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JP2000051623A - Blood filter and its manufacture - Google Patents

Blood filter and its manufacture

Info

Publication number
JP2000051623A
JP2000051623A JP10227450A JP22745098A JP2000051623A JP 2000051623 A JP2000051623 A JP 2000051623A JP 10227450 A JP10227450 A JP 10227450A JP 22745098 A JP22745098 A JP 22745098A JP 2000051623 A JP2000051623 A JP 2000051623A
Authority
JP
Japan
Prior art keywords
blood filter
blood
filter
time
acrylic acid
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
Application number
JP10227450A
Other languages
Japanese (ja)
Other versions
JP3768009B2 (en
Inventor
Tadahiro Motomura
忠広 本村
Yoriko Inomata
依子 猪俣
Masato Onishi
誠人 大西
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.)
Terumo Corp
Original Assignee
Terumo Corp
Priority date (The priority date 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 date listed.)
Filing date
Publication date
Application filed by Terumo Corp filed Critical Terumo Corp
Priority to JP22745098A priority Critical patent/JP3768009B2/en
Publication of JP2000051623A publication Critical patent/JP2000051623A/en
Application granted granted Critical
Publication of JP3768009B2 publication Critical patent/JP3768009B2/en
Anticipated expiration legal-status Critical
Expired - Lifetime legal-status Critical Current

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  • Infusion, Injection, And Reservoir Apparatuses (AREA)
  • External Artificial Organs (AREA)

Abstract

PROBLEM TO BE SOLVED: To manufacture a safety blood filter having small influence on blood by coating a cationic compound which comprises a copolymer of (meth)acrylic acid and a specific compound and has a specific structure on a substrate forming the blood filter and drying that by heating. SOLUTION: A copolymer of (meth)acrylic acid and a compound expressed by the formula is held on a surface of a substrate forming a blood filter. At this time, a critical wet surface tension is set at 90 to 95 dyn/cm. After coating the copolymer of (meth)acrylic acid and the compound expressed by the formula on the surface of the substrate forming the blood filter in manufacture, it is dried by heating. As the substrate forming the blood filter a porous material, a non woven fabric, a knitted cloth, or the like are used, and as a material a polyurethane porous body or the like is preferable. When a cationic material is used as a preferable compound, hydrophilicity can be added simultaneously together with an addition of a cationic property.

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、血液フィルターお
よびその製造方法に関する。さらに詳しくは、コーティ
ング等によってカチオン性官能基を付与されると同時に
親水性が付与された血液フィルターおよびその製造方法
に関する。
[0001] The present invention relates to a blood filter and a method for producing the same. More specifically, the present invention relates to a blood filter provided with a hydrophilic property at the same time as a cationic functional group provided by a coating or the like, and a method for producing the same.

【0002】[0002]

【従来の技術】輸血の際には、輸血後の副作用、主に白
血球が原因で引き起こされる移植片対宿主反応(GVHD:
Graft Versus Host Disease)の誘発やウイルスに感染
した白血球による感染症などを防ぐ為に遠心分離、放射
線照射、濾過による白血球除去および不活化が行われて
いる。中でも濾過による白血球除去は、簡便かつ低コス
トな為にベットサイドでも実施できる方法として多用さ
れている。
2. Description of the Related Art During blood transfusion, a graft-versus-host reaction (GVHD:
Graft Versus Host Disease) is induced and leukocyte removal and inactivation by centrifugation, irradiation, and filtration are performed to prevent infections caused by leukocytes infected with the virus. Above all, leukocyte removal by filtration is frequently used as a method that can be carried out at the bedside because of its simplicity and low cost.

【0003】濾過による白血球除去では、孔径等による
物理的な白血球除去だけではなく、血液フィルターの表
面改質を行って白血球除去性能を向上させている。先に
述べたように、血液フィルターの表面改質に際して重要
なファクターとなるのは、孔径等の物理的白血球の除
去の他に白血球が粘着し易い表面とすることである。一
般に白血球に限らず、細胞表面は負の電荷を持ってお
り、血小板や白血球を粘着、捕捉、除去する為には、正
の電荷(カチオン性)を表面に有する事が有効であるこ
とが知られている(米国特許第3242073号、米国特許第3
352424号)。血液および血液製剤の濾過を円滑に行え
るように血液フィルター表面を親水化する事である。血
液および血液製剤と血液フィルターが接触した場合、フ
ィルター表面の親水性が高ければ、血液等は抵抗無く濾
過される。この時のフィルター表面の親水性を表す一つ
の指標として臨界湿潤表面張力(以下、CWSTと略す。詳
細については後述)がある。
[0003] In leukocyte removal by filtration, not only physical leukocyte removal by pore diameter and the like, but also surface modification of a blood filter is performed to improve leukocyte removal performance. As described above, an important factor in modifying the surface of a blood filter is not only the removal of physical leukocytes such as pore size, but also a surface on which leukocytes easily adhere. In general, not only leukocytes but also cell surfaces have a negative charge, and it is known that it is effective to have a positive charge (cationic) on the surface to adhere, capture and remove platelets and leukocytes. (U.S. Pat. No. 3,224,073; U.S. Pat.
352424). The purpose is to make the surface of the blood filter hydrophilic so that blood and blood products can be filtered smoothly. When blood and a blood product come into contact with a blood filter, blood and the like are filtered without resistance if the hydrophilicity of the filter surface is high. One index indicating the hydrophilicity of the filter surface at this time is a critical wet surface tension (hereinafter abbreviated as CWST; details will be described later).

【0004】血液フィルターのCWSTが血液および血液製
剤の表面張力よりも小さな場合、圧力をかけなくては血
液等を濾過できない。これを避けるために生理食塩水等
でプライミングを行うことが行われていた。しかし、ベ
ットサイドで使用する際などプライミング操作が障害と
なる場合がある。
When the CWST of the blood filter is smaller than the surface tension of blood and blood products, blood cannot be filtered without applying pressure. To avoid this, priming has been performed with physiological saline or the like. However, the priming operation may be an obstacle when used on the bet side.

【0005】血液等によって血液フィルターが自然に湿
潤すれば、加圧することなく濾過が行え、プライミング
が不要となる。
[0005] If the blood filter is naturally moistened by blood or the like, the filtration can be performed without applying pressure, and priming is not required.

【0006】しかしながら、多くの合成高分子材料から
作られる血液フィルターの場合、そのCWSTは、血液の表
面張力(血漿で73dyn/cn、赤血球で64.5dyn/cm)よりも
小さいので、血液フィルター表面に界面活性剤等を塗布
したり、グラフト重合、プラズマ処理、薬品処理等の処
理を行い、該フィルター表面のCWSTを血液の表面張力よ
りも高くしていた(特開平5−245198号、特開平
6−24995号)。
However, in the case of a blood filter made of many synthetic polymer materials, the CWST is smaller than the surface tension of blood (73 dyn / cn for plasma and 64.5 dyn / cm for red blood cells), A CWST on the surface of the filter was made higher than the surface tension of blood by applying a surfactant or the like, or by performing a treatment such as graft polymerization, plasma treatment, or chemical treatment (Japanese Patent Application Laid-Open Nos. 5-245198 and 6-254). -24995).

【0007】このような血液フィルターの表面改質は煩
雑な処理を必要としたり、処理によっては血液フィルタ
ーの除去性能が変化したり、血液成分に影響したり、塗
布された界面活性剤等が血液に溶け出す危険性を含んで
いた。
[0007] Such surface modification of the blood filter requires complicated treatment, depending on the treatment, the removal performance of the blood filter is changed, the blood components are affected, and the applied surfactant or the like is not used. The danger of melting out was included.

【0008】故に、本発明の目的の一つは、血液に対し
て影響の少ない安全な血液フィルターおよびその製造方
法を提供することにある。
[0008] Therefore, one of the objects of the present invention is to provide a safe blood filter having little effect on blood and a method for producing the same.

【0009】また、本発明の目的の一つは、白血球除去
の為にカチオン性付与を行なうと同時に親水性を付与す
ることで、簡便に製造可能な血液フィルターおよびその
製造方法を提供することにある。
Another object of the present invention is to provide a blood filter which can be easily produced by imparting hydrophilicity while imparting cationicity for the purpose of removing leukocytes, and a method for producing the same. is there.

【0010】[0010]

【課題を解決するための手段】本発明者等は鋭意検討し
た結果、特定の構造を有するカチオン性化合物を血液フ
ィルターを構成する基材にコーテイングし、加熱乾燥さ
せることで上記課題が解決されることを見出し、本発明
を完成するに至った。
Means for Solving the Problems As a result of intensive studies, the present inventors have solved the above-mentioned problems by coating a cationic compound having a specific structure on a substrate constituting a blood filter and drying by heating. This led to the completion of the present invention.

【0011】すなわち、本発明は以下の手段によって達
成される。
That is, the present invention is achieved by the following means.

【0012】(1)(メタ)アクリル酸と一般式(1)で
表される化合物との共重合体が血液フィルターを構成す
る基材表面に保持されていることを特徴とする血液フィ
ルター。
(1) A blood filter characterized in that a copolymer of (meth) acrylic acid and a compound represented by the general formula (1) is held on the surface of a substrate constituting a blood filter.

【0013】[0013]

【化5】 Embedded image

【0014】(2)一般式(2)で表される重合体が血
液フィルターを構成する基材表面に保持されていること
を特徴とする血液フィルター。
(2) A blood filter characterized in that the polymer represented by the general formula (2) is held on the surface of a substrate constituting a blood filter.

【0015】[0015]

【化6】 Embedded image

【0016】(3)一般式(3)で表される重合体が血
液フィルターを構成する基材表面に保持されていること
を特徴とする血液フィルター。
(3) A blood filter, wherein the polymer represented by the general formula (3) is held on the surface of a substrate constituting the blood filter.

【0017】[0017]

【化7】 Embedded image

【0018】(4)メタクリル酸2-[N,N-ジメチル-N-(2
-ヒドロキシ-3-N,N,N-トリメチルアンモニオプロピル)
アンモニオ]エチル塩、アクリル酸2-[N,N-ジエチル-N-
メチルアンモニオ]エチル塩、ジメチルアミノプロピル
アクリルアミド、ジメチルアミノプロピルメタアクリル
アミドからなる群から少なくとも1つ選ばれた重合物が
血液フィルターを構成する基材表面に保持されているこ
とを特徴とする血液フィルター。
(4) Methacrylic acid 2- [N, N-dimethyl-N- (2
-Hydroxy-3-N, N, N-trimethylammoniopropyl)
Ammonio] ethyl salt, acrylic acid 2- [N, N-diethyl-N-
[Methylammonio] ethyl salt, dimethylaminopropyl acrylamide, dimethylaminopropyl methacrylamide, at least one polymer selected from the group consisting of a polymer held on the surface of a substrate constituting the blood filter. .

【0019】(5)前記血液フィルターの臨界湿潤表面
張力が90〜95dyn/cmである請求項1〜4いすれか1
項に記載の血液フィルター。
(5) The blood filter according to any one of claims 1 to 4, wherein the critical wet surface tension of the blood filter is 90 to 95 dyn / cm.
The blood filter according to the item.

【0020】(6)(メタ)アクリル酸と一般式(1)で
表される化合物との共重合体を血液フィルターを構成す
る基材表面にコーテングさせた後、加熱乾燥させること
を特徴とする血液フィルターの製造方法。
(6) A copolymer of (meth) acrylic acid and a compound represented by the general formula (1) is coated on the surface of a substrate constituting a blood filter, and then dried by heating. Manufacturing method of blood filter.

【0021】[0021]

【化8】 Embedded image

【0022】ただし、本発明の血液フィルターを構成す
る基材表面とは基材そのものの表面であり、該基材表面
に導入されたグラフト鎖あるいは官能基を持った化合物
を介して上述の化合物を固定したものではない。
However, the surface of the base material constituting the blood filter of the present invention is the surface of the base material itself, and the above-mentioned compound is introduced through a compound having a graft chain or a functional group introduced into the surface of the base material. Not a fixed one.

【0023】[0023]

【発明の実施の形態】本発明の血液フィルターを構成す
る基材は多孔体、平膜、中空糸、不織布、織布、編布も
しくはそれらの複合体であり、その材質としては木綿、
麻等の天然高分子、ナイロン、ポリエステル、ポリアク
リロニトリル、ポリオレフィン、ハロゲン化ポリオレフ
ィン、ポリウレタン、ポリスルホン、ポリエーテルスル
ホン、ポリ(メタ)アクリレート、エチレンーポリビニ
ルアルコール共重合体、ブタジエン-アクリロニトリル
共重合体等の合成高分子あるいはこれらの混合物が挙げ
られるが、加工性、血液適合性などからポリウレタン多
孔体が好ましい。
BEST MODE FOR CARRYING OUT THE INVENTION The substrate constituting the blood filter of the present invention is a porous body, a flat membrane, a hollow fiber, a nonwoven fabric, a woven fabric, a knitted fabric or a composite thereof, and the material is cotton,
Natural polymers such as hemp, nylon, polyester, polyacrylonitrile, polyolefin, halogenated polyolefin, polyurethane, polysulfone, polyethersulfone, poly (meth) acrylate, ethylene-polyvinyl alcohol copolymer, butadiene-acrylonitrile copolymer, etc. A synthetic polymer or a mixture thereof is mentioned, but a polyurethane porous material is preferred from the viewpoint of processability, blood compatibility and the like.

【0024】しかしながら、ポリウレタンを原料とする
血液フィルターは、加工性、血液適合性などから優れた
白血球除去性能を持たせることができる反面、そのまま
では疎水性が強いので、血液が細孔を通過しずらく、何
らかの親水化処理が必要である。そこで、本発明によ
り、親水性を改善すると同時に白血球除去性能を向上さ
せることが可能である。
However, a blood filter made of polyurethane as a raw material can have excellent leukocyte removal performance due to processability, blood compatibility and the like, but has a strong hydrophobicity as it is, so that blood passes through the pores. Unfortunately, some kind of hydrophilic treatment is required. Thus, according to the present invention, it is possible to improve the leukocyte removal performance at the same time as improving the hydrophilicity.

【0025】本発明に好適に使用される化合物はカチオ
ン性物質であり、その具体例を以下に示す。
The compound preferably used in the present invention is a cationic substance, and specific examples thereof are shown below.

【0026】1.アクリル酸と一般式(1)で表される
化合物のブロックあるいはランダム共重合体。この場
合、アクリル酸と一般式(1)で表される化合物のモル
比は1:99〜10:90が好ましく、5:95がより
好ましい。また、分子量は65万〜105万が好まし
く、75万〜95万がより好ましく、85万がさらに好
ましい。なぜなら、血液フィルターからの溶出物が少な
くなるからである。
1. A block or random copolymer of acrylic acid and a compound represented by the general formula (1). In this case, the molar ratio of acrylic acid to the compound represented by the general formula (1) is preferably 1:99 to 10:90, and more preferably 5:95. Further, the molecular weight is preferably from 650,000 to 1,500,000, more preferably from 750,000 to 950,000, and still more preferably from 850,000. This is because the eluate from the blood filter is reduced.

【0027】[0027]

【化9】 Embedded image

【0028】2.一般式(2)または(3)で表される
化合物。
2. A compound represented by the general formula (2) or (3).

【0029】[0029]

【化10】 Embedded image

【0030】[0030]

【化11】 Embedded image

【0031】3.メタクリル酸2-[N,N-ジメチル-N-(2-
ヒドロキシ-3-N,N,N-トリメチルアンモニオプロピル)ア
ンモニオ]エチル塩、アクリル酸2-[N,N-ジエチル-N-メ
チルアンモニオ]エチル塩、ジメチルアミノプロピルア
クリルアミド、ジメチルアミノプロピルメタアクリルア
ミド。
3. Methacrylic acid 2- [N, N-dimethyl-N- (2-
Hydroxy-3-N, N, N-trimethylammoniopropyl) ammonio] ethyl salt, 2- [N, N-diethyl-N-methylammonio] ethyl acrylate, dimethylaminopropylacrylamide, dimethylaminopropylmethacrylamide .

【0032】4.1〜3のカチオン性化合物の混合物。4.1 Mixture of 1 to 3 cationic compounds.

【0033】これらのカチオン性物質は、親水性の高い
物質であり、カチオン性の付与と同時に親水性も付与す
る事が可能である。
These cationic substances are substances having high hydrophilicity, and can impart hydrophilicity simultaneously with imparting cationicity.

【0034】これらの化合物を血液フィルター上に固定
させる方法としてはコーティング、ディピング、スプレ
ー、スピンコートを行った後、60〜100℃で加熱乾
燥すれば良い。
As a method for immobilizing these compounds on a blood filter, coating, dipping, spraying and spin coating may be performed, followed by drying by heating at 60 to 100 ° C.

【0035】ところで、本発明のCWSTとは、以下の方法
によって求められる値をいう。2ないしは4dyn/cmづつ
表面張力が異なるように水酸化カルシウム、水酸化ナト
リウム、塩化カルシウム、硝酸ナトリウム、酢酸、エタ
ノールなどの濃度を変えた水溶液を調整する。このよう
にして得た表面張力が2ないしは4dyn/cmづつ異なる水溶
液を表面張力が低い順番に血液フィルター表面に10滴
ずつ乗せて10分間放置する。10分後、10滴中9滴以上が
血液フィルターに吸収された場合に湿潤した状態である
と定義し、吸収が10滴中9滴未満の場合を非湿潤状態と
定義する。このようにして血液フィルター表面に表面張
力が小さい順番に測定してゆくと湿潤状態と非湿潤状態
が観られる。このとき、湿潤状態を観測した液体の表面
張力の値と非湿潤状態を観測した液体の表面張力の値の
平均値を血液フィルター表面のCWSTと定義する。たとえ
ば、表面張力64dyn/cmの液体で湿潤し、66dyn/cmの液体
で非湿潤であった場合、その血液フィルター表面のCWST
は65dyn/cmとなる。
Incidentally, the CWST of the present invention refers to a value obtained by the following method. An aqueous solution in which the concentration of calcium hydroxide, sodium hydroxide, calcium chloride, sodium nitrate, acetic acid, ethanol, or the like is changed so that the surface tension differs by 2 to 4 dyn / cm is prepared. The aqueous solutions thus obtained, each having a different surface tension of 2 to 4 dyn / cm, are placed on the surface of the blood filter in order of decreasing surface tension, and left for 10 minutes. After 10 minutes, a wet state is defined if more than 9 out of 10 drops are absorbed by the blood filter, and a non-wet state if less than 9 out of 10 drops is absorbed. In this way, when the surface tension is measured in ascending order on the blood filter surface, a wet state and a non-wet state are observed. At this time, the average value of the surface tension value of the liquid observed in the wet state and the surface tension value of the liquid observed in the non-wet state is defined as CWST of the blood filter surface. For example, when wet with a liquid having a surface tension of 64 dyn / cm and not wet with a liquid having a surface tension of 66 dyn / cm, the CWST of the blood filter surface
Is 65 dyn / cm.

【0036】ところで、血液濾過における律速段階の1
つが血液が血液フィルターにしみ込む時間であり、この
時間が短いほど濾過時間は短くなる。このしみ込む時間
は血液フィルターの親水性に依存しているので親水性が
高いほど、つまり、CWSTの値が高いほど血液のしみ込み
が早くなり濾過時間が短くなる。
Incidentally, one of the rate-limiting steps in hemofiltration is
One is the time for blood to soak into the blood filter, and the shorter the time, the shorter the filtration time. Since the time for soaking depends on the hydrophilicity of the blood filter, the higher the hydrophilicity, that is, the higher the value of CWST, the faster the blood soaks and the shorter the filtration time.

【0037】本発明の血液フィルターのCWSTは90〜9
5dyn/cmであり、この値を有する血液フィルターは血液
等によって自然にしみ込む(湿潤する)ので、濾過時間
が短縮されるうえ、加圧することなく濾過が行え、か
つ、プライミングが不要となる。
The blood filter of the present invention has a CWST of 90-9.
The blood filter having this value is 5 dyn / cm, which naturally permeates (wet) with blood or the like, so that the filtration time can be reduced, the filtration can be performed without applying pressure, and priming is not required.

【0038】また、本発明に用いられる血液および血液
製剤は、特定の血液成分として限定されない。
The blood and blood products used in the present invention are not limited to specific blood components.

【0039】[0039]

【実施例】次に実施例により本発明を詳細に説明する
が、本発明は、これら実施例のみに限定されない。ま
た、これら実施例および比較例に記載の実験においてCW
STの測定は、前述の方法に従った。
Next, the present invention will be described in detail with reference to examples, but the present invention is not limited to these examples. In addition, in the experiments described in these Examples and Comparative Examples, CW
ST was measured according to the method described above.

【0040】白血球除去率および血小板除去率の測定
は、各血液フィルターを直径25mmの大きさに打ち抜き、
専用のモジュール内に装着した。健康なボランティアか
ら採血したCPD加新鮮血を調整し、赤血球濃厚液を作成
した。これを落差10cmで5ml流して血液フィルター通過
前後の白血球量および血小板量を測定し、以下の式から
白血球および血小板の除去率を求めた。
The leukocyte removal rate and platelet removal rate were measured by punching each blood filter into a 25 mm diameter.
Mounted in a dedicated module. CPD-added fresh blood collected from healthy volunteers was prepared to prepare a red blood cell concentrate. The amount of leukocytes and platelets before and after passing through the blood filter was measured by flowing 5 ml of the mixture at a head of 10 cm, and the removal rate of leukocytes and platelets was determined from the following equation.

【0041】白血球除去率(%)=(1―(濾過後白血
球数 / 濾過前白血球数))×100 血小板除去率(%)=(1−(濾過後血小板数 / 濾過
前血小板数))×100 なお、白血球数および血小板数は、自動血球数測定装置
(東亜医用電子(株)SYSMEX E-9000)で求めた。
Leukocyte removal rate (%) = (1- (number of white blood cells after filtration / number of white blood cells before filtration)) × 100 Platelet removal rate (%) = (1− (number of platelets after filtration / number of platelets before filtration)) × 100 The white blood cell count and platelet count were determined using an automatic blood cell count analyzer (SYSMEX E-9000, Toa Medical Electronics Co., Ltd.).

【0042】(実施例1)平均孔径5.2ミクロン、空孔率86%
のポリウレタン多孔質体をヘキサン中で1時間超音波洗
浄した。この多孔質体を乾燥した後、0.3w/w%のポリア
クリル酸−ポリ2−(アクリロイルオキシ)エチルジエチ
ルメチルアンモニウム メチルスルファート水溶液(製
品名:エレタットU52、一方社油脂工業製)に2,2'-ヒ゛スヒ
ト゛ロキシルメチルフ゛タノール-トリス[3-(1-アシ゛リシ゛ニル)フ゜ロヒ゜オネート](製
品名:pz33、日本触媒製)を40μl/100mlの割合で添加
したコーティング水溶液に浸漬した。次に、得られた多
孔質体を80℃、2時間乾燥させた。この後、室温のシャ
ワー洗浄を4時間行い、多孔質体からの溶出物を除き、
乾燥させた。
(Example 1) Average pore size 5.2 microns, porosity 86%
Was subjected to ultrasonic cleaning in hexane for 1 hour. After drying the porous body, it was added to a 0.3 w / w% aqueous solution of polyacrylic acid-poly 2- (acryloyloxy) ethyldiethylmethylammonium methylsulfate (product name: Eretat U52, manufactured by Yasuo Yushi Kogyo Co., Ltd.). It was immersed in an aqueous coating solution to which 2'-hydroxypropylmethylphthalanol-tris [3- (1-acridinyl) fluoropionate] (product name: pz33, manufactured by Nippon Shokubai) was added at a ratio of 40 µl / 100 ml. Next, the obtained porous body was dried at 80 ° C. for 2 hours. Thereafter, a shower wash at room temperature is performed for 4 hours to remove elutes from the porous body.
Let dry.

【0043】こうして得られた血液フィルターを用い
て、CWSTならびに白血球除去率および血小板除去率を求
めた。この時に血液を流し始めて、膜が完全に血液で満
たされ、濾液側に血液がしみ出し始める時間(濡れ時
間)を親水性の尺度として併せて計測した。
Using the blood filter thus obtained, CWST, leukocyte removal rate and platelet removal rate were determined. At this time, the time when the blood was started to flow, the time when the membrane was completely filled with the blood, and the time when the blood began to seep into the filtrate side (wetting time) was also measured as a measure of hydrophilicity.

【0044】血液フィルター表面がカチオン化されてい
るかは、以下の様に膜を染色することでしらべた。
The cationization of the blood filter surface was examined by staining the membrane as follows.

【0045】直径25mmに打ち抜いたサンプルをホルダー
にセットし血液フィルターとした。0.02mMに調整したト
リパンブルー水溶液を約20mlポンプでこのフィルターに
流した。その後、RO水を50ml流して余分のトリパンブル
ーを洗浄した。
A sample punched out to a diameter of 25 mm was set in a holder and used as a blood filter. An aqueous solution of trypan blue adjusted to 0.02 mM was passed through this filter with an approximately 20 ml pump. Thereafter, excess trypan blue was washed by flowing 50 ml of RO water.

【0046】染色したサンプルは、570nmの反射吸光度
を測定した。血液フィルター表面にカチオン性高分子が
保持されていれば、この反射吸光度は、大きくなる。
The stained sample was measured for reflection absorbance at 570 nm. If the cationic polymer is held on the blood filter surface, the reflection absorbance increases.

【0047】結果を表1と表2に示す。The results are shown in Tables 1 and 2.

【0048】(実施例2)平均孔径5.2ミクロン、空孔率86
%のポリウレタン多孔質体をヘキサン中で1時間超音波
洗浄した。この多孔質体を乾燥した後、0.3w/w%のメタ
クリル酸2-[N,N-ジメチル-N-(2-ヒドロキシ-3-N,N,N-ト
リメチルアンモニオプロピル)アンモニオ]エチルクロラ
イド塩(製品名:UX101、一方社油脂工業製)に2,2'-ヒ゛
スヒト゛ロキシルメチルフ゛タノール-トリス[3-(1-アシ゛リシ゛ニル)フ゜ロヒ゜オネート]
(製品名:pz33、日本触媒製)を40μl/100mlの割合で
添加したコーティング水溶液に浸漬した。次に、得られ
た多孔質体を80℃、2時間乾燥させた。この後、室温の
シャワー洗浄を4時間行い、多孔質体からの溶出物を除
き、乾燥させた。
Example 2 An average pore diameter of 5.2 microns and a porosity of 86
% Of the polyurethane porous material was ultrasonically washed in hexane for 1 hour. After drying this porous material, 0.3 [w / w%] 2- [N, N-dimethyl-N- (2-hydroxy-3-N, N, N-trimethylammoniopropyl) ammonio] ethyl methacrylate ethyl chloride Salt (product name: UX101, on the other hand, manufactured by Yushi Yushi Kogyo Co., Ltd.) and 2,2'-bishydroxypropyl phthalanol-tris [3- (1-acylcisinyl) fluoropionate]
(Product name: pz33, manufactured by Nippon Shokubai) was immersed in a coating aqueous solution to which 40 μl / 100 ml was added. Next, the obtained porous body was dried at 80 ° C. for 2 hours. Thereafter, shower washing at room temperature was performed for 4 hours to remove the eluate from the porous body, followed by drying.

【0049】こうして得られた血液フィルターを用い
て、CWSTならびに白血球除去率および血小板除去率を求
めた。この時に血液を流し始めて、膜が完全に血液で満
たされ、濾液側に血液がしみ出し始める時間(濡れ時
間)を親水性の尺度として併せて計測した。
Using the blood filter thus obtained, CWST, leukocyte removal rate and platelet removal rate were determined. At this time, the time when the blood was started to flow, the time when the membrane was completely filled with the blood, and the time when the blood began to seep into the filtrate side (wetting time) was also measured as a measure of hydrophilicity.

【0050】血液フィルター表面がカチオン化されてい
るかは、実施例1と同様な方法でしらべた。
Whether the blood filter surface was cationized was examined in the same manner as in Example 1.

【0051】結果を表1と表2に示す。The results are shown in Tables 1 and 2.

【0052】(実施例3)平均孔径5.2ミクロン、空孔率86%
のポリウレタン多孔質体をヘキサン中で1時間超音波洗
浄した。この多孔質体を乾燥した後、1w/w%のポリジメ
チルアミノプロピルアクリルアミドの2−プロパノール
溶液に浸漬した。次ぐに、得られた多孔質体を80℃、2
時間乾燥させた。この後、室温のシャワー洗浄を4時間
行い、多孔質体からの溶出物を除き、乾燥させた。
(Example 3) Average pore diameter 5.2 microns, porosity 86%
Was subjected to ultrasonic cleaning in hexane for 1 hour. After drying the porous body, it was immersed in a 1 w / w% solution of polydimethylaminopropylacrylamide in 2-propanol. Next, the obtained porous body was heated at 80 ° C., 2
Let dry for hours. Thereafter, shower washing at room temperature was performed for 4 hours to remove the eluate from the porous body, followed by drying.

【0053】こうして得られた血液フィルターを用い
て、CWSTならびに白血球除去率および血小板除去率を求
めた。この時に血液を流し始めて、膜が完全に血液で満
たされ、濾液側に血液がしみ出し始める時間(濡れ時
間)を親水性の尺度として併せて計測した。
Using the blood filter thus obtained, CWST, leukocyte removal rate and platelet removal rate were determined. At this time, the time when the blood was started to flow, the time when the membrane was completely filled with the blood, and the time when the blood began to seep into the filtrate side (wetting time) was also measured as a measure of hydrophilicity.

【0054】血液フィルター表面がカチオン化されてい
るかは、実施例1と同様な方法でしらべた。
Whether or not the blood filter surface was cationized was examined in the same manner as in Example 1.

【0055】結果を表1と表2に示す。The results are shown in Tables 1 and 2.

【0056】(実施例4)平均孔径5.2ミクロン、空孔率86%
のポリウレタン多孔質体をヘキサン中で1時間超音波洗
浄した。この多孔質体を乾燥した後、1w/w%のポリジメ
チルアミノプロピルメタアクリルアミドの2−プロパノ
ール溶液に浸漬した後、得られた多孔質体を80℃、2時
間乾燥させた。この後、室温のシャワー洗浄を4時間行
い、多孔質体からの溶出物を除き、乾燥させた。
Example 4 An average pore diameter of 5.2 microns and a porosity of 86%
Was subjected to ultrasonic cleaning in hexane for 1 hour. After the porous body was dried, it was immersed in a 1 w / w% solution of polydimethylaminopropyl methacrylamide in 2-propanol, and the obtained porous body was dried at 80 ° C. for 2 hours. Thereafter, shower washing at room temperature was performed for 4 hours to remove the eluate from the porous body, followed by drying.

【0057】こうして得られた血液フィルターを用い
て、CWSTならびに白血球除去率および血小板除去率を求
めた。この時に血液を流し始めて、膜が完全に血液で満
たされ、濾液側に血液がしみ出し始める時間(濡れ時
間)を親水性の尺度として併せて計測した。
Using the blood filter thus obtained, CWST, leukocyte removal rate and platelet removal rate were determined. At this time, the time when the blood was started to flow, the time when the membrane was completely filled with the blood, and the time when the blood began to seep into the filtrate side (wetting time) was also measured as a measure of hydrophilicity.

【0058】血液フィルター表面がカチオン化されてい
るかは、実施例1と同様な方法でしらべた。
Whether the blood filter surface was cationized was examined in the same manner as in Example 1.

【0059】結果を表1と表2に示す。The results are shown in Tables 1 and 2.

【0060】(実施例5)平均孔径5.2ミクロン、空孔率86%
のポリウレタン多孔質体をヘキサン中で1時間超音波洗
浄した。この多孔質体を乾燥した後、0.3w/w%に調整し
たポリアクリル酸−ポリ2−(アクリロイルオキシ)エチ
ルジエチルメチルアンモニウムメチルスルファート(製
品名:エレタットU52、一方社油脂工業製)のコーティ
ング水溶液に浸漬した。次に、多孔質体を80℃、2時間
乾燥させた。この後、室温のシャワー洗浄を4時間行
い、多孔質体からの溶出物を除き、乾燥させた。
(Example 5) Average pore size 5.2 microns, porosity 86%
Was subjected to ultrasonic cleaning in hexane for 1 hour. After drying this porous body, coating with polyacrylic acid-poly 2- (acryloyloxy) ethyldiethylmethylammonium methylsulfate (product name: Eretat U52, on the other hand, manufactured by Yushi Yushi Kogyo Co.) adjusted to 0.3 w / w% Immersion in an aqueous solution. Next, the porous body was dried at 80 ° C. for 2 hours. Thereafter, shower washing at room temperature was performed for 4 hours to remove the eluate from the porous body, followed by drying.

【0061】こうして得られた血液フィルターを用い
て、CWSTならびに白血球除去率および血小板除去率を求
めた。この時に血液を流し始めて、膜が完全に血液で満
たされ、濾液側に血液がしみ出し始める時間(濡れ時
間)を親水性の尺度として併せて計測した。
Using the blood filter thus obtained, CWST, leukocyte removal rate and platelet removal rate were determined. At this time, the time when the blood was started to flow, the time when the membrane was completely filled with the blood, and the time when the blood began to seep into the filtrate side (wetting time) was also measured as a measure of hydrophilicity.

【0062】血液フィルター表面がカチオン化されてい
るかは、実施例1と同様な方法でしらべた。
Whether the blood filter surface was cationized was examined in the same manner as in Example 1.

【0063】結果を表1と表2に示す。Tables 1 and 2 show the results.

【0064】(比較例1)平均孔径5.2ミクロン、空孔率86%
のポリウレタン多孔質体をヘキサン中で1時間超音波洗
浄した。この多孔質体を乾燥した後、アルゴン気相下
(0.1Torr), 100W, 20sec低温プラズマ照射し、さらに気
相でグリシジルアクリレートを重合させた。この後、構
造式(3)で示されるカチオノンUK(一方社油脂工業
製)の5w/w%水溶液(ピリジン0.5w/w%含む)に60℃、
12時間浸漬させ、洗浄、乾燥させた。
(Comparative Example 1) Average pore size 5.2 microns, porosity 86%
Was subjected to ultrasonic cleaning in hexane for 1 hour. After drying this porous body, it is
(0.1 Torr), low-temperature plasma irradiation at 100 W for 20 sec, and glycidyl acrylate was polymerized in the gas phase. Thereafter, a 5 w / w% aqueous solution (containing 0.5 w / w% of pyridine) of cationone UK (manufactured by YAS & Co., Ltd.) represented by the structural formula (3) is added at 60 ° C.
It was immersed for 12 hours, washed and dried.

【0065】こうして得られた血液フィルターを用い
て、CWSTならびに白血球除去率および血小板除去率を求
めた。この時に血液を流し始めて、膜が完全に血液で満
たされ、濾液側に血液がしみ出し始める時間(濡れ時
間)を親水性の尺度として併せて計測した。
Using the blood filter thus obtained, CWST, leukocyte removal rate and platelet removal rate were determined. At this time, the time when the blood was started to flow, the time when the membrane was completely filled with the blood, and the time when the blood began to seep into the filtrate side (wetting time) was also measured as a measure of hydrophilicity.

【0066】血液フィルター表面がカチオン化されてい
るかは、実施例1と同様な方法でしらべた。
The same method as in Example 1 was used to determine whether the surface of the blood filter was cationized.

【0067】結果を表1と表2に示す。The results are shown in Tables 1 and 2.

【0068】(比較例2)平均孔径5.2ミクロン、空孔率86%
のポリウレタン多孔質体をヘキサン中で1時間超音波洗
浄した。この多孔質体を乾燥した。このサンプルを用い
て実施例1と同様な方法で、白血球除去率、血小板除去
率、血液を流し始めてからしみ出し始める時間(濡れ時
間)、CWST、カチオン化の様子(未処理の対照)を測定
した。
Comparative Example 2 An average pore diameter of 5.2 μm and a porosity of 86%
Was subjected to ultrasonic cleaning in hexane for 1 hour. This porous body was dried. Using this sample, the leukocyte removal rate, platelet removal rate, time to start oozing after wetting (wetting time), CWST, and state of cationization (untreated control) were measured in the same manner as in Example 1. did.

【0069】結果を表1と表2に示す。The results are shown in Tables 1 and 2.

【0070】[0070]

【表1】 [Table 1]

【0071】[0071]

【表2】 [Table 2]

【0072】以上の結果から、実施例1〜5において
は、いずれもCWSTは、90dyn/cm以上であり、カチオン性
物質のコーティングのみで血液フィルター表面のカチオ
ン性付与と同時に親水化が行なえた。比較例1、2で
は、ともにCWSTは、80dyn/cm未満であった。
From the above results, in all of Examples 1 to 5, the CWST was 90 dyn / cm or more, and the hydrophilicity was able to be imparted simultaneously with the impartation of cationicity to the blood filter surface only by coating the cationic substance. In Comparative Examples 1 and 2, the CWST was less than 80 dyn / cm.

【0073】また、実施例1〜5、比較例1のいづれも
血液フィルター表面には、カチオン性高分子が保持され
ていることが、反射吸光度から判った。
In each of Examples 1 to 5 and Comparative Example 1, it was found from the reflection absorbance that the cationic polymer was retained on the blood filter surface.

【0074】[0074]

【効果】本発明は上述の化合物を血液フィルターを構成
する基材に塗布し加熱乾燥させるといった簡便な操作で
該フィルターの親水化とカチオン化が同時に行え、これ
により得られる血液フィルターは高い白血球および血小
板除去能力を有する。
According to the present invention, hydrophilicity and cationization of the blood filter can be simultaneously performed by a simple operation such as applying the above-described compound to a base material constituting a blood filter and heating and drying the blood filter. Has the ability to remove platelets.

【0075】また、本発明の血液フィルターは高い親水
性を有するので、血液の濾過時間が短くて済み、作業時
間を短縮することができる。
Further, since the blood filter of the present invention has high hydrophilicity, the blood filtration time can be shortened, and the working time can be shortened.

───────────────────────────────────────────────────── フロントページの続き Fターム(参考) 4C066 AA07 BB01 CC01 FF01 FF04 MM10 PP05 4C077 AA12 BB02 KK10 KK11 LL23 NN02 PP10 PP19 4D019 AA03 BA12 BA13 BB02 BB03 BB07 BB08 BC09 BC13 BC20 CB06  ──────────────────────────────────────────────────続 き Continued on the front page F term (reference) 4C066 AA07 BB01 CC01 FF01 FF04 MM10 PP05 4C077 AA12 BB02 KK10 KK11 LL23 NN02 PP10 PP19 4D019 AA03 BA12 BA13 BB02 BB03 BB07 BB08 BC09 BC13 BC20 CB06

Claims (6)

【特許請求の範囲】[Claims] 【請求項1】(メタ)アクリル酸と一般式(1)で表され
る化合物との共重合体が血液フィルターを構成する基材
表面に保持されていることを特徴とする血液フィルタ
ー。 【化1】
1. A blood filter, wherein a copolymer of (meth) acrylic acid and a compound represented by the general formula (1) is held on the surface of a base material constituting a blood filter. Embedded image
【請求項2】一般式(2)で表される重合体が血液フィ
ルターを構成する基材表面に保持されていることを特徴
とする血液フィルター。 【化2】
2. A blood filter, wherein the polymer represented by the general formula (2) is held on the surface of a base material constituting the blood filter. Embedded image
【請求項3】一般式(3)で表される重合体が血液フィ
ルターを構成する基材表面に保持されていることを特徴
とする血液フィルター。 【化3】
3. A blood filter, wherein the polymer represented by the general formula (3) is held on the surface of a base material constituting the blood filter. Embedded image
【請求項4】メタクリル酸2-[N,N-ジメチル-N-(2-ヒド
ロキシ-3-N,N,N-トリメチルアンモニオプロピル)アンモ
ニオ]エチル塩、アクリル酸2-[N,N-ジエチル-N-メチル
アンモニオ]エチル塩、ジメチルアミノプロピルアクリ
ルアミド、ジメチルアミノプロピルメタアクリルアミド
からなる群から少なくとも1つ選ばれた重合物が血液フ
ィルターを構成する基材表面に保持されていることを特
徴とする血液フィルター。
(4) methacrylic acid 2- [N, N-dimethyl-N- (2-hydroxy-3-N, N, N-trimethylammoniopropyl) ammonio] ethyl salt; acrylic acid 2- [N, N- [Diethyl-N-methylammonio] ethyl salt, dimethylaminopropyl acrylamide, dimethylaminopropyl methacrylamide, and at least one polymer selected from the group consisting of the polymer is retained on the surface of the substrate constituting the blood filter. And blood filter.
【請求項5】前記血液フィルターの臨界湿潤表面張力が
90〜95dyn/cmである請求項1〜4いすれか1項に記
載の血液フィルター。
5. The blood filter according to claim 1, wherein the critical wet surface tension of the blood filter is 90 to 95 dyn / cm.
【請求項6】(メタ)アクリル酸と一般式(1)で表され
る化合物との共重合体を血液フィルターを構成する基材
表面にコーテングさせた後、加熱乾燥させることを特徴
とする血液フィルターの製造方法。 【化4】
6. A blood, characterized in that a copolymer of (meth) acrylic acid and a compound represented by the general formula (1) is coated on the surface of a substrate constituting a blood filter and then dried by heating. Manufacturing method of filter. Embedded image
JP22745098A 1998-08-11 1998-08-11 Blood filter and manufacturing method thereof Expired - Lifetime JP3768009B2 (en)

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Cited By (5)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
WO2001032236A1 (en) * 1999-11-01 2001-05-10 Asahi Medical Co., Ltd. Filter for selectively removing leukocyte
WO2001066171A1 (en) * 2000-03-10 2001-09-13 Asahi Medical Co., Ltd. Novel leukapheretic filter
WO2002060557A1 (en) * 2001-01-29 2002-08-08 Asahi Medical Co., Ltd. Filter for processing blood and process for producing the same
JP2003070904A (en) * 2001-09-07 2003-03-11 Asahi Medical Co Ltd Filter holder and filter unit for separating organism component, and performance evaluation method of hemofiltration filter using the same
JP2007014854A (en) * 2005-07-06 2007-01-25 Kawamura Inst Of Chem Res Filtration filter, manufacturing method of filtration filter, and hemofiltration method

Cited By (9)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
WO2001032236A1 (en) * 1999-11-01 2001-05-10 Asahi Medical Co., Ltd. Filter for selectively removing leukocyte
US6977044B1 (en) 1999-11-01 2005-12-20 Asahi Medical Co., Ltd. Filter for selectively removing leukocytes
WO2001066171A1 (en) * 2000-03-10 2001-09-13 Asahi Medical Co., Ltd. Novel leukapheretic filter
WO2002060557A1 (en) * 2001-01-29 2002-08-08 Asahi Medical Co., Ltd. Filter for processing blood and process for producing the same
AU2002228363B2 (en) * 2001-01-29 2006-03-16 Asahi Kasei Medical Co., Ltd Filter for processing blood and process for producing the same
US7156240B2 (en) * 2001-01-29 2007-01-02 Asahi Kasei Medical Co., Ltd. Filter for processing blood and process for producing the same
KR100771778B1 (en) * 2001-01-29 2007-10-30 아사히 카세이 메디칼 가부시키가이샤 Filter for blood treatment and manufacturing method thereof
JP2003070904A (en) * 2001-09-07 2003-03-11 Asahi Medical Co Ltd Filter holder and filter unit for separating organism component, and performance evaluation method of hemofiltration filter using the same
JP2007014854A (en) * 2005-07-06 2007-01-25 Kawamura Inst Of Chem Res Filtration filter, manufacturing method of filtration filter, and hemofiltration method

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