中空糸膜束の真円度や端部の潰れ、変形、膜素材の親水性などが、プライミング性に影響を与えると考えられるが、ポリスルホン系高分子とポリビニルピロリドンからなる中空糸膜束であって乾燥膜モジュールの場合には、中空糸膜束の親疎水バランスがプライミング性に大きく影響する。外表面のポリビニルピロリドンの存在割合が５０質量％を超すと透析液に含まれるエンドトキシン（内毒素）が血液側へ浸入する可能性が高まり、発熱等の副作用を引き起こすことにつながるとか、膜を乾燥させた時に膜外表面に存在するポリビニルピロリドンが介在し中空糸膜束同士が固着し、モジュール組み立て性が悪化する等の課題を引き起こす可能性がある。   Although the other characteristic of the hollow fiber membrane bundle in this invention is not limited, For example, it is preferable that the presence rate in the outer surface of the hollow fiber membrane bundle of polyvinylpyrrolidone is 25-50 mass%. 27-45 mass% is more preferable, and 30-45 mass% is further more preferable. When the proportion of polyvinyl pyrrolidone present on the outer surface is less than 25% by mass, the proportion of polyvinyl pyrrolidone present on the entire membrane, particularly the inner surface of the membrane, becomes too low, and blood compatibility and permeation performance may deteriorate. Even if the drying method of the present invention is applied, the priming property may be lowered. When the hemodialyzer is used for blood purification therapy, it is necessary to perform wetting and defoaming by allowing physiological saline or the like to flow inside and outside the hollow fiber membrane bundle of the hemodialyzer. In this priming operation, the roundness of the hollow fiber membrane bundle, edge crushing, deformation, hydrophilicity of the membrane material, etc. are thought to affect the priming properties. However, the hollow fiber made of polysulfone polymer and polyvinylpyrrolidone In the case of a yarn membrane bundle and a dry membrane module, the hydrophilic / hydrophobic balance of the hollow fiber membrane bundle greatly affects the priming property. If the proportion of polyvinylpyrrolidone present on the outer surface exceeds 50% by mass, the endotoxin (endotoxin) contained in the dialysate may enter the blood, leading to side effects such as fever, or drying the membrane. When this is done, polyvinyl pyrrolidone present on the outer surface of the membrane intervenes and the hollow fiber membrane bundles are fixed to each other, which may cause problems such as deterioration in module assembly.

上記の特性を付与する方法として、例えば、ポリスルホン系高分子に対するポリビニルピロリドンの構成割合を前記した範囲にしたり、中空糸膜束の製膜条件を最適化する等により達成できる。また、製膜された中空糸膜束を洗浄することも有効な方法である。製膜条件としては、ノズル出口のエアギャップ部の湿度調整、延伸条件、凝固浴の温度、凝固液中の溶媒と非溶媒との組成比等の最適化が、また、洗浄方法としては、温水洗浄、アルコール洗浄および遠心洗浄等が有効である。該方法の中で、製膜条件としては、エアギャップ部の湿度および外部凝固液中の溶媒と非溶媒との組成比の最適化が、洗浄方法としてはアルコール洗浄が特に有効である。   As a method for imparting the above properties, for example, the composition ratio of polyvinyl pyrrolidone with respect to the polysulfone-based polymer can be set to the above range, or the film forming conditions of the hollow fiber membrane bundle can be optimized. It is also an effective method to wash the formed hollow fiber membrane bundle. As film forming conditions, humidity adjustment of the air gap part at the nozzle outlet, stretching conditions, temperature of the coagulation bath, optimization of the composition ratio of the solvent and the non-solvent in the coagulation liquid, etc. Washing, alcohol washing, centrifugal washing and the like are effective. Among these methods, as the film forming conditions, optimization of the humidity of the air gap and the composition ratio of the solvent and the non-solvent in the external coagulating liquid is particularly effective as the cleaning method.

内部凝固液としては、０〜８０質量％のジメチルアセトアミド（ＤＭＡｃ）水溶液が好ましい。より好ましくは、１５〜７０質量％、さらに好ましくは２５〜６０質量％、よりさらに好ましくは３０〜５０質量％である。内部凝固液濃度が低すぎると、血液接触面のち密層が厚くなるため、溶質透過性が低下する可能性がある。また内部凝固液濃度が高すぎると、ち密層の形成が不完全になりやすく、分画特性が低下する可能性がある。外部凝固液は０〜５０質量％のＤＭＡｃ水溶液を使用するのが好ましい。外部凝固液濃度が高すぎる場合は、外表面開孔率および外表面平均孔面積が大きくなりすぎ、透析使用時エンドトキシンの血液側への逆流入の増大や、バースト圧の低下を起こす可能性がある。したがって、外部凝固液濃度は、より好ましくは４０質量％以下、さらに好ましくは３０質量％以下、よりさらに好ましくは２５質量％以下である。また、外部凝固液濃度が低すぎる場合には、紡糸溶液から持ち込まれる溶媒を希釈するために大量の水を使用する必要があり、また廃液処理のためのコストが増大する。そのため、外部凝固液濃度の下限はより好ましくは５質量％以上である。   As the internal coagulation liquid, a 0 to 80% by mass dimethylacetamide (DMAc) aqueous solution is preferable. More preferably, it is 15-70 mass%, More preferably, it is 25-60 mass%, More preferably, it is 30-50 mass%. If the concentration of the internal coagulation solution is too low, the dense layer of the blood contact surface becomes thick, which may reduce the solute permeability. On the other hand, if the concentration of the internal coagulating liquid is too high, the formation of the dense layer tends to be incomplete, and the fractionation characteristics may be deteriorated. The external coagulation liquid is preferably a 0 to 50% by weight DMAc aqueous solution. If the concentration of the external coagulation solution is too high, the outer surface open area ratio and outer surface average pore area will become too large, which may increase the backflow of endotoxin to the blood side during dialysis and decrease the burst pressure. is there. Therefore, the external coagulation liquid concentration is more preferably 40% by mass or less, further preferably 30% by mass or less, and still more preferably 25% by mass or less. If the concentration of the external coagulation liquid is too low, it is necessary to use a large amount of water to dilute the solvent brought in from the spinning solution, and the cost for waste liquid treatment increases. Therefore, the lower limit of the external coagulation liquid concentration is more preferably 5% by mass or more.

上記中空糸膜束の製造において、完全に中空糸膜束構造が固定される以前に実質的に延伸をかけないことが好ましい。実質的に延伸をかけないとは、ノズルから吐出された紡糸溶液に弛みや過度の緊張が生じないように紡糸工程中のローラー速度をコントロールすることを意味する。吐出線速度／凝固浴第一ローラー速度比（ドラフト比）は０．７〜１．８が好ましい範囲である。前記比が０．７未満では、走行する中空糸膜束に弛みが生じ生産性の低下につながることがあるので、ドラフト比は０．８以上がより好ましく、０．９以上がさらに好ましく、０．９５以上がよりさらに好ましい。１．８を超える場合には中空糸膜束のち密層が裂けるなど膜構造が破壊されることがある。そのため、ドラフト比は、より好ましくは１．７以下、さらに好ましくは１．６以下、よりさらに好ましくは１．５以下、特に好ましくは１．４以下である。ドラフト比をこの範囲に調整することにより細孔の変形や破壊を防ぐことができ、膜孔への血中タンパクの目詰まりを防ぎ経時的な性能安定性やシャープな分画特性を発現することが可能となる。   In the production of the hollow fiber membrane bundle, it is preferable that stretching is not substantially performed before the hollow fiber membrane bundle structure is completely fixed. “Substantially no stretching” means that the roller speed during the spinning process is controlled so that the spinning solution discharged from the nozzle does not become slack or excessively tensioned. The discharge linear speed / coagulation bath first roller speed ratio (draft ratio) is preferably in the range of 0.7 to 1.8. If the ratio is less than 0.7, the running hollow fiber membrane bundle may be slack and lead to a decrease in productivity. Therefore, the draft ratio is more preferably 0.8 or more, more preferably 0.9 or more, and 0 .95 or more is even more preferable. If it exceeds 1.8, the membrane structure may be destroyed, for example, the dense layer of the hollow fiber membrane bundle is torn. Therefore, the draft ratio is more preferably 1.7 or less, still more preferably 1.6 or less, still more preferably 1.5 or less, and particularly preferably 1.4 or less. By adjusting the draft ratio to this range, deformation and destruction of the pores can be prevented, clogging of blood protein into the membrane pores can be prevented, and performance stability over time and sharp fractionation characteristics can be expressed. Is possible.

水洗浴を通過した中空糸膜束は、湿潤状態のまま綛に巻き取り、３，０００〜２０，０００本の束にする。ついで、得られた中空糸膜束を洗浄し、過剰の溶媒、ポリビニルピロリドンを除去する。中空糸膜束の洗浄方法として、本発明では、７０〜１３０℃の熱水、または室温〜５０℃、１０〜４０ｖｏｌ％のエタノールまたはイソプロパノール水溶液に中空糸膜束を浸漬して処理するのが好ましい。
（１）熱水洗浄の場合は、中空糸膜束を過剰のＲＯ水に浸漬し７０〜９０℃で１５〜６０分処理した後、中空糸膜束を取り出し遠心脱水を行う。この操作をＲＯ水を更新しながら３、４回繰り返して洗浄処理を行う。
（２）加圧容器内の過剰のＲＯ水に浸漬した中空糸膜束を１２１℃で２時間程度処理する方法をとることもできる。
（３）エタノールまたはイソプロパノール水溶液を使用する場合も、（１）と同様の操作を繰り返すのが好ましい。
（４）遠心洗浄器に中空糸膜束を放射状に配列し、回転中心から４０℃〜９０℃の洗浄水をシャワー状に吹きつけながら３０分〜５時間遠心洗浄することも好ましい洗浄方法である。
前記洗浄方法を２つ以上組み合わせて行ってもよい。いずれの方法においても、処理温度が低すぎる場合には、洗浄回数を増やす等が必要になりコストアップにつながることがある。また、処理温度が高すぎるとポリビニルピロリドンの分解が加速し、逆に洗浄効率が低下することがある。上記洗浄を行うことにより、外表面ポリビニルピロリドンの存在率の適正化を行い、固着抑制や溶出物の量を減ずることが可能となる。 The hollow fiber membrane bundle that has passed through the water-washing bath is wound into a basket in a wet state to form a bundle of 3,000 to 20,000. Next, the obtained hollow fiber membrane bundle is washed to remove excess solvent, polyvinylpyrrolidone. As a method for washing the hollow fiber membrane bundle, in the present invention, it is preferable to treat the hollow fiber membrane bundle by immersing it in hot water at 70 to 130 ° C. or room temperature to 50 ° C. and 10 to 40 vol% ethanol or isopropanol aqueous solution. .
(1) In the case of hot water washing, the hollow fiber membrane bundle is immersed in excess RO water and treated at 70 to 90 ° C. for 15 to 60 minutes, and then the hollow fiber membrane bundle is taken out and subjected to centrifugal dehydration. This operation is repeated three or four times while updating the RO water to perform the cleaning process.
(2) A method of treating a hollow fiber membrane bundle immersed in excess RO water in a pressurized container at 121 ° C. for about 2 hours may be employed.
(3) When using an ethanol or isopropanol aqueous solution, it is preferable to repeat the same operation as in (1).
(4) It is also a preferable washing method that the hollow fiber membrane bundle is radially arranged in the centrifugal washer, and centrifugal washing is performed for 30 minutes to 5 hours while spraying washing water at 40 ° C. to 90 ° C. from the rotation center in a shower shape. .
Two or more cleaning methods may be combined. In any of the methods, if the processing temperature is too low, it is necessary to increase the number of times of cleaning, which may lead to an increase in cost. On the other hand, if the treatment temperature is too high, the decomposition of polyvinylpyrrolidone is accelerated, and conversely, the cleaning efficiency may be reduced. By performing the above-described cleaning, it is possible to optimize the abundance of the outer surface polyvinyl pyrrolidone, thereby suppressing sticking and reducing the amount of eluate.

また、中空糸膜束の固着に関しては、前述の中空糸膜束を長手方向に１０個に分割し、各々を透析型人工腎臓装置製造承認基準により定められた試験を実施したとき、中空糸膜の抽出液におけるＵＶ（２２０〜３５０ｎｍ）吸光度の最大値と最小値の差が０．０５以下にすることも重要である。該抽出液におけるＵＶ（２２０〜３５０ｎｍ）吸光度は、中空糸膜束の固着に悪影響を及ぼす中空糸膜表面のポリビニルピロリドン存在割合量の指標であり、該中空糸膜束の長手方向の抽出液におけるＵＶ（２２０〜３５０ｎｍ）吸光度変動を抑えることにより、中空糸膜束の長手方向における中空糸膜表面におけるポリビニルピロリドンの存在割合量の変動が抑制されるので中空糸膜束の部分固着の発生が抑制される。また、該変動の抑制は中空糸膜束全体のポリビニルピロリドンの溶出量を低いレベルに保つことにつながるので、血液浄化器用に使用した場合に安全性が向上する。したがって、０．０４５以下が好ましく、０．０４以下がさらに好ましく、０．０３５以下がよりさらに好ましい。   Further, regarding the fixation of the hollow fiber membrane bundle, when the hollow fiber membrane bundle is divided into 10 pieces in the longitudinal direction and each is subjected to a test defined by the dialysis-type artificial kidney device manufacturing approval criteria, It is also important that the difference between the maximum value and the minimum value of UV (220 to 350 nm) absorbance in the above extract is 0.05 or less. The UV (220 to 350 nm) absorbance in the extract is an indicator of the amount of polyvinylpyrrolidone present on the surface of the hollow fiber membrane that adversely affects the fixation of the hollow fiber membrane bundle, and in the extract in the longitudinal direction of the hollow fiber membrane bundle. By suppressing UV (220-350 nm) absorbance fluctuations, fluctuations in the amount of polyvinylpyrrolidone present on the surface of the hollow fiber membrane in the longitudinal direction of the hollow fiber membrane bundle are suppressed, so occurrence of partial sticking of the hollow fiber membrane bundle is suppressed. Is done. Further, the suppression of the fluctuation leads to keeping the elution amount of polyvinyl pyrrolidone in the entire hollow fiber membrane bundle at a low level, so that the safety is improved when used for a blood purifier. Therefore, 0.045 or less is preferable, 0.04 or less is more preferable, and 0.035 or less is even more preferable.

該ＵＶ吸光度の最大値は、固着に影響をおよぼす外表面の親水性高分子の存在割合が少なく、かつ抽出される溶出物が存在しないという意味からＵＶ吸光度の下限値は０であることが好ましいが、本発明に於いてＵＶ吸光度の最大値は０．０３以上０．１未満であることが好ましい。０．０３に満たなくなると膜内表面の親水性高分子の存在量が十分ではないために、膜の濡れ性に乏しく、膜性能を十分に発揮できない可能性がある。より好ましくは０．０３３以上、さらに好ましくは０．０３５以上、よりさらに好ましくは０．０３７以上である。また、UV吸光度が低いということは、すなわち溶出物量が少ないことを意味するので、UV吸光度の最大値は０．０９未満がより好ましく、０．０８５未満がさらに好ましく、０．０８未満がよりさらに好ましい。   The maximum value of the UV absorbance is preferably 0 because the ratio of the hydrophilic polymer on the outer surface that affects the fixation is small and there is no eluate to be extracted. However, in the present invention, the maximum value of UV absorbance is preferably 0.03 or more and less than 0.1. When the amount is less than 0.03, the hydrophilic polymer existing on the inner surface of the film is not sufficient, so that the film wettability is poor and the film performance may not be sufficiently exhibited. More preferably, it is 0.033 or more, More preferably, it is 0.035 or more, More preferably, it is 0.037 or more. In addition, the low UV absorbance means that the amount of eluate is small, so the maximum value of UV absorbance is more preferably less than 0.09, further preferably less than 0.085, and even more preferably less than 0.08. preferable.

上記の中空糸膜束を長手方向に１０個に分割し、各々を透析型人工腎臓装置製造承認基準により定められた試験を実施したとき、中空糸膜の抽出液におけるＵＶ（２２０〜３５０ｎｍ）吸光度の最大値と最小値の差が０．０５以下にすることも、本発明において開示する製造方法の実施により達成することができる。本要件も従来技術では明らかにされていない新規要件である。   When the above hollow fiber membrane bundle is divided into 10 pieces in the longitudinal direction and each is subjected to a test defined by the dialysis artificial kidney device manufacturing approval standard, UV (220 to 350 nm) absorbance in the hollow fiber membrane extract The difference between the maximum value and the minimum value can be made 0.05 or less by carrying out the manufacturing method disclosed in the present invention. This requirement is also a new requirement that has not been clarified in the prior art.

以下、本発明の有効性を実施例を挙げて説明するが、本発明はこれらに限定されるものではない。なお、以下の実施例における物性の評価方法は以下の通りである。   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、透水率
透析器の血液出口部回路（圧力測定点よりも出口側）を鉗子により流れを止め全ろ過とする。３７℃に保温した純水を加圧タンクに入れ、レギュレーターにより圧力を制御しながら、３７℃高温槽で保温した透析器へ純水を送り、透析液側から流出したろ液をメスシリンダーで測定する。膜間圧力差（ＴＭＰ）は
ＴＭＰ＝（Ｐｉ＋Ｐｏ）／２
とする。ここでＰｉは透析器入り口側圧力、Ｐｏは透析器出口側圧力である。ＴＭＰを４点変化させろ過流量を測定し、それらの関係の傾きから透水性（ｍＬ／ｈｒ／ｍｍＨｇ）を算出する。このときＴＭＰとろ過流量の相関係数は０．９９９以上でなくてはならない。また回路による圧力損失誤差を少なくするために、ＴＭＰは１００ｍｍＨｇ以下の範囲で測定する。中空糸膜束の透水性は膜面積と透析器の透水性から算出する。
ＵＦＲ（Ｈ）＝ＵＦＲ（Ｄ）／Ａ
ここでＵＦＲ（Ｈ）は中空糸膜束の透水性（ｍＬ／ｍ２／ｈｒ／ｍｍＨｇ）、ＵＦＲ（Ｄ）は透析器の透水性（ｍＬ／ｈｒ／ｍｍＨｇ）、Ａは透析器の膜面積（ｍ２）である。 1. The flow is stopped by forceps at the blood outlet circuit of the water-permeability dialyzer (the outlet side from the pressure measurement point) and total filtration is performed. Purified water kept at 37 ° C is placed in 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 high-temperature bath, and the 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 bundle is calculated from the membrane area and the water permeability of the dialyzer.
UFR (H) = UFR (D) / A
Here, UFR (H) is the water permeability (mL / m 2 / hr / mmHg) of the hollow fiber membrane bundle, UFR (D) is the water permeability of the dialyzer (mL / hr / mmHg), and A is the membrane area of the dialyzer (M 2 ).

２、膜面積の計算
透析器の膜面積は中空糸の内径基準として求める。
Ａ＝ｎ×π×ｄ×Ｌ
ここで、ｎは透析器内の中空糸本数、πは円周率、ｄは中空糸の内径（ｍ）、Ｌは透析器内の中空糸の有効長（ｍ）である。 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、バースト圧
約１００００本の中空糸膜束よりなるモジュールの透析液側を水で満たし栓をする。血液側から室温で乾燥空気または窒素を送り込み１分間に０．５ＭＰａの割合で加圧していく。圧力を上昇させ、中空糸膜束が加圧空気によって破裂（バースト）し、透析液側に満たした液に気泡が発生した時の空気圧をバースト圧とする。 3. Fill the dialysis solution side of the module consisting of a bundle of hollow fiber membranes with a burst pressure of about 10,000 with water and plug it. Dry air or nitrogen is fed from the blood side at room temperature and pressurized at a rate of 0.5 MPa per minute. The pressure is increased, and the air pressure when the hollow fiber membrane bundle bursts (bursts) with pressurized air and bubbles are generated in the liquid filled on the dialysate side is defined as the burst pressure.

４、偏肉度
中空糸１００本の断面を２００倍の投影機で観察する。一視野中最も膜厚差がある一本の糸断面について、最も厚い部分と最も薄い部分の厚さを測定する。
偏肉度＝最薄部／最厚部
偏肉度＝１で膜厚が完ぺきに均一となる。 4. Unevenness of thickness The cross section of 100 hollow fibers is observed with a 200 times projector. The thickness of the thickest part and the thinnest part is measured for one yarn cross section having the most difference in film thickness in one field of view.
Uneven thickness = thinnest part / thickest part Uneven thickness = 1 so that the film thickness is perfectly uniform.

５、ポリビニルピロリドンの溶出量
＜乾燥中空糸膜束モジュール＞
透析型人工腎臓装置製造基準に定められた方法で抽出し、該抽出液中のポリビニルピロリドンを比色法で定量した。
すなわち、中空糸膜束１ｇに純水１００ｍｌを加え、７０℃で１時間抽出する。得られた抽出液２．５ｍｌ、０．２モルクエン酸水溶液１．２５ｍｌ、０．００６規定のヨウ素水溶液０．５ｍｌをよく混合し、室温で１０分間放置した、後に４７０ｎｍでの吸光度を測定した。定量は標品のポリビニルピロリドンを用いて上記方法に従い測定する事により求めた検量線にて行った。
＜湿潤中空糸膜束モジュール＞
モジュールの透析液側流路に生理食塩水を５００ｍＬ／ｍｉｎで５分間通液し、ついで血液側流路に２００ｍＬ／ｍｉｎで通液した。その後血液側から透析液側に２００ｍＬ／ｍｉｎでろ過をかけながら３分間通液した後にフリーズドライをして乾燥膜を得て、該乾燥膜を用いて上記定量を行った。 5. Elution amount of polyvinylpyrrolidone <Dry hollow fiber membrane bundle module>
Extraction was performed by the method defined in the dialysis artificial kidney device production standard, and polyvinylpyrrolidone in the extract was quantified by a colorimetric method.
That is, 100 ml of pure water is added to 1 g of the hollow fiber membrane bundle 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.
<Wet hollow fiber membrane bundle module>
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 allowed to pass 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.

６、ＵＶ（２２０−３５０ｎｍ）吸光度
ポリビニルピロリドンの溶出量測定法において記載した方法で抽出した抽出液を分光光度計（日立製作所社製、Ｕ−３０００）を用いて波長範囲２００〜３５０ｎｍの吸光度を測定し、この波長範囲での最大の吸光度を求めた。
該測定は、中空糸膜束を長手方向に２．７ｃｍずつ１０個に等分し、各々の部位から乾燥状態の中空糸膜束１ｇをはかりとり全サンプルについて測定した。
湿潤中空糸膜モジュールの場合は、ポリビニルピロリドン溶出量の測定と同様に処理することにより得た乾燥膜を用いて測定した。 6. UV (220-350 nm) absorbance The extract obtained by the method described in the method for measuring the elution amount of polyvinylpyrrolidone was measured for absorbance in the wavelength range of 200 to 350 nm using a spectrophotometer (Hitachi, U-3000). Measurement was made to determine the maximum absorbance in this wavelength range.
In the measurement, the hollow fiber membrane bundle was equally divided into 10 pieces of 2.7 cm in the longitudinal direction, and 1 g of the hollow fiber membrane bundle in a dry state was weighed from each portion and measured for all samples.
In the case of a wet hollow fiber membrane module, the measurement was performed using a dry membrane obtained by processing in the same manner as the measurement of the amount of polyvinylpyrrolidone eluted.

７、過酸化水素の定量
前記した方法で抽出した抽出液２．６ｍｌに塩化アンモニウム緩衝液（ＰＨ８．６）０．２ｍｌとモル比で当量混合したＴｉＣｌ４の塩化水素溶液と４−（２−ピリジルアゾ）レゾルシノールのＮａ塩水溶液との混合液を０．４ｍＭに調製した発色試薬０．２ｍｌを加え、５０℃で５分間加温後、室温に冷却し５０８ｎｍの吸光度を測定。標品を用いて同様に測定して求めた検量線にて定量した。
該測定は、中空糸膜束を長手方向に２．７ｃｍずつ１０個に等分し、各々の部位から乾燥状態の中空糸膜束１ｇをはかりとり全サンプルについて測定した。
湿潤中空糸膜モジュールの場合は、ポリビニルピロリドン溶出量の測定と同様に処理することにより得た乾燥膜を用いて測定した。 7. 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- Pyridylazo) Resorcinol Na salt aqueous solution prepared in 0.2 mM was added to 0.2 ml of coloring reagent, heated at 50 ° C. for 5 minutes, cooled to room temperature, and the absorbance at 508 nm was measured. It quantified with the analytical curve calculated | required similarly using the sample and calculated | required.
In the measurement, the hollow fiber membrane bundle was equally divided into 10 pieces of 2.7 cm in the longitudinal direction, and 1 g of the hollow fiber membrane bundle in a dry state was weighed from each portion and measured for all samples.
In the case of a wet hollow fiber membrane module, the measurement was performed using a dry membrane obtained by processing in the same manner as the measurement of the amount of polyvinylpyrrolidone eluted.

８、血液リークテスト
クエン酸を添加し、凝固を抑制した３７℃の牛血液を、血液浄化器に２００ｍＬ／ｍｉｎで送液し、２０ｍＬ／ｍｉｎの割合で血液をろ過する。このとき、ろ液は血液に戻し、循環系とする。６０分間後に血液浄化器のろ液を採取し、赤血球のリークに起因する赤色を目視で観察する。この血液リーク試験を各実施例、比較例ともに３０本の血液浄化器を用い、血液リークしたモジュール数を調べる。 8. Blood Leak Test A 37 ° C. bovine blood to which citric acid is added and coagulation is suppressed is fed to a blood purifier at 200 mL / min, and the blood is filtered at a rate of 20 mL / min. At this time, the filtrate is returned to blood to be a circulatory system. After 60 minutes, the filtrate from the blood purifier is collected, and the red color resulting from red blood cell leakage is visually observed. In this blood leak test, 30 blood purifiers were used in each example and comparative example, and the number of blood leaked modules was examined.

９、乾燥中空糸膜束の保存安定性
前記した各種溶出量の測定に用いた乾燥状態のサンプルを、湿度５０％に調湿されたドライボックス中（雰囲気は空気）に室温で３ヶ月間保存した後、前記した方法でＵＶ（２２０−３５０ｎｍ）吸光度を測定した。該保存によるＵＶ（２２０−３５０ｎｍ）吸光度の増加度で安定性を判定した。該増加度は中空糸膜束を長手方向に２．７ｃｍずつ１０個に等分し、それぞれのサンプルについて測定し、その平均値で判定した。平均値が０．１を超えないものを合格とした。 9. Storage stability of dried hollow fiber membrane bundles The samples in the dry state used to measure the various elution amounts described above are stored in a dry box (atmosphere is air) conditioned at 50% humidity for 3 months at room temperature. After that, UV (220-350 nm) absorbance was measured by the method described above. Stability was determined by the degree of increase in UV (220-350 nm) absorbance due to the storage. The degree of increase was determined by dividing the hollow fiber membrane bundle into 10 pieces of 2.7 cm in the longitudinal direction, measuring each sample, and determining the average value. Those whose average value did not exceed 0.1 were regarded as acceptable.

（実施例１）
ポリエーテルスルホン（住化ケムテックス社製、スミカエクセル５２００Ｐ）１質量部ポリビニルピロリドン（ＢＡＳＦ社製コリドンＫ−９０）０．１４５質量部、ＤＭＡｃ１．５質量部を２軸のスクリュータイプの混練機で混練した。得られた混練物をＤＭＡｃ２．９６質量部および水０．１７質量部を仕込んだ撹拌式の溶解機に添加し、３時間撹拌をし溶解した。混練および溶解は内温が３０℃以上に上がらないように冷却した。ついで真空ポンプを用いて系内を−５００ｍｍＨｇまで減圧した後、溶媒等が蒸発して製膜溶液組成が変化しないように直ぐに系内を密閉し１５分間放置した。この操作を３回繰り返して製膜溶液の脱泡を行った。脱泡が完了した後、系内を再度窒素置換を行い弱加圧状態で維持した。なお、上記ポリビニルピロリドンとしては、過酸化水素含有量１３０ｐｐｍのものを用い、原料供給系での供給タンクや前記の溶解槽を窒素ガス置換した。また、溶解時のフルード数および撹拌レイノルズ数はそれぞれ１．１および１２０であった。製膜溶液を１０μｍ、５μｍの２段の焼結フィルターに順に通した後、７５℃に加温したチューブインオリフィスノズルから中空形成剤として予め−７００ｍｍＨｇで３０分間脱気処理した５０℃の６０質量％ＤＭＡｃ水溶液を用いて吐出、紡糸管により外気と遮断された４００ｍｍの乾式部を通過後、６０℃の２０ｗｔ％ＤＭＡｃ水溶液中で凝固させ、湿潤状態のまま綛にまき上げた。使用したチューブインオリフィスノズルのノズルスリット幅は、平均６０μｍであり、最大６１μｍ、最小５９μｍ、スリット幅の最大値、最小値の比は１．０３、ドラフト比は１．２であった。 (Example 1)
1 part by weight of polyethersulfone (manufactured by Sumika Chemtex, Sumika Excel 5200P) 0.145 parts by weight of polyvinylpyrrolidone (Collidon K-90 by BASF) and 1.5 parts by weight of DMAc are kneaded with a twin-screw type kneader. did. The obtained kneaded material was added to a stirring-type dissolver charged with 2.96 parts by mass of DMAc and 0.17 parts by mass of water, and dissolved by stirring for 3 hours. The kneading and dissolution were cooled so that the internal temperature did not rise above 30 ° C. 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 etc. evaporated and the film forming solution composition 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. 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 Froude number and the stirring Reynolds number at the time of dissolution were 1.1 and 120, respectively. The membrane-forming solution was passed through a two-stage sintered filter of 10 μm and 5 μm in order, and then degassed at −700 mmHg for 30 minutes in advance from a tube-in orifice nozzle heated to 75 ° C. for 60 mass at 50 ° C. After passing through a 400 mm dry section, which was discharged with a% DMAc aqueous solution and cut off from the outside air by a spinning tube, it was coagulated in a 20 wt% DMAc aqueous solution at 60 ° C. and wound up in a wet state. 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 1.2.

得られた湿潤中空糸膜約１０，０００本の束を中空糸膜束に接触する表面がエンボス加工されたポリエチレン製のフィルムを巻きつけた後、２７ｃｍの長さに切断し、８０℃の熱水中で３０分間×４回洗浄し、オーブン中に反射板を設置し均一加熱ができるような構造を有したマイクロ波照射方式の乾燥器に導入し、以下の条件で乾燥した。７ＫＰａの減圧下、１．５ＫＷの出力で３０分間中空糸膜束を加熱した後、マイクロ波照射を停止すると同時に減圧度１．５ｋＰａに上げ３分間維持した。つづいて減圧度を７ｋＰａに戻し、かつマイクロ波を照射し０．５ＫＷの出力で１０分間中空糸膜束を加熱した後、マイクロ波を切断し減圧度を上げ０．７ｋＰａを３分間維持した。さらに減圧度を７ｋＰａに戻し、０．２ＫＷの出力で８分間マイクロ波の照射を行い中空糸膜束の加熱をした。マイクロ波切断後、減圧度を０．５ｋＰａに上げ５分間維持することにより中空糸膜束のコンディショニングを行い乾燥を終了した。この際の中空糸膜束表面の最高到達温度は６５℃であった。乾燥前の中空糸膜束の含水率は３３５質量％、１段目終了後の中空糸膜束の含水率は、中空糸膜束の中心部、中間部および外周部などの何点かの含水率を算定の根拠にするが、それら３点の含水率の平均値を求め３５質量％、２段目終了後の中空糸膜束の含水率は１３質量％、３段目終了後の中空糸膜束の含水率は２．２質量％であった。得られた中空糸膜束の内径は１９８μｍ、膜厚は２８μｍであった。紡糸工程中、中空糸膜束が接触するローラーは全て表面が鏡面加工されたもの、ガイドは全て表面が梨地加工されたものを使用した。 A bundle of about 10,000 obtained wet hollow fiber membranes was wrapped with a polyethylene film whose surface was in contact with the hollow fiber membrane bundle, and then cut into a length of 27 cm and heated at 80 ° C. The plate was washed in water for 30 minutes x 4 times, installed in a microwave irradiation type dryer having a structure in which a reflector was installed in an oven and uniformly heated, and dried under the following conditions. After heating the hollow fiber membrane bundle for 30 minutes under a reduced pressure of 7 KPa with an output of 1.5 KW, the microwave irradiation was stopped and simultaneously the 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 10 minutes, and then the microwave was cut to increase the degree of vacuum and maintain 0.7 kPa for 3 minutes. Further, the degree of vacuum was returned to 7 kPa, and the hollow fiber membrane bundle was heated by microwave irradiation for 8 minutes at an output of 0.2 kW. After microwave cutting, the degree of vacuum was raised to 0.5 kPa and maintained for 5 minutes to condition the hollow fiber membrane bundle and finish drying. The maximum temperature reached on the surface of the hollow fiber membrane bundle at this time was 65 ° C. The moisture content of the hollow fiber membrane bundle before drying is 335% by mass, and the moisture content of the hollow fiber membrane bundle after completion of the first stage is the water content of several points such as the central part, intermediate part and outer peripheral part of the hollow fiber membrane bundle. The water content of the hollow fiber membrane bundle after the completion of the second stage is 13% by mass, and the hollow fiber after the completion of the third stage. The water content of the membrane bundle was 2.2% by mass. The obtained hollow fiber membrane bundle had an inner diameter of 198 μm and a film thickness of 28 μm. During the spinning process, all the rollers with which the hollow fiber membrane bundle contacts were mirror-finished on the surface, and the guides were all finished with a satin finish.

得られた乾燥中空糸膜束を長手方向に２．７ｃｍずつ１０個に等分し、各々の部位から乾燥状態の中空糸膜１ｇをはかりとり、透析型人工腎臓装置製造承認基準試験に準じて抽出液を得、抽出液中の過酸化水素濃度およびＵＶ（２２０−３５０ｎｍ）吸光度を測定した。過酸化水素およびＵＶ（２２０−３５０ｎｍ）吸光度は全部位において低レベルで安定していた。過酸化水素濃度測定結果を表１および２に、ＵＶ（２２０−３５０ｎｍ）吸光度測定結果を表３にまとめた。また、得られた中空糸膜束の乾燥状態での保存安定性は良好であり３ヶ月間保存後の中空糸膜束を１０等分した各部位より得られた抽出液のＵＶ（２２０−３５０ｎｍ）吸光度の最大値は０．０４であり、最大値で見ても基準値の０．１０以下が維持されていた。結果を表４にまとめた。さらに、各部位のＵＶ吸光度レベルは低レベルで安定しており、３ヶ月保存後でも部分固着の発生なくモジュール組み立ての作業性は良好であった。   The obtained dry hollow fiber membrane bundle was equally divided into 10 pieces of 2.7 cm in the longitudinal direction, and 1 g of the dry hollow fiber membrane was weighed from each part, and in accordance with the dialysis artificial kidney device production approval standard test. An extract was obtained, and the hydrogen peroxide concentration and UV (220-350 nm) absorbance in the extract were measured. Hydrogen peroxide and UV (220-350 nm) absorbance were stable at low levels at all sites. The hydrogen peroxide concentration measurement results are summarized in Tables 1 and 2, and the UV (220-350 nm) absorbance measurement results are summarized in Table 3. Further, the storage stability of the obtained hollow fiber membrane bundle in a dry state is good, and UV (220-350 nm) of the extract obtained from each part obtained by dividing the hollow fiber membrane bundle after storage for 3 months into 10 equal parts. ) The maximum value of absorbance was 0.04, and the reference value of 0.10 or less was maintained even when viewed from the maximum value. The results are summarized in Table 4. Furthermore, the UV absorbance level of each part was stable at a low level, and the workability of module assembly was good without partial sticking even after storage for 3 months.

このようにして得られた中空糸膜束を用いて血液浄化器を組み立て、リークテストを行った結果、中空糸膜同士の固着に起因するような接着不良は認められなかった。   As a result of assembling the blood purifier using the hollow fiber membrane bundle thus obtained and conducting a leak test, no adhesion failure due to the sticking of the hollow fiber membranes was observed.

該血液浄化器に、０．１ＭＰａの圧力で加圧空気を充填し、１０秒間の圧力降下が３０ｍｍＡｑ以下のリークテスト合格品を以後の試験に用いた。また、血液浄化器より中空糸膜束を取り出し、外表面を顕微鏡にて観察したところ傷等の欠陥は観察されなかった。また、クエン酸加新鮮牛血を血液流量２００ｍＬ／ｍｉｎ、ろ過速度１０ｍＬ／ｍｉｎで血液浄化器に流したが、血球リークはみられなかった。これらの結果を表５に示した。   The blood purifier was filled with pressurized air at a pressure of 0.1 MPa, and a product that passed the leak test with a pressure drop for 10 seconds of 30 mmAq or less was used in subsequent tests. Further, when the hollow fiber membrane bundle was taken out from the blood purifier and the outer surface was observed with a microscope, defects such as scratches were not observed. In addition, citrated fresh cow blood was flowed to the blood purifier at a blood flow rate of 200 mL / min and a filtration rate of 10 mL / min, but no blood cell leak was observed. These results are shown in Table 5.

該血液浄化器内に脱気したＲＯ水を充填した。血液浄化器より中空糸膜束を切り出し、溶出物試験に供したところ、ＰＶＰ溶出量は８ｐｐｍ、ＵＶ（２２０−３５０ｎｍ）吸光度は最大値でみても０．０６、過酸化水素抽出量の最大値は２ｐｐｍであり問題ないレベルであった。また、上記血液浄化器を室温で１年間保存した。保存後の血液浄化器より中空糸膜束を切り出し、溶出物試験に供したところＵＶ（２２０−３５０ｎｍ）吸光度は最大値で見ても０．０６であり透析型人工腎臓装置製造承認基準値である０．１０以下が維持されていた。




The blood purifier was filled with degassed RO water. When the hollow fiber membrane bundle was cut out from the blood purifier and subjected to the eluate test, the PVP elution amount was 8 ppm, the UV (220-350 nm) absorbance was 0.06 at the maximum value, and the hydrogen peroxide extraction amount was the maximum value. Was 2 ppm, which was a satisfactory level. The blood purifier was stored at room temperature for 1 year. When the hollow fiber membrane bundle was cut out from the blood purifier after storage and subjected to the eluate test, the UV (220-350 nm) absorbance was 0.06 in terms of the maximum value. Some 0.10 or less was maintained.




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Figure 0003659256

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（比較例１）
実施例１において、乾燥を中空糸膜束の水分率が０．２質量％になるまで行うよう変更する以外は、実施例１と同様にして中空糸膜束を得た。得られた乾燥中空糸膜束の過酸化水素濃度、ＵＶ吸光度測定値を表１〜３に示す。本比較例で得られた中空糸膜束の過酸化水素溶出量はレベルが高く、かつ過酸化水素溶出量のサンプリング個所による変動が大きく低品質であった。また、本比較例の中空糸膜束は過酸化水素溶出量が高いため、表４より明らかなごとく保存安定性が劣っていた。本比較例で得られた乾燥状態の中空糸膜束の３ヶ月保存後のＵＶ（２２０−３５０ｎｍ）吸光度は０．１７であり、約２．５ヶ月の保存で、ＵＶ（２２０−３５０ｎｍ）吸光度の基準値の０．１０を超えてしまった。また、乾燥上がりの中空糸膜束のＵＶ（２２０−３５０ｎｍ）吸光度のサンプリング部位による変動が大きく、部分固着の発生があり、モジュール組み立ての作業性が劣っていた。 (Comparative Example 1)
In Example 1, a hollow fiber membrane bundle was obtained in the same manner as in Example 1 except that the drying was performed until the moisture content of the hollow fiber membrane bundle reached 0.2% by mass. The hydrogen peroxide concentration and UV absorbance measured values of the obtained dry hollow fiber membrane bundle are shown in Tables 1-3. The amount of hydrogen peroxide eluted from the hollow fiber membrane bundle obtained in this comparative example was high, and the amount of hydrogen peroxide eluted was varied greatly depending on the sampling location, and the quality was low. Further, since the hollow fiber membrane bundle of this comparative example has a high hydrogen peroxide elution amount, as shown in Table 4, the storage stability was inferior. The UV (220-350 nm) absorbance after storage for 3 months of the dried hollow fiber membrane bundle obtained in this comparative example is 0.17, and the UV (220-350 nm) absorbance after storage for about 2.5 months. The standard value of 0.10 was exceeded. In addition, the UV (220-350 nm) absorbance of the dried hollow fiber membrane bundle varied greatly depending on the sampling site, partial sticking occurred, and the module assembly workability was poor.

実施例１と同様の方法で組み立てたモジュールの特性値を表４に示す。該モジュールにＲＯ水を充填し、室温で保存したところ、約３ヶ月でＵＶ（２２０−３５０ｎｍ）吸光度が平均値で基準値の０．１０を超えてしまった。   Table 4 shows the characteristic values of the module assembled in the same manner as in Example 1. When the module was filled with RO water and stored at room temperature, the UV (220-350 nm) absorbance exceeded the standard value of 0.10 in about 3 months.

（比較例２）
実施例１の方法において、中空糸膜中の水分率が１００質量％で乾燥を終了する以下は、実施例１と同様にして中空糸膜束を得た。得られた中空糸膜束の特性は実施例１の中空糸膜束と同様に高品質であったが、実施例１と同様にしてモジュールの組み立てを行ったところ、ウレタン樹脂が発泡し、接着不良を起こしてしまった。 (Comparative Example 2)
In the method of Example 1, the hollow fiber membrane bundle was obtained in the same manner as in Example 1 after the drying was completed when the moisture content in the hollow fiber membrane was 100% by mass. The properties of the obtained hollow fiber membrane bundle were as high as the hollow fiber membrane bundle of Example 1, but when the module was assembled in the same manner as in Example 1, the urethane resin foamed and adhered. I caused a defect.

（比較例３）
実施例１において、中空糸膜束の洗浄を取り止め、かつ該湿潤状態の中空糸膜束を比較例１と同様の方法で乾燥するように変更した以外は、実施例１と同様にして中空糸膜束および血液浄化器を得た。 (Comparative Example 3)
In Example 1, except that washing of the hollow fiber membrane bundle was stopped and the wet hollow fiber membrane bundle was changed to be dried by the same method as in Comparative Example 1, the hollow fiber was obtained in the same manner as in Example 1. A membrane bundle and blood purifier were obtained.

本比較例で得られた中空糸膜束の過酸化水素およびポリビニルピロリドンの溶出量が比較例１のものと同様に、共にレベルが高く、かつ過酸化水素溶出量のサンプリング個所による変動が大きかった。また、本比較例の中空糸膜束は過酸化水素溶出量が高いため、保存安定性が劣っていた。本比較例で得られた中空糸膜束は約２０日の保存で透析型人工腎臓装置製造承認基準を維持することができなくなった。これらの結果を表１〜５に示す。   The amount of hydrogen peroxide and polyvinylpyrrolidone eluted from the hollow fiber membrane bundle obtained in this comparative example was both high as in Comparative Example 1, and the amount of hydrogen peroxide eluted was highly variable depending on the sampling location. . In addition, the hollow fiber membrane bundle of this comparative example had a poor storage stability due to the high hydrogen peroxide elution amount. The hollow fiber membrane bundle obtained in this comparative example could not maintain the dialysis-type artificial kidney device manufacturing approval standard after storage for about 20 days. These results are shown in Tables 1-5.

（実施例２）
実施例１と同様の方法でポリエーテルスルホン（住化ケムテックス社製、スミカエクセル４８００Ｐ）１８質量％、ポリビニルピロリドン（ＢＡＳＦ社製コリドンＫ−９０）３．８質量％、ジメチルアセトアミド（ＤＭＡｃ）７３．２質量％、水５質量％からなる製膜溶液を得た。なお、上記ポリビニルピロリドンとしては、過酸化水素含有量１００ｐｐｍのものを用いた。得られた製膜溶液を１５μｍ、１５μｍの２段のフィルターに通した後、７０℃に加温したチューブインオリフィスノズルから中空形成剤として予め−７００ｍｍＨｇで２時間脱気処理した６０℃の５０質量％ＤＭＡｃ水溶液と同時に吐出し、紡糸管により外気と遮断された３５０ｍｍのエアギャップ部を通過後、６０℃の水中で凝固させた。使用したチューブインオリフィスノズルのノズルスリット幅は、平均４５μｍであり、最大４５．５μｍ、最小４４．５μｍ、スリット幅の最大値、最小値の比は１．０２、ドラフト比は１．３であった。凝固浴から引き揚げられた中空糸膜束は８５℃の水洗槽を４５秒間通過させ溶媒と過剰のポリビニルピロリドンを除去した後巻き上げた。 (Example 2)
In the same manner as in Example 1, 18% by mass of polyethersulfone (manufactured by Sumika Chemtex, Sumika Excel 4800P), 3.8% by mass of polyvinylpyrrolidone (Collidon K-90, manufactured by BASF), dimethylacetamide (DMAc) 73. A film forming solution consisting of 2% by mass and 5% by mass of water was obtained. As the polyvinyl pyrrolidone, one having a hydrogen peroxide content of 100 ppm was used. The obtained film-forming solution was passed through a two-stage filter of 15 μm and 15 μm, and then degassed at −700 mmHg for 2 hours in advance from a tube-in orifice nozzle heated to 70 ° C. for 50 mass at 60 ° C. The solution was discharged at the same time as the% DMAc aqueous solution, passed through a 350 mm air gap portion cut off from the outside air by a spinning tube, and then coagulated in water at 60 ° C. The average nozzle slit width of the tube-in-orifice nozzle used was 45 μm, the maximum was 45.5 μm, the minimum was 44.5 μm, the ratio of the maximum and minimum slit widths was 1.02, and the draft ratio was 1.3. It was. The hollow fiber membrane bundle pulled up from the coagulation bath was passed through a water washing tank at 85 ° C. for 45 seconds to remove the solvent and excess polyvinylpyrrolidone, and then wound up.

該中空糸膜約１０，０００本の束の周りに実施例１と同様のポリエチレン製のフィルムを巻きつけた後、３０℃の４０ｖｏｌ％イソプロパノール水溶液で３０分×２回浸漬洗浄し、これを長手方向に流路のとられた通風乾燥機にて６０℃で２時間加温した後、３０℃で２５時間乾燥させた。乾燥開始から乾燥終了までの間、最初の２時間は３０分おきに、後の２５時間は１時間おきに、通風の向きを１８０度反転させて乾燥を実施した。これにより乾燥した中空糸膜束を得た。このとき通風媒体としては窒素ガスを用いた。乾燥は中空糸膜束の水分率が２．８質量％になった時点で終了した。紡糸工程中の糸道変更のためのローラーは表面が鏡面加工されたものを使用し、固定ガイドは表面が梨地処理されたものを使用した。得られた中空糸膜の内径は１９９μｍ、膜厚は２７μｍであった。   A polyethylene film similar to that of Example 1 was wound around a bundle of about 10,000 hollow fiber membranes, and then immersed and washed in a 40 vol% isopropanol aqueous solution at 30 ° C. for 30 minutes × 2 times. The mixture was heated at 60 ° C. for 2 hours with a ventilator having a flow path in the direction, and then dried at 30 ° C. for 25 hours. From the start of drying to the end of drying, drying was carried out by reversing the direction of ventilation by 180 degrees every 30 minutes for the first 2 hours and every hour for the next 25 hours. As a result, a dried hollow fiber membrane bundle was obtained. At this time, nitrogen gas was used as the ventilation medium. Drying was completed when the moisture content of the hollow fiber membrane bundle reached 2.8% by mass. The roller for changing the yarn path during the spinning process was a mirror-finished surface, and the fixing guide was a satin-finished surface. The resulting hollow fiber membrane had an inner diameter of 199 μm and a film thickness of 27 μm.

得られた中空糸膜束を長手方向に２．７ｃｍずつ１０個に等分し、各々の部位から乾燥状態の中空糸膜１ｇをはかりとり、過酸化水素溶出量およびＵＶ（２２０−３５０ｎｍ）吸光度を定量した。該過酸化水素溶出量およびＵＶ（２２０−３５０ｎｍ）吸光度は全部位において低レベルで安定していた。該過酸化水素定量値を表１〜３に示した。得られた中空糸膜束の乾燥状態での保存安定性は良好であり表４より明らかなごとく３ヶ月間保存後の中空糸膜束の透析型人工腎臓装置製造承認基準であるＵＶ（２２０−３５０ｎｍ）吸光度は最大値で見ても０．０５であり、基準値の０．１０以下が維持されていた。また、部分固着の発生なくモジュール組み立ての作業性は良好であった。   The obtained hollow fiber membrane bundle was equally divided into 10 pieces of 2.7 cm in the longitudinal direction, and 1 g of a dry hollow fiber membrane was weighed from each part, and the hydrogen peroxide elution amount and UV (220-350 nm) absorbance were measured. Was quantified. The hydrogen peroxide elution amount and UV (220-350 nm) absorbance were stable at a low level at all sites. The hydrogen peroxide quantitative values are shown in Tables 1-3. The hollow fiber membrane bundle thus obtained had good storage stability in the dry state, and as is apparent from Table 4, UV (220-220), which is the standard for approval of dialysis-type artificial kidney device production of the hollow fiber membrane bundle after storage for 3 months. The 350 nm) absorbance was 0.05 at the maximum value, and the standard value of 0.10 or less was maintained. Moreover, the workability of module assembly was good without occurrence of partial sticking.

このようにして得られた中空糸膜束を用いて血液浄化器を組み立て、血液浄化器内にＲＯ水を充填した。該血液浄化器より中空糸膜束を切り出し、溶出物試験に供したところ、ポリビニルピロリドン溶出量は６ｐｐｍ、ＵＶ（２２０−３５０ｎｍ）吸光度の最大値は０．０６、過酸化水素抽出量の最大値は３ｐｐｍと良好であった。また、血液浄化器より取り出した中空糸膜束の外表面を顕微鏡にて観察したところ、傷等の欠陥は観察されず優れたバースト圧を有していた。リークテストを行った結果、中空糸同士の固着に起因するような接着不良は認められなかった。牛血液を用いた血液リークテストでは血球リークはみられなかった。分析結果を表５に示した。   A blood purifier was assembled using the hollow fiber membrane bundle thus obtained, and the blood purifier was filled with RO water. When the hollow fiber membrane bundle was cut out from the blood purifier and subjected to the eluate test, the polyvinylpyrrolidone elution amount was 6 ppm, the maximum UV (220-350 nm) absorbance was 0.06, and the maximum hydrogen peroxide extraction amount. Was as good as 3 ppm. Further, when the outer surface of the hollow fiber membrane bundle taken out from the blood purifier was observed with a microscope, defects such as scratches were not observed, and the burst pressure was excellent. As a result of the leak test, no adhesion failure caused by the sticking of the hollow fibers was found. No blood cell leak was found in the blood leak test using bovine blood. The analysis results are shown in Table 5.

（比較例４）
実施例２において、過酸化水素含有量が５００ｐｐｍのポリビニルピロリドンを原料とし、該溶解を混練を行わず撹拌機を有した溶解槽に直接仕込み溶解をし、かつ原料供給系や溶解時の窒素ガス置換を取り止め、チューブインオリフィスノズルとしてノズルスリット幅は、平均６０μmであり、最大６２μｍ、最小５８μｍ、スリット幅の最大値、最小値の比は１．０７のものを使用し、中空糸膜束の洗浄を１回とし、かつ中空糸膜束の乾燥を長手方向に流路のとられた通風乾燥機にて中空糸膜束の反転入替えなし４５℃で３０時間加温し乾燥するように変更した以外は、実施例２と同様にして中空糸膜束および血液浄化器を得た。得られた中空糸膜束および血液浄化器の特性を表１〜５に示す。 (Comparative Example 4)
In Example 2, polyvinyl pyrrolidone having a hydrogen peroxide content of 500 ppm is used as a raw material, and the dissolution is directly carried out in a dissolution tank having a stirrer without kneading, and the raw material supply system and nitrogen gas at the time of dissolution are used. As a tube-in-orifice nozzle, the nozzle slit width is an average of 60 μm, the maximum 62 μm, the minimum 58 μm, and the ratio of the maximum and minimum slit width is 1.07. The washing was performed once, and the drying of the hollow fiber membrane bundle was changed to be dried by heating at 45 ° C. for 30 hours without inversion replacement of the hollow fiber membrane bundle in a ventilation dryer having a flow path in the longitudinal direction. Except for the above, a hollow fiber membrane bundle and a blood purifier were obtained in the same manner as in Example 2. The characteristics of the obtained hollow fiber membrane bundle and blood purifier are shown in Tables 1 to 5.

本比較例で得られた乾燥中空糸膜束の過酸化水素およびポリビニルピロリドンの溶出量はレベルが高く、かつ過酸化水素溶出量のサンプリング個所による変動が大きく低品質であった。また、本比較例の中空糸膜束は過酸化水素溶出量が高いため、保存安定性が劣っていた。本比較例で得られた中空糸膜束は約５０日の乾燥状態での保存で既にＵＶ（２２０−３５０ｎｍ）吸光度の基準値である０．１０以下を維持することができなくなった。また、乾燥上がりの中空糸膜束のＵＶ（２２０−３５０ｎｍ）吸光度のサンプリング部位による変動が大きく、部分固着の発生がありモジュール組み立ての作業性が劣っていた。さらに、偏肉度が低いため、バースト圧が低く血液リークが認められた。   The amount of elution of hydrogen peroxide and polyvinylpyrrolidone in the dry hollow fiber membrane bundle obtained in this comparative example was high, and the amount of elution of hydrogen peroxide varied greatly depending on the sampling location, resulting in low quality. In addition, the hollow fiber membrane bundle of this comparative example had a poor storage stability due to the high hydrogen peroxide elution amount. The hollow fiber membrane bundle obtained in this comparative example could not maintain 0.10 or less, which is the standard value of UV (220-350 nm) absorbance, after being stored in a dry state for about 50 days. Further, the UV (220-350 nm) absorbance of the dried hollow fiber membrane bundle varied greatly depending on the sampling site, and partial sticking occurred, resulting in poor module assembly workability. Furthermore, since the uneven thickness was low, the burst pressure was low and a blood leak was observed.

また、該モジュールに予め脱気したＲＯ水を充填し、室温で保存したところ、約２ヶ月の保存でＵＶ（２２０−３５０ｎｍ）吸光度が平均値で基準値の０．１０を超えてしまった。   In addition, when the module was filled with RO water degassed in advance and stored at room temperature, the UV (220-350 nm) absorbance exceeded the standard value of 0.10 after storage for about 2 months.

（実施例３）
実施例１と同様の方法で、ポリスルホン（アモコ社製Ｐ−３５００）１８質量％、ポリビニルピロリドン（ＢＡＳＦ社製Ｋ−６０）９質量％、ジメチルアセトアミド（ＤＭＡｃ）６８質量％、水５質量％よりなる製膜溶液を得た。なお、上記ポリビニルピロリドンとしては、過酸化水素含有量１００ｐｐｍのものを用いた。得られた製膜溶液を１５μｍ、１５μｍの２種のフィルターに通した後、４０℃に加温したチューブインオリフィスノズルから中空形成剤として予め減圧脱気した６０℃の３５質量％ＤＭＡｃ水溶液と同時に吐出し、紡糸管により外気と遮断された６００ｍｍのエアギャップ部を通過後、５０℃の水中で凝固させた。使用したチューブインオリフィスノズルのノズルスリット幅は、平均６０μｍであり、最大６１μｍ、最小５９μｍ、スリット幅の最大値、最小値の比は１．０３、ドラフト比は１．１であった。凝固浴から引き揚げられた中空糸膜束は８５℃の水洗槽を４５秒間通過させ溶媒と過剰のポリビニルピロリドンを除去した後巻き上げた。該中空糸膜約１０，０００本の束を純水に浸漬し、１２１℃×１時間オートクレーブにて洗浄処理を行った。洗浄後の中空糸膜束の周りに実施例１と同様のポリエチレン製のフィルムを巻きつけた後、実施例１と同様にして乾燥した。紡糸工程中の糸道変更のためのローラーは表面が鏡面加工されたものを使用し、固定ガイドは表面が梨地処理されたものを使用した。得られた中空糸膜束の内径は２０１μｍ、膜厚は４４μｍであった。 (Example 3)
In the same manner as in Example 1, from 18% by mass of polysulfone (P-3500 manufactured by Amoco), 9% by mass of polyvinylpyrrolidone (K-60 manufactured by BASF), 68% by mass of dimethylacetamide (DMAc), and 5% by mass of water A film forming solution was obtained. As the polyvinyl pyrrolidone, one having a hydrogen peroxide content of 100 ppm was used. The obtained film-forming solution was passed through two types of filters of 15 μm and 15 μm, and simultaneously with a 35 mass% DMAc aqueous solution at 60 ° C. which was degassed in advance as a hollow forming agent from a tube-in orifice nozzle heated to 40 ° C. After discharging and passing through a 600 mm air gap portion cut off from the outside air by a spinning tube, it was solidified in 50 ° C. water. The nozzle slit width of the tube-in-orifice nozzle used was an average of 60 μm, the maximum 61 μm, the minimum 59 μm, the ratio of the maximum and minimum slit widths was 1.03, and the draft ratio was 1.1. The hollow fiber membrane bundle pulled up from the coagulation bath was passed through a water washing tank at 85 ° C. for 45 seconds to remove the solvent and excess polyvinylpyrrolidone, and then wound up. A bundle of about 10,000 hollow fiber membranes was immersed in pure water and washed in an autoclave at 121 ° C. for 1 hour. A polyethylene film similar to that in Example 1 was wound around the hollow fiber membrane bundle after washing, and then dried in the same manner as in Example 1. The roller for changing the yarn path during the spinning process was a mirror-finished surface, and the fixing guide was a satin-finished surface. The obtained hollow fiber membrane bundle had an inner diameter of 201 μm and a film thickness of 44 μm.

表１、２より明らかなごとく、過酸化水素は全部位において低レベルで安定していた。また、得られた中空糸膜束の乾燥状態での保存安定性は良好であり、３ヶ月間保存後の中空糸膜束のＵＶ（２２０−３５０ｎｍ）吸光度は最大値で見ても０．０６であり、基準値の０．１０以下が維持されていた。また、部分固着の発生なくモジュール組み立ての作業性は良好であった。   As is clear from Tables 1 and 2, hydrogen peroxide was stable at a low level at all sites. Further, the storage stability of the obtained hollow fiber membrane bundle in a dry state is good, and the UV (220-350 nm) absorbance of the hollow fiber membrane bundle after storage for 3 months is 0.06 even when viewed at the maximum value. The reference value of 0.10 or less was maintained. Moreover, the workability of module assembly was good without occurrence of partial sticking.

このようにして得られた中空糸膜束を用いて、血液浄化器を組み立てた。該血液浄化器内に脱気したＲＯ水を充填した。該血液浄化器より湿潤状態の中空糸膜束を切り出し、溶出物試験に供したところ、ＰＶＰ溶出量は７ｐｐｍ、過酸化水素抽出量の最大値は３ｐｐｍであり問題ないレベルであった。   A blood purifier was assembled using the hollow fiber membrane bundle thus obtained. The blood purifier was filled with degassed RO water. When a hollow fiber membrane bundle in a wet state was cut out from the blood purifier and subjected to the eluate test, the PVP elution amount was 7 ppm and the maximum hydrogen peroxide extraction amount was 3 ppm, which was a satisfactory level.

該血液浄化器に、０．１ＭＰａの圧力で加圧空気を充填し、１０秒間の圧力降下が３０ｍｍＡｑ以下のリークテスト合格品を以後の試験に用いた。また、血液浄化器より中空糸膜束を取り出し、外表面を顕微鏡にて観察したところ傷等の欠陥は観察されなかった。   The blood purifier was filled with pressurized air at a pressure of 0.1 MPa, and a product that passed the leak test with a pressure drop for 10 seconds of 30 mmAq or less was used in subsequent tests. Further, when the hollow fiber membrane bundle was taken out from the blood purifier and the outer surface was observed with a microscope, defects such as scratches were not observed.

また、クエン酸加新鮮牛血を血液流量２００ｍＬ／ｍｉｎ、ろ過速度１０ｍＬ／ｍｉｎで血液浄化器に流したが、血球リークはみられなかった。中空糸外側から中空糸内側にろ過されたエンドトキシンは検出限界以下であり、問題ないレベルであった。その他の分析結果を表５に示した。   In addition, citrated fresh cow blood was flowed to the blood purifier at a blood flow rate of 200 mL / min and a filtration rate of 10 mL / min, but no blood cell leak was observed. Endotoxin filtered from the outer side of the hollow fiber to the inner side of the hollow fiber was below the detection limit and was at a level with no problem. The other analysis results are shown in Table 5.

（比較例５）
実施例３の方法において、マイクロ波乾燥を常圧で２．０ｋＷの出力で４０分間照射し、次いで同じく１．０ｋＷの出力で１５分間照射するようにし、かつ中空糸膜束中の水分率が０．８質量％になるまで乾燥するように変更する以外は、実施例２と同様にして中空糸膜束を得た。なお、乾燥時の中空糸膜束表面の最高到達温度は６５℃であった。得られた中空糸膜束および血液浄化器の特性を表１〜５に示す。 (Comparative Example 5)
In the method of Example 3, microwave drying was performed for 40 minutes at an output of 2.0 kW at normal pressure, and then for 15 minutes at an output of 1.0 kW, and the moisture content in the hollow fiber membrane bundle was A hollow fiber membrane bundle was obtained in the same manner as in Example 2 except that the drying was changed to 0.8% by mass. The maximum temperature reached on the surface of the hollow fiber membrane bundle during drying was 65 ° C. The characteristics of the obtained hollow fiber membrane bundle and blood purifier are shown in Tables 1 to 5.

本比較例で得られた中空糸膜束の過酸化水素の溶出量は高く、かつ過酸化水素溶出量のサンプリング個所による変動が大きく低品質であった。また、本比較例の中空糸膜束は過酸化水素溶出量が高いため、表４で明らかなごとく保存安定性が劣っていた。本比較例で得られた中空糸膜束は保存後約４５日でＵＶ（２２０−３５０ｎｍ）吸光度が基準値の０．１０を超えてしまった。また、表３より明らかなごとく乾燥上がりの中空糸膜束のＵＶ（２２０−３５０ｎｍ）吸光度のサンプリング部位による変動が大きく、部分固着の発生がありモジュール組み立ての作業性が劣っていた。これらの結果を表１〜５に示す。   The elution amount of hydrogen peroxide in the hollow fiber membrane bundle obtained in this comparative example was high, and the variation in the elution amount of hydrogen peroxide depending on the sampling location was large and the quality was low. Further, since the hollow fiber membrane bundle of this comparative example has a high hydrogen peroxide elution amount, as shown in Table 4, the storage stability was inferior. The hollow fiber membrane bundle obtained in this comparative example had a UV (220-350 nm) absorbance exceeding the standard value of 0.10 in about 45 days after storage. Further, as apparent from Table 3, the fluctuation of the UV (220-350 nm) absorbance of the dried hollow fiber membrane bundle depending on the sampling site was large, and partial sticking occurred and the workability of module assembly was inferior. These results are shown in Tables 1-5.

（実施例４）
実施例１と同様の方法で、ポリスルホン（アモコ社製Ｐ−１７００）１７質量％、ポリビニルピロリドン（ＢＡＳＦ社製Ｋ−６０）５質量％、ジメチルアセトアミド（ＤＭＡｃ）６８質量％、水５質量％よりなる製膜溶液を得た。なお、上記ポリビニルピロリドンとしては、過酸化水素含有量１２０ｐｐｍのものを用いた。得られた製膜溶液を１５μｍ、１５μｍの２種のフィルターに通した後、４０℃に加温したチューブインオリフィスノズルから中空形成剤として減圧脱気された６５℃の３５質量％ＤＭＡｃ水溶液と同時に吐出し、紡糸管により外気と遮断された６００ｍｍのエアギャップ部を通過後、５０℃の水中で凝固させた。使用したチューブインオリフィスノズルのノズルスリット幅は、平均６０μｍであり、最大６１μｍ、最小５９μｍ、スリット幅の最大値、最小値の比は１．０３、ドラフト比は１．２であった。凝固浴から引き揚げられた中空糸膜束は８５℃の水洗槽を４５秒間通過させ溶媒と過剰のポリビニルピロリドンを除去した後巻き上げた。該中空糸膜約１０，０００本の束を純水に浸漬し、１２１℃×１時間オートクレーブにて洗浄処理を行った。紡糸工程中の糸道変更のためのローラーは表面が鏡面加工されたものを使用し、固定ガイドは表面が梨地処理されたものを使用した。 (Example 4)
In the same manner as in Example 1, polysulfone (Amoco P-1700) 17% by mass, polyvinylpyrrolidone (BASF K-60) 5% by mass, dimethylacetamide (DMAc) 68% by mass, water 5% by mass A film forming solution was obtained. As the polyvinyl pyrrolidone, one having a hydrogen peroxide content of 120 ppm was used. The obtained film-forming solution was passed through two types of filters of 15 μm and 15 μm, and simultaneously with a 35 mass% DMAc aqueous solution at 65 ° C. degassed as a hollow forming agent from a tube-in orifice nozzle heated to 40 ° C. After discharging and passing through a 600 mm air gap portion cut off from the outside air by a spinning tube, it was solidified in 50 ° C. water. The nozzle slit width of the tube-in-orifice nozzle used was an average of 60 μm, the maximum 61 μm, the minimum 59 μm, the ratio of the maximum and minimum slit widths was 1.03, and the draft ratio was 1.2. The hollow fiber membrane bundle pulled up from the coagulation bath was passed through a water washing tank at 85 ° C. for 45 seconds to remove the solvent and excess polyvinylpyrrolidone, and then wound up. A bundle of about 10,000 hollow fiber membranes was immersed in pure water and washed in an autoclave at 121 ° C. for 1 hour. The roller for changing the yarn path during the spinning process was a mirror-finished surface, and the fixing guide was a satin-finished surface.

洗浄後の中空糸膜束の周りにポリエチレン製のフィルムを巻きつけた後、熱風乾燥法により平均含水率が５０質量％になるまで乾燥し、引き続き実施例２に準じ水分率が２．２質量％になるように乾燥した。得られた中空糸膜の内径は２０１μｍ、膜厚は４３μｍであった。表１および２より明らかなごとく、過酸化水素溶出量は全部位において低レベルで安定していた。また、本実施例で得られた中空糸膜束の乾燥状態での保存安定性は良好で、３ヶ月間保存後の中空糸膜束の透析型人工腎臓装置製造承認基準であるＵＶ（２２０−３５０ｎｍ）吸光度は最大値で見ても０．０６であり、基準値の０．１０以下が維持されていた。また、乾燥上がりの中空糸膜束のＵＶ（２２０−３５０ｎｍ）吸光度は全部位において低レベルで安定しており、部分固着の発生なくモジュール組み立ての作業性は良好であった。   A polyethylene film is wound around the hollow fiber membrane bundle after washing, and then dried by a hot air drying method until the average moisture content becomes 50% by mass. Subsequently, the moisture content is 2.2% according to Example 2. % To dry. The resulting hollow fiber membrane had an inner diameter of 201 μm and a film thickness of 43 μm. As is clear from Tables 1 and 2, the hydrogen peroxide elution amount was stable at a low level in all sites. In addition, the storage stability of the hollow fiber membrane bundle obtained in this example in a dry state is good, and UV (220-220), which is a dialysis-type artificial kidney device manufacturing approval standard for the hollow fiber membrane bundle after storage for 3 months. (350 nm) The absorbance was 0.06 at the maximum value, and the standard value of 0.10 or less was maintained. Further, the UV (220-350 nm) absorbance of the hollow fiber membrane bundle after drying was stable at a low level in all parts, and the workability of module assembly was good without occurrence of partial sticking.

このようにして得られた中空糸膜束を用いて、血液浄化器を組み立てた。該血液浄化器内に脱気したＲＯ水を充填し２５ｋＧｙの吸収線量でγ線を照射し架橋処理を行った。γ線照射後の血液浄化器より中空糸膜束を切り出し、溶出物試験に供したところ、ＰＶＰ溶出量７ｐｐｍ、過酸化水素抽出量の最大値は２ｐｐｍであり問題ないレベルであった。   A blood purifier was assembled using the hollow fiber membrane bundle thus obtained. The blood purifier was filled with degassed RO water and irradiated with γ rays at an absorbed dose of 25 kGy to carry out a crosslinking treatment. When the hollow fiber membrane bundle was cut out from the blood purifier after γ-irradiation and subjected to the eluate test, the PVP elution amount was 7 ppm and the maximum hydrogen peroxide extraction amount was 2 ppm, which was a satisfactory level.

該血液浄化器に、０．１ＭＰａの圧力で加圧空気を充填し、１０秒間の圧力降下が３０ｍｍＡｑ以下のリークテスト合格品を以後の試験に用いた。また、血液浄化器より中空糸膜束を取り出し、外表面を顕微鏡にて観察したところ傷等の欠陥は観察されなかった。また、クエン酸加新鮮牛血を血液流量２００ｍＬ／ｍｉｎ、ろ過速度１０ｍＬ／ｍｉｎで血液浄化器に流したが、血球リークはみられなかった。中空糸外側から中空糸内側にろ過されたエンドトキシンは検出限界以下であり、問題ないレベルであった。これらの分析結果を表３に示した。   The blood purifier was filled with pressurized air at a pressure of 0.1 MPa, and a product that passed the leak test with a pressure drop for 10 seconds of 30 mmAq or less was used in subsequent tests. Further, when the hollow fiber membrane bundle was taken out from the blood purifier and the outer surface was observed with a microscope, defects such as scratches were not observed. In addition, citrated fresh cow blood was flowed to the blood purifier at a blood flow rate of 200 mL / min and a filtration rate of 10 mL / min, but no blood cell leak was observed. Endotoxin filtered from the outer side of the hollow fiber to the inner side of the hollow fiber was below the detection limit and was at a level with no problem. The results of these analyzes are shown in Table 3.

また、本実施例で得られた血液浄化器を室温で１年間保存した。保存後の血液浄化器より中空糸膜束を切り出し、溶出物試験に供したところＵＶ（２２０−３５０ｎｍ）吸光度の最大値は０．０６であり最大値で見ても透析型人工腎臓装置製造承認基準値である０．１０以下が維持されていた。   The blood purifier obtained in this example was stored at room temperature for 1 year. The hollow fiber membrane bundle was cut out from the blood purifier after storage and subjected to the eluate test. The maximum value of UV (220-350 nm) absorbance was 0.06, and the maximum value of dialysis artificial kidney device was approved. The reference value of 0.10 or less was maintained.

従来、中空糸膜束において、過酸化水素の挙動に着目した品質管理の手法は全く知られていない。中空糸膜束の品質の良さという点については多くの観点から検討することができるが、例えば、中空糸膜束を長手方向に２７ｃｍに切断し、それを２．７ｃｍの１０等分間隔にして、それぞれの部位で過酸化水素の溶出量を測定する。最大溶出量、最小溶出量をもとに、較差Ａが求められる。そして、それを平均することにより平均溶出量を算定する。また、最大溶出量または最小溶出量と、平均溶出量の較差の最大値Ｂを品質のバラツキ度の程度とする。図１は、実施例１のバラツキの状態を示す。比較例１の場合も同様に求めることができる。このようにして算定した値を表２にまとめた。   Conventionally, no quality control method focusing on the behavior of hydrogen peroxide in a hollow fiber membrane bundle has been known at all. The quality of the hollow fiber membrane bundle can be examined from many points of view. For example, the hollow fiber membrane bundle is cut into 27 cm in the longitudinal direction and is divided into 10 equal intervals of 2.7 cm. Measure the elution amount of hydrogen peroxide at each site. A difference A is determined based on the maximum and minimum elution amounts. And an average elution amount is calculated by averaging it. Further, the maximum value B of the difference between the maximum elution amount or the minimum elution amount and the average elution amount is set as the degree of quality variation. FIG. 1 shows a variation state of the first embodiment. In the case of Comparative Example 1, it can be obtained similarly. The values calculated in this way are summarized in Table 2.

過酸化水素溶出量が、特に５ｐｐｍ程度を境界にして、中空糸膜束の品質のバラツキ度の関係を調べると、図２のようになる。過酸化水素溶出量が多くなると、中空糸膜束の１０等分における各部位の過酸化水素溶出量にアンバランスが生じるため、各部位の溶出量の較差が大きくなる。そうすると、同じ材料で、過酸化水素の溶出に違いがあるということは、材料の性質又は特性の違いを表す指標にもなり、中空糸膜の性能、機能にも影響することになり、品質の管理上好ましくない。中空糸膜束の各部位にアンバランスがないということは、その中空糸膜の材料および構造を含む品質が均一であるということになるから、これが性能においても有意に作用することになり、品質の優れた中空糸膜であることを示すものであることが理解できる。そして、５ｐｐｍ程度の範囲は、バラツキ度を抑制するという点で、臨界的な範囲であるということが理解できる。このように、過酸化水素溶出量が中空糸膜の品質に微妙に影響を与えるという知見と、溶出量５ｐｐｍという臨界的な定量値を境界とすることによって、中空糸膜の高度な品質管理をするという手法は、本発明者らの知見に基づくものであり、それは新規な着想である。   When the hydrogen peroxide elution amount is particularly about 5 ppm as a boundary, the relationship of the degree of variation in the quality of the hollow fiber membrane bundle is examined as shown in FIG. When the hydrogen peroxide elution amount increases, an unbalance occurs in the hydrogen peroxide elution amount of each part in 10 equal parts of the hollow fiber membrane bundle, so that the difference in the elution amount of each part increases. Then, the difference in elution of hydrogen peroxide with the same material also serves as an index indicating the difference in the properties or characteristics of the material, and also affects the performance and function of the hollow fiber membrane. It is not preferable for management. The fact that there is no unbalance in each part of the hollow fiber membrane bundle means that the quality including the material and structure of the hollow fiber membrane is uniform, and this will have a significant effect on performance. It can be understood that this is an excellent hollow fiber membrane. It can be understood that the range of about 5 ppm is a critical range in terms of suppressing variation. In this way, advanced quality control of the hollow fiber membrane can be achieved by using the knowledge that the hydrogen peroxide elution amount has a subtle effect on the quality of the hollow fiber membrane and the critical quantitative value of 5 ppm elution amount as a boundary. This technique is based on the knowledge of the present inventors and is a novel idea.

図３は、乾燥中空糸膜束を室温で３ヶ月間保存した場合のＵＶ吸光度変化の挙動を示す。過酸化水素の溶出量を５ｐｐｍ以下に抑えたものは、長期間保存してもＵＶ吸光度を基準値の０．１以下に抑えることができるため、中空糸膜束中の過酸化水素存在量を５ｐｐｍ以下に抑えることは品質の安定に著しく寄与すると言える。   FIG. 3 shows the behavior of UV absorbance change when the dried hollow fiber membrane bundle is stored at room temperature for 3 months. Those whose hydrogen peroxide elution amount is suppressed to 5 ppm or less can suppress the UV absorbance to a reference value of 0.1 or less even after long-term storage, so the amount of hydrogen peroxide present in the hollow fiber membrane bundle is reduced. It can be said that suppressing to 5 ppm or less significantly contributes to quality stability.

本発明の中空糸膜束の乾燥方法は、乾燥工程における中空糸膜の性能低下や中空糸膜成分、特にポリビニルピロリドンの劣化が低減され、該劣化により生成する過酸化水素溶出量が抑制されており、該過酸化水素により引き起される乾燥中空糸膜束を長期にわたり保存した場合のポリビニルピロリドン等の劣化が抑制されるので、長期保存をしても透析型人工腎臓装置製造承認基準であるＵＶ（２２０−３５０ｎｍ）吸光度を０．１０以下に維持するができる。また、中空糸膜束の長手方向におけるポリビニルピロリドンの劣化の変動が小さく中空糸膜束の長手方向における上記のＵＶ（２２０−３５０ｎｍ）吸光度変動が抑制されるので、この変動により引き起こされる中空糸膜束の部分固着が抑制され、モジュール組み立て性の優れた中空糸膜束が安定して製造できるという特徴を有する。また、該中空糸膜束の長手方向におけるＵＶ（２２０−３５０ｎｍ）吸光度変動の抑制は、血液浄化用に使用した場合の安全性の向上にもつながる。従って、慢性腎不全の治療に用いる高透水性能を有する血液透析法中空糸型血液浄化器用等に用いられる中空糸膜束の乾燥方法として好適であるいう利点がある。また、本発明の中空糸膜束は上記の特徴を有するので、血液浄化器用等に好適に使用することができる。従って、産業界に寄与することが大である。   The drying method of the hollow fiber membrane bundle of the present invention reduces the performance degradation of the hollow fiber membrane in the drying step and the degradation of the hollow fiber membrane component, particularly polyvinylpyrrolidone, and suppresses the elution amount of hydrogen peroxide generated by the degradation. Since the degradation of polyvinylpyrrolidone and the like when the dried hollow fiber membrane bundle caused by the hydrogen peroxide is stored over a long period of time is suppressed, it is a dialysis-type artificial kidney device manufacturing approval standard even after long-term storage UV (220-350 nm) absorbance can be kept below 0.10. Moreover, since the fluctuation | variation of deterioration of the polyvinylpyrrolidone in the longitudinal direction of a hollow fiber membrane bundle is small, and said UV (220-350 nm) absorbance fluctuation | variation in the longitudinal direction of a hollow fiber membrane bundle is suppressed, The hollow fiber membrane caused by this fluctuation | variation This is characterized in that the bundle fixing of the bundle is suppressed and a hollow fiber membrane bundle excellent in module assemblability can be manufactured stably. Moreover, suppression of UV (220-350 nm) absorbance fluctuations in the longitudinal direction of the hollow fiber membrane bundle also leads to an improvement in safety when used for blood purification. Therefore, there is an advantage that it is suitable as a method for drying a hollow fiber membrane bundle used for a hemodialysis hollow fiber blood purifier having high water permeability used for the treatment of chronic renal failure. Moreover, since the hollow fiber membrane bundle of the present invention has the above characteristics, it can be suitably used for blood purifiers and the like. Therefore, it is important to contribute to the industry.

中空糸膜束を１０等分した場合の各部位における過酸化水素溶出量の分布状態を示す模式図である。It is a schematic diagram which shows the distribution state of the hydrogen peroxide elution amount in each site | part at the time of dividing a hollow fiber membrane bundle into 10 equal parts. 各部位の過酸化水素溶出量の違いが中空糸膜束の品質に与える影響とその臨界値の関係を示す模式図である。It is a schematic diagram which shows the relationship which the difference in the hydrogen peroxide elution amount of each site | part has on the quality of a hollow fiber membrane bundle, and its critical value. 人工腎臓装置製造承認基準を満たすための中空糸膜束の保存期間と過酸化水素溶出量の関係を示す模式図である。It is a schematic diagram which shows the relationship between the storage period of the hollow fiber membrane bundle for satisfying the artificial kidney apparatus manufacture approval criteria, and the hydrogen peroxide elution amount.

Claims (7)

ポリビニルピロリドンを含むポリスルホン系樹脂よりなる湿潤状態のポリスルホン系選択透過性中空糸膜束を乾燥するに当たり、中空糸膜束の含水率の低下に伴い、マイクロ波の照射出力を段階的に下げながら中空糸膜束の含水率を１重量％以上飽和含水率未満の範囲で乾燥を終了することにより、乾燥中空糸膜束を室温で３ヶ月保存した後の中空糸膜束を長手方向に１０個に分割し、各々を透析型人工腎臓装置製造承認基準により定められた試験を実施したとき、全ての抽出液におけるＵＶ（２２０〜３５０ｎｍ）吸光度の最大値を０．１０以下とすることを特徴とするポリスルホン系選択透過性中空糸膜束の乾燥方法。 When drying a wet polysulfone-based permselective hollow fiber membrane bundle made of polysulfone-based resin containing polyvinylpyrrolidone, the hollow fiber membrane bundle is hollowed while gradually reducing the microwave irradiation output as the moisture content of the hollow fiber membrane bundle decreases. Finishing the drying in the range where the moisture content of the yarn membrane bundle is 1% by weight or more and less than the saturated moisture content allows the hollow fiber membrane bundle to be ten in the longitudinal direction after the dried hollow fiber membrane bundle is stored at room temperature for 3 months. The maximum value of UV (220-350 nm) absorbance in all the extracts is 0.10 or less when each of the divided liquids is subjected to a test defined by the dialysis artificial kidney device manufacturing approval standard. A method for drying a polysulfone-based permselective hollow fiber membrane bundle. ポリビニルピロリドンを含むポリスルホン系樹脂よりなる湿潤状態のポリスルホン系選択透過性中空糸膜束を乾燥するに当たり、中空糸膜束の含水率の低下に伴い、通風向きを交互に逆転するか、または通風温度を段階的に下げながら中空糸膜束の含水率を１重量％以上飽和含水率未満の範囲で乾燥を終了することにより、乾燥中空糸膜束を室温で３ヶ月保存した後の中空糸膜束を長手方向に１０個に分割し、各々を透析型人工腎臓装置製造承認基準により定められた試験を実施したとき、全ての抽出液におけるＵＶ（２２０〜３５０ｎｍ）吸光度の最大値を０．１０以下とすることを特徴とするポリスルホン系選択透過性中空糸膜束の乾燥方法。 When drying a wet polysulfone-based selectively permeable hollow fiber membrane bundle made of a polysulfone-based resin containing polyvinylpyrrolidone , the direction of ventilation is alternately reversed or the temperature of the ventilation is decreased as the moisture content of the hollow fiber membrane bundle decreases. The hollow fiber membrane bundle after the dried hollow fiber membrane bundle has been stored at room temperature for 3 months by ending the drying in a range where the moisture content of the hollow fiber membrane bundle is 1% by weight or more and less than the saturated moisture content Is divided into 10 pieces in the longitudinal direction, and when the test defined by the dialysis-type artificial kidney device manufacturing approval standard is carried out, the maximum value of UV (220 to 350 nm) absorbance in all the extracts is 0.10 or less. A method for drying a polysulfone-based permselective hollow fiber membrane bundle characterized by: 中空糸膜束中の含水率を１．５〜１０質量％の範囲で乾燥を終了することを特徴とする請求項１または２に記載のポリスルホン系選択透過性中空糸膜束の乾燥方法。   3. The method for drying a polysulfone-based permselective hollow fiber membrane bundle according to claim 1 or 2, wherein the drying is finished when the moisture content in the hollow fiber membrane bundle is in the range of 1.5 to 10% by mass. 中空糸膜束中の含水率を２．０〜７質量％の範囲で乾燥を終了することを特徴とする請求項１または２に記載のポリスルホン系選択透過性中空糸膜束の乾燥方法。   3. The method for drying a polysulfone-based permselective hollow fiber membrane bundle according to claim 1 or 2, wherein the drying is finished when the moisture content in the hollow fiber membrane bundle is in the range of 2.0 to 7% by mass. 中空糸膜束を通風乾燥するときに中空糸膜束の乾燥による含水率の低下に伴い通風量を下げることを特徴とする請求項２〜４のいずれかに記載のポリスルホン系選択透過性中空糸膜束の乾燥方法。 The polysulfone-based permselective hollow fiber according to any one of claims 2 to 4 , wherein when the hollow fiber membrane bundle is air-dried, the air flow rate is lowered as the moisture content decreases due to drying of the hollow fiber membrane bundle. A method for drying a membrane bundle. ２０ｋＰａ以下の減圧下で乾燥することを特徴とする請求項１、３又は４に記載のポリスルホン系選択透過性中空糸膜束の乾燥方法。   The method for drying a polysulfone-based permselective hollow fiber membrane bundle according to claim 1, 3 or 4, wherein drying is performed under a reduced pressure of 20 kPa or less. ０．１〜２０ｋＰａの減圧下、２０ｋＷ以下の低出力マイクロ波を照射して乾燥することを特徴とする請求項６に記載のポリスルホン系選択透過性中空糸膜束の乾燥方法。
The method for drying a polysulfone-based selectively permeable hollow fiber membrane bundle according to claim 6 , wherein the drying is performed by irradiation with a low-power microwave of 20 kW or less under a reduced pressure of 0.1 to 20 kPa.
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JP2011041830A (en) * 2010-11-01 2011-03-03 Toyobo Co Ltd Hollow fiber membrane for blood purification, and method of manufacturing the same
CN111965023A (en) * 2020-07-31 2020-11-20 同济大学 Tensile property testing method for proton exchange membranes with different humidity

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JP2011041830A (en) * 2010-11-01 2011-03-03 Toyobo Co Ltd Hollow fiber membrane for blood purification, and method of manufacturing the same
CN111965023A (en) * 2020-07-31 2020-11-20 同济大学 Tensile property testing method for proton exchange membranes with different humidity

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