JP4297221B2 - 薬剤溶出型ステントの製造方法 - Google Patents
薬剤溶出型ステントの製造方法 Download PDFInfo
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- JP4297221B2 JP4297221B2 JP2006037389A JP2006037389A JP4297221B2 JP 4297221 B2 JP4297221 B2 JP 4297221B2 JP 2006037389 A JP2006037389 A JP 2006037389A JP 2006037389 A JP2006037389 A JP 2006037389A JP 4297221 B2 JP4297221 B2 JP 4297221B2
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Description
本発明に用いられる生体適合性ナノ粒子は、生理活性物質及び生体適合性高分子を1,000nm未満の平均粒径を有するナノ単位の大きさの粒子(ナノスフェア)に加工することができる球形晶析法を用いて、ナノ粒子の内部に生理活性物質を封入することにより製造される。球形晶析法は高剪断力を発生しない粒子調製法であるため、特に、生理活性物質が外部応力に弱い核酸化合物等の場合にも好適に用いることができる。
次に、生理活性物質が封入された生体適合性ナノ粒子をステント本体に付着させてナノ粒子層を形成する方法について説明する。ナノ粒子を付着させる方法としては、ナノ粒子懸濁液への浸漬やミストコート等によりナノ粒子をステント本体に物理的に付着させる方法を用いても良いが、上述したように本発明で用いられるナノ粒子表面は正に帯電しているため、ナノ粒子を電気的に付着させることによりステント本体に強固且つ均一にコーティング可能となる。ここでは、生体適合性ナノ粒子の懸濁液中でステント本体を負極として通電する電気泳動法と、負に帯電させたステント表面に生体適合性ナノ粒子含有液滴を付着させる噴霧法を例に挙げて説明する。
[PLGAナノスフェアの調製]
[ステント本体へのPLGAナノスフェアのコーティング]
DMEM(Dulbecco's Modified Eagle's Medium, high glucose、SIGMA社製;D5796)に1%ペニシリンストレプトマイシンを添加し、さらにリン酸緩衝液を最終濃度10%となるように添加して培養液とした。この培養液に、ラット胸部大動脈平滑筋細胞を、4×104cells/mLの濃度(細胞数)となるように懸濁し、500μL(2×104cells/well)ずつ48穴の細胞培養プレート(OAAS−48、コスモ・バイオ社製)に播種した。37℃、5%CO2雰囲気のインキュベータ内で培養し、48時間後に培養液を250μL/wellずつ、同一培養プレート上の3つのwellに入れ替えた。
2 ポリビニルアルコール
3 生理活性物質
4 カチオン性高分子
5 電気泳動装置
6 浴槽
7 懸濁液
8 ステント本体
9 正極
10 金属繊維
11 ナノ粒子層
12 生分解性高分子層
13 ナノ粒子懸濁液
14 円筒容器
15 ステンレス製パイプ
16 シリコンチューブ
17 外部電源
18 電流計
Claims (7)
- 少なくともカチオン性高分子を溶解させた水溶液に、少なくとも生理活性物質の溶液と生体適合性高分子を有機溶媒に溶解させた溶液との混合液を加えて、前記生理活性物質が前記生体適合性高分子中に封入され、且つ粒子表面が正電荷修飾された生体適合性ナノ粒子の懸濁液を生成するナノ粒子形成工程と、
前記生体適合性ナノ粒子をステント本体に電気的に付着させてナノ粒子層を形成するナノ粒子付着工程と、
前記ナノ粒子層に生分解性高分子の溶液を含浸させる含浸工程と、
前記生分解性高分子の溶液を含浸させた前記ナノ粒子層を乾燥させる乾燥工程と、
を有することを特徴とする薬剤溶出型ステントの製造方法。 - 前記ナノ粒子付着工程が、電気泳動法、超音波ミスト法、スプレー法若しくはエアーブラシ法のいずれかにより行われることを特徴とする請求項1に記載の薬剤溶出型ステントの製造方法。
- 前記ナノ粒子付着工程は、前記ステント本体に形成された前記ナノ粒子層の上にさらにナノ粒子層を積層する第2付着工程を有することを特徴とする請求項1又は請求項2に記載の薬剤溶出型ステントの製造方法。
- 前記生体適合性ナノ粒子の懸濁液に、さらにアニオン性薬物を添加することを特徴とする請求項1乃至請求項3のいずれか1項に記載の薬剤溶出型ステントの製造方法。
- 前記ナノ粒子付着工程を複数回繰り返すことにより、異なる生理活性物質が封入された生体適合性ナノ粒子から成る前記ナノ粒子層を、積層状又はモザイク状に形成することを特徴とする請求項1乃至請求項4のいずれか1項に記載の薬剤溶出型ステントの製造方法。
- 前記含浸工程において、前記生分解性高分子の溶液中にさらに生理活性物質を添加することを特徴とする請求項1乃至請求項5のいずれか1項に記載の薬剤溶出型ステントの製造方法。
- 前記含浸工程においてナノ粒子層に含浸させる生分解性高分子は、前記生体適合性ナノ粒子を形成する生体適合性高分子より生体内での分解速度が速いことを特徴とする請求項1乃至請求項6のいずれか1項に記載の薬剤溶出型ステントの製造方法。
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AU2013331003B2 (en) * | 2012-10-18 | 2016-11-24 | Micell Technologies, Inc. | Drug delivery medical device |
JP6068921B2 (ja) * | 2012-10-19 | 2017-01-25 | ホソカワミクロン株式会社 | 薬剤溶出型デバイスの製造方法 |
US20140178611A1 (en) | 2012-11-19 | 2014-06-26 | Massachusetts Institute Of Technology | Apparatus and methods employing liquid-impregnated surfaces |
CA2892073C (en) | 2012-11-19 | 2022-05-03 | Massachusetts Institute Of Technology | Apparatus and methods employing liquid-impregnated surfaces |
WO2014165264A1 (en) | 2013-03-12 | 2014-10-09 | Micell Technologies, Inc. | Bioabsorbable biomedical implants |
EP2996629B1 (en) | 2013-05-15 | 2021-09-22 | Micell Technologies, Inc. | Bioabsorbable biomedical implants |
TWI697337B (zh) | 2013-08-07 | 2020-07-01 | 學校法人近畿大學 | 奈米粒子或奈米粒子組成物之製造方法,及支架或球囊導管之製造方法 |
CN110711056A (zh) | 2014-10-28 | 2020-01-21 | 株式会社Jimro | 药物洗脱支架 |
CN112972871A (zh) * | 2014-12-29 | 2021-06-18 | 波士顿科学国际有限公司 | 用于化疗药物多级释放的组合物、装置和方法 |
CN113616860B (zh) * | 2021-06-29 | 2022-11-01 | 四川大学 | 一种具有药物缓释及抗凝、抗钙化性能的血管支架涂层材料及其制备方法 |
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