JP4678063B2 - Hollow fiber membrane module - Google Patents
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本発明は、膜からの溶出物が少ない中空糸膜モジュールおよびかかる中空糸膜を用いたモジュールおよびその製造方法に関するものである。 The present invention relates to a module and a manufacturing method thereof using a hollow fiber membrane module and such hollow fiber membranes eluate is small from the membrane.
人工腎臓などによる血液処理で用いられる半透膜として、これまでに様々な素材が用いられてきた。初期のころは、天然素材セルロース、また、その誘導体であるセルロースジアセテート、セルローストリアセテートが使用されていたが、時代の変化とともに、合成高分子が登場し、ポリスルホン、ポリメチルメタアクリレート（ＰＭＭＡ）、ポリアクリロニトリルなどが幅広く使用され、近年ではセルロースをポリエチレングリコール（ＰＥＧ）などで処理し、血液適合性を改良した改質膜も使用されるようになってきた。慢性腎不全患者の血液処理法についてはアルブミンの漏れは最小限に抑えつつ、その他の低分子蛋白を積極的に除去する試みがなされている。膜の改良だけでなく、血液透析濾過法（ＨＤＦ）や、プッシュ＆プル法が透析効率の向上や低分子蛋白の積極除去のため開発された。現在、膜素材の中で透水性能が高いポリスルホンが、このような透析手法の進歩に合致したものとして、幅広く使用されるに至っている。ポリスルホンは熱可塑性の耐熱エンジニアリングプラスチックとして自動車、電気、医療用具の分野で幅広く用いられているが、ポリスルホンのみで作られた透析膜には解決すべき問題点がある。すなわち、分子間凝集力が強く、ポアサイズのコントロールが難しく、疎水性のために血液との親和性が弱く、血小板などの血液成分が付着し、残血の原因となることがあり、膜性能の低下が起こりがちである。さらに、エアーロック現象を起こすこともあり、血液処理用には使いやすいとは言えない。
従って、孔形成材として無機塩などを混入し、脱離することで孔を形作り、後で親水化処理する方法や、予め、親水性高分子を造孔剤として混入し、脱離させてポアを形成後、残った親水性成分で同時にポリマー表面を親水化し、これを半透膜、逆浸透膜として用いる方法が考案された。例示すると（１）金属塩を入れて製膜する方法、（２）親水性高分子を入れて製膜する方法、（３）多価アルコールを入れて製膜する方法などがすでに開示されている。しかし、特許文献１、２のようにポリエチレングリコール等の多価アルコールを入れて製膜を行う場合、洗浄が不十分なとき、膜に残存するポリエチレングリコール等の溶出によって、透析時に患者の目に異常が起こることもある。金属塩類の場合はポアサイズが大きすぎて透析膜には不適である。
Various materials have been used so far as semipermeable membranes used in blood treatment with artificial kidneys and the like. In the early days, natural materials cellulose, and its derivatives cellulose diacetate and cellulose triacetate were used, but with the changing times, synthetic polymers appeared, polysulfone, polymethylmethacrylate (PMMA), Polyacrylonitrile and the like are widely used. In recent years, modified membranes in which cellulose is treated with polyethylene glycol (PEG) or the like to improve blood compatibility have been used. With regard to blood treatment methods for patients with chronic renal failure, attempts have been made to actively remove other low molecular weight proteins while minimizing albumin leakage. In addition to improving membranes, hemodiafiltration (HDF) and push-pull methods have been developed to improve dialysis efficiency and actively remove low molecular weight proteins. At present, polysulfone, which has high water permeability among membrane materials, has been widely used as one that matches the progress of such dialysis techniques. Polysulfone is widely used as a thermoplastic heat-resistant engineering plastic in the fields of automobiles, electricity, and medical devices. However, a dialysis membrane made of only polysulfone has a problem to be solved. In other words, the intermolecular cohesive force is strong, the pore size is difficult to control, the affinity with blood is weak due to hydrophobicity, blood components such as platelets adhere, and it may cause residual blood, and the membrane performance A decline tends to occur. In addition, an air lock phenomenon may occur, which is not easy to use for blood treatment.
Therefore, it is possible to form pores by mixing and removing inorganic salts as pore-forming materials and then hydrophilizing them, or by previously mixing hydrophilic polymers as pore-forming agents and removing them to remove pores. After forming the film, a method has been devised in which the remaining hydrophilic component is used to simultaneously hydrophilize the polymer surface and use it as a semipermeable membrane or a reverse osmosis membrane. For example, (1) a method of forming a film by adding a metal salt, (2) a method of forming a film by adding a hydrophilic polymer, (3) a method of forming a film by adding a polyhydric alcohol have already been disclosed. . However, when a film is formed by adding a polyhydric alcohol such as polyethylene glycol as in Patent Documents 1 and 2, when washing is insufficient, elution of polyethylene glycol or the like remaining on the film causes the eyes of the patient to undergo dialysis. Abnormalities may occur. In the case of metal salts, the pore size is too large to be suitable for a dialysis membrane.
特許文献３に、充填液を用いない中空糸膜モジュールの記載で、中空糸膜モジュール内を不活性ガス雰囲気とすることによる親水性高分子の溶出が少ない充填液を用いない中空糸膜モジュールが開示されているが、中空糸膜モジュール内を完全に不活性ガス雰囲気とすると生体適合性については低下する。 Patent Document 3 describes a hollow fiber membrane module which does not use a filling liquid, which is a hollow fiber membrane module which does not use a filling liquid. Although disclosed, if the inside of the hollow fiber membrane module is completely in an inert gas atmosphere, the biocompatibility is lowered.
血液透析膜に多く含まれる有機物は人体から見れば異物であり、長期透析による副作用、合併症が数多く報告されている。血液透析膜に含まれる有機物の溶出を抑えることは長期透析時の体内蓄積を防ぎ、副作用を防止する観点から重要な技術である。すでに水充填のγ線滅菌品では、高透水性能を有し、かつ、架橋されることにより親水性高分子の溶出が抑えられている膜が知られているが、水充填のため重く、取扱性に欠けるという問題があった。 Organic substances contained in a large amount in hemodialysis membranes are foreign substances from the human body, and many side effects and complications due to long-term dialysis have been reported. Suppressing the elution of organic substances contained in the hemodialysis membrane is an important technique from the viewpoint of preventing accumulation in the body during long-term dialysis and preventing side effects. Already water-filled γ-ray sterilized products are known to have membranes with high water permeability and cross-linking that suppresses the elution of hydrophilic polymers. There was a problem of lack of sex.
本発明は、軽い・凍結しないなどの利点がある充填液を用いない中空糸膜モジュールにおいて、従来の充填液を用いない膜において施されているエチレンオキサイドガス（以下ＥＯＧと略す。）滅菌、高圧蒸気滅菌品では困難であるとされた、膜の親水性高分子だけでなく、ポッティング材の放射線に対する分解物などを含む、モジュール全体からの溶出物を抑えた中空糸膜および中空糸膜モジュールならびにそれらの製造方法を提供することを課題とするものである。 The present invention is a hollow fiber membrane module that does not use a filling liquid, which has advantages such as lightness and freezing, and is sterilized by ethylene oxide gas (hereinafter abbreviated as EOG) applied to a membrane that does not use a filling liquid, and high pressure. Hollow fiber membranes and hollow fiber membrane modules that suppress elution from the entire module, including not only hydrophilic polymers of membranes, but also degradation products of the potting material against radiation, which are considered difficult with steam sterilized products, and It is an object of the present invention to provide a manufacturing method thereof.
本発明は、上記目的を解決するために、下記の構成を有する。
（１）ポリビニルピロリドンを構成成分として含む、その自重に対して４％以上の水分を抱液した中空糸膜を収容してなる、不活性ガスが充填され、かつ放射線照射された中空糸膜モジュールにおいて、前記中空糸膜モジュール内の酸素濃度が０．２％以上、１．０％以下であり、初期洗浄液１０ｍｌ中の溶出物に対し、溶出物の滴定のために用いられる２．０×１０−３ｍｏｌ／ｌ過マンガン酸カリウム水溶液の消費量が中空糸膜内表面１ｍ２当たり５ｍｌ以下であり、かつ前記中空糸膜内側にウサギ全血を流して行う血小板付着実験において内表面の血小板付着数が中空糸膜１×１０３μｍ２あたり１８．１個以下であることを特徴とする血液処理用の中空糸膜モジュール。
In order to solve the above object, the present invention has the following configuration.
(1) which comprises an polyvinylpyrrolidone, formed by accommodating the hollow fiber membrane抱液4% or more water relative to its own weight, the inert gas is filled hollow fiber membrane modules and is irradiated, The oxygen concentration in the hollow fiber membrane module is not less than 0.2 % and not more than 1.0%, and 2.0 × 10 0 used for titration of the eluate with respect to the eluate in 10 ml of the initial washing solution. -3mol / l consumption of potassium permanganate aqueous solution and is less hollow fiber membrane surface 1 m 2 per 5 ml, and platelet adhesion the number of the inner surface in platelet adhesion experiments performed by passing rabbit whole blood inside the hollow fiber membrane Is 18.1 or less per 1 × 10 3 μm 2 of the hollow fiber membrane.
本発明により、軽い・凍結しないなどの利点がある充填液を用いない中空糸膜モジュールであって、溶出物が少ない中空糸膜ならびに中空糸膜モジュールを提供しさらにそれらの製造方法を提供するものである。 The present invention provides a hollow fiber membrane module which does not use a fill fluid has advantages such as no light-frozen, which provides a further process for their preparation provides a hollow fiber membrane and the hollow fiber membrane module less eluate It is .
本発明にかかる中空糸膜モジュールは、モジュール内部に不活性ガスが充填されたものである。不活性ガス以外にその他の気体もしくは液体が混入することを妨げないが、放射線照射前におけるモジュール内酸素濃度が０．１％以上、３．６％以下であり、放射線照射後のモジュール内酸素濃度が０．１％以上１．０％以下のものである。 The hollow fiber membrane module according to the present invention is one in which an inert gas is filled inside the module. It does not prevent other gases or liquids from mixing in addition to the inert gas, but the oxygen concentration in the module before radiation irradiation is 0.1% to 3.6%, and the oxygen concentration in the module after radiation irradiation Is 0.1% or more and 1.0% or less.
中空糸膜を構成する成分としては、各種の高分子が用いられ、疎水性高分子、親水性高分子のいずれも用いることができる。中でも疎水性高分子と親水性高分子の両方を同時に構成成分として用いたものが、ポアサイズのコントロールの容易性、生体適合性などの点で優れている。 As a component constituting the hollow fiber membrane, various polymers are used, and either a hydrophobic polymer or a hydrophilic polymer can be used. Among them, those using both hydrophobic polymer and hydrophilic polymer as constituent components are excellent in terms of ease of pore size control and biocompatibility.
中空糸膜モジュールを構成する疎水性高分子として、例えば、ポリスルホン、ポリアミド、ポリイミド、ポリフェニルエーテル、ポリフェニレンスルフィドなどほとんどのエンジニアリングプラスチックを用いることができるが、下記示性式で表されるポリスルホンが特に好ましい。ポリスルホンは下記基本骨格からなるが、ベンゼン環部分を修飾したものも用いることができる。 As the hydrophobic polymer constituting the hollow fiber membrane module, for example, most engineering plastics such as polysulfone, polyamide, polyimide, polyphenyl ether, polyphenylene sulfide, etc. can be used, but polysulfone represented by the following formula is particularly preferred. preferable. Polysulfone is composed of the following basic skeleton, but those having a modified benzene ring portion can also be used.
親水性高分子としては、例えばポリエチレングリコール、ポリビニルアルコール、カルボキシメチルセルロース、ポリビニルピロリドンなどが用いられ、単独で用いてもよいし、混合して用いてもよい。工業的にも比較的入手しやすいポリビニルピロリドンが好ましい。 As the hydrophilic polymer, for example, polyethylene glycol, polyvinyl alcohol, carboxymethyl cellulose, polyvinyl pyrrolidone and the like may be used, which may be used alone or in combination. Polyvinylpyrrolidone which is relatively easily available industrially is preferable.
たとえば、以下のような方法で中空糸膜を製造することができる。製膜原液を芯液と同時に２重スリット管構造の口金から同時に吐出させることで、中空糸膜を製造できる。その後、所定の水洗、乾燥工程、クリンプ工程を経た後、巻き取られ、適当な長さにカットした後、ケースに挿入され、ポッティング材によって端部を封止し、モジュール化される。 For example, a hollow fiber membrane can be produced by the following method. A hollow fiber membrane can be produced by simultaneously discharging the membrane-forming stock solution from the die having a double slit tube structure simultaneously with the core solution. Then, after passing through a predetermined water washing, drying process, and crimping process, it is wound up, cut into an appropriate length, inserted into a case, and the end is sealed with a potting material to be modularized.
本発明の軽くて凍結せずかつ取り扱いが容易で溶出物が抑えられた中空糸膜を得るためには、まず放射線照射の工程において水分が必要である。本発明の製造方法においては、中空糸膜が、中空糸膜自重に対して４％以上の水分を抱液していればよく、さらに、中空糸膜に水分を付与してから余剰な水分を除去する際に、温風乾燥あるいは真空乾燥などと言った特別な工程が必要でないという点から、１００％以上が好ましい。一方、重量軽減の意味から、３００％未満が好ましい。中空糸膜湿潤後に照射する放射線の例としては、α線、β線、中性子線、Ｘ線およびγ線などの種々の電離放射線が知られており、γ線が好ましい。中空糸膜湿潤後の放射線照射・滅菌では、大気存在下での放射線照射は励起した酸素ラジカルによって高分子の主鎖が切れ、分解が起こるため、ＣＯ2、Ｎ2、Ａｒ、Ｈｅなどの不活性ガスで大気を置換し、放射線照射を行うと分解が抑制され、溶出物が抑えられる。しかしながら、中空糸膜モジュール内の大気を完全に不活性ガスで置換するのは困難である。また、生体適合性の面から見ると、中空糸膜モジュール内に酸素濃度が高い状態で放射線照射した中空糸膜モジュールの方が、血液を流した時、中空糸膜内表面に付着する血小板数が少なく、好ましい。溶出物を抑えつつ、生体適合性を上げるためには、放射線照射前の中空糸膜モジュール内の酸素濃度が０．１％以上、３．６％以下であることが好ましい。放射線照射後の中空糸膜モジュール内部の酸素濃度は、０．１％以上、１．０％以下となる。また、照射する放射線としてγ線を用いる場合、γ線吸収線量は１０〜５０ＫＧｙ、好ましくは１０〜３０ＫＧｙである。 In order to obtain the hollow fiber membrane of the present invention that is light, non-frozen, easy to handle, and with reduced effluent, water is first required in the radiation irradiation step. In the production method of the present invention, it is sufficient that the hollow fiber membrane contains 4% or more of water with respect to the weight of the hollow fiber membrane. At the time of removal, 100% or more is preferable because a special process such as hot air drying or vacuum drying is not necessary. On the other hand, from the viewpoint of weight reduction, less than 300% is preferable. As examples of radiation irradiated after the hollow fiber membrane is wet, various ionizing radiations such as α rays, β rays, neutron rays, X rays and γ rays are known, and γ rays are preferable. In irradiation and sterilization after wetting the hollow fiber membrane, irradiation in the presence of air causes the main chain of the polymer to be broken by the excited oxygen radicals, resulting in decomposition, so that CO 2 , N 2 , Ar, He, etc. When the atmosphere is replaced with an active gas and irradiation is performed, decomposition is suppressed and elution is suppressed. However, it is difficult to completely replace the atmosphere in the hollow fiber membrane module with an inert gas. Also, from the viewpoint of biocompatibility, the hollow fiber membrane module irradiated with radiation in a state where the oxygen concentration is high in the hollow fiber membrane module, when blood flows, the number of platelets adhering to the inner surface of the hollow fiber membrane Is less and preferable. In order to improve biocompatibility while suppressing the eluate, the oxygen concentration in the hollow fiber membrane module before irradiation is preferably 0.1% or more and 3.6% or less. The oxygen concentration inside the hollow fiber membrane module after irradiation is 0.1% or more and 1.0% or less. Moreover, when using a gamma ray as a radiation to irradiate, a gamma ray absorbed dose is 10-50KGy, Preferably it is 10-30KGy.
本発明にかかる初期洗浄液とは、中空糸膜モジュールからの溶出物量の測定時に、中空糸膜モジュール内に流速１００ｍｌ／ｍｉｎで生理食塩水を流し、中空糸膜モジュール内満水後に最初の１５秒間に流出した２５ｍｌの洗浄液からサンプリングされた１０ｍｌのことをいう。この初期洗浄液に含まれる溶出物量を調べるために、２．０×１０-3ｍｏ／ｌ過マンガン酸カリウム水溶液２０ｍｌ、希塩酸１ｍｌを加え３分間煮沸した後、室温まで冷却し、ヨウ化カリウム水溶液１ｍｌを加え、よく攪拌後１０分間放置し、１．０×１０-2ｍｏｌ／ｌチオ硫酸ナトリウム水溶液で滴定を行う。透析モジュールを通さなかった生理食塩水の滴定に要したチオ硫酸ナトリウム水溶液量と、初期洗浄液の滴定時に要したチオ硫酸ナトリウム水溶液量との差を、溶出物により消費された過マンガン酸カリウム水溶液量（過マンガン酸カリウム水溶液の消費量）とした。 The initial cleaning liquid according to the present invention is a method in which a physiological saline is flowed into a hollow fiber membrane module at a flow rate of 100 ml / min when measuring the amount of eluate from the hollow fiber membrane module. It means 10 ml sampled from 25 ml of washing solution that has flowed out. In order to investigate the amount of eluate contained in this initial washing solution, 20 ml of 2.0 × 10 −3 mo / l potassium permanganate aqueous solution and 1 ml of dilute hydrochloric acid were added, boiled for 3 minutes, cooled to room temperature, and 1 ml of potassium iodide aqueous solution. The mixture is allowed to stand for 10 minutes after thorough stirring and titrated with a 1.0 × 10 −2 mol / l sodium thiosulfate aqueous solution. The difference between the amount of sodium thiosulfate aqueous solution required for the titration of physiological saline that did not pass through the dialysis module and the amount of sodium thiosulfate aqueous solution required for the titration of the initial washing solution was calculated as the amount of potassium permanganate aqueous solution consumed by the eluate. (Consumption of aqueous potassium permanganate solution).
本発明の提供する中空糸膜および中空糸膜モジュールならびにそれらの製造方法の特色は、過マンガン酸カリウムによる溶出物量の測定、ジメチルアセトアミドによる不溶物の確認および血小板付着量の測定によって確認される。透析型人工腎臓承認基準における回路の溶出物試験は、溶出液１０ｍｌを用いて２．０ｘ１０-3ｍｏｌ／ｌ過マンガン酸カリウム水溶液で滴定を実施することとなっており、滴定時の過マンガン酸カリウム水溶液の消費量が１ｍｌ以下となることが同基準により定められている。同基準は回路の溶出物試験であり、透析器の承認基準より厳しい基準であるため、中空糸膜モジュールが同基準をクリアすることは必要ではないが、５００ｍｌ以上の生理食塩水での洗浄後（中空糸膜モジュールの通常の使用時と同じ条件）に該溶出物試験を実施すると、本発明に係る中空糸膜モジュールは、同基準をクリアすることができる。この中空糸膜モジュールを用いて同基準をクリアするためには、後述する過マンガン酸カリウムによる初期洗浄液中の溶出物量の測定において、中空糸膜モジュール内に生理食塩水を１００ｍｌ／ｍｉｎの流速で流し、中空糸膜モジュール内満水後、最初の１５秒間に流出する洗浄液２５ｍｌからサンプリングした１０ｍｌ（初期洗浄液）に含まれる溶出物を用いた２．０×１０-3ｍｏｌ／ｌ過マンガン酸カリウム水溶液による滴定時における過マンガン酸カリウムの消費量が、洗浄液１０ｍｌに対し中空糸膜内表面１ｍ2当たり５ｍｌ以下となることが好ましい。本発明の提供する中空糸膜モジュールは、初期洗浄液を用いた２．０×１０-3ｍｏｌ／ｌ過マンガン酸カリウム水溶液による溶出物量の測定における過マンガン酸カリウムの消費量を５ｍｌ以下にすることができた。ここで言う溶出物は膜構成成分、ポッティング材の分解物と推定できるが、本発明の方法ではモジュール全体の溶出物を減少させることができる。これらの方法で作成された中空糸膜は疎水性高分子と親水性高分子のネットワークによって、その尿毒物質の拡散、有用蛋白であるアルブミンの阻止などの血液処理膜としての性能を発揮し、溶出物が少ないという特徴を有する。 The features of the hollow fiber membrane and the hollow fiber membrane module and the production method thereof provided by the present invention are confirmed by measuring the amount of eluate with potassium permanganate, confirming insoluble matter with dimethylacetamide, and measuring the amount of platelet adhesion. The eluate test of the circuit in the dialysis-type artificial kidney approval standard is to perform titration with 2.0 x 10 -3 mol / l potassium permanganate aqueous solution using 10 ml of eluate, and permanganic acid at the time of titration. The same standard stipulates that the consumption of aqueous potassium solution is 1 ml or less. The standard is a circuit eluate test and is a stricter standard than the dialyzer approval standard, so it is not necessary for the hollow fiber membrane module to clear the standard, but after washing with 500 ml or more of physiological saline. When the eluate test is carried out under the same conditions as in normal use of the hollow fiber membrane module, the hollow fiber membrane module according to the present invention can clear the same standard. In order to clear the same standard using this hollow fiber membrane module, in the measurement of the amount of eluate in the initial washing solution with potassium permanganate described later, physiological saline is fed into the hollow fiber membrane module at a flow rate of 100 ml / min. The aqueous solution of 2.0 × 10 −3 mol / l potassium permanganate using the eluate contained in 10 ml (initial washing solution) sampled from the washing solution 25 ml flowing out in the first 15 seconds after flowing in the hollow fiber membrane module It is preferable that the consumption amount of potassium permanganate during the titration by is 5 ml or less per 1 m 2 of the hollow fiber membrane inner surface with respect to 10 ml of the washing liquid. In the hollow fiber membrane module provided by the present invention, the consumption amount of potassium permanganate in the measurement of the amount of eluate with an aqueous solution of 2.0 × 10 −3 mol / l potassium permanganate using an initial cleaning solution is 5 ml or less. I was able to. Although the eluate said here can be estimated as a membrane component and a decomposition product of the potting material, the method of the present invention can reduce the eluate of the entire module. Hollow fiber membranes created by these methods demonstrate the performance of blood treatment membranes such as the diffusion of uremic substances and the prevention of albumin, a useful protein, by the network of hydrophobic and hydrophilic polymers. It has the feature that there are few things.
さらに、本発明の提供する中空糸膜および中空糸膜モジュールならびにそれらの製造方法の特色は、ジメチルアセトアミドによる不溶物の確認によって行いうる。本発明によって得られる中空糸膜および中空糸膜モジュールは、溶出物が少ないという特徴があり、その特徴は、ジメチルアセトアミドに不溶であることにより確認した。 Furthermore, the features of the hollow fiber membrane and the hollow fiber membrane module and the production method thereof provided by the present invention can be performed by confirming insoluble matter with dimethylacetamide. The hollow fiber membrane and the hollow fiber membrane module obtained by the present invention have a feature that there are few eluates, and the feature was confirmed by being insoluble in dimethylacetamide.
さらに、本発明の特色である生体適合性の高さは、血小板付着実験によって明らかにされうる。血小板付着実験は、中空糸膜内に兎血を灌流し、さらに生理食塩水で洗浄後も中空糸膜内に付着している血小板をグルタルアルデヒドで固定後、走査型電子顕微鏡で観察し、付着している血小板数により確認した。その結果、本発明の提供する中空糸膜は、同実験によって、優れた生体適合性を持つことが示された。 Furthermore, the high biocompatibility characteristic of the present invention can be clarified by platelet adhesion experiments. In the platelet adhesion experiment, blood platelets were perfused into the hollow fiber membrane, and after washing with physiological saline, the platelets adhering to the hollow fiber membrane were fixed with glutaraldehyde and observed with a scanning electron microscope. This was confirmed by the platelet count. As a result, the hollow fiber membrane provided by the present invention was shown to have excellent biocompatibility by the same experiment.
以上の通り、本発明により得られた中空糸膜および中空糸膜モジュールは、製膜後、特定の範囲の酸素存在下で放射線照射するという製造工程を採用することにより溶出物が少ないという優れた効果を有する中空糸膜および中空糸膜モジュールとすることができると同時に、生体適合性の高い中空糸膜および中空糸膜モジュールとすることができる。また、ドライ状態で使用できるため、軽く、凍結の心配がなく、取り扱いが容易で高性能な中空糸膜および中空糸膜モジュールを提供することができ、透析コストの削減にも寄与できる。同時に人体から見れば異物である有機物の溶出を抑えることができ、医療用具の安全性を高めることができる。
As described above, the hollow fiber membranes and hollow fiber membrane module obtained by the present invention, after the film was excellent in that fewer effluent by employing a manufacturing process that irradiation in the presence of oxygen in a specific range A hollow fiber membrane and a hollow fiber membrane module having an effect can be obtained, and at the same time, a hollow fiber membrane and a hollow fiber membrane module having high biocompatibility can be obtained. In addition, since it can be used in a dry state, it is possible to provide a high-performance hollow fiber membrane and a hollow fiber membrane module that are light, free from fear of freezing, easy to handle, and can contribute to reduction of dialysis costs. At the same time, when viewed from the human body, it is possible to suppress the elution of organic substances that are foreign substances, and the safety of the medical device can be improved.
本発明の中空糸膜および中空糸膜モジュールは人工腎臓、血漿分離膜、体外循環吸着用担体などの血液処理用途やエンドトキシン除去フィルターなどの水処理分野にも適用可能である。 The hollow fiber membrane and hollow fiber membrane module of the present invention can be applied to blood treatment applications such as artificial kidneys, plasma separation membranes, and extracorporeal circulation adsorption carriers, and water treatment fields such as endotoxin removal filters.
次に実施例に基づき本発明を説明する。用いた測定法は以下の通りである。
（１）中空糸膜モジュール内酸素濃度測定
中空糸膜モジュール自体を窒素雰囲気下にいれ、中空糸膜モジュールの栓にガスタイトシリンジの針を刺し、中空糸膜モジュール内ガスを採取し、ガスクロマトグラフィーに直接注入し、分析した。
（２）透水性能の測定
中空糸膜両端部を封止したガラス管ミニモジュール（中空糸膜本数２０本：有効長８〜１２ｃｍ）の中空糸膜内側に水圧１３．３ｋＰａをかけ、外側へ流出してくる単位時間当たりの濾過量を測定した。
Next, this invention is demonstrated based on an Example. The measurement method used is as follows.
(1) Measurement of the oxygen concentration in the hollow fiber membrane module The hollow fiber membrane module itself is placed in a nitrogen atmosphere, the needle of a gas tight syringe is inserted into the stopper of the hollow fiber membrane module, the gas in the hollow fiber membrane module is collected, and gas chromatography is performed. Injected directly into the graph and analyzed.
(2) Measurement of water permeation performance A water pressure of 13.3 kPa is applied to the inside of the hollow fiber membrane of a glass tube mini-module (20 hollow fiber membranes: effective length: 8 to 12 cm) sealed at both ends of the hollow fiber membrane, and flows out to the outside. The amount of filtration per unit time was measured.
透水性能は下記の式で算出した。
透水性能（ｍｌ／ｈｒ／ｍ2／ｋＰａ）＝ＱＷ／Ｔ／Ａ／Ｐ
ここでＱＷ：濾過量（ｍｌ） Ｔ：流出時間（ｈｒ） Ｐ：圧力（ｋＰａ）
Ａ：膜面積（ｍ2）（中空糸膜内表面面積換算）
（３）溶出物量の測定
測定中空糸膜モジュールに血液側に初期洗浄液として生理食塩水（大塚製薬）を流量１００ｍｌ／ｍｉｎで流し、モジュール内満水後、１５秒間の洗浄液（２５ｍｌ）をサンプリングした。また、洗浄開始後５分経過後の溶出物量を確認するため、洗浄開始５分後から１５秒間（２５ｍｌ）の洗浄液をサンプリングした。これらのサンプルから１０ｍｌを取り出し、２．０×１０-3ｍｏｌ／ｌ過マンガン酸カリウム水溶液２０ｍｌ、希塩酸１ｍｌを加え３分間煮沸した。室温まで冷却し、ヨウ化カリウム水溶液１ｍｌを加え、よく撹拌後１０分放置し、１．０ｘ１０-2ｍｏｌ／ｌチオ硫酸ナトリウム水溶液で滴定した。別途、透析モジュールを通さなかった水について、測定サンプルと同様な操作をした。透析モジュールを通さない水の滴定に要したチオ硫酸ナトリウム水溶液量と、サンプルの滴定に要したチオ硫酸ナトリウム水溶液量との差を、溶出物により消費された過マンガン酸カリウム水溶液量（過マンガン酸カリウム水溶液の消費量）とした。
（４）不溶物の確認
放射線照射後の中空糸膜を構成する成分の架橋による不溶化を確認するため、γ線照射後の中空糸膜を高温乾燥機を用い５０℃で１日乾燥後、中空糸膜１０本をジメチルアセトアミド１ｍｌに溶解させ、１分程度経過後の中空糸膜の形態を目視により確認した。
（５）血小板付着実験
ガラス管ミニモジュール（中空糸膜本数３０本：有効長８〜１２ｃｍ）の中空糸膜内側に、ウサギの全血を０．５９ｍｌ／ｍｉｎで６０分間灌流した。その後、中空糸膜内側に生理食塩水１０〜１２ｍｌを流し洗浄し、２．５〜４％のグルタルアルデヒド水溶液をミニモジュール内に充填した。このミニモジュールを１晩〜２日間冷蔵保存することで血小板を固定化した。この中空糸膜内表面を走査型電子顕微鏡で観察し、単位面積（１×１０3μｍ2）あたりの血小板付着数を計数した。
実施例１
ポリスルホン（アモコ社 Ｕｄｅｌ−Ｐ３５００）１６部、ポリビニルピロリドン（インターナショナルスペシャルプロダクツ社；以下ＩＳＰ社と略す）Ｋ３０ ４部、ポリビニルピロリドン（ＩＳＰ社Ｋ９０）２部をジメチルアセトアミド７７部、水１部を加熱溶解し、製膜原液とした。
The water permeability was calculated by the following formula.
Water permeability (ml / hr / m 2 / kPa) = QW / T / A / P
Where QW: Filtration volume (ml) T: Outflow time (hr) P: Pressure (kPa)
A: Membrane area (m 2 ) (in terms of the surface area of the hollow fiber membrane)
(3) Measurement of the amount of eluate A physiological saline (Otsuka Pharmaceutical Co., Ltd.) was flowed to the measurement hollow fiber membrane module on the blood side as an initial washing liquid at a flow rate of 100 ml / min, and after the module was full, the washing liquid (25 ml) for 15 seconds was sampled. Further, in order to confirm the amount of eluate after 5 minutes from the start of washing, the washing solution was sampled for 15 seconds (25 ml) after 5 minutes from the start of washing. 10 ml was taken out from these samples, and 20 ml of 2.0 × 10 −3 mol / l potassium permanganate aqueous solution and 1 ml of dilute hydrochloric acid were added and boiled for 3 minutes. After cooling to room temperature, 1 ml of an aqueous potassium iodide solution was added, and after stirring well, the mixture was allowed to stand for 10 minutes and titrated with an aqueous solution of 1.0 × 10 −2 mol / l sodium thiosulfate. Separately, water that did not pass through the dialysis module was subjected to the same operation as the measurement sample. The difference between the amount of sodium thiosulfate aqueous solution required for the titration of water that does not pass through the dialysis module and the amount of sodium thiosulfate aqueous solution required for the titration of the sample was calculated as the amount of potassium permanganate aqueous solution consumed by the eluate (permanganate Consumption of potassium aqueous solution).
(4) Confirmation of insoluble matter In order to confirm insolubilization due to crosslinking of the components constituting the hollow fiber membrane after irradiation, the hollow fiber membrane after γ-irradiation is dried at 50 ° C. for one day using a high-temperature dryer and then hollow. Ten yarn membranes were dissolved in 1 ml of dimethylacetamide, and the form of the hollow fiber membrane after about 1 minute was visually confirmed.
(5) Platelet adhesion experiment Rabbit whole blood was perfused at 0.59 ml / min for 60 minutes inside the hollow fiber membrane of a glass tube mini-module (30 hollow fiber membranes: effective length: 8 to 12 cm). Thereafter, 10-12 ml of physiological saline was poured inside the hollow fiber membrane for washing, and a 2.5-4% glutaraldehyde aqueous solution was filled in the minimodule. Platelets were immobilized by refrigerated storage of this minimodule overnight to 2 days. The inner surface of the hollow fiber membrane was observed with a scanning electron microscope, and the number of platelets adhered per unit area (1 × 10 3 μm 2 ) was counted.
Example 1
16 parts of polysulfone (Amoco Udel-P3500), 4 parts of polyvinylpyrrolidone (International Special Products; hereinafter referred to as ISP) K30, 2 parts of polyvinylpyrrolidone (ISP K90) and 77 parts of dimethylacetamide and 1 part of water are heated and dissolved. And it was set as the film forming stock solution.
この原液を温度５０℃の紡糸口金部へ送り、外径０．３５ｍｍ、内径０．２５ｍｍの２重スリット管から芯液としてジメチルアセトアミド６３部、水３７部からなる溶液を吐出させ、中空糸膜を形成させた後、温度３０℃、露点３９〜４０℃で調湿し、１０ミクロン以下のドライミストを加えた３５０ｍｍのドライゾーン雰囲気を経て、ジメチルアセトアミド２０重量％、水８０重量％からなる温度４０℃の凝固浴を通過させ、６０〜７５℃９０秒の水洗工程、１４０℃の乾燥工程を２分通過させ、１６０℃のクリンプ工程を経て得られた中空糸膜を巻き取り束とした。この中空糸膜を１．６ｍ2になるように、ケースに充填し、ポッティングし、端部を両面開口させて、透析モジュールとした。 This undiluted solution is sent to a spinneret at a temperature of 50 ° C., and a solution comprising 63 parts of dimethylacetamide and 37 parts of water is discharged as a core liquid from a double slit tube having an outer diameter of 0.35 mm and an inner diameter of 0.25 mm. After forming the film, the humidity is adjusted at a temperature of 30 ° C. and a dew point of 39 to 40 ° C., and after passing through a 350 mm dry zone atmosphere to which a dry mist of 10 microns or less is added, a temperature composed of 20% by weight of dimethylacetamide and 80% by weight of water. A hollow fiber membrane obtained by passing through a coagulation bath at 40 ° C., passing through a water washing step at 60 to 75 ° C. for 90 seconds and a drying step at 140 ° C. for 2 minutes and passing through a crimping step at 160 ° C. was used as a wound bundle. The hollow fiber membrane was filled in a case so as to be 1.6 m 2 , potted, and both ends of the end portion were opened to obtain a dialysis module.
モジュール化後、ＲＯ水を充填した後、９８ｋＰａの圧空で３０秒間、充填水を押し出し含水率２７０％とした。 After modularization, after filling with RO water, the filling water was extruded with 98 kPa pressure for 30 seconds to make the water content 270%.
モジュールの透析液側、血液側それぞれに４９ｋＰａで１５秒間、窒素を流し封入しモジュール内を窒素で置換した後、空気を導入することでモジュール内の酸素濃度を３．６％にした。この状態で、γ線照射（２５ＫＧｙ）を行った。γ線照射後のモジュール内酸素濃度は０．９％であった。 Nitrogen was allowed to flow at 49 kPa for 15 seconds on each of the dialysate side and blood side of the module, and the inside of the module was replaced with nitrogen, and then air was introduced to bring the oxygen concentration in the module to 3.6%. In this state, γ-ray irradiation (25 KGy) was performed. The oxygen concentration in the module after γ-ray irradiation was 0.9%.
このγ線照射後の中空糸膜の透水性能は２５０４ｍｌ／ｈｒ／ｍ2／ｋＰａであった。また、γ線照射後の中空糸膜はジメチルアセトアミドに不溶であった。上記の溶出物の測定方法によると、このモジュールの初期洗浄液の過マンガン酸カリウム水溶液の消費量は中空糸膜内表面１ｍ2当たり３．６ｍｌであった。また、５分後の洗浄液の過マンガン酸カリウム水溶液の消費量は０．９０ｍｌであった。中空糸膜内表面の単位面積当たりの血小板付着数は、１４．６個であった。
実施例２
ポリスルホン（アモコ社 Ｕｄｅｌ−Ｐ３５００）４部、（アモコ社 Ｕｄｅｌ−Ｐ１７００）１２部、ポリビニルピロリドン（インターナショナルスペシャルプロダクツ社；以下ＩＳＰ社と略す） Ｋ３０ ２部、ポリビニルピロリドン（ＩＳＰ社Ｋ９０）４部をジメチルアセトアミド７７部、水１部を加熱溶解し、製膜原液とした。
The water permeability of the hollow fiber membrane after γ-ray irradiation was 2504 ml / hr / m 2 / kPa. Moreover, the hollow fiber membrane after γ-ray irradiation was insoluble in dimethylacetamide. According to the above eluate measurement method, the consumption of the potassium permanganate aqueous solution in the initial cleaning liquid of this module was 3.6 ml per 1 m 2 of the hollow fiber membrane inner surface. The consumption of the potassium permanganate aqueous solution in the cleaning solution after 5 minutes was 0.90 ml. The number of platelet adhesion per unit area on the inner surface of the hollow fiber membrane was 14.6.
Example 2
Polysulfone (Amoco Corporation Udel-P3500) 4 parts, (Amoco Corporation Udel-P1700) 12 parts, Polyvinylpyrrolidone (International Special Products Inc .; hereinafter abbreviated as ISP) K30 2 parts, Polyvinylpyrrolidone (ISP K90) 4 parts 77 parts of acetamide and 1 part of water were dissolved by heating to obtain a stock solution.
この原液を温度５０℃の紡糸口金部へ送り、外径０．３５ｍｍ、内径０．２５ｍｍの２重スリット管から芯液としてジメチルアセトアミド６５部、水３５部からなる溶液を吐出させ、中空糸膜を形成させた後、温度３０℃、露点２８℃で調湿し、１０ミクロン以下のドライミストを加えた３５０ｍｍのドライゾーン雰囲気を経て、ジメチルアセトアミド２０重量％、水８０重量％からなる温度４０℃の凝固浴を通過させ、８５℃６０秒の水洗工程、１４０℃の乾燥工程を２分通過させ、１８０℃のクリンプ工程を経て得られた中空糸膜を巻き取り束とした。この中空糸膜を１．３ｍ2になるように、ケースに充填し、ポッティングし、端部を両面開口させて、透析モジュールとした。 This undiluted solution is sent to a spinneret at a temperature of 50 ° C., and a solution comprising 65 parts of dimethylacetamide and 35 parts of water is discharged as a core liquid from a double slit tube having an outer diameter of 0.35 mm and an inner diameter of 0.25 mm. Then, the humidity is adjusted at a temperature of 30 ° C. and a dew point of 28 ° C., and after passing through a 350 mm dry zone atmosphere to which a dry mist of 10 microns or less is added, a temperature of 40 ° C. comprising 20% by weight of dimethylacetamide and 80% by weight of water. Was passed through a coagulation bath of 85 ° C. for 60 seconds and a drying step of 140 ° C. for 2 minutes, and the hollow fiber membrane obtained through the crimping step of 180 ° C. was used as a wound bundle. The hollow fiber membrane was filled in a case so as to be 1.3 m 2 , potted, and the ends were opened on both sides to obtain a dialysis module.
モジュール化後、実施例１と同様にＲＯ水を充填し、圧空により水を押しだした後、中空糸膜の水分を蒸発させ、含水率１００％とした。このモジュール内を窒素に置換し、モジュール内の酸素濃度を１．２％にした後、γ線照射（２５ＫＧｙ）を行った。γ線照射後のモジュール内酸素濃度は０．３％であった。 After modularization, RO water was filled in the same manner as in Example 1, and water was pushed out by compressed air, and then water in the hollow fiber membrane was evaporated to a moisture content of 100%. The inside of this module was replaced with nitrogen, and after the oxygen concentration in the module was 1.2%, γ-ray irradiation (25 KGy) was performed. The oxygen concentration in the module after γ-ray irradiation was 0.3%.
このγ線照射後の中空糸膜の透水性能は３１８０ｍｌ／ｈｒ／ｍ2／ｋＰａであった。また、γ線照射後の中空糸膜はジメチルアセトアミドに不溶であった。上記の溶出物の測定方法によると、このモジュールの初期洗浄液の過マンガン酸カリウム水溶液の消費量は中空糸膜内表面１ｍ2当たり０．９０ｍｌであった。
実施例３
実施例１と同様の条件で製膜された中空糸膜を用い、同様にモジュール化した。モジュール化後、実施例１と同様にＲＯ水を充填し、圧空により水を押しだし、含水率を２７０％にした。このモジュール内を窒素に置換し、モジュール内の酸素濃度を０．２％にした。この状態でγ線照射（２５ＫＧｙ）した。
このγ線照射後の中空糸膜の透水性能は２８１２ｍｌ／ｈｒ／ｍ2／ｋＰａであった。また、γ線照射後の中空糸膜はジメチルアセトアミドに不溶であった。上記の溶出物の測定方法によると、このモジュールの初期洗浄液の過マンガン酸カリウム水溶液の消費量は中空糸膜内表面１ｍ2当たり１．６ｍｌであった。また、生理食塩水によるモジュール内洗浄開始５分後の洗浄液の過マンガン酸カリウム水溶液の消費量は０．８０ｍｌであった。中空糸膜内表面の単位面積当たりの血小板付着数は、１８．１個であった。
実施例４
実施例１と同様の条件で製膜された中空糸膜を用い、同様にモジュール化した。モジュール化後、実施例１と同様にＲＯ水を充填し、圧空により水を押し出した後、中空糸膜の水分を蒸発させ、含水率を４％とした。このモジュール内を窒素で置換し、モジュール内の酸素濃度を０．２％にした。この状態でγ線照射（２５ＫＧｙ）した。
The water permeability of the hollow fiber membrane after γ-irradiation was 3180 ml / hr / m 2 / kPa. Moreover, the hollow fiber membrane after γ-ray irradiation was insoluble in dimethylacetamide. According to the above eluate measurement method, the consumption of the potassium permanganate aqueous solution in the initial cleaning solution of this module was 0.90 ml per 1 m 2 of the hollow fiber membrane inner surface.
Example 3
Using a hollow fiber membrane formed under the same conditions as in Example 1, it was modularized in the same manner. After modularization, RO water was filled in the same manner as in Example 1, and water was pushed out by compressed air to make the water content 270%. The inside of this module was replaced with nitrogen, so that the oxygen concentration in the module was 0.2%. In this state, γ-ray irradiation (25 KGy) was performed.
The water permeability of the hollow fiber membrane after γ-ray irradiation was 2812 ml / hr / m 2 / kPa. Moreover, the hollow fiber membrane after γ-ray irradiation was insoluble in dimethylacetamide. According to the above eluate measurement method, the consumption of the potassium permanganate aqueous solution in the initial cleaning solution of this module was 1.6 ml per 1 m 2 of the hollow fiber membrane inner surface. The consumption of the potassium permanganate aqueous solution in the cleaning solution 5 minutes after the start of cleaning in the module with physiological saline was 0.80 ml. The platelet adhesion number per unit area on the inner surface of the hollow fiber membrane was 18.1.
Example 4
Using a hollow fiber membrane formed under the same conditions as in Example 1, it was modularized in the same manner. After modularization, RO water was filled in the same manner as in Example 1, and water was pushed out by compressed air, and then water in the hollow fiber membrane was evaporated to a moisture content of 4%. The inside of this module was replaced with nitrogen, so that the oxygen concentration in the module was 0.2%. In this state, γ-ray irradiation (25 KGy) was performed.
上記の溶出物の測定方法によると、このモジュールの初期洗浄液の過マンガン酸カリウム水溶液の消費量は中空糸内表面１ｍ2当たり０．６０ｍｌであった。また、生理食塩水によるモジュール内洗浄開始５分後の洗浄液の過マンガン酸カリウム水溶液の消費量は０．０７ｍｌであった。中空糸内表面の単位面積当たりの血小板付着数は２．４個であった。
比較例１
実施例１と同様の条件で製膜された中空糸膜を用い、同様にモジュール化した。モジュール化後、モジュール内にＲＯ水を充填し、γ線照射（２５ＫＧｙ）を行った。この中空糸膜内表面の単位面積当たりの血小板付着数は、３６．６個であった。
比較例２ 実施例１と同様の条件で製膜された中空糸膜を用い、同様にモジュール化した。モジュール化後、実施例１と同様にＲＯ水を充填し、圧空により水を押しだし、含水率を２７０％にした。このモジュール内を不活性ガスで置換せず（酸素濃度２１．１％）、γ線照射（２５ＫＧｙ）を行った。
According to the above eluate measurement method, the consumption of the potassium permanganate aqueous solution in the initial cleaning liquid of this module was 0.60 ml per 1 m 2 of the hollow fiber inner surface. The consumption of the potassium permanganate aqueous solution in the cleaning solution 5 minutes after the start of cleaning in the module with physiological saline was 0.07 ml. The number of platelet adhesion per unit area of the inner surface of the hollow fiber was 2.4.
Comparative Example 1
Using a hollow fiber membrane formed under the same conditions as in Example 1, it was modularized in the same manner. After modularization, the module was filled with RO water, and γ-ray irradiation (25 KGy) was performed. The number of platelet adhesion per unit area of the inner surface of the hollow fiber membrane was 36.6.
Comparative Example 2 Using a hollow fiber membrane formed under the same conditions as in Example 1, it was modularized in the same manner. After modularization, RO water was filled in the same manner as in Example 1, and water was pushed out by compressed air to make the water content 270%. The inside of the module was not replaced with an inert gas (oxygen concentration 21.1%), and γ-ray irradiation (25 KGy) was performed.
このγ線照射後の中空糸膜の透水性能は３５３４ｍｌ／ｈｒ／ｍ2／ｋＰａであった。また、γ線照射後の中空糸膜はジメチルアセトアミドに可溶であった。上記の溶出物の測定方法によると、このモジュールの初期洗浄液の過マンガン酸カリウム水溶液の消費量は中空糸膜内表面１ｍ2当たり１１．７ｍｌであった。中空糸膜内表面の単位面積当たりの血小板付着数は、９．６個であった。
比較例３
実施例１と同様の条件で製膜された中空糸膜を用い、同様にモジュール化した。モジュール化後、実施例１と同様にＲＯ水を充填し、圧空により水を押しだし、含水率を２７０％にした。このモジュール内を実施例１と同様に窒素に置換した後、空気を導入することでモジュール内の酸素濃度を４．２％にした。この状態でγ線照射（２５ＫＧｙ）した。
The water permeability of the hollow fiber membrane after γ-irradiation was 3534 ml / hr / m 2 / kPa. Moreover, the hollow fiber membrane after γ-ray irradiation was soluble in dimethylacetamide. According to the above eluate measurement method, the consumption of the potassium permanganate aqueous solution in the initial cleaning solution of this module was 11.7 ml per 1 m 2 of the hollow fiber membrane inner surface. The number of platelet adhesion per unit area of the inner surface of the hollow fiber membrane was 9.6.
Comparative Example 3
Using a hollow fiber membrane formed under the same conditions as in Example 1, it was modularized in the same manner. After modularization, RO water was filled in the same manner as in Example 1, and water was pushed out by compressed air to make the water content 270%. After the inside of this module was replaced with nitrogen in the same manner as in Example 1, the oxygen concentration in the module was set to 4.2% by introducing air. In this state, γ-ray irradiation (25 KGy) was performed.
このγ線照射後の中空糸膜の透水性能は２２４８ｍｌ／ｈｒ／ｍ2／ｋＰａであった。また、γ線照射後の中空糸膜はジメチルアセトアミドに可溶であった。上記の溶出物の測定方法によると、このモジュールの初期洗浄液の過マンガン酸カリウム水溶液の消費量は５．３ｍｌであった。また、５分後の洗浄液の過マンガン酸カリウム水溶液の消費量は１．０１ｍｌであった。
比較例４
実施例２と同様の条件で製膜された中空糸膜を用い、同様にモジュール化した。このモジュールに水を充填せず（含水率０％）、実施例１と同様に窒素に置換した後、γ線照射（２５ＫＧｙ）を行った。
The water permeability of the hollow fiber membrane after γ-irradiation was 2248 ml / hr / m 2 / kPa. Moreover, the hollow fiber membrane after γ-ray irradiation was soluble in dimethylacetamide. According to the above eluate measurement method, the consumption of the potassium permanganate aqueous solution in the initial cleaning solution of this module was 5.3 ml. The consumption of the potassium permanganate aqueous solution in the cleaning solution after 5 minutes was 1.01 ml.
Comparative Example 4
Using a hollow fiber membrane formed under the same conditions as in Example 2, it was modularized in the same manner. This module was not filled with water (water content 0%) and replaced with nitrogen in the same manner as in Example 1, followed by γ-ray irradiation (25 KGy).
このγ線照射後の中空糸膜の透水性能は４２６３ｍｌ／ｈｒ／ｍ2／ｋＰａであった。また、γ線照射後の中空糸膜はジメチルアセトアミドに可溶であった。上記の溶出物の測定方法によると、このモジュールの初期洗浄液の過マンガン酸カリウム水溶液の消費量は中空糸膜内表面１ｍ2当たり１１．５ｍｌであった。 The water permeability of the hollow fiber membrane after γ-irradiation was 4263 ml / hr / m 2 / kPa. Moreover, the hollow fiber membrane after γ-ray irradiation was soluble in dimethylacetamide. According to the above eluate measurement method, the consumption of the potassium permanganate aqueous solution in the initial cleaning solution of this module was 11.5 ml per 1 m 2 of the inner surface of the hollow fiber membrane.
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| JP2001170167A (en) * | 1999-12-21 | 2001-06-26 | Toray Ind Inc | Method of manufacturing dialyzer and method of sterilization |
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| JPH089668B2 (en) * | 1986-10-14 | 1996-01-31 | 東レ株式会社 | Hydrophilized film and method for producing the same |
| JPS63209663A (en) * | 1987-02-25 | 1988-08-31 | 旭メデイカル株式会社 | Method for sterilizing body fluid treatment apparatus and sterilized body fluid treatment apparatus |
| JP2876320B2 (en) * | 1989-06-15 | 1999-03-31 | 株式会社ジェイ・エム・エス | Radiation sterilization method for medical equipment |
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