Development of next-generation module for blood purification that can control antithrombotic properties by nitric oxide releasing material.

• Project/Area Number: 16K09653
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Multi-year Fund
• Section: 一般
• Research Field: Kidney internal medicine
• Research Institution: Kitasato University
• Principal Investigator: Kokubo Kenichi 北里大学, 医療衛生学部, 准教授 (20287965)
• Co-Investigator(Kenkyū-buntansha): 小林 弘祐 北里大学, 医療衛生学部, 教授 (70153632) ; 小林 こず恵 北里大学, 医療衛生学部, 助教 (60448975)
• Project Period (FY): 2016-04-01 – 2019-03-31
• Project Status: Completed (Fiscal Year 2018)
• Budget Amount: ¥4,680,000 (Direct Cost: ¥3,600,000、Indirect Cost: ¥1,080,000); Fiscal Year 2018: ¥1,430,000 (Direct Cost: ¥1,100,000、Indirect Cost: ¥330,000); Fiscal Year 2017: ¥1,170,000 (Direct Cost: ¥900,000、Indirect Cost: ¥270,000); Fiscal Year 2016: ¥2,080,000 (Direct Cost: ¥1,600,000、Indirect Cost: ¥480,000)
• Keywords: 血液透析膜 / 生体適合性 / 一酸化窒素 / 抗血栓性材料 / 血液浄化器

Outline of Final Research Achievements

The aims of the present study were 1) to examine appropriate NO concentration required to exert anticoagulant ability by a rat extracorporeal model, and 2) to develop nitric oxide (NO) releasing material.
1) Extracorporeal circulation was performed for 4 hours using rat, NO gas of different concentration was added to the dialysate, and the residual blood clots to the filter after extracorporeal circulation was evaluated by the hemoglobin content and lactate dehydrogenase activity in the eluent. Appropriate NO concentration added to the dialysate was determined.
2) We tried to develop an NO-releasing material in which an NO donor was encapsulated. By examining several NO donors and macrocapsule materials to be used, we created microcapsules capable of releasing NO at a concentration required to exert antithrombotic properties.

Academic Significance and Societal Importance of the Research Achievements

本研究により、透析膜と血液が接触する際の抗血栓性を向上させるために必要なNO濃度が明らかとなり、またその濃度のNOを放出可能なマイクロカプセルを作成できた。NOを透析膜表面から放出させることで、透析膜の生体適合性、抗凝固性の向上が期待できる。また、出血性病変を有していて抗凝固剤が使いにくい患者に対しても抗血栓性を発揮でき、将来的には装着型や埋込型の人工腎臓の実現につながるモジュールにもつながる技術と考えられ、臨床的な意義も大きい。また本研究により得られた結果は、長時間血液と接触可能な材料の開発において、新たな材料設計のための指針を与えるものであり、他分野への波及効果も期待できる。

Research Products

• [Presentation] SUPPRESSION OF BLOOD COAGULATION ON THE SURFACE OF A DIALYSIS MEMBRANE USING A NITRIC OXIDE-CONTAINING DIALYSATE (2019)
  • Author(s): Kenichi Kokubo, Kozue Kobayashi, Kenya Kohagura, Yuhei Yoshida, Hirosuke Kobayashi
  • Organizer: 56th Congress of the European Renal Association (ERA) and European Dialysis and Transplant Association (EDTA)
• [Presentation] 透析液に付加した一酸化窒素による血液透析膜の表面の抗血栓性の改善 (2018)
  • Author(s): 古波蔵賢弥, 吉田裕平, 小林こず恵, 小久保謙一, 小林弘祐
  • Organizer: 第45回日本血液浄化技術学会学術大会・総会
• [Presentation] 私の考えるHPM：長期間使用可能な人工膜という側面から (2018)
  • Author(s): 小久保謙一
  • Organizer: ハイパフォーマンス・メンブレン研究会