JP2010051447A - 生体材料 - Google Patents
生体材料 Download PDFInfo
- Publication number
- JP2010051447A JP2010051447A JP2008218064A JP2008218064A JP2010051447A JP 2010051447 A JP2010051447 A JP 2010051447A JP 2008218064 A JP2008218064 A JP 2008218064A JP 2008218064 A JP2008218064 A JP 2008218064A JP 2010051447 A JP2010051447 A JP 2010051447A
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- JP
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- Prior art keywords
- sirna
- mrna
- biomaterial
- copolymer
- polyethylene glycol
- Prior art date
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Abstract
【解決手段】ヒドロキシカルボン酸とポリエチレングリコールとを主構成単位とする共重合体とNoggin mRNAのsiRNA 、Follistatin mRNAのsiRNA、Sclerostatin mRNAのsiRNA、 Chordin mRNAのsiRNA、DCR mRNAのsiRNA, BMPMER mRNAのsiRNAから選ばれた一種以上のsiRNAとを含有する生体材料である。
これにリン酸カルシウム及び/又は骨誘導活性を有する細胞成長因子を含有させると、更に骨や軟骨の形成を促進することができる。
【選択図】 なし
Description
また、本発明の第2の構成は、上記siRNAが特にNoggin mRNAのsiRNAである生体材料に関する。
また、本発明の第3の構成は、ヒドロキシカルボン酸とポリエチレングリコールとを主構成単位とする共重合体に対するsiRNAの割合が0.01質量%以上である生体材料に関する。
また、本発明の第4の構成は、上記ヒドロキシカルボン酸が、乳酸、グリコール酸、p-ジオキサノン、トリメチレンカーボネート、ε-カプロラクトンから選ばれた一種以上である生体材料に関する。
また、本発明の第5の構成は、上記ヒドロキシカルボン酸とポリエチレングリコールとを主構成単位とする共重合体の構成単量体の両者のモル比が、5〜95/95〜5の範囲である生体材料に関する。
また、本発明の第6の構成は、上記ヒドロキシカルボン酸とポリエチレングリコールとを主構成単位とする共重合体の数平均分子量が、600〜68,000である生体材料に関する。
また、本発明の第7の構成は、上記ヒドロキシカルボン酸とポリエチレングリコールとを主構成単位とする共重合体中のヒドロキシカルボン酸とポリエチレングリコールの割合が65モル%以上である生体材料に関する。
また、本発明の第8の構成は、上記生体材料に、更にリン酸カルシウムを含有させた生体材料に関する。
また、本発明の第9の構成は、上記リン酸カルシウムに対するsiRNAの割合が0.0011質量%以上である生体材料に関する。
また、本発明の第10の構成は、上記生体材料に、更に骨誘導活性を有する細胞成長因子を含有させた生体材料に関する。
また、本発明の第11の構成は、siRNAに対する上記細胞成長因子の割合が5質量%以上である生体材料に関する。
以下に本発明の実施例を掲げ説明を行なうが、本発明はこれらに限定されるものではない。尚、%は特に断らない限り全て質量%を示す。
実施例1の共重合体に代えて、ポリ−dl−ラクチド(数平均分子量990)を使用し、この30mgに、Noggin mRNAのsiRNA(Invitrogen社製)10μgを少量の水に溶解した水溶液を混合した後、更に実施例2で得たrhBMP-2の5μgを加え、凍結乾燥し、直径6mm×厚さ3mmのペレット状の複合体ペレットを調製した。これをマウス(5週)の背部筋膜下に移植し、移植4日後に、ペレットに接触した筋肉細胞内のsiRNAの有無を蛍光標識により調べたが、siRNAの含有は見られなかった。
また、移植3週間後に移植片を摘出して、移植片の軟質X線像及び組織像を観察し、更にCa含有量を測定して、骨組織の状態を調べた結果、骨の形成は移植片周辺のみであり、移植部中心にはポリ−dl−ラクチドが残存していた。
実施例1の共重合体に代えて、アテロコラーゲン((株)高研製)を30mg使用し、Noggin mRNAのsiRNA(Invitrogen社製)10μgを少量の水に溶解した水溶液を混合した後、更に実施例2で得たrhBMP-2の5μgを加え、凍結乾燥し、直径6mm×厚さ3mmのペレット状の複合体ペレットを調製した。これをマウス(5週)の背部筋膜下に移植し、移植4日後に、ペレットに接触した筋肉細胞内のsiRNAの有無を蛍光標識により調べたが、siRNAの含有はみられなかった。
また、移植3週間後に移植片を摘出して、移植片の軟質X線像及び組織像を観察し、更にCa含有量を測定して、骨組織の状態を調べた結果、骨形成量は実施例2に比べて極めて少なかった。
Noggin mRNAのsiRNAを使用しないことを除いては、実施例2と同様にして複合体ペレットを調製した。これをマウス(5週)の背部筋膜下に移植した。移植3週間後に移植片を摘出し、移植片の軟質X線像及び組織像を観察し、更にCa含有量を測定して、骨組織の状態を調べた結果、骨形成量は実施例2に比べて極めて少なかった。
また、移植3週間後に移植片を摘出して、移植片の軟質X線像及び組織像を観察し、更にCa含有量を測定して、骨組織の状態を調べた結果、実施例2と同様の骨形成が確認された。
Claims (11)
- ヒドロキシカルボン酸とポリエチレングリコールとを主構成単位とする共重合体とNoggin mRNAのsiRNA 、 Follistatin mRNAのsiRNA、Sclerostatin mRNAのsiRNA、 Chordin mRNAのsiRNA、DCR mRNAのsiRNA, BMPMER mRNAのsiRNAから選ばれた一種以上のsiRNAとを含有する生体材料。
- siRNA がNoggin mRNAのsiRNAである請求項1記載の生体材料。
- ヒドロキシカルボン酸とポリエチレングリコールとを主構成単位とする共重合体に対するsiRNAの割合が0.01質量%以上である請求項1又は2記載の生体材料。
- ヒドロキシカルボン酸が、乳酸、グリコール酸、p-ジオキサノン、トリメチレンカーボネート、ε-カプロラクトンから選ばれた一種以上である請求項1、2又は3記載の生体材料。
- ヒドロキシカルボン酸とポリエチレングリコールとを主構成単位とする共重合体の構成単量体の両者のモル比が、5〜95/95〜5の範囲である請求項1、2、3又は4記載の生体材料。
- ヒドロキシカルボン酸とポリエチレングリコールとを主構成単位とする共重合体の数平均分子量が、600〜68,000である請求項1〜5のいずれか1項に記載の生体材料。
- ヒドロキシカルボン酸とポリエチレングリコールとを主構成単位とする共重合体中のヒドロキシカルボン酸とポリエチレングリコールの割合が65モル%以上である請求項1〜6のいずれか1項に記載の生体材料。
- 前記生体材料に、更にリン酸カルシウムを含有させた請求項1〜7のいずれか1項に記載の生体材料。
- リン酸カルシウムに対するsiRNAの割合が0.0011質量%以上である請求項8記載の生体材料。
- 前記生体材料に、更に骨誘導活性を有する細胞成長因子を含有させた請求項1〜9のいずれか1項に記載の生体材料。
- siRNAに対する細胞成長因子の割合が5質量%以上である請求項10記載の生体材料。
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JP2002525404A (ja) * | 1998-10-01 | 2002-08-13 | マクロメド・インコーポレーテッド | 逆熱ゲル化特性を有する生分解性低分子量トリブロックポリエステルポリエチレングリコールコポリマー |
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JP2007099631A (ja) * | 2005-09-30 | 2007-04-19 | Hosokawa Funtai Gijutsu Kenkyusho:Kk | アニオン性薬物封入ナノ粒子の製造方法及びそれを用いた医薬製剤 |
JP2007533376A (ja) * | 2004-04-15 | 2007-11-22 | エテックス コーポレーション | 遅延凝固リン酸カルシウムペースト |
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JP2002525404A (ja) * | 1998-10-01 | 2002-08-13 | マクロメド・インコーポレーテッド | 逆熱ゲル化特性を有する生分解性低分子量トリブロックポリエステルポリエチレングリコールコポリマー |
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