JP7453334B2 - 核酸-リン酸カルシウムナノ粒子複合体及び生物鉱化におけるその使用 - Google Patents
核酸-リン酸カルシウムナノ粒子複合体及び生物鉱化におけるその使用 Download PDFInfo
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- JP7453334B2 JP7453334B2 JP2022505251A JP2022505251A JP7453334B2 JP 7453334 B2 JP7453334 B2 JP 7453334B2 JP 2022505251 A JP2022505251 A JP 2022505251A JP 2022505251 A JP2022505251 A JP 2022505251A JP 7453334 B2 JP7453334 B2 JP 7453334B2
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Classifications
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- C—CHEMISTRY; METALLURGY
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- C12N15/00—Mutation or genetic engineering; DNA or RNA concerning genetic engineering, vectors, e.g. plasmids, or their isolation, preparation or purification; Use of hosts therefor
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- A61L2300/00—Biologically active materials used in bandages, wound dressings, absorbent pads or medical devices
- A61L2300/20—Biologically active materials used in bandages, wound dressings, absorbent pads or medical devices containing or releasing organic materials
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Description
Claims (19)
- ハイドロキシアパタイト-コラーゲンの有機無機複合材料を調製するためのコラーゲン線維製品の鉱化のための鉱化剤の使用であって、
前記鉱化剤は、核酸と非晶質リン酸カルシウムナノ粒子の静電吸着により形成された複合体を含み、
前記複合体において、核酸と非晶質リン酸カルシウムナノ粒子は以下の順番:
核酸のリン酸基とナノ粒子のカルシウムイオンとの間の静電吸着、及び
遊離のリン酸イオンと核酸に吸着したカルシウムイオンのさらなる静電吸着、
で形成され、
前記鉱化剤において、カルシウムイオンの濃度は、2~5mMであり、リン酸イオンの濃度は、1~5mMであり、カルシウムイオンとリン酸イオンの濃度の比は、2:1~1:1であり、
前記核酸は、哺乳動物細胞の全DNA又は全RNAから単離され、
DNAの出発濃度は、70~250ug/mlであり、又は、RNAの出発濃度は、150~250ug/mlであり、
前記複合体の粒径は、40~100nmである、使用。 - 前記鉱化剤が、核酸溶液、塩化カルシウム溶液及びリン酸水素二カリウム溶液を混合して形成される、請求項1に記載の使用。
- 鉱化剤中のカルシウムイオンの濃度は、1.67~3.5mMであり、リン酸イオンの濃度は、1.0~2.1mMである、請求項1又は2に記載の使用。
- 鉱化剤中のカルシウムイオンとリン酸イオンの濃度の比は、1.67:1である、請求項1又は2に記載の使用。
- 前記複合体の粒径が、40~60nm又は60~100nmである、請求項1又は2に記載の使用。
- 前記哺乳動物細胞は、骨細胞前駆細胞、前骨芽細胞、骨細胞、骨形成細胞、破骨細胞又は骨髄間葉系幹細胞である、請求項1又は2に記載の使用。
- 前記哺乳動物細胞は、破骨細胞である、請求項1又は2に記載の使用。
- 前記哺乳動物細胞は、骨細胞である、請求項1又は2に記載の使用。
- 鉱化剤のpH値は、5.5~6.9である、請求項1又は2に記載の使用。
- 鉱化剤のpH値は、6.0~6.5である、請求項9に記載の使用。
- 鉱化剤が、液体形態、半固体形態、又は固体形態である、請求項1又は2に記載の使用。
- 鉱化剤が、溶液、コロイド液、ゲル、又は粉末である、請求項11に記載の使用。
- 鉱化剤が、凍結乾燥粉末である、請求項11に記載の使用。
- コラーゲン線維製品が骨修復材料から選択される、請求項1又は2に記載の使用。
- コラーゲン線維製品がコラーゲン足場から選択される、請求項1又は2に記載の使用。
- コラーゲン線維製品がコラーゲン膜及びコラーゲン線維シートから選択される、請求項1又は2に記載の使用。
- ハイドロキシアパタイト-コラーゲンの有機無機複合材料が、患者における骨関連疾患又は障害を治療し、又は骨の状態を改善するための医薬又は医療機器の製造に用いられる、請求項1又は2に記載の使用。
- 鉱化剤が以下の方法:
(1)、好ましくは哺乳動物細胞から全DNA(各種のDNAを含む)又は全RNA(各種のRNAを含む)を抽出して、核酸を得るステップと、
(2)、ステップ(1)で得られた核酸を塩化カルシウム溶液と混合するステップと、
(3)、ステップ(2)で得られた混合物にリン酸水素二カリウム溶液を添加することにより、核酸と非晶質リン酸カルシウムナノ粒子とで形成された複合体を得るステップとを含む、ことを特徴とする方法により製造される、請求項1又は2に記載の使用。 - ステップ(1)で取得された核酸の出発濃度は、1500~2500ng/μlであり,核酸分子量が40kDaよりも大きい、請求項18に記載の使用。
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Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
JP2005237632A (ja) | 2004-02-26 | 2005-09-08 | Univ Waseda | コラーゲン−リン酸カルシウム複合体の製造方法、及びそれを用いた硬組織代替材料 |
JP2009519052A (ja) | 2005-12-06 | 2009-05-14 | エテックス コーポレーション | 多孔性リン酸カルシウム骨材料 |
CN103536965A (zh) | 2013-09-24 | 2014-01-29 | 北京大学口腔医学院 | 具严格等级结构的三维矿化胶原支架的制备方法、及其产品和应用 |
JP2019043798A (ja) | 2017-08-31 | 2019-03-22 | 国立研究開発法人産業技術総合研究所 | 分散性リン酸カルシウムナノ粒子 |
CN110628767A (zh) | 2019-07-26 | 2019-12-31 | 华中农业大学 | 一种生物矿化的CRISPR/Cas9 RNPs纳米颗粒、制备方法及其用于基因编辑 |
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US20070077306A1 (en) * | 2003-12-26 | 2007-04-05 | Toshihiro Akaike | Apatite particle, method of producing the same, apatite particle-gene complex, and method of gene transfection |
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CN107929812B (zh) * | 2017-11-24 | 2020-12-25 | 天津医科大学口腔医院 | 一种仿生矿化胶原支架的制备方法 |
CN109534349B (zh) * | 2018-03-30 | 2020-09-25 | 中国科学院上海应用物理研究所 | 一种基于框架核酸编码的有机矿化结构的合成方法及应用 |
CN110693724B (zh) * | 2019-11-05 | 2020-10-30 | 浙江大学 | 一种牙齿矿化液及其矿化方法 |
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Patent Citations (5)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
JP2005237632A (ja) | 2004-02-26 | 2005-09-08 | Univ Waseda | コラーゲン−リン酸カルシウム複合体の製造方法、及びそれを用いた硬組織代替材料 |
JP2009519052A (ja) | 2005-12-06 | 2009-05-14 | エテックス コーポレーション | 多孔性リン酸カルシウム骨材料 |
CN103536965A (zh) | 2013-09-24 | 2014-01-29 | 北京大学口腔医学院 | 具严格等级结构的三维矿化胶原支架的制备方法、及其产品和应用 |
JP2019043798A (ja) | 2017-08-31 | 2019-03-22 | 国立研究開発法人産業技術総合研究所 | 分散性リン酸カルシウムナノ粒子 |
CN110628767A (zh) | 2019-07-26 | 2019-12-31 | 华中农业大学 | 一种生物矿化的CRISPR/Cas9 RNPs纳米颗粒、制备方法及其用于基因编辑 |
Non-Patent Citations (1)
Title |
---|
長澤寛道,バイオミネラリゼーションの科学,化学と生物,2004年,Vol. 42,pp. 340-345 |
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