JP3640737B2 - Polysulfone-based permselective hollow fiber membrane - Google Patents
Polysulfone-based permselective hollow fiber membrane Download PDFInfo
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【０００１】
【発明の属する技術分野】
本発明は、ポリスルホン系樹脂及び親水性高分子からなる血液処理用の中空糸膜の改良に関する。
【０００２】
【従来の技術】
近年、ポリスルホンの優れた生体適合性、耐熱性、耐薬品性などの特性を利用した中空糸膜が透析膜、血漿分離膜、血漿分画膜等の医療用分離膜として使用されている。しかしながら、ポリスルホンは疎水性物質であり、抗血栓性、血液適合性を付与するためにポリビニルピロリドン等の親水化高分子をブレンドした膜の研究がなされてきた。
【０００３】
特公平５−３３３１号公報には親水性高分子を熱処理または放射線処理によりポリスルホン膜中に架橋固定する方法、特開平４−３００６３６号公報には親水性高分子が架橋されヒドロゲル状態でポリスルホン膜構造中に存在する状態で放射線架橋させた中空糸膜が夫々開示されている。
しかし、これらの方法で得られる膜は、親水性高分子の溶出が無いように親水性高分子同士は強固に絡み合った状態で架橋・固定されている。ところが、こうして架橋し、不溶化すると中空糸に血液に流した後、生理的溶液で血液を回収した時に一部の中空糸に血液が残留する、いわゆる残血が発生するという問題点がある。
【０００４】
【発明が解決しようとする課題】
従来法では、親水性高分子の架橋の程度が低いと溶出物が増えると考え、親水性高分子をしっかり架橋・固定させようとしたため、溶出物を減らすことは出来たが、残血が増えるという新たな問題が発生してしまった。
本発明は上記問題点を解決し、高い透水性を有するにも係わらず分画分子量がシャープで、血液適合性に優れ、かつ残血の少ないポリスルホン系選択透過性中空糸膜を提供することを目的とする。
【０００５】
【課題を解決するための手段】
ところが、本発明者らが鋭意検討したところ、中空糸膜中の親水性高分子含有量がポリマー全量の１〜１８重量％であって、且つ該親水性高分子を部分架橋して総親水性高分子の量に対するジメチルアセトアミド（以下、ＤＭＡＣと略称する）可溶性の親水性高分子の量をある特定の範囲にすることにより溶出物を減らし、かつ、本発明の目的である残血性を驚くべき程に改良することに成功した。
すなわち、本発明は：
（１） ポリスルホン系樹脂と親水性高分子とからなる中空糸膜であって、親水性高分子含有量がポリマー全量の１〜１８重量％であり、かつ該親水性高分子を部分架橋してジメチルアセトアミドに可溶性の親水性高分子含有量が総親水性高分子量の２５重量％以上９５重量％以下としたポリスルホン系選択透過性中空糸膜を提供する。また、
（２） 親水性高分子がポリビニルピロリドンである点にも特徴を有する。
【０００６】
以下、本発明を詳細に説明する。
本発明で云うポリスルホン系樹脂とは、スルホン結合を有する高分子化合物の総称であり特に制限されるものではないが、例えば、下記式（１）〜式（３）のいずれかで示されるポリスルホン系樹脂が広く市販されており入手も容易なため好ましく用いられる。
特に、式（１）で示す化学構造を持つポリスルホン系樹脂は、例えばアコモ・パフォーマンス・プロダクツより「ユーデル」の商品名で市販されており、重合度等によって幾つかの種類が存在するが特にこだわるものではない。
【０００７】
【化１】
本発明で云う親水性高分子とは、親水性基を持つ高分子化合物の総称であり、例えばポリビニルピロリドン、ポリアルキレンオキシド類（例えばポリエチレングリコール、ポリエチレンオキシド等）、ポリビニルアルコール、ポリ酢酸ビニル、ポリアクリル酸、ポリアクリルアミド、ポリビニルアミン、ポリスチレンスルホン酸等を挙げることができるが、これらの親水性高分子には、各種の分子量を持つものや置換基を導入したもの等も同様に用いることができる。中でもポリビニルピロリドン（以下、ＰＶＰと略称する）が良好に用いられる。
【０００９】
特に、製膜原液に添加する親水性高分子の分子量は１万〜５００万のものが用いられるが、、分子量が大きいほど膜中への親水性高分子、特にポリビニルピロリドンの残存率が大きくなるため、分子量が大きい場合は製膜原液中の濃度が低くてもよい。
好ましくは親水性高分子の分子量は１０万以上２００万以下、更に好ましくは３０万以上１２０万以下を使用することが望ましい。
【００１０】
本発明において、中空糸膜製造原液に添加した親水性高分子は膜が形成される過程においてその一部が膜中に残存する。その残存率は親水性高分子の分子量や紡糸条件により変化してくるが、親水性高分子含有量がポリマー（ポリスルホン系樹脂＋親水性高分子）全量の１〜１８重量％であることが必要であり、好ましくは２〜１５重量％。さらに好ましくは２〜１２重量％がよい。
１重量％未満であると、中空糸膜に十分な親水性を付与することが困難であり、また１８重量％を超えると製膜原液の粘性が高くなりすぎて、中空糸同士の固着が発生し好まし
くない。
【００１１】
本発明において、ＤＭＡＣに可溶性の親水性高分子含有量は、該親水性高分子を部分架橋して総親水性高分子量の２５重量％以上９５重量％以下とすることが必要である。
該ＤＭＡＣに可溶性の親水性高分子含有量は、ＤＭＡＣに溶解する親水性高分子含有量の総親水性高分子量（もともと膜中に存在した親水性高分子の量）に対する割合の百分率であり、
下記
【数１】
【００１２】
例えば親水性高分子がポリビニルピロリドンの場合、次の方法で測定することができる。
まず、総親水性高分子重量は、中空糸を元素分析法を用いて測定し、その総窒素量から中空糸単位重量当たりの値を算出することが出来る。
即ち、秤量した中空糸膜約１ｇをＤＭＡＣ５０ｍｌに入れ、２５℃、５時間充分な撹袢を行うと、ＤＭＡＣはポリスルホンおよび３次元網目構造を有さない親水性高分子に対する溶剤であるので、架橋等によって３次元網目構造を有する親水性高分子が固形分として残る。
この固形分を予め秤量したフィルターで濾過し、水洗した後１０５℃で１６時間乾燥する。得られた固形分重量を測定することにより、中空糸単位重量当たりのＤＭＡＣに不溶性の親水性高分子重量を求めることができる。
これらを上記数式に代入し、ＤＭＡＣに可溶性の親水性高分子含有量（％）を算出することができる。
【００１３】
ＤＭＡＣに可溶性の親水性高分子含有量（％）が２５重量％未満であると、親水性高分子は強固に不溶化された状態で膜に存在し、親水性高分子溶出は極めて少ないが残血がひどくなり、９５重量％を越えると親水性高分子の溶出量増加が懸念される。
そのため本発明の好ましい範囲は３５重量％以上９０重量％以下、更に好ましくは５０重量％以上８５重量％以下である。
【００１４】
本願発明の中空糸膜では、３次元網目構造を有さない、ＤＭＡＣに溶解する親水性高分子が特定範囲量（総親水性高分子量の２５重量％以上９５重量％以下）膜表面に存在することにより残血が減ると考えられる。
即ち、３次元網目構造を有する親水性高分子は、分子鎖の運動性が悪くなるために、血液が接触する膜表面部分の親水性高分子の殆どが３次元網目構造を有すると、血液との親和性が低下することが推測される。
本発明の中空糸膜では、３次元網目構造を有さない線状（ＤＭＡＣに可溶性）の親水性高分子を上記特定範囲量含有して膜表面にも存在するため、血液との親和性が良くなり、血小板粘着および血液凝固系の活性化を抑制し、残血性が改善されるものと考えられるが詳細なメカニズムは判っていない。
【００１５】
本発明の膜中に存在する親水性高分子には、３次元網目構造となりＤＭＡＣに不溶化した状態のものが共存する。このようなＤＭＡＣに不溶な親水性高分子は、水にも不溶であり、膜からは溶出しない。
これに対して、ＤＭＡＣに可溶な親水性高分子は、水にも可溶性を示して膜から溶け出し易いが、３次元網目構造を有する（ＤＭＡＣに不溶性の）親水性高分子が共存すると、水に対して溶け出し難くなる。恐らく、３次元網目構造の親水性高分子と分子レベルでの絡み合いや水素結合等の相互作用があるためと考えられる。
このようにして３次元網目構造を有さない分子鎖の運動性が良好な（ＤＭＡＣに可溶性の）親水性高分子が、膜中および膜表面に溶出しないで存在するため、残血改善が図られているものと考えられる。
【００１６】
ポリスルホン系樹脂および親水性高分子からなる中空糸膜の製造方法については公知の方法を用いることが出来る。
例えば、ポリスルホン系樹脂および親水性高分子を下記の極性溶剤に溶解して紡糸原液を製造し、これを中空糸状の成形ノズルを経て常法に従って紡糸し、得られた糸を凝固液中に浸漬して中空糸膜を製造すれば良い。
本発明において、（親水性高分子を含めて）ポリスルホン系樹脂を溶解する有機溶剤、特に極性溶剤としては、Ｎ−メチル−２−ピロリドン、ジメチルスルホキシド、ジメチルホルムアミド又はジメチルアセトアミド（ＤＭＡＣ）等を挙げることができるが、ジメチルアセトアミドの使用が望ましい。更に、該溶剤に無機塩、例えば塩化リチウム、塩化ナトリウム、硝酸ナトリウム、硝酸カリウム、硫酸ナトリウム、塩化亜鉛等の無機酸の塩；酢酸ナトリウム、ギ酸ナトリウム等の有機酸の塩を１〜８重量％程度の少量を添加しても良い。
【００１７】
また、凝固液としては、ポリスルホン系樹脂の非溶剤であり、極性溶剤と混じり易い液体、例えば水、食塩、界面活性剤等の電解質を挙げることができる。
凝固液として水の使用が一般的である。
次に、親水性高分子を部分架橋してＤＭＡＣに可溶性の親水性高分子含有量を総親水性高分子の２５％以上９５％以下に調節する方法について説明する。
該方法を例示すると、化学架橋剤あるいは架橋触媒を紡糸段階あるいは後処理段階で用いる方法、放射線により部分架橋する方法、放射線により中空糸膜を滅菌させる場合にあっては架橋阻止剤（例えば、グリセリン、プロピレングリコール等）を共存させ、架橋させ過ぎない様にする方法、熱により架橋させる方法等が例示でき、これらの方法における薬品、処理条件等についてはＤＭＡＣに可溶性の親水性高分子量を総親水性高分子の２５％以上９５％以下に調節出来る様、適宜選択出来る。
【００１８】
上記の放射線による架橋としては、α線、β線、γ線、Ｘ線、紫外線、電子線等が用いられるが、特にγ線では浸透性が高いので単一膜だけでなく、膜集合体や膜を組み込んだモジュール状態でもポリビニルピロリドン等の親水性高分子の架橋処理が可能であり好適に用いることができる。
【００１９】
【実施例】
以下、実施例および参考例を用いて本発明を詳細に説明するが、これらは本発明の範囲を制限するものでない。
（参考例１） 中空糸（前駆体糸）の製造：
ポリスルホン樹脂（アコモ社製：Ｐー１７００）１８部と親水性高分子としてのポリビニルピロリドン（ＢＡＳＦ社製：Ｋ−９０、分子量１２０万）５部とをジメチルアセトアミド８０部に添加して、撹袢容器内５０℃で８時間溶解し製膜原液を得た。
５０℃に保温した該原液を外径４５０μｍ、内径２５０μｍ、注入孔１００μｍの環状スリット口金から５０℃に保温した空中空走行部分を経て吐出部の４５ｃｍ下方に設置した６０℃凝固浴へと含浸させ、中空糸をカセに巻取った。
【００２０】
（実施例１）
参考例１で成形された中空糸を切断後、束の切断面上方から８０℃の熱水シャワーを２時間かけて洗浄し、グリセリン水溶液を付着させて真空乾燥した。さらに、該中空糸から膜面積１．６ｍ２のモジュールを作成し、該モジュールを３lの純水で洗浄した。続いて、２５ｋＧｙのγ線を照射した。
このモジュールから中空糸を取り出しＤＭＡＣに可溶性の親水性高分子含有量を調べたところ５１重量％であった。また、充填液中のグリセリン濃度は２２０ｐｐｍであった。
【００２１】
（実施例２）
参考例１で成形された中空糸を切断後、過硫酸アンモニウム水溶液に漬浸し、８０℃で１時間加熱した。次に、束の切断上方から８０℃の熱水シャワーで２時間洗浄し、グリセリン水溶液を付着させて真空乾燥した。
さらに、該中空糸から膜面積１．６ｍ２のモジュールを作成し、該モジュールをエチレンオキサイトガスで滅菌した。このモジュールから中空糸を取り出し、ＤＭＡＣに可溶性の親水性高分子含有量を調べたところ、２９重量％であった。
【００２２】
（実施例３）
参考例１で成形された中空糸を切断後、ｐＨ＝１３の水酸化バリウム水溶液に漬浸し、９０℃で４時間加熱した。次に、束の切断上方から８０℃の熱水シャワーで2時間洗浄し、グリセリン水溶液を付着させて真空乾燥した。さらに、該中空糸から膜面積１．６ｍ２のモジュールを作成し、該モジュールをエチレンオキサイトガスで滅菌した。このモジュールから中空糸を取り出し、ＤＭＡＣに可溶性の親水性高分子含有量を調べたところ７０重量％であった。
【００２３】
（比較例１）
実施例１で製造されたモジュールを２０Ｌの純水で５時間かけゆっくり洗浄した。続いて２５ｋＧｙのγ線を照射した後、このモジュールから中空糸を取り出しＤＡＭＣに可溶性の親水性高分子含有量を調べたところ１５重量％であった。また、充填液中のグリセリン濃度は１０ｐｐｍであった。
【００２４】
（比較例２）
実施例１で製造されたモジュールを３Ｌの純水で洗浄した後、γ線を照射せずに中空糸を取り出しＤＡＭＣに可溶性の親水性高分子含有量を調べたところ１００重量％であった。
【００２５】
（参考例２）中空糸膜の残血性等の試験
約２０ｋｇの成犬を用い血液の体外循環を実施した。抗凝固剤はヘパリンを循環前に１００単位／ｋｇ投与した。動脈より血液回路を通してモジュールに血液流量７０ｍｌ／ｍｉｎで流し、その後静脈に戻した。循環時間は６０分で、循環終了後生理食塩水により、回路およびモジュール内の血液を回収した。生理食塩水の流量は７０ｍｌ／ｍｉｎで２分間流した。
【００２６】
使用したモジュールは実施例１、２および３のモジュールであり、比較として、比較例１および２のモジュールを用いた（但し、同じ製法で作成したモジュール）。
血液の残留性すなわち残血性は、モジュール内の中空糸束外周を目視し、そのうち血液の残留が認められたフィラメント数を測定し、下記の評価基準に準じて評価した。また、各モジュール内の充填液中のＰＶＰ量を測定した。
その結果を表１に示す。
【００２７】
【表１】
【表２】
それに対して、比較例１の中空糸膜モジュールは残血が多く、また比較例２の中空糸膜モジュールはＰＶＰが多量に溶出する。
【００２９】
【発明の効果】
本発明によれば、ジメチルアセトアミドに可溶性の親水性高分子量を該親水性高分子を部分架橋して或る特定の範囲にすることにより溶出物を減らし、かつ、残血性が大幅に改良されたポリスルホン系選択透過性中空糸膜となった。[0001]
BACKGROUND OF THE INVENTION
The present invention relates to an improvement in a hollow fiber membrane for blood treatment comprising a polysulfone resin and a hydrophilic polymer.
[0002]
[Prior art]
In recent years, hollow fiber membranes utilizing the characteristics of polysulfone such as excellent biocompatibility, heat resistance, and chemical resistance have been used as medical separation membranes such as dialysis membranes, plasma separation membranes, and plasma fractionation membranes. However, polysulfone is a hydrophobic substance, and studies have been made on a membrane blended with a hydrophilic polymer such as polyvinylpyrrolidone in order to impart antithrombogenicity and blood compatibility.
[0003]
Japanese Patent Publication No. 5-3331 discloses a method of crosslinking and fixing a hydrophilic polymer in a polysulfone membrane by heat treatment or radiation treatment, and Japanese Patent Application Laid-Open No. 4-300366 discloses a structure of a polysulfone membrane in a hydrogel state in which the hydrophilic polymer is crosslinked. Hollow fiber membranes that have been radiation cross-linked in the state in which they are present are each disclosed.
However, the membranes obtained by these methods are crosslinked and fixed in a state where the hydrophilic polymers are intertwined firmly so that the hydrophilic polymers are not eluted. However, when cross-linked and insolubilized in this manner, there is a problem that so-called residual blood is generated in which blood remains in some of the hollow fibers when the blood is collected in a physiological solution after flowing into the hollow fibers.
[0004]
[Problems to be solved by the invention]
In the conventional method, if the degree of cross-linking of the hydrophilic polymer is low, the amount of eluate increases, and the hydrophilic polymer is firmly cross-linked and fixed, so the amount of eluate can be reduced but the residual blood increases. A new problem has occurred.
The present invention provides a polysulfone-based permselective hollow fiber membrane that solves the above-mentioned problems, has a high molecular permeability, has a sharp molecular weight cut off, is excellent in blood compatibility, and has little residual blood. Objective.
[0005]
[Means for Solving the Problems]
However, as a result of intensive studies by the present inventors, the content of the hydrophilic polymer in the hollow fiber membrane is 1 to 18% by weight of the total amount of the polymer, and the hydrophilic polymer is partially crosslinked to give a total hydrophilicity. The amount of dimethylacetamide (hereinafter abbreviated as DMAC) soluble hydrophilic polymer relative to the amount of the polymer is reduced within a certain range to reduce the amount of eluate, and the residual blood property that is the object of the present invention is surprising. We succeeded in improving as much.
That is, the present invention provides:
(1) A hollow fiber membrane composed of a polysulfone resin and a hydrophilic polymer, the hydrophilic polymer content is 1 to 18% by weight of the total amount of the polymer, and the hydrophilic polymer is partially crosslinked. Provided is a polysulfone-based permselective hollow fiber membrane in which the content of a hydrophilic polymer soluble in dimethylacetamide is 25% by weight to 95% by weight of the total hydrophilic high molecular weight. Also,
( 2 ) Another characteristic is that the hydrophilic polymer is polyvinylpyrrolidone.
[0006]
Hereinafter, the present invention will be described in detail.
The polysulfone resin referred to in the present invention is a general term for polymer compounds having a sulfone bond and is not particularly limited. For example, the polysulfone resin represented by any one of the following formulas (1) to (3) The resin is preferably used because it is widely available and easily available.
In particular, a polysulfone resin having a chemical structure represented by the formula (1) is commercially available from, for example, Acomo Performance Products under the trade name “Udel”, and there are several types depending on the degree of polymerization and the like. It is not a thing.
[0007]
[Chemical 1]
The hydrophilic polymer referred to in the present invention is a general term for polymer compounds having a hydrophilic group. For example, polyvinyl pyrrolidone, polyalkylene oxides (eg, polyethylene glycol, polyethylene oxide, etc.), polyvinyl alcohol, polyvinyl acetate, Acrylic acid, polyacrylamide, polyvinylamine, polystyrene sulfonic acid, and the like can be mentioned. As these hydrophilic polymers, those having various molecular weights and those having a substituent introduced therein can be used as well. . Of these, polyvinylpyrrolidone (hereinafter abbreviated as PVP) is preferably used.
[0009]
In particular, the molecular weight of the hydrophilic polymer added to the film-forming stock solution is 10,000 to 5,000,000, but the higher the molecular weight, the larger the residual ratio of the hydrophilic polymer, particularly polyvinylpyrrolidone in the film. Therefore, when the molecular weight is large, the concentration in the film-forming stock solution may be low.
The molecular weight of the hydrophilic polymer is preferably 100,000 to 2,000,000, more preferably 300,000 to 1,200,000.
[0010]
In the present invention, a part of the hydrophilic polymer added to the hollow fiber membrane production stock remains in the membrane in the process of forming the membrane. The residual ratio varies depending on the molecular weight of the hydrophilic polymer and the spinning conditions, but the hydrophilic polymer content must be 1 to 18% by weight of the total amount of the polymer (polysulfone resin + hydrophilic polymer). and it is preferably 2 to 15 wt%. More preferably, it is 2 to 12% by weight.
If it is less than 1 % by weight, it is difficult to impart sufficient hydrophilicity to the hollow fiber membrane, and if it exceeds 18% by weight, the viscosity of the membrane-forming stock solution becomes too high, and the hollow fibers stick to each other. It is not preferable.
[0011]
In the present invention, the content of the hydrophilic polymer soluble in DMAC needs to be 25% by weight or more and 95% by weight or less of the total hydrophilic polymer weight by partially crosslinking the hydrophilic polymer.
The hydrophilic polymer content soluble in DMAC is a percentage of the ratio of the hydrophilic polymer content dissolved in DMAC to the total hydrophilic polymer amount (the amount of hydrophilic polymer originally present in the membrane),
Below [Equation 1]
[0012]
For example, when the hydrophilic polymer is polyvinylpyrrolidone, it can be measured by the following method.
First, the total hydrophilic polymer weight can be obtained by measuring the hollow fiber using elemental analysis and calculating the value per unit weight of the hollow fiber from the total nitrogen amount.
That is, when about 1 g of the weighed hollow fiber membrane is put in 50 ml of DMAC and sufficiently stirred at 25 ° C. for 5 hours, since DMAC is a solvent for polysulfone and a hydrophilic polymer having no three-dimensional network structure, As a result, a hydrophilic polymer having a three-dimensional network structure remains as a solid content.
The solid content is filtered through a pre-weighed filter, washed with water, and dried at 105 ° C. for 16 hours. By measuring the obtained solid content weight, the weight of the hydrophilic polymer insoluble in DMAC per unit weight of the hollow fiber can be determined.
By substituting these into the above formula, the content (%) of hydrophilic polymer soluble in DMAC can be calculated.
[0013]
When the content (%) of the hydrophilic polymer soluble in DMAC is less than 25% by weight, the hydrophilic polymer exists in the membrane in a strongly insolubilized state, and the elution of the hydrophilic polymer is extremely small, but residual blood When the amount exceeds 95% by weight, there is a concern that the amount of hydrophilic polymer eluted may increase.
Therefore, the preferable range of the present invention is 35% by weight or more and 90% by weight or less, more preferably 50% by weight or more and 85% by weight or less.
[0014]
In the hollow fiber membrane of the present invention, a hydrophilic polymer that does not have a three-dimensional network structure and dissolves in DMAC is present in a specific range amount (25% by weight to 95% by weight of the total hydrophilic high molecular weight) on the membrane surface. This is thought to reduce residual blood.
That is, since the hydrophilic polymer having a three-dimensional network structure has poor molecular chain mobility, when most of the hydrophilic polymer on the surface of the membrane in contact with blood has a three-dimensional network structure, It is presumed that the affinity of is reduced.
In the hollow fiber membrane of the present invention, a linear ( soluble in DMAC ) hydrophilic polymer that does not have a three-dimensional network structure is contained in the above-mentioned specific range amount and is also present on the membrane surface. It is thought that it improves, suppresses platelet adhesion and activation of the blood coagulation system, and improves residual bloodness, but the detailed mechanism is unknown.
[0015]
The hydrophilic polymer present in the film of the present invention coexists with a three-dimensional network structure insolubilized in DMAC. Such a hydrophilic polymer insoluble in DMAC is insoluble in water and does not elute from the membrane.
In contrast, a hydrophilic polymer that is soluble in DMAC is soluble in water and easily dissolves from the membrane, but when a hydrophilic polymer having a three-dimensional network structure ( insoluble in DMAC ) coexists, It becomes difficult to dissolve in water. This is probably due to interactions such as entanglement and hydrogen bonding at the molecular level with hydrophilic polymers having a three-dimensional network structure.
Thus, since a hydrophilic polymer ( soluble in DMAC ) having a good mobility of a molecular chain not having a three-dimensional network structure is present in the membrane and on the membrane surface, residual blood is improved. It is thought that
[0016]
As a method for producing a hollow fiber membrane comprising a polysulfone resin and a hydrophilic polymer, a known method can be used.
For example, a polysulfone-based resin and a hydrophilic polymer are dissolved in the following polar solvent to produce a spinning stock solution, which is spun according to a conventional method through a hollow fiber-shaped forming nozzle, and the obtained yarn is immersed in a coagulation solution. Thus, a hollow fiber membrane may be manufactured.
In the present invention, examples of organic solvents that dissolve polysulfone resins (including hydrophilic polymers), particularly polar solvents, include N-methyl-2-pyrrolidone, dimethyl sulfoxide, dimethylformamide, and dimethylacetamide (DMAC). Although the use of dimethylacetamide is desirable. Further, the solvent contains an inorganic salt such as a salt of an inorganic acid such as lithium chloride, sodium chloride, sodium nitrate, potassium nitrate, sodium sulfate or zinc chloride; a salt of an organic acid such as sodium acetate or sodium formate. A small amount of may be added.
[0017]
Examples of the coagulating liquid include non-solvents of polysulfone-based resins and liquids that are easily mixed with polar solvents, such as electrolytes such as water, sodium chloride, and surfactants.
The use of water as a coagulation liquid is common.
Next, a method for partially crosslinking the hydrophilic polymer to adjust the content of the hydrophilic polymer soluble in DMAC to 25% or more and 95% or less of the total hydrophilic polymer will be described.
Examples of the method include a method of using a chemical cross-linking agent or a cross-linking catalyst in the spinning stage or the post-treatment stage, a method of partially cross-linking with radiation, and a cross-linking inhibitor (for example, glycerin when sterilizing a hollow fiber membrane with radiation , Propylene glycol, etc.) can be coexisted and not crosslinked too much, and the method of crosslinking by heat, etc. The chemicals, treatment conditions, etc. in these methods can be determined by increasing the hydrophilic high molecular weight soluble in DMAC to total hydrophilicity. It can be selected as appropriate so that it can be adjusted to 25% or more and 95% or less of the conductive polymer.
[0018]
As the above-mentioned crosslinking by radiation, α rays, β rays, γ rays, X rays, ultraviolet rays, electron beams, etc. are used. Even in a module state in which a membrane is incorporated, a hydrophilic polymer such as polyvinylpyrrolidone can be cross-linked and can be suitably used.
[0019]
【Example】
EXAMPLES Hereinafter, although this invention is demonstrated in detail using an Example and a reference example, these do not restrict | limit the scope of the present invention.
Reference Example 1 Production of hollow fiber (precursor yarn):
18 parts of a polysulfone resin (Acomo: P-1700) and 5 parts of polyvinyl pyrrolidone (BASF: K-90, molecular weight of 1,200,000) as a hydrophilic polymer are added to 80 parts of dimethylacetamide and stirred. It melt | dissolved in the container at 50 degreeC for 8 hours, and obtained the film forming stock solution.
The stock solution kept at 50 ° C. is impregnated into a 60 ° C. coagulation bath installed 45 cm below the discharge part from an annular slit base having an outer diameter of 450 μm, an inner diameter of 250 μm, and an injection hole of 100 μm through an empty hollow running part kept at 50 ° C. Then, the hollow fiber was wound around a cassette.
[0020]
(Example 1)
After the hollow fiber molded in Reference Example 1 was cut, a hot water shower at 80 ° C. was washed from above the cut surface of the bundle for 2 hours, and a glycerin aqueous solution was adhered and vacuum-dried. Further, a module having a membrane area of 1.6 m 2 was prepared from the hollow fiber, and the module was washed with 3 l of pure water. Subsequently, 25 kGy of γ rays were irradiated.
The hollow fiber was taken out from this module and the content of hydrophilic polymer soluble in DMAC was examined. The glycerin concentration in the filling liquid was 220 ppm.
[0021]
(Example 2)
The hollow fiber molded in Reference Example 1 was cut, immersed in an aqueous ammonium persulfate solution, and heated at 80 ° C. for 1 hour. Next, it was washed with a hot water shower at 80 ° C. for 2 hours from above the cutting of the bundle, and an aqueous glycerin solution was adhered and dried in a vacuum.
Further, a module having a membrane area of 1.6 m 2 was prepared from the hollow fiber, and the module was sterilized with ethylene oxide gas. The hollow fiber was taken out from this module, and the content of hydrophilic polymer soluble in DMAC was examined. As a result, it was 29% by weight.
[0022]
(Example 3)
The hollow fiber molded in Reference Example 1 was cut, immersed in an aqueous barium hydroxide solution having a pH = 13, and heated at 90 ° C. for 4 hours. Next, it was washed with a hot water shower at 80 ° C. for 2 hours from above the cutting of the bundle, and an aqueous glycerin solution was adhered and dried in a vacuum. Further, a module having a membrane area of 1.6 m 2 was prepared from the hollow fiber, and the module was sterilized with ethylene oxide gas. The hollow fiber was taken out from this module, and the content of hydrophilic polymer soluble in DMAC was determined to be 70% by weight.
[0023]
(Comparative Example 1)
The module manufactured in Example 1 was slowly washed with 20 L of pure water for 5 hours. Subsequently, after irradiating 25 kGy of γ-rays, the hollow fiber was taken out from the module and the content of hydrophilic polymer soluble in DAMC was examined. The glycerin concentration in the filling liquid was 10 ppm.
[0024]
(Comparative Example 2)
After the module produced in Example 1 was washed with 3 L of pure water, the hollow fiber was taken out without irradiating γ rays, and the content of hydrophilic polymer soluble in DAMC was examined.
[0025]
(Reference Example 2) Test on residual blood property of hollow fiber membrane Extracorporeal circulation of blood was performed using an approximately 20 kg adult dog. As an anticoagulant, heparin was administered at 100 units / kg before circulation. Blood was flowed from the artery through the blood circuit to the module at a blood flow rate of 70 ml / min, and then returned to the vein. The circulation time was 60 minutes, and the blood in the circuit and the module was collected with physiological saline after the circulation. The physiological saline was flowed at 70 ml / min for 2 minutes.
[0026]
The modules used were the modules of Examples 1, 2, and 3. For comparison, the modules of Comparative Examples 1 and 2 were used (however, the modules produced by the same manufacturing method).
The blood persistence, ie, residual blood property, was evaluated according to the following evaluation criteria by visually observing the outer periphery of the hollow fiber bundle in the module and measuring the number of filaments in which blood remained. Moreover, the amount of PVP in the filling liquid in each module was measured.
The results are shown in Table 1.
[0027]
[Table 1]
[Table 2]
In contrast, the hollow fiber membrane module of Comparative Example 1 has a lot of residual blood, and the hollow fiber membrane module of Comparative Example 2 elutes a large amount of PVP.
[0029]
【The invention's effect】
According to the present invention, the amount of the hydrophilic polymer soluble in dimethylacetamide is reduced to a specific range by partially cross-linking the hydrophilic polymer, and the residual blood property is greatly improved. A polysulfone-based permselective hollow fiber membrane was obtained.
Claims (2)
Priority Applications (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| JP16253096A JP3640737B2 (en) | 1996-06-04 | 1996-06-04 | Polysulfone-based permselective hollow fiber membrane |
Applications Claiming Priority (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| JP16253096A JP3640737B2 (en) | 1996-06-04 | 1996-06-04 | Polysulfone-based permselective hollow fiber membrane |
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| Publication Number | Publication Date |
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| JPH09323031A JPH09323031A (en) | 1997-12-16 |
| JP3640737B2 true JP3640737B2 (en) | 2005-04-20 |
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Families Citing this family (11)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US7572374B2 (en) | 2000-04-13 | 2009-08-11 | Transvivo, Inc. | Anticoagulant and thrombo-resistant hollow fiber membranes for in-vivo plasmapheresis and ultrafiltration |
| US6802820B1 (en) * | 2000-04-13 | 2004-10-12 | Transvivo, Inc. | Specialized hollow fiber membranes for in-vivo plasmapheresis and ultrafiltration |
| US7585412B2 (en) | 2000-04-13 | 2009-09-08 | Transvivo, Inc. | Specialized hollow fiber membranes for plasmapheresis and ultrafiltration |
| US7195711B2 (en) | 2000-04-13 | 2007-03-27 | Transvivo Inc. | Specialized hollow fiber membranes for in-vivo plasmapheresis and ultrafiltration |
| US6899692B2 (en) | 2001-10-17 | 2005-05-31 | Transvivo, Inc. | Plasmapheresis filter device and catheter assembly |
| US6849183B2 (en) | 2002-08-13 | 2005-02-01 | Transvivo, Inc. | Method and apparatus for therapeutic apheresis |
| US7354392B2 (en) | 2004-02-25 | 2008-04-08 | Transvivo Inc. | Structurally optimized hollow fiber membranes |
| JP4587025B2 (en) * | 2004-06-01 | 2010-11-24 | 東洋紡績株式会社 | Polysulfone-based selectively permeable hollow fiber membrane with excellent blood compatibility |
| US8070964B2 (en) | 2005-03-29 | 2011-12-06 | Toray Industries, Inc. | Modified substrate and process for production thereof |
| JP2015116212A (en) * | 2013-12-16 | 2015-06-25 | 旭化成メディカル株式会社 | Hollow fiber membrane for blood treatment and blood treatment device in which membrane is embedded |
| US20220088539A1 (en) * | 2019-01-29 | 2022-03-24 | Toray Industries, Inc. | Separation membrane module |
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1996
- 1996-06-04 JP JP16253096A patent/JP3640737B2/en not_active Expired - Lifetime
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