JP2013017644A - Pcsk9の吸着体およびpcsk9の吸着器 - Google Patents
Pcsk9の吸着体およびpcsk9の吸着器 Download PDFInfo
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Abstract
【解決手段】PCSK9吸着体3は、アニオン性官能基を有する水不溶性担体からなる。また、PCSK9吸着器7は、液の入口1および出口2を有し、かつ吸着体3の容器外への流出防止手段5を備えた容器内に上記PCSK9吸着体3を充填してなる。
【選択図】図1
Description
・ 機械的強度が比較的高く強靭であるため、撹拌などの操作により破壊されたり微粉を生じたりすることが少なく、カラムに充填した場合、体液を高流速で流しても圧密化したり目詰まりしたりせず、さらに細孔構造が高圧蒸気滅菌などによって変化を受けにくい;
・ ゲルがセルロースで構成されているため親水性であり、リガンドなどの結合に利用し得る水酸基が多数存在し、非特異的吸着が少ない;
・ 空孔容積を大きくしても比較的強度が高いため軟質ゲルに劣らない吸着容量が得られる;
・ 安全性が合成高分子ゲルなどに比べて高い。
(1) アニオン性官能基を有する化合物またはアニオン性官能基へ容易に変換し得る官能基を有する化合物をモノマーとして利用し、当該化合物を重合させることにより、水不溶性担体の形成とアニオン性官能基の導入を同時に行う方法;
(2) アニオン性官能基またはアニオン性官能基へ容易に変換し得る官能基を有する化合物を有する化合物を水不溶性担体に固定化する方法;
(3) アニオン性官能基またはアニオン性官能基へ容易に変換し得る官能基を水不溶性担体と直接反応させる方法;
(4) アニオン性官能基を有する化合物またはアニオン性官能基へ容易に変換し得る官能基を有する化合物をモノマーとして用いて水不溶性担体上にグラフト重合することにより、アニオン性官能基を有する化合物を有する水不溶性担体を得る方法。
チッソ社製の多孔質セルロースゲル(球状蛋白質の排除限界分子量:5,000万、粒径:45〜105μm、沈降体積量:100mL)に、20wt%水酸化ナトリウム水溶液40g、ヘプタン120gおよび非イオン界面活性剤(花王アトラス社製、トゥイーン20)10滴を加えた。40℃で2時間撹拌した後、エピクロロヒドリン50gを加えて2時間撹拌して反応させた。反応後、ゲルを水洗濾過し、エポキシ基の導入されたセルロースゲル(以下、「エポキシ化ゲル」という)を得た。
チッソ社製の多孔質セルロースゲル(球状蛋白質の排除限界分子量:2,000万、粒径:45〜105μm)を用いた以外は実施例1と同様にして、デキストラン硫酸ナトリウムが固定されたセルロースゲル(以下、「吸着体B」という)を得た。
チッソ社製の多孔質セルロースゲル(球状蛋白質の排除限界分子量:5,000万、平均粒子径:195μm)を用いた以外は実施例1と同様にして、デキストラン硫酸ナトリウムが固定されたセルロースゲル(以下、「吸着体C」という)を得た。
(1) ヒト血漿の調製
健常人新鮮血100mLに抗凝固剤としてヘパリン500μLを添加し、穏やかに混和した。抗凝固処理した健常人新鮮血を3,000rpmで15分間遠心分離し、上清を分取することで、ヒト血漿を得た。
ポリプロピレンチューブ(エッペンドルフ社製)に、実施例1〜3で得られた吸着体A〜C0.5mLと上記ヒト血漿3mLまたは6mLを加えて、37℃にて2時間振とうした。また、比較のため、吸着体の代わりに生理食塩水を同量用いた以外は同様にして、37℃にて2時間振とうした。
各サンプルの上清を一部抜き取り、臨床検査会社にPCSK9の分析を依頼してPCSK9の濃度を測定した。
PCSK9の吸着率(%)=[(C0−C1)/C0]×100
[式中、C0は生理食塩水を用いた吸着操作におけるPCSK9の濃度を示し、C1は吸着体を用いた吸着操作におけるPCSK9の濃度を示す]
結果を表1に示す。
上部および底部に吸着体の流出防止用のフィルターを備えたカラムに、実施例1で製造した吸着体Aを約150mL充填し、血漿吸着療法装置(カネカ社製、リポソーバーLA−15システム)を用い、PCSK9が高値の患者(計12名)から血液を抜き出し、上記装置に導入して処理してから患者へ返送するというPCSK9の吸着除去を行った。処理前後で患者の血液中のPCSK9濃度を測定し、その低下率を算出した。その結果、PCSK9の低下率は平均で54.8%であった。
2:液体の流出口
3:PCSK9の吸着体
4:液体および液体に含まれる成分は通過できるがPCSK9の吸着体は通過できないフィルター
5:液体および液体に含まれる成分は通過できるがPCSK9の吸着体は通過できないフィルター
6:カラム
7:PCSK9の吸着器
Claims (8)
- アニオン性官能基を有する水不溶性担体からなることを特徴とするPCSK9吸着体。
- アニオン性官能基が、硫酸基、スルホン酸基、カルボキシ基、リン酸基よりなる群から選択される少なくとも1つの官能基である請求項1に記載のPCSK9吸着体。
- アニオン性官能基がポリマーを介して水不溶性担体に結合している請求項1または2に記載のPCSK9吸着体。
- 2以上のアニオン性官能基がポリマーに共有結合している請求項3に記載のPCSK9吸着体。
- 水不溶性担体が親水性である請求項1〜4のいずれかに記載のPCSK9吸着体。
- 水不溶性担体が多孔性である請求項1〜5のいずれかに記載のPCSK9吸着体。
- 水不溶性担体が水酸基を有するものである請求項1〜6のいずれかに記載のPCSK9吸着体。
- 液の入口および出口を有し、かつ吸着体の容器外への流出防止手段を備えた容器内に、請求項1〜7のいずれかに記載のPCSK9吸着体を充填してなることを特徴とするPCSK9吸着器。
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JPH0852303A (ja) * | 1995-05-23 | 1996-02-27 | Kanegafuchi Chem Ind Co Ltd | 体外循環治療用吸着カラムの保存安定性を改良する方法 |
WO2004098680A1 (ja) * | 2003-05-08 | 2004-11-18 | Kaneka Corporation | 全血処理が可能な低密度リポ蛋白およびフィブリノーゲンの吸着材、及び吸着器 |
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JPH0852303A (ja) * | 1995-05-23 | 1996-02-27 | Kanegafuchi Chem Ind Co Ltd | 体外循環治療用吸着カラムの保存安定性を改良する方法 |
WO2004098680A1 (ja) * | 2003-05-08 | 2004-11-18 | Kaneka Corporation | 全血処理が可能な低密度リポ蛋白およびフィブリノーゲンの吸着材、及び吸着器 |
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