JPH06228887A - Modified hollow fiber and its production - Google Patents
Modified hollow fiber and its productionInfo
- Publication number
- JPH06228887A JPH06228887A JP5033925A JP3392593A JPH06228887A JP H06228887 A JPH06228887 A JP H06228887A JP 5033925 A JP5033925 A JP 5033925A JP 3392593 A JP3392593 A JP 3392593A JP H06228887 A JPH06228887 A JP H06228887A
- Authority
- JP
- Japan
- Prior art keywords
- hollow fiber
- blood
- hydrophilic polymer
- modified
- semipermeable
- 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
Landscapes
- Treatments For Attaching Organic Compounds To Fibrous Goods (AREA)
- Spinning Methods And Devices For Manufacturing Artificial Fibers (AREA)
- External Artificial Organs (AREA)
- Separation Using Semi-Permeable Membranes (AREA)
- Chemical Or Physical Treatment Of Fibers (AREA)
Abstract
Description
【０００１】[0001]
【０００１】[0001]
【０００２】[0002]
【産業上の利用分野】本発明は、改質された中空糸およ
びその製造方法に関する。更に詳しくは、半透性中空糸
の少なくとも内表面に対し、水に不溶化した親水性高分
子物質を物理的に保持させることにより、生体適合性，
血液適合性の向上した改質中空糸およびその製造方法に
関する。TECHNICAL FIELD The present invention relates to a modified hollow fiber and a method for producing the same. More specifically, by physically retaining a hydrophilic polymer substance insolubilized in water on at least the inner surface of the semipermeable hollow fiber, biocompatibility,
TECHNICAL FIELD The present invention relates to a modified hollow fiber having improved blood compatibility and a method for producing the same.
【０００３】[0003]
【０００２】[0002]
【０００４】[0004]
【従来の技術】近年、選択的な透過性を有する膜を利用
する技術がめざましく進歩し、気体や液体の分離フィル
ター，医療分野に於ける血液透析器，血液濾過器，血液
成分選択分離フィルター等広範な分野での実用化が進ん
でいる。2. Description of the Related Art In recent years, the technology of utilizing a membrane having selective permeability has been remarkably advanced, and a gas or liquid separation filter, a hemodialyzer in the medical field, a hemofilter, a blood component selective separation filter, etc. Practical application is progressing in a wide range of fields.
【０００５】[0005]
【０００３】特に中空糸状の膜は、膜面積当りの占有体
積を小さくできるので小型化，軽量化し易く、好適に用
いられている。膜材料としては、セルロース系（再生セ
ルロース系，酢酸セルロース系，化学変性セルロース系
等），ポリアクリロニトリル系，ポリメチルメタクリレ
ート系，エチレンビニルアルコール系，ポリアミド系等
のポリマーが用いられてきた。[0003] In particular, hollow fiber membranes are preferably used because they can easily be made compact and lightweight because the volume occupied per membrane area can be made small. As the film material, polymers such as cellulose type (regenerated cellulose type, cellulose acetate type, chemically modified cellulose type), polyacrylonitrile type, polymethylmethacrylate type, ethylene vinyl alcohol type, polyamide type and the like have been used.
【０００６】[0006]
【０００４】[0004]
【０００７】[0007]
【発明が解決しようとする課題】しかしながら、従来用
いられてきた中空糸は血液と接触させた時、厚材料によ
って程度に差はあるものの或る種の血液成分と膜表面と
の間に生体反応を生起することが知られている。However, conventionally used hollow fibers, when contacted with blood, have a biological reaction between certain blood components and the surface of the membrane, although the degree varies depending on the thickness of the material. Is known to occur.
【０００８】[0008]
【０００５】例えばセルロース系中空糸の場合は補体の
副経路を活性化し、アナフィラトキシンであるＣ３ａを
生成させたり、透析器として使用した際には末梢血液中
の白血球の一時的減少を引き起こす。[0005] For example, in the case of a cellulosic hollow fiber, it activates an alternative pathway of complement to produce C3a which is an anaphylatoxin, or causes a temporary decrease of leukocytes in peripheral blood when used as a dialyzer.
【０００９】[0009]
【０００６】ポリアクリロニトリル系中空糸の場合は高
分子キニノーゲンを活性化し、ブラジキニンを生成する
と言われている。It is said that the polyacrylonitrile-based hollow fiber activates polymeric kininogen to produce bradykinin.
【００１０】[0010]
【０００７】ポリメチルメタクリレート系中空糸の場合
は血小板の粘着量が多く、透析器として用いた場合、血
液の体外循環終了後の中空糸内に血液が残留し易いと言
われており、また顆粒球の放出を生起するプロテアーゼ
であるエラスターゼが透析中高値になることも知られて
いる。[0007] In the case of polymethylmethacrylate hollow fiber, the amount of adherence of platelets is large, and when used as a dialyzer, it is said that blood tends to remain in the hollow fiber after the end of extracorporeal circulation of blood, and granules It is also known that elastase, a protease that causes the release of spheres, becomes high during dialysis.
【００１１】[0011]
【０００８】エチレンビニルアルコール系中空糸の場合
は、補体古典経路の活性化があると指摘されている。It has been pointed out that in the case of ethylene vinyl alcohol hollow fibers, there is activation of the complement classical pathway.
【００１２】[0012]
【０００９】ポリアミド系中空糸の場合は、やはり血小
板の粘着量が多く、中空糸内への血液残留量が多い。In the case of a polyamide hollow fiber, the amount of platelets adhered is large and the amount of blood remaining in the hollow fiber is large.
【００１３】[0013]
【００１０】この様に従来から使用されて来た中空糸を
そのまま使用した場合には、或る種の血液成分と膜表面
との間に生体反応が起こり、少なからず血液に対して悪
影響を与えており、その為、血液成分に対する生体反応
のより少ない中空糸が望まれていた。When the hollow fiber which has been conventionally used as described above is used as it is, a biological reaction occurs between a certain blood component and the surface of the membrane, which adversely affects blood in no small way. Therefore, a hollow fiber having less biological reaction to blood components has been desired.
【００１４】[0014]
【００１１】[0011]
【００１５】[0015]
【課題を解決するための手段】本発明者らは、上記した
従来から在る中空糸が有する問題点を解決し、或る種の
血液成分と中空糸膜表面との生体反応のより少ない中空
糸を得るために鋭意研究を重ねた結果、半透性中空糸の
少なくとも内表面（血液と接触する表面）に対して水に
不溶化した親水性高分子物質を物理的に保持させる事に
より、血液成分と内表面との生体反応が驚くべき程改善
されることを見出し、本発明を構成するに至った。Means for Solving the Problems The present inventors have solved the problems of the above-described conventional hollow fibers, and are hollow with less biological reaction between a certain blood component and the hollow fiber membrane surface. As a result of earnest studies to obtain a thread, by physically retaining at least the inner surface of the semipermeable hollow fiber (the surface in contact with blood) with a hydrophilic polymer substance insolubilized in water, It was found that the biological reaction between the component and the inner surface was surprisingly improved, and the present invention was constituted.
【００１６】[0016]
【００１２】すなわち本発明は、半透性中空糸であっ
て、少なくともその内表面に水に対して不溶化された親
水性高分子物質を物理的に保持していることを特徴とし
た改質中空糸に関するものであり、半透性中空糸の少な
くとも内表面に親水性高分子物質を接触させた後、該親
水性高分子物質を架橋することを特徴とした改質中空糸
の製造方法に関するものである。That is, the present invention is a semipermeable hollow fiber, characterized in that at least the inner surface of the modified hollow fiber physically holds a hydrophilic polymer substance insolubilized in water. The present invention relates to a yarn, and relates to a method for producing a modified hollow fiber, which comprises contacting at least the inner surface of a semipermeable hollow fiber with a hydrophilic polymer substance and then crosslinking the hydrophilic polymer substance. Is.
【００１７】[0017]
【００１３】ここで言う半透性中空糸とは、その材料，
形状，寸法，分画特性等により特に限定されるものでは
無く、血液透析，蛋白分画，血漿分離等，その目的に照
らして適切なものを選択すれば良い。The semipermeable hollow fiber referred to here is the material,
The shape, size, and fractionation characteristics are not particularly limited, and hemodialysis, protein fractionation, plasma separation, and the like may be selected appropriately depending on the purpose.
【００１８】[0018]
【００１４】材料を例示すると、再生セルロース系，酢
酸セルロース系，化学変性セルロース系等のセルロース
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，エチレンビニルアルコール共重合体を含むポリビ
ニル系，ポリアミド系，ポリエステル系，ポリオレフィ
ン系等のポリマーが挙げられ、中でもセルロース系ポリ
マーは、機械的強度が強く、中空糸膜の薄膜化が可能で
あり、好適に用いられる。Examples of the material include regenerated cellulose, cellulose acetate, chemically modified cellulose, and other cellulose, polyacrylonitrile, polymethylmethacrylate, polyvinyl containing an ethylene vinyl alcohol copolymer, polyamide, polyester. Among them, polymers such as polyolefin-based polymers are mentioned. Among them, cellulose-based polymers are preferably used because they have high mechanical strength and can form a thin hollow fiber membrane.
【００１９】[0019]
【００１５】形状は通常円筒状の物が用いられるが、円
筒の外側面にフィンの付いた形状の物も使用することが
でき、寸法は、膜厚が１〜１００μｍ，好ましくは５〜
５０μｍ，内径が５０〜５００μｍ，好ましくは１００
〜３００μｍ程度の物が使用でき、分画特性について
は、その用途により透析用であれば低分子量物質からア
ルブミンより小さい分子量の物質の透過性が高い中空
糸，蛋白分画用であれば低分子蛋白が透過し、高分子蛋
白や免疫複合体の様な物質が透過し難い中空糸，血漿分
離用であれば血漿成分は透過するが血球成分は透過しな
い中空糸などが好適に用いられる。The shape is usually a cylindrical shape, but a shape with fins on the outer surface of the cylinder can also be used, and the dimension is such that the film thickness is 1 to 100 μm, preferably 5 to 5.
50 μm, inner diameter 50-500 μm, preferably 100
About 300 to 300 μm can be used. Regarding the fractionation characteristics, depending on the application, hollow fibers with high permeability from low molecular weight substances to substances with molecular weight smaller than albumin for dialysis, low molecular weight for protein fractionation A hollow fiber through which a protein permeates and a substance such as a high molecular protein or an immune complex hardly permeates, and a hollow fiber through which a plasma component but a blood cell component does not permeate for plasma separation is preferably used.
【００２０】[0020]
【００１６】また親水性高分子物質とは、水に可溶であ
り、かつ物理的処理および／または化学的処理により架
橋し、それにより水に対し不溶化し得る物質を言い、例
示すと、ポリビニルピロリドン，ポリエチレングリコー
ル，ポリビニルアルコール，ポリプロピレングリコール
等が挙げられるが、これらに限定されるものではなく、
これらの中では、ポリビニルピロリドンおよび／または
ポリエチレングリコールが生体適合性改善の面から特に
推奨しうるものである。The hydrophilic polymer substance is a substance which is soluble in water and can be crosslinked by a physical treatment and / or a chemical treatment, thereby making it insoluble in water. Examples thereof include pyrrolidone, polyethylene glycol, polyvinyl alcohol, polypropylene glycol and the like, but are not limited thereto.
Of these, polyvinylpyrrolidone and / or polyethylene glycol are particularly recommended from the viewpoint of improving biocompatibility.
【００２１】[0021]
【００１７】親水性高分子物質の分子量は大きい方が架
橋が進み易いが、水溶液にした時の粘度が高くなり取り
扱いにくくなる。したがって、それらの分子量として
は、５００から１００万，好ましくは１万から５０万，
更に好ましくは２万から４０万が推奨しうるものであ
る。The larger the molecular weight of the hydrophilic polymer substance is, the easier the crosslinking proceeds, but the viscosity of the aqueous solution becomes high and the handling becomes difficult. Therefore, their molecular weight is 500 to 1,000,000, preferably 10,000 to 500,000,
More preferably, 20,000 to 400,000 can be recommended.
【００２２】[0022]
【００１８】親水性高分子物質が水に対し不溶化される
ということは、上記した親水性高分子物質が架橋され、
更に高分子化した結果水に対する溶解性が失なわれると
いうことである。The fact that the hydrophilic polymer substance is insolubilized in water means that the above-mentioned hydrophilic polymer substance is cross-linked.
It means that the solubility in water is lost as a result of further polymerization.
【００２３】[0023]
【００１９】また、少なくともその内表面に親水性高分
子物質が物理的に保持されるということは、水に対し不
溶化された親水性高分子物質が半透性中空糸の表面近傍
に存在し、水中に溶出あるいは遊離して行かない様に保
持されている状態、あるいは水に対し不溶化された親水
性高分子物質が半透性中空糸内部に一部浸入し、半透性
中空糸表面近傍に機械的に保持されている状態を言い、
また、親水性高分子の存在部位は内表面のみに限定され
ることなく、これ以外の部位、例えば外表面に存在して
も差支えない。Further, the fact that the hydrophilic polymer substance is physically retained on at least the inner surface means that the hydrophilic polymer substance insolubilized in water exists near the surface of the semipermeable hollow fiber, A state in which it is held so that it does not elute or release in water, or a hydrophilic polymer substance insolubilized in water partially penetrates inside the semipermeable hollow fiber, causing it to near the surface of the semipermeable hollow fiber. Mechanically held,
Further, the site where the hydrophilic polymer is present is not limited to the inner surface only, and it may be present on other sites, for example, the outer surface.
【００２４】[0024]
【００２０】親水性高分子物質を半透性中空糸に接触さ
せる方法は、親水性高分子物質を水または適当な溶剤、
あるいはこれらの混合溶媒に溶解させた後半透性中空糸
に接触させ、その後余分な溶液を気体により吹き飛ばし
てしまう方法、霧状にした親水性高分子溶液を半透性中
空糸に吹き付ける方法等、公知のコーティング方法を使
用することができ、また、上記した処理は、中空糸の状
態で行なっても良いし、中空糸を容器に充填した透析
器，蛋白分画様濾過器等モジュールの状態にした後に行
なってもよい。The method of contacting the hydrophilic polymer substance with the semipermeable hollow fiber is as follows.
Alternatively, a method of contacting the latter half permeable hollow fiber dissolved in these mixed solvents, followed by blowing off the excess solution with a gas, a method of spraying the atomized hydrophilic polymer solution onto the semipermeable hollow fiber, etc. Known coating methods can be used, and the above-mentioned treatment may be carried out in a hollow fiber state, or in a module state such as a dialyzer or a protein fractionation-like filter in which a hollow fiber is filled in a container. You may do it after.
【００２５】[0025]
【００２１】親水性高分子溶液の濃度は、親水性高分子
物質の分子量，すなわち溶液にした時の溶液粘度，架橋
後の半透性中空糸の濾過性能等を考慮して任意に選択し
うるが、０．０１から１０重量％，好ましくは０．０５
から５重量％，更に好ましくは０．１から１重量％の溶
液濃度が推奨しうるものである。The concentration of the hydrophilic polymer solution can be arbitrarily selected in consideration of the molecular weight of the hydrophilic polymer substance, that is, the solution viscosity of the solution, the filtration performance of the semipermeable hollow fiber after crosslinking, and the like. , 0.01 to 10% by weight, preferably 0.05
A solution concentration of 1 to 5% by weight, more preferably 0.1 to 1% by weight, is recommended.
【００２６】[0026]
【００２２】親水性高分子物質を架橋させる方法を例示
すると、γ線，Ｘ線等を用いる放射線架橋法，紫外線架
橋法，熱架橋法，架橋試薬を用いる方法あるいはこれら
の組み合わせ等が挙げられ、また、架橋を促進させるた
め、種々の開始剤，開始助剤あるいは重合性モノマー，
オリゴマー，ポリマー等を使用することもでき、上記し
た架橋法のうち、半透性中空糸の膜構造に与える影響が
少なく、残留試薬の問題が少ないことなどから放射線架
橋法が特に推奨しうるものである。Examples of the method for crosslinking the hydrophilic polymer substance include a radiation crosslinking method using γ-rays and X-rays, an ultraviolet crosslinking method, a thermal crosslinking method, a method using a crosslinking reagent, and a combination thereof. In order to promote crosslinking, various initiators, initiator aids or polymerizable monomers,
Of the above-mentioned cross-linking methods, which can be used as an oligomer or polymer, the radiation cross-linking method is particularly recommended because it has little effect on the membrane structure of the semipermeable hollow fiber and there are few problems with residual reagents. Is.
【００２７】[0027]
【００２３】放射線架橋法のうちγ線を用いる場合、そ
の線量の選択は親水性高分子の架橋の程度，素材の劣化
の程度を尺度に任意に選定できるが、１から１００ｋＧ
ｙ，好ましくは５から５０ｋＧｙ，更に好ましくは１０
から２５ｋＧｙが推奨しうる線量である。When γ-rays are used in the radiation crosslinking method, the dose can be selected arbitrarily on the basis of the degree of crosslinking of the hydrophilic polymer and the degree of deterioration of the material, but 1 to 100 kG
y, preferably 5 to 50 kGy, more preferably 10
To 25 kGy is a recommended dose.
【００２８】[0028]
【００２４】本発明の改質中空糸は、その多数本が容器
に接着固定されたモジュールの形で使用されるのが一般
的であり、以下、透析器を例にとり図１に則して説明す
る。図１は透析器の一例を示す模式図であるが、改質中
空糸１は透析液出入口５，５′を有する容器２にその多
数本が集束され、ウレタンの様なポッティング材３によ
り端部が接着され、容器に固定される。The modified hollow fiber of the present invention is generally used in the form of a module in which a large number of the hollow fibers are adhered and fixed to a container. Hereinafter, a dialyzer will be described as an example with reference to FIG. To do. FIG. 1 is a schematic diagram showing an example of a dialysis machine. A large number of modified hollow fibers 1 are bundled in a container 2 having dialysate inlets and outlets 5, 5 ', and end portions are formed by a potting material 3 such as urethane. Are glued and fixed to the container.
【００２９】[0029]
【００２５】改質中空糸１の中空部分は血液出入口４，
４′に開放されており、血液は改質中空糸の内側を流れ
る構造になっており、ここで改質中空糸１の本数は１０
００から２００００本，有効長は１５０から４００ｍｍ
の範囲が一般的であるがこの範囲に限定されるものでは
無い。透析液は入口５′から入り、改質中空糸１の外表
面に接触し、出口５から排出され、血液は入口４′から
入り、改質中空糸１内に入り透析された後出口４から排
出されるという使い方が一般的である。血液は改質中空
糸１の内面に接触するわけであるが、改質中空糸１内表
面には親水性高分子物質の層が形成されているので半透
性中空糸構造体の材料そのものの表面と血液とが直接接
触する頻度が低く抑えられ、その結果として、血液─膜
材料間の生体反応が驚くべき程抑制されるものと思わ
れ、その結果、各膜材料表面が持っている欠点、即ち血
液との生体反応を改善した上で、各膜材料の有している
分画特性を充分発揮しうるものである。The hollow portion of the modified hollow fiber 1 has a blood inlet / outlet port 4,
It is open to 4 ', and the blood is structured to flow inside the modified hollow fiber. Here, the number of modified hollow fibers 1 is 10
00 to 20000, effective length 150 to 400 mm
However, the range is not limited to this range. The dialysate enters through the inlet 5 ', contacts the outer surface of the modified hollow fiber 1 and is discharged through the outlet 5, and the blood enters through the inlet 4', enters the modified hollow fiber 1 and is dialyzed, and then exits the outlet 4. It is generally used to be discharged. Blood comes into contact with the inner surface of the modified hollow fiber 1, but since a layer of a hydrophilic polymer substance is formed on the inner surface of the modified hollow fiber 1, the blood itself is not the material of the semipermeable hollow fiber structure. It is thought that the frequency of direct contact between the surface and blood is suppressed to be low, and as a result, the biological reaction between blood and the membrane material is surprisingly suppressed, and as a result, the drawbacks that each membrane material surface has That is, after improving the biological reaction with blood, the fractionation characteristics possessed by each membrane material can be sufficiently exhibited.
【００３０】[0030]
【００２６】[0026]
【００３１】[0031]
実施例１〜６および比較例１ 半透性中空糸としてキュプラアンモニウムセルロース中
空糸を用い図１に示す透析器を試作した。Examples 1 to 6 and Comparative Example 1 Using the cupra ammonium cellulose hollow fiber as the semipermeable hollow fiber, the dialyzer shown in FIG. 1 was prototyped.
【００３２】[0032]
【００２７】該透析器は、中空糸の膜厚１５μｍ，内径
１８０μｍ，フィラメント数１１０００本，膜面積１．
５ｍ2 であり、この透析器に対して、親水性高分子物質
としてポリビニルピロリドン（以下ＰＶＰと称す。）処
理を施して実施例１〜６とした。表１にその処理条件を
示す。The dialyzer has a hollow fiber membrane thickness of 15 μm, an inner diameter of 180 μm, the number of filaments of 11,000, and a membrane area of 1.
It was 5 m 2 , and this dialyzer was treated with polyvinylpyrrolidone (hereinafter referred to as PVP) as a hydrophilic polymer substance to give Examples 1 to 6. Table 1 shows the processing conditions.
【００３３】[0033]
【００２８】[0028]
【００３４】[0034]
【表１】 ＰＶＰは分子量４万および分子量３６万のものを使用
し、それぞれ表１に示す濃度の水溶液を調製した。それ
ぞれの未処理透析器に対し血液入口４′から各々のＰＶ
Ｐ溶液２００ｍｌを８００ｍｌ／分の流速で流した後
０．２ｋｇ／ｃｍ2の圧縮空気で残存するＰＶＰ溶液を
吹き飛ばして血液出口４から排出した。この後１０ｋＧ
ｙのγ線を照射した。次に中空糸の内側，外側すなわち
容器２内部を水で充填して実施例１〜６の透析器とし
た。[Table 1] PVP having a molecular weight of 40,000 and a molecular weight of 360,000 were used, and aqueous solutions having the concentrations shown in Table 1 were prepared. From each blood inlet 4'to each PV for each untreated dialyzer
After 200 ml of the P solution was flowed at a flow rate of 800 ml / min, the remaining PVP solution was blown out with 0.2 kg / cm 2 of compressed air and discharged from the blood outlet 4. 10kG after this
Irradiation with y-rays of y. Next, the inside and outside of the hollow fiber, that is, the inside of the container 2 was filled with water to obtain the dialyzer of Examples 1 to 6.
【００３５】[0035]
【００２９】これに対して、ＰＶＰ処理を施さない透析
器を比較例１とした。On the other hand, a dialyzer not subjected to PVP treatment was used as Comparative Example 1.
【００３６】[0036]
【００３０】以上の様にして作成した実施例１〜６およ
び比較例１について以下の試験を行なった。The following tests were conducted on Examples 1 to 6 and Comparative Example 1 prepared as described above.
【００３７】[0037]
【００３１】１）．日本人工臓器学会の性能評価基準に
従い、透水量（以下ｕＦＲと略す，単位はｍｌ／ｈｒ／
ｍｍＨｇ），クレアチニンおよびビタミンＢ12（以下Ｖ
Ｂ12）のクリアランス（膜間圧力０ｍｍＨｇの時の値）
を測定した。1). Permeability (hereinafter abbreviated as uFR, unit: ml / hr /
mmHg), creatinine and vitamin B 12 (hereinafter V
Clearance B 12) (the value when the transmembrane pressure 0 mmHg)
Was measured.
【００３８】[0038]
【００３２】２）．日本人工臓器学会の性能測定基準に
準じミオグロビン（以下Ｍｂ）のクリアランス（但し膜
間圧力０ｍｍＨｇの時の値）を測定した。2). The clearance of myoglobin (hereinafter referred to as Mb) (however, the value when the transmembrane pressure was 0 mmHg) was measured according to the performance measurement standard of the Japan Society for Artificial Organs.
【００３９】[0039]
【００３３】３）．実施例１〜６，比較例１と同様に作
成した透析器より中空糸を切り出し、フィラメント数１
００本，長さ１５０ｍｍのミニモジュールを作成し、こ
れにヘパリン添加ヒト新鮮血液１０ｍｌを１ｍｌ／ｍｉ
ｎの流速で流し、ミニモジュールを通過した血液につき
以下の分析を行なった。 ａ） 血小板数（電気抵抗検出法） ｂ） 血小板第４因子（以下ＰＦ−４，酵素免疫分析） ｃ） Ｃ３ａ（放射免疫分析２抗体法） ｄ） ブラジキニン（以下ＢＫ，放射免疫分析ＰＥＧ
法） ｅ） 顆粒球エラスターゼ（酵素免疫分析） 各透析器について測定した結果を表２に、ミニモジュー
ルで測定した結果を表３に示す。3). Hollow fibers were cut out from a dialyzer prepared in the same manner as in Examples 1 to 6 and Comparative Example 1, and the number of filaments was 1
00 pieces, 150 mm long mini-module was prepared, and 10 ml of heparin-added human fresh blood was added to this at 1 ml / mi
The following analysis was performed on the blood that had been passed through the mini-module at a flow rate of n. a) Platelet count (electrical resistance detection method) b) Platelet factor 4 (hereinafter PF-4, enzyme immunoassay) c) C3a (radioimmunoassay 2 antibody method) d) Bradykinin (hereinafter BK, radioimmunoassay PEG)
Method) e) Granulocyte elastase (enzyme immunoassay) Table 2 shows the results measured for each dialyzer, and Table 3 shows the results measured with the mini module.
【００４０】[0040]
【００３４】表２および表３は比較例１の測定値を１０
０とした場合の各々の実施例１〜６の測定値を示す。Tables 2 and 3 show the measured values of Comparative Example 1 of 10
The measured value of each Example 1-6 when set to 0 is shown.
【００４１】[0041]
【００３５】[0035]
【００４２】[0042]
【表２】 [Table 2]
【００４３】[0043]
【００３６】[0036]
【００４４】[0044]
【表３】 実施例１〜６および比較例１の結果から、ＰＶＰを不溶
化し、セルロース内表面に物理的に保持したことによ
り、表２に示す様に透析器の性能を維持しつつ、表３に
示す様に血小板の減少が少なく、血小板第４因子の放
出，Ｃ３ａの生成，ブラジキニンの生成，顆粒球エラス
ターゼの放出が大幅に抑制されていることが判る。[Table 3] From the results of Examples 1 to 6 and Comparative Example 1, by insolubilizing PVP and physically retaining it on the inner surface of cellulose, the performance of the dialyzer was maintained as shown in Table 2 and the results shown in Table 3 were obtained. It can be seen that there is little reduction in platelets, and the release of platelet factor 4, C3a, bradykinin, and granulocyte elastase is significantly suppressed.
【００４５】[0045]
【００３７】[0037]
【００４６】[0046]
【発明の効果】以上述べた様に、本発明による改質中空
糸は、血小板付着による中空糸内血液残留，補体の活性
化，ロイコペニア，高分子キニノーゲン活性化，顆粒球
刺激等血液と半透性中空糸との接触による生体反応が抑
制され、血液適合性の良好な中空糸が得られ、本発明改
質中空糸を用いた血液透析器，血液濾過器，血液成分選
択分離フィルター等の医療用具は血液に対する刺激の少
ない、血液適合性の良好な医療器具となった。As described above, the modified hollow fiber according to the present invention is capable of retaining blood in the hollow fiber due to adhesion of platelets, activation of complement, leucopenia, high-molecular kininogen activation, granulocyte stimulation, etc. A biological reaction due to contact with a permeable hollow fiber is suppressed, a hollow fiber having good blood compatibility is obtained, and a hemodialyzer, a hemofilter, a blood component selective separation filter using the modified hollow fiber of the present invention. The medical device has become a medical device with low blood irritation and good blood compatibility.
【図１】本発明改質中空糸を用いた透析器の一例を示す
模式図である。FIG. 1 is a schematic view showing an example of a dialyzer using the modified hollow fiber of the present invention.
１ 改質中空糸 ２ 容器 ３ ポッティング材 ４ 血液出口 ４′ 血液入口 ５ 透析液出口 ５′ 透析液入口 1 modified hollow fiber 2 container 3 potting material 4 blood outlet 4'blood inlet 5 dialysate outlet 5'dialyzer inlet
───────────────────────────────────────────────────── フロントページの続き (51)Int.Cl.5 識別記号 庁内整理番号 ＦＩ 技術表示箇所 Ｄ０６Ｍ 23/16 ─────────────────────────────────────────────────── ─── Continuation of the front page (51) Int.Cl. 5 Identification code Internal reference number FI technical display location D06M 23/16
Claims (5)
内表面に水に対して不溶化された親水性高分子物質を物
理的に保持していることを特徴とする改質中空糸。1. A modified hollow fiber which is a semipermeable hollow fiber, wherein at least the inner surface of the hollow fiber physically holds a hydrophilic polymer substance insolubilized in water.
ることを特徴とする特許請求の範囲第１項記載の改質中
空糸。2. The modified hollow fiber according to claim 1, wherein the semipermeable hollow fiber is a cellulosic hollow fiber.
ンおよび／またはポリエチレングリコールであることを
特徴とする特許請求の範囲第１項記載の改質中空糸。3. The modified hollow fiber according to claim 1, wherein the hydrophilic polymer substance is polyvinylpyrrolidone and / or polyethylene glycol.
性高分子物質を接触させた後、該親水性高分子物質を架
橋することを特徴とする改質中空糸の製造方法。4. A method for producing a modified hollow fiber, which comprises contacting at least the inner surface of a semipermeable hollow fiber with a hydrophilic polymer substance and then crosslinking the hydrophilic polymer substance.
特徴とする特許請求の範囲第４項記載の改質中空糸の製
造方法。5. The method for producing a modified hollow fiber according to claim 4, wherein the method of crosslinking is radiation crosslinking.
Priority Applications (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| JP03392593A JP3297707B2 (en) | 1993-02-01 | 1993-02-01 | Modified hollow fiber and method for producing the same |
Applications Claiming Priority (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| JP03392593A JP3297707B2 (en) | 1993-02-01 | 1993-02-01 | Modified hollow fiber and method for producing the same |
Publications (2)
| Publication Number | Publication Date |
|---|---|
| JPH06228887A true JPH06228887A (en) | 1994-08-16 |
| JP3297707B2 JP3297707B2 (en) | 2002-07-02 |
Family
ID=12400098
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| JP03392593A Expired - Lifetime JP3297707B2 (en) | 1993-02-01 | 1993-02-01 | Modified hollow fiber and method for producing the same |
Country Status (1)
| Country | Link |
|---|---|
| JP (1) | JP3297707B2 (en) |
Cited By (5)
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|---|---|---|---|---|
| JP2002066276A (en) * | 2000-08-29 | 2002-03-05 | Asahi Kasei Corp | Film withstanding organic contamination |
| WO2007018284A1 (en) * | 2005-08-09 | 2007-02-15 | Asahi Kasei Kabushiki Kaisha | Separation membrane for use in treatment of liquid comprising aromatic ether polymer which is hydrophilized with hydrophilizing agent |
| JP2008113880A (en) * | 2006-11-06 | 2008-05-22 | Nikkiso Co Ltd | Blood purifier and its manufacturing method |
| JP2011183384A (en) * | 2011-04-01 | 2011-09-22 | Toray Ind Inc | Adsorption material and manufacturing method for the same |
| WO2016006041A1 (en) * | 2014-07-08 | 2016-01-14 | 国立大学法人山梨大学 | Blood purifier |
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| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN1934129B (en) | 2004-01-21 | 2010-07-14 | 东丽株式会社 | Fractionator and method of fractionation |
| CA2578202C (en) | 2004-08-30 | 2013-12-17 | Toray Industries, Inc. | Fractionation apparatus |
| WO2008102744A1 (en) | 2007-02-20 | 2008-08-28 | Toray Industries, Inc. | Method for production of molded resin article |
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Cited By (6)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| JP2002066276A (en) * | 2000-08-29 | 2002-03-05 | Asahi Kasei Corp | Film withstanding organic contamination |
| WO2007018284A1 (en) * | 2005-08-09 | 2007-02-15 | Asahi Kasei Kabushiki Kaisha | Separation membrane for use in treatment of liquid comprising aromatic ether polymer which is hydrophilized with hydrophilizing agent |
| US8602221B2 (en) | 2005-08-09 | 2013-12-10 | Asahi Kasei Kabuhiki Kaisha | Separation membrane for use in treatment of liquid comprising aromatic ether polymer hydrophilized with hydrophilizing agent |
| JP2008113880A (en) * | 2006-11-06 | 2008-05-22 | Nikkiso Co Ltd | Blood purifier and its manufacturing method |
| JP2011183384A (en) * | 2011-04-01 | 2011-09-22 | Toray Ind Inc | Adsorption material and manufacturing method for the same |
| WO2016006041A1 (en) * | 2014-07-08 | 2016-01-14 | 国立大学法人山梨大学 | Blood purifier |
Also Published As
| Publication number | Publication date |
|---|---|
| JP3297707B2 (en) | 2002-07-02 |
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