JP2018047245A - 異なる密度の成分を有する粒子状組織グラフトならびにそれを作成および使用する方法 - Google Patents
異なる密度の成分を有する粒子状組織グラフトならびにそれを作成および使用する方法 Download PDFInfo
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Abstract
Description
porcine bone)、脱塩同種移植骨、または石灰化した同種移植骨などの、骨代替材料と組み合わせ可能である。別の実施形態では、骨粒子および本発明の異なる密度のECM粒子は、接着剤、結合剤、またはあらゆるその他の添加剤を用いずに混合可能である。粒子は骨代替材料に被覆および/または注入される。骨代替材料が患者の組織部位に移植されると、骨代替材料は欠損を安定化するために強固な構造をもたらし、一方で、低密度な粒子は部位における急速な組織修復を促進する。高密度な粒子が低密度な粒子よりも低速で生体吸収されるため、長期間の間、高密度な粒子は移植部位における組織修復を維持する。高密度粒子は組織部位が修復するまで、通常は完全に生体吸収されない。
ECM粒子の混合物を、50〜1000μmの大きさで約0.05g/cm3の密度を有する60mgのUBM粒子、および50〜500μmの大きさで約0.25g/cm3の密度を有する20mgのUBM粒子を、重量に基づき3:1の粒子割合で用いて作成する。混合物を慢性皮膚潰瘍に局所的に投与する。10日以内に、0.05g/cm3の粒子が吸収され、組織再生が創傷部位において観察される。30日以内に、0.25g/cm3の粒子が吸収され、創傷部位の組織が完全に再生する。
ECM粒子の混合物を、腫瘍が切除された腎臓部位へ移植するために調製する。ECM粒子の混合物を、500〜1000μmの大きさで約0.10g/cm3の密度を有する200mgのUBM粒子、および50〜500μmの大きさで約0.35g/cm3の密度を有する1000mgのUBM粒子を、重量に基づき1:5の粒子割合で用いて作成する。混合物を患者に注射器を用いて外科的に移植する。20日以内に、0.10g/cm3の粒子が吸収され、磁気共鳴画像法によって組織再生が創傷部位において観察される。60日以内に、0.35g/cm3の粒子が吸収され、磁気共鳴画像法で観察されるよう
に、創傷部位の組織は完全に再生する。
Claims (20)
- 生体吸収性粒子状物質の組成物であって、患者の部位への移植において第1密度および第1吸収速度を有する複数の第1生体吸収性粒子、および患者の部位への移植において第2密度および第2吸収速度を有する複数の第2粒子を含み、前記第2密度は前記第1密度の少なくとも150%であり、前記第2吸収速度は前記第1吸収速度の約1〜約10倍の範囲であり、前記複数の第1および第2の生体吸収性粒子は、哺乳動物患者の組織部位に移植されると、組織の再生および修復を促進する組成物。
- 請求項1の混合物であって、前記複数の第1生体吸収性粒子は第1生体吸収性材料を含み、前記複数の第2粒子は第2生体吸収性材料を含む混合物。
- 請求項2の混合物であって、前記第1または第2の生体吸収性材料は、細胞外マトリックス、コラーゲン、吸収性ポリマー、またはヒアルロン酸から成る群より選択される混合物。
- 請求項1の混合物であって、前記第2密度は前記第1密度の150%〜500%である混合物。
- 異なる密度を有する生体吸収性粒子状物質の混合物を調製する方法であって、(a)第1密度および第1吸収速度を有する生体吸収性材料の第1シートを提供し、および前記シートを複数の第1粒子に製粉し、(b)第2密度および第2吸収速度を有する生体吸収性材料の第2シートを提供し、および前記シートの複数の第2粒子に製粉し、(c)前記複数の第1粒子の所定量を提供し、および該所定量を前記複数の第2粒子の所定量と混合することを含み、
前記複数の第2粒子の密度は前記複数の第1粒子の密度の少なくとも150%であり、前記第1吸収速度は前記第2吸収速度の少なくとも1.5倍であり、
前記複数の第1生体吸収性粒子および前記複数の第2生体吸収性粒子は、哺乳動物患者の組織部位に移植されると、組織の再生および修復を促進する方法。 - 請求項5の方法であって、製粉前に前記第2シートを圧縮または薄層化することで、その密度を前記第1シートと比較して増加させることをさらに含む方法。
- 請求項5の方法であって、製粉前に前記第1シートを凍結乾燥することで、その密度を前記第2シートと比較して減少させることをさらに含む方法。
- 請求項5の方法であって、前記第1シートおよび前記第2シートは細胞外マトリックスを含む方法。
- 請求項5の方法であって、前記第2密度は前記第1密度の150%〜500%である方法。
- 異なる密度を有する生体吸収性粒子状物質の混合物を調製する方法であって、
第1密度の生体吸収性材料シートを提供し、前記シートの一部分を圧縮することで、該一部分が前記第1密度の少なくとも150%である第2密度を含み、かつ、
前記シートを複数の粒子に製粉すること含み、
前記生体吸収性材料シートは、哺乳動物患者の組織部位に移植されると、組織の再生および修復を促進する方法。 - 修復または再生を必要とする患者の解剖学的部位における組織修復の速度を調節する方法であって、該方法は、
第1密度を有する複数の第1生体吸収性粒子、および前記第1密度の少なくとも150%の第2密度を有する複数の第2生体吸収性粒子を含む混合物を、患者の部位へ投与することを含み、
前記複数の第2生体吸収性粒子は、前記複数の第1生体吸収性粒子の吸収速度よりもゆっくりと患者の組織に吸収されるため、前記部位における前記複数の第2粒子の治療効果を延長可能であり、前記複数の第1および第2生体吸収性粒子は、哺乳動物患者の前記解剖学的部位において移植されると、組織の再生および修復を促進する方法。 - 請求項11の方法であって、前記生体吸収性粒子の混合物を調製する段階をさらに含み、前記調製は、
(a)前記患者の部位における修復または再生のための吸収性組成物の最適吸収速度を決定する段階、
(b)前記患者の部位への移植において、第1密度および段階(a)に基づく前記最適吸収速度を有するように、前記複数の第1生体吸収粒子を選択する段階、および
(c)前記患者の部位への移植において、前記複数の第1粒子の密度よりも高密度である第2密度を有し、かつ段階(a)および(b)に基づく前記複数の第1生体吸収性粒子の吸収速度よりも遅い吸収速度を有するように、前記複数の第2生体吸収性粒子を選択する段階を含む方法。 - 請求項11の方法であって、前記生体吸収性粒子は液体またはゲルの媒体にて前記患者の部位に送達される方法。
- 請求項11の方法であって、前記生体吸収性粒子は前記患者の部位に注入される方法。
- 請求項11の方法であって、前記混合物は前記部位に局所的に投与される方法。
- 第1密度の細胞外マトリックス粒子および第2密度の細胞外マトリックス粒子を含む、人間の患者に移植するための移植片であって、前記粒子は圧縮されて立体物体を形成し、第1密度の前記粒子および第2密度の前記粒子は、前記人間の患者の組織部位に移植されると、組織の再生および修復を促進する移植片。
- 請求項16の移植片であって、前記細胞外マトリックスは、UBS、SIS、またはUBMである移植片。
- 請求項16の移植片であって、前記第1密度の粒子は前記第2密度の粒子よりも高密度であり、前記第1密度の粒子は前記移植片の中心部を形成し、前記第2密度の粒子は前記移植片の外面を形成する移植片。
- 細胞外マトリックス粒子の混合物を調製する方法であって、
同一密度を有する複数の細胞外マトリックス粒子を調製し、
前記複数の粒子の第1部分を第1密度を有するコーティングで被覆し、
前記複数の粒子の第2部分を第2密度を有するコーティングで被覆し、
前記粒子の第1部分を前記粒子の第2部分と混合することで、前記粒子の混合物を形成することを含み、
前記複数の粒子は哺乳動物患者の組織部位に移植されると、組織の再生および修復を促進する方法。 - 細胞外マトリックス組成物であって、
細胞外マトリックスの第1シート、
細胞外マトリックスの第2シート、および
第1密度を有する複数の第1細胞外マトリックス粒子および前記第1密度の少なくとも150%の第2密度を有する複数の第2細胞外マトリックス粒子を含み、
前記複数の第1粒子および前記複数の第2粒子は前記細胞外マトリックスの第1シートと第2シートとの間に含まれて、前記複数の第1および第2細胞外マトリックス粒子は哺乳動物患者の組織部位に移植されると、組織の再生および修復を促進する組成物。
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