JP3982906B2

JP3982906B2 - Blood processing membrane

Info

Publication number: JP3982906B2
Application number: JP13261298A
Authority: JP
Inventors: 敏士上住; 一吉田
Original assignee: Asahi Kasei Medical Co Ltd
Current assignee: Asahi Kasei Medical Co Ltd
Priority date: 1998-04-28
Filing date: 1998-04-28
Publication date: 2007-09-26
Anticipated expiration: 2018-04-28
Also published as: JPH11309353A

Description

【０００１】
【発明の属する技術分野】
本発明は、血液透析などの分野で用いられる血液処理用膜に関する。
【０００２】
【従来の技術】
従来、血液透析あるいは血液吸着濾過などに使用される血液処理用膜は、血液中に蓄積した老廃物あるいは有害物を、拡散、濾過、吸着などの原理に基づき血中から除去し、例えば、腎機能が完全に喪失した患者の治療用途に広く施行されている。
しかし、これらの治療に際しては、人工物である膜と血液が接触するため、血液の持つ異物認識反応によって、膜に対する血小板の付着あるいは白血球の活性化などが惹起され、結果として生体適合性が悪い場合がある。この対策として、中空糸膜内表面近傍に親水性ポリマーが膜に存在した膜（特開平４−３００６３６号）、あるいは選択透過膜において該膜が凝集粒子の集合体からなり、しかも、凝集粒子の表面に親水性ポリマーが濃縮して存在し、血液との親和性を高める（特開平７−２８９８６６）などが考案され、血液との化学的親和性を高める技術が開示されている。ところが、膜の血液との接触面の形状、すなわち、平滑性が血液に及ぼす影響については検討されておらず、血液接触面上の凹凸による血液の刺激によって、生体適合性が悪くなると考えられた。
【０００３】
【発明が解決しようとする課題】
本発明は、血液との親和性を高めた血液処理用膜を提供することを目的とする。
【０００４】
【課題を解決するための手段】
本発明者らは、鋭意検討を進めた結果、被処理血液が接する膜表面に特異的な凹凸がなく、実質的に膜表面が一様に滑らかであることが、血液との親和性を著しく高めることを見出し、本発明をなすに到った。
すなわち、本発明は、ポリスルホンとポリビニルピロリドンとジメチルアセトアミドを含む製膜原液から製造された中空糸型血液処理用膜であって、ジメチルアセトアミド水溶液からなる中空剤とともに７００〜３５００ｍＰａ・ｓの粘度を有する前記製膜原液を１．１〜１．９のドラフト率で紡糸し、被処理血液と接触する膜表面の平滑性の指標であるＰＶ値を２０ｎｍ以下、かつ、Ｒａ値を６ｎｍ以下としたことを特徴とする中空糸型血液処理用膜である。
【０００５】
本発明でいう膜の平滑性は、ＰＶ値、Ｒａ値により定義される。ＰＶ値とは、膜表面の凹凸を測定した際の、基準点に対する全測定点の凹凸の最大値と最小値の差を表わし、また、Ｒａ値は、基準点に対する全測定点の凹凸の算術平均値を表わす。また、これら膜表面の平滑性は、走査型白色干渉法を用いた３次元表面構造解析顕微鏡のような解析装置により得られ、測定値から算出することができるもので、測定装置は公知の装置が利用でき、例えば、試験片に対し、走査型白色干渉顕微鏡によって干渉対物レンズを光軸方向に走査しながら干渉像を収集し、デジタル化された干渉強度の情報をワークステーションで処理し、目的のＰＶ値、Ｒａ値を得ることができる。
【０００６】
本発明の課題を満たす膜は、膜面を構成する凹凸の全平均値Ｒａ値が小さい、すなわち、単に個別の凹凸の平均を取った場合に概ね滑らかであるばかりでなく、ＰＶ値が小さい、すなわち、特異的に際立つ凹凸がなく、実質的に膜面全域を通じて一様にむらの少ない平滑な膜表面を持つものである。具体的には、ＰＶ値が２０ｎｍ以下であり、Ｒａ値が６ｎｍ以下、さらに好ましくはＲａ値が３ｎｍ以下である。
また、同時に基準面に対する測定面凹凸の数値から、二乗和の平方根（ｒｍｓ値）を算出することができるが、これは、算出方法が表すように測定値のバラツキを示すもので、上記、ＰＶ値、Ｒａ値と同様に表面の平滑性を表す尺度となる。本発明の課題を満たす膜としては、上記、ＰＶ値、Ｒａ値が所定の数値範囲を満たした上で、さらにｒｍｓ値が４ｎｍ以下であることが好ましい。ｒｍｓ値はさらに３．５ｎｍ以下であることが望ましい。
【０００７】
本発明の平滑な表面を有する膜の材質および形状は特に限定されないが、現在の血液処理用膜は、専ら中空糸膜形状が主流であり、また、公知の材質の中ではポリスルホン系、ポリアクリロニトリル系、ポリメチルメタクリレート系、ポリエステル系等からなる合成高分子膜が、中空糸形状において比較的良好な平滑性を実現しやすい。なかでもポリスルホン系高分子にポリビニルピロリドンを添加してなるものが好ましい例として挙げられるが、他にポリビニルアルコール、ポリエチレングリコールなどの親水性高分子を添加してなる中空糸膜も、本発明の好ましい具体例として挙げられる。
【０００８】
本発明の中空糸型血液処理用膜は、例えば、ポリスルホン系高分子にポリビニルピロリドンを添加してなる膜の場合には、以下のようにして製造される。
製膜原液の組成としては、ポリスルホン１０〜２０重量％、ポリビニルピロリドン２〜８％、およびこれらの溶剤からなる。溶剤はポリスルホンとポリビニルピロリドンの双方を溶解できるものであればよく、ジメチルアセトアミド、ジメチルスルホキシド、Ｎ、Ｎ−ジメチルホルムアミド、Ｎ−メチル−２−ピロリドン等が挙げられ、これらを単独あるいは任意の割合で混合して使用することができる。さらに、ポリスルホンの非溶剤として、ポリマーが析出しない程度に水を添加してもよい。
【０００９】
製膜課程においては、製膜原液からの溶剤の拡散と非溶剤の浸入により、ポリスルホンの核形成後、凝集粒子が生成し、ポリビニルピロリドンがポリスルホン凝集粒子表面に存在した状態で、血液との接触面側に緻密層が、また、それ以外の部分では支持層が形成された中空糸膜が製造される。したがって、緻密層表面の凹凸を好ましい大きさにするためには、生成過程にあるポリスルホン凝集粒子の生成速度を制御する必要がある。本発明者らは、製膜原液の粘度を特定範囲とし、かつ、その原液を特定のドラフト率で紡糸することにより、紡糸そのものが安定するばかりでなく、製造された中空糸膜が被処理血液と接触する面の凹凸が所望の滑らかさに抑えられることを見出した。本発明の平滑性を満たすためには、製膜原液の粘度は７００〜３５００ｍＰａ・ｓの範囲にあることが好ましい。また、ドラフト率についても１．１〜１．９の範囲であることが必要であり、１．１〜１．５の範囲であることが好ましい。
このようにして得られる血液処理用膜は、被処理血液と接触する表面が平滑であるため、血小板の活性化が起こりにくく、血液との親和性が良いことを見い出した。
【００１０】
【発明の実施の形態】
以下に本発明をさらに具体的に説明するために、実施例および比較例を挙げて説明するが、本発明は、これらの実施例により限定されるものではない。
なお、実施例、比較例中のＰＶ値、Ｒａ値の測定および中空糸膜への血小板の粘着は、以下の方法に従い行った。
【００１１】
（ＰＶ値、Ｒａ値の測定）
試験に供した血液処理用膜は、まず、実際に透析等で使用される際と同様に、容器内に充填された血液処理器の状態で洗浄等の前処理操作を行った。その後、容器を壊して中空糸長さ方向の中央部分の膜を取り出し、血液との接触面を露出させた後に試験片とし、走査型白色干渉顕微鏡（ＺＹＧＯ社製ＮｅｗＶｉｅｗ１００）によって、平面方向の解像度が約１μｍ、凹凸方向の解像度が０．１ｎｍの４０倍対物レンズを用いて、試験片表面を走査して２５μｍ四方の膜表面凹凸を測定し、ＰＶ値、Ｒａ値を算出した。算出の際には、中空糸10本分の数値を平均し、代表値として用いた。
【００１２】
（中空糸膜への血小板の粘着量の測定）
膜表面への粘着量を血小板活性化の指標とした。被測定中空糸膜を長さ１５ｃｍに切り、１０本束ねて小型モジュールを作成し、該小型モジュールにヘパリン添加新鮮血を線速１．０ｃｍ／ｓにて１５分間通過させ、続いて生理食塩水を1分間通過させた。次に、中空糸を細断し、０．５％トリトンＸ−１００を含む生理食塩水中で超音波照射して、膜表面に粘着した血小板から放出される乳酸脱水素酵素を定量した。酵素活性の測定は、ＬＤＨモノテストキット（ベーリンガー・マンハイム・山之内製薬）を使用した。
【００１３】
【実施例１】
ポリスルホン（ＡＭＯＣＯ社製：Ｐ−１７００）１７重量部とＰＶＰ（ＩＳＰ社製：Ｋ−９０）４．５重量部をジメチルアセトアミド７７．５重量部、水１重量部に添加し、１０時間攪拌溶解し、製膜原液を得た。この製膜原液の粘度は、４５℃で２２００ｍＰａ・ｓであった。次に、この製膜原液を４５℃に保ったまま、４０％ＤＭＡＣ水溶液からなる中空剤とともに、スリット幅５９．５μｍの環状口金より吐出して、紡速５０ｍ／分で５０ｃｍの空走部を走行させた後、紡口下部に設置した水を入れた凝固浴中を通過させた後、巻き取った。乾燥時の中空糸膜厚を４５μｍに合わせるように原液吐出量を調整したので、原液吐出線速は３５．３ｍ／分となり、ドラフト率は１．４２であった。このようにして巻き取った中空糸束は、切断後、８０℃の熱水を２時間かけて洗浄し、グリセリン水溶液を付着させて真空乾燥した。
【００１４】
得られた中空糸膜を１００本束ねてプラスチック性円筒形容器に挿入し、該中空糸の両端を、ウレタン樹脂接着剤で固定した後、血液を導くためのキャップを取り付けて有効長２５ｃｍのミニモジュールとし、γ線を２５ｋＧｙ照射し、本発明の血液処理用膜を内蔵してなる血液処理器を得た。
得られた血液処理器内の血液処理用膜について、血小板の粘着量を測定した結果を表１に示す。
【００１５】
【実施例２】
ポリスルホン（ＡＭＯＣＯ社製：Ｐ−１７００）１７重量部とＰＶＰ（ＩＳＰ社製：Ｋ−９０）３．５重量部をジメチルアセトアミド７９．５重量部に添加し、１０時間攪拌溶解し、製膜原液を得た。この製膜原液の粘度は、４５℃で１３８０ｍＰａ・ｓであった。次に、この製膜原液を４５℃に保ったまま、４０％ＤＭＡＣ水溶液からなる中空剤とともに、スリット幅５９．５μｍの環状口金より吐出して、紡側５０ｍ／分で５０ｃｍの空走部を走行させた後、紡口下部に設置した水を入れた凝固浴中を通過させ巻き取った。乾燥時の中空糸膜厚を４５μｍに合わせるように原液吐出量を調整したので、原液吐出線速は３１．６ｍ／分となり、ドラフト率は１．５８であった。このようにして巻き取った中空糸束は、その後実施例１と同じ処理を行った後、実施例と同様なγ線を２５ｋＧｙ照射し、本発明の血液処理用膜を内蔵してなる血液処理器を得た。
得られた血液処理器内の血液処理用膜について、血小板の粘着量を測定した結果を表１に示す。
【００１６】
【比較例】
実施例２と同じ製膜原液を４０％ＤＭＡＣ水溶液からなる中空剤とともに、スリット幅５０μｍの環状口金より吐出して、紡側５０ｍ／分で５０ｃｍの空走部を走行させた後、紡口下部に設置した水を入れた凝固浴中を通過させ巻き取った。乾燥時の中空糸膜厚を４５μｍに合わせるように原液吐出量を調整したので、原液吐出線速は５０．２ｍ／分となり、ドラフト率は１．０であった。このようにして巻き取った中空糸束は、その後実施例１と同じ処理を行った後、血液処理用膜を得た。
得られた血液処理用膜について、血小板の粘着量を測定した結果を表１に示す。
【００１７】
【表１】

【００１８】
【発明の効果】
本発明により、被処理血液が接触する膜表面を、剥離や溶出の可能性のある被覆処理などを表面に施したりせずに、膜自身の表面を平滑にすることにより、血液への刺激の少ない性状にすることが実現された。[0001]
BACKGROUND OF THE INVENTION
The present invention relates to a blood processing membrane used in fields such as hemodialysis.
[0002]
[Prior art]
Conventionally, blood treatment membranes used for hemodialysis or blood adsorption filtration remove waste or harmful substances accumulated in blood from the blood based on the principle of diffusion, filtration, adsorption, etc. It is widely used for the treatment of patients who have lost their function completely.
However, in these treatments, since the membrane, which is an artifact, comes into contact with blood, the foreign body recognition reaction of blood induces platelet adhesion or leukocyte activation, resulting in poor biocompatibility. There is a case. As a countermeasure, a membrane in which a hydrophilic polymer is present in the vicinity of the inner surface of the hollow fiber membrane (Japanese Patent Laid-Open No. 4-300636), or a permselective membrane, the membrane is composed of aggregates of aggregated particles. A technique in which a hydrophilic polymer is concentrated on the surface to increase affinity with blood (Japanese Patent Laid-Open No. 7-289866) has been devised, and a technique for increasing chemical affinity with blood is disclosed. However, the shape of the contact surface with the blood of the membrane, that is, the effect of smoothness on the blood has not been studied, and it was thought that biocompatibility deteriorates due to blood stimulation due to irregularities on the blood contact surface. .
[0003]
[Problems to be solved by the invention]
An object of the present invention is to provide a membrane for blood treatment having an increased affinity with blood.
[0004]
[Means for Solving the Problems]
As a result of diligent investigations, the present inventors have found that the membrane surface with which the blood to be treated is in contact has no specific irregularities, and that the membrane surface is substantially smooth, which significantly improves the affinity with blood. As a result, the present invention has been found.
That is, the present invention is a hollow fiber type blood treatment membrane produced from a membrane-forming stock solution containing polysulfone, polyvinylpyrrolidone and dimethylacetamide, and has a viscosity of 700 to 3500 mPa · s together with a hollow agent comprising a dimethylacetamide aqueous solution. The film-forming stock solution was spun at a draft rate of 1.1 to 1.9, the PV value, which is an index of the smoothness of the membrane surface in contact with the blood to be treated, was 20 nm or less, and the Ra value was 6 nm or less. Is a hollow fiber type blood treatment membrane.
[0005]
The smoothness of the film referred to in the present invention is defined by the PV value and the Ra value. The PV value represents the difference between the maximum and minimum unevenness of all measurement points relative to the reference point when the film surface unevenness is measured, and the Ra value is the arithmetic of the unevenness of all measurement points relative to the reference point. Represents the average value. Further, the smoothness of these film surfaces can be obtained from an analysis device such as a three-dimensional surface structure analysis microscope using a scanning white interference method, and can be calculated from measured values. For example, interference images are collected while scanning the interference objective lens in the optical axis direction with a scanning white interference microscope on the test piece, and the digitized interference intensity information is processed on the workstation. The PV value and Ra value can be obtained.
[0006]
The film satisfying the problems of the present invention has a small total average value Ra value of the unevenness constituting the film surface, that is, not only is smooth when simply taking the average of the individual unevenness, but also has a small PV value. That is, it has a smooth film surface with no unevenness that stands out specifically and substantially uniformly throughout the entire film surface. Specifically, the PV value is 20 nm or less, the Ra value is 6 nm or less, more preferably the Ra value is 3 nm or less.
At the same time, the square root of the sum of squares (rms value) can be calculated from the numerical value of the measurement surface unevenness with respect to the reference surface. This indicates the variation in the measured value as indicated by the calculation method. Similar to the value and Ra value, it is a measure representing the smoothness of the surface. As a film that satisfies the problems of the present invention, it is preferable that the PV value and the Ra value satisfy predetermined numerical ranges, and the rms value is 4 nm or less. The rms value is preferably 3.5 nm or less.
[0007]
The material and shape of the membrane having a smooth surface of the present invention are not particularly limited, but the current blood processing membrane is mainly in the form of a hollow fiber membrane, and among known materials, polysulfone-based, polyacrylonitrile Synthetic polymer membranes such as those based on polymethacrylate, polymethylmethacrylate, and polyester can easily achieve relatively good smoothness in a hollow fiber shape. Among them, preferred examples include those obtained by adding polyvinylpyrrolidone to a polysulfone polymer, but hollow fiber membranes obtained by adding a hydrophilic polymer such as polyvinyl alcohol or polyethylene glycol are also preferred in the present invention. A specific example is given.
[0008]
For example, in the case of a membrane obtained by adding polyvinylpyrrolidone to a polysulfone polymer, the hollow fiber blood processing membrane of the present invention is produced as follows.
The composition of the film forming stock solution is composed of 10-20% by weight of polysulfone, 2-8% of polyvinyl pyrrolidone, and these solvents. The solvent is not particularly limited as long as it can dissolve both polysulfone and polyvinylpyrrolidone, and examples thereof include dimethylacetamide, dimethylsulfoxide, N, N-dimethylformamide, and N-methyl-2-pyrrolidone. Can be used as a mixture. Furthermore, water may be added as a non-solvent for polysulfone to such an extent that the polymer does not precipitate.
[0009]
In the film-forming process, the diffusion of the solvent from the film-forming stock solution and the intrusion of a non-solvent results in the formation of aggregated particles after polysulfone nucleation, and contact with blood in the state where polyvinylpyrrolidone is present on the surface of the aggregated polysulfone particles. A hollow fiber membrane in which a dense layer is formed on the surface side and a support layer is formed in other portions is produced. Therefore, in order to make the unevenness of the dense layer surface have a preferable size, it is necessary to control the production rate of the polysulfone aggregated particles in the production process. The inventors set the viscosity of the membrane-forming stock solution in a specific range, and spinning the stock solution at a specific draft rate not only stabilizes the spinning itself but also makes the manufactured hollow fiber membrane a blood to be treated. It has been found that the unevenness of the surface in contact with can be suppressed to the desired smoothness. In order to satisfy the smoothness of the present invention, the viscosity of the film-forming stock solution is preferably in the range of 700 to 3500 mPa · s. Also, the draft rate needs to be in the range of 1.1 to 1.9, and preferably in the range of 1.1 to 1.5.
It was found that the blood treatment membrane thus obtained has a smooth surface in contact with the blood to be treated, so that platelet activation hardly occurs and affinity with blood is good.
[0010]
DETAILED DESCRIPTION OF THE INVENTION
In order to describe the present invention more specifically, examples and comparative examples will be described below, but the present invention is not limited to these examples.
In addition, measurement of PV value and Ra value in Examples and Comparative Examples and adhesion of platelets to the hollow fiber membrane were performed according to the following methods.
[0011]
(Measurement of PV value and Ra value)
The blood treatment membrane used in the test was first subjected to pretreatment operations such as washing in the state of the blood treatment device filled in the container, in the same manner as when actually used in dialysis or the like. Thereafter, the container is broken and the membrane at the center in the length direction of the hollow fiber is taken out. After exposing the contact surface with blood, it is used as a test piece, and in a plane direction by a scanning white interference microscope (New View 100 manufactured by ZYGO). Using a 40 × objective lens with a resolution of about 1 μm and a concavo-convex direction resolution of 0.1 nm, the surface of the test piece was scanned to measure 25 μm square film surface irregularities, and PV values and Ra values were calculated. In the calculation, the values for 10 hollow fibers were averaged and used as a representative value.
[0012]
(Measurement of platelet adhesion to hollow fiber membrane)
The amount of adhesion to the membrane surface was used as an indicator of platelet activation. A hollow fiber membrane to be measured is cut into a length of 15 cm to form a small module by bundling 10 pieces, and heparin-added fresh blood is passed through the small module at a linear speed of 1.0 cm / s for 15 minutes, followed by physiological saline. For 1 minute. Next, the hollow fiber was shredded and subjected to ultrasonic irradiation in physiological saline containing 0.5% Triton X-100, and lactate dehydrogenase released from platelets adhered to the membrane surface was quantified. The enzyme activity was measured using an LDH monotest kit (Boehringer Mannheim / Yamanouchi Pharmaceutical).
[0013]
[Example 1]
17 parts by weight of polysulfone (manufactured by AMOCO: P-1700) and 4.5 parts by weight of PVP (manufactured by ISP: K-90) are added to 77.5 parts by weight of dimethylacetamide and 1 part by weight of water, and dissolved by stirring for 10 hours. As a result, a film-forming stock solution was obtained. The film-forming stock solution had a viscosity of 2200 mPa · s at 45 ° C. Next, while this film-forming stock solution is kept at 45 ° C., it is discharged together with a hollow agent made of 40% DMAC aqueous solution from an annular die having a slit width of 59.5 μm, and a 50 cm idle running portion is formed at a spinning speed of 50 m / min. After running, it was wound up after passing through a coagulation bath containing water installed at the bottom of the spinning nozzle. Since the stock solution discharge rate was adjusted so that the hollow fiber film thickness during drying was adjusted to 45 μm, the stock solution discharge linear velocity was 35.3 m / min, and the draft rate was 1.42. The hollow fiber bundle wound up in this way was cut, washed with 80 ° C. hot water over 2 hours, attached with a glycerin aqueous solution, and dried in vacuum.
[0014]
100 hollow fiber membranes obtained are bundled and inserted into a plastic cylindrical container, and both ends of the hollow fiber are fixed with a urethane resin adhesive, and then a cap for guiding blood is attached to the mini 25 cm effective length. As a module, γ-rays were irradiated at 25 kGy to obtain a blood processing device incorporating the blood processing membrane of the present invention.
Table 1 shows the results of measuring the adhesion amount of platelets to the obtained blood processing membrane in the blood processing device.
[0015]
[Example 2]
17 parts by weight of polysulfone (manufactured by AMOCO: P-1700) and 3.5 parts by weight of PVP (manufactured by ISP: K-90) were added to 79.5 parts by weight of dimethylacetamide and dissolved with stirring for 10 hours. Got. The film-forming stock solution had a viscosity of 1380 mPa · s at 45 ° C. Next, while keeping this film-forming stock solution at 45 ° C., together with a hollow agent made of 40% DMAC aqueous solution, it is discharged from an annular die having a slit width of 59.5 μm, and a 50 cm idle running portion is formed at a spinning side of 50 m / min. After running, it was passed through a coagulation bath containing water installed at the bottom of the spinning nozzle and wound up. Since the stock solution discharge rate was adjusted so that the hollow fiber film thickness during drying was adjusted to 45 μm, the stock solution discharge linear velocity was 31.6 m / min, and the draft rate was 1.58. The hollow fiber bundle wound up in this way is then subjected to the same treatment as in Example 1, and then irradiated with 25 kGy of the same γ-ray as in Example, and the blood treatment containing the blood treatment membrane of the present invention is incorporated. I got a bowl.
Table 1 shows the results of measuring the adhesion amount of platelets to the obtained blood processing membrane in the blood processing device.
[0016]
[Comparative example]
After the same film-forming stock solution as in Example 2 was discharged from a ring base having a slit width of 50 μm together with a hollow agent made of a 40% DMAC aqueous solution, a 50 cm idle running part was run at a spinning side of 50 m / min, The sample was passed through a coagulation bath containing water and was wound up. Since the stock solution discharge amount was adjusted so that the hollow fiber film thickness during drying was adjusted to 45 μm, the stock solution discharge linear velocity was 50.2 m / min, and the draft rate was 1.0. The hollow fiber bundle wound up in this way was then subjected to the same treatment as in Example 1 to obtain a blood treatment membrane.
Table 1 shows the results of measuring the adhesion amount of platelets for the obtained blood processing membrane.
[0017]
[Table 1]

[0018]
【The invention's effect】
According to the present invention, the surface of the membrane that comes into contact with the blood to be treated is not subjected to a coating treatment that may cause peeling or elution, and the surface of the membrane itself is smoothed, thereby stimulating the blood. It was realized that there were few properties.

Claims

A hollow fiber type blood treatment membrane produced from a membrane-forming stock solution containing polysulfone, polyvinylpyrrolidone and dimethylacetamide, wherein the membrane-forming stock solution having a viscosity of 700 to 3500 mPa · s together with a hollow agent comprising a dimethylacetamide aqueous solution is 1 A hollow fiber having a PV value of 20 nm or less and an Ra value of 6 nm or less, which is an index of the smoothness of the membrane surface in contact with the blood to be treated. Type blood treatment membrane.

The hollow fiber blood treatment membrane according to claim 1, wherein the Ra value is 3 nm or less.