JP2003210573A - Hollow fiber type blood-purifier, and manufacturing method for hollow fiber membrane - Google Patents

Hollow fiber type blood-purifier, and manufacturing method for hollow fiber membrane

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Publication number
JP2003210573A
JP2003210573A JP2002013534A JP2002013534A JP2003210573A JP 2003210573 A JP2003210573 A JP 2003210573A JP 2002013534 A JP2002013534 A JP 2002013534A JP 2002013534 A JP2002013534 A JP 2002013534A JP 2003210573 A JP2003210573 A JP 2003210573A
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JP
Japan
Prior art keywords
hollow fiber
blood
fiber membrane
solute
sieving coefficient
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.)
Pending
Application number
JP2002013534A
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Japanese (ja)
Inventor
Sadanori Hori
禎憲 堀
Current Assignee (The listed assignees may be inaccurate. Google has not performed a legal analysis and makes no representation or warranty as to the accuracy of the list.)
Nikkiso Co Ltd
Original Assignee
Nikkiso Co Ltd
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Filing date
Publication date
Application filed by Nikkiso Co Ltd filed Critical Nikkiso Co Ltd
Priority to JP2002013534A priority Critical patent/JP2003210573A/en
Publication of JP2003210573A publication Critical patent/JP2003210573A/en
Pending legal-status Critical Current

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  • Separation Using Semi-Permeable Membranes (AREA)

Abstract

<P>PROBLEM TO BE SOLVED: To provide a hollow fiber type blood-purifier which can efficiently remove protein in a low-molecular weight region from blood without using a subsidiary liquid, and also, wherein an endotoxin from a dialysis liquid is prevented from invading. <P>SOLUTION: This hollow fiber type blood-purifier 1 is equipped with a bundle of hollow fiber membranes 2, a hollow fiber membrane case 3 which houses the bundle of the hollow fiber membranes 2, a bloods inlet 4 and a blood outlet 5 which are respectively provided on both end sections of the hollow fiber membrane case 3, a dialysis liquid inlet 6 which is provided on the blood outlet 5 side of the hollow fiber membrane case, and a dialysis liquid outlet 7 which is provided on the blood inlet 4 side of the hollow fiber membrane case 3. The hollow fiber type blood-purifier 1 is constituted in such a manner that the blood and the dialysis liquid are made to flow in the opposite directions through the hollow fiber membranes 2. In this case, a screening coefficient for a solute in the hollow fiber membranes 2 on the blood outlet 5 side is smaller than a screening coefficient for the solute in the hollow fiber membranes 2 on the blood inlet 4 side. <P>COPYRIGHT: (C)2003,JPO

Description

【発明の詳細な説明】Detailed Description of the Invention

【0001】[0001]

【発明の属する技術分野】本発明は、中空糸型血液浄化
器に関し、さらに詳しくは、血液流入口側と血液流出口
側とで溶質の篩い係数が異なる中空糸膜が装填され、血
液中に含まれる不要な低分子量のタンパク質を除去でき
ると共に、透析液からのエンドトキシンの侵入を防止す
ることができる中空糸型血液浄化器に関する。
BACKGROUND OF THE INVENTION 1. Field of the Invention The present invention relates to a hollow fiber blood purifier, and more specifically, it is loaded with a hollow fiber membrane having different solute sieving coefficients on the blood inlet side and the blood outlet side, and is filled in blood. The present invention relates to a hollow fiber blood purifier that can remove unnecessary low molecular weight proteins contained therein and can prevent endotoxin from entering from a dialysate.

【0002】[0002]

【従来の技術】慢性腎不全の患者は、生体内の老廃物等
の不必要な物質を、週に数回の透析療法で除去してい
る。近年になって、β2マイクログロブリン等の低分子
量領域のタンパク質も、透析療法によって除去する必要
があることがわかった。β2マイクログロブリンは分子
量11,800の低分子量タンパク質であり、体内で蓄
積すると、アミロイドとなり、関節等に沈着して骨を破
壊する透析アミロイド症を発症する。そこで、従来は除
去されていなかった分子量が数万単位のタンパク質を除
去する試みが行われている。
2. Description of the Related Art Patients with chronic renal failure remove unnecessary substances such as waste products in the body by dialysis therapy several times a week. Recently, it has been found that proteins in low molecular weight regions such as β2 microglobulin also need to be removed by dialysis therapy. β2 microglobulin is a low molecular weight protein having a molecular weight of 11,800, and when it accumulates in the body, it becomes amyloid, which causes dialysis amyloidosis in which bone is destroyed by depositing in joints and the like. Therefore, attempts have been made to remove proteins with a molecular weight of tens of thousands that have not been removed in the past.

【0003】β2マイクログロブリン等を除去する方法
として、例えば、血液に補液を補給しながら、濾過する
方法がある。しかし、補液を使用したこの方法は、血液
への補液のコストが大きいという欠点がある。
As a method for removing β2 microglobulin and the like, for example, there is a method of filtering blood while supplementing the blood with a replacement fluid. However, this method using a replacement fluid has a drawback that the cost of replacement fluid for blood is high.

【0004】近年の透水性の向上した透析膜は、「逆濾
過現象」が発生することが分かっている。透析器の血液
側入口ポートから流入した血液は、透析液側に比べて高
い圧力となる。このため、血液側から透析液側に向かっ
て濾過現象が起こる。一方、中空糸膜を通過する過程で
圧力損失が発生し、血液の圧力が減少するので、血液側
出口ポート付近においては、透析液側に比べて低い圧力
となる。このため、反対に透析液側から血液側に向かっ
て逆濾過現象が生じる。
It has been known that a dialysis membrane having improved water permeability in recent years causes a "back filtration phenomenon". The blood flowing in from the blood side inlet port of the dialyzer has a higher pressure than that on the dialysate side. Therefore, a filtering phenomenon occurs from the blood side toward the dialysate side. On the other hand, since a pressure loss occurs in the process of passing through the hollow fiber membrane and the blood pressure decreases, the pressure becomes lower near the blood side outlet port than on the dialysate side. Therefore, on the contrary, a back filtration phenomenon occurs from the dialysate side toward the blood side.

【0005】[0005]

【発明が解決しようとする課題】中空糸膜のポアサイズ
を大きくし、即ち、中空糸膜における溶質の篩い係数を
大きくすることにより、透水性を高めて、上記濾過現象
を利用して低分子量領域のタンパク質を効率良く透過さ
せることができる。しかし、その一方で中空糸膜の全体
にわたって、溶質の篩い係数を大きくした場合は、血液
側出口における逆濾過現象によって透析液側から血液側
への濾過が増加し、透析液中に混入する可能性のあるエ
ンドトキシンが血液中に流入しやすくなるという問題が
ある。エンドトキシンは、細菌毒素の一種で、グラム陰
性菌が壊れて、その細胞壁の構成成分であるリボ多糖が
遊離して、毒性を発揮する。
By increasing the pore size of the hollow fiber membrane, that is, by increasing the sieving coefficient of the solute in the hollow fiber membrane, the water permeability is enhanced, and the above-mentioned filtration phenomenon is utilized to make a low molecular weight region. The protein can be efficiently permeated. However, on the other hand, if the sieving coefficient of the solute is increased over the entire hollow fiber membrane, the filtration from the dialysate side to the blood side increases due to the back filtration phenomenon at the blood side outlet, and it may be mixed in the dialysate. There is a problem that sexual endotoxin easily flows into the blood. Endotoxin is a kind of bacterial toxin that breaks down Gram-negative bacteria and liberates ribopolysaccharide, which is a constituent of the cell wall, to exert toxicity.

【0006】そこで、本発明は、補液を使用せずに、効
率的に低分子量領域のタンパク質を血液中から除去する
ことができ、かつ、透析液からのエンドトキシンを侵入
させることのない中空糸型血液浄化器を提供することを
目的とする。
Therefore, the present invention is a hollow fiber type which can efficiently remove proteins in the low molecular weight region from blood without using a replacement fluid and does not allow endotoxin from infiltrating the dialysate. The purpose is to provide a blood purifier.

【0007】[0007]

【課題を解決するための手段】上記課題を解決するため
の手段は、中空糸膜の束と、前記中空糸膜の束を収容す
る中空糸膜ケースと、前記中空糸膜ケースの両端部にそ
れぞれ設けられた血液流入口及び血液流出口と、前記中
空糸膜ケースの血液流出口側に設けられた透析液流入口
と、前記中空糸膜ケースの血液流入口側に設けられた透
析液流出口とを備え、中空糸膜を介して血液と透析液と
を向流させてなる中空糸型血液浄化器であって、血液流
出口側の中空糸膜における溶質の篩い係数が、血液流入
口側の中空糸膜における溶質の篩い係数よりも小さいこ
とを特徴とする中空糸型血液浄化器であり、また、前記
溶質がアルブミンであり、前記血液流出口側の中空糸膜
におけるアルブミンの篩い係数(SC2)が、前記血液
流入口側の中空糸膜におけるアルブミンの篩い係数(S
C1)よりも小さく、かつSC2が0.5未満であり、
さらに、前記中空糸膜における溶質の篩い係数が中空糸
膜の前記血液流入口側から前記血液流出口側へ長手方向
に連続的に減少することを特徴とする中空糸型血液浄化
器であり、さらに他の手段は、一端側の溶質の篩い係数
が小さく、他端側の溶質の篩い係数が大きい中空糸膜の
製造方法であって、疎水性高分子樹脂及び有機溶媒を含
む製膜原液を、芯液と共に二重管紡糸口金から凝固液中
に吐出させ、前記疎水性高分子樹脂に対する溶解性の高
い良溶媒と前記疎水性高分子樹脂に対する溶解性の低い
貧溶媒とを含む芯液の良溶媒と貧溶媒との混合比率を製
造原液吐出時に変化させることを特徴とする中空糸膜の
製造方法である
Means for solving the above-mentioned problems are as follows: a bundle of hollow fiber membranes, a hollow fiber membrane case accommodating the bundle of hollow fiber membranes, and both ends of the hollow fiber membrane case. Blood inlet and blood outlet provided respectively, dialysate inlet provided on the blood outlet side of the hollow fiber membrane case, dialysate flow provided on the blood inlet side of the hollow fiber membrane case A hollow fiber blood purifier having an outlet and countercurrently flowing blood and dialysate through a hollow fiber membrane, wherein the sieving coefficient of the solute in the hollow fiber membrane on the blood outlet side is the blood inlet. A hollow fiber type blood purifier characterized by being smaller than the sieving coefficient of the solute in the hollow fiber membrane on the side, and the solute is albumin, and the sieving coefficient of albumin in the hollow fiber membrane on the blood outlet side. (SC2) is the hollow fiber on the blood inlet side Sieving coefficient of albumin in the (S
Smaller than C1) and SC2 is less than 0.5,
Furthermore, a hollow fiber type blood purifier characterized in that the sieving coefficient of the solute in the hollow fiber membrane is continuously reduced in the longitudinal direction from the blood inlet side of the hollow fiber membrane to the blood outlet side. Still another means is a method for producing a hollow fiber membrane in which the sieving coefficient of the solute on one end side is small and the sieving coefficient of the solute on the other end side is large, and a membrane forming stock solution containing a hydrophobic polymer resin and an organic solvent is used. A core liquid containing a good solvent having a high solubility for the hydrophobic polymer resin and a poor solvent having a low solubility for the hydrophobic polymer resin, which is discharged together with the core liquid into a coagulating liquid from a double-tube spinneret. A method for producing a hollow fiber membrane, characterized in that the mixing ratio of a good solvent and a poor solvent is changed at the time of discharging the production stock solution.

【0008】[0008]

【発明の実施の形態】本発明の中空糸型血液浄化器を図
1を用いて説明する。本発明の中空糸型血液浄化器は、
中空糸膜における溶質の篩い係数が中空糸膜の長手方向
に向かって変化する点を除いて従来の中空糸型血液浄化
器と同様である。
BEST MODE FOR CARRYING OUT THE INVENTION A hollow fiber blood purifier according to the present invention will be described with reference to FIG. The hollow fiber blood purifier of the present invention is
The hollow fiber membrane is similar to the conventional hollow fiber blood purifier except that the sieving coefficient of the solute in the hollow fiber membrane changes in the longitudinal direction of the hollow fiber membrane.

【0009】中空糸型血液浄化器1は、中空糸膜2の束
と、前記中空糸膜2の束を収容する中空糸膜ケース3
と、前記中空糸膜ケースの両端部に設けられた血液側入
口ポート4と、血液側出口ポート5と、前記中空糸膜ケ
ース3のケース側面の血液側出口ポート5側に設けられ
た透析液流入口6と、前記中空糸膜ケース3のケース側
面の血液側入口ポート4側に設けられた透析液流出口7
とを備える。
The hollow fiber blood purifier 1 comprises a bundle of hollow fiber membranes 2 and a hollow fiber membrane case 3 for containing the bundle of hollow fiber membranes 2.
A blood side inlet port 4 provided at both ends of the hollow fiber membrane case, a blood side outlet port 5, and a dialysate provided at the blood side outlet port 5 side of the hollow fiber membrane case 3. Inflow port 6 and dialysate outflow port 7 provided at the blood side inlet port 4 side of the case side surface of the hollow fiber membrane case 3.
With.

【0010】血液側入口ポート4から流入された血液
は、中空糸膜2の中空内を実線矢印方向へ図1の右から
左へ流通し血液側出口ポート5から排出される。一方、
透析液流入口6から流入された透析液は、中空糸膜同士
の外周面及び中空糸膜ケース3の内周面によって形成さ
れた空間10内を点線矢印方向へ図1の左から右へ流通
し透析液流出口7から排出される。このように血液と透
析液とを向流する構造を有する。
Blood that has flowed in from the blood side inlet port 4 flows through the hollow of the hollow fiber membrane 2 in the direction of the solid line arrow from right to left in FIG. 1 and is discharged from the blood side outlet port 5. on the other hand,
The dialysate flowing from the dialysate inlet 6 flows in the space 10 formed by the outer peripheral surfaces of the hollow fiber membranes and the inner peripheral surface of the hollow fiber membrane case 3 in the direction of the dotted arrow from left to right in FIG. It is discharged from the dialysate outlet 7. Thus, it has a structure in which blood and dialysate flow countercurrently.

【0011】中空糸型血液浄化器1の血液側入口ポート
4から中間地点にかけての第1の領域8においては、中
空糸膜2の中空内を流通する血液の流入圧力が、空間1
0内を流通する透析液の流入圧力に比べて大きくなる。
したがって、この領域8においては、拡散現象による血
液から透析液への老廃物の移動だけでなく、濾過現象に
よる血液から透析液への低分子量タンパク質の移動が生
じる。
In the first region 8 from the blood side inlet port 4 of the hollow fiber type blood purifier 1 to the intermediate point, the inflow pressure of the blood flowing through the hollow of the hollow fiber membrane 2 is the space 1
It becomes larger than the inflow pressure of the dialysate flowing through the inside of zero.
Therefore, in this region 8, not only the transfer of waste products from the blood to the dialysate due to the diffusion phenomenon but also the transfer of the low molecular weight protein from the blood to the dialysate due to the filtration phenomenon occurs.

【0012】また中間地点から中空糸型血液浄化器1の
血液側出口ポート5にかけての第2の領域9において
は、中空糸膜2の中空内を流通する血液の流入圧力が圧
力損失によって減少するので、空間10内を流通する透
析液の流入圧力に比べて小さくなる。したがって、この
領域9においては、逆濾過現象による透析液から血液へ
の溶質の移動が生じる。
In the second region 9 extending from the intermediate point to the blood side outlet port 5 of the hollow fiber blood purifier 1, the inflow pressure of the blood flowing through the hollow of the hollow fiber membrane 2 decreases due to the pressure loss. Therefore, it becomes smaller than the inflow pressure of the dialysate flowing through the space 10. Therefore, in this region 9, the solute is transferred from the dialysate to the blood due to the back filtration phenomenon.

【0013】前記中空糸膜2は、第1の領域8において
は、溶質の篩い係数が大きく、第二の領域9において
は、溶質の篩い係数が小さい。
The hollow fiber membrane 2 has a large solute sieving coefficient in the first region 8 and a small solute sieving coefficient in the second region 9.

【0014】血液流入口側である第1の領域8における
アルブミンの篩い係数をSC1、血液流出口側である第
2の領域9におけるアルブミンの篩い係数をSC2とし
た場合、SC1>SC2、かつSC2<0.5であるこ
とが好ましい。さらに望ましくはSC1>0.8であ
る。篩い係数は、濾過膜の溶質透過性を表す指標であっ
て、SCで表すことができる。SC値が1に近いほど透
過性が良く、0に近いほど悪い。血液入口濃度をCb
i、血液出口濃度をCbo、濾過液の濃度をCfとする
と、例えば
When the sieving coefficient of albumin in the first area 8 on the blood inlet side is SC1 and the sieving coefficient of albumin in the second area 9 on the blood outlet side is SC2, SC1> SC2 and SC2 <0.5 is preferable. More preferably, SC1> 0.8. The sieving coefficient is an index representing the solute permeability of the filtration membrane and can be represented by SC. The closer the SC value is to 1, the better the transparency is, and the closer the SC value is to 0, the worse the transparency is. Blood inlet concentration is Cb
i, the blood outlet concentration is Cbo, and the filtrate concentration is Cf, for example,

【数1】SC=2×Cf/(Cbi+Cbo) で示すことができる。[Equation 1] SC = 2 × Cf / (Cbi + Cbo) Can be shown as

【0015】また、第1の領域8における溶質の篩い係
数は、領域8全体で同じであってもよいし、領域8内に
おいても血液流出口に近づくほど、溶質の篩い係数が小
さくなるように変化させてもよい。第2の領域9におけ
る溶質の篩い係数についても同様である。領域8、9に
おいて、溶質の篩い係数が変化する場合は、上記溶質の
篩い係数SC1、SC2は、それぞれ第1の領域8にお
ける平均の溶質の篩い係数、及び第2の領域9における
平均の溶質の篩い係数となる。
The sieving coefficient of the solute in the first region 8 may be the same in the entire region 8 or the sieving coefficient of the solute may be smaller in the region 8 as it gets closer to the blood outlet. You may change it. The same applies to the solute sieving coefficient in the second region 9. When the solute sieving coefficient changes in the regions 8 and 9, the solute sieving coefficients SC1 and SC2 are the average solute sieving coefficient in the first region 8 and the average solute sieving in the second region 9, respectively. Becomes the sieving coefficient.

【0016】第1の領域8における濾過現象において、
中空糸膜2の溶質の篩い係数が大きいので、低分子量領
域のタンパク質を効率的に移動させることができる。特
に、透析アミロイド症の原因となるβ2マイクログロブ
リンを効率的に除去することが可能となる。
In the filtering phenomenon in the first region 8,
Since the solute sieving coefficient of the hollow fiber membrane 2 is large, proteins in the low molecular weight region can be efficiently moved. In particular, β2 microglobulin that causes dialysis amyloidosis can be efficiently removed.

【0017】尚、ここで低分子量領域のタンパク質に
は、血液中に含まれる分子量69000の血清アルブミ
ンよりも低分子量のタンパク質が含まれる。
The protein in the low molecular weight region includes a protein having a lower molecular weight than serum albumin having a molecular weight of 69000 contained in blood.

【0018】また、第2の領域9における逆濾過現象に
おいて、中空糸膜2の溶質の篩い係数が小さいので、透
析液中に断片化したエンドトキシンが混入した場合にお
いても、血液中内に侵入しにくくなる。
Further, in the back-filtration phenomenon in the second region 9, since the solute sieving coefficient of the hollow fiber membrane 2 is small, even when fragmented endotoxin is mixed in the dialysate, it penetrates into the blood. It gets harder.

【0019】本発明における中空糸膜2は、親水性高分
子及び、疎水性高分子を膜素材とすることができる。中
でも疎水性高分子が、エンドトキシン吸着能を有する点
で好ましい。
The hollow fiber membrane 2 in the present invention can be made of hydrophilic polymer and hydrophobic polymer as membrane materials. Among them, hydrophobic polymers are preferable because they have endotoxin adsorption ability.

【0020】本発明に用いることのできる疎水性高分子
としては、例えば、ポリスルホン樹脂、ポリエーテルス
ルホン樹脂、及びポリアリレート樹脂等を挙げることが
できる。これらはそれぞれ単独で使用しても、混合して
使用してもよい。
Examples of the hydrophobic polymer that can be used in the present invention include polysulfone resin, polyether sulfone resin, and polyarylate resin. These may be used alone or in combination.

【0021】本発明における中空糸膜2は、親水性を付
与するために、疎水性高分子膜にポリビニルピロリドン
等の親水性高分子を付着保持させることもできる。親水
性を膜表面に付与することにより、血栓の原因となる血
漿タンパク質の吸着を少なくすることができる。
In order to impart hydrophilicity to the hollow fiber membrane 2 of the present invention, a hydrophilic polymer such as polyvinylpyrrolidone may be attached and held on the hydrophobic polymer membrane. By imparting hydrophilicity to the membrane surface, it is possible to reduce the adsorption of plasma proteins that cause thrombus.

【0022】中空糸膜2の紡糸は、公知の方法とほぼ同
じである。すなわち、疎水性高分子樹脂、例えば、ポリ
エステル系樹脂及びポリスルホン系樹脂とをN−メチル
ピロリドン等の有機溶媒に溶解する。次に、この製膜原
液を二重管紡糸口金を用いて芯液と共に凝固液中に吐出
し、中空糸状に紡糸することで多孔性膜を得ることがで
きる。尚、この紡糸条件を変化させることによって、中
空糸膜の長手方向に対する溶質の篩い係数、すなわち膜
のポアサイズを変化させることができる。変化させる紡
糸条件としては、例えば、製膜原液の凝固液への吐出速
度、芯液の組成を挙げることができる。中でも、操作が
容易であり、数十センチ間隔で中空糸膜の溶質の篩い係
数を変化させることができる点で芯液の組成を変化させ
ることが好ましい。
The spinning of the hollow fiber membrane 2 is almost the same as the known method. That is, a hydrophobic polymer resin such as a polyester resin and a polysulfone resin is dissolved in an organic solvent such as N-methylpyrrolidone. Next, this membrane-forming stock solution is discharged together with the core solution into the coagulating solution using a double-tube spinning spinneret, and is spun into a hollow fiber to obtain a porous membrane. By changing the spinning conditions, the solute sieving coefficient in the longitudinal direction of the hollow fiber membrane, that is, the pore size of the membrane can be changed. The spinning conditions to be changed include, for example, the discharge rate of the film-forming stock solution into the coagulating solution and the composition of the core solution. Among them, it is preferable to change the composition of the core liquid because it is easy to operate and the sieving coefficient of the solute of the hollow fiber membrane can be changed at intervals of several tens of centimeters.

【0023】芯液は水単独でも使用することができる
が、中空糸膜の原料である高分子樹脂に対する溶解性の
高い良溶媒と前記高分子樹脂に対する溶解性の低い貧溶
媒との混合溶媒を芯液として用いることができる。例え
ば良溶媒としてN−メチルピロリドン、貧溶媒として水
を用いた混合溶媒は、両溶媒が分離することなく混ざり
あうので芯液として好ましい。
Although the core liquid can be used as water alone, a mixed solvent of a good solvent having a high solubility for the polymer resin as a raw material of the hollow fiber membrane and a poor solvent having a low solubility for the polymer resin can be used. It can be used as a core liquid. For example, a mixed solvent using N-methylpyrrolidone as a good solvent and water as a poor solvent is preferable as the core liquid because both solvents are mixed without separation.

【0024】芯液の混合比率、例えば水とN−メチルピ
ロリドン(以下NMPと表記する)の混合比率を変化さ
せることにより、中空糸膜の溶質の篩い係数を変化させ
ることができる。尚、水とNMPとの混合溶液の場合、
芯液中のNMP混合比率が大きい程、得られた中空糸膜
の篩い係数が大きくなる。芯液の混合比率の変化は、中
空糸膜の紡糸装置において、芯液の中のNMP濃度を可
変させる装置を設けることによって、数十センチ間隔で
中空糸膜の溶質の篩い係数を変化させることが可能とな
る。
The solute sieving coefficient of the hollow fiber membrane can be changed by changing the mixing ratio of the core liquid, for example, the mixing ratio of water and N-methylpyrrolidone (hereinafter referred to as NMP). In the case of a mixed solution of water and NMP,
The larger the NMP mixing ratio in the core liquid, the larger the sieving coefficient of the obtained hollow fiber membrane. The change of the mixing ratio of the core fluid is to change the solute sieving coefficient of the hollow fiber membrane at intervals of several tens of centimeters by providing a device for varying the NMP concentration in the core fluid in the hollow fiber membrane spinning device. Is possible.

【0025】尚、本発明における中空糸膜は、断面方向
のポアサイズが一定の均一膜であってもよいし、断面方
向にポアサイズが異なる不均一膜であってもよい。
The hollow fiber membrane of the present invention may be a uniform membrane having a constant pore size in the cross-sectional direction or a non-uniform membrane having different pore sizes in the cross-sectional direction.

【0026】[0026]

【実施例】(実施例1)疎水性高分子としてポリアリレ
ート7.5部、ポリエーテルスルホン7.5部、有機溶
剤としてNMP85部を混和し、製膜原液とした。凝固
液として、水30部、NMP70部の混合溶液を用い
た。芯液として水とNMPとの混合溶液を用いた。製膜
原液を、芯液と共に二重管紡糸口金から凝固液中に吐出
させて中空糸膜を紡糸させた。尚、中空糸膜の紡糸時に
おける芯液の混合比率は水51部NMP49部(下限
値)から水47部NMP53部(上限値)の間で周期的
に変動させた。
EXAMPLES Example 1 7.5 parts of polyarylate as a hydrophobic polymer, 7.5 parts of polyether sulfone and 85 parts of NMP as an organic solvent were mixed to prepare a stock solution for film formation. As a coagulating liquid, a mixed solution of 30 parts of water and 70 parts of NMP was used. A mixed solution of water and NMP was used as the core liquid. The membrane-forming stock solution was discharged together with the core solution into the coagulating solution from the double-tube spinneret to spin the hollow fiber membrane. The mixing ratio of the core liquid during spinning of the hollow fiber membrane was periodically changed from 51 parts NMP 49 parts water (lower limit value) to 47 parts NMP 53 parts water (upper limit value).

【0027】(実施例2)中空糸膜の紡糸時における芯
液の混合比率を水50.5部NMP49.5部から水4
4.5部NMP55.5部の間で周期的に変動させた点
を除き実施例1と同様に中空糸膜を得た。
(Example 2) When the hollow fiber membrane was spun, the mixing ratio of the core liquid was 50.5 parts of water to 49.5 parts of NMP to 4 parts of water.
A hollow fiber membrane was obtained in the same manner as in Example 1 except that it was periodically varied between 4.5 parts NMP55.5 parts.

【0028】(比較例)中空糸膜の紡糸時における芯液
の混合比率を水47部NMP53部で一定にした点を除
き実施例1と同様に中空糸膜を得た。
Comparative Example A hollow fiber membrane was obtained in the same manner as in Example 1 except that the mixing ratio of the core liquid during spinning of the hollow fiber membrane was kept constant at 47 parts of water and 53 parts of NMP.

【0029】(篩い係数の測定)中空糸膜の血液入り口
側、血液出口側の篩い係数は、以下のようにして求め
た。実施例1、実施例2及び比較例で製膜し、モジュー
ルの長さに切断された中空糸膜を中央より半分の長さに
さらに切断し、それぞれミニモジュールを作製した。各
モジュールの血液側に牛血清アルブミン(分子量690
00)を流入させ、透析液側に水を流出させて、アルブ
ミンに対する篩い係数ALBSCを測定した。血液出口
側のALBSCをSC2とし、血液入口側のALBSC
をSC1とした。半分に切断した中空糸膜のうち、芯液
が下限値側にあるときに作製された中空糸膜部分を用い
たミニモジュールの篩い係数が血液出口側の篩い係数で
あり、芯液が上限値側にあるときに作成された中空糸膜
部分を用いたミニモジュールの篩い係数が血液入口側の
篩い係数である。
(Measurement of sieving coefficient) The sieving coefficients on the blood inlet side and the blood outlet side of the hollow fiber membrane were determined as follows. The hollow fiber membranes produced in Example 1, Example 2 and Comparative Example and cut into module lengths were further cut into half lengths from the center to produce mini-modules. Bovine serum albumin (molecular weight 690
00) was made to flow in and water was made to flow out to the dialysate side, and the sieving coefficient ALBSC for albumin was measured. ALBSC on the blood outlet side is SC2, and ALBSC on the blood inlet side
Was designated as SC1. Among the hollow fiber membranes cut in half, the sieving coefficient of the mini-module using the hollow fiber membrane part produced when the core fluid is on the lower limit side is the sieving coefficient on the blood outlet side, and the core fluid is the upper limit value. The sieving coefficient of the mini-module using the hollow fiber membrane portion that was created on the side is the sieving coefficient on the blood inlet side.

【0030】(エンドトキシンとβ2マイクログロブリ
ンの透過量の測定)実施例1、実施例2及び比較例で製
膜し、モジュールの長さに切断された中空糸膜を用いて
モジュールを形成した。実施例1及び実施例2について
は、アルブミンに対する篩い係数が大きい中空糸膜側に
血液側入口を設け、アルブミンに対する篩い係数が小さ
い中空糸膜側に血液側出口を設けた。透析液側にはエン
ドトキシン(ET)を2000EU/l含む透析液を流
速500ml/minで循環させた。一方、血液側には
β2マイクログロブリン(β2MG)を30mg/l含
む牛血液を流速200ml/minで、循環させた。E
Tの血液中への透過量を評価するために、血液出口側に
てサンプルA2を、血液入口側にてサンプルA1を採取
し、各サンプルのET濃度を測定して、サンプルA2と
サンプルA1との濃度差を算出し、その濃度差をET透
過量とした。β2MGの透析液中への透過量を評価する
ために、透析液出口側にてサンプルB2を、透析液入口
側にてサンプルB1を採取し、各サンプルのβ2MG濃
度を測定して、サンプルB2とサンプルB1との濃度差
を算出し、その濃度差をβ2MG透過量とした。
(Measurement of the amount of permeation of endotoxin and β2 microglobulin) A module was formed by using the hollow fiber membranes produced in Example 1, Example 2 and Comparative Example and cut to the module length. In Examples 1 and 2, the blood side inlet was provided on the side of the hollow fiber membrane having a large sieving coefficient for albumin, and the blood side outlet was provided on the side of the hollow fiber membrane having a small sieving coefficient for albumin. On the dialysate side, a dialysate containing 2000 EU / l of endotoxin (ET) was circulated at a flow rate of 500 ml / min. On the other hand, bovine blood containing 30 mg / l of β2 microglobulin (β2MG) was circulated on the blood side at a flow rate of 200 ml / min. E
In order to evaluate the amount of T penetrating into blood, sample A2 is sampled at the blood outlet side and sample A1 is sampled at the blood inlet side, and the ET concentration of each sample is measured to obtain sample A2 and sample A1. Was calculated, and the difference in concentration was defined as the ET permeation amount. In order to evaluate the permeation amount of β2MG into the dialysate, sample B2 was sampled at the dialysate outlet side and sample B1 was sampled at the dialysate inlet side, and the β2MG concentration of each sample was measured to obtain sample B2. The concentration difference from the sample B1 was calculated, and the concentration difference was defined as the β2MG transmission amount.

【0031】[0031]

【表1】 [Table 1]

【0032】中空糸膜の長手方向に対して全体的に篩い
係数が大きく、すなわちポアサイズの大きい比較例の血
液浄化器においては、β2MGを除去することができた
が、血液中へのエンドトキシンの流入が生じた。尚、中
空糸膜の長手方向に対して全体的にポアサイズを小さく
してしまえば、血液中へのエンドトキシンの流入を阻止
できるが、β2MGを除去することができなくなる。
In the blood purifier of the comparative example, which has a large sieving coefficient in the longitudinal direction of the hollow fiber membrane, that is, a large pore size, β2MG could be removed, but endotoxin flowed into the blood. Occurred. It should be noted that if the pore size is made smaller overall in the longitudinal direction of the hollow fiber membrane, the inflow of endotoxin into the blood can be blocked, but β2MG cannot be removed.

【0033】エンドトキシンの流入が支配的な領域であ
る中空糸膜の血液出口側のポアサイズのみを小さくした
実施例1の血液浄化器においては、血液中へのエンドト
キシンの流入を阻止できると共に、β2MGを除去が達
成された。ただし、比較例の場合に比べてβ2MGの除
去効率が低かった。
In the blood purifier of Example 1 in which only the pore size on the blood outlet side of the hollow fiber membrane, in which the inflow of endotoxin is dominant, is reduced, the inflow of endotoxin into the blood can be prevented and β2MG Removal was achieved. However, the removal efficiency of β2MG was lower than that of the comparative example.

【0034】実施例1に比べて血液出口側、血液入口側
共に全体的にポアサイズを向上させた実施例2の血液浄
化器においては、血液中へのエンドトキシンの流入を阻
止できると共に、β2MGの高い除去効率が達成され
た。
In the blood purifier of Example 2 in which the pore size is improved on both the blood outlet side and the blood inlet side as compared with Example 1, the inflow of endotoxin into the blood can be prevented and β2MG is high. Removal efficiency was achieved.

【0035】[0035]

【発明の効果】本発明は、血液流入口側の中空糸膜にお
ける溶質の篩い係数を大きくする一方で、血液流出口側
の中空糸膜における溶質の篩い係数を小さくした中空糸
膜を用いることにより、補液を使用することなく効率的
に低分子量領域のタンパク質を血液中から除去すること
ができ、かつ、透析液からのエンドトキシンの侵入させ
ることのない中空糸型血液浄化器を提供することができ
る。
INDUSTRIAL APPLICABILITY The present invention uses a hollow fiber membrane in which the sieving coefficient of solute in the hollow fiber membrane on the blood inlet side is increased while the sieving coefficient of solute in the hollow fiber membrane on the blood outlet side is decreased. Thus, it is possible to efficiently remove proteins in the low molecular weight region from the blood without using a replacement fluid, and to provide a hollow fiber blood purifier that does not allow endotoxin to enter from the dialysate. it can.

【図面の簡単な説明】[Brief description of drawings]

【図1】 図1は本発明の中空糸型血液浄化器の概略を
示す図である。
FIG. 1 is a diagram showing an outline of a hollow fiber blood purifier of the present invention.

【符号の説明】[Explanation of symbols]

1 中空糸型血液浄化器 2 中空糸膜 3 中空糸膜ケース 4 血液側入口ポート 5 血液側出口ポート 6 透析液側流入口 7 透析液側流出口 8 第1の領域 9 第2の領域 10 空間 1 Hollow fiber blood purifier 2 Hollow fiber membrane 3 Hollow fiber membrane case 4 Blood side inlet port 5 Blood side outlet port 6 Dialysate side inlet 7 Dialysate side outlet 8 First area 9 Second area 10 spaces

───────────────────────────────────────────────────── フロントページの続き Fターム(参考) 4C077 AA05 BB01 KK11 LL05 LL14 LL16 LL17 NN14 PP10 PP15 4D006 GA07 HA02 MA01 MA21 MA22 MA40 MB02 MB10 MC36X MC61X MC62 NA05 NA10 NA13 PA01 PB09 PB52 PB54 PC47    ─────────────────────────────────────────────────── ─── Continued front page    F-term (reference) 4C077 AA05 BB01 KK11 LL05 LL14                       LL16 LL17 NN14 PP10 PP15                 4D006 GA07 HA02 MA01 MA21 MA22                       MA40 MB02 MB10 MC36X                       MC61X MC62 NA05 NA10                       NA13 PA01 PB09 PB52 PB54                       PC47

Claims (4)

【特許請求の範囲】[Claims] 【請求項1】 中空糸膜の束と、前記中空糸膜の束を収
容する中空糸膜ケースと、前記中空糸膜ケースの両端部
にそれぞれ設けられた血液流入口及び血液流出口と、前
記中空糸膜ケースの血液流出口側に設けられた透析液流
入口と、前記中空糸膜ケースの血液流入口側に設けられ
た透析液流出口とを備えてなる中空糸型血液浄化器であ
って、血液流出口側の中空糸膜における溶質の篩い係数
が、血液流入口側の中空糸膜における溶質の篩い係数よ
りも小さいことを特徴とする中空糸型血液浄化器。
1. A bundle of hollow fiber membranes, a hollow fiber membrane case accommodating the bundle of hollow fiber membranes, a blood inlet and a blood outlet provided at both ends of the hollow fiber membrane case, respectively. A hollow fiber type blood purifier comprising a dialysate inlet provided on the blood outlet side of a hollow fiber membrane case and a dialysate outlet provided on the blood inlet side of the hollow fiber membrane case. The hollow fiber blood purifier is characterized in that the sieving coefficient of the solute in the hollow fiber membrane on the blood outlet side is smaller than the sieving coefficient of the solute in the hollow fiber membrane on the blood inlet side.
【請求項2】 前記溶質がアルブミンであり、前記血液
流出口側の中空糸膜におけるアルブミンの篩い係数(S
C2)が、前記血液流入口側の中空糸膜におけるアルブ
ミンの篩い係数(SC1)よりも小さく、かつSC2が
0.5未満であることを特徴とする請求項1に記載の中
空糸型血液浄化器。
2. The solute is albumin, and the sieving coefficient of albumin (S
C2) is smaller than the sieving coefficient (SC1) of albumin in the hollow fiber membrane on the blood inlet side, and SC2 is less than 0.5. vessel.
【請求項3】 前記中空糸膜における溶質の篩い係数が
中空糸膜の前記血液流入口側から前記血液流出口側へと
向かって連続的に低下することを特徴とする請求項1又
は2に記載の中空糸型血液浄化器。
3. The sieving coefficient of the solute in the hollow fiber membrane continuously decreases from the blood inflow side of the hollow fiber membrane toward the blood outflow side. The hollow fiber blood purifier described.
【請求項4】 一端側の溶質の篩い係数が小さく、他端
側の溶質の篩い係数が大きい中空糸膜の製造方法であっ
て、疎水性高分子樹脂及び有機溶媒を含む製膜原液を、
芯液と共に二重管紡糸口金から凝固液中に吐出させ、前
記疎水性高分子樹脂に対する溶解性の高い良溶媒と前記
疎水性高分子樹脂に対する溶解性の低い貧溶媒とを含む
芯液の良溶媒と貧溶媒との混合比率を製造原液吐出時に
変化させることを特徴とする中空糸膜の製造方法。
4. A method for producing a hollow fiber membrane having a small sieving coefficient of a solute on one end side and a large sieving coefficient of a solute on the other end side, wherein a membrane-forming stock solution containing a hydrophobic polymer resin and an organic solvent is prepared.
A good core liquid containing a good solvent having a high solubility for the hydrophobic polymer resin and a poor solvent having a low solubility for the hydrophobic polymer resin, which is discharged together with the core liquid from the double-tube spinneret into the coagulation liquid. A method for producing a hollow fiber membrane, characterized in that the mixing ratio of the solvent and the poor solvent is changed at the time of discharging the production stock solution.
JP2002013534A 2002-01-22 2002-01-22 Hollow fiber type blood-purifier, and manufacturing method for hollow fiber membrane Pending JP2003210573A (en)

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Publication Number Publication Date
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ID=27650469

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Country Link
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Cited By (3)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
JP2005118506A (en) * 2003-10-14 2005-05-12 Shoichi Kin On-line massive fluid replacement type hemodialyzer
WO2010090174A1 (en) * 2009-02-04 2010-08-12 東洋紡績株式会社 Hollow-fiber membrane, process for producing same, and blood purification module
JP2018158275A (en) * 2017-03-22 2018-10-11 ダイセン・メンブレン・システムズ株式会社 Hollow fiber membrane for endotoxin capture filter

Cited By (5)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
JP2005118506A (en) * 2003-10-14 2005-05-12 Shoichi Kin On-line massive fluid replacement type hemodialyzer
WO2010090174A1 (en) * 2009-02-04 2010-08-12 東洋紡績株式会社 Hollow-fiber membrane, process for producing same, and blood purification module
US8840788B2 (en) 2009-02-04 2014-09-23 Toyo Boseki Kabushiki Kaisha Hollow fiber membrane, method for manufacturing the same, and blood purification module
JP5720249B2 (en) * 2009-02-04 2015-05-20 東洋紡株式会社 Hollow fiber membrane, method for producing the same, and blood purification module
JP2018158275A (en) * 2017-03-22 2018-10-11 ダイセン・メンブレン・システムズ株式会社 Hollow fiber membrane for endotoxin capture filter

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