JPH09308685A - Hollow fiber membrane for blood purification and blood purifying device - Google Patents
Hollow fiber membrane for blood purification and blood purifying deviceInfo
- Publication number
- JPH09308685A JPH09308685A JP8747697A JP8747697A JPH09308685A JP H09308685 A JPH09308685 A JP H09308685A JP 8747697 A JP8747697 A JP 8747697A JP 8747697 A JP8747697 A JP 8747697A JP H09308685 A JPH09308685 A JP H09308685A
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- Japan
- Prior art keywords
- hollow fiber
- fiber membrane
- blood
- blood purification
- 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.)
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- External Artificial Organs (AREA)
- Separation Using Semi-Permeable Membranes (AREA)
Abstract
Description
【０００１】[0001]
【発明の属する技術分野】本発明は、ポリスルホン樹脂
からなる血液浄化用中空糸膜及びそれを用いた血液浄化
器に関する。TECHNICAL FIELD The present invention relates to a hollow fiber membrane for blood purification made of polysulfone resin and a blood purifier using the same.
【０００２】[0002]
【従来の技術】腎臓の機能障害に起因する腎不全は、血
清尿素窒素量（ＢＵＮ）、血中クレアチニン量、血中メ
チルグアニジン量等が異常に増加し、種々の疾病を惹起
することから生命に直接関与する病気である。現在、腎
不全の保存療法として、各種の人工腎臓が使用されてい
るが、この人工腎臓の主要なものは、中空糸膜モジュー
ルを用いて患者の血液透析、血液濾過を行うことによ
り、尿素等の血液中老廃物を患者の血中から除去するも
のである。2. Description of the Related Art Renal failure due to renal dysfunction causes an abnormal increase in serum urea nitrogen (BUN), blood creatinine, blood methylguanidine, etc., and causes various diseases. Is a disease directly related to. Currently, various artificial kidneys are used as conservative therapy for renal failure. The main artificial kidneys are urea, etc., which are obtained by performing hemodialysis and hemofiltration of patients using hollow fiber membrane modules. It removes the waste products in the blood from the blood of patients.
【０００３】このような中空糸膜の素材としては、セル
ロース、セルロースアセテート、ポリアミド、ポリアク
リロニトリル、エチレン−ビニルアルコール共重合体、
ポリメチルメタクリレート、ポリスルホン等のポリマー
が使用されている。なかでも、ポリスルホン樹脂からな
る中空糸膜は、耐熱性、耐薬品性、機械的強度、生体適
合性等に優れ、最近注目されているものである。Materials for such hollow fiber membranes include cellulose, cellulose acetate, polyamide, polyacrylonitrile, ethylene-vinyl alcohol copolymer,
Polymers such as polymethylmethacrylate and polysulfone are used. Among them, hollow fiber membranes made of polysulfone resin have been recently attracting attention because of their excellent heat resistance, chemical resistance, mechanical strength and biocompatibility.
【０００４】特公平５−５４３７３号公報、特開平６−
２９６６８６号公報には、ポリスルホン樹脂からなる血
液浄化用中空糸膜として、親水性ポリマーであるポリビ
ニルピロリドン、ポリエチレングリコール等が含有され
た中空糸膜が開示されている。これらは、製膜前の原液
の段階でポリスルホン樹脂と親水性ポリマーとを混合し
た後、製膜する方法により得られる。JP-B-5-54373 and JP-A-6-
Japanese Patent No. 296686 discloses a hollow fiber membrane containing a hydrophilic polymer such as polyvinylpyrrolidone or polyethylene glycol as a blood purification hollow fiber membrane made of polysulfone resin. These are obtained by a method of forming a film after mixing the polysulfone resin and the hydrophilic polymer at the stage of the stock solution before film formation.
【０００５】また、特開平６−２３８１３９号公報に
は、このような親水性ポリマー含有ポリスルホン樹脂製
血液浄化用中空糸膜を、まずポリスルホン樹脂からなる
血液浄化用中空糸膜を製膜し、モジュールに組み立てた
後、中空糸の内側に親水性ポリマーの溶液を導入し、中
空糸膜内側面に親水性ポリマーをコーティングする方法
により得る技術が開示されている。In Japanese Patent Laid-Open No. 6-238139, such a hydrophilic polymer-containing polysulfone resin hollow fiber membrane for blood purification is first formed into a hollow fiber membrane for blood purification made of polysulfone resin, and a module is prepared. There is disclosed a technique in which a solution of a hydrophilic polymer is introduced into the inside of the hollow fiber after assembling the same, and the hydrophilic polymer is coated on the inner surface of the hollow fiber membrane.
【０００６】しかしながら、このような血液浄化用中空
糸膜では、臨床使用時に親水性ポリマーが溶出するおそ
れが皆無ではなく安全性に問題が残る。また、モジュー
ル組み立て後、モジュール充填液中に、親水性ポリマー
が溶出し、膜性能が経時的に変化するおそれもある。そ
こで、特開平６−２３８１３９号公報、特開平６−３３
９６２０号公報開示の技術では、放射線処理や熱処理に
よりポリビニルピロリドンを架橋し、この溶出を抑制し
ようとする試みがなされているが、充分なものではなか
った。However, in such a hollow fiber membrane for blood purification, there is no possibility that the hydrophilic polymer will elute during clinical use, and there remains a problem in safety. Further, after the module is assembled, the hydrophilic polymer may be eluted in the module filling liquid, and the membrane performance may change with time. Therefore, JP-A-6-238139 and JP-A-6-33 are used.
In the technology disclosed in Japanese Patent Publication No. 9620, an attempt has been made to cross-link polyvinylpyrrolidone by radiation treatment or heat treatment to suppress this elution, but it was not sufficient.
【０００７】また、血液浄化用中空糸膜中における親水
性ポリマーの含有量が多くなると、血液浄化用中空糸膜
の膜自体の機械的強度が低下し、透水速度も低下する欠
点もあった。更に、このような膜は、製膜後の保存中に
空気中の水分を吸収するため、保存のために特別な設備
が必要となる等の欠点もあった。Further, when the content of the hydrophilic polymer in the blood purifying hollow fiber membrane increases, the mechanical strength of the membrane itself of the blood purifying hollow fiber membrane lowers and the water permeation rate also lowers. Further, such a film has a drawback that it requires special equipment for storage because it absorbs moisture in the air during storage after film formation.
【０００８】特開昭６１−２３２８６０号公報、特開昭
６３−１０５７７０号公報には、親水性ポリマーを含有
することがないポリスルホン樹脂製中空糸膜が開示され
ているが、これらは血液から血漿を濾過分離するための
血漿分離膜や、分離された血漿から特定の血漿成分を選
択分離・回収するための血漿成分分離膜としてのみ使用
されうるものであって、血液浄化用中空糸膜としては使
用することができるものではなかった。Japanese Unexamined Patent Publication Nos. 61-232860 and 63-105770 disclose hollow fiber membranes made of polysulfone resin containing no hydrophilic polymer. It can be used only as a plasma separation membrane for filtering and separating, and a plasma component separation membrane for selectively separating and recovering a specific plasma component from the separated plasma. It wasn't something that could be used.
【０００９】特開昭６１−１１３４６０号公報には、急
性腎不全の治療のための連続的血液透析・濾過用、持続
的血液濾過用膜が開示されているが、通常の慢性腎不全
の治療のための血液透析や血液濾過用の実用的なもので
はなかった。Japanese Unexamined Patent Publication (Kokai) No. 61-113460 discloses a membrane for continuous hemodialysis / filtration and continuous hemofiltration for the treatment of acute renal failure. It wasn't practical for hemodialysis or hemofiltration.
【００１０】[0010]
【発明が解決しようとする課題】本発明は、上記現状に
鑑み、膜の成分が溶出する危険が全くなく、安全で、か
つ血液透析及び血液濾過に好適であるポリスルホン樹脂
製血液浄化用中空糸膜、並びに、血液透析器、血液透析
濾過器及び血液濾過器として好適に使用することができ
る血液浄化器を提供することを目的とするものである。In view of the above situation, the present invention is a polysulfone resin-made hollow fiber for blood purification which is safe without any danger of elution of membrane components, and is suitable for hemodialysis and hemofiltration. An object of the present invention is to provide a membrane, a hemodialyzer, a hemodialysis filter, and a blood purifier that can be suitably used as a hemofilter.
【００１１】[0011]
【課題を解決するための手段】本発明の血液浄化用中空
糸膜は、ポリスルホン樹脂からなる血液浄化用中空糸膜
であって、内表面には、平均巾０．０２〜０．１５μｍ
のスリット状微細孔を有し、外表面には、平均孔径０．
１〜１μｍの微細孔を有し、内部は、スポンジ状構造を
有し、内表面、外表面及び内部のいずれにおいても径１
０μｍを超える巨大空洞を有することがなく、透水速度
が、４００〜２５００ｍｌ／ｍ2 ・ｈｒ・ｍｍＨｇであ
り、総タンパクの透過率が、１％以下であることを特徴
とするものである。The hollow fiber membrane for blood purification of the present invention is a hollow fiber membrane for blood purification made of polysulfone resin, and the inner surface has an average width of 0.02 to 0.15 μm.
Of slit-like fine holes, and the outer surface has an average pore diameter of 0.
It has micropores of 1 to 1 μm, the inside has a sponge-like structure, and the diameter is 1 on both the inner surface, the outer surface and the inside.
It is characterized by not having a huge cavity exceeding 0 μm, a water permeation rate of 400 to 2500 ml / m 2 · hr · mmHg, and a total protein permeability of 1% or less.
【００１２】また、本発明の血液浄化器は、血液流入口
及び血液流出口と、透析液流入口及び透析液流出口、又
は、濾液流出口とを備えた筒状のハウジング内に、上記
本発明の血液浄化用中空糸膜が収納されていることを特
徴とするものである。以下に本発明を詳述する。Further, the blood purifier of the present invention comprises the above-mentioned book in a cylindrical housing provided with a blood inlet and a blood outlet and a dialysate inlet and a dialysate outlet or a filtrate outlet. The hollow fiber membrane for blood purification of the invention is stored. Hereinafter, the present invention will be described in detail.
【００１３】本発明の血液浄化用中空糸膜は、ポリスル
ホン樹脂からなる。上記ポリスルホン樹脂としては特に
限定されず、例えば、下記式（１）で表される繰り返し
単位を有する樹脂、下記式（２）で表される繰り返し単
位を有する樹脂等を挙げることができる。The blood purifying hollow fiber membrane of the present invention comprises a polysulfone resin. The polysulfone resin is not particularly limited, and examples thereof include a resin having a repeating unit represented by the following formula (1) and a resin having a repeating unit represented by the following formula (2).
【００１４】[0014]
【化１】 Embedded image
【００１５】なかでも、式（１）で表される繰り返し単
位を有する樹脂は、限外濾過膜の素材として古くから利
用されており、機械的強度、耐熱性、耐薬品性及び生体
適合性等の基本性能に優れており、本発明の血液浄化用
中空糸膜の素材として特に好ましい。Among them, a resin having a repeating unit represented by the formula (1) has been used as a material for an ultrafiltration membrane for a long time, and has mechanical strength, heat resistance, chemical resistance and biocompatibility. It has excellent basic performance and is particularly preferable as a material for the hollow fiber membrane for blood purification of the present invention.
【００１６】本発明の血液浄化用中空糸膜は、その内表
面に、多数のスリット状微細孔を有する。上記スリット
状微細孔の存在は、例えば、上記中空糸膜の内表面を走
査型電子顕微鏡（ＳＥＭ）により倍率１００００倍で観
察することにより確認することができる。The hollow fiber membrane for blood purification of the present invention has a large number of slit-shaped fine pores on its inner surface. The presence of the slit-shaped micropores can be confirmed, for example, by observing the inner surface of the hollow fiber membrane with a scanning electron microscope (SEM) at a magnification of 10,000 times.
【００１７】上記スリット状微細孔は、中空糸膜の長さ
方向に細長く存在する微細孔である。上記微細孔の中空
糸膜の長さ方向の長さは特に限定されないが、例えば、
微細孔短径の２倍以上、好ましくは３倍以上がよい。上
記スリット状微細孔の膜内表面における分布密度は、均
一であることが好ましく、また高いことが好ましい。ま
た、上記微細孔の短径は、アルブミン等の有用タンパク
の漏出を低め、安定した分画特性を得るために、均一で
あることが好ましい。The slit-shaped micropores are micropores that are elongated in the length direction of the hollow fiber membrane. The length in the length direction of the hollow fiber membrane of the fine pores is not particularly limited, but, for example,
The minor axis of the micropores is preferably twice or more, more preferably three times or more. The distribution density of the slit-shaped micropores on the inner surface of the film is preferably uniform and preferably high. Further, it is preferable that the minor diameters of the micropores are uniform in order to reduce leakage of useful proteins such as albumin and to obtain stable fractionation characteristics.
【００１８】上記スリット状微細孔の平均巾の下限は、
０．０２μｍである。ここに、平均巾とは、その微細孔
の短径の平均値を意味する。平均巾が０．０２μｍ未満
であると、透水速度が小さくなり血液濾過時の限外濾過
速度が小さくなり、また、経時的に目詰まりを起こしや
すくなり、尿素、クレアチニン等の尿毒性物質の透過率
が低下する。より好ましい平均巾の下限は、０．０４μ
ｍである。上記スリット状微細孔の平均巾の上限は、
０．１５μｍである。平均巾が０．１５μｍを超える
と、特に血液濾過の場合にタンパクの漏出が大きくなり
低タンパク血症の原因となり臨床上問題が生じる。より
好ましい平均巾の上限は、０．１μｍである。The lower limit of the average width of the slit-shaped fine holes is
It is 0.02 μm. Here, the average width means the average value of the short diameters of the fine pores. When the average width is less than 0.02 μm, the water permeation rate becomes small, the ultrafiltration rate at the time of hemofiltration becomes small, and clogging easily occurs with time, and the permeation of uremic substances such as urea and creatinine The rate drops. The more preferable lower limit of the average width is 0.04 μ
m. The upper limit of the average width of the slit-like micropores is
0.15 μm. When the average width exceeds 0.15 μm, protein leakage becomes large particularly in hemofiltration, causing hypoproteinemia and causing clinical problems. A more preferable upper limit of the average width is 0.1 μm.
【００１９】本発明の血液浄化用中空糸膜は、その外表
面に、多数の微細孔を有する。上記微細孔の存在は、例
えば、上記中空糸膜の外表面をＳＥＭにより観察し、画
像処理をすることにより確認することができる。The hollow fiber membrane for blood purification of the present invention has a large number of fine pores on its outer surface. The presence of the fine pores can be confirmed, for example, by observing the outer surface of the hollow fiber membrane with an SEM and performing image processing.
【００２０】上記微細孔の平均孔径の下限は、０．１μ
ｍである。ここに、微細孔の孔径とは、上記画像処理に
より求めた開孔面積から、その面積を円とみなして換算
した直径を意味し、平均孔径とは、個々の孔の孔径とそ
の数より算術平均して求めた孔径を意味する。上記微細
孔の平均孔径が０．１μｍ未満であると、透水速度が小
さくなり、血液処理時の限外濾過速度が低下し、また、
透析性能（クリアランス）が低下する。より好ましい平
均孔径の下限は、０．１５μｍである。The lower limit of the average pore size of the fine pores is 0.1 μm.
m. Here, the pore size of the fine pores means the diameter calculated by considering the area as a circle from the open pore area obtained by the image processing, and the average pore size is calculated from the pore size and the number of individual pores. It means the average pore size. When the average pore diameter of the fine pores is less than 0.1 μm, the water permeation rate becomes low, the ultrafiltration rate at the time of blood treatment decreases, and
Dialysis performance (clearance) decreases. A more preferable lower limit of the average pore diameter is 0.15 μm.
【００２１】上記微細孔の平均孔径の上限は、１μｍで
ある。平均孔径が１μｍを超えると、アルブミン等の有
用タンパクの漏出量が多くなり、また、表面強度が小さ
くなって、取扱時に膜が損傷しやすくなる。より好まし
い平均孔径の上限は、０．８μｍである。上記微細孔
は、均一の孔径であることが好ましいが、特に均一であ
る必要はなく、不均一であってもよい。The upper limit of the average pore size of the fine pores is 1 μm. When the average pore diameter exceeds 1 μm, the amount of useful proteins such as albumin leaked out is large, and the surface strength is small, and the membrane is easily damaged during handling. A more preferable upper limit of the average pore diameter is 0.8 μm. The fine pores preferably have a uniform pore size, but they do not have to be particularly uniform and may be non-uniform.
【００２２】本発明の血液浄化用中空糸膜の外表面微細
孔の開孔率の下限は、１％が好ましい。ここに、外表面
微細孔の開孔率とは、単位面積当たりの個々の孔の開孔
面積の総和の外表面積に対する割合を百分率で示したも
のを意味する。開孔率が１％未満であると、透水速度が
低くなる。より好ましくは５％である。本発明の血液浄
化用中空糸膜の外表面微細孔の開孔率の上限は、３０％
が好ましい。開孔率が３０％を超えると、表面強度が小
さくなり、取扱時に膜が損傷しやすくなる。より好まし
くは２５％である。The lower limit of the porosity of the outer surface fine pores of the blood purification hollow fiber membrane of the present invention is preferably 1%. Here, the open area ratio of the outer surface fine pores means the ratio of the total open area of individual holes per unit area to the outer surface area as a percentage. If the porosity is less than 1%, the water permeability will be low. It is more preferably 5%. The upper limit of the open area ratio of the outer surface fine pores of the hollow fiber membrane for blood purification of the present invention is 30%.
Is preferred. If the porosity exceeds 30%, the surface strength will be low and the film will be easily damaged during handling. It is more preferably 25%.
【００２３】本発明の血液浄化用中空糸膜は、内表面側
に１〜５μｍ程度の厚さの緻密層を有している。本発明
の血液浄化用中空糸膜の膜内部は、上記緻密層に連続し
て形成されたスポンジ状構造を有している。更に、本発
明の血液浄化用中空糸膜は内表面、外表面及び内部のい
ずれにおいても径１０μｍを超える巨大空洞を有するこ
とがない。１０μｍを超える巨大空洞が存在すると、中
空糸膜の機械的強度が低下する。上記スポンジ状構造の
孔径は、均一であることが好ましいが、特に均一である
必要はなく、不均一であってもよい。上記スポンジ状構
造の孔径は、０．１〜３μｍであるのが好ましい。The hollow fiber membrane for blood purification of the present invention has a dense layer having a thickness of about 1 to 5 μm on the inner surface side. The interior of the blood purification hollow fiber membrane of the present invention has a sponge-like structure formed continuously with the dense layer. Furthermore, the blood purification hollow fiber membrane of the present invention does not have huge cavities having a diameter of more than 10 μm on any of the inner surface, the outer surface and the inside. The presence of huge cavities exceeding 10 μm lowers the mechanical strength of the hollow fiber membrane. The pore diameter of the sponge-like structure is preferably uniform, but it does not have to be particularly uniform and may be non-uniform. The pore diameter of the sponge-like structure is preferably 0.1 to 3 μm.
【００２４】本発明の血液浄化用中空糸膜の内径は、１
００〜３００μｍがよく、より好ましくは、１８０〜２
５０μｍである。中空糸膜の内径が１００μｍ未満であ
ると、圧力損失が大きくなり、また血栓が生じやすくな
り、３００μｍを超えると、モジュール内へ収納するこ
とができる中空糸膜の本数が少なくなり、有効膜面積が
小さくなって、モジュール当たりの透析性能、濾過性能
が小さくなる。The inner diameter of the blood purification hollow fiber membrane of the present invention is 1
0 to 300 μm is preferable, and 180 to 2 is more preferable.
It is 50 μm. When the inner diameter of the hollow fiber membrane is less than 100 μm, pressure loss becomes large and thrombus is apt to occur, and when it exceeds 300 μm, the number of hollow fiber membranes that can be accommodated in the module is reduced, resulting in an effective membrane area. Becomes smaller and the dialysis performance and filtration performance per module become smaller.
【００２５】本発明の血液浄化用中空糸膜の膜厚は特に
限定されないが、膜の透析性能、透過性能、機械的強度
を適切に維持するためには、１０〜５０μｍであること
が好ましい。The thickness of the hollow fiber membrane for blood purification of the present invention is not particularly limited, but it is preferably 10 to 50 μm in order to appropriately maintain the dialysis performance, permeation performance and mechanical strength of the membrane.
【００２６】本発明の血液浄化用中空糸膜は、透水速度
の下限が、４００ｍｌ／ｍ2 ・ｈｒ・ｍｍＨｇである。
ここに、透水速度とは、中空糸膜を予めエタノール水溶
液で親水化し、ついで水でエタノール水溶液を置換した
後に測定した透水速度を意味する。透水速度が、４００
ｍｌ／ｍ2 ・ｈｒ・ｍｍＨｇ未満であると、血液濾過時
の限外濾過速度が小さくなって濾液流量が少なくなり、
効率的な治療が困難になるし、膜が目詰まりを起こしや
すくなり、血液成分の透過率が経時的に低下し、血液透
析においてはクリアランスが低下する。透水速度の下限
は、好ましくは５００ｍｌ／ｍ2 ・ｈｒ・ｍｍＨｇであ
る。In the hollow fiber membrane for blood purification of the present invention, the lower limit of water permeation rate is 400 ml / m 2 · hr · mmHg.
Here, the water permeation rate means the water permeation rate measured after previously making the hollow fiber membrane hydrophilic with an aqueous ethanol solution and then substituting the aqueous ethanol solution with water. Water penetration rate is 400
When it is less than ml / m 2 · hr · mmHg, the ultrafiltration rate at the time of hemofiltration becomes small and the flow rate of the filtrate becomes small,
Efficient treatment becomes difficult, the membrane is likely to be clogged, the permeability of blood components decreases with time, and the clearance decreases in hemodialysis. The lower limit of the water permeation rate is preferably 500 ml / m 2 · hr · mmHg.
【００２７】本発明の血液浄化用中空糸膜は、透水速度
の上限が、２５００ｍｌ／ｍ2 ・ｈｒ・ｍｍＨｇであ
る。２５００ｍｌ／ｍ2 ・ｈｒ・ｍｍＨｇを超えると、
アルブミン等の有用タンパクの漏出量が多くなる。透水
速度の上限は、好ましくは１８００ｍｌ／ｍ2 ・ｈｒ・
ｍｍＨｇである。The upper limit of the water permeation rate of the blood purification hollow fiber membrane of the present invention is 2500 ml / m 2 · hr · mmHg. When it exceeds 2500 ml / m 2 · hr · mmHg,
The leakage of useful proteins such as albumin increases. The upper limit of the water permeation rate is preferably 1800 ml / m 2 · hr ·
mmHg.
【００２８】本発明の血液浄化用中空糸膜は、総タンパ
クの透過率が、１％以下である。ここに、総タンパクの
透過率とは、上記の透水速度の場合と同様、中空糸膜を
予めエタノール水溶液で親水化し、ついで生理食塩水で
エタノール水溶液を置換した後、牛血を用いて血液濾過
を行った際の血中総タンパクの透過率を意味する。総タ
ンパクの透過率が１％を超えると、血液透析、血液濾過
の際にタンパクの漏出量が大きくなる。The blood purifying hollow fiber membrane of the present invention has a total protein permeability of 1% or less. Here, the total protein permeability is the same as in the case of the above water permeation rate, in which the hollow fiber membrane is previously hydrophilized with an aqueous ethanol solution, and then the aqueous ethanol solution is replaced with physiological saline, followed by hemofiltration using bovine blood. It means the permeation rate of the total protein in the blood when performing. If the total protein permeability exceeds 1%, the amount of protein leakage increases during hemodialysis and hemofiltration.
【００２９】本発明の血液浄化用中空糸膜は、以下のよ
うにして製造することができる。例えば、特開昭６０−
２２２１１２号公報に記載されているように、ポリスル
ホン樹脂とポリスルホン樹脂の良溶媒とからなる溶液
に、ポリスルホン樹脂の非溶媒又は膨潤剤を混合し、こ
の混合溶液が相分離を起こす直前に製膜する方法により
製造することができる。即ち、ポリスルホン樹脂を含有
する紡糸原液を、環状のノズルから内部凝固液とともに
押し出し、直ちに又はノズルから５０ｃｍ以内、好まし
くは２０ｃｍ以内の乾式距離を経た後、全体を外部凝固
液に接触させる中空糸膜の形成法において、上記紡糸原
液の組成を、温度を降下させていくと相分離を起こすよ
うな組成とし、上記紡糸原液を相分離温度以上に保持し
ながら環状ノズルから押し出し、内部凝固液、乾式距離
にある中空糸膜に接触する気体及び外部凝固液のうちの
１つ以上を、上記の相分離温度未満に保持することによ
り本発明の血液浄化用中空糸膜を製造することができ
る。The hollow fiber membrane for blood purification of the present invention can be manufactured as follows. For example, JP-A-60-
As described in JP-A-222112, a non-solvent of a polysulfone resin or a swelling agent is mixed with a solution composed of a polysulfone resin and a good solvent of the polysulfone resin, and a film is formed immediately before the mixed solution causes phase separation. It can be manufactured by a method. That is, a spinning solution containing a polysulfone resin is extruded from an annular nozzle together with an internal coagulating solution, and immediately or after a dry distance within 50 cm, preferably within 20 cm from the nozzle, the entire hollow fiber membrane is brought into contact with an external coagulating solution. In the method of forming, the composition of the spinning dope is a composition that causes phase separation when the temperature is lowered, and is extruded from an annular nozzle while maintaining the spinning dope at a temperature above the phase separation temperature, an internal coagulating liquid, a dry type The hollow fiber membrane for blood purification of the present invention can be produced by keeping at least one of the gas and the external coagulation liquid that come into contact with the hollow fiber membrane at a distance below the above-mentioned phase separation temperature.
【００３０】本発明の血液浄化用中空糸膜の製造にあた
っては、紡糸原液中のポリスルホン樹脂の濃度を、８〜
２５重量％、好ましくは１２〜２３重量％にするのがよ
い。ポリスルホン樹脂の濃度が８重量％未満であると、
紡糸原液の粘度が低くなり紡糸が困難となり、２５重量
％を超えると、中空糸膜の内外表面、特に外表面の孔径
が小さくなり、透水速度が低下する。In producing the hollow fiber membrane for blood purification of the present invention, the concentration of the polysulfone resin in the spinning dope is adjusted to 8 to 10.
It should be 25% by weight, preferably 12 to 23% by weight. When the concentration of the polysulfone resin is less than 8% by weight,
The viscosity of the stock solution for spinning becomes low and spinning becomes difficult. When it exceeds 25% by weight, the pore diameter of the inner and outer surfaces of the hollow fiber membrane, particularly the outer surface, becomes small and the water permeation rate decreases.
【００３１】本発明の血液浄化用中空糸膜の製造にあた
っては、凝固〜水洗工程後に、必要に応じて、グリセリ
ン等の孔径保持剤を付着させて中空糸膜を乾燥し、モジ
ュール化することもできる。In the production of the hollow fiber membrane for blood purification of the present invention, after the coagulation-water washing step, if necessary, a pore size-retaining agent such as glycerin may be attached and the hollow fiber membrane may be dried to be modularized. it can.
【００３２】本発明の血液浄化用中空糸膜が上記した優
れた効果を発揮する理由は明らかではないが、中空糸膜
の内表面をスリット状微細孔とすることにより、実質的
に球状であるタンパクの漏出を抑制することができ、透
水性、血液濾過性能、透析性能が高く維持されるように
なるものと考えられる。Although the reason why the hollow fiber membrane for blood purification of the present invention exerts the above-mentioned excellent effects is not clear, it is substantially spherical by forming slit-shaped fine pores on the inner surface of the hollow fiber membrane. It is considered that protein leakage can be suppressed and high water permeability, hemofiltration performance, and dialysis performance can be maintained.
【００３３】本発明の血液浄化器は、上記本発明の血液
浄化用中空糸膜を筒状のハウジング内に収納してなるも
のである。The blood purifier of the present invention comprises the above hollow fiber membrane for blood purification of the present invention housed in a cylindrical housing.
【００３４】上記筒状のハウジングは、血液が流入する
血液流入口及び血液が流出する血液流出口が備えられて
いる。また、本発明の血液浄化器を血液透析器や血液透
析濾過器として使用する場合には、透析液が流入する透
析液流入口及び透析液が流出する透析液流出口が備えら
れており、本発明の血液浄化器を血液濾過器として使用
する場合には、血液の濾液が流出する濾液流出口が備え
られている。上記ハウジングとしては、例えば、ポリカ
ーボネート等のプラスチック製のもの等を挙げることが
できる。The cylindrical housing is provided with a blood inflow port through which blood flows in and a blood outflow port through which blood flows out. When the blood purifier of the present invention is used as a hemodialyzer or a hemodialysis filter, it is provided with a dialysate inlet through which dialysate flows in and a dialysate outlet through which dialysate flows out. When the blood purifier of the invention is used as a blood filter, it is provided with a filtrate outlet through which a blood filtrate flows out. Examples of the housing include plastics such as polycarbonate.
【００３５】本発明の血液浄化器は、膜の成分が溶出す
る危険が全くなく、安全な血液浄化用中空糸膜を使用し
ているので、血液透析器、血液透析濾過器及び血液濾過
器として非常に好適である。Since the blood purifier of the present invention uses a safe hollow fiber membrane for blood purification without any risk of elution of membrane components, it can be used as a hemodialyzer, hemodialysis filter and hemofilter. Very suitable.
【００３６】[0036]
【発明の実施の形態】以下に本発明の血液浄化器を図面
を参照しながら更に詳細に説明するが、本発明の血液浄
化器はこれらに限定されるものではない。BEST MODE FOR CARRYING OUT THE INVENTION The blood purifier of the present invention will be described below in more detail with reference to the drawings, but the blood purifier of the present invention is not limited thereto.
【００３７】本発明の血液浄化器は、血液透析器、血液
透析濾過器として使用される場合、図５に示すように、
多数の血液浄化用中空糸膜１ａから構成された中空糸膜
束１を筒状のハウジング２に収納し、両端部をポリウレ
タン等の樹脂によってハウジング内壁面に接着固定して
隔壁を形成し、その両端を切断して中空部を開口させた
後、血液流入用ヘッダー３及び血液流出用ヘッダー４を
固着させたものである。本実施形態の血液浄化器は、血
液透析器、血液透析濾過器として使用されるので、ハウ
ジング２の両端側面に、中空糸束間隙部に連通した透析
液流入口５及び透析液流出口６が備えられている。When the blood purifier of the present invention is used as a hemodialyzer or hemodialyzer, as shown in FIG.
A hollow fiber membrane bundle 1 composed of a large number of blood purification hollow fiber membranes 1a is housed in a cylindrical housing 2, and both ends thereof are adhesively fixed to the inner wall surface of the housing with a resin such as polyurethane to form a partition wall. After cutting both ends to open the hollow portion, the blood inflow header 3 and the blood outflow header 4 are fixed. Since the blood purifier of the present embodiment is used as a hemodialyzer and a hemodialysis filter, a dialysate inlet 5 and a dialysate outlet 6 communicating with the hollow fiber bundle gap portion are provided on both end side surfaces of the housing 2. It is equipped.
【００３８】図６は、本発明の血液浄化器を血液濾過器
として使用する場合の一実施形態を表す概略図である。
本実施形態においては、血液の濾液を流出させるために
中空糸束間隙部に連通した濾液流出口７が備えられてい
る。FIG. 6 is a schematic diagram showing an embodiment in which the blood purifier of the present invention is used as a blood filter.
In this embodiment, a filtrate outlet 7 is provided which communicates with the hollow fiber bundle gap portion in order to let the filtrate of blood flow out.
【００３９】[0039]
【実施例】以下に実施例を掲げて本発明を更に詳しく説
明するが、本発明はこれら実施例のみに限定されるもの
ではない。The present invention will be described in more detail with reference to the following examples, but the present invention is not limited to these examples.
【００４０】実施例１ ポリスルホン樹脂（アモコ・パフォーマンス・プロダク
ツ、Ｐ−１７００）２２重量％、プロピレングリコール
２３重量％及びＮ−メチル−２−ピロリドン５５重量％
からなる相分離温度７０℃の溶液を紡糸原液とし、これ
を８０℃の状態で環状紡糸ノズルの外側吐出孔から１．
６ｇ／ｍｉｎの速度で吐出させ、内側にＮ−メチル−２
−ピロリドン５０重量％水溶液を内部凝固液として、
１．９ｇ／ｍｉｎの速度で吐出させることによって中空
糸条を形成させた。この吐出糸条を、１０ｃｍの乾式距
離を経て、５５℃の温水中に導き、凝固・水洗し、５５
ｍ／ｍｉｎの速度でカセに巻き取ることによって、内径
２００μｍ、膜厚２５μｍの中空糸膜を得た。Example 1 Polysulfone resin (Amoco Performance Products, P-1700) 22% by weight, propylene glycol 23% by weight and N-methyl-2-pyrrolidone 55% by weight
The solution having a phase separation temperature of 70 ° C. was used as a spinning dope, and this was kept at 80 ° C. from the outer discharge hole of the annular spinning nozzle.
Discharge at a rate of 6 g / min and N-methyl-2 inside
A 50% by weight aqueous solution of pyrrolidone as an internal coagulating liquid,
Hollow fiber threads were formed by discharging at a rate of 1.9 g / min. This discharge yarn is introduced into warm water at 55 ° C through a dry distance of 10 cm, coagulated and washed with water, and then 55
The hollow fiber membrane having an inner diameter of 200 μm and a film thickness of 25 μm was obtained by winding it around a cassette at a speed of m / min.
【００４１】この中空糸膜を沸騰水中で１時間熱処理・
脱溶剤処理し、乾燥させてＳＥＭで構造を観察した。画
像処理は、Ｐｅｒｓｏｎａｌ Ｉｍａｇｅ Ａｎａｌｙ
ｓｉｓ Ｓｙｓｔｅｍ−ＩＩＩ（インタークエスト社
製）を用いて行った。その結果、この中空糸膜の内表面
には平均巾０．０６μｍのスリット状微細孔が多数存在
し、外表面には平均孔径０．２μｍの微細孔が多数存在
し、かつ膜内部がスポンジ状構造であり、内外表面及び
内部のいずれにおいても径１０μｍ以上の巨大空洞は存
在しないことがわかった。これらのＳＥＭ写真を図１〜
図４に示した。This hollow fiber membrane was heat-treated in boiling water for 1 hour.
The solvent was removed, dried, and the structure was observed by SEM. Image processing is based on Personal Image Analysis
It was performed using sis System-III (manufactured by Interquest). As a result, there were many slit-shaped micropores with an average width of 0.06 μm on the inner surface of the hollow fiber membrane, many micropores with an average pore diameter of 0.2 μm on the outer surface, and the inside of the membrane was sponge-shaped. It was found that the structure had no huge cavities with a diameter of 10 μm or more on both the inner and outer surfaces and inside. These SEM photographs are shown in FIGS.
As shown in FIG.
【００４２】実施例２ 実施例１の中空糸膜を３６０本束ね、ポリカーボネート
製のケーシングに収納し、両端部をポリウレタンでポッ
ティングして、有効長１８ｃｍ、有効膜面積０．０４ｍ
2 のミニモジュールを作成した。次にエタノール水溶液
で、このミニモジュール中の中空糸膜を親水化し、次い
で水でエタノール水溶液を置換した。このミニモジュー
ルを３７℃に保温し、ローラーポンプで３７℃の水を中
空糸膜内側に６．５ｍｌ／ｍｉｎの流量で導入し、全濾
過を行いミニモジュール入口側の圧力を測定して、透水
速度を測定した。その結果、透水速度は１０００ｍｌ／
ｍ2 ・ｈｒ・ｍｍＨｇであった。Example 2 360 hollow fiber membranes of Example 1 were bundled and housed in a polycarbonate casing, and both ends were potted with polyurethane to give an effective length of 18 cm and an effective membrane area of 0.04 m.
Created 2 mini-modules. Next, the hollow fiber membrane in this mini-module was made hydrophilic with an aqueous ethanol solution, and then the aqueous ethanol solution was replaced with water. This mini module is kept warm at 37 ° C, water at 37 ° C is introduced into the inside of the hollow fiber membrane at a flow rate of 6.5 ml / min by a roller pump, and total filtration is performed to measure the pressure on the inlet side of the mini module to measure water permeability. The speed was measured. As a result, the water permeability is 1000 ml /
It was m 2 · hr · mmHg.
【００４３】実施例３ 実施例２のミニモジュール内の水を生理食塩水に置換
し、牛血による濾過試験に供した。牛血は、クエン酸ナ
トリウム加牛血を使用し、予めヘマトクリットを３０
％、総タンパク濃度が６〜７ｇ／ｄｌになるように調整
した。さらにこれに対して尿素１００ｍｇ／ｄｌ、クレ
アチニン１０ｍｇ／ｄｌ、尿酸１０ｍｇ／ｄｌの割合で
溶解した。この牛血をローラーポンプで上記ミニモジュ
ールの中空糸膜内側に血液流量６．５ｍｌ／ｍｉｎで導
入し、濾過流量を１．５〜２．５ｍｌ／ｍｉｎの範囲で
膜間圧力差（ＴＭＰ）を約１００ｍｍＨｇに保持できる
ように設定して、３７℃の温度下で濾過試験を行った。
このような牛血濾過試験を４時間行い、１時間ごとの総
タンパク、尿素、クレアチニン、尿酸の透過率を測定し
た。そして１時間目の血中総タンパク透過率を総タンパ
クの透過率とした。Example 3 The water in the mini-module of Example 2 was replaced with physiological saline and the sample was subjected to a filtration test with bovine blood. As bovine blood, use sodium citrate-added bovine blood and preliminarily add hematocrit to 30
%, The total protein concentration was adjusted to 6 to 7 g / dl. Further, to this, 100 mg / dl of urea, 10 mg / dl of creatinine and 10 mg / dl of uric acid were dissolved. This bovine blood was introduced into the hollow fiber membrane of the mini module at a blood flow rate of 6.5 ml / min by a roller pump, and the transmembrane pressure difference (TMP) was adjusted within a filtration flow rate range of 1.5 to 2.5 ml / min. The filtration test was carried out at a temperature of 37 ° C. so that the filtration test could be maintained at about 100 mmHg.
Such a bovine blood filtration test was carried out for 4 hours, and the transmittance of total protein, urea, creatinine, and uric acid was measured every hour. Then, the total protein permeability in blood at 1 hour was defined as the total protein permeability.
【００４４】ここで透過率は、各成分のミニモジュール
の入口側、出口側の血液中、及び、濾液中の濃度を測定
し、濾液中の濃度を、ミニモジュールの入口側と出口側
の血液中の平均濃度で除して求めた。濾液中の総タンパ
ク濃度は、ピロガロールレッド法で測定した。結果を表
１に示した。総タンパクの透過率（１時間値）は、０．
３７％であった。また、総タンパク、尿素、クレアチニ
ン、尿酸の透過率の経時変化はほとんどなく、安定した
血液濾過を行うことができた。Here, the transmittance is measured by measuring the concentration of each component in the blood on the inlet side and the outlet side of the mini-module, and the concentration in the filtrate, and the concentration in the filtrate is determined as the blood on the inlet side and the outlet side of the mini-module. It was calculated by dividing by the average concentration in the medium. The total protein concentration in the filtrate was measured by the pyrogallol red method. The results are shown in Table 1. The total protein transmittance (1 hour value) was 0.
It was 37%. In addition, there was almost no change with time in the transmittance of total protein, urea, creatinine, and uric acid, and stable hemofiltration could be performed.
【００４５】実施例４ 実施例１の中空糸膜を１１０００本束ね、有効長１９ｃ
ｍ、有効膜面積１．３ｍ2 のモジュールを作成した。次
にエタノール水溶液でモジュール中の中空糸膜を親水化
し、次いで水でエタノール水溶液を置換した。このモジ
ュールについて、日本人工臓器学会編「ダイアライザー
性能評価基準」の方法を準用して、血液側流量（ＱＢ）
＝２００ｍｌ／ｍｉｎ、透析液側流量（ＱＤ）＝５００
ｍｌ／ｍｉｎ、ＴＭＰ＝０ｍｍＨｇの条件でクリアラン
スを測定した。その結果、尿素については１７３ｍｌ／
ｍｉｎ、クレアチニンについては１６６ｍｌ／ｍｉｎ、
尿酸については１５８ｍｌ／ｍｉｎ、無機燐については
１６１ｍｌ／ｍｉｎという値が得られた。これから、こ
の中空糸膜は充分な透析性能を有していることがわかっ
た。Example 4 11,000 hollow fiber membranes of Example 1 were bundled together to give an effective length of 19c.
m, and an effective membrane area of 1.3 m 2 was prepared. Next, the hollow fiber membrane in the module was made hydrophilic with an aqueous ethanol solution, and then the aqueous ethanol solution was replaced with water. About this module, the blood side flow rate (QB) is applied by applying the method of “Dializer performance evaluation standard” edited by Japan Society for Artificial Organs.
= 200 ml / min, dialysate side flow rate (QD) = 500
The clearance was measured under the conditions of ml / min and TMP = 0 mmHg. As a result, for urea, 173 ml /
min, 166 ml / min for creatinine,
Values of 158 ml / min for uric acid and 161 ml / min for inorganic phosphorus were obtained. From this, it was found that this hollow fiber membrane had sufficient dialysis performance.
【００４６】比較例１ 紡糸原液を、ポリスルホン樹脂３０重量％、プロピレン
グリコール１８重量％及びＮ−メチル−２−ピロリドン
５２重量％からなる溶液とし、紡糸温度を９０℃、内部
凝固液をプロピレングリコールとしたこと以外は実施例
１と同様に紡糸を行うことによって、内径２００μｍ、
膜厚２５μｍの中空糸膜を得た。実施例１と同様の方法
で構造を調べると、この中空糸膜の内表面には、平均巾
０．０７μｍのスリット状微細孔が多数存在したが、外
表面には微細孔が認められなかった。そして膜内部はス
ポンジ状構造であり、内外表面及び内部のいずれにおい
ても径１０μｍ以上の巨大空洞は存在しないことがわか
った。ただし、膜内部のスポンジ状構造はかなり密とな
っていた。外表面の微細孔は、ポリスルホン樹脂濃度が
大きすぎ、生成しなかったものと思われた。この中空糸
膜の透水速度を、実施例２と同様の方法で測定した。そ
の結果、透水速度は１１０ｍｌ／ｍ2 ・ｈｒ・ｍｍＨｇ
であった。さらに、この中空糸膜について実施例３と同
様の方法で、牛血濾過試験を行った。その結果、濾過流
量を１．５ｍｌ／ｍｉｎ以上にすると、ＴＭＰが２００
ｍｍＨｇ以上に上昇し、濾過試験を中止せざるをえなか
った。Comparative Example 1 A spinning dope was made into a solution consisting of 30% by weight of polysulfone resin, 18% by weight of propylene glycol and 52% by weight of N-methyl-2-pyrrolidone, the spinning temperature was 90 ° C., and the internal coagulating solution was propylene glycol. Spinning was performed in the same manner as in Example 1 except that the inner diameter was 200 μm,
A hollow fiber membrane having a thickness of 25 μm was obtained. When the structure was examined in the same manner as in Example 1, a large number of slit-like micropores having an average width of 0.07 μm were present on the inner surface of this hollow fiber membrane, but no micropores were observed on the outer surface. . It was found that the inside of the film had a sponge-like structure, and there were no huge cavities with a diameter of 10 μm or more on both the inner and outer surfaces and inside. However, the sponge-like structure inside the film was quite dense. The micropores on the outer surface were considered to have not been generated because the polysulfone resin concentration was too high. The water permeation rate of this hollow fiber membrane was measured by the same method as in Example 2. As a result, the water permeability is 110 ml / m 2 · hr · mmHg.
Met. Furthermore, a bovine blood filtration test was performed on this hollow fiber membrane in the same manner as in Example 3. As a result, when the filtration flow rate is 1.5 ml / min or more, the TMP is 200
It rose above mmHg, and had to stop the filtration test.
【００４７】比較例２ 紡糸原液を、ポリスルホン樹脂１８重量％、プロピレン
グリコール２４重量％及びＮ−メチル−２−ピロリドン
５８重量％からなる溶液（相分離温度＝６８℃）とし、
これの吐出速度を３．６ｇ／ｍｉｎとし、内部凝固液と
して水を使用したこと以外は実施例１と同様に紡糸を行
うことによって、内径２００μｍ、膜厚３０μｍの中空
糸膜を得た。実施例１と同様の方法で構造を調べると、
この中空糸膜の外表面には平均孔径０．５μｍの微細孔
が多数存在したが、内表面には明確なスリット状微細孔
は認められなかった。そして膜内部はスポンジ状構造で
あり、内外表面及び内部のいずれにおいても径１０μｍ
以上の巨大空洞は存在しないことがわかった。内部凝固
液の凝固力が大きすぎ、内表面にスリット状微細孔が生
成しなかったものと思われた。Comparative Example 2 A spinning dope was a solution (phase separation temperature = 68 ° C.) consisting of 18% by weight of polysulfone resin, 24% by weight of propylene glycol and 58% by weight of N-methyl-2-pyrrolidone.
A hollow fiber membrane having an inner diameter of 200 μm and a film thickness of 30 μm was obtained by carrying out spinning in the same manner as in Example 1 except that the discharge rate was 3.6 g / min and water was used as the internal coagulating liquid. When the structure was examined by the same method as in Example 1,
There were many fine pores with an average pore diameter of 0.5 μm on the outer surface of this hollow fiber membrane, but no clear slit-like fine pores were found on the inner surface. The inside of the film has a sponge-like structure, and the diameter is 10 μm both on the inner and outer surfaces.
It turned out that the above huge cavities do not exist. It was considered that the coagulation force of the internal coagulation liquid was too large and the slit-like micropores were not formed on the inner surface.
【００４８】この中空糸膜の透水速度を、実施例２と同
様の方法で測定した。その結果、透水速度は５８０ｍｌ
／ｍ2 ・ｈｒ・ｍｍＨｇであった。さらに、この中空糸
膜について実施例３と同様の方法で、牛血濾過試験を行
った。結果を表１に示した。総タンパクの透過率（１時
間値）は、０．０４％以下であったが、経時的にＴＭＰ
が上昇し、開始後１８０分では、濾過流量を１．５ｍｌ
／ｍｉｎ以下に低下させなければならなかった。また、
尿素、クレアチニン、尿酸の透過率も経時的に低下し、
安定した血液濾過を行うことができなかった。The water permeation rate of this hollow fiber membrane was measured by the same method as in Example 2. As a result, the water permeability is 580 ml.
/ M 2 · hr · mmHg. Furthermore, a bovine blood filtration test was performed on this hollow fiber membrane in the same manner as in Example 3. The results are shown in Table 1. The total protein permeability (1 hour value) was 0.04% or less,
Increased 180 minutes after the start, the filtration flow rate was 1.5 ml.
Had to be reduced to below / min. Also,
Urea, creatinine, uric acid permeability also decreases over time,
It was not possible to perform stable hemofiltration.
【００４９】実施例５ ポリスルホン樹脂１８重量％、プロピレングリコール２
４重量％及びＮ−メチル−２−ピロリドン５８重量％か
らなる相分離温度６８℃の溶液を紡糸原液とし、これの
吐出速度を３．６ｇ／ｍｉｎとし、内部凝固液としてＮ
−メチル−２−ピロリドン４０重量％水溶液を使用した
こと以外は実施例１と同様に紡糸を行うことによって、
内径２００μｍ、膜厚３０μｍの中空糸膜を得た。実施
例１と同様の方法で構造を調べると、この中空糸膜の内
表面には平均巾０．１μｍのスリット状微細孔が多数存
在し、外表面には平均孔径０．６μｍの微細孔が多数存
在し、かつ膜内部がスポンジ状構造であり、内外表面及
び内部のいずれにおいても径１０μｍ以上の巨大空洞は
存在しなかった。Example 5 18% by weight of polysulfone resin, propylene glycol 2
A solution containing 4% by weight and 58% by weight of N-methyl-2-pyrrolidone at a phase separation temperature of 68 ° C. was used as a spinning dope, and the discharge rate thereof was 3.6 g / min.
-Methyl-2-pyrrolidone By performing spinning in the same manner as in Example 1 except that a 40% by weight aqueous solution was used,
A hollow fiber membrane having an inner diameter of 200 μm and a film thickness of 30 μm was obtained. When the structure was examined by the same method as in Example 1, a large number of slit-like micropores with an average width of 0.1 μm were present on the inner surface of this hollow fiber membrane, and micropores with an average pore diameter of 0.6 μm were present on the outer surface. There were a large number of them, and the inside of the film had a sponge-like structure, and there were no giant cavities with a diameter of 10 μm or more on both the inner and outer surfaces and inside.
【００５０】この中空糸膜の透水速度を、実施例２と同
様の方法で測定した。その結果、透水速度は１３００ｍ
ｌ／ｍ2 ・ｈｒ・ｍｍＨｇであった。さらに、この中空
糸膜について実施例３と同様の方法で、牛血濾過試験を
行った。結果を表１に示した。総タンパクの透過率（１
時間値）は、０．８９％であった。また、総タンパク、
尿素、クレアチニン、尿酸の透過率の経時変化はほとん
どなく、安定した血液濾過を行うことができた。The water permeation rate of this hollow fiber membrane was measured by the same method as in Example 2. As a result, the water permeability is 1300m.
It was 1 / m 2 · hr · mmHg. Furthermore, a bovine blood filtration test was performed on this hollow fiber membrane in the same manner as in Example 3. The results are shown in Table 1. Total protein permeability (1
The time value) was 0.89%. Also, total protein,
Urea, creatinine, and uric acid permeabilities were hardly changed with time, and stable hemofiltration could be performed.
【００５１】実施例６ 実施例１で紡糸された中空糸膜をカセに巻き取った後、
４５重量％グリセリン水溶液に中空糸膜を約５分間浸漬
し、次いで乾燥した。この中空糸膜を用いて実施例２と
同様の方法でミニモジュールを作成した。このミニモジ
ュールをエタノール水溶液で親水化せずに、実施例３と
同様の方法で、牛血濾過試験を行った。結果を表１に示
した。総タンパクの透過率（１時間値）は、０．４５％
であった。また、総タンパク、尿素、クレアチニン、尿
酸の透過率の経時変化はほとんどなく、エタノール水溶
液で親水化した場合（実施例３）と同様、安定した血液
濾過を行うことができた。Example 6 After winding the hollow fiber membrane spun in Example 1 on a cassette,
The hollow fiber membrane was immersed in a 45 wt% glycerin aqueous solution for about 5 minutes and then dried. Using this hollow fiber membrane, a mini module was prepared in the same manner as in Example 2. A bovine blood filtration test was conducted in the same manner as in Example 3 without hydrophilizing this mini module with an aqueous ethanol solution. The results are shown in Table 1. Total protein permeability (1 hour value) is 0.45%
Met. In addition, there was almost no change with time in the transmittance of total protein, urea, creatinine, and uric acid, and stable hemofiltration could be performed as in the case of making hydrophilic with an aqueous ethanol solution (Example 3).
【００５２】実施例７ ポリスルホン樹脂２２重量％、ジプロピレングリコール
３１重量％及びＮ−メチル−２−ピロリドン４７重量％
からなる相分離温度５７℃の溶液を紡糸原液とし、これ
を７５℃の状態で環状紡糸ノズルの外側吐出孔から１．
６ｇ／ｍｉｎの速度で吐出させ、内側にＮ−メチル−２
−ピロリドン４０重量％水溶液を内部凝固液として、
１．９ｇ／ｍｉｎの速度で吐出させることによって中空
糸条を形成させた。この吐出糸条を、１０ｃｍの乾式距
離を経て、５０℃の温水中に導き、凝固・水洗し、５５
ｍ／ｍｉｎの速度でカセに巻き取ることによって、内径
２００μｍ、膜厚２５μｍの中空糸膜を得た。Example 7 22% by weight of polysulfone resin, 31% by weight of dipropylene glycol and 47% by weight of N-methyl-2-pyrrolidone
The solution having a phase separation temperature of 57 ° C. was used as a spinning dope, and this was kept at 75 ° C. from the outer discharge hole of the annular spinning nozzle.
Discharge at a rate of 6 g / min and N-methyl-2 inside
A 40% by weight aqueous solution of pyrrolidone as an internal coagulation liquid,
Hollow fiber threads were formed by discharging at a rate of 1.9 g / min. This discharge yarn is introduced into warm water of 50 ° C through a dry distance of 10 cm, coagulated and washed with water, and then 55
The hollow fiber membrane having an inner diameter of 200 μm and a film thickness of 25 μm was obtained by winding it around a cassette at a speed of m / min.
【００５３】実施例１と同様の方法で構造を調べると、
この中空糸膜の内表面には、平均巾０．０３μｍのスリ
ット状微細孔が多数存在し、外表面には、平均孔径０．
２μｍの微孔が多数存在し、かつ、膜内部がスポンジ状
構造であり、内外表面及び内部のいずれにおいても１０
μｍ以上の巨大空洞は存在しなかった。When the structure was examined by the same method as in Example 1,
On the inner surface of this hollow fiber membrane, a large number of slit-like fine pores having an average width of 0.03 μm exist, and on the outer surface, an average pore diameter of 0.
There are a large number of 2 μm micropores, and the inside of the membrane has a sponge-like structure.
There were no huge cavities above μm.
【００５４】この中空糸膜の透水速度を、実施例２と同
様の方法で測定した。その結果、透水速度は５４０ｍｌ
／ｍ2 ・ｈｒ・ｍｍＨｇであった。更に、この中空糸膜
について実施例３と同様の方法で、牛血濾過試験を実施
した。その結果、総タンパクの透過率（１時間値）は、
０．０４％以下であったが、尿素、クレアチニン、尿酸
の透過率の経時変化はほとんどなく、安定した血液濾過
を行うことができた。The water permeation rate of this hollow fiber membrane was measured by the same method as in Example 2. As a result, the water permeability is 540 ml.
/ M 2 · hr · mmHg. Further, a bovine blood filtration test was performed on this hollow fiber membrane in the same manner as in Example 3. As a result, the total protein transmittance (1 hour value) was
Although it was 0.04% or less, there was almost no change with time in the transmittance of urea, creatinine, and uric acid, and stable hemofiltration could be performed.
【００５５】[0055]
【表１】 [Table 1]
【００５６】[0056]
【発明の効果】本発明の血液浄化用中空糸膜は、上述の
構成よりなるので、ポリビニルピロリドン等の高価な材
料を使用することなく、安定した血液濾過性能、高い透
析性能を発現することができ、血液透析、血液濾過等に
好適に用いることができる。また、本発明の血液浄化器
は、処理膜として上記血液浄化用中空糸膜を使用してい
るので、血液透析器、血液透析濾過器、血液濾過器等と
して好適に使用することができる。EFFECTS OF THE INVENTION Since the hollow fiber membrane for blood purification of the present invention has the above-mentioned constitution, it can exhibit stable hemofiltration performance and high dialysis performance without using expensive materials such as polyvinylpyrrolidone. Therefore, it can be suitably used for hemodialysis, hemofiltration and the like. Further, the blood purifier of the present invention uses the above-mentioned hollow fiber membrane for blood purification as a treatment membrane, and thus can be suitably used as a hemodialyzer, a hemodialysis filter, a hemofilter and the like.
【図１】実施例１において得られた血液浄化用中空糸膜
の断面形状全体の構造（倍率２００）を示すＳＥＭ写真
である。FIG. 1 is an SEM photograph showing the structure (magnification: 200) of the entire cross-sectional shape of the blood purification hollow fiber membrane obtained in Example 1.
【図２】実施例１において得られた血液浄化用中空糸膜
の膜内部の構造（倍率３０００）を示すＳＥＭ写真であ
る。2 is an SEM photograph showing the internal structure (magnification: 3000) of the hollow fiber membrane for blood purification obtained in Example 1. FIG.
【図３】実施例１において得られた血液浄化用中空糸膜
の内表面の構造（倍率１００００）を示すＳＥＭ写真で
ある。FIG. 3 is an SEM photograph showing the structure of the inner surface (magnification: 10,000) of the blood purification hollow fiber membrane obtained in Example 1.
【図４】実施例１において得られた血液浄化用中空糸膜
の外表面の構造（倍率５０００）を示すＳＥＭ写真であ
る。FIG. 4 is an SEM photograph showing the structure (magnification: 5000) of the outer surface of the blood purification hollow fiber membrane obtained in Example 1.
【図５】本発明の血液浄化器の第一の実施形態を表す概
略図である。FIG. 5 is a schematic diagram showing a first embodiment of the blood purifier of the present invention.
【図６】本発明の血液浄化器の第二の実施形態を表す概
略図である。FIG. 6 is a schematic diagram showing a second embodiment of the blood purifier of the present invention.
Claims (5)
空糸膜であって、内表面には、平均巾０．０２〜０．１
５μｍのスリット状微細孔を有し、外表面には、平均孔
径０．１〜１μｍの微細孔を有し、内部は、スポンジ状
構造を有し、内表面、外表面及び内部のいずれにおいて
も径１０μｍを超える巨大空洞を有することがなく、透
水速度が、４００〜２５００ｍｌ／ｍ2 ・ｈｒ・ｍｍＨ
ｇであり、総タンパクの透過率が、１％以下であること
を特徴とする血液浄化用中空糸膜。1. A hollow fiber membrane for blood purification made of polysulfone resin, wherein the inner surface has an average width of 0.02 to 0.1.
It has slit-like micropores of 5 μm, has micropores with an average pore diameter of 0.1 to 1 μm on the outer surface, and has a sponge-like structure on the inside, and on any of the inner surface, the outer surface and the inside. It does not have huge cavities with a diameter of more than 10 μm, and the water permeability is 400-2500 ml / m 2 · hr · mmH.
and a total protein permeability of 1% or less. A hollow fiber membrane for blood purification.
ｍのスリット状微細孔を有する請求項１記載の血液浄化
用中空糸膜。2. The inner surface has an average width of 0.04 to 0.1 μm.
The hollow fiber membrane for blood purification according to claim 1, wherein the hollow fiber membrane has slit-shaped fine pores of m.
μｍの微細孔を有する請求項１又は２記載の血液浄化用
中空糸膜。3. The outer surface has an average pore size of 0.15 to 0.8.
The hollow fiber membrane for blood purification according to claim 1 or 2, which has fine pores of µm.
2 ・ｈｒ・ｍｍＨｇである請求項１、２又は３記載の血
液浄化用中空糸膜。4. The water permeation rate is 500 to 1800 ml / m.
The hollow fiber membrane for blood purification according to claim 1, 2 or 3, which is 2 · hr · mmHg.
入口及び透析液流出口、又は、濾液流出口とを備えた筒
状のハウジング内に、請求項１〜４のいずれかに記載の
血液浄化用中空糸膜が収納されていることを特徴とする
血液浄化器。5. A tubular housing provided with a blood inlet and a blood outlet, and a dialysate inlet and a dialysate outlet or a filtrate outlet, according to any one of claims 1 to 4. The blood purifier characterized in that the hollow fiber membrane for blood purification of is stored.
Priority Applications (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| JP8747697A JPH09308685A (en) | 1996-03-21 | 1997-03-21 | Hollow fiber membrane for blood purification and blood purifying device |
Applications Claiming Priority (3)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| JP8-93267 | 1996-03-21 | ||
| JP9326796 | 1996-03-21 | ||
| JP8747697A JPH09308685A (en) | 1996-03-21 | 1997-03-21 | Hollow fiber membrane for blood purification and blood purifying device |
Publications (1)
| Publication Number | Publication Date |
|---|---|
| JPH09308685A true JPH09308685A (en) | 1997-12-02 |
Family
ID=26428747
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| JP8747697A Pending JPH09308685A (en) | 1996-03-21 | 1997-03-21 | Hollow fiber membrane for blood purification and blood purifying device |
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Cited By (7)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| KR20010055286A (en) * | 1999-12-10 | 2001-07-04 | 구광시 | A polysulfone based hollow fiber membrance for hemodialysis, and a process of preparing for the same |
| KR100416135B1 (en) * | 1997-12-30 | 2004-05-07 | 주식회사 코오롱 | Polysulfone hollow fiber membrane for hemodialysis and method for manufacturing the same |
| JP2005334318A (en) * | 2004-05-27 | 2005-12-08 | Toyobo Co Ltd | High strength and high water permeability hollow fiber membrane type hemocatharsis apparatus |
| JP2007522851A (en) * | 2004-02-19 | 2007-08-16 | メムブラーナ ゲゼルシャフト ミット ベシュレンクテル ハフツング | High flux dialysis membrane with improved separation behavior |
| JP2014073487A (en) * | 2012-09-11 | 2014-04-24 | Toray Ind Inc | Porous membrane, water purifier incorporating porous membrane and method for producing porous membrane |
| WO2015046411A1 (en) | 2013-09-30 | 2015-04-02 | 東レ株式会社 | Porous membrane, blood purifying module incorporating porous membrane, and method for producing porous membrane |
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1997
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| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| KR100416135B1 (en) * | 1997-12-30 | 2004-05-07 | 주식회사 코오롱 | Polysulfone hollow fiber membrane for hemodialysis and method for manufacturing the same |
| KR20010055286A (en) * | 1999-12-10 | 2001-07-04 | 구광시 | A polysulfone based hollow fiber membrance for hemodialysis, and a process of preparing for the same |
| JP2007522851A (en) * | 2004-02-19 | 2007-08-16 | メムブラーナ ゲゼルシャフト ミット ベシュレンクテル ハフツング | High flux dialysis membrane with improved separation behavior |
| JP2005334318A (en) * | 2004-05-27 | 2005-12-08 | Toyobo Co Ltd | High strength and high water permeability hollow fiber membrane type hemocatharsis apparatus |
| JP2014073487A (en) * | 2012-09-11 | 2014-04-24 | Toray Ind Inc | Porous membrane, water purifier incorporating porous membrane and method for producing porous membrane |
| WO2015046411A1 (en) | 2013-09-30 | 2015-04-02 | 東レ株式会社 | Porous membrane, blood purifying module incorporating porous membrane, and method for producing porous membrane |
| KR20160065047A (en) | 2013-09-30 | 2016-06-08 | 도레이 카부시키가이샤 | Porous membrane, blood purifying module incorporating porous membrane, and method for producing porous membrane |
| JP2017529238A (en) * | 2014-09-22 | 2017-10-05 | フレセニウス メディカル ケア ドイチェランド ゲーエムベーハー | Use place water purifier with polysulfone hollow fiber |
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