JP2002320669A - Method for blood filtration - Google Patents
Method for blood filtrationInfo
- Publication number
- JP2002320669A JP2002320669A JP2001129177A JP2001129177A JP2002320669A JP 2002320669 A JP2002320669 A JP 2002320669A JP 2001129177 A JP2001129177 A JP 2001129177A JP 2001129177 A JP2001129177 A JP 2001129177A JP 2002320669 A JP2002320669 A JP 2002320669A
- Authority
- JP
- Japan
- Prior art keywords
- blood
- filter
- product
- whole blood
- filtration
- 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
- 210000004369 blood Anatomy 0.000 title claims abstract description 116
- 239000008280 blood Substances 0.000 title claims abstract description 116
- 238000001914 filtration Methods 0.000 title claims abstract description 67
- 238000000034 method Methods 0.000 title claims abstract description 30
- 210000000265 leukocyte Anatomy 0.000 claims abstract description 82
- 239000010836 blood and blood product Substances 0.000 claims description 81
- 229940125691 blood product Drugs 0.000 claims description 81
- 210000000601 blood cell Anatomy 0.000 claims description 43
- 238000005534 hematocrit Methods 0.000 claims description 26
- 238000003860 storage Methods 0.000 claims description 16
- 210000001772 blood platelet Anatomy 0.000 abstract description 45
- 210000003743 erythrocyte Anatomy 0.000 abstract description 15
- 238000002360 preparation method Methods 0.000 abstract description 14
- 239000012503 blood component Substances 0.000 abstract description 11
- 210000002381 plasma Anatomy 0.000 abstract description 10
- 210000004180 plasmocyte Anatomy 0.000 abstract 1
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- SJIXRGNQPBQWMK-UHFFFAOYSA-N 2-(diethylamino)ethyl 2-methylprop-2-enoate Chemical compound CCN(CC)CCOC(=O)C(C)=C SJIXRGNQPBQWMK-UHFFFAOYSA-N 0.000 description 3
- RSGFPIWWSCWCFJ-VAXZQHAWSA-N 2-hydroxypropane-1,2,3-tricarboxylic acid;(2r,3s,4r,5r)-2,3,4,5,6-pentahydroxyhexanal;phosphoric acid Chemical compound OP(O)(O)=O.OC[C@@H](O)[C@@H](O)[C@H](O)[C@@H](O)C=O.OC(=O)CC(O)(C(O)=O)CC(O)=O RSGFPIWWSCWCFJ-VAXZQHAWSA-N 0.000 description 3
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Landscapes
- External Artificial Organs (AREA)
- Filtration Of Liquid (AREA)
Abstract
Description
【０００１】[0001]
【発明の属する技術分野】本発明は、赤血球、血小板、
血漿成分及び白血球を含む全血製剤から、白血球を効率
良く除去するための血液ろ過方法に関する。また、本発
明は、全血製剤から白血球を効率よく除去しつつ、且
つ、血小板を高率で回収するための血液ろ過方法に関す
る。The present invention relates to red blood cells, platelets,
The present invention relates to a blood filtration method for efficiently removing leukocytes from a whole blood product containing plasma components and leukocytes. The present invention also relates to a blood filtration method for efficiently removing leukocytes from a whole blood product and recovering platelets at a high rate.
【０００２】[0002]
【従来の技術】輸血医学の進歩により、受血者が必要と
する成分のみを輸血する、いわゆる成分輸血が今日の輸
血医療の主流となっている。成分輸血が普及した理由と
して、受血者の負荷を軽減できること、治療効果を高め
ることができること等の利点を挙げることができる。成
分輸血に用いられている濃厚赤血球製剤、濃厚血小板製
剤、血漿製剤などの血液成分製剤は、献血によって得ら
れた全血製剤を遠心分離することによって調整されてい
る。一方、このようにして調整された血液成分製剤に
は、多量の白血球が混入しており、この混入白血球が、
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、ウィルス感染、輸血後GVHDなどの重篤な
副作用を引き起こすことが明らかとなり、繊維素材や連
続気孔を有する多孔質体などのろ材を充填した白血球除
去フィルターが広く用いられるようになっている。2. Description of the Related Art With the advance of transfusion medicine, so-called component transfusion, which transfuses only components required by a blood recipient, has become the mainstream of transfusion medicine today. The reasons why component blood transfusion has become widespread include advantages such as the ability to reduce the burden on the recipient and the ability to enhance the therapeutic effect. Blood component preparations such as concentrated red blood cell preparations, concentrated platelet preparations, and plasma preparations used for component blood transfusion are prepared by centrifuging a whole blood preparation obtained by donating blood. On the other hand, the blood component preparation thus adjusted contains a large amount of leukocytes, and this mixed leukocyte is
Relatively minor side effects such as headache, nausea, chills, and non-hemolytic fever reaction associated with blood transfusion, or serious side effects such as alloantigen sensitization, viral infection, and GVHD after blood transfusion that have serious effects on recipients. It has become clear that the leukocyte-removing filter is filled with a filter material such as a fiber material or a porous body having continuous pores.
【０００３】白血球除去フィルターを用いた白血球の除
去は、全血製剤から除去する場合と、各血液成分製剤を
調整した後に除去する場合に大別される。後者は各血液
成分製剤毎にフィルターが必要となるのに対し、前者は
１つのフィルターで全血製剤から白血球を除去し、その
後遠心分離することによって、複数種の白血球を除去し
た血液成分製剤を調整できるため、より好ましい方法と
考えられている。特に最近では、全血製剤用バッグ、フ
ィルター、及び遠心分離後に調整される各血液成分製剤
用のバッグ等が一体となり、無菌的に白血球を除去した
血液成分製剤が調整できる、いわゆるクローズドシステ
ムが注目され、血液センター等で使用されている（特開
平１−３２００６４号公報等）。[0003] Leukocyte removal using a leukocyte removal filter is roughly classified into a case of removing from a whole blood product and a case of removing after adjusting each blood component product. The latter requires a filter for each blood component product, while the former uses a single filter to remove leukocytes from whole blood products and then centrifuges to remove blood components from which multiple types of leukocytes have been removed. It is considered a more preferable method because it can be adjusted. In particular, recently, a so-called closed system, in which a bag for whole blood products, a filter, and a bag for each blood component product that is adjusted after centrifugation are integrated, and a blood component product from which leukocytes have been removed aseptically, has attracted attention. And is used in blood centers and the like (Japanese Patent Application Laid-Open No. 1-320064).
【０００４】しかしながら、全血製剤からフィルターに
より白血球をろ過除去しようとするときには、全血製剤
は多量の白血球が混入しているため、各血液成分製剤か
ら白血球を除去した場合と同様の残存白血球数とするに
は、より容量の大きいフィルターが要求される。しか
し、フィルター容量の増加はフィルターに残留する血液
量を増やすことになり、この残留血はろ過後にフィルタ
ーと共に廃棄されるため、貴重な血液のロス量を増大さ
せるという問題を生じてしまう。However, when attempting to filter and remove leukocytes from a whole blood product using a filter, since the whole blood product contains a large amount of leukocytes, the remaining white blood cell count is the same as when white blood cells are removed from each blood component product. To do so, a filter with a larger capacity is required. However, an increase in the filter capacity increases the amount of blood remaining on the filter, and since this residual blood is discarded together with the filter after filtration, a problem of increasing the amount of precious blood loss occurs.
【０００５】また、全血製剤は、採血後長くとも３日以
内、多くは数時間以内の新鮮な状態のものがろ過対象と
なるのが一般的であるが、このような新鮮な、特に採血
後１時間未満の、非常に新鮮で温度が高い全血製剤をろ
過する場合には、フィルターの白血球除去能が低下する
ことが知られている。[0005] In addition, a whole blood product is generally to be filtered in a fresh state within at most three days after blood collection, most often within several hours. It is known that when filtering very fresh and hot whole blood products for less than one hour later, the filter's ability to remove leukocytes decreases.
【０００６】以上のように、全血製剤から白血球を効率
良く除去するには課題が残っており、より効率良く、高
い白血球除去を達成できる血液のろ過方法の確立が強く
望まれている。As described above, there remains a problem in efficiently removing leukocytes from a whole blood product, and there is a strong demand for establishing a blood filtration method that can achieve more efficient and high leukocyte removal.
【０００７】また、近年では、全血製剤から白血球のみ
を選択的に除去するだけでなく、赤血球、血漿とともに
血小板も回収する機能を有するフィルターが開発されつ
つある（Transfusion Vol．39(1999)、No．10S、Suppl
ement、S541-040K、S542-040K）。このようなフィルタ
ーを用いて全血製剤をろ過すると、最終的に白血球を除
去した濃厚赤血球製剤、濃厚血小板製剤、血漿製剤の３
成分の血液成分製剤を調整することができる。しかしな
がら、新鮮な全血製剤に含まれている血小板は、採血に
よるストレス等でやや活性化された状態にあり、フィル
ターに粘着しやすい性質となっているので、高い血小板
回収率を安定して確保できるレベルには至っていないの
が現状である。In recent years, a filter has been developed which has a function of not only selectively removing white blood cells from a whole blood product but also collecting platelets together with red blood cells and plasma (Transfusion Vol. 39 (1999), No. 10S, Suppl
ement, S541-040K, S542-040K). When a whole blood product is filtered using such a filter, three types of concentrated erythrocyte product, rich platelet product, and plasma product, which are finally leukocytes removed, are obtained.
The component blood component preparation can be adjusted. However, platelets contained in fresh whole blood products are in a slightly activated state due to the stress of blood collection, etc., and tend to stick to filters, so a high platelet recovery rate is ensured stably. At present, it is not at a level where it can be done.
【０００８】[0008]
【発明が解決しようとする課題】本発明の課題は、この
ような従来技術の問題点を解決しようとするものであっ
て、フィルターの容量を増すことなしに、極めて新鮮な
全血製剤からも白血球を高い効率で除去できる血液のろ
過方法を提供することにある。本発明のもう一つの課題
は、新鮮な全血製剤から白血球のみを選択的に除去しつ
つ、且つ、高い血小板回収率を安定して達成できる血液
のろ過方法を提供することにある。SUMMARY OF THE INVENTION An object of the present invention is to solve such problems of the prior art, and it is possible to obtain an extremely fresh whole blood product without increasing the filter capacity. An object of the present invention is to provide a blood filtration method capable of removing leukocytes with high efficiency. Another object of the present invention is to provide a blood filtration method capable of selectively removing only white blood cells from a fresh whole blood product and stably achieving a high platelet recovery rate.
【０００９】[0009]
【課題を解決するための手段】本発明者らは、上記課題
を達成するための血液のろ過方法を鋭意検討した結果、
貯留部において敢えて血球の濃度勾配を形成させること
によって、上記課題が解決できることを見出した。Means for Solving the Problems The present inventors have intensively studied a method for filtering blood to achieve the above object, and as a result,
It has been found that the above problem can be solved by intentionally forming a blood cell concentration gradient in the reservoir.
【００１０】クローズドシステムも含め、血液製剤から
フィルターにより白血球を除去するときには、血液製剤
をよく混和し、均質な状態とした直後に１〜２ｍ程度の
落差でろ過することが従来から通常に行われている。[0010] When leukocytes are removed from a blood product using a filter, including a closed system, it has been customary to mix the blood product well and filter it with a head of about 1 to 2 m immediately after it is homogenized. ing.
【００１１】血液に含まれる血球は比重が異なり、赤血
球は約１．０８、顆粒球及び単球は約１．０７、リンパ
球は約１．０６、血小板及び血漿は約１．０３であるこ
とが知られている。このような血球を含む血液をそのま
ま静置しておくと、比重差によって血球の濃度勾配が形
成される。The blood cells contained in the blood have different specific gravities, about 1.08 for erythrocytes, about 1.07 for granulocytes and monocytes, about 1.06 for lymphocytes, and about 1.03 for platelets and plasma. It has been known. When such blood containing blood cells is allowed to stand as it is, a concentration gradient of blood cells is formed due to a difference in specific gravity.
【００１２】通常、血液製剤を白血球除去フィルターで
ろ過する前に、血液の血球濃度が均質になるように混和
されるのは、血液中に含まれる微小凝集物等によるフィ
ルターの有効ろ過面積部分の閉塞が、ろ過初期段階で発
生することを防止するためである。微小凝集物は血球に
比較して大きく、かつ重いため、不均質な状態では貯留
部の下部に沈降する。このような状態でろ過を開始する
と、沈降した微小凝集物がフィルターと比較的早く接触
し、ろ過初期段階でフィルターの有効ろ過部分で閉塞が
起こってしまい、片流れによるろ過時間の大幅な延長
や、フィルター性能の著しい低下を招く恐れがある。こ
のような現象は、数日間以上保存した血液で特に起こり
やすいと考えられ、できるだけ血液を均質な状態にした
後にろ過することが好ましいとされてきた。また、血漿
含量が少ない濃厚赤血球製剤を不均質な状態でろ過する
と、比重の重い赤血球が沈降し、その部分はヘマトクリ
ット値（血液内に占める赤血球の容積比率）が高い、極
めて粘度の高い部分となる。この部分をフィルターでろ
過しようとしても通液できなかったり、無理にろ過しよ
うと圧力をかけると、赤血球が溶血してしまう等の問題
が起こりうる。以上のような現象から、血液製剤をでき
るだけ均質な状態とした後にろ過する方が血液の流れ性
の確保、及びフィルターの白血球除去性能の安定化の観
点から好ましい、と考えられていた。Usually, before the blood product is filtered through the leukocyte removal filter, the blood product is mixed so that the blood cell concentration becomes uniform, because the effective filtration area of the filter due to microaggregates and the like contained in the blood. This is to prevent blockage from occurring at the initial stage of filtration. Since the microaggregates are larger and heavier than blood cells, they sediment at the lower part of the reservoir in a heterogeneous state. When filtration is started in such a state, the sedimented microaggregates come into contact with the filter relatively quickly, and clogging occurs in the effective filtration portion of the filter in the initial stage of filtration, and the filtration time is greatly extended by one-sided flow, There is a risk that the filter performance will be significantly reduced. It is considered that such a phenomenon is particularly likely to occur in blood stored for several days or more, and it has been considered preferable to make the blood as homogeneous as possible and then filter the blood. In addition, when a concentrated red blood cell preparation with a low plasma content is filtered in an inhomogeneous state, red blood cells having a high specific gravity sediment, and the hematocrit value (volume ratio of red blood cells in the blood) is high, which is extremely high in viscosity. Become. If this part is filtered with a filter, it may not be possible to pass the liquid, or if pressure is applied to force the filtration, problems such as hemolysis of red blood cells may occur. From the above phenomena, it has been considered that it is more preferable to make the blood product as homogeneous as possible and then filter it from the viewpoints of securing blood flowability and stabilizing the leukocyte removal performance of the filter.
【００１３】しかしながら、本発明者らは、新鮮な全血
製剤を用いて鋭意検討を行った結果、血球の濃度勾配を
故意に形成させて不均質な状態とした後、赤血球や顆粒
球等の濃度が高い血液からろ過しても、上述のような不
具合を観察しなかったばかりか、驚くべきことに、白血
球除去能が格段に向上することを見出した。さらに、血
小板回収機能を有するフィルターを用い、かかる不均質
化した全血製剤をろ過すると、意外なことに血小板回収
率も格段に向上することを見出し、本発明を完成するに
至った。However, the present inventors have conducted intensive studies using fresh whole blood products, and as a result, after intentionally forming a blood cell concentration gradient to make it in an inhomogeneous state, red blood cells, granulocytes, etc. Even when filtering from blood having a high concentration, not only the above-mentioned problems were not observed, but surprisingly, it was found that the ability to remove leukocytes was significantly improved. Furthermore, it has been found that, when the heterogeneous whole blood product is filtered using a filter having a platelet collection function, the platelet collection rate is surprisingly improved, and the present invention has been completed.
【００１４】本発明は、（１）全血製剤から白血球を除
去するための血液ろ過方法において、全血製剤を貯留す
る貯留部下部の血液のヘマトクリット値が、貯留部の全
血製剤を均質に混和した場合のヘマトクリット値より高
くなるように、貯留部に血球濃度勾配を形成した後、血
液を貯留部下部から白血球除去フィルターへ導入するこ
とを特徴とする方法、（２）全血製剤を貯留する貯留部
下部の血液のヘマトクリット値が、貯留部の全血製剤を
均質に混和した場合のヘマトクリット値の１．０５倍以
上２．５０倍未満である上記（１）記載の血液ろ過方
法、（３）貯留部下部のヘマトクリット値が３５％以上
７５％未満である上記（１）又は（２）記載の血液ろ過
方法、（４）５分以上３００分未満の静置によって血球
濃度勾配が形成される上記（１）〜（３）のいずれかに
記載の血液ろ過方法、及び（５）採血後新鮮な全血製剤
から白血球を除去することを特徴とする上記（１）〜
（４）のいずれかに記載の血液ろ過方法、に関する。According to the present invention, there is provided (1) a blood filtration method for removing leukocytes from a whole blood product, wherein the hematocrit value of the blood in the lower portion of the storage portion for storing the whole blood product is uniform in the whole blood product in the storage portion. A method characterized by forming a blood cell concentration gradient in the reservoir so as to be higher than the hematocrit value when mixed, and then introducing blood from the lower part of the reservoir to a leukocyte removal filter, (2) storing a whole blood product The blood filtration method according to the above (1), wherein the hematocrit value of the blood in the lower part of the reservoir is 1.05 times or more and less than 2.50 times the hematocrit value when the whole blood product in the reservoir is homogeneously mixed. 3) The blood filtration method according to the above (1) or (2), wherein the hematocrit value at the lower part of the reservoir is 35% or more and less than 75%, and (4) a blood cell concentration gradient is formed by standing for 5 minutes or more and less than 300 minutes. (1) The method of hemofiltration according to any one of the - (3), and (5) above is from fresh whole blood product after blood collection, characterized in that the removal of leukocytes (1) -
(4) A blood filtration method according to any one of (1) to (4).
【００１５】本発明で、血球濃度勾配を形成しても、思
いがけず通液性が確保された理由として、採血後の保存
期間が短い新鮮な全血製剤は微小凝集物の含有量が少な
く、前述したような微小凝集物に由来する不具合が発生
しなかったことが考えられる。また、濃厚赤血球製剤に
比較して全血製剤は血漿が多いために著しく粘度が上昇
した部分が形成され難く、充分な通液性を確保すること
ができたとも考えられる。しかしながら、白血球除去能
と血小板回収率の大幅な向上は予想外の効果であった。
全血製剤の不均質化による、かかるろ過特性の変化のメ
カニズムは不明であるが、以下のような理由であろうと
推測している。全血製剤を不均質化し、比重の比較的重
い赤血球と白血球が貯留部の下部に沈降した場合、この
部分は血漿の割合が少なくなっている。かかる血液から
フィルターでろ過した場合、ろ過初期におけるフィルタ
ー材料は、アルブミン等の血球粘着を抑制する血漿タン
パク質で充分に覆われておらず、その結果、フィルター
材料表面に粘着する白血球数が増え、白血球の除去能が
向上したと思われる。一方、比重の軽い血小板は不均質
化した全血製剤の上層に多く存在することになり、血小
板がフィルター材料と接触するときには、フィルター材
料の表面がアルブミン等の血漿タンパクで充分に覆わ
れ、その結果、血小板が粘着し難くなって、回収率が向
上したものと思われる。In the present invention, even if a blood cell concentration gradient is formed, unexpectedly, liquid permeability is secured because fresh whole blood preparations having a short storage period after blood collection have a low content of microaggregates. It is conceivable that the above-mentioned inconvenience caused by the micro-aggregates did not occur. In addition, it is considered that, since the whole blood product has more plasma than the concentrated erythrocyte product, a portion where the viscosity is significantly increased is hardly formed, and it is considered that sufficient liquid permeability could be secured. However, the significant improvements in leukocyte removal capacity and platelet recovery were unexpected effects.
The mechanism of such a change in the filtration characteristics due to the heterogeneity of the whole blood product is unknown, but it is presumed to be as follows. If the whole blood product becomes heterogeneous and the relatively heavy red blood cells and white blood cells sediment at the bottom of the reservoir, this portion will have a reduced proportion of plasma. When such blood is filtered with a filter, the filter material in the initial stage of filtration is not sufficiently covered with plasma proteins that suppress blood cell adhesion such as albumin, and as a result, the number of white blood cells that adhere to the filter material surface increases, It is thought that the removal ability of the phenol was improved. On the other hand, platelets with a low specific gravity are present in the upper layer of the heterogeneous whole blood product, and when the platelets come into contact with the filter material, the surface of the filter material is sufficiently covered with a plasma protein such as albumin, and As a result, it is considered that the platelets were less likely to adhere and the recovery rate was improved.
【００１６】[0016]
【発明の実施の形態】以下、本発明をより詳細に説明す
る。本発明の血液ろ過方法とは、全血製剤を貯留する、
血液バッグに代表される貯留部の内部において、比重の
重い赤血球や白血球（顆粒球、単球）を多く含む血液を
貯留部下部に沈降させ、その上層に、比重の軽い白血球
（リンパ球）や血小板を多く含むような血液、血漿を多
く含む血液となるように、貯留部内における血球の濃度
が異なるように全血製剤を不均質化して後、比重の重い
血球の含有量が減少する方向で血液を貯留部下部から白
血球除去フィルターに導入し、ろ過する血液のろ過方法
である。BEST MODE FOR CARRYING OUT THE INVENTION Hereinafter, the present invention will be described in more detail. The blood filtration method of the present invention stores whole blood products,
Inside the reservoir typified by a blood bag, blood containing a large amount of red blood cells and leukocytes (granulocytes and monocytes) with a high specific gravity is sedimented at the lower part of the reservoir, and light leukocytes (lymphocytes) and After making the whole blood product heterogeneous so that the concentration of blood cells in the reservoir is different so that the blood contains a lot of platelets and blood that contains a lot of plasma, the content of heavier blood cells with a higher specific gravity decreases. This is a blood filtration method in which blood is introduced into the leukocyte removal filter from the lower part of the reservoir and filtered.
【００１７】本発明で言う全血製剤とは、採血された全
血に適切量の坑凝固剤を添加する等の、人工的な加工が
施された製剤であるが、ろ過される全血製剤の容量に特
に限定はない。より具体的には、ＡＣＤ（アシッドサイ
トレートデキストローズ）やＣＰＤ（サイトレート・フ
ォスフェート・デキストローズ）等の抗凝固剤を含む、
採血後３日以内、好ましくは１日以内、さらに好ましく
は８時間以内の血液製剤を言う。また、採血して後、フ
ィルターでろ過するまでの間、４℃以上３０℃未満、好
ましくは１５℃以上２５℃未満の温度で保存された全血
製剤であることが好ましい。採血後３日を超えて保存さ
れた全血製剤及び／または、４℃以下で保存された全血
製剤は、微小凝集物の量が多くなり、血液を不均質化し
た場合に、微小凝集物でフィルターが閉塞され、流れ不
良を起こす恐れがあるため好ましくない。３０℃を超え
て保存した場合は、血漿タンパク質の変性等が起こりや
すくなるため好ましくない。The whole blood product referred to in the present invention is a product which has been subjected to artificial processing such as adding an appropriate amount of anticoagulant to collected whole blood, Is not particularly limited. More specifically, it contains an anticoagulant such as ACD (acid citrate dextrose) and CPD (citrate phosphate dextrose).
Refers to a blood product within 3 days after blood collection, preferably within 1 day, more preferably within 8 hours. In addition, it is preferable that the whole blood product is stored at a temperature of 4 ° C. or more and less than 30 ° C., preferably 15 ° C. or more and less than 25 ° C. after blood collection and before filtration with a filter. A whole blood product stored for more than 3 days after blood collection and / or a whole blood product stored at 4 ° C. or less has a large amount of microaggregates, and when the blood becomes heterogeneous, the microaggregates It is not preferable because the filter may be clogged with the flow and poor flow may occur. It is not preferable to store at a temperature higher than 30 ° C., since denaturation of plasma proteins and the like are likely to occur.
【００１８】本発明で言う血球濃度勾配を有する全血製
剤について、詳細に記述する。本発明の血球濃度勾配を
有する全血製剤とは、ヘマトクリット値を測定すること
によって定義され、具体的には、貯留部下部のヘマトク
リット値が、均質に混和した場合のヘマトクリット値の
１．０５倍以上２．５０倍未満であるのが好ましい。貯
留部下部のヘマトクリット値が均質に混和した場合の
１．０５倍未満であると、血球濃度勾配の形成が不十分
で、白血球除去能及び血小板回収率の向上が見られない
傾向がみられ、２．５０倍を超えると、血液粘度増加に
よるろ過時間の延長や、圧力損失の増加による溶血、あ
るいは通液性の著しい低下を誘発する恐れがある。より
好ましい貯留部下部のヘマトクリット値は、均質に混和
した場合のヘマトクリット値の１．０５倍以上２．００
倍未満であり、さらには１．２０倍以上１．７０倍未満
であることが望ましい。さらに、血球濃度勾配を有する
全血製剤の貯留部下部におけるヘマトクリット値は３５
％以上７５％未満であることが望ましい。３５％未満で
あると血球濃度勾配の形成が不十分で、白血球除去能及
び血小板回収率の向上が見られない恐れがあり、７５％
以上であるとろ過時間の延長や、圧力損失の増加による
溶血、あるいは通液性の低下を誘発する恐れがあるため
である。より好ましくは４５％以上６５％未満である。The whole blood product having a blood cell concentration gradient referred to in the present invention will be described in detail. The whole blood product having a blood cell concentration gradient of the present invention is defined by measuring a hematocrit value. Specifically, the hematocrit value at the lower part of the reservoir is 1.05 times the hematocrit value when homogeneously mixed. It is preferably at least 2.50 times. When the hematocrit value at the lower part of the reservoir is less than 1.05 times that when homogeneously mixed, the formation of a blood cell concentration gradient is insufficient, and there is a tendency that the leukocyte removal ability and the platelet recovery rate are not improved, If it exceeds 2.50 times, the filtration time may be prolonged due to an increase in blood viscosity, hemolysis due to an increase in pressure loss, or a marked decrease in fluid permeability may be induced. A more preferable hematocrit value in the lower portion of the storage portion is 1.05 times or more and 2.00 times or more of a hematocrit value in the case of homogeneous mixing.
It is preferably less than 1.times. And more preferably 1.20 times or more and less than 1.70 times. Further, the hematocrit value in the lower part of the reservoir of a whole blood product having a blood cell concentration gradient is 35.
% Or more and less than 75%. If it is less than 35%, the formation of a blood cell concentration gradient is insufficient, and there is a possibility that the leukocyte removal ability and the platelet recovery rate may not be improved.
This is because the above may cause an increase in filtration time, hemolysis due to an increase in pressure loss, or a decrease in liquid permeability. More preferably, it is 45% or more and less than 65%.
【００１９】なお、貯留部下部のヘマトクリット値は、
貯留部下部から２ないし３ｍＬの血液を直接サンプリン
グして測定することが好ましいが、サンプリングが困難
である場合には全血製剤をろ過する際に、貯留部に接続
した連結管に導入された最初の２ないし３ｍＬの血液を
サンプリングして測定しても良い。ヘマトクリット値
は、ミクロヘマトクリット法等の遠心法、電導度測定
法、パルス波高法、自動血球計数装置による測定法等、
公知の方法で測定することができる。The hematocrit value at the lower part of the storage section is
It is preferable to measure by sampling 2 to 3 mL of blood directly from the lower part of the reservoir, but if sampling is difficult, when filtering a whole blood product, the first blood introduced into the connecting pipe connected to the reservoir is used. 2 to 3 mL of blood may be sampled and measured. The hematocrit value is measured by a centrifugal method such as a microhematocrit method, a conductivity measurement method, a pulse height method, a measurement method using an automatic blood cell counter, and the like.
It can be measured by a known method.
【００２０】血球濃度勾配を有する全血製剤にする方法
として、貯留部に貯めた血液を静置しておく、いわゆる
静置法と、全血製剤が入った貯留部を遠心する、いわゆ
る遠心法を挙げることができる。As a method for preparing a whole blood product having a blood cell concentration gradient, a so-called static method in which blood stored in a storage section is allowed to stand, and a so-called centrifugal method in which a storage section containing a whole blood product is centrifuged. Can be mentioned.
【００２１】静置法によって血球濃度勾配を形成させる
ためには、５分以上３００分未満の静置時間が好まし
い。５分未満では血球の充分な濃度勾配が形成されない
場合があり、３００分以上となると、静置しておく時間
が長くなりすぎ、大量の血液をろ過することが困難にな
るため好ましくない。より好ましくは１０分以上１８０
分未満、さらには３０分以上１２０分未満であることが
望ましい。In order to form a blood cell concentration gradient by the stationary method, the stationary time is preferably 5 minutes or more and less than 300 minutes. If the time is less than 5 minutes, a sufficient concentration gradient of blood cells may not be formed. If the time is more than 300 minutes, the time for standing is too long, and it is not preferable because it becomes difficult to filter a large amount of blood. More preferably 10 minutes or more 180
It is preferable that the time is less than 30 minutes, more preferably 30 minutes or more and less than 120 minutes.
【００２２】遠心によって血球濃度勾配を形成させる方
法として、貯留部下部のヘマトクリット値が前述した好
ましい値となるように軽遠心する方法と、強い遠心（重
遠心）を行った後にゆるやかな混和を行う等の操作で貯
留部下部のヘマトクリット値を好ましい値に調整する方
法が挙げられるが、操作が簡便である理由から、軽遠心
法であることがより好ましい。軽遠心によって血球濃度
勾配を形成させる場合加速時間及び減速時間を除き、お
およそ１００×ｇ以上５００×ｇ以下の遠心力で、０．
３分から１０分間、遠心を行うことが好ましい。これよ
り弱い遠心力であると、血球濃度勾配の形成が不十分と
なるため好ましくなく、これより強い遠心力の場合に
は、貯留部に沈降した部分のヘマトクリット値が高くな
り、このままの状態でろ過を行うと、血液粘度増加によ
るろ過時間の延長や、一定流速でろ過する場合には圧力
損失の増大、それによる赤血球の溶血を招く危険がある
ため好ましくない。As a method of forming a blood cell concentration gradient by centrifugation, a method of light centrifugation so that the hematocrit value in the lower part of the reservoir becomes the above-mentioned preferable value, and a method of performing gentle centrifugation after performing strong centrifugation (heavy centrifugation). There is a method of adjusting the hematocrit value of the lower part of the storage section to a preferable value by an operation such as the above, but the light centrifugation method is more preferable because the operation is simple. When a blood cell concentration gradient is formed by light centrifugation Except for the acceleration time and deceleration time, the centrifugal force is approximately 100 × g to 500 × g, and the centrifugal force is set to 0.1 g.
Preferably, centrifugation is performed for 3 to 10 minutes. If the centrifugal force is weaker than this, it is not preferable because the blood cell concentration gradient is insufficiently formed, and if the centrifugal force is stronger than this, the hematocrit value of the portion settled in the reservoir becomes high, and in this state Filtration is not preferable because there is a risk of prolonging the filtration time due to an increase in blood viscosity, or increasing the pressure loss when filtering at a constant flow rate, thereby causing hemolysis of red blood cells.
【００２３】本発明の血球濃度勾配を有する全血製剤
は、上述した静置法、遠心法の何れでも調整することが
できるが、操作の簡便性の観点から静置法であることが
より好ましい。また、血小板を通過させたい場合、遠心
法では遠心によるストレスによって血小板がやや活性化
され、血小板回収率の向上効果が静置法に比較するとや
や小さくなる傾向にある。この理由からも静置法である
ことがより好ましい。The whole blood product having a blood cell concentration gradient of the present invention can be adjusted by any of the above-mentioned stationary method and centrifugation method, but is more preferably a stationary method from the viewpoint of easy operation. . When platelets are to be passed, the centrifugal method activates the platelets slightly due to the stress caused by the centrifugation, and the effect of improving the platelet recovery rate tends to be slightly smaller than that of the stationary method. For this reason, the stationary method is more preferable.
【００２４】本発明の全血製剤を貯留する貯留部とは、
血液を貯留し保存できる容器であって、血液細胞の活性
化や血漿タンパク質の著しい吸着や変性等を起こさない
ものであれば特に限定なく如何なるものも使用できる。
より具体的には、血液の採血及び保存に広く一般的に使
用されている軟質ポリ塩化ビニル製、ポリオレフィン製
の血液バッグや、ポリプロピレン、ポリエチレン、ポリ
スチレン製のシリンジ等を挙げることができる。The storage part for storing the whole blood product of the present invention is:
Any container can be used as long as it is a container capable of storing and storing blood, as long as it does not cause activation of blood cells or significant adsorption or denaturation of plasma proteins.
More specifically, there may be mentioned blood bags made of soft polyvinyl chloride and polyolefin, and syringes made of polypropylene, polyethylene, and polystyrene, which are widely and generally used for collecting and storing blood.
【００２５】本発明で好適に使用できる白血球除去フィ
ルターは、全血製剤に混入している白血球を捕捉し、除
去できるフィルター材料を充填したフィルターであり、
公知の白血球除去フィルターがいずれも使用できる。よ
り具体的には、ろ過後の残存白血球濃度をろ過前の白血
球濃度で除した値の対数値（−Ｌｏｇ（ろ過後の白血球
濃度／ろ過前の白血球濃度））を白血球除去能と定義し
た時に、その値が２．３０以上、好ましくは３．００以
上となるフィルターを言う。The leukocyte removal filter preferably used in the present invention is a filter filled with a filter material capable of capturing and removing leukocytes mixed in a whole blood product,
Any known leukocyte removal filter can be used. More specifically, when the logarithmic value (−Log (white blood cell concentration after filtration / white blood cell concentration before filtration)) of the value obtained by dividing the residual white blood cell concentration after filtration by the white blood cell concentration before filtration is defined as the leukocyte removal ability. , A filter whose value is 2.30 or more, preferably 3.00 or more.
【００２６】フィルター材料としては、繊維状媒体、ス
ポンジ状媒体等を挙げることができる。また、血液に対
して悪影響を与えないものであれば、フィルター材料を
血液で濡れやすくする等の目的で、親水性のポリマーを
コーティングしたり、放射線グラフト重合によって、フ
ィルター材料の表面を改質しても良い。Examples of the filter material include a fibrous medium and a sponge-like medium. If the filter material does not adversely affect the blood, the surface of the filter material may be modified by coating with a hydrophilic polymer or radiation graft polymerization for the purpose of making the filter material easier to wet with blood. May be.
【００２７】白血球除去フィルターに血小板の通過機能
を付与する場合、血小板低粘着性材料をフィルター材料
の表面に導入しても良い。血小板低粘着性材料として
は、特公平６−５１０６０号や特開平１−２４９０６３
号等に記載されているような、親水性基と、アミノ基ま
たはカルボキシル基等の荷電性基を有するポリマーや、
ポリウレタンを好適な材料として挙げることができる。When imparting a platelet passage function to the leukocyte removal filter, a platelet low-adhesive material may be introduced to the surface of the filter material. Examples of the platelet low-adhesive material include Japanese Patent Publication No. 6-51060 and Japanese Patent Application Laid-Open No. 1-249063.
No., such as a hydrophilic group, a polymer having a charged group such as an amino group or a carboxyl group,
Polyurethane can be mentioned as a suitable material.
【００２８】本発明は、上記した血球濃度勾配を有する
全血製剤を貯留する貯留部と白血球除去フィルターと
を、血液が流れる中空管状の連結管で接続して実施する
ことが好ましい。フィルターと連結管との接続は、貯留
部において、血球濃度勾配を形成させた後に行っても良
いし、予め貯留部とフィルターを連結管で接続し、その
後貯留部内において血球濃度勾配を形成させても良い。
また、フィルターでろ過された全血製剤を流す連結管を
フィルターの下流側に接続し、さらにろ過血を回収する
回収部を接続しても良い。連結管の接続は、無菌接続装
置（ＳＣＤ）を使用して行っても良い。また、ここで言
う連結管とは、血球にダメージを与えないものであれば
特に限定はない。中でも、塩化ビニル、シリコン、ポリ
スルフォン、ポリアミド、ポリエステル、ウレタン、ポ
リエチレン、ポリプロピレン等の有機材料が加工性に優
れるため好ましい。回収部には、上述の貯留部と同様の
機能を有し、同様の材料からなるものを使用できる。The present invention is preferably implemented by connecting a storage section for storing a whole blood product having the above-mentioned blood cell concentration gradient and a leukocyte removal filter with a hollow tubular connecting pipe through which blood flows. The connection between the filter and the connecting pipe may be performed after the blood cell concentration gradient is formed in the storage section, or the storage section and the filter may be connected in advance by the connecting pipe, and then the blood cell concentration gradient may be formed in the storage section. Is also good.
Further, a connecting pipe for flowing the whole blood product filtered by the filter may be connected to the downstream side of the filter, and further, a collecting unit for collecting the filtered blood may be connected. The connection of the connection pipe may be performed using a sterile connection device (SCD). In addition, the connecting pipe is not particularly limited as long as it does not damage blood cells. Among them, organic materials such as vinyl chloride, silicon, polysulfone, polyamide, polyester, urethane, polyethylene, and polypropylene are preferable because of excellent workability. The collection unit has the same function as the storage unit described above, and can be made of the same material.
【００２９】本発明の血液ろ過方法は、血球濃度勾配を
有する全血製剤を白血球除去フィルターでろ過すること
に特徴を有する方法であり、ろ過操作自体は特に限定さ
れない。即ち、血液バッグ等を貯留部として、適切な落
差を確保した後にろ過を行っても良いし、ポンプ等を用
いて一定の流量でろ過を行っても良い。このようにして
白血球を除去した全血製剤を得た後、公知の遠心法によ
って、白血球が除去された血液成分製剤を調整すること
もできる。The blood filtration method of the present invention is characterized by filtering a whole blood product having a blood cell concentration gradient through a leukocyte removal filter, and the filtration operation itself is not particularly limited. That is, filtration may be performed after a suitable head is secured using a blood bag or the like as a storage unit, or filtration may be performed at a constant flow rate using a pump or the like. After obtaining a whole blood product from which leukocytes have been removed in this manner, a blood component product from which leukocytes have been removed can also be prepared by a known centrifugation method.
【００３０】[0030]
【実施例】以下に実施例により本発明をさらに詳細に説
明するが、本発明の範囲はこれらの実施例により限定さ
れるものではない。EXAMPLES The present invention will be described in more detail with reference to the following examples, but the scope of the present invention is not limited by these examples.
【実施例１】（白血球除去フィルター）平均繊維径が
１．２μｍ、目付が４０ｇ／ｍ2、厚みが０．２ｍｍの
ポリエチレンテレフタレート製不織布に、２−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）からなるランダムポリマ
ー（ＨＥＭＡとＤＭのモル組成比は９７：３。以下ＨＭ
−３と略す）を血小板低粘着性材料としてコーティング
した白血球除去フィルターを用いた。Example 1 (Leukocyte removal filter) 2-hydroxyethyl methacrylate (HEMA) and dimethylaminoethyl methacrylate were added to a polyethylene terephthalate nonwoven fabric having an average fiber diameter of 1.2 μm, a basis weight of 40 g / m 2 and a thickness of 0.2 mm. (DM) random polymer (HEMA: DM molar composition ratio is 97: 3; hereinafter HM
-3) was used as a platelet-low-adhesive material.
【００３１】（ポリマーの合成及びコーティング）ＨＭ
−３ポリマーは、エタノール中のモノマー濃度を１モル
／Ｌとし、開始剤として２，２’−アゾビス（２，４−
ジメチルバレロニトリル）（和光純薬工業社製、商品名
Ｖ−６５）を０．００５モル／Ｌの存在下、６０℃で８
時間ランダム重合することによって合成した。合成した
ＨＭ−３ポリマーを不織布表面にコーティングする場合
は以下の操作を行った。まず合成したＨＭ−３ポリマー
をエタノールと水の混合溶媒（重量比：エタノール／水
＝７０／３０）で溶解させ、濃度を７ｇ／ｄＬとした液
を調整した。次に不織布を直径２５ｍｍに打ち抜き、こ
のポリマー液に２５℃で１分間浸し、ポリカーボネート
製のホルダーに充填し、乾燥窒素を４．５分間通気さ
せ、その後６０℃で１８時間、真空乾燥することによっ
てコーティングした。(Synthesis and Coating of Polymer) HM
-3 polymer has a monomer concentration of 1 mol / L in ethanol and uses 2,2'-azobis (2,4-
Dimethylvaleronitrile) (trade name: V-65, manufactured by Wako Pure Chemical Industries, Ltd.) in the presence of 0.005 mol / L at 60 ° C.
It was synthesized by random polymerization for hours. The following operation was performed when the synthesized HM-3 polymer was coated on the surface of the nonwoven fabric. First, the synthesized HM-3 polymer was dissolved in a mixed solvent of ethanol and water (weight ratio: ethanol / water = 70/30) to prepare a solution having a concentration of 7 g / dL. Next, the nonwoven fabric is punched to a diameter of 25 mm, immersed in the polymer solution at 25 ° C. for 1 minute, filled in a polycarbonate holder, aerated with dry nitrogen for 4.5 minutes, and then vacuum-dried at 60 ° C. for 18 hours. Coated.
【００３２】（フィルターの作成）血液をろ過するフィ
ルターは、不織布を直径２０ｍｍに打ち抜いて、有効ろ
過断面積が１．３３ｃｍ2で、血液の導入口と導出口を
有する容器に１６枚充填することによって作製した。Ｈ
Ｍ−３をコーティングした不織布を使用する場合は、ポ
リカーボネート製のホルダーから乾燥後のＨＭ−３がコ
ートされた不織布を取り出し、さらに直径２０ｍｍに打
ち抜いて後、１６枚重ねて充填した。(Preparation of Filter) A filter for filtering blood is prepared by punching a non-woven fabric into a 20 mm diameter, and filling 16 containers having an effective filtration area of 1.33 cm 2 and having a blood inlet and a blood outlet. Produced by H
When using a nonwoven fabric coated with M-3, the nonwoven fabric coated with HM-3 after drying was taken out of a polycarbonate holder, punched out to a diameter of 20 mm, and filled with 16 sheets.
【００３３】（血液のろ過試験）軟質ポリ塩化ビニル製
血液バッグに採血され、室温下（２０〜２５℃）で２〜
３時間保存されたＣＰＤ添加全血製剤をよく混和した
後、この中から８ｍＬの血液をシリンジ（テルモ社製、
商品名テルモシリンジ（登録商標）ＳＳ−２０ＥＳＺ）
に採取した。全血製剤を含むシリンジにクランプを備え
た内径２．５ｍｍのポリ塩化ビニル製チューブを接続
し、チューブの反対側末端を上述したフィルターの血液
導入口と接続した。また、フィルターの血液導出口に同
じチューブを接続し、この反対側末端から導出する血液
を回収するために、ポリエチレン製のスピッツ管を配置
した。その後、全血製剤の入ったシリンジとフィルター
導入口との間のクランプを閉塞し、シリンジを垂直に立
て、６０分間静置した後、クランプを解除し、０．９ｍ
Ｌ／分の一定流速でろ過を行った。(Blood Filtration Test) Blood was collected in a soft polyvinyl chloride blood bag, and the blood was collected at room temperature (20 to 25 ° C.).
After thoroughly mixing the CPD-added whole blood product stored for 3 hours, 8 mL of the blood was syringed (from Terumo,
Trade name Thermosyringe (registered trademark) SS-20ESZ)
Was collected. A syringe containing a whole blood product was connected to a 2.5 mm id polyvinyl chloride tube equipped with a clamp, and the other end of the tube was connected to the blood inlet of the above-mentioned filter. In addition, the same tube was connected to the blood outlet of the filter, and a spitz tube made of polyethylene was arranged to collect the blood drawn from the opposite end. Thereafter, the clamp between the syringe containing the whole blood product and the filter inlet was closed, and the syringe was set upright and allowed to stand for 60 minutes.
Filtration was performed at a constant flow rate of L / min.
【００３４】（白血球除去能および血小板回収率の測
定）ろ過前の全血製剤中の白血球濃度は、均質な状態の
全血製剤よりサンプリングした血液を用い、チュルク液
で白血球を染色後、光学顕微鏡を用いて測定した。ろ過
後の全血製剤中の白血球濃度は、ポリエチレン製のスピ
ッツ管に回収した血液をサンプリングし、アクリジンオ
レンジ液で漏れてきた白血球を染色した後、蛍光顕微鏡
を用いて測定した。かくして得られたろ過前及びろ過後
の白血球濃度より、次式により、白血球除去能を求め
た。 白血球除去能＝−Ｌｏｇ（ろ過後の白血球濃度／ろ過前
の白血球濃度）(Measurement of leukocyte removal ability and platelet collection rate) The leukocyte concentration in a whole blood product before filtration was determined by using a blood sampled from a homogenous whole blood product, staining the leukocyte with a Turk's solution, and then using an optical microscope. It measured using. The leukocyte concentration in the filtered whole blood product was measured using a fluorescence microscope after sampling blood collected in a Spitz tube made of polyethylene and staining the leaked leukocytes with acridine orange solution. From the leukocyte concentrations before and after filtration thus obtained, the leukocyte removal ability was determined by the following equation. Leukocyte removal ability = -Log (white blood cell concentration after filtration / white blood cell concentration before filtration)
【００３５】血小板回収率を算出する場合は、白血球濃
度を測定した血液と同一の血液を用い、ろ過前及びろ過
後の血小板濃度を多項目自動血球計数装置（東亜医用電
子株式会社製、Ｓｙｓｍｅｘ Ｋ−４５００）で測定
し、次式により求めた。血小板回収率＝ろ過後血小板濃
度／ろ過前血小板濃度×１００（％）When calculating the platelet recovery rate, the same blood as the blood whose leukocyte concentration was measured was used, and the platelet concentration before and after filtration was measured using a multi-item automatic blood cell counter (Sysmex K, manufactured by Toa Medical Electronics Co., Ltd.). -4500) and was determined by the following equation. Platelet recovery = platelet concentration after filtration / platelet concentration before filtration x 100 (%)
【００３６】（ヘマトクリット値の測定）均質な状態で
のヘマトクリット値（以下、プレＨｔと言う）、及びシ
リンジ下部のヘマトクリット値（以下、ポストＨｔと言
う）の測定は以下の方法により行った。プレＨｔ値は、
血液バッグに残った、フィルター未処理の全血製剤をよ
く混和し、この中から２ｍＬの血液をサンプリングして
測定した。血球濃度勾配を有する全血製剤のポストＨｔ
は、全血製剤を含む同様のシリンジをもう１本用意し、
一定時間静置した後にシリンジ下部の血液を２ｍＬ採取
し、これをポストＨｔの測定に用いた。また、下記に示
す比較例においては、一定時間静置した後、再び混和
し、シリンジ下部の血液を２ｍＬ採取し、これをポスト
Ｈｔの測定に用いた。プレ及びポストＨｔの測定は、サ
ンプリングした血液をポリエチレン製のスピッツ管に入
れ、血小板濃度の測定と同様に多項目自動血球計数装置
で行った。以上の結果、プレＨｔは３４％、ポストＨｔ
は５２％（ポストＨｔ／プレＨｔ＝１．５３）であり、
白血球除去能は３．７２、血小板回収率は８４％であっ
た。(Measurement of hematocrit value) The hematocrit value in a homogeneous state (hereinafter referred to as pre-Ht) and the hematocrit value in the lower part of the syringe (hereinafter referred to as post-Ht) were measured by the following methods. The pre-Ht value is
The unfiltered whole blood product remaining in the blood bag was mixed well, and 2 mL of blood was sampled and measured. Post-Ht of whole blood product with blood cell concentration gradient
Prepares another similar syringe containing a whole blood product,
After standing for a certain period of time, 2 mL of blood under the syringe was collected and used for post-Ht measurement. In the comparative examples described below, the mixture was allowed to stand for a certain period of time, mixed again, and 2 mL of blood at the lower part of the syringe was collected and used for post-Ht measurement. The measurement of pre- and post-Ht was performed by placing a sampled blood in a polyethylene Spitz tube and using a multi-item automatic blood cell counter in the same manner as in the measurement of platelet concentration. As a result, the pre-Ht was 34% and the post-Ht
Is 52% (post-Ht / pre-Ht = 1.53),
The leukocyte removal ability was 3.72, and the platelet recovery was 84%.
【００３７】[0037]
【実施例２】静置時間を５分とした以外は実施例１と同
じフィルターと全血製剤を用い、ろ過を行った。以上の
結果、ポストＨｔは３７％（ポストＨｔ／プレＨｔ＝
１．０８）であり、白血球除去能は３．８０、血小板回
収率は７５％であった。Example 2 Filtration was performed using the same filter and whole blood preparation as in Example 1 except that the standing time was 5 minutes. As a result, the post-Ht was 37% (post-Ht / pre-Ht =
1.08), the leukocyte removal ability was 3.80, and the platelet collection rate was 75%.
【００３８】[0038]
【実施例３】静置時間を１０分とした以外は実施例１と
同じフィルターと全血製剤を用い、ろ過を行った。以上
の結果、ポストＨｔは４１％（ポストＨｔ／プレＨｔ＝
１．２１）であり、白血球除去能は３．８９、血小板回
収率は８１％であった。Example 3 Filtration was carried out using the same filter and whole blood preparation as in Example 1 except that the standing time was 10 minutes. As a result, the post Ht is 41% (post Ht / pre-Ht =
1.21), the leukocyte removal ability was 3.89, and the platelet collection rate was 81%.
【００３９】[0039]
【実施例４】静置時間を１８０分とした以外は実施例１
と同じフィルターと全血製剤を用い、ろ過を行った。以
上の結果、ポストＨｔは５７％（ポストＨｔ／プレＨｔ
＝１．６８）であり、白血球除去能は３．７０、血小板
回収率は９３％であった。Example 4 Example 1 except that the standing time was 180 minutes.
Filtration was performed using the same filter and whole blood product as described above. As a result, the post Ht was 57% (post Ht / pre-Ht).
= 1.68), the leukocyte removal ability was 3.70, and the platelet collection rate was 93%.
【００４０】[0040]
【比較例１】実施例１と同じ全血製剤をシリンジに採取
し、６０分間静置した。その後、再び混和し、血球濃度
勾配が実質的にない、均質な全血製剤とした。この全血
製剤を、実施例１と同じフィルターを用い、同じ方法で
ろ過を行った。以上の結果、ポストＨｔは３４％であ
り、プレＨｔと同等であった（ポストＨｔ／プレＨｔ＝
１．００）。また、白血球除去能は３．１４、血小板回
収率は６５％であった。Comparative Example 1 The same whole blood product as in Example 1 was collected in a syringe and allowed to stand for 60 minutes. Thereafter, they were mixed again to obtain a homogeneous whole blood product having substantially no blood cell concentration gradient. This whole blood product was filtered using the same filter as in Example 1 by the same method. As a result, the post-Ht was 34%, which was equivalent to the pre-Ht (post-Ht / pre-Ht =
1.00). The leukocyte removal ability was 3.14, and the platelet collection rate was 65%.
【００４１】[0041]
【実施例５】平均繊維径が１．４μｍ、目付が４２ｇ／
ｍ2、厚みが０．２２ｍｍのポリプロピレンテレフタレ
ート製不織布と、ＨＥＭＡとジエチルアミノエチルメタ
クリレート（ＤＥ）からなるランダムコポリマー（ＨＥ
ＭＡとＤＥのモル組成比は９５：５。以下ＨＥ−５と略
す。）を血小板低粘着性材料として用いて実験を行っ
た。ＨＥ−５ポリマーの合成、不織布へのコーティン
グ、及び血液のろ過は実施例１と同様の条件及び方法で
行った。以上の結果、白血球除去能は３．６５、血小板
回収率は８５％であった。Example 5 The average fiber diameter was 1.4 μm and the basis weight was 42 g /
m 2 , a non-woven fabric made of polypropylene terephthalate having a thickness of 0.22 mm, and a random copolymer (HE) composed of HEMA and diethylaminoethyl methacrylate (DE).
The molar composition ratio of MA and DE is 95: 5. Hereinafter, it is abbreviated as HE-5. ) Was used as a low platelet adhesion material. Synthesis of the HE-5 polymer, coating of the nonwoven fabric, and filtration of blood were performed under the same conditions and method as in Example 1. As a result, the leukocyte removal ability was 3.65 and the platelet collection rate was 85%.
【００４２】実施例１〜５の結果を比較例１の結果と対
比すると、血小板低粘着性ポリマーをコーティングした
白血球除去フィルターにおいて、血球濃度勾配を形成す
ることによって、白血球除去能のみでなく血小板回収率
が顕著に向上していることが分かる。When the results of Examples 1 to 5 are compared with the results of Comparative Example 1, a leukocyte concentration gradient is formed in a leukocyte removal filter coated with a low-adhesive platelet polymer, so that not only the leukocyte removal ability but also the platelet collection It can be seen that the rate has been significantly improved.
【００４３】[0043]
【実施例６】ＨＭ−３をコーティングしていないが、実
施例１と同じ不織布を充填したフィルターを作製した。
採血後３時間経過したＣＰＤ添加全血製剤をシリンジに
採取し、６０分間静置した後に実施例１と同じ方法でろ
過を行った。以上の結果、プレＨｔは３９％、ポストＨ
ｔは６２％（ポストＨｔ／プレＨｔ＝１．５９）であ
り、白血球除去能は４．３４であった。Example 6 A filter which was not coated with HM-3 but filled with the same nonwoven fabric as in Example 1 was produced.
CPD-added whole blood product 3 hours after blood collection was collected in a syringe, allowed to stand for 60 minutes, and then filtered in the same manner as in Example 1. As a result, the pre-Ht was 39% and the post-Ht was
t was 62% (post-Ht / pre-Ht = 1.59), and the leukocyte removal ability was 4.34.
【００４４】[0044]
【比較例２】実施例６と同じ全血製剤をシリンジに採取
し、６０分間静置した。その後、再び混和し、血球濃度
勾配が実質的にない、均質な全血製剤とした。この全血
製剤を、実施例６と同じフィルターを用い、同じ方法で
ろ過を行った。以上の結果、ポストＨｔは３９％であ
り、プレＨｔと同等であった（ポストＨｔ／プレＨ＝
１．００）。また、白血球除去能は３．５１であった。Comparative Example 2 The same whole blood product as in Example 6 was collected in a syringe and allowed to stand for 60 minutes. Thereafter, they were mixed again to obtain a homogeneous whole blood product having substantially no blood cell concentration gradient. This whole blood product was filtered using the same filter as in Example 6 by the same method. As a result, the post-Ht was 39%, which was equivalent to the pre-Ht (post-Ht / pre-H =
1.00). In addition, the leukocyte removal ability was 3.51.
【００４５】実施例６と比較例２との結果を対比する
と、血小板低粘着性ポリマーをコーティングしていない
白血球除去フィルターにおいては、血球濃度勾配を形成
することによって、白血球除去能が顕著に向上すること
が分かった。Comparing the results of Example 6 and Comparative Example 2, in the leukocyte removal filter not coated with the platelet low-adhesion polymer, the leukocyte removal ability is significantly improved by forming a blood cell concentration gradient. I understood that.
【００４６】実施例１〜６、比較例１〜２の結果を表１
に示す。The results of Examples 1 to 6 and Comparative Examples 1 and 2 are shown in Table 1.
Shown in
【表１】 [Table 1]
【００４７】[0047]
【実施例７】採血後室温下で３時間保存したＣＰＤ添加
新鮮全血を含む軟質ポリ塩化ビニル製の血液バッグを遠
心分離機（日立工機社製、型式ＣＲ７Ｂ３）に入れ、３
００×ｇの遠心力で０．５分間軽遠心し、血球密度勾配
を有する全血製剤（２８ｍＬ）を調整した。ＨＭ−３を
コーティングした不織布を、内径２５ｍｍのホルダーに
１６枚重ねて充填したフィルターを作成した。遠心によ
り血球濃度勾配を形成させた全血製剤を含む血液バッグ
に内径２．５ｍｍのポリ塩化ビニル製チューブを接続
し、このチューブの反対側末端にフィルターの血液導入
口を接続した。さらに血液導出口とろ過した全血製剤を
回収する血液バッグを、同様のチューブを介して接続し
た。プレＨｔは、遠心前の均質な状態の全血製剤より血
液をサンプリングして測定し、ポストＨｔは、遠心後の
全血製剤が入っている血液バッグの下部よりサンプリン
グして測定した。この結果、プレＨｔは３２％、ポスト
Ｈｔは６３％（ポストＨｔ／プレＨ＝１．９７）であっ
た。フィルター接続後の血球濃度勾配を有する全血製剤
を入れた血液バッグを吊し、落差４０ｃｍでろ過を行っ
た。その結果、白血球除去能は３．４８、血小板回収率
は７６％であった。Example 7 A blood bag made of soft polyvinyl chloride containing fresh whole blood with CPD and stored at room temperature for 3 hours after blood collection was put into a centrifuge (model CR7B3, manufactured by Hitachi Koki Co., Ltd.).
The mixture was lightly centrifuged at a centrifugal force of 00 × g for 0.5 minutes to prepare a whole blood product (28 mL) having a blood cell density gradient. A filter in which 16 nonwoven fabrics coated with HM-3 were stacked and filled in a holder having an inner diameter of 25 mm was prepared. A 2.5 mm inner diameter polyvinyl chloride tube was connected to a blood bag containing a whole blood product in which a blood cell concentration gradient was formed by centrifugation, and a blood inlet of a filter was connected to the opposite end of the tube. Further, the blood outlet and a blood bag for collecting the filtered whole blood product were connected via the same tube. Pre-Ht was measured by sampling blood from a homogeneous whole blood product before centrifugation, and post-Ht was measured by sampling from the lower part of the blood bag containing the centrifuged whole blood product. As a result, pre-Ht was 32% and post-Ht was 63% (post-Ht / pre-H = 1.97). A blood bag containing a whole blood product having a blood cell concentration gradient after connection of the filter was suspended, and filtration was performed at a head of 40 cm. As a result, the leukocyte removal ability was 3.48, and the platelet collection rate was 76%.
【００４８】[0048]
【比較例３】２６００×ｇの遠心力で７分間遠心を行っ
た以外は、実施例５と同じフィルターを用いて、同じ方
法でろ過を試みた。以上の結果、ポストＨｔは８５％
（ポストＨｔ／プレＨｔ＝２．６６）と極めて粘度が高
くなり、フィルターでろ過を行うことができなかった。Comparative Example 3 Filtration was attempted by the same method using the same filter as in Example 5 except that centrifugation was performed at a centrifugal force of 2600 × g for 7 minutes. As a result, post Ht was 85%
(Post-Ht / pre-Ht = 2.66), the viscosity was extremely high, and filtration could not be performed with a filter.
【００４９】[0049]
【発明の効果】本発明の血液ろ過方法によると、全血製
剤から効率良く白血球を除去することができ、さらに血
小板回収率も向上させることができる。According to the blood filtration method of the present invention, leukocytes can be efficiently removed from a whole blood product, and the platelet recovery rate can be improved.
───────────────────────────────────────────────────── フロントページの続き Ｆターム(参考） 4C077 AA12 BB02 KK11 LL02 LL12 NN02 PP02 PP07 PP14 4D064 AA29 BQ01 BQ11 BQ19 ──────────────────────────────────────────────────続 き Continued on the front page F term (reference) 4C077 AA12 BB02 KK11 LL02 LL12 NN02 PP02 PP07 PP14 4D064 AA29 BQ01 BQ11 BQ19
Claims (5)
液ろ過方法において、全血製剤を貯留する貯留部下部の
血液のヘマトクリット値が、貯留部の全血製剤を均質に
混和した場合のヘマトクリット値より高くなるように、
貯留部に血球濃度勾配を形成した後、血液を貯留部下部
から白血球除去フィルターへ導入することを特徴とする
方法。Claims: 1. A blood filtration method for removing leukocytes from a whole blood product, wherein the hematocrit of the blood at the lower part of the reservoir for storing the whole blood product is a hematocrit when the whole blood product in the reservoir is homogeneously mixed. Higher than the value
A method comprising forming a blood cell concentration gradient in a reservoir and introducing blood from a lower portion of the reservoir to a leukocyte removal filter.
が、貯留部の全血製剤を均質に混和した場合のヘマトク
リット値の１．０５倍以上２．５０倍未満である請求項
１記載の血液のろ過方法。2. The blood according to claim 1, wherein the hematocrit value of the blood in the lower part of the reservoir is 1.05 times or more and less than 2.50 times the hematocrit value when the whole blood product in the reservoir is homogeneously mixed. Filtration method.
以上７５％未満である請求項１又は２記載の血液ろ過方
法。3. The hematocrit value of the lower part of the storage part is 35%.
The blood filtration method according to claim 1 or 2, which is at least 75%.
球濃度勾配が形成される請求項１〜３のいずれかに記載
の血液ろ過方法。4. The blood filtration method according to claim 1, wherein the blood cell concentration gradient is formed by standing for 5 minutes to less than 300 minutes.
することを特徴とする請求項１〜４のいずれかに記載の
血液ろ過方法。5. The blood filtration method according to claim 1, wherein leukocytes are removed from a fresh whole blood product after blood collection.
Priority Applications (5)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| JP2001129177A JP2002320669A (en) | 2001-04-26 | 2001-04-26 | Method for blood filtration |
| AT02722812T ATE530212T1 (en) | 2001-04-26 | 2002-04-26 | BLOOD FILTRATION METHOD |
| EP02722812A EP1382357B1 (en) | 2001-04-26 | 2002-04-26 | Blood filtration method |
| US10/475,987 US7217365B2 (en) | 2001-04-26 | 2002-04-26 | Blood filtration methods |
| PCT/JP2002/004201 WO2002087660A1 (en) | 2001-04-26 | 2002-04-26 | Blood filtration methods and blood filtration apparatus |
Applications Claiming Priority (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| JP2001129177A JP2002320669A (en) | 2001-04-26 | 2001-04-26 | Method for blood filtration |
Publications (2)
| Publication Number | Publication Date |
|---|---|
| JP2002320669A true JP2002320669A (en) | 2002-11-05 |
| JP2002320669A5 JP2002320669A5 (en) | 2008-05-01 |
Family
ID=18977742
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|---|---|---|---|
| JP2001129177A Pending JP2002320669A (en) | 2001-04-26 | 2001-04-26 | Method for blood filtration |
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Cited By (1)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| EP2896416A1 (en) | 2010-03-19 | 2015-07-22 | Asahi Kasei Medical Co., Ltd. | Cell removal method, cell removal system, and white blood cell removal method |
Citations (4)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| JPH0193041A (en) * | 1987-10-03 | 1989-04-12 | Jeol Ltd | Phase difference electron microscope for magnetic domain observation |
| JPH01320064A (en) * | 1988-06-23 | 1989-12-26 | Asahi Medical Co Ltd | Blood component separating system |
| JPH11216179A (en) * | 1997-11-28 | 1999-08-10 | Terumo Corp | Leukocyte remover, method and device for blood processing |
| WO1999047235A1 (en) * | 1998-03-20 | 1999-09-23 | Lexion Medical, Llc | Biological fluid filtration method and apparatus |
-
2001
- 2001-04-26 JP JP2001129177A patent/JP2002320669A/en active Pending
Patent Citations (5)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| JPH0193041A (en) * | 1987-10-03 | 1989-04-12 | Jeol Ltd | Phase difference electron microscope for magnetic domain observation |
| JPH01320064A (en) * | 1988-06-23 | 1989-12-26 | Asahi Medical Co Ltd | Blood component separating system |
| JPH11216179A (en) * | 1997-11-28 | 1999-08-10 | Terumo Corp | Leukocyte remover, method and device for blood processing |
| WO1999047235A1 (en) * | 1998-03-20 | 1999-09-23 | Lexion Medical, Llc | Biological fluid filtration method and apparatus |
| JP2002506708A (en) * | 1998-03-20 | 2002-03-05 | レクシオン・メディカル、リミテッド・ライアビリティ・カンパニー | Method and apparatus for filtering biological fluid |
Cited By (4)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| EP2896416A1 (en) | 2010-03-19 | 2015-07-22 | Asahi Kasei Medical Co., Ltd. | Cell removal method, cell removal system, and white blood cell removal method |
| EP3050583A1 (en) | 2010-03-19 | 2016-08-03 | Asahi Kasei Medical Co., Ltd. | Cell removal system |
| US9474845B2 (en) | 2010-03-19 | 2016-10-25 | Asahi Kasei Medical Co. Ltd. | Cell removal method, cell removal system, and white blood cell removal method |
| US10117987B2 (en) | 2010-03-19 | 2018-11-06 | Asahi Kasei Medical Co., Ltd. | Cell removal method, cell removal system, and white blood cell removal method |
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