JPH09285536A - Selective permeability hollow fiber membrane - Google Patents
Selective permeability hollow fiber membraneInfo
- Publication number
- JPH09285536A JPH09285536A JP9845796A JP9845796A JPH09285536A JP H09285536 A JPH09285536 A JP H09285536A JP 9845796 A JP9845796 A JP 9845796A JP 9845796 A JP9845796 A JP 9845796A JP H09285536 A JPH09285536 A JP H09285536A
- Authority
- JP
- Japan
- Prior art keywords
- hollow fiber
- fiber membrane
- dextran
- molecular weight
- albumin
- 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.)
- Granted
Links
- 239000012510 hollow fiber Substances 0.000 title claims abstract description 57
- 239000012528 membrane Substances 0.000 title claims abstract description 45
- 230000035699 permeability Effects 0.000 title description 17
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 claims abstract description 18
- 102000009027 Albumins Human genes 0.000 claims abstract description 16
- 108010088751 Albumins Proteins 0.000 claims abstract description 16
- 229920002307 Dextran Polymers 0.000 claims abstract description 14
- 229920002678 cellulose Polymers 0.000 claims abstract description 10
- 239000001913 cellulose Substances 0.000 claims abstract description 10
- 241000283690 Bos taurus Species 0.000 claims abstract description 7
- 239000007864 aqueous solution Substances 0.000 claims abstract description 4
- 230000010412 perfusion Effects 0.000 claims abstract description 4
- 238000007873 sieving Methods 0.000 claims description 5
- 239000000243 solution Substances 0.000 abstract description 3
- 239000000126 substance Substances 0.000 description 20
- 210000004369 blood Anatomy 0.000 description 14
- 239000008280 blood Substances 0.000 description 14
- 238000000502 dialysis Methods 0.000 description 12
- 238000009987 spinning Methods 0.000 description 7
- 238000001631 haemodialysis Methods 0.000 description 5
- 230000000322 hemodialysis Effects 0.000 description 5
- IAZDPXIOMUYVGZ-UHFFFAOYSA-N Dimethylsulphoxide Chemical compound CS(C)=O IAZDPXIOMUYVGZ-UHFFFAOYSA-N 0.000 description 4
- 239000007788 liquid Substances 0.000 description 4
- 229920001059 synthetic polymer Polymers 0.000 description 4
- 239000003795 chemical substances by application Substances 0.000 description 3
- 230000001112 coagulating effect Effects 0.000 description 3
- 238000005194 fractionation Methods 0.000 description 3
- 238000000034 method Methods 0.000 description 3
- 229920000642 polymer Polymers 0.000 description 3
- 238000000926 separation method Methods 0.000 description 3
- ILJSQTXMGCGYMG-UHFFFAOYSA-N triacetic acid Chemical compound CC(=O)CC(=O)CC(O)=O ILJSQTXMGCGYMG-UHFFFAOYSA-N 0.000 description 3
- 102000004506 Blood Proteins Human genes 0.000 description 2
- 108010017384 Blood Proteins Proteins 0.000 description 2
- 229920002284 Cellulose triacetate Polymers 0.000 description 2
- PEDCQBHIVMGVHV-UHFFFAOYSA-N Glycerine Chemical compound OCC(O)CO PEDCQBHIVMGVHV-UHFFFAOYSA-N 0.000 description 2
- XSQUKJJJFZCRTK-UHFFFAOYSA-N Urea Chemical compound NC(N)=O XSQUKJJJFZCRTK-UHFFFAOYSA-N 0.000 description 2
- NNLVGZFZQQXQNW-ADJNRHBOSA-N [(2r,3r,4s,5r,6s)-4,5-diacetyloxy-3-[(2s,3r,4s,5r,6r)-3,4,5-triacetyloxy-6-(acetyloxymethyl)oxan-2-yl]oxy-6-[(2r,3r,4s,5r,6s)-4,5,6-triacetyloxy-2-(acetyloxymethyl)oxan-3-yl]oxyoxan-2-yl]methyl acetate Chemical compound O([C@@H]1O[C@@H]([C@H]([C@H](OC(C)=O)[C@H]1OC(C)=O)O[C@H]1[C@@H]([C@@H](OC(C)=O)[C@H](OC(C)=O)[C@@H](COC(C)=O)O1)OC(C)=O)COC(=O)C)[C@@H]1[C@@H](COC(C)=O)O[C@@H](OC(C)=O)[C@H](OC(C)=O)[C@H]1OC(C)=O NNLVGZFZQQXQNW-ADJNRHBOSA-N 0.000 description 2
- 229940081735 acetylcellulose Drugs 0.000 description 2
- 229920002301 cellulose acetate Polymers 0.000 description 2
- DDRJAANPRJIHGJ-UHFFFAOYSA-N creatinine Chemical compound CN1CC(=O)NC1=N DDRJAANPRJIHGJ-UHFFFAOYSA-N 0.000 description 2
- 230000000694 effects Effects 0.000 description 2
- 238000002615 hemofiltration Methods 0.000 description 2
- 238000000338 in vitro Methods 0.000 description 2
- 239000012466 permeate Substances 0.000 description 2
- 239000011550 stock solution Substances 0.000 description 2
- MYKOKMFESWKQRX-UHFFFAOYSA-N 10h-anthracen-9-one;sulfuric acid Chemical compound OS(O)(=O)=O.C1=CC=C2C(=O)C3=CC=CC=C3CC2=C1 MYKOKMFESWKQRX-UHFFFAOYSA-N 0.000 description 1
- HIQIXEFWDLTDED-UHFFFAOYSA-N 4-hydroxy-1-piperidin-4-ylpyrrolidin-2-one Chemical compound O=C1CC(O)CN1C1CCNCC1 HIQIXEFWDLTDED-UHFFFAOYSA-N 0.000 description 1
- 208000006820 Arthralgia Diseases 0.000 description 1
- 208000023275 Autoimmune disease Diseases 0.000 description 1
- 206010006002 Bone pain Diseases 0.000 description 1
- 229920001747 Cellulose diacetate Polymers 0.000 description 1
- 206010064553 Dialysis amyloidosis Diseases 0.000 description 1
- 208000031226 Hyperlipidaemia Diseases 0.000 description 1
- 102000003982 Parathyroid hormone Human genes 0.000 description 1
- 108090000445 Parathyroid hormone Proteins 0.000 description 1
- 208000003251 Pruritus Diseases 0.000 description 1
- 208000001647 Renal Insufficiency Diseases 0.000 description 1
- LEHOTFFKMJEONL-UHFFFAOYSA-N Uric Acid Chemical compound N1C(=O)NC(=O)C2=C1NC(=O)N2 LEHOTFFKMJEONL-UHFFFAOYSA-N 0.000 description 1
- TVWHNULVHGKJHS-UHFFFAOYSA-N Uric acid Natural products N1C(=O)NC(=O)C2NC(=O)NC21 TVWHNULVHGKJHS-UHFFFAOYSA-N 0.000 description 1
- SMEGJBVQLJJKKX-HOTMZDKISA-N [(2R,3S,4S,5R,6R)-5-acetyloxy-3,4,6-trihydroxyoxan-2-yl]methyl acetate Chemical compound CC(=O)OC[C@@H]1[C@H]([C@@H]([C@H]([C@@H](O1)O)OC(=O)C)O)O SMEGJBVQLJJKKX-HOTMZDKISA-N 0.000 description 1
- 239000000654 additive Substances 0.000 description 1
- 239000000853 adhesive Substances 0.000 description 1
- 230000001070 adhesive effect Effects 0.000 description 1
- 150000001298 alcohols Chemical class 0.000 description 1
- 208000007502 anemia Diseases 0.000 description 1
- 230000009286 beneficial effect Effects 0.000 description 1
- 239000004202 carbamide Substances 0.000 description 1
- 230000000052 comparative effect Effects 0.000 description 1
- 229940109239 creatinine Drugs 0.000 description 1
- 238000007599 discharging Methods 0.000 description 1
- 239000003792 electrolyte Substances 0.000 description 1
- 230000002708 enhancing effect Effects 0.000 description 1
- 230000001747 exhibiting effect Effects 0.000 description 1
- 239000012530 fluid Substances 0.000 description 1
- -1 for example Substances 0.000 description 1
- 235000011187 glycerol Nutrition 0.000 description 1
- 230000001771 impaired effect Effects 0.000 description 1
- 230000005764 inhibitory process Effects 0.000 description 1
- 201000006370 kidney failure Diseases 0.000 description 1
- 229940057995 liquid paraffin Drugs 0.000 description 1
- 230000007774 longterm Effects 0.000 description 1
- 238000004519 manufacturing process Methods 0.000 description 1
- 239000000463 material Substances 0.000 description 1
- 210000003924 normoblast Anatomy 0.000 description 1
- 239000003960 organic solvent Substances 0.000 description 1
- 239000000199 parathyroid hormone Substances 0.000 description 1
- 229960001319 parathyroid hormone Drugs 0.000 description 1
- 229920002492 poly(sulfone) Polymers 0.000 description 1
- 229920002635 polyurethane Polymers 0.000 description 1
- 239000004814 polyurethane Substances 0.000 description 1
- 239000011148 porous material Substances 0.000 description 1
- 239000000047 product Substances 0.000 description 1
- 238000001223 reverse osmosis Methods 0.000 description 1
- 238000005070 sampling Methods 0.000 description 1
- 230000001225 therapeutic effect Effects 0.000 description 1
- ZIBGPFATKBEMQZ-UHFFFAOYSA-N triethylene glycol Chemical compound OCCOCCOCCO ZIBGPFATKBEMQZ-UHFFFAOYSA-N 0.000 description 1
- 238000000108 ultra-filtration Methods 0.000 description 1
- 229940045136 urea Drugs 0.000 description 1
- 229940116269 uric acid Drugs 0.000 description 1
- 238000005406 washing Methods 0.000 description 1
- 239000002699 waste material Substances 0.000 description 1
Landscapes
- External Artificial Organs (AREA)
- Separation Using Semi-Permeable Membranes (AREA)
Abstract
Description
【０００１】[0001]
【発明の属する技術分野】本発明は選択透過性中空糸膜
に関するものである。更に詳しくは、特定の水透過性能
および透析器における特定のデキストランの総括物質移
動係数、かつアルブミンの篩係数を有し、優れた分離性
能を呈する選択透過性を有するものであり、血液透析、
血液濾過透析等の血液処理に適し、特に中高分子量領域
の有害物質を除去するのに適した選択透過性中空糸膜を
提供するものである。BACKGROUND OF THE INVENTION 1. Field of the Invention The present invention relates to a selectively permeable hollow fiber membrane. More specifically, it has a specific water permeation performance and an overall mass transfer coefficient of a specific dextran in a dialyzer, and a sieving coefficient of albumin, and has selective permeability exhibiting excellent separation performance, hemodialysis,
It is an object of the present invention to provide a selectively permeable hollow fiber membrane suitable for blood treatment such as hemofiltration dialysis, and particularly suitable for removing harmful substances in a medium-high molecular weight region.
【０００２】[0002]
【従来の技術】選択透過性中空糸膜は、逆浸透や血液透
析等において従来より実用的に使用されてきている。特
に腎不全患者の血液を浄化するために、現在では中空糸
型血液透析器がよく使用されている。これは筐体の中に
透析膜、例えば、中空糸の膜を多数本、収納し、その中
空内部に患者の血液を流し、外部、すなわち、中空糸間
隙部に透析液を流して、中空糸膜壁を介して透析によっ
て、血液中の老廃物を除去し電解質濃度を是正するとと
もに、中空糸内外に圧力差を与えて限外濾過によって血
液中の余剰水分を除去するものである。更に、血液中か
ら血漿のみを分離し、あるいは、その血漿の中から特定
成分を除去して自己免疫疾患などを治療するために、中
空糸が使用されることもある。また最近になってタンパ
ク透過性血液透析やタンパク透過性血液濾過透析に中空
糸を用いることによって治療効果が得られることが確認
されるようになってきている。2. Description of the Related Art Permselective hollow fiber membranes have been practically used in reverse osmosis and hemodialysis. In particular, hollow fiber hemodialyzers are often used at present for purifying blood of patients with renal failure. This is because a housing contains a large number of dialysis membranes, for example, hollow fiber membranes, the blood of the patient is made to flow inside the hollows, and the dialysate is made to flow to the outside, that is, the hollow fiber gaps, to form hollow fibers. By dialysis through the membrane wall, waste products in blood are removed to correct the electrolyte concentration, and a pressure difference is applied between the inside and outside of the hollow fiber to remove excess water in blood by ultrafiltration. Furthermore, hollow fibers are sometimes used to separate plasma alone from blood or to remove specific components from the plasma to treat autoimmune diseases and the like. Recently, it has been confirmed that a therapeutic effect can be obtained by using hollow fibers in protein-permeable hemodialysis or protein-permeable hemofiltration dialysis.
【０００３】このように血液処理用の中空糸は目的に応
じて特定の物質を選択的に透過せしめなければならな
い。その性能は、中空糸の素材、ポロシテイ（孔の大き
さ、数など）、膜厚などによって決定される。As described above, a hollow fiber for blood treatment must selectively allow a specific substance to permeate according to the purpose. The performance is determined by the material of the hollow fiber, the porosity (the size and number of holes), the film thickness, and the like.
【０００４】ところで、近年、透析患者の長期合併症と
関連し、透析アミロイドシスの原因物質と考えられるβ
2 ―ＭＧ（ミクログロブリン）（分子量１１，８００）
掻痒感、高脂血症と関係すると考えられる副甲状腺ホル
モン（分子量約９，５００）、貧血に関与する赤芽球抑
制因子（分子量約１，０００）、関節痛、骨痛に係わる
と考えられる分子量２〜４万の物質、など比較的中高分
子量領域の有害物質の除去の必要性がさけばれている。
一方、人体に必須のアルブミン（分子量６６，０００）
の損失は極力避けなければならない。すなわち、分子量
４〜５万以下の物質の透過性に優れ、一方分子量６万以
上の物質の阻止性のよい分画分子量のシャープカット性
の良好な選択透過性膜が望まれている。[0004] In recent years, β which is considered to be a causative substance of dialysis amyloidosis is associated with long-term complications of dialysis patients.
2- MG (microglobulin) (molecular weight 11,800)
It is thought to be related to parathyroid hormone (molecular weight of about 9,500), which is considered to be related to pruritus and hyperlipidemia, erythroblast suppressor (molecular weight of about 1,000) involved in anemia, arthralgia, and bone pain. There is no need to remove harmful substances in a relatively medium to high molecular weight range, such as substances having a molecular weight of 20,000 to 40,000.
On the other hand, albumin essential for the human body (molecular weight 66,000)
You must avoid the loss of. That is, there is a demand for a permselective membrane which is excellent in permeability of substances having a molecular weight of 40,000 or less and 50,000 or less, and which has good rejection of substances having a molecular weight of 60,000 or more and a good sharp cut property of a cut molecular weight.
【０００５】しかるに、従来、ポリサルホンなどの合成
高分子では、例えば特公平２−１８６９５号や特公平５
−５４３７３号に見られるように、比較的上記要求を満
たしたものが得られているが、セルロース誘導体特にト
リアセテートでは、例えば特公昭５８−２４１６５号に
見られるように、中空糸を湿式紡糸するときの芯剤に、
流動パラフィン、高級アルコール、イソプロピルミリス
テートなど、トリアセテート紡糸原液に対し凝固性のな
いものを使用するために、紡糸原液におけるトリアセテ
ートの濃度を高め、紡糸時の曳糸性を高くせざるを得な
い。また、紡糸原液をノズルから出糸後、中空糸外面か
ら凝固液で固化させるために、中空糸外面に緻密構造の
層が形成される。However, conventionally, in synthetic polymers such as polysulfone, for example, Japanese Patent Publication No. 2-18695 and Japanese Patent Publication No. 5
As shown in Japanese Patent No. 54373/1998, those relatively satisfying the above requirements have been obtained. However, in the case of a cellulose derivative, particularly triacetate, when a hollow fiber is wet-spun, for example, as shown in Japanese Patent Publication No. 58-24165. To the core agent of
Since liquid paraffin, higher alcohols, isopropyl myristate, and the like that do not coagulate in the triacetate spinning dope are used, the concentration of triacetate in the spinning dope must be increased to enhance the spinnability during spinning. In addition, a layer having a dense structure is formed on the outer surface of the hollow fiber in order to solidify the spinning stock solution from the nozzle and then solidify the outer surface of the hollow fiber with the coagulating liquid.
【０００６】これらの理由により、従来、セルロース誘
導体中空糸は、合成ポリマーの膜に比し、構造の緻密層
と多孔層の密度差が小さく、全体として均一層に近く、
物質の透過性能が十分とはいえなかった。そのために膜
の厚さを減少せしめ、透過性の向上を図ってきたが、十
分なものとはいえない。更に、膜構造の緻密層と多孔層
の密度差が不明確なために、透過物質の分画特性におい
ても、改良の余地のあるものであった。[0006] For these reasons, conventionally, a cellulose derivative hollow fiber has a smaller difference in density between a dense layer and a porous layer in structure than a synthetic polymer membrane, and is close to a uniform layer as a whole.
The permeability of the substance was not sufficient. For this purpose, the thickness of the film has been reduced and the permeability has been improved, but this is not sufficient. Furthermore, since the density difference between the dense layer and the porous layer having a membrane structure is unclear, there is room for improvement in the fractionation characteristics of the permeated substance.
【０００７】[0007]
【発明の目的】本発明は、このような従来技術の問題点
を解決することを目的とするものであって、セルロース
誘導体のポリマーを使用して従来の合成ポリマーの構造
に近い粗密構造を与え、高い分子量分画特性を付与する
ことである。特に血液透析や血液濾過透析においてβ2
―ＭＧ等の中高分子量領域の有害物質の除去とアルブミ
ンなどの有用物質の流出阻止を高めることが可能な選択
透過性中空糸膜を提供することを目的としている。It is an object of the present invention to solve the above problems of the prior art, and to use a polymer of a cellulose derivative to give a coarse and dense structure close to that of a conventional synthetic polymer. , To impart high molecular weight fractionation characteristics. Β 2 especially in hemodialysis and hemodiafiltration
-An object of the present invention is to provide a permselective hollow fiber membrane capable of removing harmful substances in the medium and high molecular weight region such as MG and enhancing outflow inhibition of useful substances such as albumin.
【０００８】[0008]
【発明の構成】本発明者は、かかる目的を達成するため
に鋭意研究した結果、特定の水透過性能とデキストラン
の総括物質移動係数及びアルブミンの篩係数を有する中
空糸を用いた血液浄化器が飛躍的に高められた分離性能
を発揮することを見い出し、本発明に到達した。The present inventor has conducted extensive studies in order to achieve such an object, and as a result, found that a blood purifier using a hollow fiber having a specific water permeability, a general mass transfer coefficient of dextran, and a sieve coefficient of albumin was obtained. The present invention has been achieved by discovering that the separation performance is dramatically improved.
【０００９】すなわち、本発明は、選択透過性を有する
中空糸膜において、３７℃における水透過性能（ＵＦ
Ｒ）が、２００ｍｌ／Ｈｒ，ｍｍＨｇ，ｍ2 以上であ
り、かつ該中空糸膜を透析器として組立て測定した、分
子量１０，０００のデキストランの０．１重量％を含む
水溶液を使用した該デキストランの総括物質移動係数
（Ｋ0 ）が６．７×１０-5ｃｍ／ｓｅｃ以上、牛血漿を
１時間灌流した後のアルブミンの篩係数（Ｓ．Ｃ．）が
０．０２以下であることを特徴とする実質的にセルロー
ス誘導体からなる選択透過性中空糸膜を提供するもので
ある。That is, the present invention provides a hollow fiber membrane having selective permeability with water permeability (UF) at 37 ° C.
R) is 200 ml / Hr, mmHg, m 2 or more, and the hollow fiber membrane was assembled and measured as a dialyzer to measure the dextran using an aqueous solution containing 0.1% by weight of dextran having a molecular weight of 10,000. The overall mass transfer coefficient (K 0 ) is 6.7 × 10 −5 cm / sec or more, and the sieving coefficient (SC) of albumin after perfusion of bovine plasma for 1 hour is 0.02 or less. The present invention provides a permselective hollow fiber membrane consisting essentially of a cellulose derivative.
【００１０】以下、本発明について更に詳細に説明す
る。Hereinafter, the present invention will be described in more detail.
【００１１】すなわち、本発明における中空糸膜は、選
択透過性を有するものであり、その素材としては、セル
ロース誘導体、特にアセチルセルロースであり、その中
でも一般的に使用されるものとしては、実質的にセルロ
ースジアセテート、セルローストリアセテートからなる
高分子である。なお、実質的とは、このセルロース誘導
体の特性を損わない範囲で、他の高分子、添加物などを
含有してもよいことを意味する。That is, the hollow fiber membrane of the present invention has a selective permeability, and is made of a cellulose derivative, particularly acetylcellulose. And a polymer composed of cellulose diacetate and cellulose triacetate. Note that “substantially” means that other polymers, additives, and the like may be contained as long as the properties of the cellulose derivative are not impaired.
【００１２】また本発明の中空糸膜の膜壁の構造に関し
ては、物質の分離透過特性と機械特性を機能分担させる
ような、極薄緻密層と、機械的に流体圧力に耐えられる
が、物質の透過抵抗には殆んどならない多孔層とを合せ
持つような、従来、合成高分子で実現されていた２層又
は多層構造が好ましい。特に、中空糸膜の内面を通して
血液を処理する場合には、少くとも中空糸内面に緻密層
があるのが望ましい。内面に多孔層があると、その部分
に血中蛋白が付着したり、あるいは孔中に侵入したりし
て、物質透過の阻害になる懸念がある。The structure of the membrane wall of the hollow fiber membrane of the present invention is characterized by an ultra-thin dense layer that functions to separate and permeate the separation and permeation characteristics of the substance and the mechanical properties, and is capable of mechanically withstanding fluid pressure. A two-layer or multi-layer structure conventionally realized by a synthetic polymer, which has a porous layer having almost no permeation resistance, is preferable. In particular, when blood is processed through the inner surface of the hollow fiber membrane, it is desirable that there is a dense layer at least on the inner surface of the hollow fiber. If there is a porous layer on the inner surface, there is a concern that blood proteins may adhere to that portion or penetrate into the pores, thereby impeding the permeation of substances.
【００１３】中空糸膜の膜厚は、一般に物質の透過性か
らみれば薄いのが望ましいが、本発明に係わるような２
層以上の構造のものでは、多孔層を有するために機械的
強度の点より３０μｍ以上が好ましい。なお、中空糸膜
の内径は１００〜３００μｍ、更には１５０〜２５０μ
ｍが好ましい。Generally, the thickness of the hollow fiber membrane is preferably thin in view of the permeability of the substance.
In the case of a structure having two or more layers, the thickness is preferably 30 μm or more from the viewpoint of mechanical strength because of having a porous layer. The inner diameter of the hollow fiber membrane is 100 to 300 μm, and more preferably 150 to 250 μm.
m is preferred.
【００１４】また、本発明の中空糸膜の３７℃における
水透過性能（ＵＦＲ）は２００ｍｌ／ｈｒ，ｍｍＨｇ，
ｍ2 以上である。従来の比較的均一構造の膜では、この
ような高レベルの水透過性能は得られ難かった。このよ
うなＵＦＲをもたせることで、一定量の除水をするため
のＴＭＰ（中空糸膜の両側にかかる差圧）を低めること
ができ、中空糸膜への血中蛋白質の付着などが抑えられ
る。例えば、牛血を用いた透析において、有効面積１．
５ｍ2 の透析器で４時間に２Ｌ（リッター）の除水をす
るとき、従来のセルロースアセテート系中空糸を用いた
透析器では２０〜３０ｍｍＨｇのＴＭＰが必要である
が、本発明の中空糸を用いた透析器では約１／２の２０
ｍｍＨｇ未満、例えば１０ｍｍＨｇ以上２０ｍｍＨｇ未
満のＴＭＰで十分である。また、水透過性が高いという
ことは水分子だけでなく、尿素、クレアチニン、尿酸な
どの低分子物質の透過性も高いことを意味し、透析器と
しては基本的性能として望ましいものである。The water permeability (UFR) of the hollow fiber membrane of the present invention at 37 ° C. is 200 ml / hr, mmHg,
m 2 or more. It was difficult to obtain such a high level of water permeation performance with a conventional membrane having a relatively uniform structure. By providing such a UFR, TMP (a differential pressure applied to both sides of the hollow fiber membrane) for removing a certain amount of water can be lowered, and adhesion of blood protein to the hollow fiber membrane can be suppressed. . For example, in dialysis using bovine blood, an effective area of 1.
When removing 2 L (liter) of water with a 5 m 2 dialyzer for 4 hours, a conventional dialyzer using a cellulose acetate hollow fiber requires TMP of 20 to 30 mmHg. With the dialyzer used, about 20
A TMP of less than mmHg, for example 10 mmHg or more and less than 20 mmHg is sufficient. Further, high water permeability means high permeability of not only water molecules but also low molecular weight substances such as urea, creatinine, and uric acid, which is desirable as a basic performance as a dialyzer.
【００１５】また、本発明の中空糸膜の特徴の１つとし
て、その中空糸束を用いて組み立てた透析器においてデ
キストラン１０，０００の総括物質移動係数Ｋ0 が６．
７×１０-5ｃｍ／ｓｅｃ以上であることがあげられる。
なお、かかるＫ0 の測定方法としては、円筒状容器に約
５２％の充填率で中空糸束を充填して両端を接着剤でシ
ール固化した後切断して中空部を開口することにより
１．５ｍ2 の有効膜表面積の透析器を組み立てたものを
用いて、３７℃において血液側すなわち中空部側に０．
１重量％のデキストラン１０，０００の水溶液を２００
ｍｌ／分で流し、透析液側すなわち中空糸間隙部側に水
を５００ｍｌ／分で流した場合の血液側の流出液中の濃
度を測定することによって、下記式によりＫ0 が得られ
る。サンプリング液中のデキストラン濃度は、例えばア
ンスロン―硫酸法により測定する。Further, one of the characteristics of the hollow fiber membrane of the present invention is that the overall mass transfer coefficient K 0 of dextran 10,000 in the dialyzer assembled using the hollow fiber bundle is 6.
It may be 7 × 10 −5 cm / sec or more.
The method of measuring K 0 is as follows: 1. A hollow container is filled with hollow fiber bundles at a filling rate of about 52%, both ends are sealed and solidified with an adhesive, and then cut to open the hollow portion. Using an assembled dialyzer with an effective membrane surface area of 5 m 2 , at 37 ° C.
200% 1% by weight dextran 10,000 in water
K 0 is obtained from the following formula by measuring the concentration in the effluent on the blood side when the flow rate is 500 ml / min and the flow rate is 500 ml / min on the dialysate side, that is, the hollow fiber gap side. The dextran concentration in the sampling solution is measured, for example, by the anthrone-sulfuric acid method.
【００１６】[0016]
【数１】 [Equation 1]
【００１７】本発明の中空糸膜のＫ0 としては６．７×
１０-5ｃｍ／ｓｅｃ以上、更に好ましくは９．２×１０
-5ｃｍ／ｓｅｃ以上が実用上好ましい。The K 0 of the hollow fiber membrane of the present invention is 6.7 ×
10 −5 cm / sec or more, more preferably 9.2 × 10
Practically preferable is -5 cm / sec or more.
【００１８】更に本発明に係わる中空糸膜は、その中空
糸束を用いて組み立てた透析器において、血液側に牛血
漿を１時間灌流した後に測定したアルブミンの篩係数が
０．０２以下であることを特徴としている。好ましくは
０．０１以下であり、水、低分子物質及び分子量１０，
０００のデキストランの物質透過性が良好であるのに拘
らず、分子量が約６６，０００のアルブミンの中空糸膜
を通じての透過性は十分に阻止されているものであり、
これらの分子量の間にシャープな分画特性を有してい
る。Further, in the hollow fiber membrane according to the present invention, the sieving coefficient of albumin measured after perfusing bovine plasma on the blood side for 1 hour in a dialyzer assembled using the hollow fiber bundle is 0.02 or less. It is characterized by that. It is preferably 0.01 or less, water, a low molecular weight substance and a molecular weight of 10,
Despite the good substance permeability of 000 dextran, the permeability of albumin having a molecular weight of about 66,000 through the hollow fiber membrane is sufficiently blocked.
It has sharp fractionation characteristics between these molecular weights.
【００１９】このように本発明の中空糸膜は、血液透析
器や血液濾過透析に使用した場合に、β2 ―ＭＧなどの
中高分子量の領域の有害物質の除去性能が高く、かつ低
分子量領域の有害物質の除去性能も優れている上に、人
体に有益なアルブミンの損失量が少ないという選択透過
性に優れたものである。As described above, when the hollow fiber membrane of the present invention is used in a hemodialyzer or hemodiafiltration, it has a high performance of removing harmful substances in the medium and high molecular weight regions such as β 2 -MG and a low molecular weight region. In addition to its excellent performance of removing harmful substances, it also excels in selective permeability because the amount of albumin that is beneficial to the human body is small.
【００２０】かかる本発明の中空糸膜の製造方法は特に
限定されるものではないが、望ましくはセルロース誘導
体を有機溶剤に溶解した紡糸原液を、芯剤として水溶液
を用いて、チューブインオリフィス状ノズルより吐出さ
せ、気体中を通過後、水溶性凝固液中に通し固化させる
方式が採用される。The method for producing the hollow fiber membrane of the present invention is not particularly limited, but a tube-in-orifice nozzle is preferably prepared by using an aqueous spinning solution prepared by dissolving a cellulose derivative in an organic solvent as the core agent. A method is adopted in which the liquid is further discharged, passed through gas, and then passed through a water-soluble coagulating liquid to be solidified.
【００２１】[0021]
【実施例】以下本発明について実施例をあげて更に具体
的に説明するが、本発明は、これらの実施例によって何
ら限定されるものではない。EXAMPLES Hereinafter, the present invention will be described more specifically with reference to examples, but the present invention is not limited to these examples.
【００２２】［実施例１〜８、比較例１〜３］セルロー
ストリアセテート１３部とトリエチレングリコール２０
部を、ジメチルスルホオキシド６７部に均一溶解したも
のを紡糸原液として、チューブインオリフィス型ノズル
より、ジメチルスルホオキシドの水溶液を芯剤として、
空気中に吐出させた後、凝固液の中に導いて固化させ、
水洗、グリセリン付着処理後、捲取った。得られた中空
糸膜を乾燥後束状にして、円管状の容器内に挿入充填し
て、両端をポリウレタンで接着固定し、有効面積が約
１．５ｍ2 の血液透析器を作成し、ｉｎ ｖｉｔｒｏで
の水透過性能（ＵＦＲ）とデキストラン１０，０００の
総括物質移動係数（Ｋ0 ）及び牛血漿を用いたアルブミ
ンの篩係数（Ｓ．Ｃ．）を測定した。一方、牛血漿にβ
2 ―ＭＧを０．０５％溶解したものを用い、血液側を２
００ｍｌ／分で流し、透析液を５００ｍｌ／分で流し
て、約４時間の血液透析を行った。Examples 1 to 8 and Comparative Examples 1 to 13 Cellulose triacetate 13 parts and triethylene glycol 20
Part was uniformly dissolved in 67 parts of dimethyl sulfoxide as a spinning stock solution, and an aqueous solution of dimethyl sulfoxide was used as a core agent through a tube-in-orifice type nozzle.
After discharging into the air, lead it into the coagulating liquid to solidify,
After washing with water and adhesion of glycerin, it was wound up. The obtained hollow fiber membranes were dried, bundled, inserted and filled in a cylindrical container, and both ends were adhesively fixed with polyurethane to prepare a hemodialyzer with an effective area of about 1.5 m 2. The water permeability (UFR) in vitro, the overall mass transfer coefficient (K 0 ) of dextran 10,000, and the sieving coefficient (SC) of albumin using bovine plasma were measured. Meanwhile, β in bovine plasma
2 -Use 0.05% MG dissolved, 2 on the blood side
The hemodialysis was carried out for about 4 hours by flowing the dialysate at 500 ml / min at a flow rate of 00 ml / min.
【００２３】透析前後でのβ2 ―ＭＧの除去率、すなわ
ちRemoval rate of β 2 -MG before and after dialysis, that is,
【００２４】[0024]
【数２】 [Equation 2]
【００２５】を算出した後、除水によるβ2 ―ＭＧの濃
縮効果を補正した。After calculating, the concentration effect of β 2 -MG by removing water was corrected.
【００２６】また、透析開始直後と４時間透析終了直前
でのＵＦＲの低下率、すなわちThe UFR decrease rate immediately after the start of dialysis and immediately before the end of dialysis for 4 hours, that is,
【００２７】[0027]
【数３】 (Equation 3)
【００２８】を算出した。更に透析終了後、全透析液中
のアルブミンの量を測定しアルブミン漏出量とした。Was calculated. After the dialysis was completed, the amount of albumin in the total dialysate was measured and used as the albumin leakage amount.
【００２９】表１は紡糸の条件とｉｎ ｖｉｔｒｏの特
性値及び透析性能を示したものである。本発明の中空糸
は、β2 ―ＭＧの除去率が大きく、ＵＦＲの経時変化お
よびアルブミンの透析液への漏出量が小さくなってい
る。Table 1 shows spinning conditions, in vitro characteristic values and dialysis performance. The hollow fiber of the present invention has a large β 2 -MG removal rate and a small change in UFR with time and a small amount of albumin leaked into the dialysate.
【００３０】[0030]
【表１】 [Table 1]
【００３１】本発明の中空糸膜は、その集束体を用いて
血液浄化器を組み立てた場合、β2―ＭＧ等の中高分子
量領域の有害物質の除去率が高いのみならず、除水性能
の透析中の経時変化が小さく、更にアルブミンの透析液
中への漏出量が少ないという優れた効果を奏するもので
ある。The hollow fiber membrane of the present invention not only has a high removal rate of harmful substances in the medium and high molecular weight region such as β 2 -MG when a blood purifier is assembled using the bundle, but also has a high water removal performance. It has an excellent effect that the change with time during dialysis is small and the amount of albumin leaked into the dialysate is small.
Claims (3)
３７℃における水透過性能（ＵＦＲ）が、２００ｍｌ／
Ｈｒ，ｍｍＨｇ，ｍ2 以上であり、かつ該中空糸膜を透
析器として組立て測定した、分子量１０，０００のデキ
ストランの０．１重量％を含む水溶液を使用した該デキ
ストランの総括物質移動係数（Ｋ0 ）が６．７×１０-5
ｃｍ／ｓｅｃ以上、牛血漿を１時間灌流した後のアルブ
ミンの篩係数（Ｓ．Ｃ．）が０．０２以下であることを
特徴とする実質的にセルロース誘導体からなる選択透過
性中空糸膜。1. A hollow fiber membrane having permselectivity,
Water permeation performance (UFR) at 37 ℃ is 200ml /
An overall mass transfer coefficient (K) of the dextran using an aqueous solution containing 0.1% by weight of dextran having a molecular weight of 10,000, which was Hr, mmHg, m 2 or more and was measured by assembling and measuring the hollow fiber membrane as a dialyzer. 0 ) is 6.7 × 10 -5
A permselective hollow fiber membrane consisting essentially of a cellulose derivative, wherein the sieving coefficient (SC) of albumin after perfusion of bovine plasma for 1 hour or more is 0.02 or less.
に緻密層を有することからなる特許請求の範囲第１項に
記載の選択透過性中空糸膜。2. The selectively permeable hollow fiber membrane according to claim 1, wherein the selectively permeable hollow fiber membrane has a dense layer on at least the inner surface.
以上からなる特許請求の範囲第１項に記載の選択透過性
中空糸膜。3. The selectively permeable hollow fiber membrane has a thickness of 30 μm.
The selectively permeable hollow fiber membrane according to claim 1, comprising the above.
Priority Applications (4)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| JP09845796A JP3345260B2 (en) | 1996-04-19 | 1996-04-19 | Permselective hollow fiber membrane |
| CA002202969A CA2202969C (en) | 1996-04-19 | 1997-04-17 | Selectively permeable hollow fiber membrane and process for producing same |
| EP97302660A EP0801973A1 (en) | 1996-04-19 | 1997-04-18 | Selectively permeable hollow fiber membrane and process for producing same |
| US08/837,475 US6013182A (en) | 1996-04-19 | 1997-04-18 | Selectively permeable hollow fiber membrane and process for producing same |
Applications Claiming Priority (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| JP09845796A JP3345260B2 (en) | 1996-04-19 | 1996-04-19 | Permselective hollow fiber membrane |
Publications (2)
| Publication Number | Publication Date |
|---|---|
| JPH09285536A true JPH09285536A (en) | 1997-11-04 |
| JP3345260B2 JP3345260B2 (en) | 2002-11-18 |
Family
ID=14220241
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| JP09845796A Ceased JP3345260B2 (en) | 1996-04-19 | 1996-04-19 | Permselective hollow fiber membrane |
Country Status (1)
| Country | Link |
|---|---|
| JP (1) | JP3345260B2 (en) |
Cited By (1)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| KR20210007674A (en) * | 2019-07-12 | 2021-01-20 | 한국화학연구원 | Hollow fiber membrane with improved mechanical strength, and method for manufacturing the same |
-
1996
- 1996-04-19 JP JP09845796A patent/JP3345260B2/en not_active Ceased
Cited By (1)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| KR20210007674A (en) * | 2019-07-12 | 2021-01-20 | 한국화학연구원 | Hollow fiber membrane with improved mechanical strength, and method for manufacturing the same |
Also Published As
| Publication number | Publication date |
|---|---|
| JP3345260B2 (en) | 2002-11-18 |
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