JPH07178166A - Artificial organ - Google Patents
Artificial organInfo
- Publication number
- JPH07178166A JPH07178166A JP5325652A JP32565293A JPH07178166A JP H07178166 A JPH07178166 A JP H07178166A JP 5325652 A JP5325652 A JP 5325652A JP 32565293 A JP32565293 A JP 32565293A JP H07178166 A JPH07178166 A JP H07178166A
- Authority
- JP
- Japan
- Prior art keywords
- vitamin
- body fluid
- blood
- artificial organ
- membrane
- 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
Abstract
Description
【0001】[0001]
【産業上の利用分野】本発明は、人工臓器に関するもの
である。詳しく述べると、白血球または血小板等の活性
化を抑えた生体適合性に優れた人工腎臓、人工肺、血液
分離装置等の人工臓器に関するものである。FIELD OF THE INVENTION The present invention relates to an artificial organ. More specifically, the present invention relates to artificial organs such as artificial kidneys, artificial lungs, and blood separation devices that suppress activation of white blood cells or platelets and have excellent biocompatibility.
【0002】[0002]
【従来の技術】従来より、人工腎臓、人工肺、血漿分離
器等の人工臓器が使用され、透析膜、ガス交換膜、血液
成分分離膜などにおいては、合成高分子膜が広く利用さ
れている。しかしながら、例えば人工腎臓においては、
血液透析を頻繁に行うため、白血球または血小板の活性
化が生じることにより、合併症が併発し、透析患者の深
刻な問題となっている。特に、長期的に血液透析を行っ
ている患者の血中抗酸化作用の低下や過酸化脂質の高値
などが確認されており、このため、長期透析患者の動脈
硬化性疾患が増加している。2. Description of the Related Art Conventionally, artificial organs such as artificial kidneys, artificial lungs and plasma separators have been used, and synthetic polymer membranes have been widely used in dialysis membranes, gas exchange membranes, blood component separation membranes and the like. . However, for example in artificial kidneys,
Since hemodialysis is frequently performed, activation of white blood cells or platelets causes complications, which is a serious problem for dialysis patients. In particular, it has been confirmed that the blood antioxidant in patients who are on hemodialysis for a long period of time is low, and the value of lipid peroxide is high. Therefore, arteriosclerotic diseases are increasing in long-term dialysis patients.
【0003】一方、この問題を解決するため、生体内抗
酸化作用、生体膜安定化作用、血小板凝集抑制作用など
の種々の生理作用を有するビタミンEの被膜を透析膜の
表面に被覆する人工臓器が提案されている(特公昭62
−41738号公報参照)。しかしながら、親水性素材
の表面にビタミンEを被覆すると血液流入時に血液への
溶出が認められ、血液循環後30分後には約90%のビ
タミンEが血液中に溶出することが確認されており、ビ
タミンEの効果の持続性が問題となっている。On the other hand, in order to solve this problem, an artificial organ in which the surface of a dialysis membrane is coated with a vitamin E coating having various physiological actions such as in vivo antioxidant action, biological membrane stabilizing action and platelet aggregation inhibiting action. Has been proposed (Japanese Patent Publication Sho 62
No. 41738). However, when vitamin E is coated on the surface of a hydrophilic material, elution into blood is observed at the time of blood inflow, and it has been confirmed that about 90% of vitamin E elutes into blood 30 minutes after blood circulation. The persistence of the effects of vitamin E is a problem.
【0004】また、溶解度パラメータδが高いほど親水
性が強く、透析膜が親水性素材である場合、脂溶性ビタ
ミンであるビタミンEとの親和性が悪いので、例えば、
溶解度パラメータδが15.65(cal/cm3)1/2
である再生セルロースは、血液流入時に血液への溶出が
生じることが問題となっている。Further, the higher the solubility parameter δ, the stronger the hydrophilicity, and when the dialysis membrane is a hydrophilic material, the affinity with the fat-soluble vitamin Vitamin E is poor.
Solubility parameter δ is 15.65 (cal / cm 3 ) 1/2
The regenerated cellulose, which is, has a problem that elution into blood occurs when the blood enters.
【0005】[0005]
【発明が解決しようとする課題】本発明の目的は、脂溶
性ビタミンであるビタミンEとの親和性を良好にし、血
液への溶出を抑え、生体に対して副作用の少ない人工臓
器を提供することにある。SUMMARY OF THE INVENTION It is an object of the present invention to provide an artificial organ which has a good affinity for vitamin E which is a fat-soluble vitamin, suppresses elution into blood, and has few side effects on the living body. It is in.
【0006】[0006]
【課題を解決するための手段】上記課題を解決するため
に、本発明の人工臓器は、体液透過膜を備える人工臓器
であって、該体液透過膜は、溶解度パラメータδが13
(cal/cm3)1/2以下であり、さらに、少なくとも
該体液透過膜の体液と接触し得る部位の表面にビタミン
Eを被覆してなることを特徴とする。In order to solve the above problems, the artificial organ of the present invention is an artificial organ having a body fluid permeable membrane, and the body fluid permeable membrane has a solubility parameter δ of 13
(Cal / cm 3 ) 1/2 or less, and at least the surface of the body fluid permeable membrane that can come into contact with body fluid is coated with vitamin E.
【0007】また、本発明の人工臓器は、該人工臓器内
の体液流通域の少なくとも体液と接触する部位の表面に
ビタミンEを被覆してなることが好ましい。Further, the artificial organ of the present invention is preferably formed by coating vitamin E on at least the surface of the body fluid flow region in the artificial organ which is in contact with the body fluid.
【0008】また、本発明の人工臓器は、該体液透過膜
が中空糸型膜であることが好ましい。In the artificial organ of the present invention, the body fluid permeable membrane is preferably a hollow fiber type membrane.
【0009】さらに、本発明の人工臓器は、該体液透過
膜が疎水性または疎水部分を含む合成高分子膜であるこ
とが好ましい。Further, in the artificial organ of the present invention, the body fluid permeable membrane is preferably a synthetic polymer membrane having hydrophobicity or a hydrophobic portion.
【0010】さらに、本発明の人工臓器は、該体液透過
膜がポリエチレン、ポリメチルメタクリレート、ポリス
チレン、ポリプロピレン、ポリスルホン、ポリヒドロキ
シエチルメタクリレート、ナイロン66、セルロースア
セテート、ポリアクリロニトリル、ポリビニルアルコー
ル、エチレン−ビニルアルコール共重合体、ポリカーボ
ネートの中から選ばれる少なくとも1つの高分子材料か
ら作られる中空糸型膜であることが好ましい。Further, in the artificial organ of the present invention, the body fluid permeable membrane is polyethylene, polymethyl methacrylate, polystyrene, polypropylene, polysulfone, polyhydroxyethyl methacrylate, nylon 66, cellulose acetate, polyacrylonitrile, polyvinyl alcohol, ethylene-vinyl alcohol. A hollow fiber type membrane made of at least one polymer material selected from a copolymer and a polycarbonate is preferable.
【0011】また、本発明の生体適合性人工臓器は、体
液透過膜のビタミンE被覆量が1〜1000mg/m3
であることが好ましい。In the biocompatible artificial organ of the present invention, the body fluid permeable membrane has a vitamin E coating amount of 1 to 1000 mg / m 3.
Is preferred.
【0012】本発明における人工臓器とは、人工腎臓、
人工肝臓、人工肺、血漿分離器、血液回路、人工血管等
のように人工臓器内に血液等の体液を流通する体液流通
域を有するもので、この体液流通域は、少なくともその
一部分が体液透過膜であることが望ましい。なお、この
人工臓器としては、生体から該人工臓器まで接続するチ
ューブやコネクタ等はもちろんのこと、その他血液回路
等も含まれる。The artificial organ in the present invention means an artificial kidney,
An artificial liver, an artificial lung, a plasma separator, a blood circuit, an artificial blood vessel, etc. that has a body fluid circulation region for circulating body fluid such as blood in an artificial organ. It is preferably a membrane. The artificial organ includes not only a tube and a connector for connecting a living body to the artificial organ, but also other blood circuits and the like.
【0013】また、本発明における溶解度パラメータδ
とは、ビタミンEとの親和性の度合いを表し、溶解度パ
ラメータδが高い場合には親水性が強く、溶解度パラメ
ータδが低い場合には疎水性が強いことを示す。さら
に、溶解度パラメータδが13(cal/cm3)1/2以
下のときビタミンEとの親和性が良好な疎水性である。
また、溶解度パラメータδの算出方法等については、例
えば、高分子ハンドブック(基礎編、591頁から59
3頁)等の多くの文献に記載されている。Further, the solubility parameter δ in the present invention
Represents the degree of affinity with vitamin E, and indicates that when the solubility parameter δ is high, the hydrophilicity is strong, and when the solubility parameter δ is low, the hydrophobicity is strong. Furthermore, when the solubility parameter δ is 13 (cal / cm 3 ) 1/2 or less, the affinity for vitamin E is good and the hydrophobicity.
For the calculation method of the solubility parameter δ, see, for example, Polymer Handbook (Basic Edition, pages 591 to 59).
It is described in many documents such as page 3).
【0014】[0014]
【実施例】以下、本発明の実施例を添付図面を用いて詳
細に説明する。Embodiments of the present invention will be described in detail below with reference to the accompanying drawings.
【0015】図1は、人工腎臓、すなわち中空糸型膜の
ダイアライザの一例を示すものである。このダイアライ
ザ1は、両端部付近に透析液用の入口管2および出口管
3をそれぞれ設けてなる筒状本体4に多数の中空糸より
なる中空糸束5を挿入した後、その両端部をポリウレタ
ン等のポッティング剤6,7で筒状本体4の両端部と共
にそれぞれシールしてなる。また、筒状本体4の両端に
は体液用の流入口8および排出口9をそれぞれ備えたヘ
ッダー10,11がそれぞれ当接され、キャップ12,
13によりヘッダー10,11と筒状本体4とがそれぞ
れ固着されている。さらに、筒状本体4の両端の体液流
入口8および体液排出口9には、人体に接続するチュー
ブ14,15が連結されている。FIG. 1 shows an example of an artificial kidney, that is, a dialyzer of a hollow fiber type membrane. In this dialyzer 1, a hollow fiber bundle 5 made up of a large number of hollow fibers is inserted into a tubular body 4 which is provided with an inlet pipe 2 and an outlet pipe 3 for dialysate near both ends, and then both ends thereof are made of polyurethane. The potting agents 6 and 7 are used to seal both ends of the cylindrical body 4 together. Further, headers 10 and 11 each having an inflow port 8 and a discharge port 9 for body fluid are respectively brought into contact with both ends of the cylindrical main body 4, and the cap 12,
The headers 10 and 11 and the tubular main body 4 are fixed by 13 respectively. Further, tubes 14 and 15 for connecting to a human body are connected to the body fluid inlet port 8 and the body fluid outlet port 9 at both ends of the tubular body 4.
【0016】中空糸束5を構成する中空糸は、透析膜で
あって、例えば、ポリエチレン(δ=7.70)、ポリ
メチルメタクリレート(δ=9.10)、ポリスチレン
(δ=9.15)、ポリプロピレン(δ=9.40)、
ポリスルホン(δ=9.90)、ポリヒドロキシエチル
メタクリレート(δ=10.00)、ナイロン66(δ
=11.18)、セルロースジアセテート(δ=11.
35)、ポリアクリロニトリル(δ=12.35)、ポ
リビニルアルコール(δ=12.60)、セルロースト
リアセテート、エチレン−ビニルアルコール共重合体、
ポリカーボネート等、溶解度パラメータδが13(ca
l/cm3)1/2以下であればいかなる膜でもよい。The hollow fibers constituting the hollow fiber bundle 5 are dialysis membranes and are, for example, polyethylene (δ = 7.70), polymethylmethacrylate (δ = 9.10), polystyrene (δ = 9.15). , Polypropylene (δ = 9.40),
Polysulfone (δ = 9.90), Polyhydroxyethyl methacrylate (δ = 10.00), Nylon 66 (δ
= 11.18), cellulose diacetate (δ = 11.1.
35), polyacrylonitrile (δ = 12.35), polyvinyl alcohol (δ = 12.60), cellulose triacetate, ethylene-vinyl alcohol copolymer,
Solubility parameter δ such as polycarbonate is 13 (ca
Any film may be used as long as it is 1 / cm 3 ) 1/2 or less.
【0017】本発明によれば、上述のごとき人工腎臓の
体液、例えば血液の流通域の血液との接触部位、例えば
中空糸膜内面、ヘッダー10とポッティング剤6とによ
り形成される空間の内面、ヘッダー11とポッティング
剤7とにより形成される空間の内面、血液流入口8の内
面、血液排出口9の内面、チューブ14,15の内面、
特に中空糸膜内面にビタミンEを被覆してなるものであ
る。例えば、中空糸型膜において、図2に示すように中
空糸膜16の内面にビタミンEの被膜17を被覆してな
るものである。According to the present invention, a portion of the artificial kidney as described above that comes into contact with body fluid, for example, blood in the blood circulation region, for example, the inner surface of the hollow fiber membrane, the inner surface of the space formed by the header 10 and the potting agent 6, The inner surface of the space formed by the header 11 and the potting agent 7, the inner surface of the blood inlet 8, the inner surface of the blood outlet 9, the inner surfaces of the tubes 14 and 15,
In particular, the inner surface of the hollow fiber membrane is coated with vitamin E. For example, in a hollow fiber type membrane, as shown in FIG. 2, the inner surface of the hollow fiber membrane 16 is coated with a vitamin E coating 17.
【0018】本発明で使用されるビタミンEは、脂溶性
であり、例えば、α−トコフェロール、β−トコフェロ
ール、γ−トコフェロール、δ−トコフェロール等のト
コフェロール類、α−トコトリエノール、β−トコトリ
エノール、γ−トコトリエノール、δ−トコトリエノー
ル等のトコトリエノール類等がある。また、ビタミンE
の被膜の膜厚は、0.001〜1.0μm、好ましくは
0.01〜0.3μmである。膜厚が0.001μm以
下である場合にはビタミンEを被覆したことにより得ら
れる生体適合性の効果が現れにくく、膜厚が1.0μm
以上の場合は透析性能が低下することがある。The vitamin E used in the present invention is fat-soluble and, for example, tocopherols such as α-tocopherol, β-tocopherol, γ-tocopherol, δ-tocopherol, α-tocotrienol, β-tocotrienol, γ-tocopherol. There are tocotrienols such as tocotrienol and δ-tocotrienol. Also, vitamin E
The film thickness of the film is 0.001 to 1.0 μm, preferably 0.01 to 0.3 μm. When the film thickness is 0.001 μm or less, the biocompatibility effect obtained by coating with vitamin E is unlikely to appear, and the film thickness is 1.0 μm
In the above cases, dialysis performance may decrease.
【0019】さらに、ビタミンEの被覆量は、1〜10
00mg/m3 、好ましくは10〜300mg/m3 で
ある。ビタミンEの被覆量が1mg/m3 以下のときは
ビタミンEの被覆にむらが生じ易く、生体適合性の効果
が減少する。また、1000mg/m3 以上のときはビ
タミンEの膜厚が厚くなり、ビタミンEの溶出や透析性
能が低下することがある。Further, the coating amount of vitamin E is 1 to 10
The amount is 00 mg / m 3 , preferably 10 to 300 mg / m 3 . When the amount of vitamin E coated is 1 mg / m 3 or less, the vitamin E coating is likely to be uneven and the biocompatibility effect is reduced. Further, when the amount is 1000 mg / m 3 or more, the film thickness of vitamin E becomes thick and the elution of vitamin E and the dialysis performance may decrease.
【0020】このようなビタミンEを0.01〜20w
/v%、好ましくは0.1〜10w/v%の有機溶媒溶
液として、人工臓器の体液流通域(図1および図2に示
す人工腎臓の場合には血液流通域)に流入させ、所定時
間、例えば、30秒〜60分間、好ましくは1〜10分
間接触させることにより、体液流通域の内面、例えば、
中空糸膜内面、ヘッダー10とポッティング剤6とによ
り形成される空間の内面、ヘッダー11とポッティング
剤7とにより形成される空間の内面、血液流入口8の内
面、血液排出口9の内面、チューブ14,15の内面、
特に中空糸膜内面にビタミンEを充分なじませる。つい
で、前記溶液を排出した後、10〜80℃、好ましく
は、15〜30℃の温度で前記ビタミンEに対して不活
性なガス、例えば、空気、窒素、炭酸ガス等を導入して
有機溶媒を蒸発除去することにより、接触面にビタミン
Eの被膜を形成させるもので、必要によりさらに水洗す
る。この場合、チューブ14,15を連結せずに被覆操
作を行って、主要部分特に透過膜部分にビタミンEの被
膜を形成させてもよい。0.01-20 w of such vitamin E
/ V%, preferably 0.1 to 10 w / v% as an organic solvent solution, and allowed to flow into the body fluid flow region of the artificial organ (blood flow region in the case of the artificial kidney shown in FIGS. 1 and 2) for a predetermined time. , For example, 30 seconds to 60 minutes, preferably by contacting for 1 to 10 minutes, the inner surface of the body fluid flow region, for example,
Inner surface of hollow fiber membrane, inner surface of space formed by header 10 and potting agent 6, inner surface of space formed by header 11 and potting agent 7, inner surface of blood inlet 8 and inner surface of blood outlet 9, tube Inner surface of 14, 15
Especially, the vitamin E is well spread on the inner surface of the hollow fiber membrane. Then, after discharging the solution, a gas inert to the vitamin E, for example, air, nitrogen, carbon dioxide gas or the like is introduced at a temperature of 10 to 80 ° C., preferably 15 to 30 ° C. to introduce an organic solvent. Is removed by evaporation to form a film of vitamin E on the contact surface, and further washed with water if necessary. In this case, the coating operation may be performed without connecting the tubes 14 and 15 to form the vitamin E coating on the main portion, particularly the permeable membrane portion.
【0021】なお、本発明で使用される有機溶媒は、合
成高分子膜非溶解性のものであり、例えば、メタノー
ル、エタノール、n−プロパノール、イソプロパノー
ル、n−ブタノール、イソブタノール、sec−ブタノ
ール、2−エチルヘキサノール等のアルコール類、ジエ
チルエーテル等あるいは例えば、1,2,2−トリクロ
ロ−1,2,2−トリフルオロエタン、トリクロロフル
オロメタン、1,1,2,2−テトラクロロ−1,2−
ジフルオロエタン等の塩化弗化炭化水素あるいは例え
ば、弗化メチル、四弗化炭素、テトラフルオロエタン、
テトラフルオロエチレン、パーフルオロメチルプロピル
シクロヘキサン、パーフルオロブチルシクロヘキサン等
のパーフルオロシクロアルカン類、パーフルオロデカ
ン、パーフルオロメチルデカリン、パーフルオロアルキ
ルテトラヒドロピラン等の弗化炭化水素である。The organic solvent used in the present invention is one that is insoluble in the synthetic polymer film, such as methanol, ethanol, n-propanol, isopropanol, n-butanol, isobutanol, sec-butanol, Alcohols such as 2-ethylhexanol, diethyl ether, etc. or, for example, 1,2,2-trichloro-1,2,2-trifluoroethane, trichlorofluoromethane, 1,1,2,2-tetrachloro-1, 2-
Chlorinated fluorohydrocarbons such as difluoroethane or the like, for example, methyl fluoride, carbon tetrafluoride, tetrafluoroethane,
Perfluorocycloalkanes such as tetrafluoroethylene, perfluoromethylpropylcyclohexane and perfluorobutylcyclohexane, and fluorocarbons such as perfluorodecane, perfluoromethyldecalin and perfluoroalkyltetrahydropyran.
【0022】以上は、主としてダイアライザである人工
腎臓について説明したが、その他に人工肝臓、人工肺、
血漿分離器、血液回路、人工血管等にも使用でき、その
うち体液、特に血液に対する透過膜を有する部位にビタ
ミンE被膜を形成させれば著しい効果が得られる。Although the artificial kidney, which is mainly a dialyzer, has been described above, other artificial liver, artificial lung,
It can also be used in plasma separators, blood circuits, artificial blood vessels and the like, and if a vitamin E coating is formed on a site having a permeable membrane for body fluids, especially blood, a remarkable effect can be obtained.
【0023】次に、本発明の実施例を添付図面を参照し
さらに詳細に説明する。Next, embodiments of the present invention will be described in more detail with reference to the accompanying drawings.
【0024】(実施例1)内径約200μm、外径約2
80μm、長さ約14cm、溶解度パラメータδ9.9
0(cal/cm3)1/2のポリスルホン中空糸341本
を用い、図1に示すように、筒状本体1内に挿入し、両
端をポリウレタン系ポッティング剤6,7で固定し、さ
らに両端にヘッダー10,11を取り付け、キャップ1
2,13により固着してダイアライザ(人工腎臓)1を
作成した。なお、このダイアライザ1の膜内表面積は3
00cm3 であった。(Example 1) Inner diameter of about 200 μm, outer diameter of about 2
80 μm, length about 14 cm, solubility parameter δ9.9
Using 341 0 (cal / cm 3 ) 1/2 polysulfone hollow fibers, as shown in FIG. 1, inserted into the cylindrical main body 1 and fixed at both ends with polyurethane potting agents 6 and 7, and further at both ends Attach headers 10 and 11 to the cap 1
A dialyzer (artificial kidney) 1 was prepared by fixing with 2 and 13. The internal surface area of the dialyzer 1 is 3
It was 00 cm 3 .
【0025】一方、ビタミンE(DL−α−トコフェロ
ール)1.0gをエタノール100mlに溶解してビタ
ミンEのエタノール溶液の濃度を1w/v%に調整し
た。そして、ダイアライザ1の一端に50ml用シリン
ジを接続し、他端をビタミンEの溶液に浸漬し、シリン
ジのプランジャーを作動させてダイアライザ中にビタミ
ンEの溶液を充填した。この状態で室温で2分間放置し
た。次に、ダイアライザを引き上げてビタミンEの溶液
を排出させた後、アスピレータを接続し、25℃の温度
で窒素ガスを送風して乾燥し、エタノールを排除した。
さらに、乾燥の完全を期するため、60℃のオーブン内
に一夜放置した。このようにして得られたダイアライザ
内のビタミンE被覆量は0.63mgであった。On the other hand, 1.0 g of vitamin E (DL-α-tocopherol) was dissolved in 100 ml of ethanol to adjust the concentration of the ethanol solution of vitamin E to 1 w / v%. Then, a 50 ml syringe was connected to one end of the dialyzer 1, the other end was immersed in a solution of vitamin E, and the plunger of the syringe was operated to fill the dialyzer with the solution of vitamin E. In this state, it was left at room temperature for 2 minutes. Next, after pulling up the dialyzer to discharge the solution of vitamin E, an aspirator was connected, nitrogen gas was blown at a temperature of 25 ° C. to dry, and ethanol was removed.
Furthermore, in order to ensure complete drying, the sample was left in an oven at 60 ° C. overnight. The vitamin E coating amount in the dialyzer thus obtained was 0.63 mg.
【0026】(実施例2)実施例1と同様のポリスルホ
ン中空糸を用い、ビタミンEのエタノール溶液中のビタ
ミンEの濃度を5w/v%とし、実施例1と同様の方法
によりダイアライザを製造した。このダイアライザ内の
ビタミンE被覆量は、3.13mgであった。(Example 2) Using the same polysulfone hollow fiber as in Example 1, the concentration of vitamin E in the ethanol solution of vitamin E was 5 w / v%, and a dialyzer was manufactured by the same method as in Example 1. . The amount of vitamin E coated in this dialyzer was 3.13 mg.
【0027】(実施例3)内径約250μm、外径約3
20μm、長さ約14cmのポリアクリロニトリル(以
下、単にPANと記載する。)中空糸273本を用い、
ビタミンEのエタノール溶液中のビタミンEの濃度を5
w/v%とし、実施例1と同様の方法によりダイアライ
ザを製造した。このダイアライザの膜表面積は300c
m3 で、ダイアライザ内のビタミンE被覆量は、4.1
9mgであった。Example 3 Inner diameter about 250 μm, outer diameter about 3
Using 273 hollow polyacrylonitrile (hereinafter, simply referred to as PAN) 20 μm and a length of about 14 cm,
Adjust the concentration of vitamin E in the ethanol solution of vitamin E to 5
A w / v% was set and a dialyzer was manufactured by the same method as in Example 1. The membrane surface area of this dialyzer is 300c
At m 3 , the vitamin E coating amount in the dialyzer is 4.1.
It was 9 mg.
【0028】(実施例4)ポリスルホン10gをジクロ
ロメタン20mlに溶解させ、200mlのメタノール
に沈殿させ精製した。得られた沈殿を濾過し、60℃で
乾燥した。精製したポリスルホン4.5gとポリビニル
ピロリドン0.25gをジメチルアセトアミド25ml
に溶解させた後、10×10cmのガラス板に100μ
mの厚さでキャストし、水浴槽にて凝固させた。得られ
たポリスルホンの平膜は充分水洗した後、60℃で乾燥
した。ついで、ポリスルホンの平膜を5w/v%のビタ
ミンEのエタノール溶液に5分間浸漬させた後、前記平
膜を引き上げ、25℃の温度で送風乾燥した。さらに、
乾燥の完全を期するため、60℃のオーブン内に一夜放
置した。このようにして得られたダイアライザ内のビタ
ミンE被覆量は50cm3 で0.72mgであった。Example 4 10 g of polysulfone was dissolved in 20 ml of dichloromethane and precipitated in 200 ml of methanol for purification. The resulting precipitate was filtered and dried at 60 ° C. 4.5 g of purified polysulfone and 0.25 g of polyvinylpyrrolidone are added to 25 ml of dimethylacetamide.
After being dissolved in a glass plate, 100μ on a glass plate of 10 × 10cm
It was cast at a thickness of m and solidified in a water bath. The obtained flat membrane of polysulfone was thoroughly washed with water and then dried at 60 ° C. Then, the flat membrane of polysulfone was immersed in an ethanol solution containing 5 w / v% of vitamin E for 5 minutes, and then the flat membrane was pulled up and blow-dried at a temperature of 25 ° C. further,
To ensure complete drying, it was left in an oven at 60 ° C overnight. The amount of vitamin E coated in the dialyzer thus obtained was 0.72 mg at 50 cm 3 .
【0029】(比較例1)比較対照のために、内径約2
00μm、外径約240μm、長さ約14cmの再生セ
ルロース中空糸341本を用い、ビタミンEのエタノー
ル溶液中のビタミンEの濃度を5w/v%とし、実施例
1と同様の方法によりダイアライザを製造した。このダ
イアライザの膜表面積は300cm3 で、ダイアライザ
内のビタミンE被覆量は、3.25mgであった。(Comparative Example 1) For comparison, an inner diameter of about 2
A dialyzer was manufactured by the same method as in Example 1, using 341 regenerated cellulose hollow fibers having a diameter of 00 μm, an outer diameter of about 240 μm, and a length of about 14 cm, and the concentration of vitamin E in the ethanol solution of vitamin E was 5 w / v%. did. The membrane surface area of this dialyzer was 300 cm 3 , and the amount of vitamin E coating in the dialyzer was 3.25 mg.
【0030】(比較例2)比較対照のために、実施例1
と同様のポリスルホン中空糸を用い、ビタミンEのエタ
ノール溶液で処理せずに、実施例1と同様の方法により
ダイアライザを製造した。Comparative Example 2 For comparison and comparison, Example 1 was used.
Using a polysulfone hollow fiber similar to that described above, a dialyzer was produced by the same method as in Example 1 without treatment with an ethanol solution of vitamin E.
【0031】(比較例3)比較対照のために、実施例4
と同様のポリスルホンを用い、ビタミンEのエタノール
溶液で処理せずに、実施例4と同様の方法によりポリス
ルホンの平膜を製造した。(Comparative Example 3) As a comparative control, Example 4 was used.
A polysulfone flat membrane was produced in the same manner as in Example 4, except that the same polysulfone as in Example 1 was used and the solution was not treated with an ethanol solution of vitamin E.
【0032】(実験例1)実施例1〜3および比較例1
のダイアライザを用いて、血漿中のビタミンE溶出量を
調べた。(Experimental Example 1) Examples 1 to 3 and Comparative Example 1
The amount of vitamin E eluted in plasma was examined using a dialyzer of No.
【0033】まず、牛血液500mlを50mlのポリ
プロピレン製試験管に分注し、3000rpmで15分
間遠心分離し、牛血漿200mlを得た。さらに、50
mlのポリプロピレン製試験管に牛血漿50mlを分注
し、この牛血漿入り試験管をポンプを介してダイアライ
ザ1の血液流入口8に塩化ビニル製チューブ14で連結
し、さらにダイアライザ1の血液排出口9と前記牛血漿
入り試験管とを塩化ビニル製チューブ15で連結して、
実験回路を準備した。そして、牛血漿入り試験管は37
℃の恒温槽で維持し、牛血漿をポンプにて10ml/m
inの流量で4時間ダイアライザ内を循環させ、4時間
後の牛血漿へのビタミンE溶出量を測定した。First, 500 ml of bovine blood was dispensed into a 50 ml polypropylene test tube and centrifuged at 3000 rpm for 15 minutes to obtain 200 ml of bovine plasma. Furthermore, 50
50 ml of bovine plasma was dispensed into a polypropylene test tube of ml, and the test tube containing bovine plasma was connected to the blood inlet 8 of the dialyzer 1 with a vinyl chloride tube 14 via a pump, and the blood outlet of the dialyzer 1 was connected. 9 and the test tube containing bovine plasma are connected by a vinyl chloride tube 15,
An experimental circuit was prepared. And the test tube containing bovine plasma is 37
Keep in a constant temperature bath at ℃, pump 10 ml / m of bovine plasma
The amount of vitamin E eluted into bovine plasma after 4 hours was measured by circulating the dialyzer at a flow rate of in for 4 hours.
【0034】血漿中のビタミンE溶出量は、以下のよう
に測定した。The amount of vitamin E eluted in plasma was measured as follows.
【0035】最初に、循環終了後の牛血漿1mlを採取
し、これにエタノール1mlを添加して30秒間混合す
ることにより、牛血漿中の蛋白質を除去した。次に、ヘ
キサン5mlを添加して1分間混合することにより、牛
血漿中のビタミンEをヘキサン層に移行させた。これを
1500rpmで10分間遠心分離し、上層のヘキサン
層中のビタミンE量を液体クロマトグラフィーにより定
量した。なお、液体クロマトグラフィーの測定条件は、
カラム:Amide−80,4.6×25cm(東ソT
SKゲル)、移動層としてn−ヘキサン:i−プロパノ
ール=98:2、流速:1.5ml/min、インジェ
クション量:10μl、検出:UVモニター292nm
で行った。First, 1 ml of bovine plasma after the end of circulation was collected, and 1 ml of ethanol was added thereto and mixed for 30 seconds to remove the protein in bovine plasma. Next, 5 ml of hexane was added and mixed for 1 minute to transfer vitamin E in bovine plasma to the hexane layer. This was centrifuged at 1500 rpm for 10 minutes, and the amount of vitamin E in the upper hexane layer was quantified by liquid chromatography. The measurement conditions for liquid chromatography are:
Column: Amide-80, 4.6 x 25 cm (Tosoh T
SK gel), n-hexane: i-propanol = 98: 2 as a moving layer, flow rate: 1.5 ml / min, injection amount: 10 μl, detection: UV monitor 292 nm
I went there.
【0036】実験例1の血漿中のビタミンE溶出量の測
定結果を表1に示す。Table 1 shows the measurement results of the amount of vitamin E eluted in plasma of Experimental Example 1.
【0037】[0037]
【表1】 [Table 1]
【0038】(実験例2)実施例1〜2および比較例2
のダイアライザを用いて、ビタミンEの生体適合性を評
価するために、ウサギの体外循環実験を行い、体外循環
終了後の中空糸内に血液が残存している中空糸の本数を
調べた。Experimental Example 2 Examples 1 and 2 and Comparative Example 2
In order to evaluate the biocompatibility of vitamin E using the dialyzer of No. 3, a rabbit extracorporeal circulation experiment was performed, and the number of hollow fibers in which blood remained in the hollow fibers after completion of extracorporeal circulation was examined.
【0039】まず、ウサギを北島式固定台に背位固定
し、電動バリカンで術野の毛を刈り、酒精綿で清拭し
た。ついで、ハサミで顎下から鎖骨に入るまで正中線に
沿って切開し、さらに筋膜を開き、神経、分枝血管およ
び周囲の組織を損傷しないように注意しながら右(左)
総頸動脈を剥離した。ついで、左(右)顔面静脈を同様
に注意深く剥離した。そして、血管をクランプした状態
で、生理食塩水を満たした混注用ゴムキャップを付けた
テルモ株式会社製のサーフロー(テルモ株式会社の登録
商標)留置針を静脈に挿入し、結紮固定した。さらに、
回路の片側(静脈側)が生理食塩水で満たされたダイア
ライザの静脈側を生理食塩水で満たされた塩化ビニル製
チューブにより連結した。同様に、前記動脈にも留置針
を挿入し、結紮固定した後、生理食塩水で満たされた塩
化ビニル製チューブを用いポンプを介してダイアライザ
の動脈側に連結した。First, the rabbit was fixed on its back on a Kitajima type fixed base, the hair of the surgical field was shaved with an electric hair clipper, and wiped with alcoholic cotton. Then, make an incision along the midline from below the jaw to the clavicle with scissors and open the fascia, taking care not to damage the nerves, branch vessels, and surrounding tissues.
The common carotid artery was dissected. The left (right) facial vein was then carefully removed as well. Then, with the blood vessel clamped, a Surflow (registered trademark of Terumo Corp.) indwelling needle made by Terumo Corp. with a mixed rubber cap filled with physiological saline was inserted into the vein and fixed by ligation. further,
One side (venous side) of the circuit was connected to the venous side of a dialyzer filled with physiological saline by a vinyl chloride tube filled with physiological saline. Similarly, an indwelling needle was inserted into the artery, fixed by ligation, and then connected to the arterial side of the dialyzer via a pump using a vinyl chloride tube filled with physiological saline.
【0040】このようにして作られたウサギの体外循環
回路を用いて、体外循環実験を以下のように行った。Using the rabbit extracorporeal circuit, an extracorporeal circulation experiment was conducted as follows.
【0041】最初に、血管のクランプをはずし、ポンプ
にて10ml/minの流量に保ち、2時間体外循環を
行った。循環終了後、再度動静脈の血管をクランプし、
留置針に近い部分で動脈側回路および静脈側回路を切断
した。そして、生理食塩水50mlをポンプにて10m
l/minの流量でシングルパスして、回路およびダイ
アライザ内を洗浄した。洗浄終了後のダイアライザの中
心部分で中空糸を切断して、顕微鏡で残血のある中空糸
本数を数え、ダイアライザ内の全ての中空糸本数と残血
のある中空糸本数とにより残血率を算出した。First, the blood vessel was unclamped, and the pump was kept at a flow rate of 10 ml / min to perform extracorporeal circulation for 2 hours. After the circulation is completed, the arteriovenous blood vessels are clamped again,
The arterial side circuit and the venous side circuit were cut at a portion near the indwelling needle. Then, 50 ml of physiological saline is pumped for 10 m.
The inside of the circuit and the dialyzer was cleaned by making a single pass at a flow rate of 1 / min. After cleaning, cut the hollow fibers at the center of the dialyzer, count the number of hollow fibers with residual blood with a microscope, and determine the residual blood ratio by the total number of hollow fibers in the dialyzer and the number of hollow fibers with residual blood. It was calculated.
【0042】実験例2の体外循環終了後の残血率の算出
結果を表2に示す。Table 2 shows the calculation results of the residual blood rate after the end of extracorporeal circulation in Experimental Example 2.
【0043】[0043]
【表2】 [Table 2]
【0044】(実験例3)実施例4および比較例3の平
膜をポリスルホン製の平膜を用いて、活性酸素産生量を
評価のため発光強度積算値を測定した。(Experimental Example 3) Using the flat membranes of Example 4 and Comparative Example 3 made of polysulfone, the emission intensity integrated value was measured to evaluate the amount of active oxygen produced.
【0045】まず、20U/mlのヘパリン加ヒト血液
に6%デキストランT−70の生理食塩水溶液を9:1
の割合で静かに混合し、約2時間倒立静置した。そし
て、上澄液を静かに採取し、この上澄液中の白血球食細
胞をHank's ballance salt solutionで1×106 ce
ll/mlに調整し、これを試験液とした。ついで、キ
ュベットに40cm2 の平膜と試験液1.2mlを添加
し、膜全体が試験液に浸るようにした。なお、キュベッ
トは、ガラス製でNCT−911(東芝シリコーン)に
より、あらかじめシリコーンコートしたものを用いた。
さらに、キュベットに0.1mMの2−メチル−6(−
p−メトキシフェノール)−3,7−ジヒドロイミダゾ
(−1,2−a)−ピラジン−3−オン10μlを添加
し、直ちにルネッセンスリーダーで37℃、15分間の
発光強度積算値を測定した。また、比較対照のためにキ
ュベットのみの発光強度積算値も測定した。First, 20 U / ml heparinized human blood was treated with 6% dextran T-70 in a physiological saline solution at a ratio of 9: 1.
The mixture was gently mixed at a ratio of 2 and left standing upside down for about 2 hours. Then, the supernatant was gently collected and leukocyte phagocytic cells in this supernatant were treated with Hank's ballance salt solution at 1 × 10 6 ce.
It was adjusted to 11 / ml and used as a test solution. Then, a 40 cm 2 flat membrane and 1.2 ml of the test solution were added to the cuvette so that the entire membrane was immersed in the test solution. The cuvette was made of glass and was previously silicone-coated with NCT-911 (Toshiba Silicone).
Furthermore, 0.1 mM 2-methyl-6 (-
10 μl of p-methoxyphenol) -3,7-dihydroimidazo (-1,2-a) -pyrazin-3-one was added, and the integrated value of luminescence intensity was immediately measured with a luminescence reader at 37 ° C. for 15 minutes. Further, the integrated value of the emission intensity of only the cuvette was measured for comparison and control.
【0046】実験例3の活性酸素産生量を評価のための
発光強度積算値の測定結果を表3に示す。Table 3 shows the measurement results of the integrated value of the emission intensity for evaluating the active oxygen production amount of Experimental Example 3.
【0047】[0047]
【表3】 [Table 3]
【0048】以上の実験例1〜3の実験結果を示す表1
〜3よりわかることは、表1において、比較例1のセル
ロース膜は溶解度パラメータδが15.70(cal/
cm3)1/2であり、また親水性が高いのでビタミンE被
覆量の88%が血漿循環で溶出した。これに対し、実施
例1および実施例2のポリスルホン膜は溶解度パラメー
タδが9.90(cal/cm3)1/2であり、また疎水
部分を有するのでビタミンEの血漿への溶出が全くみら
れず、ビタミンEとの疎水−疎水結合により強く固定化
されている。また実施例3のPAN膜は溶解度パラメー
タδが12.35(cal/cm3)1/2であるが、ビタ
ミンEの溶出率は約1%であり、セルロース膜に比べる
とわずかな溶出率であった。Table 1 showing the experimental results of the above Experimental Examples 1 to 3.
It can be seen from Table 3 that in Table 1, the cellulose membrane of Comparative Example 1 has a solubility parameter δ of 15.70 (cal / cal).
cm 3 ) 1/2 and high hydrophilicity, 88% of vitamin E coating amount was eluted in plasma circulation. On the other hand, the polysulfone membranes of Example 1 and Example 2 have a solubility parameter δ of 9.90 (cal / cm 3 ) 1/2 and also have a hydrophobic portion, so that elution of vitamin E into plasma is completely observed. However, it is strongly immobilized by a hydrophobic-hydrophobic bond with vitamin E. The solubility parameter δ of the PAN membrane of Example 3 is 12.35 (cal / cm 3 ) 1/2 , but the elution rate of vitamin E is about 1%, which is a slight elution rate compared to the cellulose membrane. there were.
【0049】表2において、比較例2のビタミンE無処
理のポリスルホン膜の残血率は37.9%であったのに
対し、実施例1の1w/v%のビタミンEで処理された
ポリスルホン膜においては残血率は27.0%、実施例
2の5w/v%のビタミンEで処理されたポリスルホン
膜においては残血率は18.6%であり、明らかにビタ
ミンEの血小板凝集抑制作用により、ウサギの体外循環
後の残血率が減少しており、優れた生体適合性を示して
いる。In Table 2, the residual blood rate of the polysulfone membrane not treated with vitamin E of Comparative Example 2 was 37.9%, whereas the polysulfone treated with 1 w / v% of vitamin E of Example 1 was used. The residual blood rate was 27.0% in the membrane, and the residual blood rate was 18.6% in the polysulfone membrane treated with 5 w / v% of vitamin E of Example 2, clearly indicating that vitamin E inhibits platelet aggregation. Due to the action, the residual blood rate after extracorporeal circulation in rabbits is reduced, and it shows excellent biocompatibility.
【0050】実験例3においては、中空糸形状では血液
と接触しない中空糸外面(内面)を含む測定となるの
で、素材の全ての面が血液と接触すると仮定して平膜形
状での測定を行ったが、これは中空糸膜の内面(外面)
のみを測定するのと何ら代わりはない。表3において、
比較例3のビタミンE無処理のポリスルホン膜の発光強
度積算値は378kcpmであったのに対し、実験例4
のビタミンEで処理させたポリスルホン膜の発光強度積
算値は203kcpmであり、膜の刺激による活性酸素
産生量をビタミンEを被覆することにより抑えているこ
とは明らかである。さらに、キュベットのみの発光強度
積算値は192kcpmであり、実験例4のビタミンE
で処理させたポリスルホン膜の発光強度積算値との差は
わずかであることがわかる。これにより、ビタミンEを
被覆することにより活性酸素の産生が抑えられ、活性酸
素が原因とされている種々の疾患を軽減することが可能
であることが考えられる。In Experimental Example 3, the hollow fiber shape includes the outer surface (inner surface) of the hollow fiber that does not come into contact with blood. I did this, but this is the inner surface (outer surface) of the hollow fiber membrane
There is no substitute for measuring only. In Table 3,
The emission intensity integrated value of the polysulfone film not treated with vitamin E of Comparative Example 3 was 378 kcpm, while that of Experimental Example 4
The integrated emission value of the polysulfone film treated with Vitamin E is 203 kcpm, and it is clear that the amount of active oxygen produced by the film stimulation is suppressed by coating Vitamin E. Furthermore, the integrated value of the emission intensity of only the cuvette is 192 kcpm.
It can be seen that the difference from the integrated value of the emission intensity of the polysulfone film treated in step 1 is slight. Therefore, it is considered that by coating with vitamin E, production of active oxygen is suppressed, and it is possible to reduce various diseases caused by active oxygen.
【0051】以上は、ポリスルホン中空糸膜、ポリアク
リロニトリル(PAN)中空糸膜を用いて本実施例を説
明したが、本発明はこれに限られるものではなく、溶解
度パラメータδが13(cal/cm3)1/2以下である
膜であればよく、中空糸膜に限らず、平膜等でもよい。Although the present embodiment has been described above using the polysulfone hollow fiber membrane and the polyacrylonitrile (PAN) hollow fiber membrane, the present invention is not limited to this, and the solubility parameter δ is 13 (cal / cm). 3 ) Membranes of 1/2 or less may be used, and not limited to hollow fiber membranes, flat membranes and the like may be used.
【0052】[0052]
【発明の効果】以上説明したように、本発明の人工臓器
によれば、体液透過膜を備える人工臓器であって、該体
液透過膜は、溶解度パラメータδが13(cal/cm
3)1/2以下であり、さらに、少なくとも該体液透過膜の
体液と接触し得る部位の表面にビタミンEを被覆してな
ることを特徴とすることにより、脂溶性ビタミンである
ビタミンEとの親和性を良好にし、血液への溶出を抑え
ることにより、生体に対して副作用が少なく、生体適合
性が向上した人工臓器を提供することができる。さら
に、残血率を減少することがでる。また、活性酸素の産
生が抑えられ、活性酸素が原因とされている種々の疾患
を軽減することが可能である。As described above, the artificial organ of the present invention is an artificial organ having a body fluid permeable membrane, and the body fluid permeable membrane has a solubility parameter δ of 13 (cal / cm).
3 ) 1/2 or less, and at least the surface of the body fluid permeable membrane that can come into contact with body fluid is coated with vitamin E. By improving the affinity and suppressing elution into blood, it is possible to provide an artificial organ with few side effects on the living body and improved biocompatibility. Furthermore, the residual blood rate can be reduced. In addition, production of active oxygen is suppressed, and various diseases caused by active oxygen can be reduced.
【0053】また、本発明の人工臓器は、該人工臓器内
の体液流通域の少なくとも体液と接触する部位の表面に
ビタミンEを被覆してなることを特徴とすることによ
り、さらに生体適合性が向上し、残血率を減少させるこ
とができる。さらに、活性酸素の産生が抑えられる。Further, the artificial organ of the present invention is characterized in that at least the surface of the body fluid flow region in the artificial organ which is in contact with the body fluid is coated with vitamin E, whereby the biocompatibility is further improved. It can improve and reduce the residual blood rate. Furthermore, production of active oxygen is suppressed.
【0054】また、本発明の人工臓器は、該体液透過膜
が中空糸型膜であることを特徴とすることにより、有効
膜面積が大きくなり、透析性が向上する。Further, the artificial organ of the present invention is characterized in that the body fluid permeable membrane is a hollow fiber type membrane, so that the effective membrane area is increased and the dialysis property is improved.
【0055】さらに、本発明の人工臓器は、該体液透過
膜が疎水性または疎水部分を含む合成高分子膜であるこ
とを特徴とすることにより、さらにビタミンEとの親和
性を良好にし、血液への溶出を抑えることができ、生体
適合性を向上させることができる。Further, the artificial organ of the present invention is characterized in that the body fluid permeable membrane is a hydrophobic or synthetic polymer membrane containing a hydrophobic portion, thereby further improving the affinity with vitamin E and It is possible to suppress the elution to the above and improve the biocompatibility.
【0056】また、本発明の生体適合性人工臓器は、体
液透過膜のビタミンE被覆量が1〜1000mg/m3
であることを特徴とすることにより、ビタミンEの被覆
にむらができず、かつ透析性能を低下させずに生体適合
性を向上することができる。In the biocompatible artificial organ of the present invention, the body fluid permeable membrane has a vitamin E coating amount of 1 to 1000 mg / m 3.
The biocompatibility can be improved without causing unevenness in the vitamin E coating and without lowering the dialysis performance.
【図1】本発明の実施例を示すダイアライザの一部切欠
部を有する斜視図である。FIG. 1 is a perspective view showing a part of a dialyzer showing an embodiment of the present invention.
【図2】本発明の実施例を示す中空糸膜の縦断面図であ
る。FIG. 2 is a vertical cross-sectional view of a hollow fiber membrane showing an example of the present invention.
1 ダイアライザ 2 透析液入口管 3 透析液出口管 4 筒状本体 5 中空糸膜 6,7 ポッティング剤 8 体液流入口 9 体液排出口 10,11 ヘッダー 12,13 キャップ 14,15 チューブ 16 中空糸膜 17 被膜 1 dialyzer 2 dialysate inlet pipe 3 dialysate outlet pipe 4 tubular body 5 hollow fiber membrane 6,7 potting agent 8 body fluid inlet 9 body fluid outlet 10,11 header 12,13 cap 14,15 tube 16 hollow fiber membrane 17 Film
フロントページの続き (72)発明者 渡辺 秀樹 神奈川県足柄上郡中井町井ノ口1500番地 テルモ株式会社内Front page continued (72) Inventor Hideki Watanabe 1500 Inoguchi, Nakai-cho, Ashigarakami-gun, Kanagawa Terumo Corporation
Claims (1)
cm3)1/2以下であり、 さらに、少なくとも該体液透過膜の体液と接触し得る部
位の表面にビタミンEを被覆してなることを特徴とする
人工臓器。1. An artificial organ having a body fluid permeable membrane, wherein the body fluid permeable membrane has a solubility parameter δ of 13 (cal / cal).
cm 3 ) 1/2 or less, and an artificial organ characterized in that at least the surface of the body fluid permeable membrane that can come into contact with body fluid is coated with vitamin E.
Priority Applications (1)
Application Number | Priority Date | Filing Date | Title |
---|---|---|---|
JP32565293A JP3193819B2 (en) | 1993-12-24 | 1993-12-24 | Artificial organ |
Applications Claiming Priority (1)
Application Number | Priority Date | Filing Date | Title |
---|---|---|---|
JP32565293A JP3193819B2 (en) | 1993-12-24 | 1993-12-24 | Artificial organ |
Publications (2)
Publication Number | Publication Date |
---|---|
JPH07178166A true JPH07178166A (en) | 1995-07-18 |
JP3193819B2 JP3193819B2 (en) | 2001-07-30 |
Family
ID=18179216
Family Applications (1)
Application Number | Title | Priority Date | Filing Date |
---|---|---|---|
JP32565293A Expired - Lifetime JP3193819B2 (en) | 1993-12-24 | 1993-12-24 | Artificial organ |
Country Status (1)
Country | Link |
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JP (1) | JP3193819B2 (en) |
Cited By (10)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
EP0749775A1 (en) * | 1995-06-22 | 1996-12-27 | Terumo Kabushiki Kaisha | Method for production of hollow-fiber membrane, hollow-fiber membrane, and dialyzer |
US6001288A (en) * | 1996-12-25 | 1999-12-14 | Terumo Kabushiki Kaisha | Process for producing a hollow fiber membrane having a hydrophobic coating |
US6478960B1 (en) * | 1997-12-17 | 2002-11-12 | Asahi Medical Co., Ltd. | Manufacturing method of artificial organ, hollow fiber, and dialyzer of hollow fiber membrane type |
WO2008146775A1 (en) | 2007-05-25 | 2008-12-04 | Asahi Kasei Kuraray Medical Co., Ltd. | Polysulfone-based membrane for treating blood and method of producing the same |
WO2011090197A1 (en) | 2010-01-25 | 2011-07-28 | 旭化成クラレメディカル株式会社 | Hollow fiber membrane type blood purifier |
WO2012169529A1 (en) | 2011-06-09 | 2012-12-13 | 旭化成メディカル株式会社 | Hollow fiber membrane for blood treatment and hollow fiber membrane-type blood treatment apparatus |
WO2013015046A1 (en) | 2011-07-27 | 2013-01-31 | 旭化成メディカル株式会社 | Hollow fiber membrane type blood purifier |
WO2014171172A1 (en) | 2013-04-19 | 2014-10-23 | 旭化成メディカル株式会社 | Hollow fiber membrane for blood treatment and production method for said hollow fiber membrane for blood treatment |
WO2015093493A1 (en) | 2013-12-16 | 2015-06-25 | 旭化成メディカル株式会社 | Hollow fiber membrane blood purification device |
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-
1993
- 1993-12-24 JP JP32565293A patent/JP3193819B2/en not_active Expired - Lifetime
Cited By (15)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
EP0749775A1 (en) * | 1995-06-22 | 1996-12-27 | Terumo Kabushiki Kaisha | Method for production of hollow-fiber membrane, hollow-fiber membrane, and dialyzer |
US6001288A (en) * | 1996-12-25 | 1999-12-14 | Terumo Kabushiki Kaisha | Process for producing a hollow fiber membrane having a hydrophobic coating |
US6478960B1 (en) * | 1997-12-17 | 2002-11-12 | Asahi Medical Co., Ltd. | Manufacturing method of artificial organ, hollow fiber, and dialyzer of hollow fiber membrane type |
WO2008146775A1 (en) | 2007-05-25 | 2008-12-04 | Asahi Kasei Kuraray Medical Co., Ltd. | Polysulfone-based membrane for treating blood and method of producing the same |
US8220642B2 (en) | 2007-05-25 | 2012-07-17 | Asahi Kasei Medical Co., Ltd. | Polysulfone-based blood treatment membrane and method of producing the same |
JP5409816B2 (en) * | 2010-01-25 | 2014-02-05 | 旭化成メディカル株式会社 | Hollow fiber membrane blood purification device |
WO2011090197A1 (en) | 2010-01-25 | 2011-07-28 | 旭化成クラレメディカル株式会社 | Hollow fiber membrane type blood purifier |
WO2012169529A1 (en) | 2011-06-09 | 2012-12-13 | 旭化成メディカル株式会社 | Hollow fiber membrane for blood treatment and hollow fiber membrane-type blood treatment apparatus |
WO2013015046A1 (en) | 2011-07-27 | 2013-01-31 | 旭化成メディカル株式会社 | Hollow fiber membrane type blood purifier |
WO2014171172A1 (en) | 2013-04-19 | 2014-10-23 | 旭化成メディカル株式会社 | Hollow fiber membrane for blood treatment and production method for said hollow fiber membrane for blood treatment |
JP6078641B2 (en) * | 2013-04-19 | 2017-02-08 | 旭化成メディカル株式会社 | Hollow fiber membrane for blood treatment and method for producing the hollow fiber membrane for blood treatment |
JPWO2014171172A1 (en) * | 2013-04-19 | 2017-02-16 | 旭化成メディカル株式会社 | Hollow fiber membrane for blood treatment and method for producing the hollow fiber membrane for blood treatment |
WO2015093493A1 (en) | 2013-12-16 | 2015-06-25 | 旭化成メディカル株式会社 | Hollow fiber membrane blood purification device |
US10029216B2 (en) | 2013-12-16 | 2018-07-24 | Asahi Kasei Medical Co., Ltd. | Hollow-fiber membrane blood purification device |
KR20190038763A (en) * | 2016-08-05 | 2019-04-09 | 도레이 카부시키가이샤 | Biomaterial adhesion inhibiting material |
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