JP4026037B2 - Hollow fiber membrane gas-liquid gas exchange device and gas exchange method thereof - Google Patents
Hollow fiber membrane gas-liquid gas exchange device and gas exchange method thereof Download PDFInfo
- Publication number
- JP4026037B2 JP4026037B2 JP25642598A JP25642598A JP4026037B2 JP 4026037 B2 JP4026037 B2 JP 4026037B2 JP 25642598 A JP25642598 A JP 25642598A JP 25642598 A JP25642598 A JP 25642598A JP 4026037 B2 JP4026037 B2 JP 4026037B2
- Authority
- JP
- Japan
- Prior art keywords
- hollow fiber
- fiber membrane
- gas
- gas exchange
- membrane
- Prior art date
- Legal status (The legal status is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the status listed.)
- Expired - Lifetime
Links
Images
Landscapes
- External Artificial Organs (AREA)
- Separation Using Semi-Permeable Membranes (AREA)
- Degasification And Air Bubble Elimination (AREA)
Description
【０００１】
【発明が属する技術分野】
本発明は、中空糸膜を利用した外部灌流型気液ガス交換装置として使用され、例えば工業用途として、ボイラー用水の脱酸素、配管の腐食防止を目的としたビル空調用水の脱気、半導体の製造に使用される超純水の脱気、イオン交換水の脱気、逆浸透膜供給水の脱気、発電用水の脱酸素及び脱炭酸ガス等に使用される。また、食品工業用途として、ビール及び清酒の製造、食品製造用水の脱気等に使用される。さらに、本発明は医療用途として透析モジュールの充填液の脱気や注射用水の脱気等に使用され、特に心臓手術時等の血液体外循環において患者の血液を蘇生させる人工肺に好適に適用できる。
【０００２】
【従来の技術】
人工肺は開心術時あるいは長期の呼吸補助時に生体肺の代替または補助として使用され、種々のタイプが開発されている。これら人工肺は生体肺の持つ機能の中で血液に酸素を供給し、二酸化炭素を除去するガス交換機能を代行するものである。現在、中空糸膜型人工肺が主流となっており、大きく２つの種類に分類される。一つは血液を中空糸内部に流しガス交換を行ういわゆる内部灌流型人工肺であり、もう一つは血液を中空糸の外側に接触させ、中空糸内部に酸素混合ガスを流しガス交換を行ういわゆる外部灌流型人工肺である。外部灌流型人工肺は血液流れの圧力損失を低く抑える事ができ且つ、ガス交換効率に優れ、中空糸膜型人工肺の主流となりつつある。
【０００３】
例えば特公平５−２０１１１にはシート状に配列されたガス透過性中空糸を多孔性芯体に巻回し、酸素を中空糸内部を通し、血液を中空糸の外部に流し、ガス交換を行う人工肺が開示されている。
【０００４】
特公平４−２０６６号公報には、隣接する中空糸同士が互いに交差するよう環状に巻かれて、その中心に中空部を有する環状の中空糸層を形成しているとともに、該中空糸層における中空糸の充填率を０．４５〜０．８０とした人工肺が開示されている。
【０００５】
特公平６−９６０９８号公報には中空糸シートを積層してハウジング内に組み込んだ人工肺において中空糸シートを形成する縦糸の密度及び、シートの厚みを特定の値とするとともにシートの中空糸密度とシートの積層密度の積を中空糸外径をもとに計算される値の特定値範囲値とする事により血液のチャネリングおよび滞留を抑えた人工肺が開示されている。
【０００６】
特公平７−９８０６１号公報には簾状中空糸シートの積層体を角筒状のハウジングに組み込んだ人工肺において、血液を流す方向に垂直な単位断面積当たりの血液流量が５０ｍＬ／ｍｉｎ／ｃｍ ２ の時の圧力損失を△Ｐとした時に△Ｐ／Ｔ・Ｉ・ｎ≦１なる関係を保つことにより血流のチャネリングと滞留を抑えた人工肺が開示されている。
【０００７】
通常、気液ガス交換装置に必須な要求性能は優れたガス交換能力である。特に医療用途である人工肺には、血液への優れた酸素供給能力及び血液からの二酸化炭素の優れた除去能力が要求される。これに加え人工肺には、患者に対する生体負担が小さいことが要求され、血液と直接接触する膜面積が小さく、小型で血液のプライミング量が小さく、且つ血流の圧力損失が小さく、体外循環中に血液損傷を起こさない事が要求される。
【０００８】
膜型人工肺のガス交換性能は血液側の境膜が律速となっていることが広く知られており、血液側の境膜を可能な限り破壊すべく種々の人工肺の構造が盛んに検討されている。
【０００９】
近年、血流の圧力損失を低く抑えることができ且つ単位膜面積当たりのガス交換能力の向上が期待できる中空糸膜外部灌流型人工肺の研究開発が活発に行われ、商品化されつつある。しかしながら、従来の技術は性能向上、特に血液側の境膜を効率的に破壊しそのガス交効率を向上する為に必要となる技術要素が不明確であり、その結果としてそのガス交換効率おいて未だ満足のゆく人工肺が開発されていない。
【００１０】
【発明が解決しようとする課題】
本研究者らは、中空糸膜シートを積層してハウジング内に組み込んだ外部灌流型中空糸膜型気液ガス交換装置の最適設計について鋭意研究し、驚くべき事に、特定の範囲の外径を有する中空糸を使用し、中空糸膜を実質的に平行に配列した特定の中空糸膜間隔を有する中空糸シートを使用し、該中空糸膜シートを特定の相当直径となるよう積層してハウジング内に組み込むことにより従来のものと比較し飛躍的にガス交換効率を向上でき、且つ液流（血流）圧損をも極めて低値に抑える事ができる外部灌流型中空糸膜型気液ガス交換装置にかかる発明を提供する。
【００１１】
【課題を解決するための手段】
即ち本発明は、
（１）外部灌流型中空糸膜型気液ガス交換装置において、中空糸膜の外径 が１５０μｍ〜３９０μｍであり、中空糸膜の間隔が１２０μｍ〜２８０μｍである中空糸膜が実質的に平行に配列された中空糸膜シートを使用し、（式１）Ｄｖ＝４×（シート積層体の占める全空間体積）／（中空糸膜の全有効外表面積）
で計算される相当直径が１６５μｍ〜３２５μｍとなるよう積層された状態でハウジング内に組み込まれていることを特徴とする外部灌流型中空糸膜型気液ガス交換装置であり、
（２）中空糸膜の外径が１８０μｍ〜２５０μｍであり、且つ中空糸シートの中空糸間隔が１５０μｍ〜２６０μｍであり且つＤｖが２１５μｍ〜３２０μｍであることを特徴とする（１）の外部灌流型中空糸膜型気液ガス交換装置であり、（３）中空糸膜が 中空糸膜の酸素透過速度が５×１０ −５ ［ｃｍ ３ （ＳＴＰ）／ｃｍ ２ ／ｓ／ｃｍＨｇ］〜３５０×１０−５［ｃｍ ３ （ＳＴＰ）／ｃｍ ２ ／ｓ／ｃｍＨｇ］であるポリ（４−メチルペンテン−１）系樹脂からなる中空糸非対称膜であることを特徴とする（１）または（２）に記載の外部灌流型気液ガス交換装置であり、（４）外部灌流型中空糸膜型気液ガス交換装置において、中空糸膜の外径 が１５０μｍ〜３９０μｍであり、中空糸膜の間隔が１２０μｍ〜２８０μｍである中空糸膜が実質的に平行に配列された中空糸膜シートを使用し、（式１）
Ｄｖ＝４×（シート積層体の占める全空間体積）／（中空糸膜の全有効外表面積）で計算される相当直径が１６５μｍ〜３２５μｍとなるよう積層された状態でハウジング内に組み込まれていることを特徴とする外部灌流型中空糸膜型気液ガス交換装置を使用し、液体を積層された中空糸膜シートに実質的に垂直にクロスして流すことによりガス交換を行う事を特徴とする気液ガス交換方法である。
【００１２】
ここで言う相当直径（Ｄｖ）とは
（式１）
Ｄｖ＝４×（シート積層体の占める全空間体積）／（中空糸膜の全有効外表面積）で計算される値であり、ここで式の分子は中空糸膜シート積層体の占める体積から中空糸膜の占める体積を差し引いた空間の体積である。
【００１３】
【発明の実施の形態】
本発明の実施の形態の典型的なもの及び最良の状態は、後記の実施例に具体的に示されるが、その概要は以下の通りである。
【００１４】
本発明の中空糸の外径は１５０μｍ〜３９０μｍであれば良く、適用用途により適切な外径を選択できる。
【００１５】
また、中空糸膜の膜厚は１５μｍ〜８０μｍである事が好ましい。膜厚は中空糸膜の強度及び耐久性を支配し、膜を構成する素材及び膜の構造、及び本発明の適用用途等に最適な膜厚を選定できる。一般に外径が細ければ強度、耐久性保持のために必要となる膜厚も薄くできる。
【００１６】
驚くべき事に本発明において、膜モジュール内の中空糸の充填率を同じとしても中空糸の外径を本発明の範囲内において細くするほどガス交換効率を向上させることができる。さらに、細径化により中空糸の耐久性及び強度を飛躍的に向上でき好ましいが、中空糸外径が１５０μｍ以下となると膜モジュール製造時におけるハンドリングが困難となる。
【００１７】
中空糸内側に酸素含有気体を流し中空糸外側を流れる血液とガス交換を行う人工肺用途として好適に使用する場合、ガス交換効率を高め、少ない膜面積で十分なガス交換能力を有し、小型で血液のプライミング量が小さい人工肺モジュールを実現する為には細径中空糸が好ましいが、一方中空糸外径を細くする事により内径は必然的に細くなる。
【００１８】
気相側の気体圧力は、血液側に気泡が発生しないように、血液側の圧力と比較し十分に低く保つ必要がある。また、臨床使用中には血液側から中空糸内に相当量の水蒸気が透過し、使用条件によっては、この水蒸気が人工肺ガス出口で凝集し、中空糸膜が閉塞し、ガス交換能力の経時的な低下を引き起こす場合がある。これらを現象を防止するために中空糸の内径はある程度の太さが必要とされる。
【００１９】
人工肺用途として好ましくは外径が１８０μｍ〜２５０μｍの範囲であり、内径は１４０μｍ以上が好ましい。特にＥＣＭＯやＰＣＰＳ用途等の数日から数週間に亘る連続使用の可能性のある用途においては、中空糸の外径は２００μｍ〜２５０μが好ましく、内径は１５０μｍ以上が好ましい。
【００２０】
本発明では、中空糸膜が少なくとも同一積層面においては中空糸膜間隔が均等間隔で平行に配列された中空糸膜シートを積層しハウジング内に組み込んで使用する事をも特徴とする。
【００２１】
中空糸膜シートの形成方法に制限は無く例えばポリエステル、ポリアミド、ポリウレタン、ポリアクリルニトリル等からなるのモノフィラメント又はマルチフィラメントからなる糸を縦糸として、横糸となる中空糸膜を均等間隔で編組する事により好ましく形成できる。工業的に中空糸膜シートを形成する方法として例えばラッセル編み等が知られている。
【００２２】
縦糸の太さは５〜３０デニールが好ましい。特にポリエステルからなる１０〜２５デニールのマルチフィラメントは柔軟性と強度に優れ、また経時変化が少なく、シート形成時及び経時的にも中空糸に損傷与える事がなく、特に好ましい。
【００２３】
本発明は中空糸膜シートの中空糸膜の間隔が１２０μｍ〜２８０μｍの範囲であり、且つ（式１）で表される積層された中空糸シートの相当直径Ｄｖが１６５μｍ〜３２５μｍの範囲である事を特徴とする。これにより高いガス交換効率と低液流圧損を同時に満足する外部灌流型気液ガス交換装置を実現できる。
【００２４】
また、中空糸膜シートの積層数は２０層以上である事が好ましく、さらに好ましくは５０層以上であり、最も好ましくは７０層以上である。
本発明に記載の外部灌流方式によるガス交換効率は中空糸膜シートの中空糸膜間隔を狭くし、且つＤｖを小さくすることにより程飛躍的に向上できるが、中空糸膜の間隔が１２０μｍ以下及び／又はＤｖが１６５μｍ以下となると液流の圧損が極めて大きくなり、各種産業実用用途への展開の範囲が限られる。
【００２５】
シートの中空糸膜間隔及びＤｖは気液ガス交換装置の適用用途の要求性能に応じて本発明の範囲で適宜選択することができる。
【００２６】
例えば、水からの溶存気体の脱気用として使用される半導体製造用超純水の製造において、比較的処理流量が少なく、溶存酸素濃度１ｐｐｂ以下の高度の脱気が要求されるサブシステムでの適用を目的とする場合、中空糸間隔は１２０μｍ〜２６０μｍが好ましく、Ｄｖは１６５μｍ〜２６０μｍが好ましい。
【００２７】
また、電力用水の製造等の溶存酸素濃度５０ＰＰＢ程度の比較的低脱気水準の水を多量に必要とする用途には中空糸シートの中空糸膜の間隔は２００μｍ〜２８０μｍが好ましく、Ｄｖは２００μｍ〜３２５μｍが好ましい。
【００２８】
医療用途である人工肺に使用する場合、低血流圧損と高い気体交換効率が要求されることから中空糸膜シートの中空糸間隔は１５０μｍ〜２６０μｍが好ましく、Ｄｖは２１５μｍ〜３２５μｍであることが好ましい。
【００２９】
人工肺用途に於いて特に数日に亘る長期連続使用を前提とするＰＣＰＳ及びＥＣＭＯ等の用途においては、中空糸間隔が１８０μｍ〜２６０ｍであり、Ｄｖが２３０μｍ〜３２５μｍが好適である。
【００３０】
本発明に適用する中空糸膜は適度の耐久性と機械的強度及びガス透過性を有しておれば良くその素材、製法、膜構造等特に制限は無く、例えば、膜素材としてポリエチレン、ポリプロピレン、ポリブチレン、ポリ（４−メチルペンテン−１）等のポリオレフィン系樹脂、ジメチルシロキサン等のシリコーン系樹脂、ポリテトラフルオロエチレン、パーフルオロアルコキシフッ素樹脂等の各種フッ素樹脂、各種ポリイミド系樹脂が好適に使用できる。
【００３１】
また、中空糸膜の膜構造においては、微多孔膜、均質膜、不均質膜、複合膜、ウレタン等の薄膜を微多孔膜で挟んだいわゆるサンドイッチ構造を有する各種膜が適用できる。
【００３２】
また、これら膜の製造法にも制限は無く例えば、溶融法、湿式法、乾湿式等で製造された膜が適用できる。
【００３３】
特に、ポリ（４−メチルペンテン−１）系樹脂を膜素材とする膜壁に緻密層を有する中空糸不均質膜は酸素、窒素、炭酸ガス等のガスの透過性に優れ、疎水性が高く水蒸気バリヤー性に優れ工業用及び、医療用の気液ガス交換装置に最も好適である。
中空糸膜の緻密層の形成位置に特に制限は無く、中空糸膜の外表面及び／又は内表面に形成していても良いが、特に中空糸膜の外表面に緻密層を形成しているポリ（４−メチルペンテン−１）系樹脂からなる中空糸膜は、血液の補体活性が低く、血液との親和性に優れ、且つ長期に亘り血漿リークが無く、ガス交換性能の低下も無く外部灌流型人工肺用として最も好適に適用される。また、ポリ（４−メチルペンテン−１）系樹脂は人工肺用として一般使用されているポリプロピレンと比較し素材自体のガス透過性が約１０倍であり、本質的に中空糸膜壁を連通した微多孔部分でのみしかガス交換を行わないポリプロピレン微多孔膜と比較し、膜表面全体でガス交換を行うことができ極めて好ましい。
【００３４】
溶融法によるポリ（４−メチルペンテン−１）系樹脂を膜素材とする不均質膜については、例えば特願平５−６６５６号公報、及び特公平７−１２１３４０号公報に開示されている。
【００３５】
また、湿式法もしくは乾湿式法等の溶剤を使用し樹脂溶液の相分離を利用して膜を形成させるポリ（４−メチルペンテン−１）系樹脂を膜素材とする不均質膜は、例えば、Ｊｏｕｒｎａｌ ｏｆ Ｍｅｍｂｒａｎｅ Ｓｃｉｅｎｃｅ １１８（１９９６）４９−６１及びＰＯＬＹＭＥＲ，１９８９，Ｖｏｌ ３０，Ｄｅｃｅｍｂｅｒ ページ２２７９−２２８２等に記載の方法を応用して公知の紡糸法により容易に製造する事ができる。本発明は、膜のガス透過性の指標となる中空糸膜の酸素透過速度が５×１０ −５ ［ｃｍ ３ （ＳＴＰ）／ｃｍ ２ ／ｓ／ｃｍＨｇ］〜３５０×１０ −５ ［ｃｍ ３ （ＳＴＰ）／ｃｍ ２ ／ｓ／ｃｍＨｇ］のポリ（４−メチルペンテン−１）系樹脂を膜素材とする不均質膜を適用する事を特長とし、適用用途分野に応じて本発明の範囲内で最適なガス透過特性を有する膜を選択できる。
【００３６】
人工肺に適用する場合、膜の酸素透過速度は好ましくは１０×１０ −５ ［ｃｍ ３ （ＳＴＰ）／ｃｍ ２ ／ｓ／ｃｍＨｇ］〜３５０×１０ −５ ［ｃｍ ３ （ＳＴＰ）／ｃｍ ２ ／ｓ／ｃｍＨｇ］であり、さらに好ましくは２５×１０ −５ ［ｃｍ ３ （ＳＴＰ）／ｃｍ ２ ／ｓ／ｃｍＨｇ］〜３５０×１０ −５ ［ｃｍ ３ （ＳＴＰ）／ｃｍ ２ ／ｓ／ｃｍＨｇ］である。酸素透過速度はＡＳＴＭ Ｄ１４３４に準じて測定した値である。
【００３７】
膜の酸素透過速度が５×１０ −５ ［ｃｍ ３ （ＳＴＰ）／ｃｍ ２ ／ｓ／ｃｍＨｇ］以下であると、特に血液からの炭酸ガスの除去能力に劣り、必要となる膜面積の増大を招きコンパクトな人工肺の実現が困難となる。
【００３８】
本発明の中空糸膜型気液ガス交換装置に適用する、ガス交換にあずかる実質的な有効膜面積が大きいポリ（４−メチルペンテン−１）系樹脂からなる不均質膜の酸素透過速度の上限は３５０×１０ −５ ［ｃｍ ３ （ＳＴＰ）／ｃｍ ２ ／ｓ／ｃｍＨｇ］である。
【００３９】
膜の酸素透過速度が高い事自体による不都合は特に無いものの、膜の酸素透過速度のさらなる増加は、製膜時において血漿の漏出を許す膜壁を貫く大きな孔径、いわゆるピンホールの発生の可能性を増長する結果を招く。人工肺に適用する場合、膜の緻密層の緻密度は連通孔の孔径は大きくとも０．０４μｍ以下である事が好ましくまたその面積開口率は３％以下である事が好ましい。
本発明はまた液流圧損を極めて低く抑え、気体と液体との間で高効率でガス交換を行う方法を提示する。即ち、外部灌流型中空糸膜型気液ガス交換装置において、中空糸膜の外径 が１５０μｍ〜３９０μｍであり且つ隣り合う中空糸膜の間隔が１２０μｍ〜２８０μｍとなるよう中空糸膜が実質的に平行に配列された中空糸膜シートがＤｖが１６５μｍ〜３２５μｍとなるよう積層された状態で人工肺ハウジング内に組み込まれていることを特徴とする中空糸膜型気液ガス交換装置を使用し、液体を積層された中空糸膜シート面に実質的に垂直に横切るように流しガス交換を行う事を特徴とする。
【００４０】
液体を中空糸膜シートとクロスフローとすることにより液流の撹拌効率を高め、これにより、気体ー液体系のガス交換効率の律速となっているガスの移動に対する液体側の境膜の厚さを効率良く低減できる。これにより極めて高いガス交換効率を実現できる。
【００４１】
驚くべき事に、本発明によれば、液体の流量増加に伴う膜を介しての気体と液体間のガス移動効率の向上度合いを特異的に高める事ができる。これによりガス交換能を大幅に向上を実現している。これは本発明により、液体側のガス移動境膜層の薄膜化の液体流速依存性を極めて大きくできる為であると推定している。むろんこれは本発明をなんら制限するものでは無い。
【００４２】
本発明に記載のごとく中空糸膜シートを積層する事によりクロスフローでの液流圧損が、中空糸膜シートの中空糸の方向に平行して液体を流す場合の液流圧損と比較し、極めて低くできる。これにより、クロスフーロータイプの気液ガス交換装置を容易に構成することができる。
【００４３】
本発明を実施するにあたり、本発明に記載の外部灌流型中空糸膜型気液ガス交換装置の好ましい実施形態のいくつかの例のモデルを図１、図２、図３に示す。
【００４４】
図１は多孔のパイプの周りに中空糸膜シートを巻気付け、円筒状のハウジングに組み込んだ外部灌流型気液ガス交換装置のモデル図である。図中実線で示す矢印は液体の流れをモデル的に示している。図中６は樹脂封止部であり、ウレタン樹脂及び／又はエポキシ樹脂及び／又はシリコーン樹脂等を使用し中空糸をハウジングに液密に支持固定している。中空糸膜は両封止樹脂の外側にその内側を開口している。人工肺として使用する場合は図中１より血液を中空糸簾を巻き付けた多孔パイプに流し入れる。血液は主にその多孔部より中空糸簾巻体の半径方向に均等に流れ、シート巻き体とハウジングの空間部を流れて図中２から排出される。この間、図中３より、例えば酸素混合ガスを適切な流量で中空糸内部に流し込み中空糸膜を介して血液に酸素を供給すると共に、血液から炭酸ガスを除去する。また、必要に応じて、例えば、多孔パイプの内部及び／又は外側にフィンタイプやチューブタイプ゜等の熱交換機構を付与する事ができる。
図３に示す外部灌流型気液ガス交換装置のモデル図は中心の多孔パイプを中央の仕切で二つの部分に分割している事を特長としている。図中１より流し入れた液体は多孔パイプの多孔部より中空糸膜シート巻き体の中空糸間隔をクロスフローで半径方向に流れ、再び中空糸膜シートをクロスして多孔パイプ内に流入して図中２より流出する。
【００４５】
人工肺として使用する場合、血液を流すと同時に図３中３より酸素混合ガスを中空糸の内側に流し入れガス交換を行う事ができる。また、工業用途として脱気された水等を製造する場合、図３中の３及び／又は４から真空ポンプ等で中空糸内部を減圧し液体の脱気を行うことができる。
【００４６】
図３にモデルで示す基本構造を有する気液ガス交換装置は、液体がシートとクロスして流れる実質のシート厚を厚くでき、液流速度を上げる事ができる。これにより、液体側の撹拌効果向上させ、液側境膜をさらに薄くでき、ガス交換効率の大幅な向上が期待できる。
【００４７】
図４は角筒型ハウジングに中空糸膜シートを積層し組み込んだ形状を有する気液ガス交換装置のモデル図である。人工肺用として使用する場合は図中１より血液を流し入れ中空糸シート積層面に垂直に血液を流しガス交換を行う事ができる。また必要に応じて血液入り側に熱交換機構を付与する事ができる。
【００４８】
【実施例】
実施例１
中空糸外径２６０μｍ、内径２０５μｍ、膜の酸素透過速度４０×１０ −５ ［ｃｍ ３ （ＳＴＰ）／ｃｍ ２ ／ｓ／ｃｍＨｇ］のポリ（４−メチルペンテン−１）系樹脂を素材とする中空糸不均質膜を使用し、２０デニールのポリエステルのマルチフィラメントを縦糸として中空糸打ち込み本数を２１本／ｃｍとした中空糸間隔が２２７μｍの中空糸膜シートをラッセル編みにより形成した。この中空糸膜シートを相当直径Ｄｖが３２０μｍとなるように図５にモデル図で示す様に折り畳み積層した。次いでこの中空糸シート積層体を図４にモデル図で示すごとく角筒型モジュールに組み込み、中空糸の両端をポリウレタン樹脂で公知の遠心封止法により封止し、モジュールの両端面に中空の内側が開口するよう端面をカッティングした。また、液体（血液）がシート折り畳み体の側面からリークしないようにシート積層体の両側面とハウジング側面をウレタン樹脂を使用し接着し、血液が通過する有効断面積が約５０ｃｍ ２ で有効膜面積（中空糸外径）が約１．２ｍ ２ である角筒型のモジュールを作成した。ＡＡＭＩ（ＡＳＳＯＣＩＡＴＩＯＮ ＦＯＲ ＴＨＥ ＡＤＯＶＡＮＣＥＭＥＮＴ ＯＦ ＭＥＤＩＣＡＬ ＩＮＳＴＲＵＭＥＮＴＡＴＩＯＮ）に準じ、酸素飽和度：６５％、ヘモグロビン：１２ｇ／ｄＬ、過剰塩基：０ｍＥｑ／Ｌ、溶存二酸化炭素分圧：４５ｍｍＨｇ、温度３７℃に調整した牛血を使用して、図４中１より牛血を流し入れると同時に図中３より酸素ガスをＶ／Ｑ＝１（ガス流量／血液流量）で中空糸内部に流し入れモジュールのガス交換性能能を測定した。標準Ｏ２（酸素）血液流量が６．５Ｌ／ｍｉｎであり、標準ＣＯ２（二酸化炭素）血液流量が５．８Ｌ／ｍｉｎであった。またモジュールを流れる血液流量が６Ｌ／ｍｉｎの時の血流圧力損失は４８ｍｍＨｇであった。
【００４９】
ここで、標準Ｏ2血液流量とは、３７℃で１２ｇ／ｄＬのＨｂを含有し、Ｏ2飽和度６５％で過剰塩基（ＢＥ）０の血液が、人工肺を通ることによりそのＯ2含有量が４５ｍＬ／Ｌ（標準状態）だけ増加させることのできる最大血液流量を示し、標準ＣＯ2血流量とは３７℃で１２ｇ／ｄＬのＨｂを含有し、Ｏ2飽和度６５％で過剰塩基（ＢＥ）０の血液が、人工肺を通ることによりそのＣＯ2含有量が３８ｍＬ／Ｌ（標準状態）だけ減少させることのできる最大血液流量を示す。
【００５０】
実施例２
外径２２５μｍ、内径１７０μｍ、膜の酸素透過速度５４×１０ −５ ［ｃｍ ３ （ＳＴＰ）／ｃｍ ２ ／ｓ／ｃｍＨｇ］のポリ（４−メチルペンテン−１）系樹脂を素材とする中空糸膜不均質膜を使用し、２０デニールのポリエステルのマルチフィラメントを縦糸として中空糸打ち込み本数を２４本／ｃｍとし、中空糸間隔を２００μｍとした中空糸膜シートをラッセル編みにより形成した。このシートを相当直径が２８０μｍとなるように積層し、実施例１と同様に血液が通過する有効面積が約５０ｍ ２ で有効巻き面積が１．２ｍ ２ である角筒型のモジュールを作成した。実施例１と同様に牛血を使用してモジュールのガス交換性能を測定した。結果、標準Ｏ２血液流量が１５．３Ｌ／ｍｉｎであり、標準ＣＯ２血液流量が１３Ｌ／ｍｉｎであった。またモジュールを流れる血液流量が６Ｌ／ｍｉｎの時の血流圧力損失は５２ｍｍＨｇであった。
【００５１】
実施例３
外径２０５μｍ、内径１５０μｍ、膜の酸素透過速度が６７×１０ −５ ［ｃｍ ３ （ＳＴＰ）／ｃｍ ２ ／ｓ／ｃｍＨｇ］のポリ（４−メチルペンテン−１）系樹脂を素材とする中空糸膜不均質膜を使用し、２０デニールのポリエステルのマルチフィラメントを縦糸として中空糸の打ち込み本数を約２８本／ｃｍとし、中空糸間隔を約１５８μｍとした中空糸膜シートをラッセル編みにより作成した。このシートを相当直径が２１５μｍとなるよう積層し、実施例１と同様に血液が通過する有効面積が約５０ｃｍ ２ で有効巻き面積が１．２ｍ ２ である角筒型のモジュールを作成した。実施例１と同様に牛血を使用してモジュールのガス交換能を測定した。血液流量が１６Ｌ／ｍｉｎの時に酸素移行量が４８ｍＬ／ｍｉｎであり標準Ｏ２血液流量は測定不能であった。標準ＣＯ２血液流量は１５．２ｍＬ／ｍｉｎであった。またモジュールを流れる血液流量が６Ｌ／ｍｉｎの時の血流圧力損失は１２０ｍｍＨｇであった。
【００５２】
実施例４
外径３３０μｍ、内径２２０μｍ、膜の酸素透過速度が７２×１０ −５ ［ｃｍ ３ （ＳＴＰ）／ｃｍ ２ ／ｃｍＨｇ］のポリ（４−メチルペンテ−１）系樹脂を素材とした中空糸膜不均質を使用し、２０デニールのポリエステルからなるマルチフィラメントを縦糸として中空糸打ち込み本数２１本／ｃｍとし、中空糸間隔約１５４μｍとした中空糸シートをラッセル編みににより形成した。この中空糸シートを図１中７にモデル図で示す多数の孔をあけた直径約２ｃｍの円筒パイプに、パイプと中空糸シートの巻き初めのクリアランスが約０．２ｃｍであり、中空糸シートの占める部分の相当直径が２９０μｍとなるようスパイラル状に巻きつけた。次いでこの中空糸シート巻き体を、内径約７．５ｃｍの円筒状ハウジングに組み入れ、モジュールの両端をポリウレタン樹脂を使用し公知の遠心封止法により封止し、次いでモジュールの両端面をカッティングし中空糸膜の内側を開口させた。中空糸シート巻き体の有効長が約６ｃｍで、中空糸シート巻体の外周部と円筒ハウジングとのクリアランスが約０．５ｃｍで、中空糸有効膜面積が１．２ｍ ２ の円筒型モジュールを作成した。
【００５３】
実施例１と同様に牛血を調整し、図１中１より牛血を流し入れると同時に図中３より酸素ガスをＶ/Ｑ＝１で中空糸内側に流し入れガス交換性能を測定した。結果、標準Ｏ2血液流量が７．８Ｌ／ｍｉｎであり、標準ＣＯ2血液流量が６．３Ｌ／ｍｉｎであった。
【００５４】
また、モデル実験により中心部の多孔管から流れ出た血液は中空糸巻き体をほぼ垂直に半径方向に流れ中空糸シート巻き体とモジュール外側ハウジングとの間隙に達し図１中２より流出する事を確認した。
【００５５】
実施例５
実施例２で使用した中空糸膜シートを使用し、図３中９にモデル図で示す中心部に仕切を設けた外周に多数の孔を有する直径約３０ｍｍの円筒パイプに、パイプと中空糸シートの巻き初めのクリアランスが約０．２ｃｍであり、中空糸シートの占める部分の相当直径が２６５μｍとなるようにスパイラル状に巻きつけた。次いでこの中空糸シート巻き体を、内径約７ｃｍの円筒状ハウジングに組み入れ、モジュールの両端をポリウレタン樹脂を使用し公知の遠心封止法により封止し、次いでモジュールの両端面をカッティングし中空糸の内側を開口させた。中空糸シート巻き体の有効長が約６ｃｍで、中空糸膜有効膜面積が１．２ｍ ２ の円筒型モジュールを作成した。
【００５６】
実施例１と同様に牛血を調整し、図３中１より牛血を流し入れると同時に図中３より酸素ガスをＶ/Ｑ＝１で中空糸内側に流し入れガス交換性能を測定した。
血液流量が１６ｍＬ／ｍｉｎにおいて、血液への酸素移行量は約５０ｍＬ／ｍｉｎで、ＣＯ2除去量は約４２ｍＬ／ｍｉｎであり、酸素、二酸化炭素共に標準血液流量は測定できないほど大きかった。また、血液流量６Ｌ／ｍｉｎの時の血流圧力損失は７７ｍｍＨｇであった。
【００５７】
また、モデル実験により図３に実線の矢印で流れを示すように、中心部の多孔管から流れ出た血液は中空糸シート巻き体をほぼ垂直に半径方向に流れ中空糸シート巻き体とモジュール外側ハウジングとの間隙に達し、次いで中空糸膜シート巻き体をほぼ垂直に多孔パイプ側に流れ込み図３中２より流出する事を確認した。
【００５８】
実施例６
中空糸外径が１８０μｍ、内径１２０μｍ、膜の酸素透過速度が２５×１０ −５ ［ｃｍ ３ ／ｃｍ ２ ／ｃｍＨｇ］のポリ（４−メチルペンテ−１）系樹脂を素材とした中空糸不均質膜を使用し、２０デニールのポリエステルからなるマルチフィラメントを縦糸として中空糸打ち込み本数３１本／ｃｍとし、中空糸間隔約１４７μｍとした中空糸膜シート作成した。このシートを外周に多数の穴を開口させた呼び径約３ｃｍのパイプにシート巻き体の相当直径が１９０μｍとなるように巻付け、中空糸膜外径基準の膜面積が９０ｍ ２ のシート巻き体を作成した。このシート巻き体を呼び径２５ｃｍの硬質塩化ビニルパイプからなる長さ約５０ｃｍのモジュールケースに装填し、封止樹脂としてウレタン樹脂及びエポキシ樹脂を使用して公知の遠心封止法により第１図にモデル図で示す工業用の外部灌流型モジュールを作成した。図１中の３及び４を排気速度約４８ｍ３／ｈｒの油回転式真空ポンプに接続し、中空糸膜の内側の真空圧力を約２３ｍｍＨｇに保ちながら、図１中１より２５℃の空気で飽和した水を流し入れた。図１中２より流れ出た脱気水の溶存酸素濃度をポーラグラフィック酸素濃度計により測定した。溶存酸素濃度が約１ｐｐｂに脱気された水を約３６Ｌ／ｍｉｎ得ることができた。
【００５９】
比較例１
外径２６０μｍ、内径２０５μｍ、膜の酸素透過速度３０×１０ −５ ［ｃｍ ３ （ＳＴＰ）／ｃｍ ２ ／ｓ／ｃｍＨｇ］のポリ（４−メチルペンテン−１）系樹脂を素材とする 中空糸不均質膜を使用し、３０デニールのポリエステルのマルチフィラメントを縦糸として中空糸打ち込み本数を２２本／ｃｍとした中空糸間隔を２０４μｍの中空糸シートをラッセル編みにより形成した。このシートを相当直径Ｄｖが３６０μｍとなるように積層し、実施例１と同様に血液が通過する有効断面積が５０ｃｍ ２ で有効膜面積が（中空糸外径基準）が１．２ｍ ２ である角筒型のモジュールを作成した。
【００６０】
実施例１と同様に牛血を使用してガス交換性能を測定した。結果、標準Ｏ2血液流量が４．２Ｌ／ｍｉｎであり、標準ＣＯ2血液流量が３．８Ｌ／ｍｉｎであった。まモジュールを流れる血液流量が６Ｌ／ｍｉｎの時の血流圧力損失は４６ｍｍＨｇであった。
【００６１】
比較例２
外径約２６０μｍ、内径約２００μｍ、膜の酸素透過速度が約４００×１０ −５ ［ｃｍ ３ ／ｃｍ ２ ／ｓ／ｃｍＨｇ］のポリプロピレン系樹脂を素材とする中空糸微多孔膜を使用し、３０デニールのポリエステルからなるマルチフィラメントを縦糸として中空糸打ち込み本数を１８本／ｃｍとし、中空糸間隔を３１３μｍとした中空糸シートを形成した。このシートを相当直径Ｄｖが２７５μｍとなるよう積層し、実施例１と同様に血液が通過する有効断面積が約５０ｃｍ ２ で有効膜面積が１．２ｍ ２ である角筒型のモジュールを作成した。実施例１と同様に牛血を使用してモジュールのガス交換性能を測定した。結果、標準Ｏ２血液流量が２．９Ｌ／ｍｉｎであり、標準ＣＯ２血液流量が２．５Ｌ／ｍｉｎであった。またモジュールを流れる血液流量が６Ｌ／ｍｉｎの時の血流圧力損失は４６ｍｍＨｇであった。
【００６２】
比較例３
外径約３８０μｍ、内径約３３０μｍ、膜の酸素透過速度が約７００×１０ −５ ［ｃｍ ３ ／ｃｍ ２ ／ｓ／ｃｍＨｇ］のポリプロピレン系ポリマーを素材とする中空糸微多孔膜を使用し、３０デニールのポリエステルからなるマルチフィラメントを縦糸として中空糸打ち込み本数を１７本／ｃｍとし、中空糸間隔を約２２０μｍとした中空糸シートを形成した。この中空糸シートを相当直径Ｄｖが約４７０μｍとなるよう積層し、実施例１と同様に血液が通過する有効面積が約５０ｃｍ ２ で有効巻き面積が１．２ｍ ２ である角筒型のモジュールを作成した。実施例１と同様に牛血を使用してモジュールのガス交換性能を測定した。結果、標準Ｏ２血液流量が２．３Ｌ／ｍｉｎであり、標準ＣＯ２血液流量が２．２Ｌ／ｍｉｎであった。またモジュールを流れる血液流量が６Ｌ／ｍｉｎの時の血流圧力損失は４２ｍｍＨｇであった。
【００６３】
【発明の効果】
中空糸膜シートを積層してモジュールに組み込んだ外部灌流型気液ガス交換装置において、中空糸膜の外径及び、実質的に中空糸を平行に配列したシートの中空糸膜間隔及び、（式１）
Ｄｖ＝４×（シート積層体の占める全空間体積）／（中空糸膜の全有効外表面積）
で表される相当直径を規定し、液体をシート積層面にクロスして流す事により外部灌流型気液ガス交換装置のガス交換効率を大幅に向上できる。
特に、血液への優れた酸素供給能力と、血液からの優れた二酸化炭素除去能力が要求され、且つ小型で、低プライミング量で、且つ低血流圧損であることが要求される人工肺に最適に適用できる。
【００６４】
【図面の簡単な説明】
【図１】本発明の実施例で用いた円筒型の外部灌流型気液ガス交換装置の構造を示すモデル図であり、図中矢印は液体の流れのモデルを示す。
【図２】図１及び図３に構造のモデル図を示す円筒型の外部灌流型気液ガス交換装置に組み込んだ中空糸膜シートの積層状態を示すモデル図である。
【図３】本発明の実施例で用いた多孔パイプの中心部に仕切を有する円筒型の外部灌流型ガス交換装置の構造モデル図である。図中矢印は液体の流れのモデルを示す。
【図４】本発明で用いた角筒型の外部灌流型気液ガス交換装置の構造モデル図であり、図中矢印は液体の流れのモデルを示す。
【図５】図４の角型の外部灌流型気液ガス交換装置に組み込んだ中空糸膜シートの積層状態を示すモデル図である。
【符号の説明】
１，２ 液体流入／流出口
３，４ ガス流入／流出口，脱気口
５ 中空糸膜
６ 封止樹脂部
７ 多孔パイプ
８ 中空糸膜シート縦糸
９ 多孔パイプ[0001]
[Technical field to which the invention belongs]
The present invention is used as an external perfusion-type gas-liquid gas exchange device utilizing a hollow fiber membrane. For example, for industrial use, deaeration of water for boiler air conditioning for the purpose of deoxidation of boiler water, corrosion prevention of piping, It is used for deaeration of ultrapure water, ion exchange water, reverse osmosis membrane feed water, deoxygenation and decarbonation gas for power generation used in production. Further, as food industry uses, it is used for production of beer and sake, deaeration of water for food production, and the like. Furthermore, the present invention is used for medical purposes such as degassing of filling liquid of dialysis module and degassing of water for injection, and can be suitably applied to an artificial lung for reviving a patient's blood in extracorporeal blood circulation such as during cardiac surgery. .
[0002]
[Prior art]
Artificial lungs are used as an alternative or supplement to living lungs during open heart surgery or long-term respiratory assistance, and various types have been developed. These artificial lungs substitute for a gas exchange function that supplies oxygen to blood and removes carbon dioxide among the functions of living lungs. Currently, hollow fiber membrane oxygenators are the mainstream, and are roughly classified into two types. One is a so-called internal perfusion type artificial lung that exchanges gas by flowing blood into the hollow fiber, and the other is to exchange blood by bringing blood into contact with the outside of the hollow fiber and flowing oxygen mixed gas inside the hollow fiber. This is a so-called external perfusion oxygenator. The external perfusion oxygenator can keep the pressure loss of the blood flow low, has excellent gas exchange efficiency, and is becoming the mainstream of the hollow fiber membrane oxygenator.
[0003]
For example, in Japanese Patent Publication No. 5-20111, an artificial gas wrapping gas-permeable hollow fibers arranged in a sheet form around a porous core, allowing oxygen to pass through the hollow fibers, and allowing blood to flow outside the hollow fibers, thereby performing gas exchange. The lung is disclosed.
[0004]
In Japanese Examined Patent Publication No. 4-2066, adjacent hollow fibers are wound in an annular shape so as to cross each other to form an annular hollow fiber layer having a hollow portion at the center thereof. An artificial lung having a hollow fiber filling rate of 0.45 to 0.80 is disclosed.
[0005]
Japanese Examined Patent Publication No. 6-96098 discloses a density of warp yarns forming a hollow fiber sheet in an artificial lung in which hollow fiber sheets are laminated and incorporated in a housing, and the sheet thickness is set to a specific value and the hollow fiber density of the sheet And an artificial lung in which blood channeling and retention are suppressed by setting the product of the stacking density of the sheet and a specific value range value calculated based on the outer diameter of the hollow fiber.
[0006]
Japanese Examined Patent Publication No. 7-98061 discloses a blood flow per unit cross-sectional area perpendicular to the direction of blood flow in an artificial lung in which a laminated body of saddle-shaped hollow fiber sheets is incorporated in a rectangular tube-shaped housing.50 mL / min / cm 2 An artificial lung is disclosed in which channeling and retention of blood flow are suppressed by maintaining the relationship of ΔP / T · I · n ≦ 1 when the pressure loss at this time is ΔP.
[0007]
Usually, the required performance required for a gas-liquid gas exchange device is an excellent gas exchange capacity. In particular, an oxygenator for medical use is required to have an excellent ability to supply oxygen to blood and an excellent ability to remove carbon dioxide from blood. In addition, artificial lungs are required to have a low burden on the patient, have a small membrane area that is in direct contact with blood, are small in size, have a small amount of blood priming, and have a low blood pressure loss. It is required not to cause blood damage.
[0008]
The gas exchange performance of membrane oxygenators is widely known to be rate-limiting in the blood-side membrane, and various oxygenator structures are actively studied to destroy the blood-side membrane as much as possible. Has been.
[0009]
In recent years, research and development of a hollow fiber membrane external perfusion oxygenator that can suppress the pressure loss of blood flow to a low level and can be expected to improve the gas exchange capacity per unit membrane area has been actively conducted and commercialized. However, in the conventional technology, technical elements necessary for improving the performance, in particular, destroying the blood-side membrane efficiently and improving the gas exchange efficiency are unclear. As a result, the gas exchange efficiency is not clear. A satisfactory oxygenator has not yet been developed.
[0010]
[Problems to be solved by the invention]
The researchers have intensively studied the optimum design of external perfusion type hollow fiber membrane type gas-liquid gas exchange device in which hollow fiber membrane sheets are laminated and incorporated in the housing. A hollow fiber sheet having a specific hollow fiber membrane interval in which the hollow fiber membranes are arranged substantially in parallel, and the hollow fiber membrane sheets are laminated to have a specific equivalent diameter. External perfusion type hollow fiber membrane type gas-liquid gas that can dramatically improve the gas exchange efficiency compared to conventional ones by incorporating it in the housing, and can also suppress liquid flow (blood flow) pressure loss to an extremely low value. An invention relating to an exchange apparatus is provided.
[0011]
[Means for Solving the Problems]
That is, the present invention
(1) In an external perfusion type hollow fiber membrane type gas-liquid gas exchange device, hollow fiber membranes having an outer diameter of the hollow fiber membrane of 150 μm to 390 μm and a spacing of the hollow fiber membranes of 120 μm to 280 μm are substantially parallel Using the arranged hollow fiber membrane sheets, (Equation 1) Dv = 4 × (total space volume occupied by the sheet laminate) / (total effective outer surface area of the hollow fiber membrane)
An external perfusion type hollow fiber membrane type gas-liquid gas exchange device, which is incorporated in a housing in a state of being laminated so that the equivalent diameter calculated in 165 μm to 325 μm,
(2) The outer diameter of the hollow fiber membrane is 180 μm to 250 μm, the hollow fiber interval of the hollow fiber sheet is 150 μm to 260 μm, and Dv is 215 μm to 320 μm, This is a hollow fiber membrane type gas-liquid gas exchange device. (3) The hollow fiber membrane has an oxygen transmission rate of the hollow fiber membrane.5 × 10 -5 [Cm 3 (STP) / cm 2 / S / cmHg] to 350 × 10 −5 [cm 3 (STP) / cm 2 / S / cmHg]The external perfusion-type gas-liquid gas exchange device according to (1) or (2), which is a hollow fiber asymmetric membrane made of a poly (4-methylpentene-1) -based resin, In the external perfusion type hollow fiber membrane type gas-liquid gas exchange device, hollow fiber membranes having an outer diameter of the hollow fiber membrane of 150 μm to 390 μm and an interval of the hollow fiber membranes of 120 μm to 280 μm were arranged substantially in parallel Using hollow fiber membrane sheet (Equation 1)
Dv = 4 × (total space volume occupied by sheet laminate) / (total effective outer surface area of hollow fiber membrane) is incorporated in the housing in a state where the equivalent diameter is 165 μm to 325 μm. Using an external perfusion-type hollow fiber membrane type gas-liquid gas exchange device characterized in that the liquid is exchanged by flowing the liquid in a substantially vertical cross to the laminated hollow fiber membrane sheet This is a gas-liquid gas exchange method.
[0012]
What is the equivalent diameter (Dv) here?
(Formula 1)
Dv = 4 × (total space volume occupied by the sheet laminate) / (total effective outer surface area of the hollow fiber membrane) where the numerator of the formula is hollow from the volume occupied by the hollow fiber membrane sheet laminate. It is the volume of the space after subtracting the volume occupied by the yarn membrane.
[0013]
DETAILED DESCRIPTION OF THE INVENTION
The typical and best modes of the embodiment of the present invention are specifically shown in the following examples, and the outline thereof is as follows.
[0014]
The outer diameter of the hollow fiber of the present invention may be 150 μm to 390 μm, and an appropriate outer diameter can be selected depending on the application.
[0015]
Moreover, it is preferable that the film thickness of a hollow fiber membrane is 15 micrometers-80 micrometers. The film thickness governs the strength and durability of the hollow fiber membrane, and the optimum film thickness can be selected for the material constituting the membrane, the structure of the membrane, and the application application of the present invention. Generally, if the outer diameter is small, the film thickness required for maintaining strength and durability can be reduced.
[0016]
Surprisingly, in the present invention, even if the filling rate of the hollow fibers in the membrane module is the same, the gas exchange efficiency can be improved as the outer diameter of the hollow fibers is reduced within the scope of the present invention. Furthermore, it is preferable because the durability and strength of the hollow fiber can be drastically improved by reducing the diameter, but if the outer diameter of the hollow fiber is 150 μm or less, handling during manufacture of the membrane module becomes difficult.
[0017]
When used suitably as an artificial lung application in which oxygen-containing gas flows inside the hollow fiber and exchanges blood with the blood flowing outside the hollow fiber, the gas exchange efficiency is increased, the gas exchange capacity is sufficient with a small membrane area, and the size is small. In order to realize an artificial lung module with a small amount of blood priming, a hollow hollow fiber is preferable. On the other hand, by reducing the outer diameter of the hollow fiber, the inner diameter is necessarily reduced.
[0018]
The gas pressure on the gas phase side needs to be kept sufficiently lower than the pressure on the blood side so that bubbles are not generated on the blood side. In addition, during clinical use, a considerable amount of water vapor permeates into the hollow fiber from the blood side, and depending on the conditions of use, this water vapor aggregates at the oxygenator gas outlet, and the hollow fiber membrane is blocked. May cause a general decline. In order to prevent these phenomena, the hollow fiber needs to have a certain thickness inside diameter.
[0019]
The outer diameter is preferably in the range of 180 μm to 250 μm for artificial lung use, and the inner diameter is preferably 140 μm or more. Particularly in applications where there is a possibility of continuous use over several days to several weeks, such as ECMO and PCPS applications, the outer diameter of the hollow fiber is preferably 200 μm to 250 μm, and the inner diameter is preferably 150 μm or more.
[0020]
The present invention is also characterized in that a hollow fiber membrane sheet in which hollow fiber membranes are arranged in parallel at equal intervals at least on the same lamination surface is laminated and incorporated in a housing.
[0021]
There is no limitation on the method of forming the hollow fiber membrane sheet, for example, by braiding monofilament or multifilament yarns made of polyester, polyamide, polyurethane, polyacrylonitrile, etc. with warp yarns, and braiding hollow fiber membranes at equal intervals Preferably it can be formed. As a method for industrially forming a hollow fiber membrane sheet, for example, Russell knitting or the like is known.
[0022]
The thickness of the warp is preferably 5 to 30 denier. In particular, a 10-25 denier multifilament made of polyester is particularly preferred because it is excellent in flexibility and strength, has little change over time, and does not damage the hollow fiber during sheet formation or over time.
[0023]
In the present invention, the interval between the hollow fiber membranes of the hollow fiber membrane sheet is in the range of 120 μm to 280 μm, and the equivalent diameter Dv of the laminated hollow fiber sheet represented by (Formula 1) is in the range of 165 μm to 325 μm. It is characterized by. As a result, an external perfusion-type gas-liquid gas exchange device that can simultaneously satisfy high gas exchange efficiency and low liquid flow pressure loss can be realized.
[0024]
Further, the number of laminated hollow fiber membrane sheets is preferably 20 layers or more, more preferably 50 layers or more, and most preferably 70 layers or more.
The gas exchange efficiency by the external perfusion method described in the present invention can be improved dramatically by narrowing the hollow fiber membrane interval of the hollow fiber membrane sheet and reducing Dv, but the interval between the hollow fiber membranes is 120 μm or less and When the Dv is 165 μm or less, the pressure loss of the liquid flow becomes extremely large, and the range of development for various industrial practical applications is limited.
[0025]
The hollow fiber membrane interval and Dv of the sheet can be appropriately selected within the scope of the present invention in accordance with the required performance of the application application of the gas-liquid gas exchange device.
[0026]
For example, in the production of ultrapure water for semiconductor production used for degassing dissolved gas from water, it is a subsystem that requires a relatively high degassing with a relatively low processing flow rate and a dissolved oxygen concentration of 1 ppb or less. For the purpose of application, the hollow fiber interval is preferably 120 μm to 260 μm, and Dv is preferably 165 μm to 260 μm.
[0027]
In addition, for applications that require a large amount of water with a relatively low degassing level of about 50 PPB in dissolved oxygen concentration, such as in the production of power water, the distance between the hollow fiber membranes of the hollow fiber sheet is preferably 200 μm to 280 μm, and Dv is 200 μm. ˜325 μm is preferred.
[0028]
When used for an artificial lung for medical purposes, low blood flow pressure loss and high gas exchange efficiency are required, so that the hollow fiber interval of the hollow fiber membrane sheet is preferably 150 μm to 260 μm, and Dv is 215 μm to 325 μm. preferable.
[0029]
In an artificial lung application, especially in applications such as PCPS and ECMO that are premised on long-term continuous use over several days, the hollow fiber spacing is preferably 180 μm to 260 m, and Dv is preferably 230 μm to 325 μm.
[0030]
The hollow fiber membrane applied to the present invention is not particularly limited as long as it has moderate durability, mechanical strength, and gas permeability, and there are no particular limitations on the material, manufacturing method, membrane structure, etc., for example, polyethylene, polypropylene, Polyolefins such as polybutylene and poly (4-methylpentene-1), silicone resins such as dimethylsiloxane, various fluororesins such as polytetrafluoroethylene and perfluoroalkoxy fluororesin, and various polyimide resins can be suitably used. .
[0031]
In addition, in the membrane structure of the hollow fiber membrane, various membranes having a so-called sandwich structure in which a thin film such as a microporous membrane, a homogeneous membrane, a heterogeneous membrane, a composite membrane, or urethane is sandwiched between the microporous membranes can be applied.
[0032]
Moreover, there is no restriction | limiting also in the manufacturing method of these films | membranes, For example, the film | membrane manufactured by the melting method, the wet method, the dry-wet etc. is applicable.
[0033]
In particular, a hollow fiber heterogeneous membrane having a dense layer on a membrane wall made of a poly (4-methylpentene-1) -based resin is excellent in gas permeability such as oxygen, nitrogen, carbon dioxide gas, and has high hydrophobicity. It is excellent in water vapor barrier property and is most suitable for industrial and medical gas-liquid gas exchange devices.
The formation position of the dense layer of the hollow fiber membrane is not particularly limited and may be formed on the outer surface and / or the inner surface of the hollow fiber membrane, but in particular, the dense layer is formed on the outer surface of the hollow fiber membrane. A hollow fiber membrane made of a poly (4-methylpentene-1) resin has low blood complement activity, excellent affinity with blood, no plasma leakage over a long period of time, and no deterioration in gas exchange performance It is most suitably applied as an external perfusion oxygenator. In addition, the poly (4-methylpentene-1) resin has a gas permeability of the material itself of about 10 times that of polypropylene generally used for artificial lungs, and essentially communicates with the hollow fiber membrane wall. Compared to a polypropylene microporous membrane that exchanges gas only at the microporous portion, gas exchange can be performed on the entire membrane surface, which is extremely preferable.
[0034]
A heterogeneous film made of a poly (4-methylpentene-1) -based resin by a melting method is disclosed in, for example, Japanese Patent Application No. 5-6656 and Japanese Patent Publication No. 7-121340.
[0035]
In addition, a heterogeneous film using a poly (4-methylpentene-1) -based resin that forms a film using phase separation of a resin solution using a solvent such as a wet method or a dry-wet method, for example, Journal of Membrane Science 118 (1996) 49-61 and POLYMER, 1989, Vol 30, December pages 2279-2282, etc. can be applied for easy production by a known spinning method. In the present invention, the oxygen transmission rate of the hollow fiber membrane, which is an indicator of the gas permeability of the membrane,5 × 10 -5 [Cm 3 (STP) / cm 2 / S / cmHg]~350 × 10 -5 [Cm 3 (STP) / cm 2 / S / cmHg]It is characterized by the application of a heterogeneous membrane using poly (4-methylpentene-1) resin as a membrane material, and a membrane having optimum gas permeation characteristics within the scope of the present invention is selected according to the application field it can.
[0036]
When applied to an oxygenator, the membrane oxygen transmission rate is preferably10x10 -5 [Cm 3 (STP) / cm 2 / S / cmHg]~350 × 10 -5 [Cm 3 (STP) / cm 2 / S / cmHg]And more preferably25 × 10 -5 [Cm 3 (STP) / cm 2 / S / cmHg]~350 × 10 -5 [Cm 3 (STP) / cm 2 / S / cmHg]It is. The oxygen transmission rate is a value measured according to ASTM D1434.
[0037]
The oxygen transmission rate of the membrane5 × 10 -5 [Cm 3 (STP) / cm 2 / S / cmHg]If it is below, the ability to remove carbon dioxide from blood is inferior, and the required membrane area increases, making it difficult to realize a compact oxygenator.
[0038]
The upper limit of the oxygen permeation rate of a heterogeneous membrane composed of a poly (4-methylpentene-1) resin having a large effective membrane area for gas exchange, which is applied to the hollow fiber membrane gas-liquid gas exchange device of the present invention. Is350 × 10 -5 [Cm 3 (STP) / cm 2 / S / cmHg]It is.
[0039]
Although there is no particular inconvenience due to the high oxygen permeation rate of the membrane itself, the further increase in the oxygen permeation rate of the membrane is the possibility of the generation of a so-called pinhole, a large pore diameter that penetrates the membrane wall that allows plasma leakage during film formation. Will lead to increased results. When applied to an artificial lung, the density of the dense layer of the membrane is preferably 0.04 μm or less, and the area opening ratio is preferably 3% or less.
The present invention also presents a method for performing gas exchange with high efficiency between gas and liquid with extremely low liquid flow pressure loss. That is, in the external perfusion type hollow fiber membrane type gas-liquid gas exchange device, the hollow fiber membrane is substantially such that the outer diameter of the hollow fiber membrane is 150 μm to 390 μm and the interval between adjacent hollow fiber membranes is 120 μm to 280 μm. Using a hollow fiber membrane type gas-liquid gas exchange device, wherein hollow fiber membrane sheets arranged in parallel are incorporated in an artificial lung housing in a state of being laminated so that Dv is 165 μm to 325 μm, The liquid exchange is performed by flowing the liquid so as to cross the surface of the laminated hollow fiber membrane sheet substantially perpendicularly.
[0040]
By making the liquid into a hollow fiber membrane sheet and cross flow, the stirring efficiency of the liquid flow is increased, and thereby the thickness of the liquid-side film against the movement of gas, which is the rate-determining gas exchange efficiency of the gas-liquid system Can be efficiently reduced. Thereby, extremely high gas exchange efficiency can be realized.
[0041]
Surprisingly, according to the present invention, it is possible to specifically increase the degree of improvement in the gas transfer efficiency between the gas and the liquid through the membrane accompanying the increase in the liquid flow rate. As a result, the gas exchange capacity is greatly improved. This is presumed to be because the liquid flow rate dependence of the thinning of the gas transfer film layer on the liquid side can be greatly increased by the present invention. Of course, this does not limit the present invention.
[0042]
By laminating the hollow fiber membrane sheets as described in the present invention, the liquid flow pressure loss at the cross flow is extremely low compared to the liquid flow pressure loss when flowing the liquid parallel to the direction of the hollow fibers of the hollow fiber membrane sheet. Can be lowered. Thereby, the cross-floor type gas-liquid gas exchange apparatus can be configured easily.
[0043]
In practicing the present invention, models of some examples of preferred embodiments of the external perfusion-type hollow fiber membrane gas-liquid gas exchange device described in the present invention are shown in FIGS. 1, 2, and 3.
[0044]
FIG. 1 is a model diagram of an external perfusion type gas-liquid gas exchange device in which a hollow fiber membrane sheet is wound around a porous pipe and incorporated in a cylindrical housing. The arrows indicated by solid lines in the figure indicate the flow of the liquid as a model. In the figure,
The model of the external perfusion type gas-liquid gas exchange device shown in FIG. 3 is characterized in that a central porous pipe is divided into two parts by a central partition. The liquid poured from 1 in the figure flows from the porous part of the perforated pipe in the radial direction through the hollow fiber interval of the hollow fiber membrane sheet winding body, crosses the hollow fiber membrane sheet again, and flows into the perforated pipe. Out of
[0045]
When used as an artificial lung, the oxygen exchange gas can be poured into the hollow fiber from 3 in FIG. Moreover, when manufacturing the deaerated water etc. for an industrial use, the inside of a hollow fiber can be pressure-reduced with a vacuum pump etc. from 3 and / or 4 in FIG. 3, and a liquid can be deaerated.
[0046]
The gas-liquid gas exchange apparatus having the basic structure shown in FIG. 3 can increase the substantial sheet thickness in which the liquid flows crossing the sheet and can increase the liquid flow speed. Thereby, the stirring effect on the liquid side can be improved, the liquid side film can be further thinned, and a significant improvement in gas exchange efficiency can be expected.
[0047]
FIG. 4 is a model diagram of a gas-liquid gas exchange device having a shape in which hollow fiber membrane sheets are laminated and incorporated in a rectangular tube type housing. In the case of use for an artificial lung, blood can be poured from 1 in the figure, and gas can be exchanged by flowing blood perpendicularly to the hollow fiber sheet lamination surface. Further, if necessary, a heat exchange mechanism can be provided on the side containing blood.
[0048]
【Example】
Example 1
Hollow fiber outer diameter 260μm, inner diameter 205μm, membrane oxygen transmission rate40x10 -5 [Cm 3 (STP) / cm 2 / S / cmHg]The hollow fiber spacing was obtained by using a hollow fiber heterogeneous membrane made of a poly (4-methylpentene-1) -based resin and having a multifilament of 20 denier polyester as a warp thread and the number of driven hollow fibers was 21 / cm. A 227 μm hollow fiber membrane sheet was formed by Russell knitting. This hollow fiber membrane sheet was folded and laminated as shown in the model diagram of FIG. 5 so that the equivalent diameter Dv was 320 μm. Next, this hollow fiber sheet laminate is incorporated into a rectangular tube module as shown in the model diagram of FIG. 4, and both ends of the hollow fiber are sealed with polyurethane resin by a known centrifugal sealing method. The end face was cut so as to open. In addition, both sides of the sheet laminate and the side of the housing are bonded using urethane resin so that liquid (blood) does not leak from the side of the sheet folded body, and the effective cross-sectional area through which blood passes is increased.About 50cm 2 Effective membrane area (hollow fiber outer diameter) is1.2m 2 A square tube module was created. Oxygen saturation: 65%, hemoglobin: 12 g / dL, excess base: 0 mEq / L, dissolved carbon dioxide partial pressure: 45 mmHg, temperature 37 ° C., in accordance with AAMI In use, bovine blood was poured from 1 in FIG. 4 and oxygen gas was poured from 3 in the figure into the hollow fiber at V / Q = 1 (gas flow rate / blood flow rate) to measure the gas exchange performance ability of the module. Standard O2(Oxygen) blood flow is 6.5 L / min, standard CO2(Carbon dioxide) The blood flow rate was 5.8 L / min. The blood flow pressure loss when the blood flow rate through the module was 6 L / min was 48 mmHg.
[0049]
Where standard O2Blood flow is 12 g / dL Hb at 37 ° C.2The blood of excess base (BE) 0 with a saturation degree of 65% passes through the oxygenator and its O2Shows the maximum blood flow that the content can be increased by 45 mL / L (standard condition), standard CO2The blood flow rate contains 12 g / dL of Hb at 37 ° C.2Oversaturated (BE) 0 blood with 65% saturation passes through the oxygenator and its CO2The maximum blood flow that the content can be reduced by 38 mL / L (standard condition) is shown.
[0050]
Example 2
Outer diameter 225μm, inner diameter 170μm, membrane oxygen transmission rate54 × 10 -5 [Cm 3 (STP) / cm 2 / S / cmHg]Hollow fiber membrane heterogeneous membrane made of poly (4-methylpentene-1) resin of 20 denier polyester multifilaments as warp yarns, and the number of hollow fibers to be driven is 24 / cm, hollow fiber spacing A hollow fiber membrane sheet having a thickness of 200 μm was formed by Russell knitting. This sheet is laminated so that the equivalent diameter is 280 μm, and the effective area through which blood passes is the same as in Example 1.About 50m 2 The effective winding area is1.2m 2 A square tube module was created. As in Example 1, the gas exchange performance of the module was measured using bovine blood. Result, standard O2Blood flow is 15.3 L / min, standard CO2The blood flow rate was 13 L / min. The blood flow pressure loss was 52 mmHg when the blood flow rate through the module was 6 L / min.
[0051]
Example 3
The outer diameter is 205μm, the inner diameter is 150μm, and the oxygen transmission rate of the membrane is67 × 10 -5 [Cm 3 (STP) / cm 2 / S / cmHg]Hollow fiber membrane heterogeneous membrane made of a poly (4-methylpentene-1) resin of 20 denier polyester multifilaments as warp yarns, the number of hollow fibers to be driven is about 28 / cm, hollow A hollow fiber membrane sheet with a yarn spacing of about 158 μm was prepared by Russell knitting. This sheet is laminated so that the equivalent diameter is 215 μm, and the effective area through which blood passes is the same as in Example 1.About 50cm 2 The effective winding area is1.2m 2 A square tube module was created. The gas exchange capacity of the module was measured using bovine blood in the same manner as in Example 1. When the blood flow rate is 16 L / min, the oxygen transfer rate is 48 mL / min, and the standard O2Blood flow was not measurable. Standard CO2The blood flow rate was 15.2 mL / min. The blood flow pressure loss when the blood flow rate through the module was 6 L / min was 120 mmHg.
[0052]
Example 4
The outer diameter is 330μm, the inner diameter is 220μm, and the oxygen transmission rate of the membrane is72 × 10 -5 [Cm 3 (STP) / cm 2 / CmHg]Hollow fiber membrane heterogeneity made of a poly (4-methylpent-1) -based resin, multifilament made of 20 denier polyester is used as the warp thread, the number of hollow fibers driven is 21 / cm, and the hollow fiber spacing is about 154 μm The hollow fiber sheet was formed by raschel knitting. This hollow fiber sheet is formed into a cylindrical pipe having a diameter of about 2 cm with a large number of holes shown in a model diagram in FIG. 1. The clearance at the beginning of winding between the pipe and the hollow fiber sheet is about 0.2 cm. It was wound in a spiral shape so that the equivalent diameter of the occupied portion was 290 μm. Next, this hollow fiber sheet wound body is incorporated into a cylindrical housing having an inner diameter of about 7.5 cm, both ends of the module are sealed by a known centrifugal sealing method using polyurethane resin, and then both ends of the module are cut and hollowed. The inside of the thread membrane was opened. The effective length of the hollow fiber sheet roll is about 6 cm, the clearance between the outer periphery of the hollow fiber sheet roll and the cylindrical housing is about 0.5 cm, and the effective area of the hollow fiber is1.2m 2 A cylindrical module was created.
[0053]
Bovine blood was adjusted in the same manner as in Example 1, and at the same time as bovine blood was poured from 1 in FIG. 1, oxygen gas was poured from 3 in the figure at V / Q = 1 to measure the gas exchange performance. Result, standard O2Blood flow rate is 7.8 L / min, standard CO2The blood flow rate was 6.3 L / min.
[0054]
In addition, it was confirmed by model experiments that blood flowing out from the perforated tube at the center flows in the radial direction in the hollow fiber wound body almost vertically, reaches the gap between the hollow fiber sheet winding body and the module outer housing, and flows out from 2 in FIG. did.
[0055]
Example 5
The hollow fiber membrane sheet used in Example 2 was used, and the pipe and the hollow fiber sheet were formed on a cylindrical pipe having a diameter of about 30 mm having a plurality of holes on the outer periphery provided with a partition at the center shown in 9 in FIG. The winding was wound in a spiral shape so that the clearance at the beginning of winding was about 0.2 cm, and the equivalent diameter of the portion occupied by the hollow fiber sheet was 265 μm. Next, this hollow fiber sheet wound body is incorporated into a cylindrical housing having an inner diameter of about 7 cm, both ends of the module are sealed by a known centrifugal sealing method using polyurethane resin, and then both end faces of the module are cut to form a hollow fiber. The inside was opened. The effective length of the hollow fiber sheet roll is about 6 cm, and the effective area of the hollow fiber membrane is1.2m 2 A cylindrical module was created.
[0056]
Bovine blood was prepared in the same manner as in Example 1. At the same time, bovine blood was poured from 1 in FIG. 3, and oxygen gas was poured from 3 in the inside of the hollow fiber at V / Q = 1 to measure gas exchange performance.
At a blood flow rate of 16 mL / min, the amount of oxygen transferred to the blood is about 50 mL / min, and CO2The removal amount was about 42 mL / min, and the standard blood flow rate for both oxygen and carbon dioxide was so large that it could not be measured. The blood flow pressure loss at a blood flow rate of 6 L / min was 77 mmHg.
[0057]
Further, as shown by the solid line arrow in FIG. 3 in the model experiment, the blood flowing out from the central perforated tube flows in the radial direction in the hollow fiber sheet wound body substantially vertically, and the hollow fiber sheet wound body and the module outer housing. Then, it was confirmed that the hollow fiber membrane sheet winding body flowed almost vertically to the perforated pipe side and flowed out from 2 in FIG.
[0058]
Example 6
Hollow fiber outer diameter is 180μm, inner diameter is 120μm, membrane oxygen transmission rate is25 × 10 -5 [Cm 3 / Cm 2 / CmHg]A hollow fiber heterogeneous membrane made of a poly (4-methylpent-1) -based resin, a multifilament made of 20 denier polyester as a warp thread, the number of hollow fibers to be driven is 31 / cm, and the distance between hollow fibers is about 147 μm A hollow fiber membrane sheet was prepared. This sheet is wound around a pipe having a nominal diameter of about 3 cm with a large number of holes on the outer periphery so that the equivalent diameter of the sheet winding body is 190 μm, and the membrane area based on the outer diameter of the hollow fiber membrane90m 2 A sheet roll was created. This sheet roll is loaded into a module case of about 50 cm in length consisting of a rigid polyvinyl chloride pipe with a nominal diameter of 25 cm, and urethane resin and epoxy resin are used as the sealing resin, as shown in FIG. 1 by a known centrifugal sealing method. An industrial external perfusion module shown in the model diagram was created. 1 and 3 are connected to an oil rotary vacuum pump with an exhaust speed of about 48 m3 / hr, and the vacuum pressure inside the hollow fiber membrane is maintained at about 23 mmHg, and saturated with air at 25 ° C from 1 in FIG. Poured water. The dissolved oxygen concentration of the deaerated water flowing out from 2 in FIG. 1 was measured with a polarographic oximeter. About 36 L / min of water deaerated to a dissolved oxygen concentration of about 1 ppb could be obtained.
[0059]
Comparative Example 1
Outer diameter 260μm, inner diameter 205μm, oxygen permeation rate of membrane30x10 -5 [Cm 3 (STP) / cm 2 / S / cmHg]Using a hollow fiber heterogeneous membrane made of a poly (4-methylpentene-1) -based resin, a hollow fiber spacing of 22 / cm hollow fibers driven with 30 denier polyester multifilaments as warps A 204 μm hollow fiber sheet was formed by Russell knitting. This sheet is laminated so that the equivalent diameter Dv is 360 μm, and the effective cross-sectional area through which blood passes is the same as in Example 1.50cm 2 The effective membrane area (based on hollow fiber outer diameter) is1.2m 2 A square tube module was created.
[0060]
Gas exchange performance was measured using bovine blood in the same manner as in Example 1. Result, standard O2Blood flow rate is 4.2 L / min, standard CO2The blood flow rate was 3.8 L / min. The blood flow pressure loss when the blood flow rate through the module was 6 L / min was 46 mmHg.
[0061]
Comparative Example 2
The outer diameter is about 260μm, the inner diameter is about 200μm, and the oxygen transmission rate of the membrane is about400x10 -5 [Cm 3 / Cm 2 / S / cmHg]A hollow fiber sheet using a hollow fiber microporous membrane made of a polypropylene resin, a multifilament made of 30 denier polyester as a warp, the number of hollow fibers to be driven is 18 / cm, and the distance between the hollow fibers is 313 μm. Formed. This sheet is laminated so that the equivalent diameter Dv is 275 μm, and the effective cross-sectional area through which blood passes is about the same as in Example 1.50cm 2 The effective membrane area is1.2m 2 A square tube module was created. As in Example 1, the gas exchange performance of the module was measured using bovine blood. Result, standard O2Blood flow rate is 2.9 L / min, standard CO2The blood flow rate was 2.5 L / min. The blood flow pressure loss when the blood flow rate through the module was 6 L / min was 46 mmHg.
[0062]
Comparative Example 3
The outer diameter is about 380μm, the inner diameter is about 330μm, and the membrane oxygen transmission rate is about700x10 -5 [Cm 3 / Cm 2 / S / cmHg]A hollow fiber sheet using a hollow fiber microporous membrane made of polypropylene polymer of the above, a multifilament made of 30 denier polyester as a warp thread, the number of hollow fibers to be driven is 17 / cm, and the distance between the hollow fibers is about 220 μm Formed. This hollow fiber sheet is laminated so that the equivalent diameter Dv is about 470 μm, and the effective area through which blood passes is about the same as in Example 1.50cm 2 The effective winding area is1.2m 2 A square tube module was created. As in Example 1, the gas exchange performance of the module was measured using bovine blood. Result, standard O2Blood flow rate is 2.3 L / min, standard CO2The blood flow rate was 2.2 L / min. The blood flow pressure loss was 42 mmHg when the blood flow rate through the module was 6 L / min.
[0063]
【The invention's effect】
In an external perfusion type gas-liquid gas exchange device in which hollow fiber membrane sheets are stacked and incorporated in a module, the outer diameter of the hollow fiber membrane, the hollow fiber membrane interval of the sheet in which the hollow fibers are arranged substantially in parallel, and (formula 1)
Dv = 4 × (total volume of space occupied by sheet laminate) / (total effective outer surface area of hollow fiber membrane)
The gas exchange efficiency of the external perfusion-type gas-liquid gas exchange device can be greatly improved by defining the equivalent diameter represented by
Especially suitable for artificial lungs that require excellent oxygen supply ability to blood and excellent carbon dioxide removal ability from blood, and that are small, low priming, and low blood pressure loss. Applicable to.
[0064]
[Brief description of the drawings]
FIG. 1 is a model diagram showing a structure of a cylindrical external perfusion type gas-liquid gas exchange device used in an embodiment of the present invention, and arrows in the figure indicate a model of liquid flow.
FIG. 2 is a model diagram showing a laminated state of hollow fiber membrane sheets incorporated in a cylindrical external perfusion type gas-liquid gas exchange device whose model diagram is shown in FIG. 1 and FIG. 3;
FIG. 3 is a structural model diagram of a cylindrical external perfusion type gas exchange device having a partition at the center of a perforated pipe used in an embodiment of the present invention. The arrow in the figure indicates a model of liquid flow.
FIG. 4 is a structural model diagram of a rectangular tube type external perfusion type gas-liquid gas exchange device used in the present invention, and an arrow in the figure indicates a model of liquid flow.
5 is a model diagram showing a laminated state of hollow fiber membrane sheets incorporated in the rectangular external perfusion type gas-liquid gas exchange device of FIG. 4. FIG.
[Explanation of symbols]
1, 2 Liquid in / out
3, 4 Gas inflow / outflow, deaeration
5 Hollow fiber membrane
6 Sealing resin part
7 Perforated pipe
8 Hollow fiber membrane sheet warp
9 Perforated pipe
Claims (4)
Ｄｖ＝４×（シート積層体の占める全空間体積）／（中空糸膜の全有効外表面積）
で計算される相当直径（Ｄｖ）が１６５μｍ〜３２５μｍとなるように積層された状態でハウジング内に組み込まれていることを特徴とする外部灌流型中空糸膜型気液ガス交換装置。In the external perfusion type hollow fiber membrane type gas-liquid gas exchange device, hollow fiber membranes having an outer diameter of 150 μm to 390 μm and an interval between the hollow fiber membranes of 120 μm to 280 μm are arranged substantially in parallel Using hollow fiber membrane sheet (Equation 1)
Dv = 4 × (total space volume occupied by sheet laminate) / (total effective outer surface area of hollow fiber membrane)
The external perfusion-type hollow fiber membrane gas-liquid gas exchange device is incorporated in the housing in a state of being laminated so that the equivalent diameter (Dv) calculated in (1) is 165 μm to 325 μm.
Ｄｖ＝４×（シート積層体の占める全空間体積）／（中空糸膜の全有効外表面積）
で計算される相当直径（Ｄｖ）が１６５μｍ〜３２５μｍとなるように積層された状態でハウジング内に組み込まれている外部灌流型中空糸膜型気液ガス交換装置を使用し、液体を積層された中空糸膜シートに実質的に垂直にクロスして流すことによりガス交換を行う事を特徴とする気液ガス交換方法。In the external perfusion type hollow fiber membrane type gas-liquid gas exchange device, hollow fiber membranes having an outer diameter of 150 μm to 390 μm and an interval between the hollow fiber membranes of 120 μm to 280 μm are arranged substantially in parallel Using hollow fiber membrane sheet (Equation 1)
Dv = 4 × (total space volume occupied by sheet laminate) / (total effective outer surface area of hollow fiber membrane)
Liquid was layered using an external perfusion-type hollow fiber membrane gas-liquid gas exchange device built in the housing in a state where the equivalent diameter (Dv) calculated in step 165 was 165 μm to 325 μm. A gas-liquid gas exchange method characterized in that gas exchange is performed by crossing the hollow fiber membrane sheet substantially vertically and flowing.
Priority Applications (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| JP25642598A JP4026037B2 (en) | 1998-09-10 | 1998-09-10 | Hollow fiber membrane gas-liquid gas exchange device and gas exchange method thereof |
Applications Claiming Priority (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| JP25642598A JP4026037B2 (en) | 1998-09-10 | 1998-09-10 | Hollow fiber membrane gas-liquid gas exchange device and gas exchange method thereof |
Publications (2)
| Publication Number | Publication Date |
|---|---|
| JP2000084369A JP2000084369A (en) | 2000-03-28 |
| JP4026037B2 true JP4026037B2 (en) | 2007-12-26 |
Family
ID=17292496
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| JP25642598A Expired - Lifetime JP4026037B2 (en) | 1998-09-10 | 1998-09-10 | Hollow fiber membrane gas-liquid gas exchange device and gas exchange method thereof |
Country Status (1)
| Country | Link |
|---|---|
| JP (1) | JP4026037B2 (en) |
Cited By (1)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US9199023B2 (en) | 2011-03-31 | 2015-12-01 | Terumo Kabushiki Kaisha | Oxygenator |
Families Citing this family (17)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US6402818B1 (en) * | 2000-06-02 | 2002-06-11 | Celgard Inc. | Degassing a liquid with a membrane contactor |
| JP5138840B2 (en) * | 2000-07-28 | 2013-02-06 | ニプロ株式会社 | Hollow fiber microporous membrane and membrane oxygenator incorporating the same |
| DE10048153A1 (en) * | 2000-09-28 | 2002-04-25 | Natural Energy Solutions Ag | Device for generating singlet oxygen |
| JP4610715B2 (en) * | 2000-11-06 | 2011-01-12 | Ｎｏｋ株式会社 | Humidifier |
| US6558450B2 (en) * | 2001-03-22 | 2003-05-06 | Celgard Inc. | Method for debubbling an ink |
| JP2002370006A (en) * | 2001-06-15 | 2002-12-24 | Mitsubishi Rayon Co Ltd | Liquid treatment apparatus and treatment method using the same |
| JP2006280391A (en) * | 2005-03-31 | 2006-10-19 | Terumo Corp | Cassette for infusion pump with deaeration module and portable infusion pump used for the same |
| JP2007203187A (en) * | 2006-02-01 | 2007-08-16 | Pokka Corp | Washing method of hollow fiber deairing membrane |
| JP5012109B2 (en) * | 2006-03-24 | 2012-08-29 | Ｎｏｋ株式会社 | Hollow fiber membrane module |
| KR101747272B1 (en) * | 2010-05-20 | 2017-06-14 | 코오롱인더스트리 주식회사 | Hollow Fiber Membrane Module and Method for Manufacturing the same |
| JP5413317B2 (en) * | 2010-06-29 | 2014-02-12 | ニプロ株式会社 | Hollow fiber microporous membrane and membrane oxygenator incorporating the same |
| JP5708619B2 (en) * | 2012-11-26 | 2015-04-30 | Nok株式会社 | Hollow fiber membrane module |
| WO2014094139A1 (en) | 2012-12-22 | 2014-06-26 | Dmf Medical Incorporated | An anesthetic circuit having a hollow fiber membrane |
| EP2777801B1 (en) * | 2013-03-15 | 2019-08-28 | Maquet Cardiopulmonary AG | Device for eliminating CO2 from patient blood |
| WO2015118607A1 (en) * | 2014-02-04 | 2015-08-13 | Nok株式会社 | Hollow fiber membrane module |
| KR101721849B1 (en) * | 2016-06-24 | 2017-04-04 | 한국산업기술시험원 | Gas separation membrane module |
| TW202330078A (en) * | 2021-12-28 | 2023-08-01 | 日商Ｄｉｃ股份有限公司 | Degassing module and method for degassing liquid |
-
1998
- 1998-09-10 JP JP25642598A patent/JP4026037B2/en not_active Expired - Lifetime
Cited By (2)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US9199023B2 (en) | 2011-03-31 | 2015-12-01 | Terumo Kabushiki Kaisha | Oxygenator |
| JP5890827B2 (en) * | 2011-03-31 | 2016-03-22 | テルモ株式会社 | Artificial lung |
Also Published As
| Publication number | Publication date |
|---|---|
| JP2000084369A (en) | 2000-03-28 |
Similar Documents
| Publication | Publication Date | Title |
|---|---|---|
| JP4026037B2 (en) | Hollow fiber membrane gas-liquid gas exchange device and gas exchange method thereof | |
| JP4795536B2 (en) | Potting a tubular bundle into the housing | |
| US5137531A (en) | Outside perfusion type blood oxygenator | |
| US5429184A (en) | Wound heat exchanger oxygenator | |
| US5395525A (en) | Apparatus for exchanging substances | |
| JPH0286817A (en) | Hollow yarn-type fluid treating device | |
| WO1990007943A1 (en) | Oxygenator wedge configuration | |
| JPS6327022B2 (en) | ||
| CN107929839A (en) | A kind of portable membrane oxygenator and preparation method and its oxygen close method | |
| US20050163656A1 (en) | Device for treating blood for extracorporeal circulation | |
| US20220409797A1 (en) | Extracorporeal blood conditioning devices and methods | |
| EP0041692B1 (en) | Blood oxygenator | |
| JP2975000B2 (en) | Composite hollow fiber membrane for artificial lung | |
| JPH02109572A (en) | Hollow yarn type fluid treating device | |
| JPH02213356A (en) | Fluid treatment apparatus | |
| JP2792048B2 (en) | Hollow fiber type fluid treatment device | |
| JPH11197469A (en) | Spiral membrane module | |
| JP2003111837A (en) | Hollow fiber membrane type artificial lung | |
| JP2827228B2 (en) | Hollow fiber type fluid treatment device | |
| JPH042067B2 (en) | ||
| JPH10296005A (en) | Method for ultradeaeration of liquid and deaeration apparatus thereof | |
| JP5347602B2 (en) | Blood processing equipment | |
| JPH05337175A (en) | Membrane-type artificial lungs and preparation thereof | |
| JPH09234245A (en) | Outside perfusion type artificial lung | |
| JP2023177563A (en) | artificial lung |
Legal Events
| Date | Code | Title | Description |
|---|---|---|---|
| RD01 | Notification of change of attorney |
Free format text: JAPANESE INTERMEDIATE CODE: A7421 Effective date: 20050704 |
|
| A621 | Written request for application examination |
Free format text: JAPANESE INTERMEDIATE CODE: A621 Effective date: 20050712 |
|
| A977 | Report on retrieval |
Free format text: JAPANESE INTERMEDIATE CODE: A971007 Effective date: 20070426 |
|
| A131 | Notification of reasons for refusal |
Free format text: JAPANESE INTERMEDIATE CODE: A131 Effective date: 20070522 |
|
| A521 | Written amendment |
Free format text: JAPANESE INTERMEDIATE CODE: A523 Effective date: 20070720 |
|
| A131 | Notification of reasons for refusal |
Free format text: JAPANESE INTERMEDIATE CODE: A131 Effective date: 20070816 |
|
| A521 | Written amendment |
Free format text: JAPANESE INTERMEDIATE CODE: A523 Effective date: 20070822 |
|
| TRDD | Decision of grant or rejection written | ||
| A01 | Written decision to grant a patent or to grant a registration (utility model) |
Free format text: JAPANESE INTERMEDIATE CODE: A01 Effective date: 20070913 |
|
| A61 | First payment of annual fees (during grant procedure) |
Free format text: JAPANESE INTERMEDIATE CODE: A61 Effective date: 20070926 |
|
| FPAY | Renewal fee payment (event date is renewal date of database) |
Free format text: PAYMENT UNTIL: 20101019 Year of fee payment: 3 |
|
| R150 | Certificate of patent or registration of utility model |
Free format text: JAPANESE INTERMEDIATE CODE: R150 |
|
| FPAY | Renewal fee payment (event date is renewal date of database) |
Free format text: PAYMENT UNTIL: 20111019 Year of fee payment: 4 |
|
| FPAY | Renewal fee payment (event date is renewal date of database) |
Free format text: PAYMENT UNTIL: 20111019 Year of fee payment: 4 |
|
| FPAY | Renewal fee payment (event date is renewal date of database) |
Free format text: PAYMENT UNTIL: 20121019 Year of fee payment: 5 |
|
| FPAY | Renewal fee payment (event date is renewal date of database) |
Free format text: PAYMENT UNTIL: 20121019 Year of fee payment: 5 |
|
| S533 | Written request for registration of change of name |
Free format text: JAPANESE INTERMEDIATE CODE: R313533 |
|
| FPAY | Renewal fee payment (event date is renewal date of database) |
Free format text: PAYMENT UNTIL: 20121019 Year of fee payment: 5 |
|
| R350 | Written notification of registration of transfer |
Free format text: JAPANESE INTERMEDIATE CODE: R350 |
|
| FPAY | Renewal fee payment (event date is renewal date of database) |
Free format text: PAYMENT UNTIL: 20121019 Year of fee payment: 5 |
|
| FPAY | Renewal fee payment (event date is renewal date of database) |
Free format text: PAYMENT UNTIL: 20121019 Year of fee payment: 5 |
|
| FPAY | Renewal fee payment (event date is renewal date of database) |
Free format text: PAYMENT UNTIL: 20131019 Year of fee payment: 6 |
|
| R250 | Receipt of annual fees |
Free format text: JAPANESE INTERMEDIATE CODE: R250 |
|
| R250 | Receipt of annual fees |
Free format text: JAPANESE INTERMEDIATE CODE: R250 |
|
| R250 | Receipt of annual fees |
Free format text: JAPANESE INTERMEDIATE CODE: R250 |
|
| R250 | Receipt of annual fees |
Free format text: JAPANESE INTERMEDIATE CODE: R250 |
|
| R250 | Receipt of annual fees |
Free format text: JAPANESE INTERMEDIATE CODE: R250 |
|
| EXPY | Cancellation because of completion of term |