JPH1057477A - White blood cell removing filter material and white blood cell removing filter device - Google Patents
White blood cell removing filter material and white blood cell removing filter deviceInfo
- Publication number
- JPH1057477A JPH1057477A JP8240972A JP24097296A JPH1057477A JP H1057477 A JPH1057477 A JP H1057477A JP 8240972 A JP8240972 A JP 8240972A JP 24097296 A JP24097296 A JP 24097296A JP H1057477 A JPH1057477 A JP H1057477A
- Authority
- JP
- Japan
- Prior art keywords
- leukocyte
- porous particles
- filter material
- less
- leukocytes
- 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.)
- Pending
Links
- 210000000265 leukocyte Anatomy 0.000 title claims abstract description 166
- 239000000463 material Substances 0.000 title claims abstract description 52
- 239000002245 particle Substances 0.000 claims abstract description 109
- 230000008961 swelling Effects 0.000 claims abstract description 17
- 239000011148 porous material Substances 0.000 claims description 46
- 238000000034 method Methods 0.000 claims description 15
- 210000003934 vacuole Anatomy 0.000 claims description 12
- 239000012528 membrane Substances 0.000 claims description 5
- 239000006285 cell suspension Substances 0.000 abstract 1
- 230000001939 inductive effect Effects 0.000 abstract 1
- 239000000725 suspension Substances 0.000 description 57
- 238000001914 filtration Methods 0.000 description 16
- 238000012545 processing Methods 0.000 description 16
- 210000004369 blood Anatomy 0.000 description 13
- 239000008280 blood Substances 0.000 description 13
- 238000012856 packing Methods 0.000 description 13
- 239000004745 nonwoven fabric Substances 0.000 description 10
- 229920002678 cellulose Polymers 0.000 description 7
- 239000001913 cellulose Substances 0.000 description 7
- 241000283690 Bos taurus Species 0.000 description 6
- 238000004891 communication Methods 0.000 description 6
- 230000000694 effects Effects 0.000 description 6
- 239000000835 fiber Substances 0.000 description 5
- 239000010836 blood and blood product Substances 0.000 description 4
- 229940125691 blood product Drugs 0.000 description 4
- 230000000052 comparative effect Effects 0.000 description 4
- 230000017531 blood circulation Effects 0.000 description 3
- 210000004027 cell Anatomy 0.000 description 3
- 230000006835 compression Effects 0.000 description 3
- 238000007906 compression Methods 0.000 description 3
- 238000005534 hematocrit Methods 0.000 description 3
- 239000007788 liquid Substances 0.000 description 3
- 239000002504 physiological saline solution Substances 0.000 description 3
- 206010019233 Headaches Diseases 0.000 description 2
- 206010028813 Nausea Diseases 0.000 description 2
- 206010037660 Pyrexia Diseases 0.000 description 2
- 206010070834 Sensitisation Diseases 0.000 description 2
- 230000000961 alloantigen Effects 0.000 description 2
- 230000008859 change Effects 0.000 description 2
- 239000013256 coordination polymer Substances 0.000 description 2
- 238000000635 electron micrograph Methods 0.000 description 2
- 238000002474 experimental method Methods 0.000 description 2
- 231100000869 headache Toxicity 0.000 description 2
- 230000007246 mechanism Effects 0.000 description 2
- 230000008693 nausea Effects 0.000 description 2
- 229920000728 polyester Polymers 0.000 description 2
- 230000008569 process Effects 0.000 description 2
- 230000008313 sensitization Effects 0.000 description 2
- 230000009385 viral infection Effects 0.000 description 2
- 208000036142 Viral infection Diseases 0.000 description 1
- 230000009471 action Effects 0.000 description 1
- 230000002411 adverse Effects 0.000 description 1
- 239000011324 bead Substances 0.000 description 1
- 230000000903 blocking effect Effects 0.000 description 1
- 230000006378 damage Effects 0.000 description 1
- 210000003743 erythrocyte Anatomy 0.000 description 1
- 208000024908 graft versus host disease Diseases 0.000 description 1
- 230000005484 gravity Effects 0.000 description 1
- 230000002949 hemolytic effect Effects 0.000 description 1
- 125000002887 hydroxy group Chemical group [H]O* 0.000 description 1
- 208000015181 infectious disease Diseases 0.000 description 1
- 239000003446 ligand Substances 0.000 description 1
- 238000004519 manufacturing process Methods 0.000 description 1
- 230000003287 optical effect Effects 0.000 description 1
- 230000000149 penetrating effect Effects 0.000 description 1
- 238000011084 recovery Methods 0.000 description 1
- 230000004044 response Effects 0.000 description 1
- 239000000243 solution Substances 0.000 description 1
- 238000001179 sorption measurement Methods 0.000 description 1
- 239000012798 spherical particle Substances 0.000 description 1
- 239000002344 surface layer Substances 0.000 description 1
Landscapes
- External Artificial Organs (AREA)
- Filtering Materials (AREA)
Abstract
Description
【０００１】[0001]
【産業上の利用分野】本発明は、白血球浮遊液から白血
球を除去するための白血球除去フィルター材および白血
球除去フィルター装置に関するものである。BACKGROUND OF THE INVENTION 1. Field of the Invention The present invention relates to a leukocyte removal filter material and a leukocyte removal filter device for removing leukocytes from a leukocyte suspension.
【０００２】[0002]
【従来の技術】近年、輸血分野においては、血液製剤中
に含まれる混入白血球を除去して輸血する、いわゆる白
血球除去輸血が普及してきている。これは、輸血に伴う
頭痛、吐き気、悪寒、非溶血性発熱反応などの比較的軽
微な副作用や、受血者に深刻な影響を及ぼすアロ抗原感
作、輸血後ＧＶＨＤ、ウィルス感染などの重篤な副作用
が、主として輸血に用いられた血液製剤中に混入してい
る白血球が原因で引き起こされることが明らかにされた
ためである。頭痛、吐き気、悪寒、発熱などの比較的軽
微な副作用を防止するためには、血液製剤中の白血球の
残存率を１０-1〜１０-2以下になるまで除去すれば良い
と言われている。また、重篤な副作用であるアロ抗原感
作やウィルス感染では、白血球の残存率を１０-4〜１０
-6以下になるまで除去することで予防できると言われて
いる。血液製剤から白血球を除去する方法には、大きく
分けて遠心分離機を用いて赤血球と白血球の比重の違い
を利用して分離する方法と、多孔質素子からなるフィル
ター材を用いて白血球を除去するフィルター法の２種類
がある。フィルター法のうちフィルター材として不織布
を用いて白血球を粘着除去する方法は、白血球除去能に
優れていること、操作が簡便であること、およびコスト
が安いことなどの利点を有するため現在普及してきてい
る。2. Description of the Related Art In recent years, in the field of blood transfusion, so-called leukocyte-free blood transfusion, which removes contaminating leukocytes contained in blood products and transfuses blood, has become widespread. These include relatively minor side effects such as headache, nausea, chills, and non-hemolytic fever response associated with blood transfusion, alloantigen sensitization that has a serious effect on the recipient, GVHD after blood transfusion, and serious infections such as viral infection. It has been clarified that such adverse side effects are mainly caused by leukocytes mixed in blood products used for blood transfusion. It is said that in order to prevent relatively minor side effects such as headache, nausea, chills, and fever, it is only necessary to remove the residual ratio of leukocytes in blood products to 10 -1 to 10 -2 or less. . In addition, in the case of alloantigen sensitization and virus infection, which are serious side effects, the residual ratio of leukocytes is 10 −4 to 10
It is said that it can be prevented by removing it to -6 or less. Methods for removing leukocytes from blood products can be broadly divided into methods that use centrifugal separators to separate red blood cells and leukocytes using specific gravity, and methods that remove leukocytes using a filter element made of a porous element. There are two types of filter methods. Among the filter methods, the method of adhesively removing leukocytes using a non-woven fabric as a filter material has been widely used because it has advantages such as excellent leukocyte removal ability, easy operation, and low cost. I have.
【０００３】白血球除去の機構は、主に白血球のフィル
ター材への粘着によるとされている。このため、同じ素
材で同様の表面を有するフィルター材の白血球除去能の
差は、フィルター材と白血球の衝突頻度の大小により生
じると考えられる。従って、白血球除去能を高めるため
には、白血球が衝突することができるフィルター材の表
面積が大きいほど良い。特公平２−１３５８７には、不
織布をフィルター材として用い、不織布の平均繊維直径
を０．３μｍ以上３．０μｍ未満と細くすることにより
フィルター材の表面積を大きくし、白血球除去能を向上
させる技術手段が開示されている。フィルター材として
不織布を用いる場合、白血球除去能を高める技術手段と
しては、フィルター材の充填密度を高める、更に繊維径
の細いフィルター材を使用する等が挙げられる。しか
し、フィルター材の充填密度を高めたり繊維径を細くす
ると、何れの場合も血液の流路が狭められるために白血
球除去能の向上は見られるものの、白血球浮遊液を通過
させる際の圧力損失が上昇し、期待する血液量を処理し
終わる前に、処理速度が著しく低下し、短時間で白血球
浮遊液を処理できなくなることがある。従来の不織布等
のフィルター材では、白血球浮遊液の処理が進むにつれ
て、フィルター材に捕捉される白血球数は増加するが、
フィルター材に捕捉された白血球は血液の流路を狭める
ために、白血球浮遊液を通過させる際の圧力損失が処理
時間と共に上昇し、短時間で白血球浮遊液を処理できな
くなることがある。また、フィルター材に白血球が局所
的に捕捉されてしまうと、白血球除去フィルター装置内
部で白血球浮遊液の流れに偏りが生じ、フィルター材の
一部が白血球捕捉に有効に利用されなくなり、白血球除
去フィルターの白血球除去能は極端に低下し、期待する
残存白血球数にまで白血球を減ずることができないこと
もある。[0003] The mechanism of leukocyte removal is mainly based on the adhesion of leukocytes to the filter material. For this reason, it is considered that the difference in the leukocyte removal ability of the filter material having the same material and the same surface is caused by the magnitude of the frequency of collision between the filter material and the leukocyte. Therefore, in order to enhance the leukocyte removal ability, the larger the surface area of the filter material with which leukocytes can collide, the better. Japanese Patent Publication No. Hei 2-13587 discloses a technique for using a nonwoven fabric as a filter material, and increasing the surface area of the filter material by reducing the average fiber diameter of the nonwoven fabric to 0.3 μm or more and less than 3.0 μm, thereby improving the leukocyte removal ability. Is disclosed. When a nonwoven fabric is used as the filter material, examples of the technical means for improving the leukocyte removal ability include increasing the packing density of the filter material and using a filter material having a smaller fiber diameter. However, when the packing density of the filter material is increased or the fiber diameter is reduced, the blood flow path is narrowed in any case, and although the leukocyte removal ability is improved, the pressure loss when passing the leukocyte suspension is reduced. In some cases, the processing speed is significantly reduced before the expected amount of blood is processed, and the leukocyte suspension cannot be processed in a short time. In conventional filter materials such as nonwoven fabric, as the processing of leukocyte suspension proceeds, the number of leukocytes captured by the filter material increases,
Since the leukocytes captured by the filter material narrow the blood flow path, the pressure loss when passing the leukocyte suspension increases with the processing time, and the leukocyte suspension may not be processed in a short time. Also, if leukocytes are locally trapped in the filter material, the flow of leukocyte suspension will be biased inside the leukocyte removal filter device, and part of the filter material will not be effectively used for leukocyte capture, and the leukocyte removal filter Has an extremely low leukocyte removal ability, and it may not be possible to reduce the number of leukocytes to the expected number of remaining leukocytes.
【０００４】不織布以外の白血球除去フィルター材とし
て、シート状の多孔質体を使用した技術手段が、特公昭
６３−２６０８９、特開昭６４−７５０１４、特開平３
−１７３８２５等に開示されている。シート状の多孔質
体における白血球除去の機構は、フィルター材内面への
粘着と細孔による濾過であると考えられ、この作用によ
り白血球が効率良く捕捉されると言われている。シート
状の多孔質体は多孔質体のおもて面から、裏面まで貫く
連続した細孔（連通孔）が多数存在していることが構造
上の特徴である。この様な多孔質体の場合でも、連通孔
に白血球が捕捉されると、捕捉された白血球が連通孔を
塞ぎ、血液の流路を狭めるために、白血球浮遊液を通過
させる際の圧力損失が上昇し、短時間で白血球浮遊液を
効率良く処理できなくなることがある。また、白血球は
シート状の多孔質体の表層で捕捉されやすく、一旦白血
球が連通孔に捕捉されると、その連通孔は、捕捉された
白血球によって塞がれてしまい、白血球浮遊液がほとん
ど流れなくなる。このため、連通孔内部にはまだ白血球
を十分に捕捉することができる表面積が存在しているに
もかかわらず、これが利用されなくなるので非常に効率
が悪く、期待する残存白血球数にまで白血球を減ずるこ
とができないこともある。以上説明した通り、従来の技
術手段では、不織布またはシート状多孔質体を白血球除
去フィルター材として用いており、何れの場合も白血球
浮遊液の処理に伴ってフィルター材に捕捉された白血球
が、白血球浮遊液の流路を狭めるために圧力損失が上昇
する。その結果、処理速度が著しく低下し、短時間で白
血球浮遊液を処理できなくなることがある。また、フィ
ルター材に捕捉された白血球が、白血球浮遊液の流路を
狭めることによって、白血球浮遊液の偏流れを生じさせ
たりするために、白血球浮遊液の処理に伴ってフィルタ
ー材の一部と白血球浮遊液との接触が困難となる。その
結果フィルター材の一部が白血球除去に利用されなくな
ることがあった。Technical means using a sheet-like porous material as a leukocyte removal filter material other than a nonwoven fabric are disclosed in JP-B-63-26089, JP-A-64-75014, and JP-A-Hei.
173825 and the like. The mechanism of leukocyte removal in the sheet-shaped porous body is considered to be adhesion to the inner surface of the filter material and filtration by pores, and it is said that leukocytes are efficiently captured by this action. The structural characteristic of the sheet-shaped porous body is that there are many continuous pores (communication holes) penetrating from the front surface to the back surface of the porous body. Even in the case of such a porous body, when leukocytes are captured in the communication holes, the captured white blood cells close the communication holes and narrow the blood flow path. The leukocyte suspension may rise and may not be able to process the leukocyte suspension efficiently in a short time. In addition, leukocytes are easily captured by the surface layer of the sheet-shaped porous body, and once the leukocytes are captured in the communication holes, the communication holes are blocked by the captured leukocytes, and almost all of the leukocyte suspension flows. Disappears. For this reason, even though there is still a surface area capable of sufficiently capturing leukocytes inside the communication hole, this is not used, so the efficiency is extremely low, and the number of leukocytes is reduced to the expected number of remaining leukocytes. Sometimes you can't. As described above, in the conventional technical means, a nonwoven fabric or a sheet-like porous body is used as a leukocyte removal filter material, and in each case, leukocytes captured by the filter material with the treatment of the leukocyte suspension liquid are leukocytes. The pressure loss increases because the flow path of the suspension liquid is narrowed. As a result, the processing speed is significantly reduced, and it may not be possible to process the leukocyte suspension in a short time. In addition, the leukocytes trapped in the filter material narrow the flow path of the leukocyte suspension, causing an uneven flow of the leukocyte suspension. Contact with leukocyte suspension becomes difficult. As a result, a part of the filter material may not be used for leukocyte removal.
【０００５】[0005]
【発明が解決しようとする課題】本発明は、上記で説明
したような課題を解決するためになされたものであり、
白血球浮遊液の処理に伴う圧力損失の上昇が起こりにく
い白血球除去フィルター材、および白血球除去フィルタ
ー装置を提供することを目的とする。SUMMARY OF THE INVENTION The present invention has been made to solve the problems described above,
An object of the present invention is to provide a leukocyte removal filter material and a leukocyte removal filter device in which a pressure loss due to the treatment of a leukocyte suspension is unlikely to occur.
【０００６】[0006]
【課題を解決するための手段】本発明者等は以上のよう
な点を鑑み、鋭意研究を重ねた結果、平均開孔径が３μ
ｍ以上５０μｍ未満で、かつ粒子径が５０μｍ以上５０
０μｍ未満である多孔質粒子状の白血球除去フィルター
材が上記課題を解決することを見出した。また、多孔質
粒子状の白血球除去フィルター材の比表面積が０．５ｍ
2 ／ｇ以上５．０ｍ2 ／ｇ未満であるとより効果的に上
記課題を解決できることを見出した。特に、多孔質粒子
状の白血球除去フィルター材が膜で隔てられた多数の空
胞を有し、空胞が連通した連続孔構造を形成して、か
つ、連通した空胞の連続孔が多孔質粒子の表面から内部
まで放射状に達する構造を有するマクロポーラス化した
球状粒子を用いると、極めて効果的に上記課題が解決で
きることを見出した。更に、本発明は、平均開孔径が３
μｍ以上５０μｍ未満で、かつ粒子径が５０μｍ５００
μｍ未満である多孔質粒子状の白血球除去フィルター材
を膨潤体積の３０％以上１００％以下となるように圧縮
して容器に充填した白血球除去フィルター装置が上記課
題を解決することを見出した。即ち、本発明は、白血球
浮遊液の処理に伴って圧力損失の上昇を引き起こすこと
なく白血球を除去できる白血球除去フィルター材、およ
びこれを充填した白血球除去フィルター装置に関するも
のである。Means for Solving the Problems In view of the above points, the present inventors have conducted intensive studies and as a result, have found that the average opening diameter is 3 μm.
m or more and less than 50 μm, and the particle size is 50 μm or more and 50 or less.
It has been found that a porous particulate leukocyte removal filter material having a particle size of less than 0 μm solves the above-mentioned problem. The specific surface area of the porous leukocyte removal filter material is 0.5 m.
It was can be solved more effectively the problem is less than 2 / g or more 5.0 m 2 / g. In particular, a porous particulate leukocyte removal filter material has a large number of vacuoles separated by a membrane, forms a continuous pore structure in which the vacuoles are connected, and the continuous pores of the connected vacuoles are porous. It has been found that the above problem can be solved very effectively by using macroporous spherical particles having a structure that extends radially from the surface to the inside of the particles. Further, the present invention relates to
not less than 50 μm and a particle diameter of 50 μm
It has been found that a leukocyte-removing filter device in which a porous particle-like leukocyte-removing filter material having a size of less than μm is compressed so as to have a swelling volume of 30% or more and 100% or less and filled in a container solves the above problem. That is, the present invention relates to a leukocyte removal filter material capable of removing leukocytes without causing an increase in pressure loss accompanying the processing of a leukocyte suspension, and a leukocyte removal filter device filled with the leukocyte removal filter device.
【０００７】本発明の多孔質粒子は、平均開孔径が３μ
ｍ以上５０μｍ未満で、かつ粒子径が５０μｍ以上５０
０μｍ未満の粒子である。ここで言う平均開孔径とは、
乾燥状態で粒子表面に開孔した孔の平均孔径であり、平
均開孔径の測定方法としては、多孔質粒子を走査型電子
顕微鏡で細孔の開孔部分の直径を測定する方法があげら
れる。また、レーザー光を利用した顕微鏡を用いて写真
撮影し、より精度良く細孔の開孔部分の直径を測定する
こともできる。粒子径とは、乾燥状態の多孔質粒子を走
査型電子顕微鏡で写真撮影を行い、その写真から多孔質
粒子の直径を測定して得た値である。多孔質粒子の形状
が球状とみなせない場合は、長径と短径を測定し、長径
と短径の和の２分の１の値を便宜上多孔質粒子の直径と
する。白血球浮遊液を白血球除去フィルター装置で処理
する際の圧力損失は、白血球浮遊液の流れに対して垂直
方向のフィルター材断面に存在している空間部分の占め
る面積の大小に依存していると考えられる。従って、有
効濾過部分の断面積が同じ白血球除去フィルター装置で
も、フィルター材断面に存在している空間部分の占める
面積が大きい白血球除去フィルター装置は、白血球浮遊
液を処理する際の圧力損失が小さいと考えられる。不織
布またはシート状多孔質体から構成される白血球除去フ
ィルターでは、白血球浮遊液を処理すると、捕捉された
白血球が、フィルター材断面に存在している空間部分を
閉塞させ、白血球浮遊液の流路を狭める。これにより白
血球浮遊液の処理に伴って圧力損失が上昇する。その結
果、処理速度が著しく低下し、短時間で白血球浮遊液を
処理できなくなることもある。一方、本発明の多孔質粒
子では、多孔質粒子間の間隙が白血球浮遊液の流路とし
て確保されている上に、白血球は、多孔質粒子の最表面
のみに捕捉されるのではなく、大部分は多孔質粒子の内
部に捕捉され、白血球が捕捉されても多孔質粒子の粒子
径は見かけ上大きくならない。従って、白血球の捕捉が
進んでも多孔質粒子間の間隙が狭められることが起こり
にくい。この結果、白血球浮遊液の処理に伴う圧力損失
の上昇は回避される。The porous particles of the present invention have an average pore size of 3 μm.
m or more and less than 50 μm, and the particle size is 50 μm or more and 50 or less.
The particles are smaller than 0 μm. The average pore size here is
It is the average pore diameter of the pores formed on the particle surface in a dry state, and examples of the method of measuring the average pore diameter include a method of measuring the diameter of the pores of the porous particles with a scanning electron microscope. Further, it is also possible to take a photograph using a microscope using a laser beam and measure the diameter of the opening portion of the pore with higher accuracy. The particle diameter is a value obtained by taking a photograph of a porous particle in a dry state with a scanning electron microscope and measuring the diameter of the porous particle from the photograph. When the shape of the porous particles cannot be regarded as spherical, the major axis and the minor axis are measured, and the value of half the sum of the major axis and the minor axis is defined as the diameter of the porous particles for convenience. It is considered that the pressure loss when processing leukocyte suspension with the leukocyte removal filter device depends on the area occupied by the space occupying the cross section of the filter material perpendicular to the flow of leukocyte suspension. Can be Therefore, even in the leukocyte removal filter device having the same cross-sectional area of the effective filtration portion, the leukocyte removal filter device having a large area occupied by the space existing in the filter material cross-section has a small pressure loss when processing the leukocyte suspension. Conceivable. In a leukocyte removal filter composed of a nonwoven fabric or a sheet-like porous material, when the leukocyte suspension is treated, the captured leukocytes block the space existing in the cross section of the filter material, thereby blocking the flow path of the leukocyte suspension. Narrow. Thereby, the pressure loss increases with the processing of the leukocyte suspension. As a result, the processing speed is significantly reduced, and the leukocyte suspension may not be processed in a short time. On the other hand, in the porous particles of the present invention, the gap between the porous particles is secured as a flow path of the leukocyte suspension, and the leukocytes are not trapped only on the outermost surface of the porous particles, but are large. The portion is trapped inside the porous particles, and even if leukocytes are trapped, the particle size of the porous particles does not increase apparently. Therefore, even if the capture of leukocytes progresses, it is unlikely that the gap between the porous particles is narrowed. As a result, an increase in pressure loss due to the processing of the leukocyte suspension is avoided.
【０００８】本発明の多孔質粒子は、平均開孔径が３μ
ｍ以上５０μｍ未満である。即ち、平均開孔径が３μｍ
未満であると、多孔質粒子表面の細孔の開孔径が白血球
よりも小さいために、白血球は細孔の内部には入り込ま
ずに多孔質粒子の表面近傍に捕捉される。これにより、
白血球浮遊液の処理に伴って、多孔質粒子の粒子径は捕
捉された白血球によって見かけ上大きくなり、白血球浮
遊液の流路が狭められる。この結果、白血球浮遊液を処
理する際の圧力損失が上昇するので好ましくない。ま
た、平均開孔径が５０μｍ以上であると、多孔質粒子の
強度が不足し、白血球浮遊液を処理する際に破壊につな
がるので好ましくない。多孔質粒子の平均開孔径は、５
μｍ以上４５μｍ未満であることがより好ましく、さら
には、８μｍ以上４０μｍ未満であることが最も好まし
い。多孔質粒子の粒子径は、５０μｍ以上５００μｍ未
満である。多孔質粒子の粒子径が５０μｍ未満である
と、粒子間の間隙、即ち、白血球浮遊液の流路が狭く、
白血球浮遊液を処理するためには大きな圧力を加えなけ
ればならないので好ましくない。また、多孔質粒子の粒
子径が５００μｍ以上であると、粒子間の間隙が極めて
大きく、白血球浮遊液の大部分が多孔質粒子と接触しな
いまま素通りするので、効率良く白血球を捕捉すること
ができないため好ましくない。多孔質粒子の粒子径とし
て好ましいのは７０μｍ以上３００μｍ未満であり、最
も好ましいのは８０μｍ以上２５０μｍ未満である。多
孔質粒子の粒子径と平均開孔径の比（粒子径／平均開孔
径）は２以上１５０未満が好ましい。多孔質粒子の粒子
径／平均開孔径比が小さくなりすぎると、粒子径に対し
て平均開孔径が大きくなるために、多孔質粒子の強度が
不足して白血球浮遊液を処理する際に破壊される恐れが
あるので好ましくない。また、粒子径／平均開孔径比が
大きくなりすぎると、粒子径が大きすぎることにつなが
り、粒子間隙が広く、白血球浮遊液の大部分が多孔質粒
子と接触しないまま素通りするため、効率良く白血球を
捕捉することができ難くなるので好ましくない。粒子径
／平均開孔径比は、好ましくは３以上１００未満であ
り、最も好ましくは３以上５０未満である。多孔質粒子
の形状は特に限定されないが、容器内での充填効果を高
めるために、球形、長球形、扁平球形などの形状の多孔
質粒子を利用することができるが、球形状のものが特に
好ましい。The porous particles of the present invention have an average pore size of 3 μm.
m and less than 50 μm. That is, the average pore diameter is 3 μm
If it is less than 1, since the pore diameter of the pores on the surface of the porous particles is smaller than that of the leukocytes, the leukocytes are trapped near the surface of the porous particles without entering the pores. This allows
With the treatment of the leukocyte suspension, the particle size of the porous particles becomes apparently larger due to the captured leukocytes, and the flow path of the leukocyte suspension is narrowed. As a result, the pressure loss when processing the leukocyte suspension increases, which is not preferable. On the other hand, if the average pore diameter is 50 μm or more, the strength of the porous particles becomes insufficient, which may lead to destruction when processing the leukocyte suspension, which is not preferable. The average pore size of the porous particles is 5
It is more preferably at least 8 μm and less than 45 μm, and most preferably at least 8 μm and less than 40 μm. The particle size of the porous particles is 50 μm or more and less than 500 μm. When the particle size of the porous particles is less than 50 μm, the gap between the particles, that is, the flow path of the leukocyte suspension is narrow,
Large pressure must be applied to treat the leukocyte suspension, which is not preferable. Further, when the particle size of the porous particles is 500 μm or more, the gap between the particles is extremely large, and most of the leukocyte suspension passes without contacting the porous particles, so that it is not possible to efficiently capture leukocytes. Therefore, it is not preferable. The particle size of the porous particles is preferably from 70 μm to less than 300 μm, and most preferably from 80 μm to less than 250 μm. The ratio of the particle diameter of the porous particles to the average pore diameter (particle diameter / average pore diameter) is preferably 2 or more and less than 150. If the ratio of the particle diameter to the average opening diameter of the porous particles becomes too small, the average opening diameter becomes larger than the particle diameter, and the strength of the porous particles becomes insufficient, and the particles are destroyed when processing the leukocyte suspension. This is not preferred because On the other hand, if the particle diameter / average pore diameter ratio is too large, the particle diameter will be too large, the particle gap will be wide, and most of the leukocyte suspension will pass through without contacting the porous particles. Is difficult to capture. The particle diameter / average pore diameter ratio is preferably 3 or more and less than 100, and most preferably 3 or more and less than 50. The shape of the porous particles is not particularly limited, but in order to enhance the filling effect in the container, spherical, oval, and porous particles having a shape such as a flat sphere can be used. preferable.
【０００９】本発明の多孔質粒子を用いた白血球除去フ
ィルター材は、白血球を高密度に、しかも多孔質粒子の
最表面ではなく、内部に効率良く白血球を捕捉すること
で白血球浮遊液の処理に伴う圧力損失の上昇を回避して
いることが特徴である。このような特徴を多孔質粒子が
持つためには、乾燥状態の多孔質粒子の比表面積が０．
５ｍ2 ／ｇ以上５．０ｍ2 ／ｇ未満であることが好まし
い。比表面積の測定は、低温ガス吸着法（ＢＥＴ一点
法）により行い、流動式比表面積自動測定装置（ＢＥＴ
法、フローソーブＩＩ２３００、島津製作所製）、また
は同等の装置を用いて測定できる。比表面積が０．５ｍ
2 ／ｇより小さくなると、多孔質粒子の白血球捕捉能が
低くなる傾向にあり、高い白血球除去能を得るには多孔
質粒子を大量に使用しなければならなくなる。これはフ
ィルター装置の大型化を招き、フィルター装置内に有用
成分が残留し、回収量が低下するため好ましくない。ま
た、表面積が５．０ｍ2 ／ｇより大きくなると、多孔質
粒子の強度が小さくなり、白血球浮遊液を処理する際に
破壊される恐れがあるので好ましくない。１．０ｍ2／
ｇ以上４．０ｍ2 ／ｇ未満であることがより好ましく、
最も好ましくは１．５ｍ2 ／ｇ以上３．５ｍ2 ／ｇ未満
である。The leukocyte-removing filter material using the porous particles of the present invention is useful for treating leukocyte suspensions by capturing leukocytes at high density and efficiently capturing leukocytes inside the porous particles, not on the outermost surface. The feature is that the accompanying increase in pressure loss is avoided. In order for the porous particles to have such a characteristic, the specific surface area of the porous particles in a dry state is 0.1.
5m is preferably less than 2 / g or more 5.0 m 2 / g. The specific surface area is measured by a low-temperature gas adsorption method (BET one-point method), and a flow-type specific surface area automatic measuring device (BET)
Method, Flowsorb II2300, manufactured by Shimadzu Corporation) or an equivalent device. 0.5m specific surface area
If it is less than 2 / g, the ability of the porous particles to capture leukocytes tends to be low, and a large amount of porous particles must be used to obtain high leukocyte removal ability. This undesirably increases the size of the filter device, leaves useful components in the filter device, and reduces the recovery amount. On the other hand, if the surface area is larger than 5.0 m 2 / g, the strength of the porous particles is reduced, and the porous particles may be destroyed when the leukocyte suspension is processed, which is not preferable. 1.0m 2 /
g or more and less than 4.0 m 2 / g,
Most preferably, it is 1.5 m 2 / g or more and less than 3.5 m 2 / g.
【００１０】本発明に使用される多孔質粒子は、平均開
孔径が３μｍ以上５０μｍ未満、粒子径が５０μｍ以上
５００μｍ未満であることを特徴とする多孔質粒子であ
り、細孔の形状については限定されない。多孔質粒子の
細孔形状は、膜で隔てられた多数の空胞が作り出す細孔
の形状や、３次元網目状構造体が作り出す細孔の形状で
あっても良い。中でも、膜で隔てられた多数の空胞を有
し、空胞が連通した連続孔構造を形成し、連通した空胞
の連続孔が多孔質粒子の表面から内部まで放射状に達す
る構造を形成していることを特徴とする多孔質粒子は、
平均開孔径、比表面積、空孔率の大きい多孔質粒子であ
っても機械的強度が強く好ましい。また、平均開孔径が
大きいので、白血球が多孔質粒子の内部に進入し易く、
比表面積が大きいので白血球が粘着する活性点が多いた
め、多孔質粒子単位体積あたりに捕捉することができる
白血球数が極めて多く、少量の多孔質粒子を使用し高効
率で白血球浮遊液から白血球を除去することができる。The porous particles used in the present invention are characterized by having an average pore size of 3 μm or more and less than 50 μm and a particle size of 50 μm or more and less than 500 μm, and the shape of the pores is limited. Not done. The pore shape of the porous particles may be the shape of pores created by a large number of vacuoles separated by a membrane, or the shape of pores created by a three-dimensional network structure. Above all, it has a number of vacuoles separated by a membrane, forms a continuous pore structure in which the vacuoles communicate, and forms a structure in which the continuous pores of the communicated vacuoles extend radially from the surface to the inside of the porous particles. The porous particles are characterized in that:
Even porous particles having a large average pore diameter, specific surface area and porosity have high mechanical strength and are preferred. In addition, since the average pore size is large, leukocytes easily enter the interior of the porous particles,
Since the specific surface area is large, there are many active sites to which leukocytes adhere, so the number of leukocytes that can be captured per unit volume of porous particles is extremely large, and leukocytes can be efficiently separated from leukocyte suspension using a small amount of porous particles. Can be removed.
【００１１】本発明の、平均開孔径が３μｍ以上５０μ
ｍ未満で、かつ粒子径が５０μｍ以上５００μｍ未満で
ある多孔質粒子状の白血球除去フィルター材を用いるこ
とにより、白血球浮遊液を処理する際の圧力損失の上昇
の回避を達成することができるため、多孔質粒子の素材
としては、各種の公知の素材を用いることができる。好
ましい素材としてはセルロースが利用できる。セルロー
スは容易に反応する水酸基を有しているので、種々の白
血球高親和性リガンドの導入を行うことで、更に白血球
との親和性を高めることも容易である。セルロースを用
いて本発明の多孔質粒子を製造する方法としては、特公
平４−４１６９８などに開示されている。各種の公知の
多孔質粒子の中でも、図１に示したマクロポーラス化し
た球状セルロース粒子（Ｃｅｌｌｕｌｏｓｅ ｍａｃｒ
ｏ Ｐｏｒｏｕｓ Ｂｅａｄｓ（ＣＰＢ）：旭化成工業
株式会社製）は、膜で隔てられた多数の空胞を有し、空
胞が連通した連続孔構造を形成し、連通した空胞の連続
孔が多孔質粒子の表面から内部まで放射状に達する構造
を形成していることを特徴とする多孔質粒子であり、平
均開孔径が３μｍ以上５０μｍ未満、粒子径が５０μｍ
以上５００μｍ未満である多孔質粒子を作製することが
できるので特に好ましい。In the present invention, the average pore diameter is 3 μm or more and 50 μm or more.
m, and by using a porous particulate leukocyte removal filter material having a particle diameter of 50 μm or more and less than 500 μm, it is possible to avoid an increase in pressure loss when processing a leukocyte suspension, As the material of the porous particles, various known materials can be used. Cellulose can be used as a preferable material. Since cellulose has a hydroxyl group that reacts easily, it is easy to further increase the affinity with leukocytes by introducing various leukocyte high-affinity ligands. A method for producing the porous particles of the present invention using cellulose is disclosed in Japanese Patent Publication No. 4-41698. Among various known porous particles, the macroporous spherical cellulose particles (Cellulose macr) shown in FIG.
o Porous Beads (CPB): manufactured by Asahi Kasei Kogyo Co., Ltd.) has a large number of vacuoles separated by a membrane, forms a continuous pore structure in which the vacuoles communicate, and the continuous pores of the communicated voids are porous. It is a porous particle characterized by forming a structure reaching radially from the surface to the inside of the particle, having an average pore size of 3 μm or more and less than 50 μm, and a particle size of 50 μm.
This is particularly preferable because porous particles having a size of at least 500 μm can be produced.
【００１２】本発明の白血球除去フィルター装置は、前
記の多孔質粒子を膨潤体積の３０％以上１００％以下と
なるように圧縮して充填した白血球除去フィルター装置
である。膨潤体積とは、多孔質粒子を生理食塩水に浸漬
し、２５℃で２４時間静置、沈降させた時の多孔質粒子
の体積である。多孔質粒子の充填密度が膨潤体積の３０
％未満であると、多孔質粒子間の間隙が小さく、白血球
浮遊液の流路が小さくなるために、白血球浮遊液を処理
する際の圧力損失が大きくなるので好ましくない。更
に、鋭意研究を重ねた結果、多孔質粒子を充填する容器
の形状は、容器断面積（ｃｍ2 ）の平方根／容器厚み
（ｃｍ）の比が、０．０２以上１．５０未満であること
が好ましいことがわかった。容器断面積（ｃｍ2 ）の平
方根／容器厚み（ｃｍ）の比が、０．０２未満である
と、容器厚みが長くなるため、白血球浮遊液を処理する
際の圧力損失が大きくなり好ましくない。また、容器断
面積（ｃｍ2 ）の平方根／容器厚み（ｃｍ）の比が、
１．５０以上の場合、多孔質粒子を容器に充填すると、
平板状に充填することになり多孔質粒子の充填状態に疎
密の斑が生じやすくなる。このため、局所的に粒子間の
間隙が極めて大きい部分が生じ、白血球浮遊液の大部分
が多孔質粒子と接触しないまま素通りするようになるの
で、効率良く白血球を捕捉することができないことがあ
り好ましくない。容器断面積（ｃｍ2 ）の平方根／容器
厚み（ｃｍ）の比は、０．０３以上１．３０未満である
ことが好ましく、最も好ましくは０．０５以上１．２０
未満である。The leukocyte-removing filter device of the present invention is a leukocyte-removing filter device in which the porous particles are compressed and filled so as to have a swelling volume of 30% to 100%. The swelling volume is the volume of the porous particles when the porous particles are immersed in physiological saline, allowed to stand at 25 ° C. for 24 hours, and settle. The packing density of the porous particles is 30% of the swollen volume.
% Is not preferable because the gap between the porous particles is small and the flow path of the leukocyte suspension becomes small, so that the pressure loss when processing the leukocyte suspension increases. Furthermore, as a result of intensive studies, the shape of the container filled with the porous particles is such that the ratio of the square root of the container cross-sectional area (cm 2 ) / the container thickness (cm) is 0.02 or more and less than 1.50. Was found to be preferable. If the ratio of the square root of the container cross-sectional area (cm 2 ) / the thickness of the container (cm) is less than 0.02, the thickness of the container becomes long, and the pressure loss when processing the leukocyte suspension is undesirably large. Further, the ratio of the square root of the container cross-sectional area (cm 2 ) / the container thickness (cm) is
1.50 or more, when the porous particles are filled in a container,
Since the packing is performed in a flat plate shape, unevenness of the packing density of the porous particles tends to occur. For this reason, a part where the gap between particles is extremely large locally occurs, and most of the leukocyte suspension liquid passes without contacting the porous particles, so that it may not be possible to efficiently capture leukocytes. Not preferred. The ratio of the square root of the container cross-sectional area (cm 2 ) to the container thickness (cm) is preferably 0.03 or more and less than 1.30, and most preferably 0.05 or more and 1.20.
Is less than.
【００１３】[0013]
【発明の実施の態様】以下、実施例により本発明を詳細
に説明する。DESCRIPTION OF THE PREFERRED EMBODIMENTS Hereinafter, the present invention will be described in detail with reference to examples.
【実施例１】平均開孔径が３０μｍ、粒子径が１５０μ
ｍ、表面積２．８ｍ2 ／ｇ、膨潤体積が２１．５ｍＬ／
ｇのマクロポーラス化した球状セルロース粒子（ＣＰ
Ｂ：旭化成工業株式会社製）を、内径が９．０ｍｍの円
筒形の容器に、厚さ８．０ｍｍとなるよう膨潤体積の３
８．８％に圧縮、即ち、充填密度が０．１２０ｇ／ｃｍ
3 となるように充填した。このフィルター装置の容器断
面積（ｃｍ2 ）の平方根／容器厚み（ｃｍ）の比は１．
００である。このフィルター装置内部をあらかじめ生理
食塩水で満たした後、白血球浮遊液であるＡＣＤ添加新
鮮牛全血（ヘマトクリット値３９％）５ｍＬをシリンジ
ポンプを用いて、０．１ｍＬ／分の流速で流した。実験
中、圧力損失の変化をデジタル圧力計を用いて測定し
た。フィルター装置で濾過する前後のＡＣＤ添加新鮮牛
全血中に存在する白血球濃度は、チュルク液によって１
０倍希釈した濾過前後のＡＣＤ添加新鮮牛全血を、ビル
ケルチュルク型の血球計算盤に注入し、光学顕微鏡を用
いて白血球数を計数することにより求めた。濾過前の白
血球濃度は１９１３個／μＬであった。以上の結果、濾
過中の圧力損失は最大１８ｍｍＨｇ、白血球除去率は９
９．７％であった。また、白血球浮遊液を濾過した後の
ＣＰＢの断面を走査型電子顕微鏡で観察したところ、図
２に示したようにＣＰＢ内部に白血球が捕捉されている
様子が観察された。Example 1 The average pore size was 30 μm and the particle size was 150 μm.
m, surface area 2.8 m 2 / g, swelling volume 21.5 mL /
g of macroporous spherical cellulose particles (CP
B: manufactured by Asahi Kasei Kogyo Co., Ltd.) in a cylindrical container having an inner diameter of 9.0 mm and a swelling volume of 3 mm so as to have a thickness of 8.0 mm.
8.8% compression, ie packing density 0.120 g / cm
3 was filled. The ratio of the square root of the container cross-sectional area (cm 2 ) to the container thickness (cm) of this filter device was 1.
00. After the inside of the filter device was filled with physiological saline in advance, 5 mL of ACD-added fresh bovine whole blood (hematocrit value of 39%) as a leukocyte suspension was flowed at a flow rate of 0.1 mL / min using a syringe pump. During the experiment, the change in pressure loss was measured using a digital manometer. The concentration of leukocytes present in ACD-added fresh bovine whole blood before and after filtration with a filter device was 1% by Turk's solution.
ACD-added fresh bovine whole blood before and after filtration, diluted to 0-fold, was injected into a Birkelturk-type hemocytometer, and the number of leukocytes was determined using an optical microscope. The leukocyte concentration before filtration was 1913 cells / μL. As a result, the pressure loss during filtration was a maximum of 18 mmHg, and the leukocyte removal rate was 9
9.7%. When the cross section of the CPB after filtering the leukocyte suspension was observed with a scanning electron microscope, it was observed that leukocytes were trapped inside the CPB as shown in FIG.
【００１４】[0014]
【比較例１】平均繊維直径が１．８μｍ、厚さ０．４ｍ
ｍのポリエステル製不織布を、直径９．０ｍｍの円形に
切断し充填密度が０．１６５ｇ／ｃｍ3 となるよう調整
し、内径が９．０ｍｍの円筒形の容器に充填した。この
フィルター装置で、実施例１と同じ操作によって同一の
白血球浮遊液を濾過した。この結果、白血球除去率は９
９．７％であったが、濾過中の圧力損失は、最大４３ｍ
ｍＨｇまで上昇した。Comparative Example 1 Average fiber diameter is 1.8 μm, thickness 0.4 m
m polyester non-woven fabric was cut into a circular shape having a diameter of 9.0 mm, adjusted to a packing density of 0.165 g / cm 3, and filled in a cylindrical container having an inner diameter of 9.0 mm. The same leukocyte suspension was filtered by the same operation as in Example 1 using this filter device. As a result, the leukocyte removal rate was 9
9.7%, but the pressure loss during filtration was up to 43 m
mHg.
【００１５】[0015]
【実施例２】平均開孔径が３０μｍ、粒子径が２３０μ
ｍ、表面積２．８ｍ2 ／ｇ、膨潤体積が２８．２ｍＬ／
ｇのマクロポーラス化した球状セルロース粒子（ＣＰ
Ｂ：旭化成工業株式会社製）を、内径が９．０ｍｍの円
筒形の容器に、厚さ８．０ｍｍとなるよう、膨潤体積の
３８．８％に圧縮、即ち、充填密度が０．０９１ｇ／ｃ
ｍ3 となるように充填した。このフィルター装置の容器
断面積（ｃｍ2 ）の平方根／容器厚み（ｃｍ）の比は
１．００である。このフィルター装置に、白血球浮遊液
であるＡＣＤ添加新鮮牛全血（ヘマトクリット値４１
％）５ｍＬをシリンジポンプを用いて、０．１ｍＬ／分
の流速で流した。濾過前の白血球濃度は５９２５個／μ
Ｌであった。実施例１と同様に、フィルター装置で濾過
する前後のＡＣＤ添加新鮮牛全血中に存在する白血球濃
度を求め、この値から白血球除去率を求めた。この結
果、白血球除去率は９９．７％であった。濾過中の圧力
損失は、最大１５ｍｍＨｇで白血球浮遊液の流れは良好
であった。Example 2 The average pore size is 30 μm and the particle size is 230 μm
m, surface area 2.8 m 2 / g, swelling volume 28.2 mL /
g of macroporous spherical cellulose particles (CP
B: Asahi Kasei Kogyo Co., Ltd.) was compressed to 38.8% of the swelling volume in a cylindrical container having an inner diameter of 9.0 mm to a thickness of 8.0 mm, that is, a packing density of 0.091 g / c
m 3 . The ratio of the square root of container cross-sectional area (cm 2 ) / container thickness (cm) of this filter device is 1.00. In this filter device, fresh bovine whole blood containing ACD as a leukocyte suspension (haematocrit value of 41) was added.
%) Using a syringe pump at a flow rate of 0.1 mL / min. Leukocyte concentration before filtration is 5925 cells / μ
L. In the same manner as in Example 1, the leukocyte concentration present in the whole blood of the ACD-added fresh cow before and after filtration with the filter device was determined, and the leukocyte removal rate was determined from this value. As a result, the leukocyte removal rate was 99.7%. The maximum pressure loss during filtration was 15 mmHg, and the flow of leukocyte suspension was good.
【００１６】[0016]
【実施例３】平均開孔径が３０μｍ、粒子径が２３０μ
ｍ、表面積２．８ｍ2 ／ｇ、膨潤体積が２８．２ｍＬ／
ｇのＣＰＢを、内径が９．０ｍｍの円筒形の容器に、厚
さ１６ｍｍとなるよう、膨潤体積の７７．６％、即ち、
充填密度が０．０４６ｇ／ｃｍ3 となるように充填し
た。このフィルター装置で、実施例２と同じ操作によっ
て同一の白血球浮遊液を濾過した。この結果、白血球除
去率は８６．６％であった。濾過中の圧力損失は、最大
１０ｍｍＨｇで白血球浮遊液の流れは良好であった。Example 3 The average pore size was 30 μm and the particle size was 230 μm.
m, surface area 2.8 m 2 / g, swelling volume 28.2 mL /
g of CPB was placed in a cylindrical container having an inner diameter of 9.0 mm so as to have a thickness of 16 mm.
The packing was performed so that the packing density became 0.046 g / cm 3 . The same leukocyte suspension was filtered by the same operation as in Example 2 using this filter device. As a result, the leukocyte removal rate was 86.6%. The pressure loss during the filtration was 10 mmHg at the maximum, and the flow of the leukocyte suspension was good.
【００１７】実施例１から実施例３と比較例１の結果を
表１に示した。表１から、本発明の多孔質粒子は、従来
のフィルター材に比べて、白血球浮遊液を処理する際の
圧力損失は低いことがわかる。Table 1 shows the results of Examples 1 to 3 and Comparative Example 1. From Table 1, it can be seen that the porous particles of the present invention have a lower pressure loss when treating leukocyte suspensions than conventional filter materials.
【００１８】 注１：膨潤体積に対する圧縮率 注２：平均繊維直径１．８μｍのポリエステル製不織布 [0018] Note 1: Compression ratio to swelling volume Note 2: Polyester nonwoven fabric with average fiber diameter of 1.8 μm
【００１９】[0019]
【比較例２】平均開孔径が３０μｍ、粒子径が２３０μ
ｍ、表面積２．８ｍ2 ／ｇ、膨潤体積が２８．２ｍＬ／
ｇのＣＰＢを、内径が９．０ｍｍの円筒形の容器に、厚
さ４．７ｍｍとなるよう、膨潤体積の２３．３％に圧
縮、即ち、充填密度が０．１５２ｇ／ｃｍ3 となるよう
に充填した。このフィルター装置で、実施例２と同じ操
作によって同一の白血球浮遊液を濾過した。この結果、
白血球除去率は６７．１％であった。濾過中の圧力損失
は、４３８ｍｍＨｇにまで上昇した。Comparative Example 2 Average opening diameter is 30 μm and particle diameter is 230 μm
m, surface area 2.8 m 2 / g, swelling volume 28.2 mL /
g CPB in a cylindrical container having an inner diameter of 9.0 mm is compressed to 23.3% of the swollen volume so as to have a thickness of 4.7 mm, that is, a packing density of 0.152 g / cm 3. Was filled. The same leukocyte suspension was filtered by the same operation as in Example 2 using this filter device. As a result,
The leukocyte removal rate was 67.1%. The pressure drop during filtration rose to 438 mmHg.
【００２０】実施例２、実施例３及び比較例２の結果を
表２に示した。表２から、本発明の多孔質粒子を、膨潤
体積の３０％以上１００％以下となるようフィルター容
器に充填することにより、白血球浮遊液を処理する際の
圧力損失が低い、白血球除去フィルター装置となること
がわかる。The results of Example 2, Example 3, and Comparative Example 2 are shown in Table 2. From Table 2, it can be seen that by filling the porous container of the present invention into a filter container so as to have a swelling volume of 30% or more and 100% or less, a leukocyte removal filter device having a low pressure loss when treating a leukocyte suspension. It turns out that it becomes.
【００２１】 注１：膨潤体積に対する圧縮率 [0021] Note 1: Compression ratio to swelling volume
【００２２】[0022]
【実施例４】平均開孔径が３０μｍ、粒子径が１５０μ
ｍ、表面積２．８ｍ2 ／ｇ、膨潤体積が２１．５ｍＬ／
ｇのＣＰＢを、内径が４．５ｍｍの円筒形の容器に、厚
さ５６ｍｍとなるよう、膨潤体積の７７．６％、即ち、
充填密度が０．０６０ｇ／ｃｍ3 となるように充填し
た。このフィルター装置の容器断面積（ｃｍ2 ）の平方
根／容器厚み（ｃｍ）の比は０．０７１である。このフ
ィルター装置内部を、あらかじめ生理食塩水で満たした
後、白血球浮遊液であるＡＣＤ添加新鮮牛全血（ヘマト
クリット値３７％）５ｍＬをシリンジポンプを用いて、
０．２ｍＬ／分の流速で流した。実験中、圧力損失の変
化をデジタル圧力計を用いて測定した。濾過前の白血球
濃度は９８６個／μＬであった。以上の結果、濾過中の
圧力損失は最大３１ｍｍＨｇ、白血球除去率は９９．７
％であった。Example 4 The average pore size was 30 μm and the particle size was 150 μm.
m, surface area 2.8 m 2 / g, swelling volume 21.5 mL /
g of CPB was placed in a cylindrical container having an inner diameter of 4.5 mm so as to have a thickness of 56 mm by 77.6% of the swelling volume, that is,
The packing was performed so that the packing density became 0.060 g / cm 3 . The ratio of the square root of the container cross-sectional area (cm 2 ) to the container thickness (cm) of this filter device is 0.071. After filling the inside of the filter device with a physiological saline solution in advance, 5 mL of ACD-added fresh bovine whole blood (hematocrit value 37%), which is a leukocyte suspension, was used using a syringe pump.
The flow was at a flow rate of 0.2 mL / min. During the experiment, the change in pressure loss was measured using a digital manometer. The leukocyte concentration before filtration was 986 cells / μL. As a result, the pressure loss during filtration was 31 mmHg at maximum, and the leukocyte removal rate was 99.7.
%Met.
【００２３】[0023]
【発明の効果】本発明の白血球選択除去フィルター材
は、平均開孔径が３μｍ以上５０μｍ未満で、かつ粒子
径が５０μｍ以上５００μｍ未満である多孔質粒子状で
あり、白血球浮遊液の処理に伴って圧力損失の上昇を引
き起こすことなく白血球を除去できる白血球除去フィル
ター材を提供することができた。本発明の白血球除去フ
ィルター材を、膨潤体積の３０％以上１００％以下とな
るように容器に充填することにより、白血球浮遊液の処
理に伴って圧力損失の上昇を引き起こすことなく白血球
を除去できる、白血球除去フィルター装置を提供するこ
とができた。The filter material for selectively removing leukocytes of the present invention is in the form of porous particles having an average pore size of 3 μm or more and less than 50 μm and a particle size of 50 μm or more and less than 500 μm. A leukocyte removal filter material capable of removing leukocytes without causing an increase in pressure loss can be provided. By filling the container with the leukocyte-removing filter material of the present invention so as to have a swelling volume of 30% or more and 100% or less, leukocytes can be removed without causing an increase in pressure loss accompanying the treatment of leukocyte suspension. A leukocyte removal filter device could be provided.
【図１】本発明の白血球除去フィルター材の電子顕微鏡
写真（倍率３５０倍）。FIG. 1 is an electron micrograph (× 350) of a leukocyte removal filter material of the present invention.
【図２】白血球浮遊液を濾過した後の、本発明の白血球
除去フィルター材断面の電子顕微鏡写真（倍率６００
倍）。FIG. 2 is an electron micrograph (600 magnifications) of a cross section of a leukocyte removal filter material of the present invention after filtering a leukocyte suspension.
Times).
Claims (4)
で、かつ粒子径が５０μｍ以上５００μｍ未満の多孔質
粒子であることを特徴とする白血球除去フィルター材。1. A leukocyte removal filter material comprising porous particles having an average pore diameter of 3 μm or more and less than 50 μm and a particle diameter of 50 μm or more and less than 500 μm.
2 ／ｇ未満である請求項１に記載された白血球除去フィ
ルター材。2. The specific surface area is 0.5 m 2 / g or more and 5.0 m or more.
2. The leukocyte-removing filter material according to claim 1, which is less than 2 / g.
は連通した連続孔構造を形成し、連通した空胞の連続孔
が多孔質粒子の表面から内部まで放射状に達する構造を
形成していることを特徴とする請求項１および請求項２
に記載された白血球除去フィルター材。3. A structure having a large number of vacuoles separated by a membrane, wherein the vacuoles form a continuous continuous pore structure, and the continuous pores of the continuous vacuoles radiate from the surface to the inside of the porous particles. 3. The method according to claim 1, wherein
A leukocyte removal filter material described in 1.
で、かつ粒子径が５０μｍ以上５００μｍ未満の多孔質
粒子である白血球除去フィルター材を、膨潤体積の３０
％以上１００％以下となるように圧縮して容器に充填し
たことを特徴とする白血球除去フィルター装置。4. A leukocyte removal filter material, which is a porous particle having an average pore diameter of 3 μm or more and less than 50 μm and a particle diameter of 50 μm or more and less than 500 μm, has a swelling volume of 30 μm.
%. The leukocyte-removing filter device, which is compressed so as to be not less than 100% and filled in a container.
Priority Applications (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| JP8240972A JPH1057477A (en) | 1996-08-26 | 1996-08-26 | White blood cell removing filter material and white blood cell removing filter device |
Applications Claiming Priority (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| JP8240972A JPH1057477A (en) | 1996-08-26 | 1996-08-26 | White blood cell removing filter material and white blood cell removing filter device |
Publications (1)
| Publication Number | Publication Date |
|---|---|
| JPH1057477A true JPH1057477A (en) | 1998-03-03 |
Family
ID=17067405
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| JP8240972A Pending JPH1057477A (en) | 1996-08-26 | 1996-08-26 | White blood cell removing filter material and white blood cell removing filter device |
Country Status (1)
| Country | Link |
|---|---|
| JP (1) | JPH1057477A (en) |
Cited By (2)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| WO2005120600A1 (en) * | 2004-06-09 | 2005-12-22 | Asahi Kasei Medical Co., Ltd. | Method for removing leukocyte and filter for use therein |
| WO2007133147A1 (en) | 2006-05-12 | 2007-11-22 | Ibd Column Therapies International Ab | Method and means for treating inflammatory bowel disease |
-
1996
- 1996-08-26 JP JP8240972A patent/JPH1057477A/en active Pending
Cited By (7)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| WO2005120600A1 (en) * | 2004-06-09 | 2005-12-22 | Asahi Kasei Medical Co., Ltd. | Method for removing leukocyte and filter for use therein |
| JPWO2005120600A1 (en) * | 2004-06-09 | 2008-04-03 | 旭化成メディカル株式会社 | Leukocyte removal method and filter used in the method |
| KR100845063B1 (en) | 2004-06-09 | 2008-07-09 | 아사히 가세이 메디컬 가부시키가이샤 | Method for removing leukocyte and filter for use therein |
| CN100512890C (en) | 2004-06-09 | 2009-07-15 | 旭化成医疗株式会社 | Method for removing leukocyte and filter for use therein |
| JP4854083B2 (en) * | 2004-06-09 | 2012-01-11 | 旭化成メディカル株式会社 | Leukocyte removal method and filter used in the method |
| US8900462B2 (en) | 2004-06-09 | 2014-12-02 | Asahi Kasei Medical Co., Ltd | Method for removing leukocyte and filter for use therein |
| WO2007133147A1 (en) | 2006-05-12 | 2007-11-22 | Ibd Column Therapies International Ab | Method and means for treating inflammatory bowel disease |
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