JP4178057B2 - Blood purifier - Google Patents

Description

ただし、式中、Ｒ¹及びＲ²は炭素数が１〜５の低級アルキル基である。Ｒ¹及びＲ²は互いに同一であっても良く、あるいは相違していても良い。Ｒ¹及びＲ²としては、例えばメチル基、エチル基、プロピル基、ブチル基、及びペンチル基を挙げることができる。この発明においては、Ｒ¹及びＲ²がメチル基であるのが好ましい。
【００１４】
前記ポリアリレート樹脂は、例えば分子量２０，０００〜５０，０００程度であるのが好ましい。前記ポリアリレートとしては、二価フェノールと芳香族ジカルボン酸とを重縮合することにより適宜に合成したポリアリレートを用いても良く、また市販品を用いても良い。市販品としては、商標名「Ｕポリマー」として販売されているユニチカ（株）による製品、商標名「ＡＰＥ」として販売されているバイエル社による製品、商標名「ＤＵＲＥＬ」として販売されているセラニーズ社による製品、商標名「Ａｒｙｌｏｎ」として販売されているデュポン社による製品等を挙げることができる。
【００１５】
ポリスルホン膜を形成するのに使用するポリスルホン系樹脂としては、下記の式２〜式５で表される繰り返し単位の少なくともいずれかを有するポリエーテルスルホン樹脂を挙げることができる。
【００１６】
【化２】

ただし、式中、Ｒ³及びＲ⁴は炭素数が１〜５の低級アルキル基である。Ｒ³及びＲ⁴は互いに同一であっても良く、あるいは相違していても良い。Ｒ³及びＲ⁴としては、例えばメチル基、エチル基、プロピル基、ブチル基、ペンチル基を挙げることができる。この発明においては、Ｒ³及びＲ⁴がメチル基であるのが好ましい。
【００１７】
【化３】

【００１８】
【化４】

【００１９】
【化５】

前記ポリエーテルスルホン樹脂は、例えば分子量２０，０００〜４０，０００程度であるのが好ましい。前記ポリエーテルスルホンとしては、適宜に合成したポリエーテルスルホンを用いても良く、また市販品を用いても良い。市販品としては、商品名「Ｐ−３５００」として販売されているユニオンカーバイド社製の製品、商標名「スミカエクセルＰＥＳ」として販売されている住友化学工業（株）による製品等を挙げることができる。
【００２０】
前記ポリエステル系ポリマーアロイ膜は、中でも、ポリアリレート樹脂とポリエーテルスルホン樹脂とを組み合わせたものが好ましい。ポリアリレート樹脂とポリエーテルスルホン樹脂との組み合わせにおいて、ポリアリレート樹脂（Ａ）とポリエーテルスルホン樹脂（Ｂ）との混合重量比（Ａ／Ｂ）は、０．１〜１０、好ましくは０．３〜４、さらに好ましくは０．４〜２．５であるのが好ましい。
【００２１】
前記中空糸膜は公知の方法で作製することができる。例えば、前記二種の樹脂を有機溶媒に溶解することにより調製されたポリマー原液を、二重管となった紡糸口金又は押し出しダイスから押し出して凝固液中に導入することにより、中空の紐状体もしくは糸状体として、形成することができる。
【００２２】
この発明におけるスペーサーフィラメントは、その断面が異形である。この発明においては、断面異形のスペーサーフィラメントは、中空糸束中に介在することにより中空糸束の強度を確保すると共に中空糸膜同士の密着を防止して中空糸膜同士の空隙が確保される限り、スペーサーフィラメントの断面形状に特に制限がない。そのようなスペーサーフィラメントの断面形状の具体例として、楕円形、三角形、四角形、五角形以上の多角形、Ｙ字形、三葉型、十字形、五葉型、八葉型など多様な形の断面が挙げられる。スペーサーフィラメントの異形断面を形成する方法としては、様々な形状例えば楕円形、三角形、四角形、五角形以上の多角形、三つ葉形、Ｙ字形等の形状をしたノズル孔を有する紡糸口金を用いてスペーサーフィラメントを紡糸する方法等を挙げることができる。図２に、スペーサーフィラメントの異形断面の一例を示す。
【００２３】
この発明において好適なスペーサーフィラメントはその異形度が１．５〜５であり、好ましくは２．０〜４．０である。ここで前記異形度は、図２に示されるように、スペーサーフィラメントの断面において仮想的な内接円の直径（Ａ）と仮想的な外接円の直径（Ｂ）との比（Ｂ／Ａ）により決定される。スペーサーフィラメントの異形度が１．５未満であると、スペーサーフィラメントの断面が円形に近くなってしまい、この発明の目的を達成することができないことがあり、また、異形度が５を越えると、紡糸口金を大きくする必要があるため不経済であり、また、スペーサ−フィラメントの強度が低くなることにより中空糸束全体の強度も低くなってしまうという不都合を生じることがある。
【００２４】
スペーサーフィラメントの断面を異形にすることにより、中空糸束全体の強度が高められ、衝撃に対する中空糸膜の損傷を少なくすることができ、さらに、スペーサーフィラメントの外径を中空糸膜のそれよりも大きくすることによって、中空糸膜中空糸膜同士の接触を少なくし、中空糸膜と透析液の接触面積を増やすことで溶質透過性を向上させることができ、低分子物質のクリアランス性能を向上させることができる。
【００２５】
スペーサーフィラメントの外径、すなわち、仮想的な外接円の直径は、通常２００μｍより大きく、中空糸膜の外径に対して、１〜５倍であるのが好ましく、さらには２〜４倍であるのが好ましい。スペーサ−フィラメントの外径が２００μｍ以下であると、中空糸間の空間形成が困難となり、たとえ空間ができたとしても血液又は透析液の流れが悪くなる、といった不都合を生じる。
【００２６】
前記スペーサーフィラメントは、中実であっても、また中空であってもよい。
【００２７】
スペーサーフィラメントの長さは、中空糸膜と同程度の長さであるのが好ましい。さらに、スペーサフィラメントは、それ自身を嵩高くして空間を保持するために、捲縮加工が施されていてもよい。
【００２８】
前記スペーサーフィラメントは、中空糸膜を補強でき、また、効果的に中空糸膜間の空間形成をすることができる繊維であればいずれの繊維を使用することもでき、特に、疎水性繊維が好ましい。疎水性繊維は、透析液中に含まれる人体に悪影響を及ぼす物質、例えば、エンドトキシンを吸着する機能を有するので、血液中にエンドトキシンが入り込むことを防止できるという利点を有する。
【００２９】
疎水性繊維としては、例えば、ポリスルホン、ポリエーテルスルホン、ポリアリレート、ポリスチレン、ポリエチレン、ポリプロピレン、ポリ塩化ビニル、ポリ塩化ビニリデン、１，２−ポリブタジエン、１，４−ポリブタジエン、ポリスチレン−ポリブタジエンブロックポリマー、ポリイソプレン、ポリクロロプレン、ポリアクリロニトリル、ポリメチルメタクリレート、ポリエチレンテレフタレート、及びポリブチレンテレフタレート等を挙げることができる。この発明におけるポリマーはこれらの一種単独で使用されても良く、又併用されても良い。これらの素材は、異形断面の繊維を容易に形成することができる。
【００３０】
この発明において、スペーサーフィラメントは、既に説明した中空糸膜と同じ材料で形成されるのが好ましく、中でも、前記ポリアリレート樹脂とポリエーテルスルホン樹脂とを組み合わせたポリエステル系ポリマーアロイが特に好ましい。このようにスペーサーフィラメントと中空糸膜との材料が共に前記ポリエステル系ポリマーアロイであると、エンドトキシンの吸着が促進されて良好な透析が行われることができる。
【００３１】
前記スペーサーフィラメントは、公知の溶融紡糸方法、乾式紡糸方法、湿式紡糸方法等により製造することができる。
【００３２】
中空糸束は、複数の中空糸膜と複数のスペーサーフィラメントとを有して成る。通常、中空糸束を形成するための中空糸膜は、５,０００〜２０,０００本である。この場合、スペーサーフィラメントは、中空糸束１００本当り５〜５０本の割合で、中空糸束内に含まれている。スペーサーフィラメントの中空糸束内における本数が、５本よりも少ないと効果的に空間形成ができないという不都合を生じることがあり、また５０本よりも多いとケーシング内に装填される中空糸膜の充填率が低くなるという不都合を生じることがある。
【００３３】
図３に前記中空糸束の間に中実のスペーサーフィラメントを介在させた一例を示す。この例では、ケーシング１内に中空糸膜３とスペーサーフィラメント２とがほぼ均一に分散して配置されている。図３に示すように中空糸束４における中空糸膜３とスペーサーフィラメント２との断面分布状態としては、中空糸束４内にスペーサーフィラメント２が均一に分布していることが望ましい。スペーサーフィラメントが均一に分布することにより、中空糸膜がよりいっそう補強され、血液浄化器の強度をより高めることができる。
【００３４】
スペーサ−フィラメント２が中空糸束４中に存在すると、図４に示されるように、中空糸膜３同士の密着が防止され、中空糸膜３同士の間に空間が確保されることにより血液浄化器の溶質透過性を向上させることができ、図５に示されるように、中空糸膜３同士の密着が防止され、また中空糸束４全体の強度を向上させることができてこの血液浄化器に衝撃を加えても中空糸膜自体が容易に破損するといった欠点が解消される。
【００３５】
前記多数の中空糸膜の集合体中にスペーサーフィラメントを分布させる方法としては、特殊な紡糸口金を用いて中空糸膜とスペーサーフィラメントとを同時に紡糸する方法等を挙げることができる。前記特殊な紡糸口金としては、中空糸膜を紡糸することができるように二重管構成としたノズル孔と、中実で断面異形のスペーサーフィラメントを紡糸することのできるようにしたノズル孔とを備えて成り、かつ中空糸膜とスペーサ−フィラメントとの構成本数に従って決められたノズル孔数を有する紡糸口金を挙げることができる。また、中空糸膜とスペーサフィラメントとを別個独立に紡糸し、製造された中空糸膜とスペーサフィラメントとを後の工程で混繊することにより、前記多数の中空糸膜の集合体中にスペーサーフィラメントを分散させるのも、良い。
【００３６】
この発明に係る血液浄化器は、通常、血液透析療法、血液濾過療法、血液透析濾過療法、血液吸着療法、及び血漿交換療法等の血液浄化療法等に使用することができる。
【００３７】
【実施例】
（実施例１）
Ｎ−メチルピロリドン中に前記式（１）に示す構造式を持つポリアリレート樹脂（株）ユニチカ製、商品名Ｕポリマー）と前記式（３）に示す構造式を持つポリエーテルスルホン樹脂（住友化学（株）製、商品名スミカエクセルＰＥＳ）とをそれぞれ８重量％となるように溶解し、中実で断面異形のスペーサーフィラメント（以下、中実糸と表記する）及び中空糸の紡糸原液とした。またＮ−メチルピロリドンの５０重量％水溶液をそれぞれ芯液及び凝固液とし、ポリエステル系ポリマーアロイ（以下、ＰＥＰＡと表記する）の中実で断面異形のスペーサーフィラメント及び中空糸膜をそれぞれ別個独立に紡糸した。
【００３８】
それら中空糸膜及びスペーサーフィラメントそれぞれの内径及び膜厚、スペーサーフィラメントを紡糸するノズル孔の形状を表１に示した。
【００３９】
表１に示す本数の中空糸膜と表１に示す本数のスペーサーフィラメントとを用いて中空糸束を作成した。続いてこの中空糸束を円筒状のケーシング内に装填し、ウレタン樹脂にて端部を接着してモジュール化した。このモジュールの両端部に血液ポートを接続して血液浄化器を作成した。
【００４０】
（比較例１）
実施例１と同じ材料を用いて表１に示す内径及び膜厚を有する中空糸膜を製造した。また、実施例１と同じ材料を用いて表１に示す外径を有するスペーサーフィラメントを、表１に示すような円形のノズル孔を有する紡糸口金により、紡糸して得た。
【００４１】
表１にそれぞれ示す本数の中空糸膜とスペーサーフィラメントとを用いて中空糸束を作製した。
【００４２】
（比較例２）
実施例１と同じ中空糸膜を用いて、表１に示す本数の中空糸束を作成し、この中空糸束を用いて実施例１と同様にして血液浄化器を作製した。
【００４３】
【表１】

【００４４】
（耐衝撃性試験）
実施例１、比較例１、比較例２の血液浄化器を用いて落下試験を行い、その後のリーク率を調べた。落下試験はＪＩＳ Ｚ２０２包装貨物−落下試験方法に準じ、高さ８０ｃｍからの自由落下とした。リークの検出は、血液浄化器の透析液側流路に水を満たし、血液浄化器の血液側流路に空気で１ｋｇｆ／ｃｍ^２の圧力を加え、透析液側流路への空気の漏出の有無で判断した。尚リーク率は、リーク本数／総試験本数×１００で算出した。
【００４５】
（溶質透過性試験）
実施例１、比較例１、比較例２の血液浄化器について、牛血漿系クリアランスを測定した。測定方法は以下の通りである。
【００４６】
総タンパク質濃度を６．５±０．５ｇ／ｄｌに調整した牛血漿を、血液浄化器の血液側流路に流量２００ｍｌ／ｍｉｎで流した。また血液浄化器の透析液側流路に透析液を流量５００ｍｌ／ｍｉｎで流した。尚、牛血漿と透析液は対向流とした。透析開始から６０分後に血液入口側及び血液出口側の牛血漿を取り出し、各溶質濃度を測定した。クリアランスは以下の式（６）より算出した。測定対象溶質は、尿素及びβ_２−マイクログロブリン（以下β２−ＭＧと表記する）とした。
【００４７】
【数１】

ここで、ＣＬはクリアランス（ｍｌ／ｍｉｎ）、Ｃ_Ｂｉは血液入口側溶質濃度、Ｃ_Ｂｏは血液出口側溶質濃度、Ｑ_Ｂｉは血液入口側血漿流量である。
【００４８】
耐衝撃性試験及び溶質透過性試験の結果を表２に示した。
【００４９】
中実糸を介在させた実施例１は、比較例１に用いた中空糸と同材料及び同形状の中空糸を用いているにも関わらず比較例１と比べて、低いリーク率を示した。
一方、中実糸を介在させずに中空糸の膜厚を３０μｍとした比較例２は、実施例１よりも低い尿素クリアランス及びβ２−ＭＧクリアランスを示し、さらに、リーク率も高く、機械的強度が劣る。
【００５０】
比較例１に比べて実施例１は、比較例１よりもさらに高い尿素クリアランス及びβ２−ＭＧクリアランスを示し、また、低いリーク率を示した。
【００５１】
【表２】

【００５２】
【発明の効果】
中実糸を中空糸束に介在させることにより、また、該中実糸の断面形状を従来使用していた円形から多角形へと変えることにより、血液浄化器の機械的強度を向上させることができた。また、機械的強度を保持できるため、従来よりも細いあるいは薄い中空糸膜が使用可能となり、さらには、溶質除去性能を格段に向上させることができた。
【図面の簡単な説明】
【図１】図１は、本発明の血液浄化器の一例を示す側面図である。
【図２】図２は、一例として示されたスペーサーフィラメントの断面を示す断面図である。
【図３】図３は、本発明の血液浄化器の一例を示す断面図である。
【図４】図４は、本発明の血液浄化器に使用される一例としての中空糸束の部分を拡大して示す部分拡大斜視図である。
【図５】図５は、従来の血液浄化器に使用される中空糸膜の一例を示す一部拡大斜視図である。
【符号の説明】
１ ケーシング １６ 透析液流出口
２ スペーサーフィラメント １７ 血液注入口
３ 中空糸膜 １８ 血液流出口
４ 中空糸束 ２０ 内接円
５ 孔 ２１ 外接円
１０ 血液浄化器
１３ 注入側エンドキャップ
１４ 排出側エンドキャップ
１５ 透析液流入口[0001]
BACKGROUND OF THE INVENTION
The present invention relates to a blood purifier, and more particularly, is used for hemodialysis therapy and the like, has high dialysis efficiency, and is damaged by impact even though an ultrathin hollow fiber membrane is used. In addition, the present invention relates to a blood purifier having high filtration efficiency in plasma exchange.
[0002]
[Prior art]
In the medical field, blood purifiers are used for blood purification therapy such as hemodialysis therapy, hemofiltration therapy, hemodiafiltration therapy, blood adsorption therapy, and plasma exchange therapy.
[0003]
For example, hollow fibers having a diameter of about 280 μm and an inner diameter of about 200 μm have been conventionally used for hollow fiber membranes used in hemodialysis therapy. In order to shorten the dialysis time and reduce the burden on dialysis therapists, blood purifiers with good solute removal efficiency are required in the medical field. Moreover, in the internal filtration promotion type blood filter that positively promotes internal filtration generated inside the blood purifier and improves the solute removal efficiency, the hollow fiber tends to be thin. One method for obtaining a blood purifier with good solute removal efficiency is to use a hollow fiber membrane with high solute permeability. In order to obtain a hollow fiber membrane having a high solute permeability, a hollow fiber membrane having a thinner average membrane thickness or a thin hollow fiber membrane tends to be developed. However, the mechanical strength of the hollow fiber membrane is lowered by reducing the average thickness of the membrane. If it does so, the new problem that the hollow fiber membrane with which the blood purifier is excessively vibrated or dropped accidentally will be broken by bending etc. will arise. As means for increasing the mechanical strength of the hollow fiber membrane, a method of selecting a strong membrane material, a method of increasing the average thickness of the hollow fiber membrane, the ratio of the occupied cross-section of the hollow fiber membrane to the cross-sectional area in the casing, that is, the hollow fiber Methods for increasing the film filling rate are known.
[0004]
However, it is difficult to newly select a membrane material having a high solute permeability and capable of forming a hollow fiber membrane having a high strength and having a good compatibility with a living body. Further, if the average thickness of the hollow fiber membrane is increased, the strength is increased, but the solute permeability is decreased. This tendency is strong particularly in a homogeneous membrane having a uniform structure in the thickness direction of the hollow fiber membrane. By making the hollow fiber membrane an asymmetric structure, the strength can be increased, but that alone is insufficient in strength. Further, if the total cross-sectional area of the hollow fiber bundle relative to the cross-sectional area in the case, that is, the filling rate of the hollow fiber membrane is excessively increased, the dialysate does not reach the center of the hollow fiber bundle in the casing, and the dialysate is outside the hollow fiber bundle. There is a problem in that the phenomenon of drifting flow occurs and the solute permeability decreases.
[0005]
[Problems to be solved by the invention]
Accordingly, the present invention provides a blood purifier loaded with an ultrathin hollow fiber membrane, whereby the solute permeability of the hollow fiber membrane is improved by having the ultrathin hollow fiber membrane, and the hollow fiber membrane is affected by impact or the like. An object of the present invention is to provide a blood purifier that does not cause any damage, deformation or the like. Another object of the present invention is that the solute permeability of the hollow fiber membrane is improved by having an ultrathin hollow fiber membrane, and that the hollow fiber membrane is not damaged or deformed by impact or the like. An object of the present invention is to provide a blood purifier capable of capturing endotoxin and fine particles therein.
[0006]
[Means for Solving the Problems]
Means for solving the above problems are as follows:
(1) a hollow fiber membrane, interposed between the hollow fiber membranes, Ri formed with a hollow fiber bundle having a spacer filaments in cross-section irregular, the spacer filaments, the diameter of the imaginary circumscribed circle There greater than the cross-sectional diameter of the hollow fiber membranes, a blood purifier that modification degree is characterized 1.5-5 der Rukoto,
(2) The hollow fiber membrane of (1) and the spacer filament of (1) are both formed of the same material,
(3) The material of (2) is a hydrophobic resin,
(4) The hydrophobic resin of (3) is a polymer alloy comprising a polyarylate resin and a polyethersulfone resin.
[0007]
DETAILED DESCRIPTION OF THE INVENTION
FIG. 1 shows an example of a blood purifier using a hollow fiber membrane. As shown in FIG. 1, the blood purifier 10 includes a cylindrical casing 1, an injection-side end cap 13 and a discharge-side end cap 14 that are detachably screwed into both end openings of the casing 1, and the casing. 1 and a dialysate inflow port 15 provided at an end on the discharge end cap 14 side, and a dialysate outflow port 16 provided at an end on the injection end cap 13 side. A hollow fiber bundle 4 formed by bundling the hollow fiber membrane 3 and the spacer filament 2 is loaded in the internal space of the casing 1.
[0008]
In this example, the internal space of the hollow fiber membrane 3 serves as a blood flow path, and the space outside the hollow fiber membrane formed by the casing 1 and the outer surface of the hollow fiber membrane 3 serves as a dialysate flow path. . The blood injected from the injection port 17 of the injection side end cap 13 is discharged from the discharge port 18 of the discharge side end cap 14 through the internal space of the hollow fiber membrane 3. The dialysate injected from the inflow port 15 flows through the space outside the hollow fiber membrane 3 to the outflow port 16, and both solutions counter-flow across the hollow fiber membrane 3. The hollow fiber membrane 3 has a porous structure and does not permeate relatively large blood proteins and the like but permeates relatively small blood wastes. Moves to the dialysate side, and as a result, blood is purified. In contrast to this example, the inner space of the hollow fiber membrane 3 can be used as a dialysate flow path, and the outer space of the hollow fiber membrane 3 can be used as a blood flow path.
[0009]
The hollow fiber membrane 3 is a hollow cylindrical membrane having an internal space through which blood and dialysate can be circulated. Innumerable small holes are formed in the hollow fiber membrane, and a substance that passes through the membrane is selected depending on its size. The diameter of a general hole is about 30 to 100 mm (3 × 10 ⁻³ to 1 × 10 ⁻² μm) as an average pore size. The hollow fiber membrane may be a homogeneous membrane having a uniform structure in the thickness direction, or a dense layer is formed on the surface of the hollow fiber membrane on the blood channel side, and pores that are considerably coarser than the dense layer inside the hollow fiber membrane and on the dialysis channel side surface. An asymmetric structure film in which a support layer having s is formed may be used. The asymmetric structure film is superior to the uniform film because the solute permeability hardly decreases even when the film thickness is increased and the strength is increased by the support layer.
[0010]
The hollow fiber membrane in the present invention is a hollow fiber membrane having a thickness of 60 μm at the maximum. By reducing the thickness of the membrane, the solute permeability of the membrane can be enhanced as compared with the conventional case. In particular, the thickness of the film is preferably 10 to 30 μm. The inner diameter and outer diameter of the hollow fiber membrane are not particularly limited as long as they are thinner than the above-mentioned film thickness, but the inner diameter of the hollow fiber membrane is preferably in the range of 100 to 1000 μm. The length of the hollow fiber membrane is determined by the length of the casing filled with the hollow fiber membrane.
[0011]
As the hollow fiber membrane, a hydrophilic membrane represented by a cellulose membrane, and a hydrophobic membrane represented by a polysulfone membrane and a polyester membrane can be selected. Among them, a polyester polymer alloy film containing a polyarylate resin and a polysulfone resin is preferable because it not only has excellent mechanical strength, heat resistance, and chemical resistance, but also has an excellent ability to adsorb substances.
[0012]
Examples of the polyester resin used for forming the polyester film include a polyarylate resin having a repeating unit represented by the following formula 1.
[0013]
[Chemical 1]

In the formula, R ¹ and R ² is a lower alkyl group having 1 to 5 carbon atoms. R ¹ and R ² may be the same as or different from each other. Examples of R ¹ and R ² include a methyl group, an ethyl group, a propyl group, a butyl group, and a pentyl group. In the present invention, R ¹ and R ² are preferably methyl groups.
[0014]
The polyarylate resin preferably has a molecular weight of about 20,000 to 50,000, for example. As the polyarylate, a polyarylate appropriately synthesized by polycondensation of a dihydric phenol and an aromatic dicarboxylic acid may be used, or a commercially available product may be used. Commercially available products include a product by Unitika Co., Ltd. sold under the trade name “U Polymer”, a product by Bayer, which is sold under the trade name “APE”, and Celanese, which is sold under the trade name “DUREL”. And a product by DuPont, which is sold under the trade name “Arylon”.
[0015]
Examples of the polysulfone-based resin used for forming the polysulfone membrane include polyethersulfone resins having at least one of the repeating units represented by the following formulas 2 to 5.
[0016]
[Chemical formula 2]

In the formula, R ³ and R ⁴ is a lower alkyl group having 1 to 5 carbon atoms. R ³ and R ⁴ may be the same as or different from each other. Examples of R ³ and R ⁴ include a methyl group, an ethyl group, a propyl group, a butyl group, and a pentyl group. In the present invention, R ³ and R ⁴ are preferably methyl groups.
[0017]
[Chemical 3]

[0018]
[Formula 4]

[0019]
[Chemical formula 5]

The polyethersulfone resin preferably has a molecular weight of about 20,000 to 40,000, for example. As the polyethersulfone, appropriately synthesized polyethersulfone may be used, or a commercially available product may be used. Examples of commercially available products include products manufactured by Union Carbide, sold under the trade name “P-3500”, products manufactured by Sumitomo Chemical Co., Ltd., sold under the trade name “Sumika Excel PES”, and the like. .
[0020]
The polyester polymer alloy membrane is preferably a combination of a polyarylate resin and a polyethersulfone resin. In the combination of the polyarylate resin and the polyethersulfone resin, the mixing weight ratio (A / B) of the polyarylate resin (A) and the polyethersulfone resin (B) is 0.1 to 10, preferably 0.3. -4, more preferably 0.4-2.5.
[0021]
The hollow fiber membrane can be produced by a known method. For example, the polymer stock solution prepared by dissolving the two kinds of resins in an organic solvent is extruded from a spinneret or an extrusion die that is a double tube and introduced into the coagulation liquid, thereby forming a hollow string-like body. Or it can form as a filament.
[0022]
The spacer filament in the present invention has an irregular cross section. In the present invention, the spacer filament having a deformed cross section is interposed in the hollow fiber bundle to ensure the strength of the hollow fiber bundle and prevent the hollow fiber membranes from sticking to each other, thereby ensuring the space between the hollow fiber membranes. As long as the cross-sectional shape of the spacer filament is not particularly limited. Specific examples of the cross-sectional shape of such a spacer filament include various cross-sections such as an ellipse, a triangle, a quadrangle, a pentagon or more polygon, a Y-shape, a trilobal shape, a cross shape, a five-leaf shape, and an eight-leaf shape. It is done. Spacer filaments can be formed by using a spinneret having a nozzle hole having various shapes such as an ellipse, a triangle, a quadrangle, a pentagon or more polygon, a trefoil, and a Y-shape. And the like. FIG. 2 shows an example of an irregular cross section of the spacer filament.
[0023]
A spacer filament suitable for the present invention has a degree of deformity of 1.5 to 5, preferably 2.0 to 4.0. Here, as shown in FIG. 2, the degree of irregularity is a ratio (B / A) of a virtual inscribed circle diameter (A) and a virtual circumscribed circle diameter (B) in the cross section of the spacer filament. Determined by. If the profile of the spacer filament is less than 1.5, the cross-section of the spacer filament becomes nearly circular and the object of the present invention may not be achieved. If the profile is more than 5, Since it is necessary to enlarge the spinneret, it is uneconomical, and the strength of the entire hollow fiber bundle may be lowered due to the reduced strength of the spacer filaments.
[0024]
By making the cross section of the spacer filament irregular, the strength of the entire hollow fiber bundle can be increased, the damage of the hollow fiber membrane against impact can be reduced, and the outer diameter of the spacer filament can be made smaller than that of the hollow fiber membrane. By increasing the size, the contact between the hollow fiber membranes can be reduced, the solute permeability can be improved by increasing the contact area between the hollow fiber membrane and the dialysate, and the clearance performance of low-molecular substances is improved. be able to.
[0025]
The outer diameter of the spacer filament, that is, the diameter of the virtual circumscribed circle is usually larger than 200 μm, preferably 1 to 5 times, more preferably 2 to 4 times the outer diameter of the hollow fiber membrane. Is preferred. When the outer diameter of the spacer-filament is 200 μm or less, it becomes difficult to form a space between the hollow fibers, and even if a space is created, the flow of blood or dialysate becomes poor.
[0026]
The spacer filament may be solid or hollow.
[0027]
The length of the spacer filament is preferably the same as that of the hollow fiber membrane. Furthermore, the spacer filaments may be crimped to make them bulky and maintain space.
[0028]
As the spacer filament, any fiber can be used as long as it can reinforce the hollow fiber membrane and can effectively form a space between the hollow fiber membranes, and a hydrophobic fiber is particularly preferable. . The hydrophobic fiber has a function of adsorbing a substance that adversely affects the human body contained in the dialysate, for example, endotoxin, and therefore has an advantage that endotoxin can be prevented from entering blood.
[0029]
Examples of hydrophobic fibers include polysulfone, polyethersulfone, polyarylate, polystyrene, polyethylene, polypropylene, polyvinyl chloride, polyvinylidene chloride, 1,2-polybutadiene, 1,4-polybutadiene, polystyrene-polybutadiene block polymer, poly Examples include isoprene, polychloroprene, polyacrylonitrile, polymethyl methacrylate, polyethylene terephthalate, and polybutylene terephthalate. The polymers in this invention may be used alone or in combination. These materials can easily form fibers having irregular cross sections.
[0030]
In this invention, the spacer filament is preferably formed of the same material as the hollow fiber membrane already described, and among them, a polyester polymer alloy in which the polyarylate resin and the polyethersulfone resin are combined is particularly preferable. Thus, when both the material of the spacer filament and the hollow fiber membrane is the polyester polymer alloy, the adsorption of endotoxin is promoted and good dialysis can be performed.
[0031]
The spacer filament can be produced by a known melt spinning method, dry spinning method, wet spinning method or the like.
[0032]
The hollow fiber bundle includes a plurality of hollow fiber membranes and a plurality of spacer filaments. Usually, the number of hollow fiber membranes for forming a hollow fiber bundle is 5,000 to 20,000. In this case, the spacer filament is contained in the hollow fiber bundle at a rate of 5 to 50 per 100 hollow fiber bundles. If the number of spacer filaments in the hollow fiber bundle is less than 5, there may be a disadvantage that the space cannot be formed effectively, and if it is more than 50, the hollow fiber membrane loaded in the casing is filled. There may be an inconvenience that the rate is low.
[0033]
FIG. 3 shows an example in which a solid spacer filament is interposed between the hollow fiber bundles. In this example, the hollow fiber membrane 3 and the spacer filament 2 are disposed in the casing 1 so as to be almost uniformly dispersed. As shown in FIG. 3, as a cross-sectional distribution state of the hollow fiber membrane 3 and the spacer filament 2 in the hollow fiber bundle 4, it is desirable that the spacer filament 2 is uniformly distributed in the hollow fiber bundle 4. By uniformly distributing the spacer filaments, the hollow fiber membrane can be further reinforced and the strength of the blood purifier can be further increased.
[0034]
When the spacer-filament 2 is present in the hollow fiber bundle 4, as shown in FIG. 4, the close contact between the hollow fiber membranes 3 is prevented, and a space is secured between the hollow fiber membranes 3, thereby purifying blood. The solute permeability of the vessel can be improved, and as shown in FIG. 5, the close contact between the hollow fiber membranes 3 can be prevented, and the strength of the entire hollow fiber bundle 4 can be improved. Even if an impact is applied to the hollow fiber membrane, the disadvantage that the hollow fiber membrane itself is easily broken is eliminated.
[0035]
Examples of the method for distributing the spacer filaments in the aggregate of the numerous hollow fiber membranes include a method of simultaneously spinning the hollow fiber membranes and the spacer filaments using a special spinneret. As the special spinneret, there are a nozzle hole having a double tube configuration so that a hollow fiber membrane can be spun, and a nozzle hole that can spin a spacer filament having a solid cross-sectional shape. Examples thereof include a spinneret having a number of nozzle holes determined according to the number of hollow fiber membranes and spacer filaments. Further, the hollow fiber membranes and spacer filaments are separately spun independently, and the produced hollow fiber membranes and spacer filaments are mixed in a later step, whereby spacer filaments are assembled into the aggregate of the numerous hollow fiber membranes. It is also good to disperse.
[0036]
The blood purifier according to the present invention can be generally used for blood purification therapy such as hemodialysis therapy, hemofiltration therapy, hemodiafiltration therapy, blood adsorption therapy, and plasma exchange therapy.
[0037]
【Example】
(Example 1)
Polyarylate resin having the structural formula represented by the above formula (1) in N-methylpyrrolidone (trade name U polymer manufactured by Unitika Co., Ltd.) and polyethersulfone resin having the structural formula represented by the above formula (3) (Sumitomo Chemical) Co., Ltd., trade name SUMIKAEXCEL PES) was dissolved so as to be 8% by weight, respectively, and was used as a spinning dope for solid and cross-shaped spacer filaments (hereinafter referred to as solid yarns) and hollow fibers. . In addition, a 50% by weight aqueous solution of N-methylpyrrolidone is used as the core solution and coagulation solution, respectively, and a polyester filament (hereinafter referred to as PEPA) with a solid and deformed spacer filament and hollow fiber membrane is spun independently. did.
[0038]
Table 1 shows the inner diameter and film thickness of each hollow fiber membrane and spacer filament, and the shape of the nozzle hole for spinning the spacer filament.
[0039]
A hollow fiber bundle was prepared using the number of hollow fiber membranes shown in Table 1 and the number of spacer filaments shown in Table 1. Subsequently, this hollow fiber bundle was loaded into a cylindrical casing, and the ends were bonded with urethane resin to form a module. A blood purifier was created by connecting blood ports to both ends of this module.
[0040]
(Comparative Example 1)
A hollow fiber membrane having the inner diameter and film thickness shown in Table 1 was manufactured using the same material as in Example 1. Further, a spacer filament having the outer diameter shown in Table 1 using the same material as in Example 1 was obtained by spinning with a spinneret having a circular nozzle hole as shown in Table 1.
[0041]
A hollow fiber bundle was prepared using the number of hollow fiber membranes and spacer filaments shown in Table 1, respectively.
[0042]
(Comparative Example 2)
Using the same hollow fiber membrane as in Example 1, the number of hollow fiber bundles shown in Table 1 was prepared, and using this hollow fiber bundle, a blood purifier was prepared in the same manner as in Example 1.
[0043]
[Table 1]

[0044]
(Impact resistance test)
A drop test was performed using the blood purifiers of Example 1, Comparative Example 1, and Comparative Example 2 , and the subsequent leak rate was examined. The drop test was a free drop from a height of 80 cm according to the JIS Z202 packaged cargo-drop test method. In the detection of the leak, the dialysate side channel of the blood purifier is filled with water, a pressure of 1 kgf / cm ² is applied to the blood side channel of the blood purifier with air, and the leakage of air to the dialysate side channel is detected. Judgment by presence or absence. The leak rate was calculated by the number of leaks / total number of tests × 100.
[0045]
(Solute permeability test)
Regarding the blood purifiers of Example 1, Comparative Example 1, and Comparative Example 2 , bovine plasma clearance was measured. The measuring method is as follows.
[0046]
The bovine plasma whose total protein concentration was adjusted to 6.5 ± 0.5 g / dl was passed through the blood side channel of the blood purifier at a flow rate of 200 ml / min. In addition, dialysate was flowed through the dialysate side channel of the blood purifier at a flow rate of 500 ml / min. Cow plasma and dialysate were counterflowed. After 60 minutes from the start of dialysis, the bovine plasma on the blood inlet side and the blood outlet side was taken out and each solute concentration was measured. The clearance was calculated from the following formula (6). The solutes to be measured were urea and β ₂ -microglobulin (hereinafter referred to as β2-MG).
[0047]
[Expression 1]

Here, CL is the clearance (ml / min), C _Bi is the blood inlet side solute concentration, C _Bo is the blood outlet side solute concentration, and Q _Bi is the blood inlet side plasma flow rate.
[0048]
The results of the impact resistance test and the solute permeability test are shown in Table 2.
[0049]
Example 1 in which a solid yarn was interposed showed a low leak rate as compared with Comparative Example 1 in spite of using the same material and the same shape as the hollow fiber used in Comparative Example 1. .
On the other hand, Comparative Example 2 in which the thickness of the hollow fiber was 30 μm without any solid yarn showed lower urea clearance and β2-MG clearance than Example 1, and also had a high leak rate and mechanical strength. Is inferior.
[0050]
Compared with Comparative Example 1 , Example 1 showed higher urea clearance and β2-MG clearance than Comparative Example 1 , and also showed a low leak rate.
[0051]
[Table 2]

[0052]
【The invention's effect】
It is possible to improve the mechanical strength of the blood purifier by interposing the solid yarn in the hollow fiber bundle and changing the cross-sectional shape of the solid yarn from the conventionally used circular shape to a polygonal shape. did it. Further, since the mechanical strength can be maintained, a hollow fiber membrane that is thinner or thinner than the conventional one can be used, and the solute removal performance can be remarkably improved.
[Brief description of the drawings]
FIG. 1 is a side view showing an example of a blood purifier of the present invention.
FIG. 2 is a cross-sectional view showing a cross section of a spacer filament shown as an example.
FIG. 3 is a cross-sectional view showing an example of a blood purifier according to the present invention.
FIG. 4 is a partially enlarged perspective view showing an enlarged portion of a hollow fiber bundle as an example used in the blood purifier of the present invention.
FIG. 5 is a partially enlarged perspective view showing an example of a hollow fiber membrane used in a conventional blood purifier.
[Explanation of symbols]
DESCRIPTION OF SYMBOLS 1 Casing 16 Dialysate outflow port 2 Spacer filament 17 Blood injection port 3 Hollow fiber membrane 18 Blood outflow port 4 Hollow fiber bundle 20 Inscribed circle 5 Hole 21 Outer circle 10 Blood purifier 13 Injection side end cap 14 Outlet side end cap 15 Dialysate inlet

Claims (4)

A hollow fiber membrane, interposed between the hollow fiber membranes, Ri formed with a hollow fiber bundle having a spacer filaments in cross-section irregular, the spacer filaments, hollow fiber diameter of the imaginary circumscribed circle greater than the cross-sectional diameter of the membrane, the blood purifier of the modification degree is characterized 1.5-5 der Rukoto. The blood purifier according to claim 1 , wherein the hollow fiber membrane and the spacer filament are both formed of the same material. The blood purifier according to claim 2 , wherein the material is a hydrophobic resin. The blood purifier according to claim 3 , wherein the hydrophobic resin is a polymer alloy comprising a polyarylate resin and a polyethersulfone resin.

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