JP2700170B2 - Membrane oxygenator - Google Patents
Membrane oxygenatorInfo
- Publication number
- JP2700170B2 JP2700170B2 JP63170783A JP17078388A JP2700170B2 JP 2700170 B2 JP2700170 B2 JP 2700170B2 JP 63170783 A JP63170783 A JP 63170783A JP 17078388 A JP17078388 A JP 17078388A JP 2700170 B2 JP2700170 B2 JP 2700170B2
- Authority
- JP
- Japan
- Prior art keywords
- membrane
- hollow fiber
- blood
- oxygenator
- oxygen
- 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
Description
【発明の詳細な説明】 ［産業上の利用分野］ 本発明は血液体外循環において、血液に酸素を添加
し、二酸化炭素を除去するための膜型人工肺に関するも
のである。Description: FIELD OF THE INVENTION The present invention relates to a membrane oxygenator for adding oxygen to blood and removing carbon dioxide in extracorporeal blood circulation.
［従来の技術と解決しようとする課題］ 人工肺は開心術の補助手段あるいは長期の呼吸補助手
段として研究され、種々のタイプのものが開発されてい
る。これら人工肺は生体肺の持つ機能のなかで血液に酸
素を添加し、二酸化炭素を除去するガス交換機能を代行
するものであって、開心術用の人工肺として現在気泡型
人工肺と膜型人工肺が実用化されている。また呼吸補助
用の人工肺として膜型人工肺が開発されている。[Prior Art and Problems to be Solved] Artificial lungs have been studied as auxiliary means for open heart surgery or long-term respiratory assist means, and various types have been developed. These artificial lungs substitute for the gas exchange function of adding oxygen to the blood and removing carbon dioxide among the functions of the living lung, and are currently used as open-heart oxygenator artificial lungs and membrane-type oxygenators. Artificial lungs have been put into practical use. Also, a membrane oxygenator has been developed as an oxygenator for assisting respiration.
気泡型人工肺は臨床に広く用いられているが、酸素を
血液中に直接吹き込むために、溶血、蛋白変性、血液凝
固、微小血栓の発生、白血球や補体の活性化が生じ易
く、また長時間使用すると消泡効果が弱くなり、微小気
泡が血液中へ混入する恐れがあるなどの欠点を有する。Bubble oxygenator is widely used in the clinic, but because oxygen is directly blown into blood, hemolysis, protein denaturation, blood coagulation, generation of microthrombi, activation of leukocytes and complement are likely to occur, and long When used for a long time, the defoaming effect is weakened, and there are drawbacks that microbubbles may be mixed into blood.
膜型人工肺は膜を隔てて静脈血とガスとを接触させ
て、静脈血中へ酸素を吸収させると同時に、ガス中へ炭
酸ガスを放出させるもので、気泡型人工肺にくらべて、
より生理的であり、血液損傷が少ない、プライミングボ
リュームが小さいなどの利点を有し、近年、臨床的にも
次第に用いられるようになった。Membrane-type artificial lungs contact venous blood and gas across the membrane to absorb oxygen into venous blood and release carbon dioxide into gas at the same time.
It has the advantages of being more physiological, having less blood damage, and having a smaller priming volume, and has recently been gradually used clinically.
現在膜型人工肺に用いられている膜には弗素系重合体
やシリコン系の高分子よりなる均質膜が知られている。As a membrane currently used for a membrane oxygenator, a homogeneous membrane made of a fluorine-based polymer or a silicon-based polymer is known.
これらの均質膜を用いた人工肺のガス交換速度は、膜
へのガスの溶解速度と膜中でのガスの拡散速度に大きく
依存するが、前者では溶解拡散速度が小さすぎるという
問題があり、また後者ではシリコンゴムの機械的強度が
小さくて、薄膜化が困難であるという問題がある。The gas exchange rate of the oxygenator using these homogeneous membranes largely depends on the dissolution rate of the gas in the membrane and the diffusion rate of the gas in the membrane, but the former has a problem that the dissolution and diffusion rate is too small. In the latter case, there is a problem that the mechanical strength of the silicon rubber is small and it is difficult to make the film thin.
また膜型人工肺のもう一つのタイプとして、いわゆる
多孔質人工肺即ち均質膜のような溶解拡散機構と全く異
なる透過機構による疎水性の連通孔型多孔質膜を用いた
人工肺が知られている。かかる人工肺では、膜の有する
連通細孔（例えば0.08〜４μｍ）が透過すべき気体分子
に比べて著しく大きいため、気体分子は体積流として膜
の細孔を通過する。従って、ガス透過速度は均質膜より
３ケタ程大きいが、水蒸気も多量に透過するため、気相
側の膜面での結露によって性能が低下するだけでなく、
長時間血液を循環させて使用すると、血漿が漏出すると
いう問題があった。この血漿の漏出は、血漿中の蛋白成
分等が膜表面に付着してゆくことによって次第に疎水性
が失なわれていくためと推定されるが、血漿の漏出が起
こると、膜のガス交換能は大巾に低下し、使用不能の状
態におちいる場合もある。As another type of membrane oxygenator, a so-called porous oxygenator, that is, an oxygenator using a hydrophobic communicating-pore porous membrane with a completely different permeation mechanism from the dissolution-diffusion mechanism like a homogeneous membrane is known. I have. In such an artificial lung, since the communicating pores (for example, 0.08 to 4 μm) of the membrane are significantly larger than the gas molecules to be transmitted, the gas molecules pass through the pores of the membrane as a volume flow. Accordingly, although the gas permeation rate is about three orders of magnitude higher than that of the homogeneous membrane, a large amount of water vapor is also permeated, so that not only performance deteriorates due to condensation on the gas phase side membrane surface, but also
When blood is circulated for a long time, there is a problem that plasma leaks. This plasma leakage is presumed to be due to the gradual loss of hydrophobicity due to the attachment of protein components and the like in the plasma to the surface of the membrane. May drop significantly and become unusable.
均質膜や多孔質膜が有するこの様な諸欠点を解消する
ために、例えば特公昭54−17052号および特開昭60−249
969号には、多孔質膜の細孔内部と膜表面、または細孔
内部のみを既知の物質の中でも特にガス透過性の高いシ
リコン系化合物でコートあるいは目詰した中空繊維膜に
よる複合膜人工肺が提案されている。シリコンコートま
たはシリコン目詰多孔膜人工肺は、原理的には均質膜肺
よりもシリコンコート層（目詰層）の厚みを薄くできる
ため、ガスの拡散透過性が改善され、ガス交換能が均質
膜肺より高くなるが、例えば特開昭60−249969号に開示
されているような複雑な目詰処理を必要とし、目詰層の
厚さ、強度、ピンホール発生防止などの制御が技術的に
困難であり、コストが高くなるという問題があるなど技
術的に未解決な問題が多く、実用化されていない。In order to eliminate such disadvantages of the homogeneous membrane and the porous membrane, for example, Japanese Patent Publication No. Sho 54-17052 and Japanese Patent Laid-Open No. Sho 60-249
No. 969 describes a composite membrane oxygenator with a hollow fiber membrane coated or clogged with a gas-permeable silicon-based compound among known substances, only inside the pores and membrane surface of the porous membrane, or inside the pores. Has been proposed. Silicon-coated or silicon-clogged porous membrane oxygenators can in principle reduce the thickness of the silicon-coated layer (clogged layer) compared to homogeneous membrane lungs, so gas diffusion and permeability are improved and gas exchange capacity is uniform. Although it is higher than the membrane lung, it requires complicated clogging treatment as disclosed in, for example, JP-A-60-249969, and the control of the thickness, strength, and prevention of pinhole generation of the clogging layer is technically required. However, there are many technically unsolved problems such as a problem that the cost is high, and the technology has not been put to practical use.
以上に述べたように、従来の膜型人工肺において、均
質膜人工肺は、実質的に細孔を有さないので血漿の漏出
がないという利点はあるものの、体積流が存在しないた
め、細孔を通して、体積流でガスを透過させる多孔膜人
工肺よりもガス交換能が劣るという欠点を有する。一
方、連通孔型多孔膜人工肺は、膜の疎水性が維持されて
いる限りは高いガス交換能を有しているが、20時間以上
たつと疎水性が失われ、血漿漏出と、それに伴うガス交
換能の大巾な低下が起るという本質的欠点を有する。さ
らに、これまでの複合膜は低い生産性とそれによる高価
格という欠点を有している。As described above, in the conventional membrane oxygenator, the homogeneous membrane oxygenator has the advantage that there is no leakage of plasma because it has substantially no pores, but there is no volume flow. It has the disadvantage that the gas exchange capacity is inferior to that of a porous membrane oxygenator that allows gas to permeate through a hole in a volume flow. On the other hand, the communication hole type porous membrane oxygenator has a high gas exchange capacity as long as the hydrophobicity of the membrane is maintained, but after 20 hours or more, the hydrophobicity is lost, and plasma leakage and accompanying It has the essential disadvantage that a significant reduction in gas exchange capacity takes place. In addition, previous composite membranes have the disadvantage of low productivity and consequently high cost.
従って、膜人工肺には、均質膜や複合膜型人工肺と同
様に、長時間の使用が可能であること、多孔質膜型人工
肺と同等以上のガス交換能を有することおよび低コスト
で得られること等の夫々の長所を兼ね備えることが求め
られている。Therefore, membrane oxygenators can be used for a long time, have gas exchange capacity equal to or higher than that of porous membrane oxygenators, and can be manufactured at low cost, like homogeneous membranes and composite membrane oxygenators. It is required to have each of the advantages such as gain.
［課題を解決する手段］ 本発明者らは、膜型人工肺に使用するための、血液−
気体間のガス交換能に優れかつ長時間の使用においても
血漿の漏出を完全に防止できる、安価な膜を探索した結
果、或る種の特徴的な膜構造を有するポリオレフィン系
重合体からなる膜が従来の人工肺用の膜に比べて優れた
性能を有する事を見出し、それを用いた膜型人工肺を発
明した。[Means for Solving the Problems] The present inventors have developed a blood-type artificial lung.
As a result of searching for an inexpensive membrane that has excellent gas exchange ability between gases and can completely prevent plasma leakage even during long-term use, a membrane made of a polyolefin polymer having a certain characteristic membrane structure was found. Found that it had better performance than conventional membranes for artificial lungs, and invented a membrane oxygenator using the same.
即ち、本発明によれば、膜の一方の側に血液を流し膜
の他方の側に酸素もしくは酸素含有気体を流すことによ
り膜を介して血液と気体間でガス交換を起う膜型人工肺
において、該膜は25℃における酸素透過速度Ｑ（O2）が
１×10-6［cm3（STP）/cm2・sec・cmHg］以上でありか
つエタノールを実質的に不透過とする遮断層を有し、空
孔率が７〜50％であり、主としてポリオレフィン系重合
体からなり、内径が10〜500μｍでかつ厚さが５〜100μ
ｍの中空繊維膜であることを特徴とする膜型人工肺が提
供される。That is, according to the present invention, a membrane-type oxygenator in which gas is exchanged between blood and gas through the membrane by flowing blood to one side of the membrane and flowing oxygen or an oxygen-containing gas to the other side of the membrane. Wherein the membrane has an oxygen permeation rate Q (O 2 ) at 25 ° C. of 1 × 10 −6 [cm 3 (STP) / cm 2 · sec · cmHg] or more and is substantially impermeable to ethanol. A layer having a porosity of 7 to 50%, mainly comprising a polyolefin polymer, an inner diameter of 10 to 500 μm, and a thickness of 5 to 100 μm.
m is a hollow fiber membrane.
又、本発明によれば上記膜型人工肺に於いて、該膜の
外側に酸素含有気体を流し、一方該膜の内側に血液を流
すか、若しくは該膜の外側に血液を流し、一方該膜の内
側に酸素含有気体を流して血液と該気体とのガス交換を
行うことを特徴とする膜型人工肺の使用法が提供され
る。Further, according to the present invention, in the above membrane-type oxygenator, an oxygen-containing gas is caused to flow outside the membrane, while blood is caused to flow inside the membrane, or blood is caused to flow outside the membrane, There is provided a method of using a membrane oxygenator, wherein an oxygen-containing gas is flowed inside a membrane to exchange gas with the blood.
本発明に用いる膜は、膜内部に微細な細孔（空隙）を
有するものの、膜の表裏は実質上細孔によって連通して
いない、所謂非連通孔のタイプの多孔質膜である。膜内
部に細孔が多く存在するほど酸素や二酸化炭素のガス透
過速度が高くなり、血液への酸素移行量や血液からの二
酸化炭素の除去量が増す。しかしながら、空孔率を高く
し過ぎると細孔は互いに連結し、膜の表裏を連通する細
孔（連通孔）が発生し、血漿の漏出を生ぜしめる。従っ
て、本発明に用い得る膜は、その空孔率（体積空孔率）
が７〜50％のものであり、膜の製造方法によって多少異
なるが、10〜35％のものがより好ましい。本発明に用い
る膜は、上記の様に実質上連通孔を有しない多孔質膜、
換言すると、部分的な連通孔および独立気泡の一方また
は両方を複雑に保有する多孔質膜であるが、さらにその
構造について詳しく論じると、膜の一方の側（中空繊維
膜の外表面もしくは内表面）には細孔が開孔しているが
他の側に細孔が開孔していない場合、膜の内部には細孔
が存在するものの膜の内外両表面には細孔が開孔してい
ない場合、膜の内外両表面共に細孔が開孔しているもの
の該細孔が膜内部で途切れていて、表裏を連通していな
い場合等があり、実際にはこれらの構造が混在する事が
多い。膜表面における細孔の開口状態は、走査型電子顕
微鏡（SEM）による表面からの観察で視認できる。本発
明に用いる膜は上記のいずれの構造であっても良いが、
膜の少なくとも一方の側に細孔が開孔していない層を持
つものが好ましい。細孔の大きさに特に制限は無いが、
酸素透過速度や膜強度等の点から、直径0.005〜10μｍ
が好ましく、0.03〜１μｍがさらに好ましい。The membrane used in the present invention is a so-called non-communication pore type porous membrane having fine pores (voids) inside the membrane, but the front and back of the membrane are not substantially communicated by the pores. The more pores present inside the membrane, the higher the gas permeation rate of oxygen and carbon dioxide, and the greater the amount of oxygen transferred to blood and the amount of carbon dioxide removed from blood. However, if the porosity is too high, the pores are connected to each other, and pores (communication pores) communicating between the front and back of the membrane are generated, thereby causing leakage of plasma. Therefore, the film that can be used in the present invention has a porosity (volume porosity).
Is 7 to 50%, and slightly varies depending on the film production method, but 10 to 35% is more preferable. The membrane used in the present invention is a porous membrane having substantially no communication hole as described above,
In other words, it is a porous membrane in which one or both of the partial communication pores and the closed cells are intricately held, and when the structure is further discussed in detail, one side of the membrane (the outer surface or inner surface of the hollow fiber membrane) is used. ) Has pores open but no pores on the other side, there are pores inside the membrane, but pores open on both the inner and outer surfaces of the membrane. If not, the pores are open on both the inner and outer surfaces of the membrane, but the pores are interrupted inside the membrane, and there may be cases where the front and back are not connected, and these structures are actually mixed. There are many things. The opening state of the pores on the membrane surface can be visually recognized by observation from the surface with a scanning electron microscope (SEM). The film used in the present invention may have any of the above structures,
Preferably, the membrane has a layer with no pores open on at least one side of the membrane. There is no particular limitation on the size of the pores,
0.005-10μm in diameter from the viewpoint of oxygen transmission rate and membrane strength
Is preferably, and more preferably 0.03 to 1 μm.
本発明に用いる膜は酸素透過速度Ｑ（O2）が１×10-6
［cm3（STP）/cm2・sec・cmHg］以上、好ましくは７×1
0-6［cm3（STP）/cm2・sec・cmHg］以上、より好ましく
は５×10-5〜１×10-3［cm3（STP）／（cm2・sec・cmH
g）］のものである。（酸素透過速度はASTM D1434に準
拠して測定される）酸素透過速度がこの値より低い場合
は、血液とのガス交換速度が遅くなり、均質膜型人工肺
に比べメリットが無くなる。本発明に用いる膜の場合、
二酸化炭素の透過速度は酸素の透過速度とほぼ同程度若
しくは高くなるため、酸素透過速度が上記値であれば、
血液からの二酸化炭素除去量は十分である。酸素透過速
度は高い方が好ましいのは勿論である。酸素透過速度を
高めるには酸素透過係数の大きな素材を選定すること、
空孔率を高めること、気体が膜素材の重合体中を溶解・
拡散機構で透過すべき実質膜厚を薄くすること、といっ
た方法をとる事ができる。しかし、その達し得る酸素透
過速度には自ずと限界はあろうが、高いこと自体による
不都合はないので、その意味から酸素透過速度に上限を
定めることを要しない。The membrane used in the present invention has an oxygen transmission rate Q (O 2 ) of 1 × 10 −6.
[Cm 3 (STP) / cm 2 · sec · cmHg] or more, preferably 7 × 1
0 -6 [cm 3 (STP) / cm 2 · sec · cmHg] or more, more preferably 5 × 10 -5 to 1 × 10 -3 [cm 3 (STP) / (cm 2 · sec · cmH)
g)]. (Oxygen transmission rate is measured according to ASTM D1434.) When the oxygen transmission rate is lower than this value, the rate of gas exchange with blood becomes slow, and there is no merit as compared with a homogeneous membrane oxygenator. In the case of the film used in the present invention,
Since the transmission rate of carbon dioxide is almost the same as or higher than the transmission rate of oxygen, if the oxygen transmission rate is the above value,
The amount of carbon dioxide removed from the blood is sufficient. Of course, the higher the oxygen permeation rate, the better. To increase the oxygen transmission rate, select a material with a large oxygen transmission coefficient.
Increasing porosity, gas dissolves in polymer of membrane material
A method of reducing the substantial film thickness to be transmitted by the diffusion mechanism can be adopted. However, although the achievable oxygen permeation rate is naturally limited, there is no disadvantage due to the high permeation rate itself, and in this sense, it is not necessary to set an upper limit on the oxygen permeation rate.
本発明の中空繊維膜はエタノールを実質的に不透過と
する、即ち実質的に非多孔性のエタノール遮断層を有
し、膜の表裏を連通した細孔、所謂連通孔が存在しな
い。The hollow fiber membrane of the present invention is substantially impermeable to ethanol, that is, has a substantially non-porous ethanol barrier layer, and has no pores communicating between the front and back of the membrane, so-called communication holes.
連通孔が存在すると、酸素透過速度は高くなるもの
の、血漿の漏出が生じ好ましくない。連通孔の有無と存
在量は、エタノールの透過量で判定できる。エタノール
は、膜に連通孔が存在すれば、その内部に浸入して液状
のまま膜を透過する。例えば、多孔膜型人工肺に用いら
れる連通孔タイプのポリプロピレン膜の場合、膜の一方
の側より0.5kgf/cm2の加圧下に70％エタノールを圧入す
ると、1000〜40000ml/（min・m2）の速度でエタノール
が透過してくるが、本発明の膜ではエタノール透過量は
著しく少なく、実質的に不透過である。ここでいう「実
質的に不透過」とは、同じ測定条件下でエタノール透過
量が30ml/（min・m2）以下であることを意味する。エタ
ノール透過量は、好ましくは10ml/（min・m2）以下、さ
らに好ましくは2ml/（min・m2）以下である。The presence of the communication hole increases the oxygen permeation rate, but undesirably causes leakage of plasma. The presence or absence and the amount of the communication hole can be determined by the amount of permeation of ethanol. If there is a communication hole in the membrane, ethanol penetrates into the inside of the membrane and passes through the membrane in a liquid state. For example, in the case of a through-hole type polypropylene membrane used for a porous membrane oxygenator, if 70% ethanol is injected from one side of the membrane under a pressure of 0.5 kgf / cm 2 , 1000 to 40,000 ml / (min · m 2 Although ethanol permeates at the rate of (1), the amount of ethanol permeated by the membrane of the present invention is extremely small, and is substantially impermeable. Here, “substantially impermeable” means that the ethanol permeation amount is 30 ml / (min · m 2 ) or less under the same measurement conditions. The ethanol permeation amount is preferably 10 ml / (min · m 2 ) or less, more preferably 2 ml / (min · m 2 ) or less.
本発明の膜における連通していない部分、即ちこのエ
タノールを「実質的に不透過」とするエタノール遮断層
が本発明の膜のどの位置に存在するかを特定すること
は、本発明において必須ではなく、膜の表面の片側また
は両側に存在しても良いことは勿論、膜の内部に、単
層、複層を問わず、複雑な形状で実質的に存在するので
あっても良い。It is essential in the present invention to specify where in the membrane of the present invention the non-communicating part of the membrane of the present invention, that is, the position of the ethanol blocking layer that makes this ethanol "substantially impermeable" is present. Instead, it may exist on one or both sides of the surface of the film, and may exist substantially in a complicated shape inside the film irrespective of a single layer or multiple layers.
しかしながら、その様な遮断層が血液に接する側の膜
表面に形成された膜構造が、血漿あるいは凝結水分によ
る空隙部の閉そくを防ぐ意味で好ましい。即ち、血液を
中空繊維膜の外側に流す外部灌流型人工肺にあつては中
空繊維膜の外表面に、又、血液を中空繊維膜の内側に流
す内部灌流型人工肺にあつては中空繊維膜の内表面にエ
タノール遮断層を形成する事が好ましい。さらに、遮断
層の厚みを薄くする目的から、遮断層は１層である事が
好ましい。この様な遮断層（非多孔層）が膜表面に形成
されているかどうかは、走査型電子顕微鏡（SEM）で確
認する事ができる。However, a membrane structure in which such a barrier layer is formed on the membrane surface on the side in contact with blood is preferable from the viewpoint of preventing clogging of voids by plasma or condensed water. That is, in the case of an externally perfused oxygenator, which allows blood to flow outside the hollow fiber membrane, the hollow fiber is used, and in the case of an internal perfusion oxygenator, which allows blood to flow inside the hollow fiber membrane. It is preferred to form an ethanol barrier layer on the inner surface of the membrane. Further, in order to reduce the thickness of the barrier layer, it is preferable that the barrier layer is a single layer. Whether such a blocking layer (non-porous layer) is formed on the film surface can be confirmed by a scanning electron microscope (SEM).
エタノール遮断層の膜全体に於る平均的な全実質厚み
は気体透過速度の実測値から計算により推定する事がで
きる。即ち、膜を透過する気体は、膜中の遮断層を溶解
・拡散流れで透過する部分と膜の表裏を連結する連通孔
をクヌーセン流れで透過する部分の和であるとして（並
列構造）解いた式（１）を用い、酸素透過速度および窒
素透過速度の実測値から計算される。The average total substantial thickness of the entire ethanol barrier layer can be estimated by calculation from the measured gas permeation rate. That is, the gas permeating through the membrane was solved as a sum of a portion permeating through the barrier layer in the membrane by the dissolution / diffusion flow and a portion permeating through the communication hole connecting the front and back of the membrane with the Knudsen flow (parallel structure). It is calculated from the actually measured values of the oxygen transmission rate and the nitrogen transmission rate using the equation (1).
Ｐ（O2）［＊１］：素材ポリマーの酸素透過係数 Ｐ（N2）［＊１］：素材ポリマーの窒素透過係数 Ｑ（O2）［＊２］：膜の酸素透過速度（実測値） Ｑ（N2）［＊２］：膜の窒素透過速度（実測値） Ｌ ［ cm ］：遮断層の平均厚み （注） ［＊１］:cm3（STP）・cm/（cm2・sec・cmHg） ［＊２］:cm3（STP）／（cm2・sec・cmHg） 本発明者等は同じ酸素透過速度Ｑ（O2）を示す膜で
も、（１）式で計算される遮断層の厚みＬが小さいほど
血液への酸素加能力が高い事を見出した。その理由の詳
細については不明であるが、血液への酸素供給に際し
て、連通孔透過部の寄与は、遮断層透過部の寄与に比べ
て小さい事によるものであろう。本発明に用いる事ので
きる、（１）式で計算される中空繊維膜の遮断層厚みは
10μｍ以下、好ましくは２μｍ以下、さらに好ましくは
0.7μｍ以下である。しかしながら製造技術上、遮断層
厚みを0.01μｍ以下にする事は極めて困難である。 P (O 2 ) [* 1]: Oxygen permeability coefficient of material polymer P (N 2 ) [* 1]: Nitrogen permeability coefficient of material polymer Q (O 2 ) [* 2]: Oxygen permeability of membrane (actual value) ) Q (N 2 ) [* 2]: Nitrogen permeation rate of membrane (actually measured value) L [cm]: Average thickness of barrier layer (Note) [* 1]: cm 3 (STP) · cm / (cm 2 · sec · cmHg) [* 2] : cm 3 (STP) / (cm 2 · sec · cmHg) the present inventors have also a film showing the same oxygen transmission rate Q (O 2), is calculated by equation (1) It has been found that the smaller the thickness L of the barrier layer, the higher the ability to add oxygen to blood. Although the details of the reason are not clear, the contribution of the communication hole permeation part in supplying oxygen to the blood may be due to a smaller contribution than the contribution of the blocking layer permeation part. The thickness of the barrier layer of the hollow fiber membrane calculated by the formula (1) that can be used in the present invention is
10 μm or less, preferably 2 μm or less, more preferably
0.7 μm or less. However, it is extremely difficult to reduce the thickness of the blocking layer to 0.01 μm or less due to manufacturing technology.
上記（１）式で計算される遮断層の厚みはα＜１の場
合には誤差が大きくなる。この様な場合には、酸素／窒
素の測定の代わりに二酸化炭素／窒素の測定から求める
ことができる。The error of the thickness of the barrier layer calculated by the above equation (1) increases when α <1. In such a case, it can be determined from the measurement of carbon dioxide / nitrogen instead of the measurement of oxygen / nitrogen.
又、本発明に用いられる膜としては、上述のα（酸素
／窒素の分離係数）が好ましくは0.94〜1.15、より好ま
しくは0.95〜1.09のものがより有効である。As the membrane used in the present invention, the above-mentioned α (oxygen / nitrogen separation coefficient) is preferably 0.94 to 1.15, more preferably 0.95 to 1.09.
而して、中空繊維膜は、25℃における酸素透過速度Ｑ
（O2）が１×10-5以上、酸素／窒素の分離係数αが0.94
〜1.15、酸素透過速度と窒素透過速度から計算される遮
断層（非多孔層）の厚みが２μｍ以下であり、かつ圧力
差0.5kgf/cm2でのエタノール透過量が30ml/（min・m2）
以下、空孔率が７〜50％であり、内径が10〜500μｍ
で、且つ厚さが５〜100μｍであるものが好適である。
かかる膜は、特開昭59−196706号に開示されている、多
孔質層と非多孔質層とからなり、酸素／窒素の分離係数
αが1.2以上の中空繊維膜に比べて、人工肺に適用した
場合に於いて、より優れた血液処理量を呈することにな
る。Thus, the hollow fiber membrane has an oxygen permeation rate Q at 25 ° C.
(O 2 ) is 1 × 10 -5 or more and oxygen / nitrogen separation coefficient α is 0.94
1.15, the thickness of the barrier layer (non-porous layer) calculated from the oxygen transmission rate and the nitrogen transmission rate is 2 μm or less, and the ethanol transmission rate at a pressure difference of 0.5 kgf / cm 2 is 30 ml / (min · m 2 )
Hereinafter, the porosity is 7 to 50%, and the inner diameter is 10 to 500 μm.
And a thickness of 5 to 100 μm is preferred.
Such a membrane is composed of a porous layer and a non-porous layer disclosed in JP-A-59-196706, and is more suitable for an artificial lung than a hollow fiber membrane having an oxygen / nitrogen separation coefficient α of 1.2 or more. When applied, it will exhibit better blood throughput.
本発明の膜型人工肺の特徴は、特徴的な構造と気体透
過特性を持った中空繊維膜を人工肺のガス交換膜に用い
る点にあり、その構造については外部灌流型、内部灌流
型その他任意の構造を採る事ができるが、本発明に用い
る中空繊維膜の特徴、即ち外表面に遮断層が形成可能な
点、小径の中空繊維膜でも高性能、安価に製造可能な
点、径に対して肉厚を薄くできる点等を十分生かす為に
は、外部灌流型にする事が効果的である。さらに、外部
灌流型人工肺を組立てるに当たって、中空繊維膜を簾状
に織つたシートに形成して組み込み、血液のチヤンネリ
ングを防止するといった方法を採る事により、膜性能を
より発揮させる事ができる。The feature of the membrane oxygenator of the present invention resides in that a hollow fiber membrane having a characteristic structure and gas permeation characteristics is used for a gas exchange membrane of an artificial lung, and the structure thereof is an external perfusion type, an internal perfusion type, and the like. Although any structure can be adopted, the characteristics of the hollow fiber membrane used in the present invention include the point that a barrier layer can be formed on the outer surface, high performance even with a small diameter hollow fiber membrane, the point that it can be manufactured at low cost, and the diameter. In order to take full advantage of the fact that the thickness can be reduced, it is effective to use an external perfusion type. Further, in assembling the external perfusion type oxygenator, by adopting a method in which a hollow fiber membrane is formed into a sheet woven like a cord and incorporated to prevent channeling of blood, the membrane performance can be further enhanced.
尚、本発明の膜型人工肺は、内部灌流で用いる場合に
は、通常中空繊維の内側の総面積が0.1〜7m2で、中空繊
維の本数が1000〜100,000本となるように中空繊維を包
含し、又、そのガス交換部の大きさが略、外径25cm以
下、及び長さ30cm以下の円筒タイプのものが代表的であ
る。Incidentally, membrane oxygenator of the present invention, when used for internal perfusion, with usually hollow inside of total area 0.1～7M 2 fibers, the hollow fibers as the number of hollow fibers is present 1,000 to 100,000 A typical example is a cylindrical type in which the size of the gas exchange portion is substantially the same, the outer diameter is 25 cm or less, and the length is 30 cm or less.
また。外部灌流で用いる場合には、通常中空繊維の外
側の総面積が0.1〜3.5m3で、中空繊維の本数が1,000〜6
0,000本となるように中空繊維を包含し、又、そのガス
交換部の大きさが略、外径20cm以下、及び長さ30cm以下
の円筒タイプのものが代表的である。Also. When used in external perfusion, the total area of the outer normal hollow fibers in 0.1～3.5M 3, the number of hollow fibers 1,000～6
A typical example is a cylindrical type in which hollow fibers are included so that the number becomes 0,000, and the size of the gas exchange portion is substantially the same, the outer diameter is 20 cm or less, and the length is 30 cm or less.
本発明に用いる膜を構成する重合体はポリオレフィン
が好適である。ポリオレフィン系重合体は、素材として
の酸素および二酸化炭素の透過係数が大きいこと、血液
適合性に優れること、非連通孔形多孔質膜に成形し易い
こと、残留溶剤の恐れの無い溶融法で膜を成形できるこ
と、機械的強度が強くて膜厚を小さく出来るため装置が
コンパクトになること、有害な不純物を含有しにくいこ
と、吸水性が無く取扱いが容易なこと、耐薬品性があり
滅菌が容易なこと、安価であること、といった特長を有
している。本発明に用いるポリオレフィン系重合体とし
ては、例えばポリ−４−メチルペンテン−１、ポリプロ
ピレン、ポリエチレン、ポリブテン−１およびこれらの
共重合体等を例示することができるが、これらの中でポ
リ−４−メチルペンテン−１が気体透過係数が大きいこ
とにより酸素透過速度Ｑ（O2）を高くして遮断層厚みＬ
を薄くする事ができ、かつ膜表面に遮断層を形成し易い
ので特に好ましい。また、素材の血液適合性からみて、
ポリオレフィンが膜素材として好適であることは前記し
たが、ポリ−４−メチルペンテン−１は、その表面エネ
ルギーが前記例示の各ポリオレフィン系重合体の中で最
も小さいため、いわゆるWETLUNG（膜表面に凝縮した水
蒸気が膜を濡らして広がり、ガス交換面積を低下させる
現象）が起こりにくく、また血液学的には補体を活性化
する事が少ないなど、今後要望が高まつて行くであろう
長時間使用可能な膜型人工肺の素材として特に優れた適
性を有している。従って、この点からもポリ−４−メチ
ルペンテン−１は本発明において好適な素材である。The polymer constituting the film used in the present invention is preferably a polyolefin. Polyolefin polymers have high permeability coefficients for oxygen and carbon dioxide as materials, have excellent blood compatibility, are easy to mold into non-porous porous membranes, and are formed by a melting method without fear of residual solvent. Can be molded, the mechanical strength is strong and the film thickness can be reduced, so the device can be made compact, it does not contain harmful impurities, it is easy to handle without water absorption, it has chemical resistance and it is easy to sterilize And that it is inexpensive. Examples of the polyolefin polymer used in the present invention include poly-4-methylpentene-1, polypropylene, polyethylene, polybutene-1, and copolymers thereof, among which poly-4 is used. -Oxygen permeation rate Q (O 2 ) is increased due to the large gas permeability coefficient of methylpentene-1 so that the barrier layer thickness L
Is particularly preferable because the thickness of the film can be reduced and a barrier layer can be easily formed on the film surface. Also, in view of the blood compatibility of the material,
As described above, polyolefin is suitable as a film material. However, since poly-4-methylpentene-1 has the smallest surface energy among the polyolefin polymers exemplified above, so-called WETLUNG (condensed on the film surface) is used. The phenomenon that reduced water vapor spreads by wetting the membrane and reduces the gas exchange area) is unlikely to occur, and hematology rarely activates complement. It has particularly excellent suitability as a material for a usable membrane oxygenator. Therefore, also from this point, poly-4-methylpentene-1 is a preferable material in the present invention.
本発明で用いられる主としてポリオレフィン系重合体
から成る素材は、ポリオレフィンの１種以上を主要成分
とするものであればよく、他の物質を含有することも可
能である。例えば、架橋剤や抗菌剤等を含有しても良い
し、他のポリマーとブレンドする事もできる。また、プ
ラズマ処理等の表面処理や放射線架橋等の処理を行なう
事も可能である。The material mainly composed of a polyolefin-based polymer used in the present invention may be one containing at least one polyolefin as a main component, and may contain other substances. For example, it may contain a crosslinking agent, an antibacterial agent, or the like, or may be blended with another polymer. It is also possible to perform a surface treatment such as a plasma treatment or a treatment such as radiation crosslinking.
本発明に用いる膜の形状は、中空繊維状もしくは管状
であり、内径は10〜500μｍ、好ましくは100〜300μ
ｍ、膜厚は５〜100μｍ、好ましくは10〜40μｍであ
る。本発明の膜はシリコン均質膜に比べて、内径に対す
る膜厚が小さく、人工肺モジュールに占める膜の体積が
小さい為、高い気体透過速度と相まって人工肺をコンパ
クトに製作でき、プライミングボリュームを小さくでき
ると同時に安価に製造する事が可能になる。又、本発明
の膜は、中空繊維を簾状のシートとして用いるのが好ま
しい。かかる簾状シートは中空繊維に対して垂直方向に
縦糸又は粘着テープで中空繊維を編組するか、接着剤が
付着した糸で中空接着剤を接着する等によつて得たもの
が使用できる。勿論、該簾状シートは上記のもののみに
限定されるものではない。The shape of the membrane used in the present invention is a hollow fiber or tubular, the inner diameter is 10 ~ 500μm, preferably 100 ~ 300μ
m, the film thickness is 5 to 100 μm, preferably 10 to 40 μm. The membrane of the present invention has a smaller film thickness with respect to the inner diameter and a smaller volume of the membrane occupying the oxygenator module than the silicon homogenous membrane. At the same time, it can be manufactured at low cost. In the membrane of the present invention, the hollow fibers are preferably used as a cord-like sheet. Such a mat-like sheet may be obtained by braiding the hollow fiber with a warp or an adhesive tape in a direction perpendicular to the hollow fiber, or bonding the hollow adhesive with a thread to which an adhesive is attached, or the like. Of course, the mat-like sheet is not limited to the above.
この様に構成される本発明の人工肺は、例えば、ポリ
−４−メチルペンテン−１で作った膜厚27μｍ、外径27
2μｍ、空孔率18％の中空膜内面に平滑な遮断層を有す
る中空繊維膜を用いた、有効膜面積0.8m2の人工肺にお
いて、血液を中空繊維膜の内側に流し、血液温度37℃、
血液の酸素分圧38mmHg、二酸化炭素分圧45mmHgの条件下
で酸素移行量および二酸化炭素の除去量を測定したとこ
ろ、全く同様の膜面積および条件で行った膜厚100μ
ｍ、外径400μｍのシリコン均質膜を用いた人工肺にく
らべて酸素移行量は1.4倍、二酸化炭素除去量は1.5倍と
なった。また、膜厚25μｍ、外径250μｍで空孔率40％
のポリプロピレン多孔膜を用いた人工肺にくらべて、本
発明の該人工肺は、酸素移行量および二酸化炭素除去量
にやや勝り、ポリプロピレン多孔膜が血漿の漏出を生じ
るのに対しその漏出が全く認められなかった。さらに中
空繊維の簾状シートの繊維膜の外側に血液を流したとこ
ろ繊維膜の内側に流した場合に比べて酸素移行量で2.0
倍、二酸化炭素除去量で2.0倍で、しかも圧力損失が極
めて小さかった。これらの事実は、本発明の人工肺が従
来の人工肺にくらべて優れた性能を有することを示して
いる。The thus constructed oxygenator of the present invention has a thickness of 27 μm and an outer diameter of 27 μm made of poly-4-methylpentene-1, for example.
In an artificial lung having an effective membrane area of 0.8 m 2 using a hollow fiber membrane having a smooth blocking layer on the inner surface of a hollow membrane having a pore size of 2 % and a porosity of 18%, blood is allowed to flow inside the hollow fiber membrane, and a blood temperature of 37 ° C. ,
When the oxygen transfer rate and the carbon dioxide removal rate were measured under the conditions of an oxygen partial pressure of blood of 38 mmHg and a carbon dioxide partial pressure of 45 mmHg, a film thickness of 100 μm was performed under exactly the same film area and conditions.
The oxygen transfer rate and the carbon dioxide removal rate were 1.4 times and 1.5 times, respectively, as compared with an artificial lung using a silicon homogenous membrane having an outer diameter of 400 μm. The porosity is 40% with a thickness of 25 μm and an outer diameter of 250 μm.
Compared with the oxygenator using a polypropylene porous membrane of the present invention, the oxygenator of the present invention slightly outperforms the oxygen transfer amount and the carbon dioxide removal amount, and the polypropylene porous membrane causes plasma leakage, while no leakage is observed. I couldn't. Furthermore, when blood was flowed outside the fiber membrane of the hollow fiber blind sheet, the amount of oxygen transfer was 2.0 in comparison with the case where blood was flown inside the fiber membrane.
Twice as much as the amount of carbon dioxide removed, and the pressure loss was extremely small. These facts show that the oxygenator of the present invention has superior performance as compared with the conventional oxygenator.
本発明に用いる膜は、その製法については特に限定は
ないが、一般には溶融法、乾式法および乾湿式法が適し
ており（中でも溶融法が膜の性能および生産性の両面に
於て特に好適であり）、例えば、特開昭59−196706、特
開昭59−229320、特開昭61−101206、特開昭61−101227
に開示されている方法で製造する事ができる。しかしな
がら、これらの溶融成形法において、人工肺に要求され
る、高い血液酸素加能力、血漿漏洩防止能力および長時
間使用時に性能が劣化しない能力を中空糸膜に与えるに
は、次の様な条件で製造するのが好ましい。即ち、溶融
温度を（Tm＋15）〜（Tm＋65）℃（但し、Tmはポリマー
の結晶融点）、非晶延伸のDRを1.0〜1.1熱処理の温度を
（Tm−35）〜（Tm−10）℃、熱処理時間を２〜30秒、DR
を1.0〜1.2、冷延伸DRを1.1〜1.6、熱延伸DRを1.3〜2.0
の範囲で製造する。そして各々の工程の条件を上記範囲
で調節する事により実施例に記載の様に、酸素透過速
度、空孔率、遮断層厚み等を人工肺としての使用目的に
合致するよう、任意に設定する事ができる。又、到達結
晶化度20％以上のポリオレフィン重合体を中空繊維状に
溶融押出成形し、これを必要に応じ配向延伸と熱処理を
行ない、冷延伸と熱固定を行なう事により中空繊維膜の
少なくとも一方の側に平滑な遮断層を有する多孔質膜を
製造する事ができる。この方法で製造した膜は、その生
成機構に由来して膜中の細孔が膜表面に対して垂直方向
に長い構造を持つためか、比較的低い空孔率で十分に高
い酸素透過速度と実質的にアルコール不透過性を示し、
しかも高い機械的強度を持ち膜厚を小さくできる事、溶
剤等を一切使用しないので有害物の溶出が無い事、生産
性が高く複合膜に比べてはるかに低コストの膜を製造で
きる事、といった特徴を持つ。The film used in the present invention is not particularly limited in its production method, but generally a fusion method, a dry method and a dry-wet method are suitable (in particular, the fusion method is particularly suitable in terms of both performance and productivity of the film). For example, JP-A-59-196706, JP-A-59-229320, JP-A-61-101206, JP-A-61-101227.
Can be produced by the method disclosed in US Pat. However, in order to give the hollow fiber membrane the high oxygenation ability required for artificial lungs, the ability to prevent plasma leakage, and the ability not to deteriorate during long-term use in these melt molding methods, the following conditions are required. It is preferable to manufacture with. That is, the melting temperature is (Tm + 15) to (Tm + 65) ° C. (where Tm is the crystalline melting point of the polymer), the DR of the amorphous stretching is 1.0 to 1.1, and the temperature of the heat treatment is (Tm−35) to (Tm−10) ° C. Heat treatment time 2-30 seconds, DR
1.0-1.2, cold drawing DR 1.1-1.6, hot drawing DR 1.3-2.0
Manufacture in the range. Then, by adjusting the conditions of each step within the above range, the oxygen transmission rate, the porosity, the thickness of the barrier layer, and the like are arbitrarily set so as to match the purpose of use as the artificial lung, as described in the Examples. Can do things. Also, a polyolefin polymer having a reached crystallinity of 20% or more is melt-extruded into a hollow fiber shape, and this is subjected to orientation stretching and heat treatment as necessary, and then cold stretched and heat-set to perform at least one of the hollow fiber membranes. A porous membrane having a smooth barrier layer on the side of the film can be produced. The membrane produced by this method has a structure in which the pores in the membrane are long in the direction perpendicular to the membrane surface due to the generation mechanism, and it has a relatively low porosity and a sufficiently high oxygen permeation rate. Substantially alcohol-impermeable,
In addition, it has high mechanical strength and can reduce the film thickness, it does not use any solvents, etc., so there is no elution of harmful substances, and it can produce a film with high productivity and much lower cost than composite membrane. Has features.
［発明の効果］ 本発明の人工肺は、従来の均質膜人工肺に比べた場
合、膜内部に細孔を持つ構造に由来する高い気体透過速
度を示し、これにより血液への酸素移行量及び血液から
の二酸化炭素除去量が大きくなる。従って、より小型の
装置で同じ目的を達する事ができ、装置のプライミング
ボリュームの減少と廉価化が可能になる。また、シリコ
ン均質膜に比べて膜の剛性と強度が高く、取扱性と加工
性に優れるという特徴も有する。その一方で、均質膜型
人工肺の有していた長所すなわち血漿の漏出が無く長時
間の使用に耐えるという長所については、同等の性能を
持っている。[Effects of the Invention] The oxygenator of the present invention exhibits a higher gas permeation rate derived from a structure having pores inside the membrane as compared with a conventional homogeneous membrane oxygenator, thereby increasing the amount of oxygen transferred to blood and The amount of carbon dioxide removed from blood increases. Therefore, the same purpose can be achieved with a smaller device, and the priming volume of the device can be reduced and the cost can be reduced. In addition, it has a feature that the film has higher rigidity and strength than a silicon homogeneous film, and is excellent in handleability and workability. On the other hand, the homogenous membrane-type oxygenator has the same advantages as the advantages of the oxygenator, namely, the advantage that there is no leakage of plasma and that it can be used for a long time.
また、本発明の人工肺は、従来の連通孔型多孔質膜を
用いた人工胚が持っていた欠点すなわち長時間の使用に
耐えないという欠点を除去し、しかも血液とのガス交換
能力について同等以上の性能を有しておりながらその膜
の製造の難易度、強度、コスト等については全く損色が
ない。In addition, the artificial lung of the present invention eliminates the drawbacks of the artificial embryo using the conventional through-hole type porous membrane, that is, the drawback that it cannot withstand long-time use, and has the same gas exchange ability with blood. Despite having the above performance, there is no color loss in the difficulty, strength, cost, etc. of the production of the film.
さらにまた、本発明の人工肺は、複合膜型人工肺と比
べて同等の性能を有するのみならず、複合膜人工肺が多
孔質膜の製膜とその複合膜化という二工程が必要なのに
対して、一段階で製膜が可能である事、複合膜の製造に
は通常溶剤が用いられ、作業環境、大気汚染、残留溶
剤、乾燥時間等の点で問題があるのに対して、これらの
問題が全くない溶融法で膜の製造が可能である事、複合
膜と異なり中空繊維膜の内表面、外表面のいずれでも、
あるいはその両面に平滑な遮断層を容易に形成でき、使
用目的に応じた膜が供給できる事、といった長所を有し
ている。Furthermore, the oxygenator of the present invention not only has the same performance as the composite membrane oxygenator, but also requires two steps of forming the porous membrane and forming the composite membrane. However, the fact that the film can be formed in one step and that the production of the composite film usually uses a solvent, and there are problems in the working environment, air pollution, residual solvent, drying time, etc. The fact that the membrane can be produced by a melting method without any problems, unlike the composite membrane, either on the inner surface of the hollow fiber membrane or on the outer surface,
Alternatively, there is an advantage that a smooth blocking layer can be easily formed on both surfaces, and a film can be supplied according to the purpose of use.
［実 施 例］ 以下実施例等によって本発明をさらに具体的に説明す
る。[Examples] Hereinafter, the present invention will be described more specifically with reference to Examples and the like.
製造例１ メルトインデックス（ASTM D1238による）26のポリ
−４−メチルペンテン−１を、直径6mmの円環型中空繊
維用ノズルを用いて、紡糸温度290℃、引取速度300m/
分、ドラフト270で溶融紡糸し、外径343μｍ、膜厚34μ
ｍの中空繊維を得た。この時ノズル口下３〜35cmの範囲
を温度25℃、風速1.5m/秒の風で冷却した。得られた中
空繊維を温度35℃、延伸倍率（DR）1.05で、ローラー系
を用いて連続的に非晶延伸し、次いで200℃、DR1.3で熱
風循環型恒温槽中に導入して５秒間滞留させる事により
熱処理を行ない、引続き35℃、DR1.2の冷延伸、150℃、
DR1.2の熱延伸、および200℃、DR0.9の熱固定を行なっ
て、外径272μｍ、膜厚27μｍの中空繊維膜を得た。こ
の膜の内外表面を12,000倍のSEMで観察したところ、第
１図および第２図に見られる様に、内表面は平滑で、細
孔が全く認められず、外表面には0.2μｍ程度の微細孔
が多数認められた。Production Example 1 Poly-4-methylpentene-1 having a melt index of 26 (according to ASTM D1238) was spun at a spinning temperature of 290 ° C. and a take-up speed of 300 m / using a 6 mm-diameter annular hollow fiber nozzle.
Minutes, melt spinning with draft 270, outer diameter 343μm, film thickness 34μ
m hollow fibers were obtained. At this time, a range of 3 to 35 cm below the nozzle opening was cooled by a wind at a temperature of 25 ° C. and a wind speed of 1.5 m / sec. The obtained hollow fiber was continuously subjected to amorphous drawing using a roller system at a temperature of 35 ° C. and a draw ratio (DR) of 1.05, and then introduced into a hot-air circulating thermostat at 200 ° C. and DR 1.3. Heat treatment is performed by staying for 2 seconds, followed by 35 ° C, cold stretching of DR1.2, 150 ° C,
Heat stretching at DR1.2 and heat setting at 200 ° C and DR0.9 were performed to obtain a hollow fiber membrane having an outer diameter of 272 µm and a film thickness of 27 µm. When the inner and outer surfaces of this film were observed with a 12,000-fold SEM, as shown in FIGS. 1 and 2, the inner surface was smooth and no pores were observed, and the outer surface was about 0.2 μm thick. Many micropores were observed.
この中空繊維膜0.5gを長さ約10mmに切って比重びんに
詰め、真空ポンプで１×10-2Torr以下に脱気したのち水
銀を充填し、重量を計ったところ25℃における中空繊維
膜の体積は0.72cm3であった。ポリ−４−メチルペンテ
ン−１の真比重0.82を用いて計算すると、この中空繊維
膜の空孔率は18％となる。またこの中空繊維膜をガラス
管に封入し、ASTM D1434圧力法に準拠して25℃にて気
体透過速度を測定したところ、Ｑ（O2）＝4.5×10-5cm3
（STP）／（cm2・sec・cmHg）、Ｑ（CO2）＝3.4×10-5c
m3（STP）／（cm2・sec・cmHg）、α（O2/N2）＝1.2、
Ｌ（遮断層）＝1.3μｍであった。0.5 g of this hollow fiber membrane was cut into a length of about 10 mm, packed in a specific gravity bottle, degassed to 1 × 10 -2 Torr or less by a vacuum pump, filled with mercury, and weighed. Had a volume of 0.72 cm 3 . When calculated using the true specific gravity of poly-4-methylpentene-1 of 0.82, the porosity of this hollow fiber membrane is 18%. When this hollow fiber membrane was sealed in a glass tube and the gas permeation rate was measured at 25 ° C. in accordance with the ASTM D1434 pressure method, Q (O 2 ) = 4.5 × 10 −5 cm 3
(STP) / (cm 2 · sec · cmHg), Q (CO 2 ) = 3.4 × 10 -5 c
m 3 (STP) / (cm 2 · sec · cmHg), α (O 2 / N 2 ) = 1.2,
L (blocking layer) = 1.3 μm.
実施例１ 製造例１で得た中空繊維膜を用いて第３図に示す如き
人工肺を製作した。Example 1 An artificial lung as shown in FIG. 3 was produced using the hollow fiber membrane obtained in Production Example 1.
該人工肺はハウジング３、中空繊維膜５及び両端部の
高分子重合体隔壁６からなる。ハウジング３内には例え
ば8000本程度の中空繊維膜５が配列され、その両端部分
で高分子重合体隔壁６によって液密に封止されると同時
に開口され、ハウジング３とも液密に封止されている。
ハウジング３にはガスの入口４及び出口4aが設けられる
と同時に隔壁６の外側にキャップ１及び1aがリング２に
よってかぶせられており、キャップ１及び1aには血液の
入口７と出口7aが設けられている。The oxygenator comprises a housing 3, a hollow fiber membrane 5, and polymer polymer partitions 6 at both ends. Approximately 8000 hollow fiber membranes 5, for example, are arranged in the housing 3, and both ends thereof are liquid-tightly sealed by polymer polymer partition walls 6 and simultaneously opened, and the housing 3 is also liquid-tightly sealed. ing.
The housing 3 is provided with a gas inlet 4 and a gas outlet 4a, and at the same time, caps 1 and 1a are covered by a ring 2 on the outside of the partition wall 6. The caps 1 and 1a are provided with a blood inlet 7 and a blood outlet 7a. ing.
該人工肺（有効膜面積0.8m2）の中空部側に、膜を濡
らす液体である70％エタノールを200cm3/minで流し、0.
5kgf/cm2の膜間圧力差を設定したところ、70％エタノー
ルの膜透過量は0.8cm3/（min・m2）であり、該膜が実質
的に液体を透過させない遮断層を有する事が明らかとな
った。70% ethanol, which is a liquid for wetting the membrane, was flowed at 200 cm 3 / min through the hollow part of the oxygenator (effective membrane area 0.8 m 2 ) at 0.
When setting the transmembrane pressure difference of 5 kgf / cm 2, membrane permeation amount of 70% ethanol is 0.8cm 3 / (min · m 2 ), it has a barrier layer membrane is impermeable to substantially liquid Became clear.
次いで、該人工肺のガス交換能を調べるため、新鮮ヘ
パリン添加牛血を用い、36℃、ヘモグロビン含量12.1g/
dl、酸素飽和度65％、炭酸ガス分圧45mmHgの状態の標準
静脈血を調製し、これを該人工肺の中空部に通し、中部
繊維膜外部側には100％酸素を１/minの流速で流した
場合に、人工肺出口側の酸素飽和度が95％以上を保つ最
大血液流血（MBF）を求めた。Then, in order to examine the gas exchange capacity of the oxygenator, using fresh heparin-added bovine blood, 36 ° C., hemoglobin content 12.1 g /
Prepare standard venous blood in a state of dl, oxygen saturation of 65%, carbon dioxide partial pressure of 45 mmHg, pass this through the hollow part of the oxygenator, and supply 100% oxygen at a flow rate of 1 / min to the outside of the middle fiber membrane. The maximum blood flow (MBF) at which the oxygen saturation at the outlet side of the artificial lung maintained 95% or more when the blood flow was set at (1).
さらに、雑種成犬を用い、静脈−人工肺−動脈の部分
体外循環を24時間施行し、血漿の漏出量を測定した。表
−１に示した結果より、本発明の人工肺は血漿の漏出が
なく、実用上十分なガス交換能を有する事が明らかであ
る。Furthermore, partial extracorporeal circulation of vein-artificial lung-artery was performed for 24 hours using adult mongrel dogs, and the amount of plasma leakage was measured. From the results shown in Table 1, it is clear that the oxygenator of the present invention does not leak plasma and has a sufficient gas exchange capacity for practical use.
製造例２ 紡糸温度が300℃である事および非晶延伸の延伸倍率
が1.2である事以外は製造例１と全く同様にして中空繊
維膜を製造した。この中空繊維膜には、SEM観察によれ
ば、内表面、外表面共にSEMの解像力（約30Å）以上の
孔径の細孔は全く認められなかった。また、この膜の外
径は250μｍ、膜厚は25μｍ、空孔率は11％、酸素透過
速度Ｑ（O2）は８×10-6cm3（STP）／（cm2・sec・cmH
g）、αは4.1、Ｌは2.5μｍ、Ｑ（CO2）は3.9×10-5cm3
（STP）／（cm2・sec・cmHg）であった。Production Example 2 A hollow fiber membrane was produced in exactly the same manner as in Production Example 1 except that the spinning temperature was 300 ° C. and the draw ratio of amorphous stretching was 1.2. According to the SEM observation, no pores having a pore size larger than the resolving power of the SEM (about 30 °) were recognized on both the inner surface and the outer surface of the hollow fiber membrane. The outer diameter of this film is 250 μm, the film thickness is 25 μm, the porosity is 11%, and the oxygen permeation rate Q (O 2 ) is 8 × 10 −6 cm 3 (STP) / (cm 2 · sec · cmH).
g), α is 4.1, L is 2.5 μm, Q (CO 2 ) is 3.9 × 10 −5 cm 3
(STP) / (cm 2 · sec · cmHg).
実施例２ 製造例２で得た中空繊維幕を用いて実施例１と同様に
して作製した人工肺は、70％エタノールの透過量が0.15
cm3/（min・m2）であつた。この人工肺について実施例
１と同様にして測定したMBFと血漿漏出量を表−１に示
す。Example 2 An artificial lung produced in the same manner as in Example 1 using the hollow fiber curtain obtained in Production Example 2 had a permeation amount of 70% ethanol of 0.15.
cm 3 / (min · m 2 ). Table 1 shows the MBF and the amount of plasma leakage of this artificial lung measured in the same manner as in Example 1.
製造例３ メルトインデックス（ASTM D1238による）3.5のポリ
プロピレンを、直径6mmの円環型中空繊維用ノズルを用
いて、紡糸温度250℃、引取速度300m/分、ドラフト270
で溶融紡糸し、外径345μｍ、膜厚34μｍの中空繊維を
得た。この時ノズル口下３〜35cmの範囲を温度８℃、風
速1.5m/秒の風で冷却した。得られた中空繊維を温度35
℃、延伸倍率（DR）1.2で、ローラー系を用いて連続的
に非晶延伸し、次いで140℃、DR1.3で熱風循環型恒温槽
中に導入して５秒間滞留させる事により熱処理を行な
い、引続き10℃、DR1.2の冷延伸、140℃、DR1.2の熱延
伸、および140℃、DR0.9の熱固定を行なって、外径257
μｍ、内径205μｍ、膜厚26μｍの中空繊維膜を得た。
この膜の内外表面を12,000倍のSEMで観察したところ、
内表面には微細孔がほとんど認められず、外表面には0.
1μｍ程度の微細孔が多数存在した。この膜の空孔率は3
1％、酸素透過速度Ｑ（O2）は3.4×10-4cm3（STP）／
（cm2・sec・cmHg）、αは0.94、Ｌは1.6μｍ、Ｑ（C
O2）は2.92×10-4cm3（STP）／（cm2・sec・cmHg）であ
った。尚、Ｌの計算はＱ（O2）を用いた場合は誤差が大
きいため、Ｑ（CO2）に基づいた。Production Example 3 A polypropylene having a melt index of 3.5 (according to ASTM D1238) was spun at a spinning temperature of 250 ° C., a take-up speed of 300 m / min, and a draft of 270 using an annular hollow fiber nozzle having a diameter of 6 mm.
To obtain hollow fibers having an outer diameter of 345 μm and a film thickness of 34 μm. At this time, a range of 3 to 35 cm below the nozzle opening was cooled by wind at a temperature of 8 ° C. and a wind speed of 1.5 m / sec. The obtained hollow fiber was cooled to a temperature of 35.
Amorphous stretching is continuously performed using a roller system at a temperature of 140 ° C. and a draw ratio (DR) of 1.2, and then heat treatment is performed at 140 ° C. and a DR of 1.3 by introducing into a hot-air circulating thermostat and remaining for 5 seconds. Then, cold stretching at 10 ° C and DR1.2, hot stretching at 140 ° C and DR1.2, and heat setting at 140 ° C and DR0.9 were performed to obtain an outer diameter of 257.
A hollow fiber membrane having a thickness of 26 μm was obtained.
When the inner and outer surfaces of this film were observed with a 12,000-fold SEM,
Almost no micropores are found on the inner surface and 0.
Many micropores of about 1 μm were present. The porosity of this film is 3
1%, oxygen transmission rate Q (O 2 ) is 3.4 × 10 -4 cm 3 (STP) /
(Cm 2 · sec · cmHg), α is 0.94, L is 1.6 μm, Q (C
O 2 ) was 2.92 × 10 −4 cm 3 (STP) / (cm 2 · sec · cmHg). Note that the calculation of L was based on Q (CO 2 ) because the error was large when Q (O 2 ) was used.
実施例３ 製造例３で得た中空繊維膜を用いて実施例１と同様に
して人工肺を作製した。その70％エタノールの膜透過量
は22cm3/（min・m2）であった。人工肺としてのガス交
換能および血漿漏出量を実施例１と同様に測定した結果
を、表−１に示す。Example 3 An artificial lung was produced in the same manner as in Example 1 using the hollow fiber membrane obtained in Production Example 3. The membrane permeation amount of the 70% ethanol was 22 cm 3 / (min · m 2 ). Table 1 shows the results of measuring the gas exchange capacity and the amount of plasma leakage as an artificial lung in the same manner as in Example 1.
製造例４ メルトインデックス1.8、密度0.96のポリエチレン
を、直径10mmの円環型中空繊維用ノズルを用いて、紡糸
温度230℃、ドラフト700、冷却風温12℃、冷却風速1.5m
/sで溶融紡糸した。得られた中空繊維を、ローラー系に
て連続的に、20℃、DR1.2で非晶延伸し、80℃、DR1.2、
滞留時間５秒で熱処理し、20℃、DR1.3で冷延伸し、60
℃、DR1.2で熱延伸し、80℃、DR1.0で熱固定して、内径
200μｍ、膜厚24μｍの中空繊維膜を得た。SEM観察によ
れば、この膜は、内外両表面共に細孔は認められず、膜
断面の内外表面間は孔径約１μｍの細孔から成る多孔質
層であった。またこの膜の空孔率は25％、酸素透過速度
Ｑ（O2）は1.5×10-4cm3（STP）／（cm2・sec・cmH
g）、αは0.95、Ｌは0.6μｍ、Ｑ（CO2）は1.33×10-4c
m3（STP）／（cm2・sec・cmHg）であった。尚、Ｌは製
造例３と同様にして算出した。Production Example 4 Polyethylene having a melt index of 1.8 and a density of 0.96 was spun at a spinning temperature of 230 ° C., a draft of 700, a cooling air temperature of 12 ° C., and a cooling air speed of 1.5 m using an annular hollow fiber nozzle having a diameter of 10 mm.
/ s melt spinning. The obtained hollow fibers are continuously stretched in an amorphous state at 20 ° C. and DR 1.2 by a roller system, and are then stretched at 80 ° C. and DR 1.2.
Heat treatment with a residence time of 5 seconds, cold drawing at 20 ° C, DR1.3, 60
℃, DR1.2 hot stretch, 80 ℃, DR1.0 heat fixing,
A hollow fiber membrane having a thickness of 200 μm and a thickness of 24 μm was obtained. According to SEM observation, no pore was recognized on both the inner and outer surfaces of this film, and a porous layer composed of pores having a pore diameter of about 1 μm was formed between the inner and outer surfaces of the film cross section. The porosity of this film is 25%, and the oxygen transmission rate Q (O 2 ) is 1.5 × 10 −4 cm 3 (STP) / (cm 2 · sec · cmH
g), α is 0.95, L is 0.6 μm, and Q (CO 2 ) is 1.33 × 10 -4 c
m 3 (STP) / (cm 2 · sec · cmHg). Note that L was calculated in the same manner as in Production Example 3.
実施例４ 製造例４で得た中空繊維膜を用いて実施例１と同様に
して人工肺を作製した。70％エタノールの透過速度は1
4.8cm3（min・m2）であり、本実施例の膜も、実質的に
液体が透過しないエタノール遮断層を有していた。表−
１にガス交換能と血漿漏出量の評価結果を示す。Example 4 An artificial lung was produced in the same manner as in Example 1 using the hollow fiber membrane obtained in Production Example 4. The permeation rate of 70% ethanol is 1
It was 4.8 cm 3 (min · m 2 ), and the membrane of this example also had an ethanol barrier layer that was substantially impermeable to liquid. Table-
1 shows the results of evaluation of gas exchange capacity and plasma leakage.
比較例 １ 中空繊維膜として、内径200μｍ、膜厚30μ、空孔率4
0％、最大孔径0.6μの連通孔タイプの多孔質ポリプロピ
レン中空繊維膜を用いた他は実施例１と同様にして0.8m
2の人工肺を作製し、血液でのMBFおよび血漿漏出量を測
定した。結果を表−１に示す。Comparative Example 1 As hollow fiber membrane, inner diameter 200 μm, thickness 30 μ, porosity 4
0.8% in the same manner as in Example 1 except that a porous polypropylene hollow fiber membrane of a communication hole type having 0% and a maximum pore diameter of 0.6 μm was used.
Two artificial lungs were prepared, and the MBF in blood and the amount of plasma leakage were measured. The results are shown in Table 1.
比較例 ２ 中空繊維膜として、内径200μ、膜厚100μのシリコン
中空繊維膜を用いた他は実施例１と同様にして0.8m2の
人工肺を作製し、血液でのMBFおよび血液漏出量を測定
した。結果を表−１に示す。Comparative Example 2 A 0.8 m 2 artificial lung was prepared in the same manner as in Example 1 except that a silicon hollow fiber membrane having an inner diameter of 200 μ and a film thickness of 100 μ was used as the hollow fiber membrane, and the MBF and blood leakage amount of blood were measured. It was measured. The results are shown in Table 1.
製造例５ 紡糸ドラフトが350、熱処理条件が220℃、DR1.1、熱
延伸DRが1.4であること以外には実施例１と同条件で製
造した中空繊維膜は、外径255μｍ、膜厚26μｍであつ
た。SEMにより観察すると、中空糸内表面には孔径約0.1
μｍり細孔が1cm2当り約50×109個開口しているのが観
察されるのに対し、外表面にはその1/50程度の開口しか
存在しなかつた。この膜の気体透過性はＱ（O2）＝３×
10-4cm3（STP）／（cm2・sec・cmHg）、α＝1.02、Ｑ
（CO2）＝3.4×10-4cm3（STP）／（cm2・sec・cmHg）で
あり、第（１）式およびポリ４メチルペンテン−１の特
性値Ｐ（O2）＝2.0×10-9cm3（STP）／（cm2・sec・cmH
g）、α１＝4.1、を用いて計算した遮断層厚みＬは0.6
μｍであつた。製造例１と同様にして測定したこの中空
糸の空孔率は23.5％であつた。 Production Example 5 A hollow fiber membrane produced under the same conditions as in Example 1 except that the spinning draft was 350, the heat treatment conditions were 220 ° C., DR 1.1, and the hot drawing DR was 1.4, the outer diameter was 255 μm and the film thickness was 26 μm. It was. Observation by SEM revealed that the inner diameter of the hollow fiber was about 0.1
It was observed that about 50 × 10 9 μm pores were opened per cm 2 , whereas only about 1/50 of the openings were present on the outer surface. The gas permeability of this membrane is Q (O 2 ) = 3 ×
10 -4 cm 3 (STP) / (cm 2 · sec · cmHg), α = 1.02, Q
(CO 2 ) = 3.4 × 10 −4 cm 3 (STP) / (cm 2 · sec · cmHg), and the formula (1) and the characteristic value P (O 2 ) of poly-4-methylpentene-1 = 2.0 × 10 -9 cm 3 (STP) / (cm 2 · sec · cmH
g), the barrier layer thickness L calculated using α 1 = 4.1 is 0.6
μm. The porosity of this hollow fiber measured in the same manner as in Production Example 1 was 23.5%.
実施例５ 製造例５で得た中空繊維膜Ｂを第４図に示すように縦
糸で簾状に編組して成形した中空繊維シートＡを丸めて
第３図に示すように円筒状ハイジング３内に収容して、
断面積2.5m2の膜型人工肺を組み立てた。この膜型人工
肺の70％エタノール透過速度は2.1cm3/（min・m2）であ
つた。また中空繊維膜の外側に実施例１で使用した牛血
液を流し、内側に100％酸素を１/minの流速で流した
場合の人工肺出口側の酸素飽和度が95％以上を保つ最大
血液流量は2950cm3/（min・m2）であつた。また、この
膜型人工肺は１週間の連続使用においても、血漿のリー
クは全くなく、ガス交換能の経時的低下も殆んど認めら
れなかつた。さらに使用後に生理食塩水で血液を洗浄除
去したところ、中空糸外表面への血栓の付着も極めて少
なかつた。Example 5 A hollow fiber sheet A obtained by braiding the hollow fiber membrane B obtained in Production Example 5 with a warp into braided shape as shown in FIG. 4 and rolling the hollow fiber sheet A into a cylindrical shape 3 as shown in FIG. Housed in
A membrane oxygenator with a cross section of 2.5 m 2 was assembled. The 70% ethanol permeation rate of this membrane oxygenator was 2.1 cm 3 / (min · m 2 ). In addition, when the bovine blood used in Example 1 is flown outside the hollow fiber membrane and 100% oxygen is flowed at a flow rate of 1 / min inside the hollow fiber membrane, the maximum blood that maintains the oxygen saturation at the outlet side of the artificial lung at 95% or more. The flow rate was 2950 cm 3 / (min · m 2 ). In addition, this membrane-type oxygenator did not leak plasma at all even after one week of continuous use, and almost no decrease in gas exchange ability with time was observed. Further, when the blood was washed off with a physiological saline solution after use, adhesion of the thrombus to the outer surface of the hollow fiber was extremely small.
実施例６ 製造例５と同じ膜を細い粘着テープを用いて簾状に配
列した他は実施例５と同様にして膜面積2.0m2の外部灌
流型人工肺を組み立て、評価したところ、この肺のMBF
は2200cm3/（min・m2）であつた。Example 6 An externally perfused oxygenator having a membrane area of 2.0 m 2 was assembled and evaluated in the same manner as in Example 5 except that the same membrane as that in Production Example 5 was arranged in the form of a blind using a thin adhesive tape. MBF
Was 2200 cm 3 / (min · m 2 ).
製造例６ 熱処理の時間が10秒、冷延伸倍率が1.3、熱延伸倍率
が1.8であること以外は製造例５と同様の方法で製造し
た中空繊維膜の特性はＱ（O2）＝3.0×10-4cm3（STP）
／（cm2・sec・cmHg）、α＝0.98、Ｌ＝1.1μｍ、Ｑ（C
O2）＝3.0×10-4cm3（STP）／（cm2・sec・cmHg）、空
孔率＝27％であつた。Production Example 6 The characteristics of the hollow fiber membrane produced by the same method as in Production Example 5 except that the heat treatment time was 10 seconds, the cold stretching ratio was 1.3, and the hot stretching ratio was 1.8 were Q (O 2 ) = 3.0 × 10 -4 cm 3 (STP)
/ (Cm 2 · sec · cmHg), α = 0.98, L = 1.1 μm, Q (C
O 2 ) = 3.0 × 10 −4 cm 3 (STP) / (cm 2 · sec · cmHg), and the porosity was 27%.
実施例７ 製造例６で得た中空繊維膜を用いて実施例５と同様に
して人工肺を製作した。この肺のエタノール透過速度は
3.9cm3/（min・m2）であり、MBFは2500cm3/（min・m2）
であつた。Example 7 An artificial lung was produced in the same manner as in Example 5 using the hollow fiber membrane obtained in Production Example 6. The rate of ethanol permeation through this lung is
3.9cm 3 / (min ・ m 2 ), MBF 2500cm 3 / (min ・ m 2 )
It was.
実施例８ 中空繊維膜に実施例５と同じ物を用いたほかは実施例
１と同じ人工肺を製作し、実施例１と同じ試験を行つ
た。この人工肺のエタノール透過速度は2.1cm3/（min・
m2）、最大血流量は1410cm3/minであつた。Example 8 An artificial lung similar to that of Example 1 was manufactured except that the same hollow fiber membrane as that of Example 5 was used, and the same test as that of Example 1 was performed. Ethanol permeation rate of this oxygenator is 2.1 cm 3 / (min
m 2 ) and the maximum blood flow was 1410 cm 3 / min.
実施例９ 中空繊維膜に実施例７と同じ物を用いたほかは実施例
１と同じ人工肺を製作し、実施例１と同じ試験を行つ
た。この人工肺のエタノール透過速度は3.9cm3（/min・
m2）、最大血流量は1260cm3/minであつた。Example 9 An artificial lung similar to that of Example 1 was manufactured except that the same hollow fiber membrane as that of Example 7 was used, and the same test as that of Example 1 was performed. The oxygen transmission rate of this oxygenator is 3.9cm 3 (/ min ・
m 2 ) and the maximum blood flow was 1260 cm 3 / min.
第１図および第２図は、製造例１の中空繊維の形状（表
面の微細構造）を示すための走査型電子顕微鏡写真で、
第１図は該中空繊維の内表面（孔の存在は観察されな
い）を示し、第２図は該中空繊維の外表面（約0.2μｍ
の細孔が認められる）を示す。写真の倍率は12,000倍
で、写真の右下の短かい白線の長さが0.5μｍに相当す
る。第３図は、本発明の人工肺の実施例の縦断面図であ
る。又、第４図は、実施例５〜７で用いられる簾状中空
繊維膜シートを示す状態図である。尚、第３図中の符号
は次の通りである。 １……キャップ、1a……キャップ、２……リング、３…
…ハウジング、４……ガス入口／血液入口、4a……ガス
出口／血液出口、５……中空繊維膜、６……高分子重合
体隔壁、７……血液入口／ガス入口、7a……血液出口／
ガス出口。 又、第４図中の符号は次の通りである。 Ａ……簾状の中空繊維シート Ｂ……中空繊維膜。1 and 2 are scanning electron micrographs showing the shape (fine structure of the surface) of the hollow fiber of Production Example 1,
FIG. 1 shows the inner surface of the hollow fiber (the presence of pores is not observed), and FIG. 2 shows the outer surface of the hollow fiber (about 0.2 μm).
Are observed). The magnification of the photograph is 12,000 times, and the length of the short white line at the lower right of the photograph is equivalent to 0.5 μm. FIG. 3 is a longitudinal sectional view of an embodiment of the oxygenator according to the present invention. FIG. 4 is a state diagram showing a cord-like hollow fiber membrane sheet used in Examples 5 to 7. The reference numerals in FIG. 3 are as follows. 1 ... Cap, 1a ... Cap, 2 ... Ring, 3 ...
... Housing, 4 ... Gas inlet / blood inlet, 4a ... Gas outlet / blood outlet, 5 ... Hollow fiber membrane, 6 ... Polymer partition, 7 ... Blood inlet / gas inlet, 7a ... Blood Exit/
Gas outlet. The reference numerals in FIG. 4 are as follows. A: hollow fiber sheet in the shape of a blind B: hollow fiber membrane
───────────────────────────────────────────────────── フロントページの続き (56)参考文献 特開 昭62−106770（ＪＰ，Ａ) 特開 昭61−31164（ＪＰ，Ａ) 特開 昭60−150757（ＪＰ，Ａ) 特開 昭62−64373（ＪＰ，Ａ) 特開 昭60−249968（ＪＰ，Ａ) 特開 昭59−108563（ＪＰ，Ａ) ──────────────────────────────────────────────────続 き Continuation of the front page (56) References JP-A-62-106770 (JP, A) JP-A-61-31164 (JP, A) JP-A-60-150575 (JP, A) 64373 (JP, A) JP-A-60-249968 (JP, A) JP-A-59-108563 (JP, A)
Claims (1)
酸素もしくは酸素含有気体を流すことにより膜を介して
血液と気体間でガス交換を行う膜型人工肺において、該
膜は25℃における酸素透過速度Ｑ（O2）が１×10-6［cm
3（STP）/cm2・sec・cmHg］以上でありかつエタノール
を実質的に不透過とする遮断層を有し、空孔率が７〜50
％であり、主としてポリオレフイン系重合体からなり、
内径が10〜500μｍでかつ厚さが５〜100μｍの中空繊維
膜であることを特徴とする膜型人工肺。1. A membrane-type oxygenator in which gas is exchanged between blood and gas through a membrane by flowing blood on one side of the membrane and flowing oxygen or an oxygen-containing gas on the other side of the membrane. Has an oxygen transmission rate Q (O 2 ) at 25 ° C. of 1 × 10 −6 [cm
3 (STP) / cm 2 · sec · cmHg] or more and a barrier layer substantially impermeable to ethanol, and has a porosity of 7 to 50.
%, Mainly consisting of a polyolefin-based polymer,
A membrane-type oxygenator comprising a hollow fiber membrane having an inner diameter of 10 to 500 µm and a thickness of 5 to 100 µm.
Priority Applications (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| JP63170783A JP2700170B2 (en) | 1987-07-11 | 1988-07-11 | Membrane oxygenator |
Applications Claiming Priority (3)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| JP62-172067 | 1987-07-11 | ||
| JP17206787 | 1987-07-11 | ||
| JP63170783A JP2700170B2 (en) | 1987-07-11 | 1988-07-11 | Membrane oxygenator |
Related Child Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| JP4073308A Division JPH07121340B2 (en) | 1987-07-11 | 1992-02-25 | Hollow fiber membrane |
Publications (2)
| Publication Number | Publication Date |
|---|---|
| JPH01104271A JPH01104271A (en) | 1989-04-21 |
| JP2700170B2 true JP2700170B2 (en) | 1998-01-19 |
Family
ID=26493679
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| JP63170783A Expired - Lifetime JP2700170B2 (en) | 1987-07-11 | 1988-07-11 | Membrane oxygenator |
Country Status (1)
| Country | Link |
|---|---|
| JP (1) | JP2700170B2 (en) |
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