JP3270125B2 - Leukocyte trapping material - Google Patents

Leukocyte trapping material

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Publication number
JP3270125B2
JP3270125B2 JP20426592A JP20426592A JP3270125B2 JP 3270125 B2 JP3270125 B2 JP 3270125B2 JP 20426592 A JP20426592 A JP 20426592A JP 20426592 A JP20426592 A JP 20426592A JP 3270125 B2 JP3270125 B2 JP 3270125B2
Authority
JP
Japan
Prior art keywords
leukocyte
volume
blood
surface area
pore
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
Application number
JP20426592A
Other languages
Japanese (ja)
Other versions
JPH0624995A (en
Inventor
達也 福田
直邦 山脇
隆雄 西村
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.)
Asahi Kasei Medical Co Ltd
Original Assignee
Asahi Medical Co Ltd
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
Priority to JP20426592A priority Critical patent/JP3270125B2/en
Application filed by Asahi Medical Co Ltd filed Critical Asahi Medical Co Ltd
Priority to DE69231566T priority patent/DE69231566T2/en
Priority to AT92917988T priority patent/ATE197547T1/en
Priority to ES92917988T priority patent/ES2151492T3/en
Priority to PCT/JP1992/001064 priority patent/WO1993003740A1/en
Priority to EP92917988A priority patent/EP0554460B1/en
Publication of JPH0624995A publication Critical patent/JPH0624995A/en
Priority to US08/353,335 priority patent/US5478470A/en
Priority to US08/531,700 priority patent/US5665233A/en
Application granted granted Critical
Publication of JP3270125B2 publication Critical patent/JP3270125B2/en
Anticipated expiration legal-status Critical
Expired - Fee Related legal-status Critical Current

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Description

【発明の詳細な説明】DETAILED DESCRIPTION OF THE INVENTION

【0001】[0001]

【産業上の利用分野】本発明は、白血球浮遊液から白血
球を捕捉する白血球捕捉材に関する。より詳しくは、輸
血用の血液製剤、即ち全血、赤血球製剤、血小板製剤等
に混入している白血球を捕捉するための白血球捕捉材に
関する。
BACKGROUND OF THE INVENTION 1. Field of the Invention The present invention relates to a leukocyte capturing material for capturing leukocytes from a leukocyte suspension. More specifically, the present invention relates to a leukocyte capturing material for capturing leukocytes mixed in a blood product for transfusion, that is, whole blood, an erythrocyte product, a platelet product or the like.

【0002】[0002]

【従来の技術】近年、免疫学、輸血学の進歩に伴い、従
来の全血輸血から種々の疾患の治療に必要な成分のみを
輸血する成分輸血が行われる様になってきている。成分
輸血は輸血による患者への負荷を軽減し、かつ治療効果
が高まる優れた輸血療法であり、成分輸血に用いられて
いる各種の血液製剤、即ち、濃厚赤血球(CRC)、濃
厚血小板(PC)、乏血小板血漿(PPP)は献血によ
って得られた全血を遠心操作で分離して調整される。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、この混入白血球が原因
で輸血後副作用が誘発されることが明らかになってき
た。
2. Description of the Related Art In recent years, with the advancement of immunology and transfusion, component blood transfusion, which transfuses only components necessary for treatment of various diseases, from conventional whole blood blood transfusion has been performed. Component blood transfusion is an excellent blood transfusion therapy that reduces the burden on a patient due to blood transfusion and increases the therapeutic effect. Various blood products used for component blood transfusion, namely, rich red blood cells (CRC) and rich platelets (PC) Platelet-poor plasma (PPP) is prepared by separating whole blood obtained by donating blood by centrifugation. However, the blood product fractionated by centrifugation contains many leukocytes, and it has been revealed that this contaminated leukocyte causes post-transfusion side effects.

【0003】輸血後副作用としては、頭痛、吐き気、悪
寒、非溶血性発熱反応などの比較的軽微な副作用から、
免疫障害をもつ患者に対しては、輸血された白血球が受
血者の皮膚、内部器官に致死的影響を与える移植片対宿
主反応(GVH)の誘発や、サイトメガロウィルス感染
等の白血球中に存在するウィルスによる感染、アロ抗原
感作などの重篤な副作用が知られている。このような輸
血後副作用を防止するためには、血液製剤に混入してい
る白血球を捕捉、除去することが有効である。通常、全
血、赤血球製剤等の輸血に用いられる血液製剤中には1
7 個/mlの白血球が含まれている。頭痛、吐き気、
悪寒、発熱反応などの比較的軽微な副作用を防止するた
めには、1回の輸血で受血者に輸注される白血球数を1
億個程度以下に抑える必要があるとされており、このた
めには血液製剤中の白血球の残存率を10-1〜10-2
下になるまで除去する必要がある。またアロ抗原感作及
びウィルス感染を予防するためには、白血球残存率を1
-4〜10-5以下にまで除去することで予防しうると期
待されている。
[0003] Post-transfusion side effects include relatively minor side effects such as headache, nausea, chills, and non-hemolytic fever.
For patients with immune disorders, transfused leukocytes can induce graft-versus-host reactions (GVHs), which can have a lethal effect on the recipient's skin and internal organs, and can be found in leukocytes such as cytomegalovirus infections. Serious side effects such as infection by existing viruses and alloantigen sensitization are known. In order to prevent such side effects after blood transfusion, it is effective to capture and remove leukocytes mixed in blood products. Usually, blood products used for transfusion such as whole blood and erythrocyte products contain 1
It contains 0 7 cells / ml of white blood cells. Headache, nausea,
In order to prevent relatively minor side effects such as chills and fever reactions, the number of white blood cells transfused to the recipient in one transfusion should be 1
It is said that it is necessary to suppress the number of leukocytes to about 100 million or less. For this purpose, it is necessary to remove the residual ratio of leukocytes in the blood product to 10 -1 to 10 -2 or less. In order to prevent alloantigen sensitization and viral infection, the leukocyte residual rate should be 1%.
It is expected that it can be prevented by removing 0 -4 to 10 -5 or less.

【0004】血液製剤から白血球を除去する方法として
は、血液の比重差を利用した遠心分離方法と不織布など
の繊維状媒体や三次元網目状連続細孔を有する多孔質体
などの多孔質素子を白血球捕捉材としたフィルター法の
2種に大別されるが、白血球除去効率の良いこと、操作
の簡便なこと、コストの低いことの利点からフィルター
法が広く用いられている。
[0004] As a method for removing leukocytes from a blood product, a centrifugal separation method utilizing a specific gravity difference of blood and a fibrous medium such as a nonwoven fabric or a porous element such as a porous body having three-dimensional mesh-like continuous pores are used. The filter method is roughly classified into two types, a filter method using a leukocyte trapping material. The filter method is widely used because of its advantages of good leukocyte removal efficiency, easy operation, and low cost.

【0005】[0005]

【発明が解決しようとする課題】白血球捕捉フィルター
装置に充填される白血球捕捉材は、不織布などの繊維状
媒体や三次元網目状連続組織を有するスポンジ状構造物
が主として用いられている。白血球の除去機構は主とし
て粘着によると考えられているため、同じ素材で同様な
表面を有する白血球捕捉材の白血球除去能の差は、白血
球捕捉材と白血球の衝突頻度の大小により生ずるとされ
ている。そのため、白血球除去能を高めるには、白血球
が粘着すべき白血球捕捉材の表面積が大きい方が白血球
捕捉材と白血球との衝突頻度が増すため好ましく、一般
に細い繊維径を有する繊維状媒体は表面積が大きく、高
い白血球除去能を有することになる。そのため、不織布
を白血球捕捉材とする場合には、平均繊維径が1〜3μ
m程度の極細繊維が主として用いられている。しかしな
がら、このような極細繊維径を有する従来の不織布を用
いて、単位容積当たりの白血球除去能を高める為には、
不織布の充填密度を高めて実質的に捕捉材量を増量する
か、さらに、繊維径の細い不織布に切り替える必要があ
った。通常充填密度の上限は、0.4g/cm3 程度で
あり、これ以上高めると、不織布の反発力によって、容
器内に充填することが困難になるか、これを避けるため
に熱プレスなどを行えば、不織布がフィルム状につぶれ
てしまい、もはや捕捉材としての機能を果たさなくな
る。従って、白血球除去能を高めるための方法として
は、充填密度0.4g/cm3 以下の範囲内で白血球捕
捉材を増量するか、より繊維径の小さな白血球捕捉材を
用いなければならない。
As the leukocyte-trapping material to be filled in the leukocyte-trapping filter device, a fibrous medium such as a nonwoven fabric or a sponge-like structure having a three-dimensional network-like continuous structure is mainly used. Since the mechanism of removing leukocytes is considered to be mainly based on adhesion, the difference in the leukocyte removal ability of the leukocyte capturing material having the same material and a similar surface is considered to be caused by the magnitude of the frequency of collision between the leukocyte capturing material and leukocytes. . Therefore, in order to increase the leukocyte removal ability, it is preferable that the surface area of the leukocyte capturing material to which the leukocytes should adhere is large because the frequency of collision between the leukocyte capturing material and the leukocytes increases.In general, a fibrous medium having a small fiber diameter has a small surface area. It will have a large and high leukocyte removal ability. Therefore, when the nonwoven fabric is used as a leukocyte capturing material, the average fiber diameter is 1 to 3 μm.
Ultrafine fibers of about m are mainly used. However, in order to increase the leukocyte removal ability per unit volume using a conventional nonwoven fabric having such an ultrafine fiber diameter,
It was necessary to increase the packing density of the nonwoven fabric to substantially increase the amount of the trapping material, or to switch to a nonwoven fabric having a smaller fiber diameter. Normally, the upper limit of the packing density is about 0.4 g / cm 3. If the packing density is further increased, it becomes difficult to fill the container due to the repulsive force of the non-woven fabric. For example, the nonwoven fabric is crushed into a film, and no longer functions as a capturing material. Therefore, as a method for increasing the leukocyte removing ability, it is necessary to increase the amount of leukocyte-trapping material or to use a leukocyte-trapping material having a smaller fiber diameter within a packing density of 0.4 g / cm 3 or less.

【0006】しかしながら、これら何れの場合において
も、白血球除去能の向上にともなって、血液製剤を通過
させる際の圧力損失が増大してしまい、期待する血液量
を処理し終わる前に、処理速度が極端に低下するという
問題があった。
[0006] In any of these cases, however, the pressure loss at the time of passing the blood product increases with the improvement of the leukocyte removal ability, and the processing speed increases before the expected blood volume is processed. There was a problem of extremely lowering.

【0007】一方、スポンジ状構造物については、特開
平1−224324号に白血球による目詰まりの恐れの
ない白血球分離材として、バブルポイントが0.08〜
0.3kg/cm2 である多孔質体が開示されている。
しかしながら、本発明者等が検討した結果、該白血球分
離材は血液製剤中に混入している白血球を10-2〜10
-3に減ずるに適したものであり、本発明で目的とする白
血球残存率10-4を達成するに必要な、比較的小さな平
均孔径を有する多孔質体を用いる場合には、次のような
問題を有するものであった。即ち、多孔質体は至適な平
均孔径のものを用いれば不織布に比べ、数分の一の厚み
で同等の白血球除去能を示し、小型化を達成する上で有
力な手段を提供し得るものであるが、このような高い白
血球除去能を示すものは、同時に白血球の目詰まりによ
る圧力損失が高く、繊維径が細い不織布を用いるのと同
様に、血液の処理速度が著しく低下するという問題を有
していた。
On the other hand, as for a sponge-like structure, Japanese Unexamined Patent Publication (Kokai) No. 1-224324 discloses a white blood cell separating material which is not likely to be clogged with white blood cells and has a bubble point of 0.08 to 0.08.
A porous body of 0.3 kg / cm 2 is disclosed.
However, as a result of the study by the present inventors, the leukocyte separating material can reduce leukocytes mixed in blood products by 10 −2 to 10 −10.
-3 , which is suitable for reducing the leukocyte residual ratio of 10 -4 intended in the present invention, when using a porous body having a relatively small average pore size, the following: Had a problem. In other words, if the porous body has an optimum average pore diameter, compared to a nonwoven fabric, the porous body exhibits equivalent leukocyte removal ability at a fraction of the thickness, and can provide an effective means for achieving miniaturization. However, those exhibiting such high leukocyte removal ability have a high pressure loss due to white blood cell clogging at the same time, and similarly to the use of a non-woven fabric having a small fiber diameter, there is a problem that the blood processing speed is significantly reduced. Had.

【0008】本発明者等は、上記のような問題の残る従
来の白血球捕捉材について検討した結果、該白血球捕捉
材の細孔の孔径分布と白血球除去能との間に明らかな相
関のあることを見いだした。即ち、従来の白血球捕捉材
のうち、白血球除去能が低いものは、平均孔径が大き
く、かつ白血球捕捉にほとんど寄与しない大孔径の細孔
の割合が高いという構造的特徴を有し、また、目詰まり
を生じ易い多孔質素子は、平均孔径が小さく、かつ血球
成分が通過し得ない小孔径の細孔の割合が高いという構
造的特徴を有すものであった。
[0008] The present inventors have examined the conventional leukocyte-trapping material having the above-mentioned problems, and found that there is a clear correlation between the pore size distribution of the pores of the leukocyte-trapping material and the leukocyte-removing ability. Was found. That is, among the conventional leukocyte-trapping materials, those having a low leukocyte-removing ability have a large average pore diameter and a high percentage of large-pore diameter pores that hardly contribute to leukocyte trapping. The porous element which is liable to be clogged has a structural feature that the average pore diameter is small and the ratio of small pores through which blood cell components cannot pass is high.

【0009】本発明の目的は、孔径分布が従来の白血球
捕捉材と比較して、白血球捕捉に有効な細孔部分を多く
有し、白血球漏出のない、かつ血球による目詰まりの起
こりにくい新規な白血球捕捉材を提供すること、より詳
しくは、単位体積あたりの白血球捕捉能を高め、白血球
残存率が10-4以下と高い白血球捕捉能を有し、かつ該
白血球捕捉材を用いて血液を処理すると処理速度が減少
しない、即ち、血球による目詰まりや圧力損失の増加が
見られない新規な白血球捕捉材を提供することである。
[0009] An object of the present invention is to provide a novel material having a pore size distribution that has a large number of pores effective for trapping leukocytes as compared with a conventional leukocyte trapping material, does not cause leukocyte leakage, and is less likely to be clogged by blood cells. Providing a leukocyte-trapping material, more specifically, enhancing leukocyte-trapping capacity per unit volume, having a high leukocyte-trapping ability with a leukocyte residual rate of 10 -4 or less, and treating blood using the leukocyte-trapping material Accordingly, it is an object of the present invention to provide a novel leukocyte-trapping material in which the processing speed does not decrease, that is, clogging by blood cells and increase in pressure loss are not observed.

【0010】[0010]

【課題を解決するための手段】本発明は圧力損失を増大
させずにしかも単位体積当たりの白血球除去能を高めた
新規な白血球捕捉材を提供することを目的とする。より
詳しくは、全血、濃厚赤血球(CRC)、濃厚血小板
(PC)、乏血小板血漿(PPP)などの白血球浮遊液
から白血球を高い効率で捕捉除去する新規な白血球捕捉
材を提供することを目的とする。上記目的は、平均孔径
が1〜25μm、全細孔容積が0.40〜0.95ml
/ml(多孔質素子)、全細孔表面積が0.50〜5.
70m /mlの多孔質素子からなる白血球浮遊液か
ら白血球を捕捉するための白血球捕捉材であって、該多
孔質素子の1〜30μmの細孔部分の容積が全細孔容積
の90%以上、該多孔質素子の1〜30μmの細孔部分
の表面積が全細孔表面積の60%以上であることを特徴
とする白血球捕捉材を用いることによって達成される。
SUMMARY OF THE INVENTION It is an object of the present invention to provide a novel leukocyte-trapping material which does not increase pressure loss and has an improved ability to remove leukocytes per unit volume. More specifically, an object of the present invention is to provide a novel leukocyte-capturing material that captures and removes leukocytes from leukocyte suspensions such as whole blood, concentrated red blood cells (CRC), concentrated platelets (PC), and platelet poor plasma (PPP) with high efficiency. And The above purpose is for the average pore diameter of 1 to 25 μm and the total pore volume of 0.40 to 0.95 ml.
/ Ml (porous element), the total pore surface area is 0.50-5.
A leukocyte suspension consisting of a 70 m 2 / ml porous element
A leukocyte capturing material for capturing leukocytes,
The volume of the 1-30 μm pore portion of the porous element is 90% or more of the total pore volume, and the 1-30 μm pore portion of the porous element is
Characterized in that the surface area is at least 60% of the total pore surface area
This is achieved by using a leukocyte trapping material.

【0011】本発明における多孔質素子の平均孔径と
は、水銀ポロシメーター(島津製作所、ポアサイザ93
20または同等の装置)で測定した値であり、水銀が多
孔質素子の細孔に全く入ってない状態を水銀圧入量0
%、多孔質素子の全ての細孔に入っている状態を水銀圧
入量100%とした時、水銀圧入量50%に当たる点が
本発明でいう平均孔径である。従って、多孔質素子の平
均孔径よりも大きい直径を有する粒子は通過し難いとい
う径を表わすものであって、これ以上の直径の粒子は絶
対に通過しないというものではない。また、本発明にお
ける多孔質素子の全細孔容積とは、水銀ポロシメーター
で測定した細孔容積(cc/gまたはml/g)に多孔
質素子のかさ密度(g/cm3 またはg/ml)を乗じ
た値であり、実際に白血球捕捉に用いられる状態と同等
またはそれに近い状態で測定されるものである。
In the present invention, the average pore size of the porous element is defined as a mercury porosimeter (Shimadzu Corporation, Poisizer 93).
20 or an equivalent device), and the state where mercury does not enter into the pores of the porous element at all is 0 for mercury intrusion.
%, When a state where all the pores of the porous element are in the pores is defined as a mercury intrusion amount of 100%, a point corresponding to a mercury intrusion amount of 50% is the average pore diameter referred to in the present invention. Therefore, particles having a diameter larger than the average pore diameter of the porous element represent a diameter that is difficult to pass, and particles having a diameter larger than this do not mean that particles never pass. The total pore volume of the porous element in the present invention is defined as the pore volume (cc / g or ml / g) measured by a mercury porosimeter and the bulk density (g / cm 3 or g / ml) of the porous element. And is measured in a state equivalent to or close to a state actually used for capturing leukocytes.

【0012】本発明における多孔質素子とは、水銀ポロ
シメーターで測定しうる細孔を有するものである。但
し、非常に柔軟なためそのままでは水銀ポロシメーター
で測定する時に圧変形を受け、細孔が検出できないよう
な多孔質体であっても、細孔が圧変形されないように固
定化する等の予備調整を施すことにより上記測定が可能
となる多孔質体も本発明にいう多孔質素子に含まれる。
The porous element in the present invention has pores that can be measured with a mercury porosimeter. However, since it is very flexible, it undergoes pressure deformation when measured with a mercury porosimeter as it is, and even if it is a porous body where pores cannot be detected, pre-adjustment such as fixing the pores so that they are not pressure deformed The porous element referred to in the present invention also includes a porous body capable of performing the above measurement by performing the above.

【0013】本発明の白血球捕捉材に用いられる多孔質
素子の素材としては、血球にダメージを与えにくいもの
であれば特に限定はなく各種のものを用いることがで
き、有機高分子、無機高分子、金属等が挙げられる。そ
の中でも有機高分子は、切断等の加工性に優れるため好
ましい素材である。有機高分子としては、例えば、ポリ
ウレタン、ポリアクリロニトリル、ポリビニルアルコー
ル、ポリビニルアセタール、ポリエステル、ポリアミ
ド、ポリスチレン、ポリスルホン、セルロース、セルロ
ースアセテート、ポリエチレン、ポリプロピレン、ポリ
フッ化ビニル、ポリフッ化ビニリデン、ポリトリフルオ
ロクロロビニル、フッ化ビニリデン−テトラフルオロエ
チレン共重合体、ポリエーテルスルホン、ポリ(メタ)
アクリレート、ブタジエン−アクリロニトリルコポリマ
ー、ポリエーテル−ポリアミドブロツクコポリマー、エ
チレン−ビニルアルコールコポリマー等が挙げられる
が、本発明の多孔質素子の素材は上記例示に限定される
ものではない。
The material of the porous element used in the leukocyte capturing material of the present invention is not particularly limited as long as it does not easily damage blood cells, and various materials can be used. , Metals and the like. Among them, organic polymers are preferable materials because of their excellent workability such as cutting. As the organic polymer, for example, polyurethane, polyacrylonitrile, polyvinyl alcohol, polyvinyl acetal, polyester, polyamide, polystyrene, polysulfone, cellulose, cellulose acetate, polyethylene, polypropylene, polyvinyl fluoride, polyvinylidene fluoride, polytrifluorochlorovinyl, Vinylidene fluoride-tetrafluoroethylene copolymer, polyether sulfone, poly (meth)
Examples thereof include acrylate, butadiene-acrylonitrile copolymer, polyether-polyamide block copolymer, and ethylene-vinyl alcohol copolymer, but the material of the porous element of the present invention is not limited to the above examples.

【0014】本発明で用いる多孔質素子とは、血液を濾
過し得る細孔を有し、前述の孔径分布を有するものであ
れば特に限定はなく、何れの形態を有する物も含まれる
が、具体的には、天然繊維、ガラス繊維、織布、編布、
不織布等の繊維状媒体や多孔膜、三次元網目状連続組織
を有するスポンジ状構造物等が挙げられ、この中でも、
不織布やスポンジ状構造物は特に好ましいものである。
また、繊維状媒体を多孔質素子として用いる場合には、
平均繊維径が0.3〜3.0μm程度の不織布が特に好
ましいものである。
The porous element used in the present invention is not particularly limited as long as it has pores through which blood can be filtered and has the above-mentioned pore size distribution, and includes those having any form. Specifically, natural fiber, glass fiber, woven fabric, knitted fabric,
Fibrous media such as non-woven fabrics and porous membranes, sponge-like structures having a three-dimensional network continuous structure and the like, among them,
Nonwoven fabrics and spongy structures are particularly preferred.
When a fibrous medium is used as a porous element,
Nonwoven fabrics having an average fiber diameter of about 0.3 to 3.0 μm are particularly preferred.

【0015】更に、本発明の白血球捕捉材として用いる
多孔質素子は公知の方法で製造されるものでも良く、具
体的にメルトブロー法やフラッシュ紡糸等で製造した繊
維状媒体や必要に応じて通常の方法で製造された繊維に
プレス圧縮や熱収縮、適当な液体による処理等の2次加
工を施し、本発明で規定する孔径分布になるように制御
した物が好ましい。また、スポンジ状構造物の製造とし
ては常圧発泡法、加圧発泡法、押出発泡法、射出発泡法
等の発泡分解法、溶剤気散法、気体混入法、化学反応
法、溶出法、燒結法等が挙げられ、熱プレス圧縮、適当
な液体による膨潤等の2次加工を施し、本発明で規定す
る孔径分布になるように制御したものが好ましい。
Further, the porous element used as the leukocyte-trapping material of the present invention may be manufactured by a known method, and specifically, a fibrous medium manufactured by a melt blow method, flash spinning or the like, or a normal medium if necessary. The fibers produced by the method are preferably subjected to secondary processing such as press compression, heat shrinkage, treatment with an appropriate liquid, etc., and controlled to have a pore size distribution defined in the present invention. In addition, sponge-like structures include foaming decomposition methods such as normal pressure foaming, pressure foaming, extrusion foaming, and injection foaming, solvent diffusion, gas mixing, chemical reaction, elution, and sintering. A method in which secondary processing such as hot press compression and swelling with an appropriate liquid is performed to control the pore diameter distribution specified in the present invention is preferable.

【0016】本発明でいう白血球浮遊液とは、全血、濃
厚赤血球、洗浄赤血球、白血球除去赤血球、解凍赤血球
濃厚液、解凍赤血球浮遊液の赤血球製剤、乏血小板血
漿、多血小板血漿、新鮮凍結血漿、新鮮液状血漿、クリ
オプレシピテートの血漿製剤、濃厚血小板、バフィーコ
ート、バフィーコート除去血等である。
The leukocyte suspension in the present invention includes whole blood, concentrated erythrocytes, washed erythrocytes, leukocyte-removed erythrocytes, thawed erythrocyte concentrate, erythrocyte preparation of thawed erythrocyte suspension, platelet-poor plasma, platelet-rich plasma, and fresh frozen plasma. , Fresh liquid plasma, plasma preparation of cryoprecipitate, concentrated platelets, buffy coat, blood removed from buffy coat, and the like.

【0017】血液製剤に含まれている血球成分には赤血
球、血小板、及び顆粒球、単球、リンパ球を総称する白
血球があり、血小板は2〜4μm程度、赤血球は4〜9
μm程度、リンパ球は6〜12μm程度、顆粒球は10
〜15μm程度、単球は13〜20μm程度の粒子径を
有する。更に各血球成分は赤血球に代表されるような変
形能を多かれ少なかれ有しており、また、高分子材料に
対する粘着性は単球>顆粒球>血小板>リンパ球>赤血
球の順であると考えられている。
The blood cell components contained in blood products include red blood cells, platelets, and leukocytes, which are collectively referred to as granulocytes, monocytes, and lymphocytes. Platelets are about 2 to 4 μm, and red blood cells are 4 to 9
μm, lymphocytes about 6-12 μm, granulocytes about 10
Monocytes have a particle size of about 13-20 μm. Furthermore, each blood cell component has more or less deformability represented by red blood cells, and the adhesiveness to the polymer material is considered to be in the order of monocytes>granulocytes>platelets>lymphocytes> red blood cells. ing.

【0018】本発明者等はそのような各血球成分の粒子
径、粘着性に着目し、鋭意検討した結果、白血球捕捉に
有効な細孔孔径は1〜30μmであることを見いだし、
本発明の白血球捕捉材を開発するに至ったものである。
即ち、単球、顆粒球は比較的大きな粒子径を有し、かつ
粘着能が高いため、高分子材料との接触頻度が幾分少な
い孔径部分でも容易に除去することができ、30μm程
度の孔径までが該白血球の除去に有効であったこと、ま
た、リンパ球は単球、顆粒球に比較すると粒子径が小さ
く、かつ粘着能も低いため、リンパ球の除去は粘着によ
る機構以外に粒子径によるふるい分けも考慮する必要が
あり、そのため、リンパ球除去に有効な最小孔径はリン
パ球の変形を考慮すると、1μm程度の孔径までが有効
であることを見いだしたのである。
The present inventors have focused on such particle diameters and adhesiveness of each blood cell component, and as a result of intensive studies, have found that the pore diameter effective for capturing leukocytes is 1 to 30 μm.
This has led to the development of the leukocyte-trapping material of the present invention.
That is, since monocytes and granulocytes have relatively large particle diameters and have high adhesiveness, even pores having a frequency of contact with a polymer material which are somewhat less can be easily removed, and a pore diameter of about 30 μm is obtained. Was effective in removing the leukocytes, and lymphocytes have a smaller particle size than monocytes and granulocytes, and also have a lower adhesive ability. Therefore, it has been found that the minimum pore size effective for lymphocyte removal is effective up to about 1 μm in consideration of lymphocyte deformation.

【0019】したがって、血液製剤から白血球を効率よ
く捕捉除去するためには1〜30μmの細孔部分に注目
すべきであり、本発明の白血球捕捉材は平均孔径が1〜
25μmであり、かつ白血球捕捉に有効な1〜30μm
細孔の細孔容積の割合が高い点に特徴を有している。
Therefore, in order to efficiently capture and remove leukocytes from blood products, attention should be paid to the pore portion of 1 to 30 μm, and the leukocyte-trapping material of the present invention has an average pore diameter of 1 to 30 μm.
25 μm, and 1 to 30 μm effective for capturing leukocytes
The feature is that the ratio of the pore volume of the pores is high.

【0020】また、本発明の白血球捕捉材において、全
細孔表面積が0.50〜5.70m /mlであり、
このうち1〜30μmの細孔部分の表面積が全細孔表面
積の60%以上であることが好ましい表面積も細孔容
積と同様に白血球捕捉材を規定する重要な物性値であ
り、白血球捕捉に有効な1〜30μm細孔の表面積が大
きく、且つ割合が高い白血球捕捉材は優れた白血球捕捉
能を有するものである。
In the leukocyte-trapping material of the present invention, the total pore surface area is 0.50 to 5.70 m 2 / ml,
It is preferable that the surface area of the pore portion of 1 to 30 μm is 60% or more of the total pore surface area . The surface area is also an important physical property value that defines the leukocyte capturing material as well as the pore volume, and the surface area of the effective 1 to 30 μm pores for capturing leukocytes is large, and the leukocyte capturing material having a high ratio has excellent leukocyte capturing ability. Have

【0021】本発明に係わる上記のごとき構造を有する
白血球捕捉材において、全細孔容積が0.40〜0.9
5ml/ml(多孔質素子)であり、このうち1〜30
μmの細孔部分の容積が90%以上、30μmを超える
細孔部分の容積が6%以下であることが好ましい。より
望ましくは全細孔容積が0.50〜0.95ml/ml
(多孔質素子)、最も望ましくは0.60〜0.95m
l/ml(多孔質素子)であることが好ましく、このう
ち1〜30μmの細孔部分の容積が95%以上、最も好
ましくは98%以上であることがより好ましい。また、
30μmを超える細孔部分の容積は4%以下、最も好ま
しくは2%以下であることがより好ましい。全細孔容積
が0.40ml/ml(多孔質素子)未満であると血液
が通過するための細孔の空間容積が不足し、血球による
目詰まりが生じ、0.95ml/ml(多孔質素子)を
超えると多孔質素子の強度が低下し、もはや濾材として
の機能を果たさなくなるため不適である。また、1〜3
0μmの細孔部分の容積が90%未満であるような多孔
質素子は、白血球捕捉に有効な細孔量が低下し、白血球
漏出または目詰まりが起こるため不適であり、30μm
を超える細孔の部分細孔容積が6%を超えると白血球漏
出の危険性が高まり、効率よく白血球を捕捉できなくな
るため不適である。また、本発明の白血球捕捉材は全細
孔表面積が0.50〜5.70m /mlであり、こ
のうち1〜30μmの細孔部分の表面積が60%以上、
1μm未満の細孔部分の表面積が38%以下であること
が好ましい。望ましくは全細孔表面積が0.70〜5.
70m /ml、更に望ましくは0.80〜5.70
/ml、最も望ましくは0.90〜5.70m
mlであることが好ましく、このうち1〜30μmの細
孔部分の表積が65%以上最も望ましくは70%以上
であることがより好ましい。また、1μm未満の細孔部
分の表面積が30%以下、最も望ましくは28%以下で
あることがより好ましい。全細孔表面積が0.50m
/ml未満であると白血球が粘着する表面積が少ない
ため、白血球漏出が起こり、5.70m /mlを超
えると血液処理に要する時間が長くなったり、白血球の
みならず赤血球や血小板も捕捉除去され易くなり、目詰
まりによる圧力損失の増加が生ずるため不適である。ま
た、1〜30μmの細孔部分の表面積が60%未満であ
るような多孔質素子は白血球捕捉に有効な細孔の表面積
が低下し、白血球漏出または目詰まりが起こるため不適
であ る。また、1μm未満の細孔部分は血球が通過で
きない細孔であるため、1μm未満の細孔部分の表面積
が38%を超えると、濾過されずに多孔質素子の表面に
集積する血球が増加することになる。従って、白血球以
外の血球、即ち赤血球や血小板を回収する場合に、1μ
m未満の細孔部分の表面積が高ければ赤血球や血小板の
回収量が低下するため不適である。更に、本発明の白血
球捕捉材の平均孔径は1〜25μm、より望ましくは3
〜20μm、最も望ましくは5〜18μmであることが
好ましい。平均孔径は、多孔質素子の孔径分布を反映
し、平均孔径が1μm未満であると目詰まりが起こり、
25μmを超えると白血球漏出が顕著となるため不適で
ある。
In the leukocyte-trapping material having the above structure according to the present invention, the total pore volume is 0.40 to 0.9.
5 ml / ml (porous element), of which 1 to 30
It is preferable that the volume of the pore portion of μm is 90% or more, and the volume of the pore portion exceeding 30 μm is 6% or less. More preferably, the total pore volume is 0.50 to 0.95 ml / ml.
(Porous element), most preferably 0.60 to 0.95 m
1 / ml (porous element), and more preferably, the volume of the pore portion of 1 to 30 μm is 95% or more, most preferably 98% or more. Also,
More preferably, the volume of the pore portion exceeding 30 μm is 4% or less, most preferably 2% or less. If the total pore volume is less than 0.40 ml / ml (porous element), the space volume of the pores for blood to pass through becomes insufficient, clogging with blood cells occurs, and 0.95 ml / ml (porous element). When the value exceeds ()), the strength of the porous element is reduced, and the porous element no longer functions as a filter medium. Also, 1-3
A porous element in which the volume of the 0 μm pore portion is less than 90% is unsuitable because the amount of pores effective for capturing leukocytes is reduced and leukocyte leakage or clogging occurs.
If the partial pore volume of the pores exceeding 6% exceeds 6%, the risk of leukocyte leakage increases, and it becomes impossible to efficiently capture leukocytes, which is not suitable. The leukocyte-trapping material of the present invention has a total pore surface area of 0.50 to 5.70 m 2 / ml, of which the surface area of the 1 to 30 μm pore portion is 60% or more,
It is preferable that the surface area of the pore portion having a diameter of less than 1 μm is 38% or less. Desirably, the total pore surface area is 0.70-5.
70 m 2 / ml, more preferably 0.80 to 5.70
m 2 / ml, and most preferably 0.90~5.70m 2 /
It is preferably ml, and more preferably the front surface the product of the pore portions of these 1~30μm is most preferably 65% or more is 70% or more. Further, it is more preferable that the surface area of the pore portion of less than 1 μm is 30% or less, most preferably 28% or less. The total pore surface area is 0.50 m 2
If it is less than / ml, the surface area to which the leukocyte adheres is small, so that leukocyte leakage occurs. If it exceeds 5.70 m 2 / ml, the time required for blood treatment becomes longer, and not only leukocytes but also red blood cells and platelets are captured and removed. This is not suitable because the pressure loss increases due to clogging. In addition, a porous element having a pore area of 1 to 30 μm having a surface area of less than 60% is not suitable because the surface area of pores effective for capturing leukocytes is reduced and leukocyte leakage or clogging occurs. Further, since the pores of less than 1 μm are pores through which blood cells cannot pass, if the surface area of the pores of less than 1 μm exceeds 38%, blood cells which are not filtered and accumulate on the surface of the porous element increase. Will be. Therefore, when collecting blood cells other than white blood cells, that is, red blood cells and platelets, 1 μm
If the surface area of the pore portion smaller than m is large, the recovery amount of red blood cells and platelets decreases, which is not suitable. Further, the average pore size of the leukocyte capturing material of the present invention is 1 to 25 μm, more preferably 3 to 25 μm.
It is preferably from 20 to 20 μm, most preferably from 5 to 18 μm. The average pore size reflects the pore size distribution of the porous element, and if the average pore size is less than 1 μm, clogging occurs.
If it exceeds 25 μm, leakage of leukocytes becomes remarkable, which is not suitable.

【0022】なお、本発明における多孔質素子の表面積
は、水銀ポロシメーターで測定した表面積(m2 /g)
に多孔質素子のかさ密度(g/cm3 またはg/ml)
を乗じた値であり、実際に白血球捕捉に用いられる状態
と同等またはそれに近い状態で測定されるものである。
なお、水銀ポロシメーターでの上記物性値の測定は、1
〜2650psiaの圧力範囲で測定した値である。
Incidentally, the surface area of the porous element in the present invention is the surface area (m 2 / g) measured with a mercury porosimeter.
And the bulk density of the porous element (g / cm 3 or g / ml)
And is measured in a state equivalent to or close to a state actually used for capturing leukocytes.
The measurement of the above physical properties with a mercury porosimeter is 1
It is a value measured in a pressure range of 262650 psia.

【0023】また、本発明の白血球捕捉材に用いられる
多孔質素子の臨界湿潤表面張力(CWST)は、65d
yn/cm以上であることが好ましい。CWSTとは多
孔質素子の表面特性に関連し、多孔質素子のぬれ特性を
規定するのに使用される物性値である。即ち、液体を多
孔質素子の表面と接触させ、わずかに圧力を加えた場
合、多孔質素子への湿潤が起こるか否かを規定する表面
特性値であり、ある液体の表面張力より大きなCWST
値を有する多孔質素子は、その液体による湿潤が起こる
ことになる。本発明は血液製剤中に混入している白血球
を捕捉する捕捉材に関するものであり、実際、血液製剤
から白血球を捕捉するためには、血液と多孔質素子が接
触した時に、血液で多孔質素子が自然湿潤する条件が好
ましい。そのため、本発明で用いる多孔質素子の表面は
濾過する血液の表面張力と同等もしくはそれ以上のCW
ST値を有するものが好ましい。実際、血漿及び赤血球
の表面張力はそれぞれ73dyn/cm、64.5dy
n/cmと測定されている(血球及びタンパク質の表面
張力の測定、エイ.ダブル.ニューマン他、ニューヨー
クアカデミーオブサイエンス 1983年、276ペー
ジ)ため、65dyn/cm未満の表面を有する多孔質
素子ではかなりの圧力を負荷しなければ血液の濾過を行
うことができなくなるため不適である。また、CWST
値が65dyn/cm未満である多孔質素子であって
も、グラフト重合、コーティング、薬品処理、プラズマ
処理等の表面改質技術を用いて、多孔質素子の表面に親
水性のモノマーやポリマーを導入し、CWST値を65
dyn/cm以上に表面改質した場合も本発明でいう多
孔質素子に含まれるものである。
The critical wet surface tension (CWST) of the porous element used for the leukocyte capturing material of the present invention is 65 d.
It is preferably at least yn / cm. CWST is a physical property value related to the surface characteristics of the porous element and used to define the wetting characteristics of the porous element. That is, when the liquid is brought into contact with the surface of the porous element and a slight pressure is applied, it is a surface characteristic value that determines whether or not wetting of the porous element occurs.
A porous element having a value will be wetted by the liquid. The present invention relates to a capturing material that captures leukocytes mixed in a blood product, and in fact, in order to capture leukocytes from a blood product, when blood contacts the porous device, the porous device Are preferably wet. Therefore, the surface of the porous element used in the present invention has a CW equal to or higher than the surface tension of the blood to be filtered.
Those having an ST value are preferred. In fact, the surface tensions of plasma and red blood cells were 73 dyn / cm and 64.5 dy, respectively.
n / cm (measurement of surface tension of blood cells and proteins, A. Double Newman et al., New York Academy of Sciences, 1983, p. 276), so that a porous element having a surface of less than 65 dyn / cm is quite significant. If the pressure is not applied, the blood cannot be filtered, which is not suitable. Also, CWST
Even if the porous element has a value of less than 65 dyn / cm, a hydrophilic monomer or polymer is introduced to the surface of the porous element by using a surface modification technique such as graft polymerization, coating, chemical treatment, or plasma treatment. And the CWST value is 65
The case where the surface is modified to dyn / cm or more is also included in the porous element according to the present invention.

【0024】なお、本発明におけるCWSTとは、以下
の方法に従って求められる値をいう。即ち、2ないし4
dyn/cmづつ表面張力が変化するように水酸化ナト
リウム、塩化カルシウム、硝酸ナトリウム、酢酸及びエ
タノールの濃度の異なる水溶液を調整する。各水溶液の
表面張力(dyn/cm)は、水酸化ナトリウム水溶液
で94−115、塩化カルシウム水溶液で90−94、
硝酸ナトリウム水溶液で75−87、純粋な水で72.
4、酢酸水溶液で38−69、エタノール水溶液で22
−35のものが得られる(「化学便覧 基礎編II」改訂
2版、日本化学会編、丸善、1975年、164ペー
ジ)。このようにして得た表面張力が2ないし4dyn
/cm異なる水溶液を表面張力が低いものから順番に多
孔質素子上に10滴づつ乗せ10分間放置する。10分
間放置後、10滴中9滴以上が多孔質素子に吸収された
場合に湿潤した状態であると定義し、吸収が10滴中9
滴未満である場合に非湿潤状態であると定義する。この
ようにして多孔質素子上に表面張力が小さい液体から順
次測定していくと湿潤状態と非湿潤状態が出現する。こ
の時湿潤状態を観察した液体の表面張力の値と非湿潤状
態を観察した液体の表面張力の値の平均値をその多孔質
素子のCWST値と定義する。例えば、64dyn/c
mの表面張力を有する液体で湿潤し、66dyn/cm
の表面張力を有する液体で非湿潤であった場合、その多
孔質素子のCWST値は65dyn/cmとなる。
Note that the CWST in the present invention refers to a value obtained according to the following method. That is, 2 to 4
Aqueous solutions having different concentrations of sodium hydroxide, calcium chloride, sodium nitrate, acetic acid and ethanol are adjusted so that the surface tension changes by dyn / cm. The surface tension (dyn / cm) of each aqueous solution was 94-115 for an aqueous sodium hydroxide solution, 90-94 for an aqueous calcium chloride solution,
75-87 with aqueous sodium nitrate solution and 72. with pure water
4, 38-69 with acetic acid aqueous solution, 22 with ethanol aqueous solution
-35 is obtained ("Chemical Handbook Basic Edition II" 2nd revised edition, edited by The Chemical Society of Japan, Maruzen, 1975, p. 164). The surface tension thus obtained is 2 to 4 dyn
/ Cm different aqueous solutions are placed on the porous element by 10 drops in ascending order of surface tension and left for 10 minutes. After standing for 10 minutes, when 9 or more of the 10 drops were absorbed by the porous element, it was defined as a wet state, and the absorption was 9 out of 10 drops.
It is defined as non-wet when less than a drop. In this way, when the measurement is sequentially performed on the porous element from a liquid having a small surface tension, a wet state and a non-wet state appear. 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 the CWST value of the porous element. For example, 64 dyn / c
m, wet with a liquid having a surface tension of 66 dyn / cm
When the porous element is non-wet with a liquid having a surface tension of, the CWST value of the porous element is 65 dyn / cm.

【0025】更に、本発明の白血球捕捉材に用いられる
多孔質素子の表面はグラフト重合、コーティング、アル
カリ、酸等の薬品処理、プラズマ処理等で改質されてい
ることが好ましい。中でもグラフト重合やコーティング
は高分子材料表面を改質する手法として古くから知られ
ている技術であり、高分子表面のぬれ特性や電気的作用
等を任意のものとすることができる優れた表面改質技術
である。特に、生体細胞と高分子材料表面との界面反応
において、その高分子材料表面の化学的構造が大きく影
響すると考えられているため、白血球捕捉材の設計にお
いては白血球捕捉材の物理的構造のみでなく表面化学構
造にも注目すべきである。即ち白血球捕捉材に用いられ
る多孔質素子表面を好ましい構造に改質するための簡便
で優れた改質法の好ましい例としてグラフト重合やコー
ティングが挙げられるのである。
Further, the surface of the porous element used in the leukocyte-trapping material of the present invention is preferably modified by graft polymerization, coating, chemical treatment with an alkali or acid, plasma treatment, or the like. Among them, graft polymerization and coating are technologies that have long been known as techniques for modifying the surface of a polymer material, and have excellent surface modification that can make the wetting characteristics and electrical action of the polymer surface arbitrary. Quality technology. In particular, it is thought that the chemical structure of the surface of the polymer material greatly affects the interfacial reaction between the living cells and the surface of the polymer material, so the design of the leukocyte-trapping material requires only the physical structure of the leukocyte-trapping material. Also note the surface chemical structure. That is, preferred examples of a simple and excellent modification method for modifying the surface of the porous element used for the leukocyte-trapping material into a preferable structure include graft polymerization and coating.

【0026】白血球捕捉材に用いられる多孔質素子表面
の改質の目的は、第1に白血球がよく粘着する表面とす
ること、第2に血液濾過を円滑に行えるようにすること
である。このような目的のためには種々の化学種、即ち
ヒドロキシル基、ポリエチレンオイサイド鎖等の親水性
の官能基を有する化学種や荷電性の化学種の捕捉材表面
への導入が有効である。
The purpose of modifying the surface of the porous element used for the leukocyte-trapping material is firstly to provide a surface to which leukocytes adhere well, and secondly to to facilitate blood filtration. For such a purpose, it is effective to introduce various chemical species, that is, a chemical species having a hydrophilic functional group such as a hydroxyl group or a polyethylene oiside chain or a charged chemical species onto the surface of the capturing material.

【0027】更に、本発明の白血球捕捉材において、多
孔質素子の表面積あたり、塩基性官能基が10-6〜3m
eq/m2 、より望ましくは10-5〜1meq/m2
または酸性官能基が10-4〜5meq/m2 、より望ま
しくは5×10-3〜1meq/m2 の密度で含有されて
いることが好ましい。白血球の高分子材料に対する粘着
性は高分子材料の表面性状にも影響され、一般に白血球
に限らず血球細胞は負の荷電を細胞表面に有している。
そのため、白血球を捕捉、除去するためには正の荷電を
表面に有している高分子材料が一般に有効であることが
知られている(WO/05812号)。また、それとは
逆に負の荷電を有する表面も白血球捕捉に有効である。
本来負の荷電を有する細胞と、同じく負の荷電を有する
酸性官能基との間には静電的な反発力が働き、細胞の粘
着量は減少してもよさそうであるが、恐らくは細胞が負
の荷電を有する材料表面に粘着するよりも早く、血漿中
に含まれるある種のタンパク質が粘着し、このタンパク
質の仲介によって白血球の粘着が促進されるのではない
かと思われる。しかし、多孔質素子の表面積あたりの塩
基性官能基の密度が10-6meq/m2 未満である、ま
たは酸性官能基の密度が10-4meq/m2 未満である
と静電的な作用が不十分となりやすく、また多孔質素子
の表面積あたりの塩基性官能基の密度が3meq/m2
を超える、または酸性官能基の密度が5meq/m2
超えると白血球のみならず他の成分、即ち赤血球や血小
板にも影響をおよぼすようになり、溶血等の現象が起こ
る傾向にあるため不適である。また、グラフト重合、コ
ーティング、プラズマ処理等によって多孔質素子の表面
に官能基を導入する場合には、多孔質素子表面に導入さ
れたポリマーなどの量が過多で、多孔質素子の細孔を塞
ぎ、処理しようとする血液製剤の流れを著しく阻害する
恐れがあるため好ましくない。
Further, in the leukocyte-trapping material of the present invention, the basic functional group per surface area of the porous element is 10 -6 to 3 m.
eq / m 2 , more preferably 10 −5 to 1 meq / m 2 ,
Alternatively, it is preferable that the acidic functional group is contained at a density of 10 −4 to 5 meq / m 2 , more preferably 5 × 10 −3 to 1 meq / m 2 . The adhesion of leukocytes to a polymer material is also affected by the surface properties of the polymer material. Generally, not only leukocytes but also blood cells have a negative charge on the cell surface.
Therefore, it is known that a polymer material having a positive charge on its surface is generally effective for capturing and removing leukocytes (WO / 05812). Conversely, a surface having a negative charge is also effective for capturing leukocytes.
An electrostatic repulsion acts between cells that originally have a negative charge and acidic functional groups that also have a negative charge, and it is likely that the amount of cell adhesion may decrease, but perhaps the cells It is likely that certain proteins contained in plasma will adhere faster than they do to the surface of negatively charged materials, and that the mediation of this protein will promote the adhesion of leukocytes. However, if the density of the basic functional group per surface area of the porous element is less than 10 -6 meq / m 2 , or if the density of the acidic functional group is less than 10 -4 meq / m 2 , the electrostatic action is performed. Tends to be insufficient, and the density of the basic functional groups per surface area of the porous element is 3 meq / m 2.
If the density exceeds 5 meq / m 2 , it affects not only leukocytes but also other components, that is, erythrocytes and platelets, and phenomena such as hemolysis tend to occur. is there. In addition, when a functional group is introduced into the surface of the porous element by graft polymerization, coating, plasma treatment, or the like, the amount of the polymer or the like introduced on the surface of the porous element is excessive, and the pores of the porous element are blocked. However, it is not preferable because the flow of the blood product to be processed may be significantly impaired.

【0028】多孔質素子表面の塩基性官能基または酸性
官能基の密度は公知の測定技術、即ち赤外線吸収スペク
トル法、核磁気共鳴スペクトル法、元素分析法等で定量
することができるが、簡便な方法として滴定法や色素吸
着法等が挙げられる。また、塩基性官能基または酸性官
能基を表面に有さない多孔質素子であっても、そのよう
な多孔質素子の表面に塩基性官能基または酸性官能基を
有するモノマーやポリマーをグラフト重合またはコーテ
ィングで導入し、多孔質素子の表面積あたりの塩基性官
能基の密度を10-6〜3meq/m2 に、または酸性官
能基の密度を10-4〜5meq/m2 の範囲内になるよ
うに表面改質を施した多孔質素子も本発明でいう多孔質
素子に含まれるものである。
The density of a basic functional group or an acidic functional group on the surface of the porous element can be determined by a known measuring technique, that is, an infrared absorption spectrum method, a nuclear magnetic resonance spectrum method, an elemental analysis method or the like. Examples of the method include a titration method and a dye adsorption method. Further, even in a porous element having no basic functional group or acidic functional group on the surface, a monomer or polymer having a basic functional group or acidic functional group on the surface of such a porous element is graft-polymerized or Introduced by coating, the density of the basic functional group per surface area of the porous element is set to 10 -6 to 3 meq / m 2 , or the density of the acidic functional group is set to 10 -4 to 5 meq / m 2. The porous element obtained by performing a surface modification on is also included in the porous element referred to in the present invention.

【0029】本発明において塩基性官能基としては、第
一級アミノ基、第二級アミノ基、第三級アミノ基、四級
アンモニウム基、及びピリジル基、イミダゾイル基など
の含窒素芳香環基等が挙げられ、これらの官能基を有す
るモノマーとしては、アリルアミン、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)アクリレート、ジメチルアミノプロピル(メタ)ア
クリレート、3−ジメチルアミノ−2−ヒドロキシプロ
ピル(メタ)アクリレート等の(メタ)アクリル酸誘導
体、p−ジメチルアミノメチルスチレン、p−ジエチル
アミノエチルスチレン等のスチレン誘導体、2−ビニル
ピリジン、4−ビニルピリジン、4−ビニルイミダゾー
ル等の含窒素芳香族化合物のビニル誘導体、及び上記の
ビニル化合物をハロゲン化アルキル等によって四級アン
モニウム塩とした誘導体等を挙げることができるが、本
発明の塩基性官能基を有する化学種は、上記に例示した
化学種に限定されるものではない。
In the present invention, the basic functional group includes a primary amino group, a secondary amino group, a tertiary amino group, a quaternary ammonium group, and a nitrogen-containing aromatic ring group such as a pyridyl group and an imidazoyl group. And monomers having these functional groups include allylamine, dimethylaminoethyl (meth) acrylate, diethylaminoethyl (meth) acrylate, dimethylaminopropyl (meth) acrylate, and 3-dimethylamino-2-hydroxypropyl (meth). A) acrylate derivatives such as acrylates; styrene derivatives such as p-dimethylaminomethylstyrene and p-diethylaminoethylstyrene; and nitrogen-containing aromatic compounds such as 2-vinylpyridine, 4-vinylpyridine and 4-vinylimidazole. Vinyl derivative and the above vinyl compound Although the Gen alkyl, and the like derivatives comprising quaternary ammonium salts, chemical species having a basic functional group of the present invention is not limited to the species exemplified above.

【0030】また、本発明において酸性官能基としては
カルボキシル基、燐酸基、スルホン酸基、フェノール基
等が挙げられ、これらの官能基を有するモノマーとして
は、アクリル酸、メタアクリル酸、2−メタクリロイル
オキシエチルコハク酸、モノ(2−メタクリロイルオキ
シエチル)アシッドフォスフェート、2−スルホエチル
メタクリレート等のアクリル酸もしくはメタクリル酸の
誘導体や、p−スチレンスルホン酸ナトリウム等のスチ
レン誘導体、ビニルフェノール等のフェノール誘導体、
アリルスルホン酸ナトリウム等のアリル化合物等の各種
のビニルモノマー、アセチレン誘導体、トリオキサン誘
導体、等を挙げることができるが、本発明の酸性官能基
を有する化学種は、上記に例示した化学種に限定される
ものではない。
In the present invention, examples of the acidic functional group include a carboxyl group, a phosphoric acid group, a sulfonic acid group, and a phenol group. Examples of the monomer having these functional groups include acrylic acid, methacrylic acid, and 2-methacryloyl. Derivatives of acrylic acid or methacrylic acid such as oxyethyl succinic acid, mono (2-methacryloyloxyethyl) acid phosphate and 2-sulfoethyl methacrylate, styrene derivatives such as sodium p-styrenesulfonate, and phenol derivatives such as vinylphenol ,
Various vinyl monomers such as allyl compounds such as sodium allyl sulfonate, acetylene derivatives, trioxane derivatives, and the like can be mentioned, but the chemical species having an acidic functional group of the present invention are limited to the chemical species exemplified above. Not something.

【0031】また、本発明の白血球捕捉材の多孔質素子
として織布、編布、不織布等の繊維状媒体を用いる場
合、該繊維状媒体の平均繊維径は、0.3〜3.0μ
m、より望ましくは0.5〜2.5μmあることが好ま
しい。繊維状媒体を濾材とした白血球捕捉材において、
繊維径が3.0μmを超えると白血球捕捉能が減少する
ために不適である。また、平均繊維径が0.3μm未満
のものは、もはや安定して製造することが難しく、血液
の粘性抵抗も高くなり過ぎるために不適である。なお、
本発明における平均繊維径とは、以下の方法に従って求
められる値をいう。即ち、多孔質素子を構成する一枚ま
たは複数枚の繊維体から実質的に均一と認められる部分
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、繊維体の有効濾過断
面積部分を、1辺が0.5cmの正方形によって区分
し、その中から6ケ所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、必要ケ所の
区分を選べば良い。また初めにサンプリングした3区分
は、上流側の面について、また残りの3区分は下流側の
面について、その中央部分を拡大倍率2500倍で写真
に撮る。サンプリングした各区分について中央部分及び
その近傍の箇所の写真を撮っていき、その写真に撮られ
た繊維の合計本数が100本を超えるまで写真を撮る。
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。また、上流側と下流側とで明らかに平均繊維直径
が異なる場合には、もはやこれを単一な多孔質素子とは
認めない。ここで「明らかに平均繊維直径が異なる」と
は統計的に有意差が認められる場合をいう。この場合は
上流側と下流側とを異なる多孔質素子としてとらえ、両
者の境界面を見つけた後両者の平均繊維直径を測定し直
す。
When a fibrous medium such as a woven fabric, a knitted fabric, or a non-woven fabric is used as the porous element of the leukocyte capturing material of the present invention, the average fiber diameter of the fibrous medium is 0.3 to 3.0 μm.
m, more preferably 0.5 to 2.5 μm. In a leukocyte capturing material using a fibrous medium as a filter material,
If the fiber diameter exceeds 3.0 μm, it is not suitable because the leukocyte-capturing ability decreases. In addition, those having an average fiber diameter of less than 0.3 μm are no longer suitable for stable production and the viscosity resistance of blood is too high. In addition,
The average fiber diameter in the present invention refers to a value determined according to the following method. That is, a portion recognized as substantially uniform is sampled from one or a plurality of fibrous bodies constituting the porous element, and photographed using a scanning electron microscope or the like. At the time of sampling, the effective filtration sectional area of the fibrous body is divided by a square having a side of 0.5 cm, and six places 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 may be selected by a method such as using a random number table. The first three sections are taken on the upstream side, and the remaining three sections are taken on the downstream side, and the central part thereof is photographed at a magnification of 2500 times. For each of the sampled sections, take a photograph of the central portion and the vicinity thereof, and take photographs until the total number of fibers taken in the photograph exceeds 100.
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 the width cannot be measured due to the shadow of other fibers, or when multiple fibers are melted and become thick fibers, fibers with significantly different diameters are used. If these are mixed, etc., these data are deleted. Further, when the average fiber diameter is clearly different between the upstream side and the downstream side, this is no longer recognized as a single porous element. Here, "apparently different average fiber diameters" refers to the case where a statistically significant difference is recognized. In this case, the upstream side and the downstream side are regarded as different porous elements, and after finding the boundary between them, the average fiber diameter of both is measured again.

【0032】一般に、血液製剤とは全血(WB)、濃厚
赤血球(CRC)等の赤血球を多量に含んだ赤血球製剤
と多血小板血漿(PRP)、濃厚血小板(PC)等の血
小板を多量に含んだ血小板製剤に大別される。前述した
ように各血球成分は異なる粒子径及び粘着能を有し、血
液製剤によって血液粘性等も異なるものである。従っ
て、濾過しようとする血液製剤が異なれば、用いる白血
球捕捉材も物理構造的、化学構造的に多少異なるべきも
のであり、以下に赤血球製剤用の白血球捕捉材と血小板
製剤用の白血球捕捉材について述べる。
Generally, a blood product is a red blood cell product containing a large amount of red blood cells such as whole blood (WB) and concentrated red blood cells (CRC) and a large amount of platelets such as platelet-rich plasma (PRP) and concentrated platelets (PC). It is roughly divided into platelet preparations. As described above, each blood cell component has a different particle size and adhesive ability, and the blood viscosity and the like vary depending on the blood product. Therefore, if the blood product to be filtered is different, the leukocyte-trapping material to be used should be somewhat different in physical structure and chemical structure.Below, the leukocyte-trapping material for erythrocyte products and the leukocyte-trapping material for platelet products will be described below. State.

【0033】WBやCRCの赤血球製剤とは血球成分の
含量が約40〜70%の比較的血液粘性の高い製剤であ
り、混入している白血球も粘着能が高く、粒子径の大き
い顆粒球と単球が約60%を占め、粘着能が低く、粒子
径の小さいリンパ球が40%程度である。このような赤
血球製剤から赤血球は通過させ、かつ白血球は捕捉、除
去するための白血球捕捉材としては、平均孔径が3〜2
5μm、より望ましくは5〜20μm、全細孔容積が
0.40〜0.95ml/ml(多孔質素子)、このう
ち2〜30μmの細孔部分の容積が全細孔容積の85%
以上であり、より望ましくは90%以上、更に望ましく
は96%以上であることが好ましく、全表面積が0.5
0〜5.70m2 /ml、このうち2〜30μmの細孔
部分の表面積が全表面積の50%以上、より望ましくは
60%以上である多孔質素子が白血球捕捉材として好適
な物理的構造である。更に、赤血球製剤中の赤血球は変
形能が高いため、比較的小さい細孔部分でも変形しなが
ら通過することが可能であるが、2μm未満の細孔を通
過する時には、赤血球の通過抵抗に起因する圧力損失の
増加が懸念される。そのため、赤血球製剤から白血球を
捕捉する白血球捕捉材としては、2μm未満の細孔部分
の容積が8%以下、より望ましくは5%以下表面積が5
0%未満、より望ましくは40%未満である多孔質素子
が好適である。平均孔径が3μm未満であると、血球目
詰まりが生じ易くかつ赤血球の通過抵抗が高まるため、
圧力損失の増大が懸念され、25μmを超えると、白血
球漏出の危険性が高まるため不適である。また、2〜3
0μmの細孔部分の容積が85%未満または表面積が5
0%未満であると、目詰まりなく、かつ白血球残存率が
10-4以下になるような高効率で白血球を捕捉すること
が難しくなるため不適である。また、2μm未満の細孔
部分の容積が8%を超えるまたは表面積が50%以上で
あると、目詰まりや圧力損失の増加による血液処理速度
が低下し、かつ赤血球の通過率が減少するため不適であ
る。
Red blood cell preparations such as WB and CRC are preparations having a relatively high blood viscosity with a blood cell component content of about 40 to 70%, and mixed leukocytes have high adhesion and granulocytes having a large particle diameter. Monocytes occupy about 60%, and lymphocytes having low adhesiveness and small particle size are about 40%. As a leukocyte-capturing material for allowing red blood cells to pass therethrough and capturing and removing white blood cells from such a red blood cell preparation, the average pore size is 3 to 2
5 μm, more preferably 5 to 20 μm, the total pore volume is 0.40 to 0.95 ml / ml (porous element), and the volume of the pore portion of 2 to 30 μm is 85% of the total pore volume.
And more preferably 90% or more, and still more preferably 96% or more.
A porous element having a pore area of 0 to 5.70 m 2 / ml, of which 2 to 30 μm has a surface area of 50% or more, more preferably 60% or more of the total surface area, has a physical structure suitable as a leukocyte-trapping material. is there. Further, since the red blood cells in the red blood cell preparation have a high deformability, it is possible to pass while deforming even a relatively small pore portion, but when passing through a pore of less than 2 μm, it is caused by the passage resistance of the red blood cells. An increase in pressure loss is a concern. Therefore, as a leukocyte-capturing material for capturing leukocytes from an erythrocyte preparation, the volume of a pore portion having a pore size of less than 2 μm is 8% or less, more preferably 5% or less, and
Porous elements with less than 0%, more desirably less than 40% are preferred. When the average pore diameter is less than 3 μm, clogging of blood cells easily occurs and the resistance to passage of red blood cells increases,
There is a concern about an increase in pressure loss, and if it exceeds 25 μm, the risk of leukocyte leakage increases, which is not suitable. Also, 2-3
The volume of the pore portion of 0 μm is less than 85% or the surface area is 5%.
If it is less than 0%, it is not suitable because it is difficult to capture leukocytes with high efficiency without clogging and with a leukocyte residual rate of 10 −4 or less. Further, when the volume of the pore portion of less than 2 μm exceeds 8% or the surface area is 50% or more, the blood processing speed is reduced due to clogging and an increase in pressure loss, and the passage rate of red blood cells is reduced, which is not suitable. It is.

【0034】更に、赤血球製剤から白血球を捕捉する捕
捉材のCWST値は65〜90dyn/cm、多孔質素
子の表面に塩基性官能基を導入する場合には、多孔質素
子の表面積あたりの塩基性官能基の密度が10-4〜3m
eq/m2 、望ましくは10-3〜1meq/m2 、より
望ましくは10-2〜10-1meq/m2 である方が好ま
しく、多孔質素子の表面に酸性官能基を導入する場合に
は、多孔質素子の表面積あたりの酸性官能基の密度が5
×10-2〜5meq/m2 、望ましくは8×10-2〜1
meq/m2 、より望ましくは10-1〜5×10-1me
q/m2 であることが好ましい。通常の合成高分子材料
のCWST値は55dyn/cm以下のものがほとんど
であるため、血液の合成高分子材料への自然湿潤は起こ
りにくい。しかし、CWST値をグラフト重合やコーテ
ィング等で表面改質し、CWST値を65〜90dyn
/cmに増加させた多孔質素子や親水性の官能基を有す
る高分子材料から合成され、表面改質を施さなくともC
WST値が上記の範囲内に入る多孔質素子を用いると、
血液による多孔質素子への湿潤が容易になるため、血液
濾過速度の低下は目詰まりがないかぎり起こらないので
ある。また、多孔質素子表面への塩基性含窒素官能基ま
たは酸性官能基の導入は、白血球細胞と多孔質素子表面
での静電的相互作用により白血球の捕捉能が向上するた
め好ましい。
Further, the CWST value of the capturing material for capturing white blood cells from the red blood cell preparation is 65 to 90 dyn / cm, and when a basic functional group is introduced on the surface of the porous element, the basic property per surface area of the porous element is The density of the functional groups is 10 -4 to 3 m
eq / m 2 , desirably 10 −3 to 1 meq / m 2 , more desirably 10 −2 to 10 −1 meq / m 2. When an acidic functional group is introduced into the surface of the porous element, Means that the density of acidic functional groups per surface area of the porous element is 5
× 10 -2 to 5 meq / m 2 , preferably 8 × 10 -2 to 1
meq / m 2 , more preferably 10 −1 to 5 × 10 −1 me
It is preferably q / m 2 . Since most synthetic polymers have a CWST value of 55 dyn / cm or less, spontaneous wetting of blood onto the synthetic polymer does not easily occur. However, the CWST value is surface-modified by graft polymerization, coating, etc., and the CWST value is 65 to 90 dyn.
/ Cm and synthesized from a porous element and a polymer material having a hydrophilic functional group.
When a porous element having a WST value within the above range is used,
Since the blood is easily wetted by the porous element, the blood filtration rate does not decrease unless clogging occurs. It is preferable to introduce a basic nitrogen-containing functional group or an acidic functional group into the surface of the porous element because the leukocyte-capturing ability is improved by electrostatic interaction between the white blood cells and the surface of the porous element.

【0035】PRPやPCの血小板製剤は血球成分の含
量が低く、ほとんどが水であるため比較的血液粘性の低
い製剤であり、混入している白血球も粘着能が低く、粒
子径の小さいリンパ球が約90%を占めるという特徴が
ある。このような血小板製剤から血小板は通過させ、か
つ白血球は捕捉、除去するための白血球捕捉材として
は、平均孔径が1〜15μm、全細孔容積が0.40〜
0.95ml/ml(多孔質素子)、このうち1〜25
μmの細孔部分の容積が全細孔容積の85%以上より望
ましくは90%以上であることが好ましく、全表面積が
0.50〜5.70m2 /ml、このうち1〜25μm
の細孔部分の表面積が全表面積の58%以上、より望ま
しくは65%以上である多孔質素子が白血球捕捉材とし
て好適な物理的構造である。更に、血小板製剤中の白血
球は粘着能が低く粒子径の小さいリンパ球が大部分であ
るため、25μmを超える細孔は実質的にリンパ球捕捉
に有効ではなくなる。そのため、血小板製剤から白血球
を捕捉する白血球捕捉材としては、25μmを超える細
孔部分の容積が10%以下、より望ましくは5%以下、
表面積が4%以下、より望ましくは2%以下である多孔
質素子が好適である。平均孔径が1μm未満であると、
血球目詰まりが生じ易くかつ粘着能の高い血小板をも吸
着捕捉される恐れが高まり、15μmを超えると、粒子
径の小さいリンパ球漏出の危険性が高まるため不適であ
る。また、1〜25μmの細孔部分の容積が85%未満
または表面積が58%未満であると、目詰まりなく、か
つ白血球残存率が10-4以下になるような高効率で白血
球を捕捉することが難しくなるため不適である。更に、
血小板製剤から白血球を捕捉する捕捉材のCWST値は
85dyn/cm以上、より望ましくは95dyn/c
m以上、多孔質素子の表面に塩基性官能基を導入する場
合には、多孔質素子の表面積あたりの塩基性官能基の密
度が10-6〜10-1meq/m2 、望ましくは10-5
10-1meq/m2、より望ましくは10-4〜10-2
eq/m2 である方が好ましく、多孔質素子の表面に酸
性官能基を導入する場合には、多孔質素子の表面積あた
りの酸性官能基の密度が10-4〜1meq/m2 、望ま
しくは5×10-3〜5×10-1meq/m2 、より望ま
しくは5×10-3〜10-2meq/m2 であることが好
ましい。グラフト重合やコーティング等で多孔質素子の
表面を改質し、CWST値を85dyn/cm以上に増
加させた多孔質素子や親水性の官能基を有する高分子材
料から合成され、表面改質を施さなくともCWST値が
上記の範囲内に入る多孔質素子を用いて血小板製剤を処
理すると血液による多孔質素子への湿潤が容易になるば
かりか、血小板の粘着を抑制する効果も付与することが
できるため好適である。また、多孔質素子表面への塩基
性含窒素官能基または酸性官能基の導入は、白血球細胞
と多孔質素子表面での静電的相互作用により白血球の捕
捉能が向上するため好ましい。但し、多孔質素子の表面
積あたりの塩基性含窒素官能基の密度が10-6meq/
2 密度、または酸性官能基の密度が10-4meq/m
2 未満であると白血球捕捉が不十分になる恐れがあり、
また、塩基性含窒素官能基の密度が10-1meq/m2
を超える、または酸性官能基の密度が1meq/m2
超えると白血球のみならず血小板も除去されてしまうた
め不適である。
Platelet preparations such as PRP and PC have a low blood cell component content and are relatively low in blood viscosity because most of them are water, and mixed leukocytes have low adhesion and lymphocytes with a small particle size. Occupies about 90%. Platelets are passed from such a platelet preparation, and leukocytes are trapped, and as a leukocyte-trapping material for removal, the average pore diameter is 1 to 15 μm and the total pore volume is 0.40 to 0.40.
0.95 ml / ml (porous element), of which 1 to 25
It is preferable that the volume of the pore portion of μm is 85% or more, more preferably 90% or more of the total pore volume, and the total surface area is 0.50 to 5.70 m 2 / ml, of which 1 to 25 μm
A porous element in which the surface area of the pore portion is 58% or more, more preferably 65% or more of the total surface area is a physical structure suitable as a leukocyte capturing material. Furthermore, since leukocytes in platelet preparations are mostly lymphocytes with low adhesion and small particle diameter, pores larger than 25 μm are substantially ineffective for trapping lymphocytes. Therefore, as a leukocyte-capturing material for capturing leukocytes from a platelet preparation, the volume of the pore portion exceeding 25 μm is 10% or less, more preferably 5% or less,
A porous element having a surface area of 4% or less, more preferably 2% or less, is suitable. When the average pore diameter is less than 1 μm,
Blood cell clogging is likely to occur and platelets having high adhesiveness are also likely to be adsorbed and trapped. If the thickness exceeds 15 μm, the risk of leakage of lymphocytes having a small particle size increases, which is not suitable. Further, when the volume of the pore portion of 1 to 25 μm is less than 85% or the surface area is less than 58%, it is possible to capture leukocytes with high efficiency without clogging and having a leukocyte residual rate of 10 −4 or less. It is not suitable because it becomes difficult. Furthermore,
The CWST value of a capturing material for capturing leukocytes from a platelet preparation is 85 dyn / cm or more, more preferably 95 dyn / c.
m or more, when a basic functional group is introduced into the surface of the porous element, the density of the basic functional group per surface area of the porous element is 10 −6 to 10 −1 meq / m 2 , preferably 10 −. 5 to
10 -1 meq / m 2 , more preferably 10 -4 to 10 -2 m
eq / m 2 is preferable, and when an acidic functional group is introduced into the surface of the porous element, the density of the acidic functional group per surface area of the porous element is 10 −4 to 1 meq / m 2 , desirably. It is preferably from 5 × 10 −3 to 5 × 10 −1 meq / m 2 , more preferably from 5 × 10 −3 to 10 −2 meq / m 2 . The surface of the porous element is modified by graft polymerization, coating, etc., and is synthesized from a porous element having a CWST value of at least 85 dyn / cm or a polymer material having a hydrophilic functional group. When a platelet preparation is treated using a porous element having a CWST value within the above range, not only is it easy to wet the porous element with blood, but also an effect of suppressing platelet adhesion can be imparted. Therefore, it is suitable. It is preferable to introduce a basic nitrogen-containing functional group or an acidic functional group into the surface of the porous element because the leukocyte-capturing ability is improved by electrostatic interaction between the white blood cells and the surface of the porous element. However, the density of the basic nitrogen-containing functional group per surface area of the porous element is 10 −6 meq /.
m 2 density or density of acidic functional group is 10 −4 meq / m
If it is less than 2 , leukocyte capture may be insufficient,
Further, the density of the basic nitrogen-containing functional group is 10 -1 meq / m 2.
If the density exceeds 1, or the density of the acidic functional group exceeds 1 meq / m 2 , not only leukocytes but also platelets are removed, which is not suitable.

【0036】更に、本発明の白血球捕捉材を血液の入口
と出口を有する白血球捕捉フィルター装置内に充填する
場合には、該白血球捕捉材の上流側に血液製剤中に含ま
れるゲルや微小凝集物を捕捉するための繊維体またはス
ポンジ状構造物を積層することが好ましい。また、ゲル
や微小凝集物を捕捉するための捕捉材と本発明の白血球
捕捉材の間に、血液製剤中に混入している全白血球の6
0%以上を捕捉するような第1ステージの白血球捕捉材
として繊維体またはスポンジ状構造物を積層することが
好ましい。血液製剤には白血球、赤血球、血小板の血球
成分や血漿成分以外にゲル、微小凝集物(マイクロアグ
リゲート:MA)が含まれる場合が多々ある。ゲルは一
般に200μm以下の大きさ、MAは一般に50μm以
下の大きさであり、血液製剤の保存日数が長くなればな
るほどその数が増える傾向にある。このようなゲル、M
Aが多量に含まれている保存血から白血球を除去する場
合には、ゲル及びMAによる目詰まりを考慮する必要が
あり、上記の繊維体またはスポンジ状構造物を本発明の
白血球捕捉材の上流側に配置すると、ゲルやMAによる
目詰まりを効果的に防止し得る白血球捕捉フィルター装
置を提供することができる。用いるゲル用の捕捉材とし
ては平均繊維径が8〜45μm、好ましくは10〜32
μm、より好ましくは15〜28μmの繊維体や平均孔
径が20〜200μm、好ましくは25〜180μmの
スポンジ状構造物が好ましい例として挙げられる。また
MA捕捉材としては、3μm以上の平均繊維径、好まし
くは3〜10μmの平均繊維径を有する織布、編布、不
織布などの繊維体や平均孔径が10μm以上、好ましく
は10〜50μmの平均孔径を有するスポンジ状構造物
が挙げられる。
Further, when the leukocyte-trapping material of the present invention is filled in a leukocyte-trapping filter device having a blood inlet and an outlet, the gel or microaggregate contained in the blood product may be provided upstream of the leukocyte-trapping material. It is preferable to laminate a fibrous body or a sponge-like structure for trapping water. Further, between the capturing material for capturing the gel or the microaggregate and the leukocyte capturing material of the present invention, 6% of the total leukocytes mixed in the blood product is contained.
It is preferable to laminate a fibrous body or a sponge-like structure as a first stage leukocyte capturing material that captures 0% or more. Blood products often include gels and microaggregates (microaggregates: MA) in addition to blood cell components and plasma components of white blood cells, red blood cells, and platelets. Gels generally have a size of 200 μm or less, and MAs generally have a size of 50 μm or less, and the number tends to increase as the number of storage days of blood products increases. Such a gel, M
When removing leukocytes from stored blood containing a large amount of A, it is necessary to consider clogging with gel and MA, and the above fibrous body or sponge-like structure is placed upstream of the leukocyte trapping material of the present invention. When arranged on the side, it is possible to provide a leukocyte capturing filter device that can effectively prevent clogging by gel or MA. The average fiber diameter is 8 to 45 μm, and preferably 10 to 32 μm, as a capturing material for the gel to be used.
Preferred examples include a fibrous body having a thickness of 15 μm, more preferably 15 to 28 μm, and a sponge-like structure having an average pore diameter of 20 to 200 μm, preferably 25 to 180 μm. Further, as the MA capturing material, an average fiber diameter of 3 μm or more, preferably a fibrous body such as a woven fabric, a knitted fabric, or a nonwoven fabric having an average fiber diameter of 3 to 10 μm or an average pore diameter of 10 μm or more, preferably 10 to 50 μm A sponge-like structure having a pore diameter is exemplified.

【0037】更に、ゲル及びMA捕捉材と本発明の白血
球捕捉材の間に挿入する第1ステージの白血球捕捉材と
しては、平均繊維径が0.8〜3μmの織布、編布、不
織布などの繊維体や平均孔径が6〜30μmのスポンジ
状構造物が挙げられる。第1ステージの白血球捕捉材
は、全細孔容積及び全細孔表面積がそれぞれ0.20m
l/ml(多孔質素子)以上、0.25m2 /ml以上
であり、白血球捕捉に有効な1〜30μmの細孔部分の
容積及び表面積がそれぞれ35%以上、40%以上有す
ものであることが好ましい。また、ゲル捕捉用の繊維体
としてはニードル繊維構造体が好適である。ニードル繊
維構造体とは血液の流れ方向への繊維の配向性を高めた
構造体のことであり、血液の流れ方向に垂直な方向への
繊維配向性が高い、すなわち平面平行繊維構造体とは構
造が異なる物である。このニードル繊維構造体を有する
繊維体をゲル捕捉材として用いると、ゲルはニードル繊
維構造体の表面だけでなく内部までも侵入できるように
なる。そのためゲル捕捉材表面のみでゲルを捕捉する平
面平行繊維構造体よりも単位体積当たりのゲル捕捉能が
向上し、使用する捕捉材量を少なくすることができ、小
型でホールドアップ体積の小さいフィルター装置を提供
することが可能となる。ホールドアップ体積とはフィル
ター装置の内容積を指す。白血球除去操作終了後、フィ
ルター装置内に残留する血液は通常フィルター装置と共
に廃棄される。それゆえ、無駄に捨ててしまう血液の量
をできるだけ少なくするために、フィルター装置の小型
化は好ましい。なお、本発明における白血球捕捉フィル
ター装置内に充填する白血球捕捉材の有効濾過断面積は
1.0〜100cm2 、白血球捕捉材の厚みは0.05
〜100mmの範囲内にあることが好ましい。
Further, as the leukocyte-trapping material of the first stage inserted between the gel and MA trapping material and the leukocyte-trapping material of the present invention, woven cloth, knitted cloth, non-woven cloth, etc. having an average fiber diameter of 0.8 to 3 μm can be used. And a sponge-like structure having an average pore diameter of 6 to 30 μm. The leukocyte capture material of the first stage has a total pore volume and a total pore surface area of 0.20 m each.
1 / ml (porous element) or more, 0.25 m 2 / ml or more, and the volume and surface area of 1 to 30 μm pores effective for capturing leukocytes have a volume and surface area of 35% or more and 40% or more, respectively. Is preferred. Further, a needle fiber structure is preferable as the fiber body for gel capture. The needle fiber structure is a structure in which the orientation of the fiber in the blood flow direction is enhanced, and the fiber orientation in the direction perpendicular to the blood flow direction is high, that is, a plane parallel fiber structure. They have different structures. When the fibrous body having the needle fiber structure is used as a gel capturing material, the gel can penetrate not only into the surface of the needle fiber structure but also into the inside thereof. Therefore, the gel trapping capacity per unit volume is improved as compared with the plane parallel fiber structure that traps gel only on the surface of the gel trapping material, and the amount of trapping material to be used can be reduced, and the filter device is small and has a small hold-up volume. Can be provided. Hold-up volume refers to the internal volume of the filter device. After the leukocyte removal operation, the blood remaining in the filter device is usually discarded together with the filter device. Therefore, it is preferable to reduce the size of the filter device in order to minimize the amount of wasteful blood. The effective filtration cross-sectional area of the leukocyte-trapping material to be filled in the leukocyte-trapping filter device of the present invention is 1.0 to 100 cm 2 , and the thickness of the leukocyte-trapping material is 0.05.
It is preferably within the range of 〜100 mm.

【0038】本発明の白血球捕捉材の上流側に血液製剤
中に混入している全白血球の60%以上を捕捉する第1
ステージの白血球捕捉材、及びゲル、MAを捕捉し、ゲ
ルやMAによる目詰まりを防止する捕捉材を充填したフ
ィルター装置を用いると、ゲルやMAが多量に含まれて
いる保存血でも血液の処理速度が低下することなく、か
つ圧力損失が増加することなく白血球を高収率で捕捉、
除去することが可能となる。また、本発明で規定した物
性値を有する多孔質素子が充填されていればその他に如
何なるものが充填されていても本発明でいう白血球捕捉
フィルター装置に含まれるものである。本発明の白血球
捕捉材を白血球捕捉フィルター装置内に充填する場合
は、血液の最下流側に位置するよう充填することが好ま
しい。更に、本発明で規定した物性値を有する多孔質素
子は、厚み、素材、形態等によって限定されるものでは
ない。
The first method for capturing 60% or more of the total leukocytes mixed in the blood product on the upstream side of the leukocyte capturing material of the present invention.
Using a stage leukocyte-capturing material and a filter device filled with a capturing material that captures gel and MA and prevents clogging with gel and MA, enables processing of blood even from stored blood that contains a large amount of gel or MA Capture leukocytes in high yield without slowing down and without increasing pressure loss,
It can be removed. Further, if the porous element having the physical property values specified in the present invention is filled, any other filled element is included in the leukocyte capture filter device according to the present invention. When the leukocyte-trapping material of the present invention is filled in the leukocyte-trapping filter device, it is preferable to fill the leukocyte-trapping material so as to be located at the most downstream side of blood. Furthermore, the porous element having the physical properties specified in the present invention is not limited by thickness, material, form, and the like.

【0039】また、繊維体を本発明の白血球捕捉材やゲ
ル捕捉材及びMA捕捉材として使用する場合には、白血
球捕捉フィルター装置内に該捕捉材を充填される前にあ
らかじめ熱間圧縮がなされていることが好ましい。熱間
圧縮は、ホールドアップ体積の小さいフィルターの提供
を可能とするためである。熱間圧縮による予備成形は、
外部から熱を加えて圧縮したり、高周波等によって繊維
体内部から加熱し圧縮する方法が挙げられる。また、こ
こで言う熱間圧縮は本発明の白血球捕捉材、血液製剤中
に混入している全白血球の60%以上を捕捉する第1ス
テージの白血球捕捉材、ゲル捕捉材、MA捕捉材の各捕
捉材についてそれぞれ単独に行っても良いし、2つない
し全ての捕捉材について同時に行っても良い。以下実施
例に基づき本発明の白血球捕捉材について詳細に説明す
る。
When the fibrous body is used as the leukocyte-trapping material, the gel-trapping material and the MA-trapping material of the present invention, hot compression is performed before the leukocyte-trapping filter is filled with the trapping material. Is preferred. Hot compression is to enable the provision of a filter with a small hold-up volume. Preforming by hot compression
A method of compressing by applying heat from the outside or a method of heating and compressing from the inside of the fibrous body by high frequency or the like may be used. In addition, the hot compression referred to herein includes the leukocyte-trapping material of the present invention, the first-stage leukocyte-trapping material that captures 60% or more of the total leukocytes mixed in the blood product, the gel-trapping material, and the MA-trapping material. It may be performed independently for each of the capturing materials, or may be performed simultaneously for two or all of the capturing materials. Hereinafter, the leukocyte capturing material of the present invention will be described in detail based on examples.

【0040】[0040]

【実施例】【Example】

【実施例1】血液の入口と出口を有し、有効濾過断面積
が4.9cm×4.9cmの白血球捕捉フィルター装置
にポリエチレンテレフタレート(PET)からなり、あ
らかじめ熱間圧縮を施した、平均繊維径が1.8μmの
不織布を充填し、厚みを3.3mmとした。この白血球
捕捉材は平均孔径が9.2μmであり、全細孔容積が
0.85ml/ml(多孔質素子)、全細孔表面積が
0.95m2 /ml、1〜30μmの細孔部分の容積及
び表面積がそれぞれ98%、71%、2〜30μmの細
孔部分の容積及び表面積がそれぞれ94%、60%、3
0μmを超える細孔部分の容積が1%、1μm未満の細
孔部分の表面積が28%、2μm未満の細孔部分の容積
及び表面積がそれぞれ5%、39%の孔径分布を有する
ものを用いた。
Example 1 An average fiber made of polyethylene terephthalate (PET) in a leukocyte trapping filter device having an inlet and an outlet for blood and having an effective filtration area of 4.9 cm × 4.9 cm, which was previously subjected to hot compression. A non-woven fabric having a diameter of 1.8 μm was filled to a thickness of 3.3 mm. This leukocyte trapping material has an average pore diameter of 9.2 μm, a total pore volume of 0.85 ml / ml (porous element), a total pore surface area of 0.95 m 2 / ml, and a pore portion of 1 to 30 μm. The volume and the surface area of the pore portion having a volume and a surface area of 98%, 71%, and 2 to 30 μm are respectively 94%, 60%, and 3%.
The pores having a pore size distribution having a volume of pores exceeding 0 μm of 1%, a surface area of pores of less than 1 μm of 28%, and a volume and surface area of pores of less than 2 μm of 5% and 39%, respectively, were used. .

【0041】450mlの血液に63mlのCPDを加
えて調整した全血523mlから、採血後8時間以内に
遠心分離によって多血小板血漿243mlを除去して調
整し、4℃で15日間保存した赤血球製剤(ヘマトクリ
ット68%)を、25℃になるまで室温(26℃)に放
置した後、ゲル捕捉材として平均繊維径が20μmのニ
ードル繊維構造体、MA捕捉材として平均繊維径が3μ
mの不織布、第1ステージの白血球捕捉材として平均繊
維径が2.2μmの不織布を、有効濾過断面積が6.7
cm×6.7cmの容器に充填して作成したフィルター
で処理し、ゲル、MA及び90%の白血球を除去した後
の該赤血球製剤200mlを新しい血液バツグに移し、
上記の白血球捕捉フィルター装置で濾過した。
From 523 ml of whole blood prepared by adding 63 ml of CPD to 450 ml of blood, 243 ml of platelet-rich plasma was removed by centrifugation within 8 hours after blood collection, adjusted, and stored at 4 ° C. for 15 days. Hematocrit 68%) was allowed to stand at room temperature (26 ° C.) until it reached 25 ° C., and then a needle fiber structure having an average fiber diameter of 20 μm as a gel capturing material and an average fiber diameter of 3 μm as an MA capturing material.
m, a nonwoven fabric having an average fiber diameter of 2.2 μm as a leukocyte capturing material of the first stage, and an effective filtration cross-sectional area of 6.7.
200 ml of the erythrocyte preparation after removing the gel, MA and 90% of leukocytes by treating with a filter prepared by filling a container having a size of 6.7 cm and transferring to a new blood bag,
Filtration was performed using the above leukocyte capture filter device.

【0042】濾過を開始するに当たり、フィルター装置
を血液回路を介して赤血球製剤が入っている血液バッグ
に接続した後、血液バッグを手でつかんで加圧し、フィ
ルター装置内に血液を満たした。かくして血液がフィル
ター装置内に満たされた後、ペリスタポンプを用いて
4.5ml/分の一定流速で流し続け、濾過に伴う圧力
損失をデジタル式の圧力計で測定した。濾過の終了は、
血液バッグ内の血液がなくなった時点とし、フィルター
装置下流に血液回路を介して接続した回収バッグをフィ
ルター装置の血液出口の下流30〜40cmのところで
回路ごと切断し、回路及び回収バッグ内の赤血球製剤を
回収液とした。
To start filtration, the filter device was connected to a blood bag containing a red blood cell preparation via a blood circuit, and then the blood bag was grasped by hand and pressurized to fill the filter device with blood. After the blood was thus filled in the filter device, the blood was continuously flowed at a constant flow rate of 4.5 ml / min using a peristaltic pump, and the pressure loss caused by the filtration was measured with a digital pressure gauge. End of filtration
When the blood in the blood bag is exhausted, the collection bag connected to the downstream of the filter device via the blood circuit is cut at 30 to 40 cm downstream of the blood outlet of the filter device, and the red blood cell preparation in the circuit and the collection bag is cut. Was used as a recovered liquid.

【0043】濾過前の赤血球製剤(以下、濾過前液とい
う)及び回収液の体積、ヘマトクリット、白血球数を測
定し、赤血球回収率及び白血球残存率を求めた。 赤血球回収率={回収液体積×ヘマトクリット(回収
液)}/{濾過前液体積×ヘマトクリット(濾過前
液)} 白血球残存率={白血球数(回収液)}/{濾過前液体
積×白血球濃度(濾過前液)} なお、濾過前液及び回収液の体積は、各々の重量を比重
1.075で割った値とした。また、白血球濃度の測定
は次の方法で行った。濾過前液の白血球濃度の測定:チ
ュルク液によって、10倍希釈した濾過前液をバーカー
チュルク型の血球計算板に注入し、光学顕微鏡を用いて
大区画4区画中に存在する白血球をカウントし、この値
をnpre とした。 白血球濃度(濾過前)=npre ×0.25×105 個/
ml
The volume, hematocrit, and white blood cell count of the red blood cell preparation before filtration (hereinafter, referred to as a pre-filtration liquid) and the recovered liquid were measured, and the red blood cell recovery rate and the white blood cell residual rate were determined. Erythrocyte recovery rate = {recovery liquid volume x hematocrit (recovery liquid)} / {liquid volume before filtration x hematocrit (pre-filtration liquid)} Leukocyte residual rate = {white blood cell count (recovery liquid)} / {volume of liquid before filtration x leukocyte concentration (Pre-filtration liquid) 体積 The volumes of the pre-filtration liquid and the recovered liquid were each obtained by dividing each weight by a specific gravity of 1.075. The measurement of leukocyte concentration was performed by the following method. Measurement of leukocyte concentration of pre-filtration solution: A 10-fold diluted pre-filtration solution was injected into a Barker-Turk type hemocytometer using a Turck solution, and the number of leukocytes present in four large compartments was counted using an optical microscope. This value was set to n pre . Leukocyte concentration (before filtration) = npre x 0.25 x 10 5 cells /
ml

【0044】また、回収液の白血球数の測定は、以下に
記す、極めて高感度の方法によった。回収液の入ったバ
ッグ内に5%フィコール400DLのEBSS溶液(以
下フィコール液という)を回収液と同容量を振とう混和
しながら加え、血漿分離スタンド上で回収バッグを固定
し、40分間静置した。静置後、沈降している赤血球層
を乱さぬように、静かに上澄を回収した後、再びフィコ
ールを前回と同容量回収液バッグに加え、同様の操作を
繰り返した。2回の操作により回収された上澄をコーニ
ング25350遠心チューブ4本に分注し、840×
g、15分遠心し、沈査を吸い上げぬように注意しなが
ら、上澄をアスピレーターで廃棄した。各遠心チューブ
に200mlの溶血液(1.145%しゅう酸アンモニ
ウム生理食塩液)を加えて振とう混和し、ただちに46
8×g、10分間遠心し、前述と同様の注意を払いなが
ら、上澄をアスピレーターで廃棄した。
The measurement of the leukocyte count of the recovered solution was carried out by the following method with extremely high sensitivity. A 5% Ficoll 400DL EBSS solution (hereinafter referred to as Ficoll solution) is added to the bag containing the recovered solution while shaking and mixing with the same volume as the recovered solution, and the recovery bag is fixed on the plasma separation stand and left for 40 minutes. did. After standing, the supernatant was gently collected so as not to disturb the sedimented erythrocyte layer, and then Ficoll was again added to the same volume of the collection liquid bag as before, and the same operation was repeated. The supernatant collected by the two operations was dispensed into four Corning 25350 centrifuge tubes, and 840 ×
g, and centrifuged for 15 minutes. The supernatant was discarded with an aspirator, taking care not to suck up the sediment. Add 200 ml of hemolyzed blood (1.145% ammonium oxalate saline) to each centrifuge tube, mix by shaking, and immediately add 46 ml.
After centrifugation at 8 × g for 10 minutes, the supernatant was discarded with an aspirator while paying the same attention as described above.

【0045】4本分の沈査を15mlの遠心チューブに
集め、溶血液を加えて全量を15mlとした後、10分
間室温に静置し、468×g、10分間遠心し、沈査を
含む0.5mlを残し、上澄を慎重に廃棄した。沈査を
含む液を十分に攪拌して単一細胞浮遊液とした後、蛍光
染色液(69.9mg/1アクリジンオレンジ液)50
μlを加え、更に攪拌した。この液を、改良型ノイパウ
エル式血球計算板6枚に注入し、落射式蛍光顕微鏡を用
いて大区画108区画中に存在する白血球をカウントし
た。このカウント値npostから次式によって、白血球数
(回収液)を算出した。 白血球数(回収液)=post×(1/108)×104
×0.55×(1/0.55)
The four sediments were collected in a 15 ml centrifuge tube, and the total volume was made up to 15 ml by adding hemolyzed blood. The mixture was allowed to stand at room temperature for 10 minutes, centrifuged at 468 × g for 10 minutes, and the sediment was added. The supernatant was carefully discarded, leaving 5 ml. The solution containing the sediment was sufficiently stirred to obtain a single cell suspension, and then a fluorescent staining solution (69.9 mg / 1 acridine orange solution) 50
μl was added and further stirred. This solution was injected into six improved Neu Powell-type hemocytometers, and the white blood cells present in the 108 large sections were counted using an epifluorescence microscope. The white blood cell count (recovery liquid) was calculated from the count value n post by the following equation. White blood cell count (recovery solution) = n post x (1/108) x 10 4
× 0.55 × (1 / 0.55)

【0046】下線部が回収液からフィコール液を用いて
最終的に0.55mlまで濃縮した液(以下濃縮液とい
う)中の白血球濃度(個/ml)であり、これに濃縮液
の体積0.55mlを乗じて白血球数を算出する。更に
0.55で割るのは、フィコール液を用いて白血球を回
収する際の回収率が55%であるためである。以上の結
果、赤血球回収率は95%、白血球残存率は10-4.2
濾過終了時の圧力損失は103mmHgであった。
The underlined part indicates the leukocyte concentration (cells / ml) in a liquid (hereinafter, referred to as a concentrated liquid) which was finally concentrated to 0.55 ml from the recovered liquid using Ficoll liquid, and the volume of the concentrated liquid was 0.1%. Multiply by 55 ml to calculate the white blood cell count. The reason for further dividing by 0.55 is that the recovery rate when recovering leukocytes using Ficoll solution is 55%. As a result, the red blood cell recovery rate was 95%, the leukocyte residual rate was 10 −4.2 ,
The pressure loss at the end of the filtration was 103 mmHg.

【0047】[0047]

【比較例1】血液の入口と出口を有し、有効濾過断面積
が4.9cm×4.9cmの白血球捕捉フィルター装置
にポリエチレンテレフタレート(PET)からなり、あ
らかじめ熱間圧縮を施した、平均繊維径が1.8μmの
不織布を充填し、厚みを3.3mmとした。この白血球
捕捉材は平均孔径が14.2μmであり、全細孔容積が
0.72ml/ml(多孔質素子)、全細孔表面積が
0.56m2 /ml、1〜30μmの細孔部分の容積及
び表面積がそれぞれ78%、56%、2〜30μmの細
孔部分の容積及び表面積がそれぞれ74%、34%、3
0μmを超える細孔部分の容積が16%、1μm未満の
細孔部分の表面積が42%、2μm未満の細孔部分の容
積及び表面積がそれぞれ10%、57%の孔径分布を有
するものを用いた。実施例1と同様な条件下で実験を行
ったところ、赤血球回収率は91%、白血球残存率は1
-2.2、濾過終了時の圧力損失は118mmHgであっ
た。
[Comparative Example 1] An average fiber made of polyethylene terephthalate (PET) in a leukocyte trapping filter device having an inlet and an outlet for blood and having an effective filtration area of 4.9 cm x 4.9 cm, which was previously subjected to hot compression. A non-woven fabric having a diameter of 1.8 μm was filled to a thickness of 3.3 mm. This leukocyte capturing material has an average pore diameter of 14.2 μm, a total pore volume of 0.72 ml / ml (porous element), a total pore surface area of 0.56 m 2 / ml, and a pore portion of 1 to 30 μm. The volume and the surface area of the pore portion having a volume and a surface area of 78%, 56%, and 2 to 30 μm are respectively 74%, 34%, and 3%.
The pores having a pore size distribution of 16% having a pore size exceeding 0 μm, a surface area of a pore portion having a pore size of less than 1 μm being 42%, a volume and a surface area of a pore portion having a pore size of less than 2 μm being 10% and 57%, respectively were used. . When an experiment was performed under the same conditions as in Example 1, the erythrocyte recovery rate was 91% and the leukocyte residual rate was 1
0 -2.2 , the pressure loss at the end of the filtration was 118 mmHg.

【0048】[0048]

【実施例2】血液の入口と出口を有し、有効濾過断面積
が6.7cm×6.7cmの白血球捕捉フィルター装置
に血液上流側から下流側に向かって、ゲル捕捉材、MA
捕捉材、第1ステージの白血球捕捉材、本発明の白血球
捕捉材を充填し、厚みを5mmとした。ゲル捕捉材、M
A捕捉材、第1ステージの白血球捕捉材、白血球捕捉材
は実施例1と同様のものを用いた。また、ゲル捕捉材、
MA捕捉材、第1ステージの白血球捕捉材、本発明の白
血球捕捉材はあらかじめ熱間圧縮を施したものを用い
た。このようにして作製した、白血球捕捉フィルター装
置にヒドロキシエチルメタクリレート(HEMA)とジ
メチルアミノエチルメタクリレート(DM)からなるポ
リマー(ポリマー中のDM含量は30モル%)の0.5
%エタノール溶液を通液することによりコーティング
し、その後、窒素ガスを通気し、更に1mmHg以下の
真空下、40℃で24時間乾燥した。乾燥後の白血球捕
捉材のCWST値及び塩基性官能基の密度を測定したと
ころ、CWST値が80dyn/cm、塩基性官能基の
密度が4.8×10-3meq/m2 であった。450m
lの血液に63mlのCPDを加えて調整した全血52
3mlから、採血後8時間以内に遠心分離によって多血
小板血漿243mlを除去した調整し、4℃で3日間保
存した後、生理食塩水を加えて352mlとした赤血球
製剤(ヘマトクリット55%)を、25℃になるまで室
温(26℃)に放置した後、上記のフィルター装置を組
み込んだ血液回路を用いて濾過した。処理流速はペリス
タポンプで10ml/分の一定流速に調整し、濾過に伴
う圧力損失をデジタル式の圧力計で測定した。以上の結
果、赤血球回収率は92%、白血球残存率は10-5.2
濾過終了時の圧力損失は132mmHgであった。
EXAMPLE 2 A leukocyte-capturing filter device having an inlet and an outlet for blood and having an effective filtration cross-sectional area of 6.7 cm × 6.7 cm was applied to a gel capturing material, MA from upstream to downstream of blood.
The trapping material, the leukocyte trapping material of the first stage, and the leukocyte trapping material of the present invention were filled to have a thickness of 5 mm. Gel trapping material, M
The A capturing material, the first stage leukocyte capturing material, and the leukocyte capturing material used were the same as those in Example 1. Also, a gel capturing material,
As the MA capturing material, the first stage leukocyte capturing material, and the leukocyte capturing material of the present invention, those subjected to hot compression in advance were used. The thus prepared leukocyte-capturing filter device contains 0.5% of a polymer composed of hydroxyethyl methacrylate (HEMA) and dimethylaminoethyl methacrylate (DM) (DM content in the polymer is 30 mol%).
% Ethanol solution, and then dried under a vacuum of 1 mmHg or less at 40 ° C. for 24 hours. When the CWST value and the density of the basic functional group of the dried leukocyte capturing material were measured, the CWST value was 80 dyn / cm, and the density of the basic functional group was 4.8 × 10 −3 meq / m 2 . 450m
52 whole blood prepared by adding 63 ml of CPD to 1 blood
From 3 ml, 243 ml of platelet-rich plasma was removed by centrifugation within 8 hours after blood collection, and the mixture was stored at 4 ° C. for 3 days. After allowing to stand at room temperature (26 ° C.) until the temperature reached 90 ° C., filtration was performed using a blood circuit incorporating the above filter device. The processing flow rate was adjusted to a constant flow rate of 10 ml / min using a peristaltic pump, and the pressure loss due to filtration was measured with a digital pressure gauge. As a result, the erythrocyte recovery rate was 92%, the leukocyte residual rate was 10 −5.2 ,
The pressure loss at the end of the filtration was 132 mmHg.

【0049】[0049]

【比較例2】ゲル捕捉材、MA捕捉材、第1ステージの
白血球捕捉材は実施例1と同様の物、最下流側の白血球
捕捉材は比較例1と同様の物を用い、厚みを5mmとし
た(有効濾過断面積6.7cm×6.7cm)。また、
上記の各捕捉材は実施例2と同様な熱間圧縮を施したも
のである。このようにして作製した白血球捕捉フィルタ
ー装置も実施例2と同様のポリマー(HEMAとDMか
らなるポリマー、ポリマー中のDM含量は30モル%)
をコーティングしたものであり、CWST値は80dy
n/cm、塩基性官能基の密度は4.7×10-3meq
/m2 であった。実施例2と同様な条件下で実験を行っ
たところ、赤血球回収率は90%、白血球残存率は10
-3.2、濾過終了時の圧力損失は148mmHgであっ
た。
Comparative Example 2 The gel capturing material, the MA capturing material, and the first stage leukocyte capturing material were the same as in Example 1, and the most downstream leukocyte capturing material was the same as in Comparative Example 1, and had a thickness of 5 mm. (Effective filtration sectional area: 6.7 cm × 6.7 cm). Also,
Each of the above-described trapping members was subjected to the same hot compression as in Example 2. The leukocyte trapping filter device thus produced was also the same polymer as in Example 2 (polymer composed of HEMA and DM, DM content in the polymer was 30 mol%)
And a CWST value of 80 dy
n / cm, the density of the basic functional group is 4.7 × 10 −3 meq.
/ M 2 . When an experiment was performed under the same conditions as in Example 2, the red blood cell recovery rate was 90%, and the white blood cell remaining rate was 10%.
-3.2 , the pressure loss at the end of the filtration was 148 mmHg.

【0050】[0050]

【比較例3】ゲル捕捉材、MA捕捉材、第1ステージの
白血球捕捉材は実施例1と同様の物を用い、最下流側に
平均繊維径が1.8μmのPETからなる不織布を充填
し、厚みを5mmとした(有効濾過断面積6.7cm×
6.7cm)。また、上記の各捕捉材は実施例2と同様
な熱間圧縮を施したものである。最下流側の白血球捕捉
材は平均孔径が5.1μmであり、全細孔容積が0.3
7ml/ml(多孔質素子)、全細孔表面積が0.55
2 /ml、1〜30μmの細孔部分の容積及び表面積
がそれぞれ87%、38%、2〜30μmの細孔部分の
容積及び表面積がそれぞれ86%、35%、30μmを
超える細孔部分の容積が1%、1μm未満の細孔部分の
表面積が61%、2μm未満の細孔部分の容積及び表面
積がそれぞれ13%、64%の孔径分布を有するものを
用いた。このようにして作製した白血球捕捉フィルター
装置も実施例1と同様のポリマー(HEMAとDMから
なるポリマー、ポリマー中のDM含量は30モル%)を
コーティングしたものであり、CWST値は80dyn
/cm、塩基性官能基の密度は4.8×10-3meq/
2 であった。実施例2と同様な条件下で実験を行った
ところ、赤血球回収率は79%、白血球残存率は10
-4.8、濾過終了時の圧力損失は500mmHg以上であ
った。
Comparative Example 3 A gel capturing material, a MA capturing material, and a leukocyte capturing material of the first stage were the same as those in Example 1, and the most downstream side was filled with a nonwoven fabric made of PET having an average fiber diameter of 1.8 μm. And the thickness was set to 5 mm (effective filtration area: 6.7 cm ×
6.7 cm). In addition, each of the above-described trapping members was subjected to the same hot compression as in Example 2. The most downstream leukocyte trapping material has an average pore size of 5.1 μm and a total pore volume of 0.3 μm.
7 ml / ml (porous element), total pore surface area is 0.55
The volume and the surface area of the pore portion of m 2 / ml, 1 to 30 μm are 87%, 38%, and the volume and the surface area of the pore portion of 2 to 30 μm are respectively 86%, 35%, and 30 μm. A pore having a pore size distribution of 1%, a surface area of a pore portion of less than 1 μm of 61%, and a volume and a surface area of a pore portion of less than 2 μm of 13% and 64%, respectively, was used. The leukocyte-trapping filter device thus produced was also coated with the same polymer as in Example 1 (a polymer composed of HEMA and DM, DM content in the polymer was 30 mol%), and had a CWST value of 80 dyn.
/ Cm, the density of the basic functional group is 4.8 × 10 −3 meq /
m 2 . When an experiment was performed under the same conditions as in Example 2, the erythrocyte recovery rate was 79% and the leukocyte residual rate was 10%.
-4.8 , The pressure loss at the end of the filtration was 500 mmHg or more.

【0051】[0051]

【実施例3】ゲル捕捉材、MA捕捉材、第1ステージの
白血球捕捉材は実施例1と同様の物を用い、最下流側に
ポリビニルホルマール(PVF)からなる三次元網目状
連続細孔を有するスポンジ状構造物を充填し、厚みを4
mmとした(有効濾過断面積6.7cm×6.7c
m)。また、上記捕捉材のうちゲル捕捉材、MA捕捉
材、第1ステージの白血球捕捉材は実施例2と同様な熱
間圧縮による予備成形を施したものである。最下流側の
白血球捕捉材は平均孔径が9.4μmであり、全細孔容
積が0.90ml/ml(多孔質素子)、全細孔表面積
が0.75m2 /ml、1〜30μmの細孔部分の容積
及び表面積がそれぞれ98%、73%、2〜30μmの
細孔部分の容積及び表面積がそれぞれ96%、61%、
30μmを超える細孔部分の容積が2%、1μm未満の
細孔部分の表面積が26%、2μm未満の細孔部分の容
積及び表面積がそれぞれ4%、38%の孔径分布を有す
るものを用いた。このようにして作製した白血球捕捉フ
ィルター装置も実施例1と同様のポリマー(HEMAと
DMからなるポリマー、ポリマー中のDM含量は30モ
ル%)をコーティングしたものであり、CWST値は8
2dyn/cm、塩基性官能基の密度は4.7×10-3
meq/m2 であった。実施例2と同様な条件下で実験
を行ったところ、赤血球回収率は95%、白血球残存率
は10-5.1、濾過終了時の圧力損失は108mmHgで
あった。
Example 3 A gel capturing material, a MA capturing material, and a leukocyte capturing material in the first stage were the same as those in Example 1, and three-dimensional network-like continuous pores made of polyvinyl formal (PVF) were provided at the most downstream side. With a sponge-like structure having a thickness of 4
mm (effective filtration area 6.7 cm x 6.7 c)
m). Among the above-mentioned trapping materials, the gel trapping material, the MA trapping material, and the leukocyte trapping material of the first stage were preformed by hot compression in the same manner as in Example 2. The most downstream leukocyte-trapping material has an average pore size of 9.4 μm, a total pore volume of 0.90 ml / ml (porous element), a total pore surface area of 0.75 m 2 / ml, and a fineness of 1 to 30 μm. The volume and the surface area of the pore portion are 98% and 73%, and the volume and the surface area of the pore portion of 2 to 30 μm are 96% and 61%, respectively.
The pores having a pore size distribution in which the volume of pore portions exceeding 30 μm is 2%, the surface area of pore portions less than 1 μm is 26%, and the volume and surface area of pore portions less than 2 μm are 4% and 38%, respectively are used. . The leukocyte trapping filter device thus prepared was also coated with the same polymer as in Example 1 (a polymer composed of HEMA and DM, the DM content in the polymer was 30 mol%), and the CWST value was 8
2 dyn / cm, density of basic functional group is 4.7 × 10 -3
meq / m 2 . The experiment was performed under the same conditions as in Example 2. As a result, the red blood cell recovery rate was 95%, the white blood cell residual rate was 10 −5.1 , and the pressure loss at the end of the filtration was 108 mmHg.

【0052】[0052]

【比較例4】ゲル捕捉材、MA捕捉材、第1ステージの
白血球捕捉材は実施例1と同様の物を用い、最下流側に
PVFからなるスポンジ状構造物を充填し、厚みを4m
mとした(有効濾過断面積6.7cm×6.7cm)。
また、上記捕捉材のうちゲル捕捉材、MA捕捉材、第1
ステージの白血球捕捉材は実施例2と同様な熱間圧縮を
施したものである。最下流側の白血球捕捉材は平均孔径
が8.0μmあり、全細孔容積が0.41ml/ml
(多孔質素子)、全細孔表面積が0.59m2 /ml、
1〜30μmの細孔部分の容積及び表面積がそれぞれ8
1%、54%、2〜30μmの細孔部分の容積及び表面
積がそれぞれ78%、41%、30μmを超える細孔部
分の容積が9%、1μm未満の細孔部分の表面積が44
%、2μm未満の細孔部分の容積及び表面積がそれぞれ
13%、57%の孔径分布を有するものを用いた。この
ようにして作製した白血球捕捉フィルター装置も実施例
1と同様のポリマー(HEMAとDMからなるポリマ
ー、ポリマー中のDM含量は30モル%)をコーティン
グしたものであり、CWST値は82dyn/cm、塩
基性官能基の密度は4.6×10-3meq/m2 であっ
た。実施例2と同様な条件下で実験を行ったところ、赤
血球回収率は89%、白血球残存率は10-3.4、濾過終
了時の圧力損失は205mmHgであった。
Comparative Example 4 A gel capturing material, an MA capturing material, and a leukocyte capturing material of the first stage were the same as those in Example 1, and the lowermost stream was filled with a sponge-like structure made of PVF and had a thickness of 4 m.
m (effective filtration cross-sectional area: 6.7 cm × 6.7 cm).
Further, among the above-mentioned trapping materials, a gel trapping material, a MA trapping material, a first trapping material,
The leukocyte capturing material of the stage was subjected to the same hot compression as in Example 2. The most downstream leukocyte capturing material has an average pore size of 8.0 μm and a total pore volume of 0.41 ml / ml.
(Porous element), the total pore surface area is 0.59 m 2 / ml,
The volume and surface area of the pore portion of 1 to 30 μm are 8
The volume and the surface area of the pore portion of 1%, 54%, and 2 to 30 μm are 78%, 41%, and the volume of the pore portion exceeding 30 μm is 9%, respectively, and the surface area of the pore portion of less than 1 μm is 44%.
%, And those having a pore diameter distribution of 13% and 57%, respectively, having a volume and surface area of pore portions smaller than 2 μm. The leukocyte trapping filter device thus produced was also coated with the same polymer as in Example 1 (a polymer composed of HEMA and DM, the DM content in the polymer was 30 mol%), and the CWST value was 82 dyn / cm. The density of the basic functional group was 4.6 × 10 −3 meq / m 2 . When the experiment was performed under the same conditions as in Example 2, the red blood cell recovery rate was 89%, the white blood cell residual rate was 10 −3.4 , and the pressure loss at the end of the filtration was 205 mmHg.

【0053】[0053]

【比較例5】ゲル捕捉材、MA捕捉材、第1ステージの
白血球捕捉材は実施例1と同様の物を用い、最下流側に
PVFからなるスポンジ状構造物を充填し、厚みを4m
mとした(有効濾過断面積6.7cm×6.7cm)。
また、上記捕捉材のうちゲル捕捉材、MA捕捉材、第1
ステージの白血球捕捉材は実施例2と同様な熱間圧縮を
施したものである。最下流側の白血球捕捉材は平均孔径
が25.4μmであり、全細孔容積が0.55ml/m
l(多孔質素子)、全細孔表面積が0.60m2 /m
l、1〜30μmの細孔部分の容積及び表面積がそれぞ
れ70%、58%、2〜30μmの細孔部分の容積及び
表面積がそれぞれ69%、46%、30μmを超える細
孔部分の容積が28%、1μm未満の細孔部分の表面積
が33%、2μm未満の細孔部分の容積及び表面積がそ
れぞれ3%、46%の孔径分布を有するものを用いた。
このようにして作製した白血球捕捉フィルター装置も実
施例1と同様のポリマー(HEMAとDMからなるポリ
マー、ポリマー中のDM含量は30モル%)をコーティ
ングしたものであり、CWST値は82dyn/cm、
塩基性官能基の密度は4.8×10-3meq/m2 であ
った。 実施例2と同様な条件下で実験を行ったとこ
ろ、赤血球回収率は97%、白血球残存率は10-1.4
濾過終了時の圧力損失は51mmHgであった。
[Comparative Example 5] A gel capturing material, an MA capturing material, and a leukocyte capturing material of the first stage were the same as in Example 1, and the lowermost side was filled with a sponge-like structure made of PVF and had a thickness of 4 m.
m (effective filtration cross-sectional area: 6.7 cm × 6.7 cm).
Further, among the above-mentioned trapping materials, a gel trapping material, a MA trapping material, a first trapping material,
The leukocyte capturing material of the stage was subjected to the same hot compression as in Example 2. The most downstream leukocyte capturing material has an average pore diameter of 25.4 μm and a total pore volume of 0.55 ml / m 2.
1 (porous element), the total pore surface area is 0.60 m 2 / m
1, the volume and the surface area of the pore portion of 1 to 30 μm are 70% and 58%, and the volume and the surface area of the pore portion of 2 to 30 μm are 69%, 46% and the volume of the pore portion exceeding 30 μm are 28%, respectively. %, The surface area of the pore portion smaller than 1 μm was 33%, and the volume and the surface area of the pore portion smaller than 2 μm were 3% and 46%, respectively.
The leukocyte trapping filter device thus produced was also coated with the same polymer as in Example 1 (a polymer composed of HEMA and DM, the DM content in the polymer was 30 mol%), and the CWST value was 82 dyn / cm.
The density of the basic functional group was 4.8 × 10 −3 meq / m 2 . When an experiment was performed under the same conditions as in Example 2, the erythrocyte recovery rate was 97%, the leukocyte residual rate was 10 −1.4 ,
The pressure loss at the end of the filtration was 51 mmHg.

【0054】[0054]

【実施例4】血液の入口と出口を有し、有効濾過断面積
が3.0cm×3.0cmの白血球捕捉フィルター装置
に血液上流側から下流側に向かって、ゲル捕捉材とし
て、平均繊維径が15μmのニードル繊維構造体、MA
捕捉材として平均繊維径が3μmの不織布、第1ステー
ジの白血球捕捉材として平均繊維径が2.2μmの不織
布、最下流側に本発明の白血球捕捉材として平均繊維径
が1.2μmの不織布を充填し、厚みを5mmとした。
また、ゲル捕捉材、MA捕捉材、第1ステージの白血球
捕捉材、本発明の白血球捕捉材はあらかじめ熱間圧縮を
施したものを用いた。最下流側の白血球捕捉材はPET
からなり、平均孔径が9.2μmであり、全細孔容積が
0.83ml/ml(多孔質素子)、全細孔表面積が
1.02m2/ml、1〜30μmの細孔部分の容積及
び表面積がそれぞれ95%、72%、1〜25μmの細
孔部分の容積及び表面積がそれぞれ92%、71%、3
0μmを超える細孔部分の容積が2%、1μm未満の細
孔部分の表面積が27%、25μmを超える細孔部分の
容積及び表面積がそれぞれ5%、2%の孔径分布を有す
るものを用いた。このようにして作製した白血球捕捉フ
ィルター装置にHEMAとDMからなるポリマー(ポリ
マー中のDM含量は3モル%)の1.0%エタノール溶
液を通液することによりコーティングし、その後、窒素
ガスを通気し、更に1mmHgの真空下、40℃で24
時間乾燥した。乾燥後の白血球捕捉材のCWST値及び
塩基性官能基の密度を測定したところ、CWST値が1
02dyn/cm、塩基性含窒素官能基の密度が9.5
×10-4meq/m2 であった。
Example 4 A leukocyte-capturing filter device having an inlet and an outlet for blood and having an effective filtration area of 3.0 cm × 3.0 cm was used as a gel capturing material from the upstream side to the downstream side of the blood as an average fiber diameter. Is 15 μm needle fiber structure, MA
A nonwoven fabric having an average fiber diameter of 3 μm as a capturing material, a nonwoven fabric having an average fiber diameter of 2.2 μm as a leukocyte capturing material of the first stage, and a nonwoven fabric having an average fiber diameter of 1.2 μm as a leukocyte capturing material of the present invention are provided at the most downstream side. It was filled to a thickness of 5 mm.
The gel capturing material, the MA capturing material, the leukocyte capturing material of the first stage, and the leukocyte capturing material of the present invention were those that had been subjected to hot compression in advance. The most downstream leukocyte capturing material is PET
Having an average pore diameter of 9.2 μm, a total pore volume of 0.83 ml / ml (porous element), a total pore surface area of 1.02 m 2 / ml, a volume of pore portions of 1 to 30 μm, and The volume and the surface area of the pore portions having a surface area of 95%, 72%, and 1 to 25 μm are 92%, 71%, and 3%, respectively.
The pores having a pore size distribution having a pore size distribution of 2% for the pore portion exceeding 0 μm, 27% for the surface area of the pore portion for less than 1 μm, and 5% for the volume and the surface area of the pore portion for over 25 μm and 2%, respectively were used. . The thus-prepared leukocyte-capturing filter device was coated by passing a 1.0% ethanol solution of a polymer consisting of HEMA and DM (DM content in the polymer was 3 mol%), and then nitrogen gas was introduced. And further at 40 ° C. under a vacuum of 1 mmHg for 24 hours.
Dried for hours. When the CWST value and the density of the basic functional group of the dried leukocyte capturing material were measured, the CWST value was 1
02 dyn / cm, density of basic nitrogen-containing functional group is 9.5
× 10 -4 meq / m 2 .

【0055】200ml採血由来の濃度血小板10単位
(230ml、CPD30ml加)、2日間室温で振と
う保存し、上記のフィルター装置を組み込んだ血液回路
を用いて濾過した。濾過を開始するに当たり、フィルタ
ー装置を血液回路を介して血小板製剤が入っている血液
バッグに接続した後、フィルター装置内に血液を満たし
た。かくして血液がフィルター内に満たされた後、ペリ
スタポンプを用いて5ml/分の一定流速で流し続け、
濾過に伴う圧力損失をデジタル式の圧力計で測定した。
濾過の終了は、血液バッグ内の血液がなくなった時点と
し、フィルター装置下流に血液回路を介して接続した回
収バッグをフィルター装置の血液出口の下流30〜40
cmのところで回路ごと切断し、回路及び回収バッグ内
の血小板製剤を回収液とした。濾過前の血小板製剤(以
下、濾過前液という)及び回収液の体積、血小板数、白
血球数を測定し、血小板回収率及び白血球残存率を求め
た。 血小板回収率={回収液体積×血小板濃度(回収液)}
/{濾過前液体積×血小板濃度(濾過前液)} 白血球残存率={白血球数(回収液)}/{濾過前液体
積×白血球濃度(濾過前液)} なお、濾過前液及び回収液の体積は、各々の重量を比重
1.030で割った値とした。また、白血球濃度の測定
は次の方法で行った。濾過前液の白血球濃度の測定:チ
ュルク液によって、10倍希釈した濾過前液をビルケル
チュルク型の血球計算板に注入し、光学顕微鏡を用いて
大区画8区画中に存在する白血球をカウントし、この値
をnpre とした。 白血球濃度(濾過前)=npre ×1/8×105 個/m
l また、回収液の白血球数の測定は、実施例1と同様な極
めて高感度の方法によった。また、血小板濃度の測定
は、250000倍希釈した検体を自動血球カウンター
で測定して求めた。以上の結果、血小板回収率は93
%、白血球残存率は10-5.0、濾過終了時の圧力損失は
48mmHgであった。
Concentration derived from 200 ml blood collection 10 units of platelets (230 ml, CPD 30 ml added) were stored by shaking at room temperature for 2 days, and filtered using a blood circuit incorporating the above filter device. To start filtration, the filter device was connected to a blood bag containing a platelet product via a blood circuit, and then the filter device was filled with blood. After the blood is thus filled in the filter, the blood is continuously flown at a constant flow rate of 5 ml / min using a peristaltic pump.
The pressure loss due to filtration was measured with a digital pressure gauge.
The end of the filtration is when the blood in the blood bag is exhausted, and the collection bag connected to the downstream of the filter device via the blood circuit is connected to the downstream of the blood outlet of the filter device 30-40.
The plate and the platelet in the circuit and the collection bag were used as a collection liquid. The volume, platelet count, and white blood cell count of the platelet preparation before filtration (hereinafter, referred to as pre-filtration liquid) and the recovered liquid were measured, and the platelet recovery rate and white blood cell residual rate were determined. Platelet collection rate = {collected liquid volume x platelet concentration (collected liquid)}
/ {Liquid volume before filtration × platelet concentration (liquid before filtration)} Leukocyte residual rate = {white blood cell count (recovery liquid)} / {volume of liquid before filtration × white blood cell concentration (liquid before filtration)} Liquid before filtration and recovered liquid Was determined by dividing each weight by a specific gravity of 1.030. The measurement of leukocyte concentration was performed by the following method. Measurement of leukocyte concentration of pre-filtration solution: A 10-fold diluted pre-filtration solution was injected into a Birkel-Turk type hemocytometer with Turk's solution, and white blood cells present in eight large sections were counted using an optical microscope. , And this value was set to n pre . Leukocyte Concentration (before filtration) = n pre × 1/8 × 10 5 cells / m
l The measurement of the leukocyte count in the recovered solution was carried out by the same method as in Example 1 with extremely high sensitivity. The platelet concentration was determined by measuring a sample diluted 250,000 times with an automatic blood cell counter. As a result, the platelet collection rate was 93
%, The leukocyte residual rate was 10 −5.0 , and the pressure loss at the end of the filtration was 48 mmHg.

【0056】[0056]

【比較例6】ゲル捕捉材、MA捕捉材、第1ステージの
白血球捕捉材は実施例3と同様の物を用い、最下流側に
平均繊維径が1.2μmのPETからなる不織布を充填
し、厚みを4mmとした(有効濾過断面積3.0cm×
3.0cm)。また、上記の各捕捉材は、実施例1と同
様な熱間圧縮を施したものである。最下流側の白血球捕
捉材は平均孔径が10.6μmであり、全細孔容積が
0.79ml/ml(多孔質素子)、全細孔表面積が
0.58m /ml、1〜30μmの細孔部分の容積
及び表面積がそれぞれ84%、54%、1〜25μmの
細孔部分の容積及び表面積がそれぞれ80%、53%、
30μmを超える細孔部分の容積が8%、1μm未満の
細孔部分の表面積が42%、25μmを超える細孔部分
の容積及び表面積がそれぞれ14%、5%の孔径分布を
有するものを用いた。このようにして作製した白血球捕
捉フィルター装置も実施例3と同様のポリマー(HEM
AとDMからなるポリマー、ポリマー中のDM含量は3
モル%)をコーティングしたものであり、CWST値は
102dyn/cm、塩基性官能基の密度は9.6×1
−4meq/m であった。実施例4と同様な条件
下で実験を行ったところ、血小板回収率は87%、白血
球残存率は10−2.9、濾過終了時の圧力損失は85
mmHgであった。
Comparative Example 6 The gel capturing material, the MA capturing material, and the leukocyte capturing material of the first stage were the same as in Example 3, and the lowermost stream was filled with a nonwoven fabric made of PET having an average fiber diameter of 1.2 μm. , And the thickness was 4 mm (effective filtration area: 3.0 cm ×
3.0 cm). In addition, each of the above-described trapping members was subjected to the same hot compression as in Example 1. The most downstream leukocyte-trapping material has an average pore diameter of 10.6 μm, a total pore volume of 0.79 ml / ml (porous element), a total pore surface area of 0.58 m 2 / ml, and a fineness of 1 to 30 μm. The volume and the surface area of the pore portion are 84% and 54%, and the volume and the surface area of the pore portion of 1 to 25 μm are 80% and 53%, respectively.
The pores having a pore size distribution in which the volume of pores exceeding 30 μm is 8%, the surface area of pores less than 1 μm is 42%, and the volume and surface area of pores exceeding 25 μm are 14% and 5%, respectively. . The leukocyte trapping filter device produced in this manner is also the same polymer (HEM) as in Example 3.
Polymer consisting of A and DM, DM content in the polymer is 3
Mol%), the CWST value was 102 dyn / cm, and the density of the basic functional groups was 9.6 × 1.
It was 0 -4 meq / m 2. When an experiment was performed under the same conditions as in Example 4, the platelet recovery rate was 87%, the leukocyte residual rate was 10 −2.9 , and the pressure loss at the end of filtration was 85.
mmHg.

【0057】[0057]

【比較例7】ゲル捕捉材、MA捕捉材、第1ステージの
白血球捕捉材は実施例3と同様の物を用い、最下流側に
平均繊維径が1.2μmのPETからなる不織布を充填
し、厚みを4mmとした(有効濾過断面積3.0cm×
3.0cm)。また、上記の各捕捉材は、実施例1と同
様な熱間圧縮を施したものである。最下流側の白血球捕
捉材は平均孔径が16.2μmであり、全細孔容積が
0.86ml/ml(多孔質素子)、全細孔表面積が
0.51m2 /ml、1〜30μmの細孔部分の容積及
び表面積がそれぞれ77%、51%、1〜25μmの細
孔部分の容積及び表面積がそれぞれ71%、49%、3
0μmを超える細孔部分の容積が20%、1μm未満の
細孔部分の表面積が40%、25μmを超える細孔部分
の容積及び表面積がそれぞれ26%、11%の孔径分布
を有するものを用いた。このようにして作製した白血球
捕捉フィルター装置も実施例3と同様のポリマー(HE
MAとDMからなるポリマー、ポリマー中のDM含量は
3モル%)をコーティングしたものであり、CWST値
は102dyn/cm、塩基性官能基の密度は9.4×
10-4meq/m2 であった。実施例4と同様な条件下
で実験を行ったところ、血小板回収率は98%、白血球
残存率は10-0.8、濾過終了時の圧力損失は26mmH
gであった。
Comparative Example 7 The same material as in Example 3 was used as the gel capturing material, the MA capturing material, and the leukocyte capturing material in the first stage, and the most downstream side was filled with a nonwoven fabric made of PET having an average fiber diameter of 1.2 μm. , And the thickness was 4 mm (effective filtration area: 3.0 cm ×
3.0 cm). In addition, each of the above-described trapping members was subjected to the same hot compression as in Example 1. The most downstream leukocyte-trapping material has an average pore size of 16.2 μm, a total pore volume of 0.86 ml / ml (porous element), a total pore surface area of 0.51 m 2 / ml, and a fineness of 1 to 30 μm. The volume and surface area of the pore portion are 77%, 51%, and the volume and surface area of the pore portion of 1 to 25 μm are 71%, 49%, and 3%, respectively.
The pores having a pore size distribution in which the volume of pores exceeding 0 μm is 20%, the surface area of pores less than 1 μm is 40%, and the volume and surface area of pores exceeding 25 μm are 26% and 11%, respectively. . The leukocyte-capturing filter device produced in this manner is also the same polymer (HE
A polymer composed of MA and DM, the content of DM in the polymer being 3 mol%), a CWST value of 102 dyn / cm, and a density of a basic functional group of 9.4 ×.
It was 10 -4 meq / m 2 . When an experiment was performed under the same conditions as in Example 4, the platelet recovery rate was 98%, the leukocyte residual rate was 10 −0.8 , and the pressure loss at the end of filtration was 26 mmH.
g.

【0058】[0058]

【実施例5】ゲル捕捉材、MA捕捉材、第1ステージの
白血球捕捉材は実施例1と同様の物を用い、最下流側に
ポリウレタン(PU)からなる三次元網目状連続細孔を
有するスポンジ状構造物を充填し、厚みを3mmとした
(有効濾過断面積6.7cm×6.7cm)。また、上
記捕捉材のうちゲル捕捉材、MA捕捉材、第1ステージ
の白血球捕捉材は実施例1と同様な熱間圧縮を施したも
のである。最下流側の白血球捕捉材は平均孔径が7.4
μmであり、全細孔容積が0.73ml/ml(多孔質
素子)、全細孔表面積が0.94m2 /ml、1〜30
μmの細孔部分の容積及び表面積がそれぞれ96%、6
6%、1〜25μmの細孔部分の容積及び表面積がそれ
ぞれ94%、65%、30μmを超える細孔部分の容積
が1%、1μm未満の細孔部分の表面積が34%、25
μmを超える細孔部分の容積及び表面積がそれぞれ3
%、1%の孔径分布を有するものを用いた。このように
して作製した白血球捕捉フィルター装置も実施例3と同
様のポリマー(HEMAとDMからなるポリマー、ポリ
マー中のDM含量は3モル%)をコーティングしたもの
であり、CWST値は102dyn/cm、塩基性官能
基の密度は9.6×10-4meq/m2 であった。実施
例4と同様な条件下で実験を行ったところ、血小板回収
率は95%、白血球残存率は10-5.3、濾過終了時の圧
力損失は62mmHgであった。
Example 5 A gel capturing material, an MA capturing material, and a leukocyte capturing material of the first stage were the same as those in Example 1, and had a three-dimensional network-like continuous pore made of polyurethane (PU) at the most downstream side. The sponge-like structure was filled to a thickness of 3 mm (effective filtration cross-sectional area: 6.7 cm × 6.7 cm). Among the above trapping materials, the gel trapping material, the MA trapping material, and the leukocyte trapping material of the first stage were subjected to the same hot compression as in Example 1. The most downstream leukocyte trapping material has an average pore size of 7.4.
μm, the total pore volume is 0.73 ml / ml (porous element), the total pore surface area is 0.94 m 2 / ml, 1 to 30
The volume and surface area of the micrometer pore portion are 96% and 6%, respectively.
The volume and the surface area of the pore portion of 6%, 1 to 25 μm are 94%, 65%, and the volume of the pore portion exceeding 30 μm is 1%, and the surface area of the pore portion of less than 1 μm is 34%, 25%.
The volume and surface area of the pore portion exceeding μm are 3
%, Having a pore size distribution of 1%. The leukocyte trapping filter device thus prepared was also coated with the same polymer as in Example 3 (a polymer composed of HEMA and DM, the DM content in the polymer was 3 mol%), and the CWST value was 102 dyn / cm. The density of the basic functional group was 9.6 × 10 −4 meq / m 2 . When the experiment was carried out under the same conditions as in Example 4, the platelet recovery rate was 95%, the leukocyte residual rate was 10 −5.3 , and the pressure loss at the end of the filtration was 62 mmHg.

【0059】[0059]

【比較例8】ゲル捕捉材、MA捕捉材、第1ステージの
白血球捕捉材は実施例1と同様の物を用い、最下流側に
PUからなるスポンジ状構造物を充填し、厚みを3mm
とした(有効濾過断面積3.0cm×3.0cm)。ま
た、上記捕捉材のうちゲル捕捉材、MA捕捉材、第1ス
テージの白血球捕捉材は実施例1と同様な熱間圧縮を施
したものである。最下流側の白血球捕捉材は平均孔径が
8.1μmあり、全細孔容積が0.58ml/ml(多
孔質素子)、全細孔表面積が0.78m2 /ml、1〜
30μmの細孔部分の容積及び表面積がそれぞれ81
%、50%、1〜25μmの細孔部分の容積及び表面積
がそれぞれ79%、48%、30μmを超える細孔部分
の容積が10%、1μm未満の細孔部分の表面積が47
%、25μmを超える細孔部分の容積及び表面積がそれ
ぞれ12%、5%の孔径分布を有するものを用いた。こ
のようにして作製した白血球捕捉フィルター装置も実施
例3と同様のポリマー(HEMAとDMからなるポリマ
ー、ポリマー中のDM含量は3モル%)をコーティング
したものであり、CWST値は102dyn/cm、塩
基性官能基の密度は9.4×10-4meq/m2 であっ
た。 実施例4と同様な条件下で実験を行ったところ、
血小板回収率は89%、白血球残存率は10-2 .5、濾過
終了時の圧力損失は90mmHgであった。
Comparative Example 8 The same material as in Example 1 was used as the gel capturing material, the MA capturing material, and the leukocyte capturing material of the first stage, and the lowermost side was filled with a sponge-like structure made of PU, and the thickness was 3 mm.
(Effective filtration area: 3.0 cm × 3.0 cm). Among the above trapping materials, the gel trapping material, the MA trapping material, and the leukocyte trapping material of the first stage were subjected to the same hot compression as in Example 1. The most downstream leukocyte capturing material has an average pore diameter of 8.1 μm, a total pore volume of 0.58 ml / ml (porous element), a total pore surface area of 0.78 m 2 / ml, and
The volume and surface area of the 30 μm pore portion are 81
%, 50%, the volume and the surface area of the pore portion of 1 to 25 μm are 79%, 48%, the volume of the pore portion exceeding 30 μm is 10%, and the surface area of the pore portion of less than 1 μm is 47%.
%, And those having a pore size distribution in which the volume and surface area of the pore portion exceeding 25 μm are 12% and 5%, respectively. The leukocyte trapping filter device thus prepared was also coated with the same polymer as in Example 3 (a polymer composed of HEMA and DM, the DM content in the polymer was 3 mol%), and the CWST value was 102 dyn / cm. The density of the basic functional group was 9.4 × 10 −4 meq / m 2 . When an experiment was performed under the same conditions as in Example 4,
Platelet recovery rate is 89%, the leukocyte residual rate 10-2 .5, pressure loss during filtration ends was 90 mmHg.

【0060】[0060]

【比較例9】ゲル捕捉材、MA捕捉材、第1ステージの
白血球捕捉材は実施例1と同様の物を用い、最下流側に
PUからなるスポンジ状構造物を充填し、厚みを3mm
とした(有効濾過断面積3.0cm×3.0cm)。ま
た、上記捕捉材のうちゲル捕捉材、MA捕捉材、第1ス
テージの白血球捕捉材は実施例1と同様な熱間圧縮を施
したものである。最下流側の白血球捕捉材は平均孔径が
2.5μmあり、全細孔容積が0.11ml/ml(多
孔質素子)、全細孔表面積が0.49m2 /ml、1〜
30μmの細孔部分の容積及び表面積がそれぞれ67
%、14%、1〜25μmの細孔部分の容積及び表面積
がそれぞれ66%、13%、30μmを超える細孔部分
の容積が3%、1μm未満の細孔部分の表面積が85
%、25μmを超える細孔部分の容積及び表面積がそれ
ぞれ4%、2%の孔径分布を有するものを用いた。この
ようにして作製した白血球捕捉フィルター装置も実施例
3と同様のポリマー(HEMAとDMからなるポリマ
ー、ポリマー中のDM含量は3モル%)をコーティング
したものであり、CWST値は102dyn/cm、塩
基性官能基の密度は9.6×10-4meq/m2 であっ
た。実施例4と同様な条件下で実験を行ったところ、血
小板回収率は51%、白血球残存率は10-5.4、濾過終
了時の圧力損失は500mmHg以上であった。上述の
実施例及び比較例の結果を、表1及び表2に示す。
Comparative Example 9 The same gel capturing material, MA capturing material, and leukocyte capturing material of the first stage as those in Example 1 were used, and the lowermost stream side was filled with a sponge-like structure made of PU and had a thickness of 3 mm.
(Effective filtration area: 3.0 cm × 3.0 cm). Among the above trapping materials, the gel trapping material, the MA trapping material, and the leukocyte trapping material of the first stage were subjected to the same hot compression as in Example 1. The most downstream leukocyte capturing material has an average pore size of 2.5 μm, a total pore volume of 0.11 ml / ml (porous element), a total pore surface area of 0.49 m 2 / ml, and
The volume and surface area of the 30 μm pore portion are each 67
%, 14%, the volume and surface area of the pore portion of 1 to 25 μm are 66%, 13%, the volume of the pore portion exceeding 30 μm is 3%, and the surface area of the pore portion of less than 1 μm is 85%.
%, And those having pore volume distributions of 4% and 2%, respectively, having a volume and surface area of pore portions exceeding 25 μm were used. The leukocyte trapping filter device thus prepared was also coated with the same polymer as in Example 3 (a polymer composed of HEMA and DM, the DM content in the polymer was 3 mol%), and the CWST value was 102 dyn / cm. The density of the basic functional group was 9.6 × 10 −4 meq / m 2 . The experiment was performed under the same conditions as in Example 4. As a result, the platelet recovery rate was 51%, the leukocyte residual rate was 10 −5.4 , and the pressure loss at the end of the filtration was 500 mmHg or more. Tables 1 and 2 show the results of the above Examples and Comparative Examples.

【0061】[0061]

【表1】 [Table 1]

【0062】[0062]

【表2】 [Table 2]

【0063】[0063]

【発明の効果】本発明の白血球捕捉材は、白血球の捕捉
に有効な1〜30μmの細孔の割合が高い点に特徴を有
すことから、白血球の残存率を極めて低くすることが可
能となる。
As described above, the leukocyte-trapping material of the present invention is characterized in that the ratio of pores of 1 to 30 μm effective for trapping leukocytes is high, so that the leukocyte retention rate can be extremely reduced. Become.

───────────────────────────────────────────────────── フロントページの続き (56)参考文献 特開 平3−173825(JP,A) 特開 昭55−136955(JP,A) 特開 平2−286171(JP,A) 特開 平3−47131(JP,A) 国際公開91/4088(WO,A1) (58)調査した分野(Int.Cl.7,DB名) A61K 35/14 B01D 39/16 B01D 71/48 ──────────────────────────────────────────────────続 き Continuation of the front page (56) References JP-A-3-173825 (JP, A) JP-A-55-136955 (JP, A) JP-A-2-286171 (JP, A) JP-A-3-173 47131 (JP, A) International Publication 91/4088 (WO, A1) (58) Fields investigated (Int. Cl. 7 , DB name) A61K 35/14 B01D 39/16 B01D 71/48

Claims (1)

(57)【特許請求の範囲】(57) [Claims] 【請求項1】平均孔径が1〜25μm、全細孔容積が
0.40〜0.95ml/ml(多孔質素子)、全細孔
表面積が0.50〜5.70m /mlの多孔質素子
からなる白血球浮遊液から白血球を捕捉するための白血
球捕捉材であって、該多孔質素子の1〜30μmの細孔
部分の容積が全細孔容積の90%以上、該多孔質素子の
1〜30μmの細孔部分の表面積が全細孔表面積の60
%以上であることを特徴とする白血球捕捉材。
1. A average pore diameter of 1 to 25 m, total pore volume 0.40~0.95ml / ml (porous element), the total pore
A leukocyte-trapping material for trapping leukocytes from a leukocyte suspension comprising a porous element having a surface area of 0.50 to 5.70 m 2 / ml , wherein the volume of a 1 to 30 μm pore portion of the porous element is 90% or more of the total pore volume of the porous element
The surface area of the pore portion of 1 to 30 μm is 60% of the total pore surface area.
% Or more .
JP20426592A 1991-08-22 1992-07-09 Leukocyte trapping material Expired - Fee Related JP3270125B2 (en)

Priority Applications (8)

Application Number Priority Date Filing Date Title
JP20426592A JP3270125B2 (en) 1992-07-09 1992-07-09 Leukocyte trapping material
AT92917988T ATE197547T1 (en) 1991-08-22 1992-08-24 FILTER MEDIUM FOR SELECTIVE REMOVAL OF LEUKOCYTES AND CORRESPONDING DEVICE
ES92917988T ES2151492T3 (en) 1991-08-22 1992-08-24 FILTER MATERIAL TO SELECTLY REMOVE LEUCOCITS AND APPLIANCE WITH FILLING OF THE SAME.
PCT/JP1992/001064 WO1993003740A1 (en) 1991-08-22 1992-08-24 Filter medium for selective removal of leukocytes and device packed therewith
DE69231566T DE69231566T2 (en) 1991-08-22 1992-08-24 FILTER MEDIUM FOR SELECTIVE REMOVAL OF LEUKOCYTES AND APPROPRIATE DEVICE
EP92917988A EP0554460B1 (en) 1991-08-22 1992-08-24 Filter medium for selective removal of leukocytes and device packed therewith
US08/353,335 US5478470A (en) 1991-08-22 1994-12-05 Filter material for selectively removing leukocytes
US08/531,700 US5665233A (en) 1991-08-22 1995-09-21 Filter apparatus for selectively removing leukocytes

Applications Claiming Priority (1)

Application Number Priority Date Filing Date Title
JP20426592A JP3270125B2 (en) 1992-07-09 1992-07-09 Leukocyte trapping material

Publications (2)

Publication Number Publication Date
JPH0624995A JPH0624995A (en) 1994-02-01
JP3270125B2 true JP3270125B2 (en) 2002-04-02

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ID=16487608

Family Applications (1)

Application Number Title Priority Date Filing Date
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Country Link
JP (1) JP3270125B2 (en)

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* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
ES2202491T3 (en) * 1995-12-26 2004-04-01 Asahi Medical Co., Ltd. FILTRATION MATERIAL FOR THE ELIMINATION OF LEUCOCITS.
JPH09183626A (en) 1995-12-28 1997-07-15 Central Glass Co Ltd Reinforced thin glass plate
JP2002102626A (en) * 2000-09-29 2002-04-09 Terumo Corp Leucocyte removing filter and leucocyte removing device
FR2835752B1 (en) * 2002-02-13 2004-11-26 Maco Pharma Sa FILTRATION UNIT COMPRISING CALENDERED DECOOLING LAYERS
WO2004000444A1 (en) * 2002-06-19 2003-12-31 Northwest Biotherapeutics, Inc. Tangential flow filtration devices and methods for leukocyte enrichment
EP1380550B1 (en) 2002-07-10 2011-09-21 Asahi Glass Co., Ltd. Tempered glass sheet having a central zone of higher compressive stress, process and apparatus therefor
ITTO20020736A1 (en) * 2002-08-21 2004-02-22 Fresenius Hemocare Italia Srl LEukocyte filter and its use for the depletion of leukocyte blood products.
US8211310B2 (en) * 2006-11-20 2012-07-03 Cytosorbents, Inc. Size-selective polymer system
JP5424688B2 (en) * 2009-03-31 2014-02-26 旭化成メディカル株式会社 Selective removal material for granulocytes and monocytes
JP6698870B2 (en) * 2016-11-29 2020-05-27 富士フイルム株式会社 Blood component selective adsorption filter and blood filter

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