銭谷 平¹, 鈴木 亮 ², 丸山 一雄², 古幡 博¹

Taira ZENITANI¹, Ryo SUZUKI², Kazuo MARUYAMA², Hiroshi FURUHATA¹

¹東京慈恵会医科大学総合医科学研究センター 医用エンジニアリング研究室, ²帝京大学 薬学部生物薬剤学教室

¹Medical Engineering Laboratory, Research Center for Medical Science, Jikei University School of Medicine, ²Department of Biopharmaceutics, School of Pharmaceutical Sciences, Teikyo University

キーワード : ultrasound, thrombolysis, bubble, liposome

目的：バブルリポソーム（Bubble Liposomes: BLs）と低周波超音波（連続波，500kHz）の併用による血栓溶解効果加速化をin vitro実験によって検証した．対象と方法：血栓としてウシ血漿にトロンビンを加えたフィブリン塊を用いた．その血栓塊を加圧容器内溶液に封入し，その圧力150mmHg，37℃の状態で超音波（Ultrasound: US）を照射し，血栓重量減少率を測定した．重量減少率は（封入前重量‐超音波照射後摘出時重量）／封入前重量とした．超音波条件は連続波500kHz，暴露時間60秒，音響強度0.7W/cm² （非加圧状態での容器内）．容器内溶液として，生理食塩水（control群），BLs溶液（脂質量として0.5mg/ml） （BLs群），rt-PA（monteplase）溶液 1000IU/ml（rt-PA群），BLs（脂質量として0.5mg/ml）を含むrt-PA溶液 1000IU/ml（rt-PA＋BLs群）を用いた．それぞれに対し超音波照射・非照射を行い，各群（各n＝10）について重量減少率を2群間比較（t検定）した．結果と考察：BLsを加えたrt-PA＋US群の血栓溶解増強効果は，60秒ではrt-PA，BLs，USの単独および，どの2因子の組み合わせに対しても有意であった（0.001＜p＜0.027）．結論：BLsはrt-PA併用超音波血栓溶解効果を60秒で促進した．

Purpose: The accelerating effect on thrombolysis by combined use of 500-kHz low-frequency ultrasound (US), recombinant tissue plasminogen activator (rt-PA), and bubble liposomes (BLs) was verifi ed in vitro. Methods: A fibrin clot was formed by adding thrombin to bovine plasma. It was enclosed in a pressurized container, the pressure and temperature of which were maintained at 150 mmHg and 37°C, respectively. Ultrasonic conditions were set at a continuous wave, a frequency of 500kHz, an intensity of 0.7 W/ cm², and a sonication time of 60s. We derived the rate of reduction in clot weight from the decreased clot weight and the weight before sonication. We compared the rate of reduction in groups combining physiological saline, rt-PA, BLs, and US. Results: Only the rt-PA+US+BL group showed a signifi - cantly accelerated thrombolytic effect compared with any other group or with any combination of two factors in the 60-s period (0.001〈P〈0.027). Conclusion: BLs have great potential to accelerate the thrombolytic effect of rt-PA with low-frequency, 500-kHz, continuous-wave ultrasound.