JP3250833B2 - Leukocyte selective capture filter material - Google Patents
Leukocyte selective capture filter materialInfo
- Publication number
- JP3250833B2 JP3250833B2 JP02591892A JP2591892A JP3250833B2 JP 3250833 B2 JP3250833 B2 JP 3250833B2 JP 02591892 A JP02591892 A JP 02591892A JP 2591892 A JP2591892 A JP 2591892A JP 3250833 B2 JP3250833 B2 JP 3250833B2
- Authority
- JP
- Japan
- Prior art keywords
- filter material
- platelet
- filter
- blood
- leukocyte
- 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.)
- Expired - Fee Related
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- External Artificial Organs (AREA)
- Medicines Containing Material From Animals Or Micro-Organisms (AREA)
- Treatment Of Liquids With Adsorbents In General (AREA)
- Filtering Materials (AREA)
- Infusion, Injection, And Reservoir Apparatuses (AREA)
Description
【0001】[0001]
【産業上の利用分野】本発明は、白血球を選択的に捕捉
し、血小板を通過させる白血球選択捕捉フィルター材料
に関する。詳しくは、輸血や体外循環を行う時に、血液
中の白血球を選択的に捕捉除去したり、血液から濃縮血
小板血漿を調整する際に混入している白血球を選択的に
捕捉除去するための白血球選択捕捉フィルター材料に関
する。BACKGROUND OF THE INVENTION 1. Field of the Invention The present invention relates to a filter material for selectively capturing leukocytes, which selectively captures leukocytes and allows platelets to pass therethrough. Specifically, when performing transfusion or extracorporeal circulation, leukocyte selection to selectively capture and remove leukocytes in blood or to selectively capture and remove leukocytes mixed when preparing concentrated platelet plasma from blood For capture filter materials.
【0002】[0002]
【従来の技術】近年、免疫学、輸血学の進歩に伴い、従
来の全血輸血から患者が本当に必要とする血液成分のみ
を輸血する成分輸血の考え方が普及し実施されてきてい
る。成分輸血に用いられる赤血球濃厚液(CRC)、濃
厚血小板液(PC)、乏血小板血漿(PPP)などの各
種血液製剤は、献血によって得られた血液を遠心操作で
分離、分画して調整される。2. Description of the Related Art In recent years, with the progress of immunology and blood transfusion, the concept of component transfusion for transfusing only blood components that a patient really needs from conventional whole blood transfusion has become widespread and implemented. Various blood products such as erythrocyte concentrate (CRC), platelet concentrate (PC), and platelet poor plasma (PPP) used for component transfusion are adjusted by separating and fractionating blood obtained by donating blood by centrifugation. You.
【0003】しかしながら、遠心操作によって、分画さ
れた血液製剤中には多くの白血球が含まれており、この
混入白血球が頭痛、非溶血性発熱反応、悪寒、吐き気な
どの比較的軽微な副作用から、アロ抗原感作、輸血後G
VHD、ウィルス感染などの重篤な副作用を誘発させる
ことが問題視され、血液製剤から白血球を除去する工夫
がなされている。[0003] However, the blood product fractionated by the centrifugation operation contains many leukocytes, and this mixed leukocyte may cause relatively minor side effects such as headache, non-hemolytic fever reaction, chills, and nausea. , Alloantigen sensitization, G after blood transfusion
Inducing serious side effects such as VHD and viral infection has been regarded as a problem, and various measures have been taken to remove leukocytes from blood products.
【0004】白血球を血液製剤から除去する方法として
は、血液成分の比重差を利用した遠心分離方法と不織布
などの極細繊維や連続孔を有する多孔質体をフィルター
材料としたフィルター法に大別されるが、白血球除去効
率の良いこと、操作が簡単なこと、コストが低いことの
理由によりフィルター法が広く用いられている。[0004] Methods for removing leukocytes from blood products are roughly classified into a centrifugal separation method utilizing a difference in specific gravity of blood components and a filter method using a fine material such as a nonwoven fabric or a porous material having continuous pores as a filter material. However, the filter method is widely used because of its high leukocyte removal efficiency, simple operation, and low cost.
【0005】ところが、上記フィルター材料の多くは疎
水性高分子材料よりなるため、白血球のみならず一般的
に高い粘着能を持つ血小板をも吸着除去してしまうもの
であった。再生不良性貧血、血小板減少性紫斑病、白血
病などの疾患がある患者に対し、血小板を補給する目的
で全血、濃厚血小板、赤血球濃厚液などの血小板を多量
に含む血液製剤を輸血することは不可欠であるが、上記
のフィルターをそのまま用いると白血球は捕捉されるが
患者に必要な血小板も吸着除去されてしまい、また、フ
ィルターを用いず輸血すると輸血後副作用が懸念される
ものであった。このため、血小板損失を抑制し、かつ白
血球を選択的に捕捉するフィルターの開発が切望されて
きた。However, most of the above filter materials are made of a hydrophobic polymer material, so that not only leukocytes but also platelets generally having high adhesiveness are adsorbed and removed. For patients with diseases such as aplastic anemia, thrombocytopenic purpura, and leukemia, transfusing a blood product containing a large amount of platelets such as whole blood, concentrated platelets, and red blood cell concentrate to replenish platelets is not possible. Indispensable, if the above-mentioned filter is used as it is, leukocytes are captured, but platelets necessary for the patient are also adsorbed and removed, and if transfusion is performed without using a filter, there is a concern about post-transfusion side effects. Therefore, development of a filter that suppresses platelet loss and selectively captures white blood cells has been desired.
【0006】血小板の材料表面への付着は材料表面の性
質に依存する。こうした考えにのっとって、血小板の粘
着を抑制する手法としては、フィルター材料表面に親水
性のモノマーをグラフト重合したり、親水性のポリマー
をフィルター材料表面にコーティングしたりする方法が
公知の技術として知られている。しかし、こうして得ら
れる材料は血小板の粘着を抑制するのと同時に白血球も
粘着除去されにくくなり、白血球のみを選択的に捕捉す
る本目的のフィルターとしては用いる事のできないもの
であった。[0006] The attachment of platelets to the material surface depends on the nature of the material surface. Based on this idea, known techniques for suppressing platelet adhesion include methods of graft polymerizing a hydrophilic monomer on the surface of a filter material and coating a hydrophilic polymer on the surface of the filter material. Have been. However, the material obtained in this way suppresses the adhesion of platelets and makes it difficult for white blood cells to be easily removed, and thus cannot be used as a filter for the purpose of selectively capturing only white blood cells.
【0007】特開昭55−129755号には不織布表
面に抗血栓性材料をコーティングしたフィルターを用い
た、赤血球及び血小板の混入の少ない白血球及びリンパ
球の採取方法が開示されている。しかしながら、このフ
ィルターを用いると血小板の損失は少ないが、白血球の
捕捉力も小さく満足のいくものではなかった。Japanese Patent Application Laid-Open No. 55-129755 discloses a method of collecting leukocytes and lymphocytes containing little red blood cells and platelets using a filter having a nonwoven fabric surface coated with an antithrombotic material. However, when this filter is used, although the loss of platelets is small, the capturing power of leukocytes is also small and not satisfactory.
【0008】WO87/05812号には繊維の表面部
分が非イオン性親水基と塩基性含窒素官能基を含有して
いるフィルター材料を用いて血小板捕捉は少なくかつ白
血球を効率的に捕捉する白血球選択除去フィルターが開
示されている。このフィルターを用いると、白血球を選
択的に捕捉除去する事が可能となり、血小板の捕捉を抑
制させ得る効果を有するが、粘着能の高い血小板を更に
高収率で回収できるフィルターの開発が望まれてきた。[0008] WO 87/05812 discloses a leukocyte selection method that uses a filter material in which the surface portion of the fiber contains a nonionic hydrophilic group and a basic nitrogen-containing functional group to reduce platelet capture and efficiently capture leukocytes. A removal filter is disclosed. The use of this filter makes it possible to selectively capture and remove leukocytes and has the effect of suppressing the capture of platelets, but the development of a filter that can collect platelets with high adhesiveness in higher yield is desired. Have been.
【0009】白血球を選択的に捕捉除去し、かつ血小板
は通過させるには、フィルター材料の物理的因子と化学
的因子を考慮する必要がある。物理的因子とは、フィル
ター材料の物理的な構造を示し、不織布などの繊維状媒
体では繊維径、密度、厚み等がこれに当たり、連続孔を
有する多孔質体の場合、孔径、気孔率、密度、厚み等が
これに相当する。一般的に、白血球の捕捉にはフィルタ
ー材料の物理的因子が大きく寄与し、捕捉能を高めるに
は、繊維径の細い極細繊維を用いる、充填密度を高め
る、孔径を小さくすることにより構成されることが知ら
れている。しかしながら、この方法で白血球の捕捉能を
向上させると、血球の目詰まりが起こり易く、濾過の長
時間化を引き起こしかねない上、血小板のフィルター材
料への吸着、付着による血小板損失の増大も生ずるもの
であった。このため、血小板のフィルター材料への吸着
を抑制する目的で、繊維径を太くしたり、また、多孔質
体の孔径を大きくしたりすることを試みると、血小板の
通過能は向上するが、白血球の捕捉能が低下してしまう
問題があった。このため、本目的の白血球選択捕捉フィ
ルターを開発するためには、白血球は捕捉するが、血小
板は通過させるようにフィルター材料の表面を化学的に
改質する必要があった。しかし、前述したように親水性
のモノマーやポリマーをグラフト重合またはコーティン
グすると血小板の通過能は向上するが、白血球の捕捉能
は低下する恐れがある。従って、本目的の白血球選択捕
捉フィルターの化学的処理には、白血球の捕捉能を維持
しつつ、かつ血小板は通過させる親水化が必要であり、
特殊な構造、組成を有するモノマーあるいはポリマーを
探索する必要があった。In order to selectively capture and remove leukocytes and allow platelets to pass, it is necessary to consider the physical and chemical factors of the filter material. The physical factor refers to the physical structure of the filter material.For a fibrous medium such as a nonwoven fabric, the fiber diameter, density, thickness, etc. correspond to this.For a porous body having continuous pores, the pore diameter, porosity, density , Thickness and the like correspond to this. Generally, the physical factor of the filter material greatly contributes to the capture of leukocytes, and to enhance the capture ability, it is configured by using ultrafine fibers with a small fiber diameter, increasing the packing density, and reducing the pore size. It is known. However, when the leukocyte capturing ability is improved by this method, clogging of blood cells is liable to occur, which may cause a long filtration time, and also increases platelet loss due to adsorption and adhesion of platelets to the filter material. Met. Therefore, if an attempt is made to increase the fiber diameter or increase the pore diameter of the porous body in order to suppress the adsorption of platelets to the filter material, the platelet passage ability is improved, There is a problem that the capturing ability of the phenol decreases. For this reason, in order to develop a target leukocyte selective capture filter for this purpose, it was necessary to chemically modify the surface of the filter material so as to capture leukocytes but pass platelets. However, as described above, grafting or coating a hydrophilic monomer or polymer improves platelet passage ability, but may decrease leukocyte capture ability. Therefore, in the chemical treatment of the leukocyte selective capture filter of the present purpose, it is necessary to maintain the leukocyte capture ability, and to hydrophilize platelets,
It was necessary to search for a monomer or polymer having a special structure and composition.
【0010】塩基性含窒素官能基がフィルター材料の少
なくとも周囲表面部分に存在すると、フィルター材表面
は正荷電を帯びるようになる。このように正に荷電した
フィルター材料に白血球や血小板が接触すると、白血球
や血小板は負の荷電を有しているため、フィルター材に
よく粘着するようになる。しかしながら、本発明の白血
球選択捕捉フィルター材料は白血球を捕捉し、かつ血小
板は通過させる性質を有するものであらねばならない。
そのため、正荷電を付与する塩基性含窒素官能基の存在
だけでは血小板をも捕捉してしまい、目的のフィルター
材料として使用することはできないものであった。When a basic nitrogen-containing functional group is present on at least a peripheral surface portion of the filter material, the surface of the filter material becomes positively charged. When white blood cells and platelets come into contact with such positively charged filter material, the white blood cells and platelets have a negative charge and thus adhere well to the filter material. However, the leukocyte selective capture filter material of the present invention must be capable of capturing leukocytes and allowing platelets to pass therethrough.
Therefore, the presence of a basic nitrogen-containing functional group that imparts a positive charge alone also captures platelets, and cannot be used as a target filter material.
【0011】一方、血液を様々な高分子材料に接触させ
ると、材料表面の選択によって血栓の有無、細胞崩壊の
有無に差が出てくる。これは未だに解明されていないこ
とであるが血液に含まれている細胞と用いた材料表面と
の複雑な相互作用の大小によるものと考えられている
(「医用高分子材料」、医用高分子材料編集委員会編、
1981)。親水性、疎水性という観点から材料表面を
分類すると、一般的に親水性表面を有する高分子材料は
材料表面と血液との界面エネルギーが小さく、従ってタ
ンパク質や血球細胞との相互作用が小さくなり、血栓の
形成や細胞の変態が抑制される傾向があるといわれてい
る(「バイオマテリアルサイエンス」第2集、135、
1982)。そのため血小板を通過させる性質をフィル
ター材料に付与するためには、フィルター材料が親水性
でなければならず、フィルター材料が疎水性表面である
場合には、フィルター材料に親水性のモノマーやポリマ
ーをグラフト重合やコーティングによって導入する必要
がある。On the other hand, when blood is brought into contact with various polymer materials, there is a difference between the presence or absence of thrombus and the presence or absence of cell disruption depending on the selection of the material surface. Although this has not been elucidated yet, it is thought to be due to the magnitude of the complex interaction between the cells contained in blood and the surface of the material used ("medical polymer materials", "medical polymer materials"). Editorial Committee,
1981). When classifying the material surface from the viewpoint of hydrophilicity and hydrophobicity, polymer materials having a hydrophilic surface generally have low interfacial energy between the material surface and blood, and therefore have a small interaction with proteins and blood cells, It is said that the formation of blood clots and the metamorphosis of cells tend to be suppressed ("Biomaterials Science" Vol. 2, 135,
1982). Therefore, the filter material must be hydrophilic in order to impart platelet-passing properties to the filter material.If the filter material has a hydrophobic surface, a hydrophilic monomer or polymer is grafted to the filter material. It must be introduced by polymerization or coating.
【0012】親水性物質とは、一般的にヒドロキシル
基、カルボキシル基、カルボニル基、アミド基、スルホ
ン酸基などの水との親和性の高い官能基を有する物質の
ことであるが、なかでも、ポリエチレンオキサイド鎖を
有する物質は、ポリエチレンオキサイド鎖が高い極性を
示すため水によく溶ける性質がある。また、ポリエチレ
ンオキサイド鎖を有する物質は抗血栓性を有する優れた
血液適合性材料であることが知られている。例えば、ポ
リエチレンオキサイド鎖が存在する高分子材料表面に血
液を接触させてもアルブミンやグロブミンなどの血漿タ
ンパク質が材料表面に吸着せず、血小板の反応性も低く
なり血栓形成が見られないことが知られている(筏 義
人 医用高分子材料、共立出版、1989)。また、血
漿成分を血液中から分離する際、ポリエチレンオキサイ
ド鎖を有する物質とアクリロニトリルからなる多孔膜を
用いると、白血球、赤血球、血小板の多孔膜表面への吸
着がないため高い透水速度で血漿成分を分離することが
でき、かつ血漿中に含まれているタンパク質も多孔膜表
面に吸着しないため、高収率で回収することができるこ
とが開示されている(特開昭61−176359号)。The hydrophilic substance is generally a substance having a functional group having a high affinity for water, such as a hydroxyl group, a carboxyl group, a carbonyl group, an amide group, and a sulfonic acid group. A substance having a polyethylene oxide chain has a property of being highly soluble in water because the polyethylene oxide chain has high polarity. It is known that a substance having a polyethylene oxide chain is an excellent blood compatible material having antithrombotic properties. For example, it is known that even when blood is brought into contact with the surface of a polymer material on which polyethylene oxide chains are present, plasma proteins such as albumin and globumin do not adsorb to the material surface, platelet reactivity decreases, and no thrombus formation is observed. (Yoshihito Raft, Medical Polymer Materials, Kyoritsu Shuppan, 1989). In addition, when separating the plasma component from the blood, if a porous membrane made of a substance having a polyethylene oxide chain and acrylonitrile is used, leukocytes, erythrocytes, and platelets are not adsorbed to the surface of the porous membrane, so the plasma component can be separated at a high water permeation rate. It is disclosed that the protein can be separated and the protein contained in the plasma is not adsorbed on the surface of the porous membrane, so that it can be recovered in a high yield (Japanese Patent Application Laid-Open No. 61-176359).
【0013】このような優れた血液適合性材料であるポ
リエチレンオキサイド鎖を有する物質をフィルター材料
の少なくとも表面部分に導入すると、上記のような細胞
低付着性、血液適合性が付与され、血小板がフィルター
材料表面に付着することなく通過するようになる。しか
し、白血球も同時に通過するようになり、目的のフィル
ター材料として用いることのできないものであった。こ
のように、白血球の捕捉に重点を置くと、血小板も捕捉
され、血小板の通過性に重点を置くと、白血球も同時に
通過するようになる場合が一般的であった。When such a substance having a polyethylene oxide chain, which is an excellent blood-compatible material, is introduced into at least the surface portion of the filter material, the above-mentioned low cell adhesion and blood compatibility are imparted, and the platelets are filtered. It passes without adhering to the material surface. However, the leukocytes also passed at the same time, and could not be used as a target filter material. As described above, when emphasis is placed on capturing leukocytes, platelets are also captured, and when focusing on platelet permeability, leukocytes are generally allowed to pass at the same time.
【0014】[0014]
【発明が解決しようとする課題】本発明は血小板吸着を
できるだけ抑制しかつ白血球を選択的に高収率で捕捉除
去する白血球選択捕捉フィルター材料を提供することを
目的とする。本発明はまた、血小板輸血や血液の体外循
環白血球除去療法に有効に用いることのできる血小板吸
着が少なくかつ白血球を効率よく除去する白血球選択捕
捉フィルターに用いられるフィルター材料を提供するこ
とを目的とする。SUMMARY OF THE INVENTION An object of the present invention is to provide a leukocyte selective capture filter material which suppresses platelet adsorption as much as possible and selectively captures and removes leukocytes at a high yield. Another object of the present invention is to provide a filter material used in a leukocyte selective capture filter that can be effectively used for platelet transfusion or extracorporeal circulating leukocyte removal therapy for blood and that efficiently removes white blood cells with little platelet adsorption. .
【0015】[0015]
【課題を解決するための手段】上記目的は塩基性含窒素
官能基及び繰り返し単位が2〜15のポリエチレンオキ
サイド鎖を繊維または連続孔を有する高分子多孔質体の
少なくとも周囲表面部分に含有させることにより達成さ
れる。SUMMARY OF THE INVENTION It is an object of the present invention to include a basic nitrogen-containing functional group and a polyethylene oxide chain having 2 to 15 repeating units in at least the peripheral surface portion of a fiber or a porous polymer having continuous pores. Is achieved by
【0016】即ち、塩基性含窒素官能基とポリエチレン
オキサイド鎖の両方がフィルター材料の少なくとも表面
部分に導入されると、意外なことに白血球の捕捉能は維
持しつつ、かつ血小板はほとんど粘着せず通過する性質
が付与されることが判明し、本発明のフィルター材料を
開発するに至ったのである。That is, when both the basic nitrogen-containing functional group and the polyethylene oxide chain are introduced into at least the surface portion of the filter material, surprisingly, the ability to capture leukocytes is maintained, and platelets hardly adhere. It was found that the material had the property of passing through, and the filter material of the present invention was developed.
【0017】即ち、本発明の白血球選択捕捉フィルター
材料とは、塩基性含窒素官能基とポリエチレンオキサイ
ド鎖が繊維または連続孔を有する高分子多孔質体の少な
くとも周囲表面部分に含有されているフィルター材料で
ある。That is, the filter material for selective capture of leukocytes of the present invention is a filter material containing a basic nitrogen-containing functional group and a polyethylene oxide chain at least in the peripheral surface of a polymer or a porous polymer having continuous pores. It is.
【0018】本発明のフィルター材料の表面部分中の塩
基性窒素原子の含量は0.2〜4.0重量%、より好ま
しくは0.3〜1.5重量%が望ましい。ポリエチレン
オキサイド鎖の繰り返し単位は2〜15、ポリエチレン
オキサイド鎖部分の含量は2.0〜22.0重量%、よ
り好ましくは3.0〜15.0重量%が望ましい。塩基
性含窒素官能基の含量が0.2重量%未満であるとフィ
ルター材料表面の正荷電量が不足し、白血球の捕捉能が
低下する恐れがあり、4.0重量%を超えると血小板の
フィルター材料表面への粘着が起こり、血小板通過性が
低下する恐れがあるためである。また、ポリエチレンオ
キサイド鎖の繰り返し単位が15を超える、または、2
2.0重量%を超えると白血球の捕捉能が低下する恐れ
があり、2.0重量%未満であると血小板のフィルター
材料への付着が起こりやすくなるためである。また、塩
基性含窒素官能基の含量及びポリエチレンオキサイド鎖
の含量は例えば、元素分析、赤外線吸収スペクトル、核
磁気共鳴スペクトルによって測定することができる。The content of the basic nitrogen atoms in the surface portion of the filter material of the present invention is desirably 0.2 to 4.0% by weight, more preferably 0.3 to 1.5% by weight. The repeating unit of the polyethylene oxide chain is preferably 2 to 15, and the content of the polyethylene oxide chain portion is preferably 2.0 to 22.0% by weight, more preferably 3.0 to 15.0% by weight. When the content of the basic nitrogen-containing functional group is less than 0.2% by weight, the positive charge on the surface of the filter material becomes insufficient, and the ability to capture leukocytes may be reduced. This is because sticking to the surface of the filter material may occur and platelet permeability may decrease. Further, the repeating unit of the polyethylene oxide chain exceeds 15, or 2
If the content is more than 2.0% by weight, the capturing ability of leukocytes may be reduced. If the content is less than 2.0% by weight, platelets tend to adhere to the filter material. The content of the basic nitrogen-containing functional group and the content of the polyethylene oxide chain can be measured, for example, by elemental analysis, infrared absorption spectrum, and nuclear magnetic resonance spectrum.
【0019】本発明の白血球選択捕捉フィルター材料に
導入可能な塩基性含窒素官能基を有する材料としては、
第1級アミノ基、第2級アミノ基、第3級アミノ基、4
級アンモニウム基、及びピリジル基、イミダゾイル基等
の含窒素芳香環基等があげられ、具体的には入手のし易
さ、取り扱い性などから、ジメチルアミノエチルメタア
クリレート、ジエチルアミノエチルメタクリレートなど
がある。また、本発明のポリエチレンオキサイド鎖を有
する材料としては、メトキシトリエチレングリコール、
メタクリレート(ポリエチレンオキサイド鎖の繰り返し
単位=3)、メトキシテトラエチレングリコール、メタ
クリレート(ポリエチレンオキサイド鎖の繰り返し単位
=4)、メトキシペンタエチレングリコール メタクリ
レート(ポリエチレンオキサイド鎖の繰り返し単位=
5)などがあげられる。Examples of the material having a basic nitrogen-containing functional group which can be introduced into the leukocyte selective capture filter material of the present invention include:
Primary amino group, secondary amino group, tertiary amino group, 4
Examples thereof include a quaternary ammonium group, and a nitrogen-containing aromatic ring group such as a pyridyl group and an imidazoyl group. Specific examples include dimethylaminoethyl methacrylate and diethylaminoethyl methacrylate from the viewpoint of easy availability and handleability. Further, as the material having a polyethylene oxide chain of the present invention, methoxytriethylene glycol,
Methacrylate (polyethylene oxide chain repeating unit = 3), methoxytetraethylene glycol, methacrylate (polyethylene oxide chain repeating unit = 4), methoxypentaethylene glycol methacrylate (polyethylene oxide chain repeating unit =
5) and the like.
【0020】以上のように、本発明のフィルター材料
は、塩基性含窒素官能基と繰り返し単位が2〜15のポ
リエチレンオキサイド鎖がフィルター材料の少なくとも
表面部分に含有されている点に特徴を有している。換言
すれば、本発明のフィルター材料はそのボディー部分と
表面部分が別に形成され、表面部分だけが前記の塩基性
含窒素官能基と繰り返し単位が2〜15のポリエチレン
オキサイド鎖を有する物質からなっていてもよいし、ボ
ディー部分と表面部分とが一体的に形成されており、或
いはボディー部分と表面部分の両者、即ちフィルター材
料全体が前記の塩基性含窒素官能基と繰り返し単位が2
〜15のポリエチレンオキサイド鎖を有する物質からな
っていてもよい。As described above, the filter material of the present invention is characterized in that a basic nitrogen-containing functional group and a polyethylene oxide chain having 2 to 15 repeating units are contained in at least the surface of the filter material. ing. In other words, the filter material of the present invention has a body portion and a surface portion formed separately, and only the surface portion is made of a substance having the basic nitrogen-containing functional group and a polyethylene oxide chain having 2 to 15 repeating units. The body portion and the surface portion may be integrally formed, or both the body portion and the surface portion, that is, the entire filter material may contain two or more of the basic nitrogen-containing functional group and the repeating unit.
It may consist of a substance having up to 15 polyethylene oxide chains.
【0021】一般的には不織布などの繊維状媒体や連続
孔を有する多孔質体は疎水性表面を有しており、このよ
うな疎水性表面を有するフィルター材料への前記塩基性
官能基やポリエチレンオキサイド鎖の導入は、塩基性含
窒素官能基と繰り返し単位が2〜15のポリエチレンオ
キサイド鎖を有する重合性単量体のコポリマーをフィル
ター材料にコーティングすることにより、また、該重合
性単量体をフィルター材料にグラフト重合させることに
より達成される。Generally, a fibrous medium such as a non-woven fabric or a porous body having continuous pores has a hydrophobic surface, and the above-mentioned basic functional group or polyethylene is added to a filter material having such a hydrophobic surface. The introduction of an oxide chain is performed by coating a filter material with a copolymer of a polymerizable monomer having a basic nitrogen-containing functional group and a polyethylene oxide chain having a repeating unit of 2 to 15; It is achieved by graft polymerization to the filter material.
【0022】また、塩基性含窒素官能基とポリエチレン
オキサイド鎖を含むポリマーをコーティングによって材
料表面に導入する場合、塩基性含窒素官能基とポリエチ
レンオキサイド鎖を有しない他の血液適合性に富む重合
性単量体との共重合体を用いることも好ましい。用い得
る重合性単量体としては、特に限定はないが、例えば、
アクリル酸誘導体、メタクリル酸誘導体、アリルアルコ
ール、スチレン誘導体、アクリロニトリル等が挙げられ
る。この中でも、入手のし易さ、取扱い性の点からアク
リル酸またはメタクリル酸エステルが好ましく、2−ヒ
ドロキシエチルアクリレート、2−ヒドロキシエチルメ
タクリレート等は、特にコーティング材を材料表面に安
定的に保持させる効果もあり優れている。When a polymer containing a basic nitrogen-containing functional group and a polyethylene oxide chain is introduced onto the surface of the material by coating, other blood-compatible polymerizable polymers that do not have a basic nitrogen-containing functional group and a polyethylene oxide chain. It is also preferable to use a copolymer with a monomer. The polymerizable monomer that can be used is not particularly limited, for example,
Acrylic acid derivatives, methacrylic acid derivatives, allyl alcohol, styrene derivatives, acrylonitrile and the like can be mentioned. Among them, acrylic acid or methacrylic acid ester is preferable from the viewpoint of availability and handleability, and 2-hydroxyethyl acrylate, 2-hydroxyethyl methacrylate, and the like are particularly effective in stably holding the coating material on the material surface. There is also excellent.
【0023】本発明の白血球を捕捉するフィルター材料
としては不織布などの繊維状媒体や連続孔を有する多孔
質体が好ましい。フィルター材料の物理的な構造は白血
球の捕捉に大きく寄与することが知られており、更に白
血球の捕捉能を向上させるには該フィルター材料の選択
も重要な因子となる。即ち、不織布などの繊維状媒体を
フィルター材料とする場合、平均繊維径は0.3μm以
上、3.0μm未満、より好ましくは1.0μm以上、
2.0μm未満が望ましい。また、容器内に該繊維状媒
体を充填した時の充填密度は0.1g/cm3 以上、
0.3g/cm3未満が好ましい。平均繊維径が0.3
μm未満、充填密度が0.3g/cm3 以上であると、
血球の目詰まりや圧力損失の増大化を引き起こす恐れが
あり、また、平均繊維径が3.0μm以上、充填密度が
0.1g/cm3 未満だと白血球の捕捉能が低下する恐
れがあるためである。As the filter material for capturing leukocytes of the present invention, a fibrous medium such as a nonwoven fabric or a porous body having continuous pores is preferable. It is known that the physical structure of the filter material greatly contributes to the capture of leukocytes, and the selection of the filter material is also an important factor in improving the leukocyte capture ability. That is, when a fibrous medium such as a nonwoven fabric is used as the filter material, the average fiber diameter is 0.3 μm or more and less than 3.0 μm, more preferably 1.0 μm or more,
Desirably less than 2.0 μm. Further, the filling density when the fibrous medium is filled in a container is 0.1 g / cm 3 or more,
Less than 0.3 g / cm 3 is preferred. Average fiber diameter is 0.3
μm, the packing density is 0.3 g / cm 3 or more,
Clogging of blood cells and an increase in pressure loss may be caused, and if the average fiber diameter is 3.0 μm or more and the packing density is less than 0.1 g / cm 3 , the ability to capture leukocytes may be reduced. It is.
【0024】なお、本発明における平均繊維径とは、以
下の手順に従って求められる値をいう。即ちフィルター
を構成する、実質的に均一と認められるフィルター要素
の一部をサンプリングし、走査電子顕微鏡などを用い
て、写真に撮る。サンプリングに際しては、フィルター
要素の有効濾過断面積部分を、1辺が0.5〜1cmの
正方形によって区分し、その中から3ケ所以上、好まし
くは5ケ所以上をランダムサンプリングする。ランダム
サンプリングするには、例えば上記各区分に番地を指定
した後、乱数表を使うなどの方法で、必要ケ所以上の区
分を選べば良い。またサンプリングした各区分につい
て、3ケ所以上好ましくは5ケ所以上を写真に撮る。こ
のようにして得た写真について、写っている全ての繊維
の直径を測定する。ここで直径とは、繊維軸に対して直
角方向の繊維の幅をいう。測定した全ての繊維の直径の
和を、繊維の数で割った値を平均繊維径とする。但し、
複数の繊維が重なり合っており、他の繊維の陰になって
その幅が測定できない場合、また複数の繊維が溶融する
などして、太い繊維になっている場合、更に著しく直径
の異なる繊維が混在している場合、等々の場合には、こ
れらのデータは削除する。以上の方法により、100本
以上、好ましくは1000本以上のデータにより平均繊
維径を求める。In the present invention, the average fiber diameter means a value determined according to the following procedure. That is, a part of the filter element, which is regarded as substantially uniform, constituting the filter is sampled and photographed using a scanning electron microscope or the like. At the time of sampling, the effective filtration sectional area of the filter element is divided by a square having a side of 0.5 to 1 cm, and three or more, preferably five or more are randomly sampled from among them. In order to perform random sampling, for example, after specifying an address in each of the above sections, a section at a necessary place or more may be selected by a method such as using a random number table. For each sampled section, three or more, preferably five or more locations are photographed. The diameter of all the fibers in the photograph thus obtained is measured. Here, the diameter refers to the width of the fiber in a direction perpendicular to the fiber axis. The value obtained by dividing the sum of the diameters of all the measured fibers by the number of fibers is defined as the average fiber diameter. However,
When multiple fibers are overlapped and their width cannot be measured due to the shadow of other fibers, or when multiple fibers are melted and become thicker, fibers with significantly different diameters are mixed. If so, these data are deleted. By the above method, the average fiber diameter is determined from data of 100 or more, preferably 1,000 or more.
【0025】連続孔を有する多孔質体をフィルター材料
とする場合には、3〜50μmの平均孔径を有している
ことが望ましい。平均孔径が3μm未満だと血球の目詰
まり、圧力損失の増大化、濾過の長時間化が懸念され、
平均孔径が50μmを超えると白血球の捕捉能が低下す
る恐れが生ずるためである。ここで、本発明における平
均孔径とは、容器に充填する前の多孔質体1枚の平均ポ
アサイズであり、コールターポロメーター2(コールタ
ー エレクトロニクス アンド リミテッド、米国)に
よって測定したMFP(Mean Flow Pore
Size)をいう。When a porous body having continuous pores is used as a filter material, it is desirable that the porous body has an average pore diameter of 3 to 50 μm. If the average pore size is less than 3 μm, clogging of blood cells, an increase in pressure loss, and a longer filtration time are concerned.
If the average pore size exceeds 50 μm, there is a possibility that the ability to capture leukocytes may be reduced. Here, the average pore diameter in the present invention is an average pore size of one porous body before filling in a container, and is an MFP (Mean Flow Pore) measured by a Coulter Porometer 2 (Coulter Electronics and Limited, USA).
Size).
【0026】また、疎水性フィルター材料に塩基性含窒
素官能基とポリエチレンオキサイド鎖を有するポリマー
をコーティングする場合は、適当な溶媒に該ポリマーを
溶解させた溶液にフィルター材料を浸した後、余分な溶
液をフィルター材料からしぼって除き、次いで熱風乾燥
させるなどの簡単な操作で実施できる。また、フィルタ
ー材料からポリマーが脱落するのを防ぐ目的で、コーテ
ィング後のフィルター材料に熱を加え、フィルター材料
とポリマーとの接着性を更に高めることもできる。ま
た、フィルター材料への上記塩基性含窒素官能基と繰り
返し単位が2〜15のポリエチレンオキサイド鎖を有す
る重合性単量体のグラフト重合は、フィルター材料を重
合性単量体の溶液に含浸後、放射線を照射し、水などの
適当な洗液で洗浄する簡単な方法で実施できる。When the hydrophobic filter material is coated with a polymer having a basic nitrogen-containing functional group and a polyethylene oxide chain, the filter material is immersed in a solution obtained by dissolving the polymer in a suitable solvent, A simple operation such as squeezing the solution from the filter material and then drying with hot air can be performed. Further, in order to prevent the polymer from falling off from the filter material, heat can be applied to the coated filter material to further enhance the adhesion between the filter material and the polymer. Further, the graft polymerization of the polymerizable monomer having a polyethylene oxide chain having a basic nitrogen-containing functional group and a repeating unit of 2 to 15 to the filter material, after impregnating the filter material with a solution of the polymerizable monomer, Irradiation can be performed by a simple method of irradiating and washing with an appropriate washing liquid such as water.
【0027】[0027]
【実施例】以下本発明をより詳細に記述するために実施
例によって説明する。なお、以下の例における白血球除
去率並びに血小板回収率はそれぞれ次式(1)及び
(2)によって求められる値である。 尚、濾過前の白血球濃度の測定はチュルク液にて10倍
に希釈した血液を光学顕微鏡で白血球数をカウントして
求め、濾過後の白血球濃度の測定はアクリジンオレンジ
液で1.1倍に希釈した検体を蛍光顕微鏡で漏出白血球
数をカウントして求めた。血小板濃度の測定は自動血球
カウンターで250,000倍に希釈した検体を測定し
て求めた。DESCRIPTION OF THE PREFERRED EMBODIMENTS The present invention will be described below in more detail with reference to embodiments. The leukocyte removal rate and platelet recovery rate in the following examples are values obtained by the following equations (1) and (2), respectively. The leukocyte concentration before filtration was determined by counting the number of leukocytes of the blood diluted 10-fold with the Turk's solution using an optical microscope, and the leukocyte concentration after filtration was diluted 1.1-fold with acridine orange solution. The number of the leaked white blood cells was counted for the specimen thus obtained using a fluorescence microscope. The platelet concentration was determined by measuring a sample diluted 250,000 times with an automatic blood cell counter.
【0028】[0028]
【実施例1】メトキシトリエチレングリコールメタクリ
レート(以下MTGMAと略す。ポリエチレンオキサイ
ド鎖の繰り返し単位=3)と2−ヒドロキシエチルメタ
クリレート(以下HEMAと略す)とジメチルアミノエ
チルメタクリレート(以下DMAMAと略す)のコポリ
マーを通常の溶液ラジカル重合によって合成した。重合
条件としては、HEMAとDMAMAとMTGMAのモ
ル分率を0.92、0.03、0.05とし、全量が1
モル/lになるように調節したエタノール溶液に、開始
剤として2.2´−アゾビス(2.4−ジメチルパレロ
ニトリル)(V−65)を1/200モル/1加え、5
5℃で8時間重合反応を行った。ポリマーの精製は反応
後の溶液を水に添加し、ポリマーを析出させることによ
って精製した。Example 1 Copolymer of methoxytriethylene glycol methacrylate (hereinafter abbreviated as MTGMA; repeating unit of polyethylene oxide chain = 3), 2-hydroxyethyl methacrylate (hereinafter abbreviated as HEMA), and dimethylaminoethyl methacrylate (hereinafter abbreviated as DMAMA) Was synthesized by conventional solution radical polymerization. The polymerization conditions were such that the molar fractions of HEMA, DMAMA and MTGMA were 0.92, 0.03 and 0.05, and the total amount was 1
To an ethanol solution adjusted to mol / l, 2.2′-azobis (2.4-dimethylpareronitrile) (V-65) as an initiator was added at 1/200 mol / 1, and 5
The polymerization reaction was performed at 5 ° C. for 8 hours. The polymer was purified by adding the solution after the reaction to water and precipitating the polymer.
【0029】平均繊維径が1.8μmの不織布10枚
(約0.1g)を有効濾過断面積が21.5×21.5
mmの血液の入口と出口を有する容器内に不織布の充填
密度が0.2g/cm3 になるように充填し、上記ポリ
マーの1%エタノール溶液をこの容器に空気が入らない
ように入れ、窒素を2l/minの流速で20分間流し
て余分なポリマー溶液を取り除いた。更に、40℃で1
5時間コーティング後の容器を真空乾燥させ、その後ポ
リマーと不織布との接着性をあげるために120℃で4
時間熱処理した。得られた白血球選択捕捉フィルターの
フィルター材料表面に含まれる塩基性窒素原子の含量は
0.31重量%であり、ポリエチレンオキサイド鎖の含
量は4.86重量%であった。Ten nonwoven fabrics (about 0.1 g) having an average fiber diameter of 1.8 μm were obtained by measuring the effective filtration area to 21.5 × 21.5.
mm in a container having an inlet and an outlet for blood, so that the packing density of the nonwoven fabric is 0.2 g / cm 3, and a 1% ethanol solution of the above polymer is charged into the container so that air does not enter. Was flowed at a flow rate of 2 l / min for 20 minutes to remove excess polymer solution. Furthermore, at 40 ° C., 1
The container after coating is vacuum dried for 5 hours, and then dried at 120 ° C. for 4 hours in order to improve the adhesion between the polymer and the nonwoven fabric.
Heat treated for hours. The content of basic nitrogen atoms contained in the filter material surface of the obtained leukocyte selective capture filter was 0.31% by weight, and the content of polyethylene oxide chains was 4.86% by weight.
【0030】上記白血球選択除去フィルターを血液回路
に組み込み、シリンジポンプを用いて0.79g/mi
nの一定流速で濃厚血小板液31.6gを処理した。濾
過前及び濾過後の血液の体積、白血球濃度、血小板濃度
を求め、式(1)及び式(2)により白血球除去率及び
血小板回収率を求めたところ、白血球除去率が94.0
%、血小板回収率が92.4%であった。The above-mentioned leukocyte selective removal filter was incorporated in a blood circuit, and 0.79 g / mi using a syringe pump.
31.6 g of concentrated platelet solution was treated at a constant flow rate of n. The blood volume, leukocyte concentration, and platelet concentration before and after filtration were determined, and the leukocyte removal rate and platelet recovery rate were determined by equations (1) and (2). The leukocyte removal rate was 94.0.
% And the platelet recovery rate was 92.4%.
【0031】[0031]
【実施例2】HEMA、DMAMA、MTGMAのモル
分率を0.85、0.10、0.05とする以外は実施
例1と同様な操作でポリマーを合成し、実施例1と同様
の不織布からなるフィルター素材に該ポリマーをコーテ
ィングして白血球選択捕捉フィルターを得、同様な血液
回路で濃厚血小板液を処理し、白血球除去率及び血小板
回収率を求めた。結果を表1に示す。Example 2 A polymer was synthesized in the same manner as in Example 1 except that the mole fractions of HEMA, DMAMA, and MTGMA were set to 0.85, 0.10, and 0.05, respectively. The filter material was coated with the polymer to obtain a leukocyte selective capture filter. The platelet concentrate was treated in the same blood circuit, and the leukocyte removal rate and platelet recovery rate were determined. Table 1 shows the results.
【0032】[0032]
【比較例1】コーティングポリマーとしてHEMAのみ
のホモポリマーを実施例1と同様な操作で合成し、実施
例1と同様の不織布からなるフィルター素材に該ポリマ
ーをコーティングして白血球選択捕捉フィルターを得、
同様な血液回路で濃厚血小板液を処理し、白血球除去率
及び血小板回収率を求めた。結果を表1に示す。Comparative Example 1 A homopolymer composed of only HEMA was synthesized as a coating polymer by the same operation as in Example 1, and the polymer was coated on a filter material made of a nonwoven fabric similar to that in Example 1 to obtain a leukocyte selective capture filter.
The concentrated platelet solution was processed in the same blood circuit, and the leukocyte removal rate and the platelet recovery rate were determined. Table 1 shows the results.
【0033】[0033]
【比較例2】MTGMAを含まず、HEMAとDMAM
Aのモル分率が0.97、0.03のコポリマーを合成
し、実施例1と同様の不織布からなるフィルター素材に
該ポリマーをコーティングして白血球捕捉用フィルター
を得、実施例1と同様な血液回路で濃厚血小板液を処理
し、白血球除去率及び血小板回収率を求めた。結果を表
1に示す。[Comparative Example 2] HEMA and DMM containing no MTGMA
A copolymer having a molar fraction of A of 0.97 and 0.03 was synthesized, and the polymer was coated on a filter material made of the same nonwoven fabric as in Example 1 to obtain a filter for capturing leukocytes. The concentrated platelet solution was processed in the blood circuit, and the leukocyte removal rate and the platelet recovery rate were determined. Table 1 shows the results.
【0034】[0034]
【比較例3】MTGMAを含まず、HEMAとDMAM
Aのモル分率が0.90、0.10のコポリマーを合成
し、実施例1と同様の不織布からなるフィルター素材に
該ポリマーをコーティングして白血球捕捉用フィルター
を得、実施例1と同様な血液回路で濃厚血小板液を処理
し、白血球除去率及び血小板回収率を求めた。結果を表
1に示す。[Comparative Example 3] HEMA and DDMA not containing MTGMA
A copolymer having a molar fraction of A of 0.90 and 0.10 was synthesized, and the polymer was coated on a filter material made of the same nonwoven fabric as in Example 1 to obtain a filter for capturing leukocytes. The concentrated platelet solution was processed in the blood circuit, and the leukocyte removal rate and the platelet recovery rate were determined. Table 1 shows the results.
【0035】[0035]
【比較例4】濾材になにもコーティングしていない不織
布を用いて、実施例1と同様の血液回路で濃厚血小板液
を処理し、白血球除去率及び血小板回収率を求めた。結
果を表1に示す。[Comparative Example 4] Using a non-woven fabric having no coating on the filter medium, the concentrated platelet solution was treated in the same blood circuit as in Example 1, and the leukocyte removal rate and the platelet recovery rate were determined. Table 1 shows the results.
【0036】[0036]
【実施例3】HEMAとDMAMAとポリエチレンオキ
サイド鎖の繰り返し単位数の異なるメトキシポリエチレ
ングリコールメタクリレート(以下MPGMAと略す)
の三元共重合体を不織布にコーティングし、濃厚血小板
液を処理し、白血球除去率及び血小板回収率を求めた。
MPGMAとしてはポリエチレンオキサイド鎖の繰り返
し単位数が3のものを用い、DMAMAのモル含量%は
10モル%、MPGMAのモル含量%は5モル%で一定
としたコポリマー(以下HDM−3と略す)の重合を上
記の実施例1、2及び比較例1〜4と同じ条件で行っ
た。フィルター材料としては平均繊維径が1.2μmの
不織布を用い、これを有効濾過断面積が30×30mm
の血液の入口と出口を有する容器内に不織布10枚(約
0.6g)の充填密度が0.15g/cm3 になるよう
に充填して白血球選択捕捉フィルターを得た。HDM−
3コポリマーを不織布へコーティングして白血球選択捕
捉フィルターを得た。該フィルターを組み込んだ血液回
路を用いて1.2m落差、5g/minの流速で濃厚血
小板液230gを処理したところ、白血球除去率が9
9.8%、血小板回収率が90.5%であった。結果を
表1に示す。Example 3 HEMA, DMAMA and methoxypolyethylene glycol methacrylate having different numbers of repeating units of polyethylene oxide chain (hereinafter abbreviated as MPGMA)
Was coated on a nonwoven fabric, and the concentrated platelet solution was treated to determine the leukocyte removal rate and the platelet recovery rate.
As the MPGMA, a copolymer having a polyethylene oxide chain having three repeating units was used, and the molar content of DMAMA was 10 mol% and the molar content of MPGMA was 5 mol%. The polymerization was carried out under the same conditions as in Examples 1 and 2 and Comparative Examples 1 to 4 described above. A non-woven fabric having an average fiber diameter of 1.2 μm was used as a filter material, and the effective filtration cross-sectional area was 30 × 30 mm.
Then, 10 nonwoven fabrics (about 0.6 g) were packed in a container having an inlet and an outlet for blood so that the packing density became 0.15 g / cm 3 to obtain a leukocyte selective capture filter. HDM-
The non-woven fabric was coated with the 3 copolymer to obtain a leukocyte selective capture filter. When 230 g of the concentrated platelet solution was treated at a flow rate of 1.2 m and a flow rate of 5 g / min using a blood circuit incorporating the filter, the leukocyte removal rate was 9%.
9.8% and the platelet recovery was 90.5%. Table 1 shows the results.
【0037】[0037]
【実施例4】MTGMAの繰り返し単位数が9である以
外は、実施例3と同様な操作でポリマー(以下HDM−
9と略す)を合成して、実施例3と同様の不織布フィル
ター材料をコーティングし、実施例3と同様な血液回路
を用いて濃厚血小板液を処理し、白血球除去率及び血小
板回収率を求めたところ、白血球除去率が98.0%、
血小板回収率が92.7%であった。結果を表1に示
す。Example 4 Except that the number of repeating units of MTGMA was 9, a polymer (hereinafter referred to as HDM-
9), coated with the same nonwoven fabric filter material as in Example 3, processed the concentrated platelet liquid using the same blood circuit as in Example 3, and determined the leukocyte removal rate and platelet recovery rate. However, the leukocyte removal rate is 98.0%,
The platelet recovery was 92.7%. Table 1 shows the results.
【0038】[0038]
【実施例5】繰り返し単位数が9のMPGMAとDMA
MAをモル含量で33%、67%含み、重合性単量体の
重量%が2.0重量%の水溶液(1000ml)中に平
均繊維径が1.2μmの不織布を浸漬し、窒素を通気し
て脱気した。この水溶液にγ線を3.6kGy(1.2
kGy/時間)照射してグラフト重合させた。不織布を
取り出し、水で充分に水洗し、40℃で15時間熱風乾
燥した後、更に2時間真空乾燥して、不織布を乾燥させ
たところ、グラフト率が12.8%であった。このよう
にして得たグラフト後の不織布を実施例3と同様な血液
回路を用いて濃厚血小板液を処理し、白血球除去率及び
血小板回収率を求めたところ、白血球除去率が98.4
%、血小板回収率が91.3%であった。尚、グラフト
率とは下式(3)に従って求めた値である。結果を表1
に示す。 Embodiment 5 MPGMA and DMA Having 9 Repeating Units
A nonwoven fabric having an average fiber diameter of 1.2 μm is immersed in an aqueous solution (1000 ml) containing MA in a molar content of 33% or 67% and a polymerizable monomer in a weight% of 2.0% by weight. And degassed. 3.6 gGy (1.2 gamma) was applied to this aqueous solution.
(kGy / h) irradiation for graft polymerization. The nonwoven fabric was taken out, sufficiently washed with water, dried with hot air at 40 ° C. for 15 hours, and further vacuum-dried for 2 hours to dry the nonwoven fabric. As a result, the graft ratio was 12.8%. The nonwoven fabric after grafting thus obtained was treated with a concentrated platelet liquid using the same blood circuit as in Example 3, and the leukocyte removal rate and platelet recovery rate were determined. The leukocyte removal rate was 98.4.
%, And the platelet recovery was 91.3%. The graft ratio is a value determined according to the following equation (3). Table 1 shows the results
Shown in
【0039】[0039]
【比較例5】MPGMAの繰り返し単位数が18である
以外は、実施例3と同様なポリマー(以下HDM−18
と略す)を合成し、実施例3と同様な血液回路を用いて
濃厚血小板を処理し、白血球除去率及び血小板回収率を
求めたところ、白血球除去率が87.2%、血小板回収
率が94.0%であった。結果を表1に示す。Comparative Example 5 A polymer similar to that of Example 3 except that the number of repeating units of MPGMA was 18 (hereinafter referred to as HDM-18).
The platelet was processed using the same blood circuit as in Example 3, and the leukocyte removal rate and the platelet recovery rate were determined. The leukocyte removal rate was 87.2% and the platelet recovery rate was 94. 0.0%. Table 1 shows the results.
【0040】[0040]
【比較例6】MPGMAの繰り返し単位数が30である
以外は、実施例3と同様なポリマー(以下HDM−30
と略す)を合成し、実施例3と同様な血液回路を用いて
濃厚血小板を処理し、白血球除去率及び血小板回収率を
求めたところ、白血球除去率が80.3%、血小板回収
率が96.4%であった。結果を表1に示す。Comparative Example 6 A polymer similar to that of Example 3 except that the number of repeating units of MPGMA was 30 (hereinafter HDM-30).
The platelet was processed using the same blood circuit as in Example 3, and the leukocyte removal rate and the platelet recovery rate were determined. The leukocyte removal rate was 80.3%, and the platelet recovery rate was 96. 0.4%. Table 1 shows the results.
【0041】[0041]
【比較例7】MPGMAの繰り返し単位数が30である
マクロマーのみを2.0重量%含む水溶液(1000m
l)中に平均繊維径が1.2μmの不織布を浸漬し、窒
素を通気して脱気した。この水溶液にγ線を3.6kG
y(1.2kGy/時間)照射してグラフト重合させ
た。不織布を取り出し、水で充分に水洗し、40℃で1
5時間熱風乾燥した後、更に2時間真空乾燥して、不織
布を乾燥させたところ、グラフト率が18%であった。
このようにして得たグラフト後の不織布を実施例3と同
様な血液回路を用いて濃厚血小板液を処理し、白血球除
去率及び血小板回収率を求めたところ、白血球除去率が
64.6%、血小板回収率が98.8%であった。結果
を表1に示す。Comparative Example 7 An aqueous solution containing only 2.0% by weight of a macromer having 30 repeating units of MPGMA (1000 m
A non-woven fabric having an average fiber diameter of 1.2 μm was immersed in l), and deaerated by passing nitrogen through. 3.6 kG of γ-ray was added to this aqueous solution.
Irradiation of y (1.2 kGy / hour) was performed to perform graft polymerization. Take out the non-woven fabric and wash it thoroughly with water.
After drying with hot air for 5 hours, vacuum drying was further performed for 2 hours, and the nonwoven fabric was dried. As a result, the graft ratio was 18%.
The nonwoven fabric after grafting thus obtained was treated with a concentrated platelet liquid using the same blood circuit as in Example 3, and the leukocyte removal rate and platelet recovery rate were determined. The leukocyte removal rate was 64.6%. The platelet recovery was 98.8%. Table 1 shows the results.
【0042】[0042]
【表1】 [Table 1]
【0043】[0043]
【発明の効果】本発明のフィルター材料を白血球除去用
フィルターに用いることにより、血小板の損失を少なく
抑えつつ白血球を効率良く除去できるので、血小板輸血
及び免疫異常疾患に対する白血球除去療法の分野におい
て有効な手段を提供するものである。By using the filter material of the present invention for a leukocyte removal filter, leukocytes can be efficiently removed while suppressing the loss of platelets, which is effective in the fields of platelet transfusion and leukocyte removal therapy for immunological disorders. It provides a means.
───────────────────────────────────────────────────── フロントページの続き (51)Int.Cl.7 識別記号 FI // B01D 39/00 A61M 5/16 334X (58)調査した分野(Int.Cl.7,DB名) A61K 35/14 A61M 1/02 A61M 1/34 A61M 5/165 B01D 15/00 B01D 39/00 BIOSIS(STN) CAPLUS(STN) MEDLINE(STN) EMBASE(STN)──────────────────────────────────────────────────の Continued on the front page (51) Int.Cl. 7 identification symbol FI // B01D 39/00 A61M 5/16 334X (58) Investigated field (Int.Cl. 7 , DB name) A61K 35/14 A61M 1/02 A61M 1/34 A61M 5/165 B01D 15/00 B01D 39/00 BIOSIS (STN) CAPLUS (STN) MEDLINE (STN) EMBASE (STN)
Claims (1)
部分からなる繊維または連続孔を有する高分子多孔質体
であって、該フィルター材料の少なくとも表面部分が塩
基性含窒素官能基及び繰り返し単位が2〜15のポリエ
チレンオキサイド鎖を含有することを特徴とする白血球
選択捕捉フィルター材料。1. A filter material comprising a fiber comprising a body portion and a surface portion or a polymer porous body having continuous pores, wherein at least the surface portion of the filter material has a basic nitrogen-containing functional group and a repeating unit of 2 to 2. 15. A leukocyte selective capture filter material comprising 15 polyethylene oxide chains.
Priority Applications (1)
Application Number | Priority Date | Filing Date | Title |
---|---|---|---|
JP02591892A JP3250833B2 (en) | 1992-01-17 | 1992-01-17 | Leukocyte selective capture filter material |
Applications Claiming Priority (1)
Application Number | Priority Date | Filing Date | Title |
---|---|---|---|
JP02591892A JP3250833B2 (en) | 1992-01-17 | 1992-01-17 | Leukocyte selective capture filter material |
Publications (2)
Publication Number | Publication Date |
---|---|
JPH05194243A JPH05194243A (en) | 1993-08-03 |
JP3250833B2 true JP3250833B2 (en) | 2002-01-28 |
Family
ID=12179163
Family Applications (1)
Application Number | Title | Priority Date | Filing Date |
---|---|---|---|
JP02591892A Expired - Fee Related JP3250833B2 (en) | 1992-01-17 | 1992-01-17 | Leukocyte selective capture filter material |
Country Status (1)
Country | Link |
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JP (1) | JP3250833B2 (en) |
Families Citing this family (9)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
US5647985A (en) * | 1994-10-17 | 1997-07-15 | Baxter International Inc. | Whole blood leukodepletion and platelet filter |
US6746482B2 (en) | 1994-10-17 | 2004-06-08 | Baxter International Inc. | Method for producing medical devices and devices so produced |
US5972217A (en) * | 1994-10-17 | 1999-10-26 | Baxter International Inc. | Blood cell separation devices having a membrane with particular coating |
US6045701A (en) * | 1994-10-17 | 2000-04-04 | Baxter International Inc. | Method of filtering a fluid suspension with a membrane having a particular coating |
US6306454B1 (en) | 1994-10-17 | 2001-10-23 | Baxter International Inc. | Method for producing improved medical devices and devices so produced |
US5728306A (en) * | 1994-12-23 | 1998-03-17 | Baxter International Inc. | Leukodepletion filter and method for filtering leukocytes from freshly drawn blood |
CA2464351A1 (en) * | 2001-10-16 | 2003-04-24 | Asahi Medical Co., Ltd. | Method for selectively removing virus and leukocytes, removing material and removing apparatus |
JP2005006704A (en) * | 2003-06-16 | 2005-01-13 | Chisso Corp | Biocompatible material and medical article using the same |
JP6080356B2 (en) * | 2009-03-30 | 2017-02-15 | テルモ株式会社 | Surface treatment agent, filter medium, and blood treatment filter |
-
1992
- 1992-01-17 JP JP02591892A patent/JP3250833B2/en not_active Expired - Fee Related
Also Published As
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JPH05194243A (en) | 1993-08-03 |
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