JP5568103B2 - 赤血球の保存のための組成物及び方法 - Google Patents
赤血球の保存のための組成物及び方法 Download PDFInfo
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- JP5568103B2 JP5568103B2 JP2012034275A JP2012034275A JP5568103B2 JP 5568103 B2 JP5568103 B2 JP 5568103B2 JP 2012034275 A JP2012034275 A JP 2012034275A JP 2012034275 A JP2012034275 A JP 2012034275A JP 5568103 B2 JP5568103 B2 JP 5568103B2
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Description
このような工程は、「調節性容量減少」と呼ばれる。この工程の間にRBCに存在するチロシンホスファターゼ活性が阻害される、又はチロシン・キナーゼが活性化されると考えられる。これらの酵素は、RBCの膜に大量に存在することが示された(Zipser, Y. and Kosower, N. S. (1996) Biochem. J. 314:881; Mallozzi C. et al. (1997) FASEB J. 11 :1281)。RBC膜のバンド3タンパクのリン酸化反応により、バンド3タンパクに結合しているホスホフルクトキナーゼ、アルドラーゼ、及びグリセロアルデヒド−3−リン酸デヒドロゲナーゼが細胞質に放出されると考えられる(Harrison, M. L. et al. (1991) J. Biol. Chem. 266:4106; Cossins, A. R. and Gibson J. S. (1997) J. Exper. Biol. 200:343; Low, P. S. et al. (1993) J. Biol. Chem. 268:14627; Low, P. S. et al. (1995) Protoplasma 184:1961)。解凍経路にこれらの3つの酵素が作用すると、RBCによるグルコースの代謝が増加し、それにより、ATPの合成が増大し、RBC内のATPの濃度が増加すると考えられる。したがって、添加液組成物の調製の目的は、ATPの合成ができる限り高い率でできる限り長く維持されることである。
この実施例は、EAS−81(表1を参照)として表す本発明に係る添加液のある実施形態の性能の分析結果及び利点を説明するためである。EAS−81及びその比較対象であるAS−3(Nutricel, Pal Biomedical製造)は従来の容量で使用されており、一方、比較対象EAS−61及びEAS−76v6は希釈された状態及びさらに大きな容量で使用されている。EAS−81及びEAS−76v6は、両方とも重炭酸塩を含む。図1では、重炭酸塩を含む組成物は丸印で表されており、重炭酸塩を含まないものはダイアモンド印で表されている。容量の大きい組成物は塗りつぶされた印で表されており、従来と同じ容量の組成物は中空の印で表されている。本明細書で開示されている添加液の全ての容量は全血500mL当たりであり、添加液と全血との比は1:4.5である。
トリプルバッグ回収システム(triple-bag collection system)(品目番号 #127-23, Pall Corporation, East Hills, NY)内の70mLのCP2D溶液に標準ユニットの血液(500±55mL)を回収した。それぞれのユニットの白血球を内部白血球フィルターで除去した。遠心分離を5分間行い、血漿を65mLだけ残し、それ以外の血漿を除去し、表示した容量のAS又はEASを無菌的に加える。各ユニットを直立状態で10週間に1〜6℃で保存する(毎週の混合及び15mLのサンプル採取のときを除いて)。
白血球除去(全血からの白血球の除去)は、フローサイトメトリー法で確認する。全ヘモグロビン(Hb)濃度は、血液分析装置(Hematology Cell Counter System Series 9110+, Baker, Allentown, PA)で測定する。細胞の平均容積(Mean cell volume:MCV)は、RBCの数の測定及び保存懸濁液のミクロへマトクリット値で求める。「A micromodification of the Drabkin hemoglobin assay for measuring plasma hemoglobin in the range of 5 to 2000 mg/dl(Moore et al., Biochem Med 26:167-173, 1981)」(参照により本明細書に組み込まれるものとする)で記載されているように、上精Hbは、分光光度法を用いて改良ドラブキン・アセイ(modified Drabkin assay)で測定する。溶血のパーセンテージは、全Hbに対する遊離のHbの比及びヘマトクリット値を測定することによって求める。
本実施例は、従来の容量でEAS製剤を使用することでRBCを8週間保存することができ、かつその際には6週間の保存に使用される従来の溶液よりも、RBCの回収率が良く、溶血率が低く、RBCの膜がさらに維持されることを示すものである。
Claims (10)
- 赤血球(RBCs)を保存するための組成物であって、
前記組成物は、外部由来の塩化物イオンを含まず、
前記組成物は、2mMのアデニンと、80mMのデキストロースと、55mMの非代謝性の膜保護糖と、26mMの重炭酸ナトリウムと、12mMのリン酸2ナトリウムとからなることを特徴とする組成物。 - 請求項1に記載の組成物であって、
前記組成物のpHは、8.5であることを特徴とする組成物。 - 請求項1に記載の組成物であって、
前記組成物と前記採取された全血との比は、それぞれ1:4.5であることを特徴とする組成物。 - 請求項1に記載の組成物であって、
200〜310mOsmのオスモル濃度を有することを特徴とする組成物。 - 請求項4に記載の組成物であって、
前記オスモル濃度は、221〜280mOsmであることを特徴とする組成物。 - 請求項5に記載の組成物であって、
前記オスモル濃度は、270mOsmであることを特徴とする組成物。 - 請求項1に記載の組成物であって、
前記組成物が加えられた前記赤血球(RBCs)懸濁液のpHを6.4〜7.2の間に維持する働きがあること特徴とする組成物。 - 請求項7に記載の組成物であって、
前記組成物が加えられた前記赤血球(RBCs)懸濁液のpHを7.0〜7.2の間に維持する働きがあること特徴とする組成物。 - 請求項8に記載の組成物であって、
前記組成物が加えられた前記赤血球(RBCs)懸濁液のpHを7.1よりも高く、7.2よりも低い値に維持する働きがあることを特徴とする組成物。 - 赤血球(RBCs)を保存するための組成物であって、
前記組成物は、外部由来の塩化物イオンを含まず、
前記組成物は、
1〜3mMのアデニンと、
20〜115mMのデキストロースと、
15〜60mMの非代謝性の膜保護糖と、
20〜130mMの重炭酸ナトリウムと、
4〜20mMのリン酸2ナトリウムとからなることを特徴とする組成物。
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