JP6224776B2 - キレート化複合ミセルを有する薬物キャリア及びその応用 - Google Patents
キレート化複合ミセルを有する薬物キャリア及びその応用 Download PDFInfo
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Description
使用する組成物及び形成方法に関する。
を攻撃しながら正常細胞を保護することは焦点と考えられる。化学療法及び放射線療法の作用機構は、遊離基による損傷に部分的に起因するので、抗酸化剤及び遊離基を有する物質を選択的に利用すると、これらの治療は正常細胞への損傷を減らすことができる。
ルラジカル(OH)関連のスピントラップ信号、過酸化物アニオン及びドキソルビシン(doxorubicin)から誘導した過酸化物アニオンを効果的に除去することができる。WR−1065のROS除去効果はブレオマイシン誘発肺の炎症及び線維症を予防するために用いることができる。
一又は複数の層によって形成される球状の担体である。これらのリポソームの構造制約は内核で親水性薬物を運ぶことを許すだけである。これらのキャリアは、特に肝臓に蓄積する傾向があり、温度変化に非常に敏感で、格納が難しく、乾燥粉末形態で運送は簡単なことではない(非特許文献1を参照)。
薬物に適用できる。しがしながら、これらの金属含有薬物はルイス酸とし、キャリアと結合した場合に、その官能基が置換され、その構造の変化は新薬として考えられるので、薬物の安全性及び有効性を再び評価する必要がある。これはコストの大幅な増加を引きこす可能性があるため、新た薬物キャリアの開発は業界にとって主な目標である。
700ダルトン)、10mgのFeCl2を秤り取り、得られた混合原料を5mLの緩衝液に25℃で異なる時間攪拌した。薬物放出の模擬のために、それを分子量3500の透析膜内に置いた。結果は、24時間攪拌する場合に、アミフォスチンを透析膜外に放出する割合は比較的に低く、大部分の薬物は鉄イオンとPEG−b−PGAと直接自己組織化によってキレート化複合ミセルを形成し、透析膜内に留まれて放出していない。前述の緩衝液は0.05MのHEPES(4−(2−hydroxyethyl)−1−piperazinee −thanesulfonic acid)であり、そのpH値が7.0である。
長し、また、人体に対する毒性(EDTAは人体内での金属元素をつかむ)を起こさない
。一方、配位結合はイオン結合の弱い相互作用を補う。また、金属イオンは容易に沈殿す
るが、PEGは良い流体分散度を有しても他の物質を受ける官能基を持っていないので、
PGAの変性により金属イオンと結合することができ、キャリアを流体中で均質に分散さ
せ、金属イオンによる沈殿に起因するブロッキング現象を引き起こさない。注意すべき点
は本発明のキャリアを親水性薬物又は疎水性薬物に適用することができ、応用価値を非常
に高める。一方、FDA又は関連医薬品の試験規格に準拠する薬物にとって、原薬物の構
造を破壊すれば、非常に僅かな割合があるでも、新た薬物と見らされる可能性があり、安
全性及び有効性を再び検証する必要があり、コストが非常にかかる。それに対して、本発
明は薬物の構造に変更することなく、従って再確認の問題を起こさない。従って、プロセ
スの互換性のために、本発明は非常に高いコスト価値を有する。
きる。そして、それらは以下の特許請求の範囲内で解釈されるべきである。上述の詳細な
説明に加えて、本発明を広く他の実施例に実施することができる。以上の実施例は本発明
を説明するために提示されたものであり、本発明の範囲を制限するものではなく、本発明
の要旨より離脱せずに当業者がなしうる各種の変更或いは修飾は、本発明の請求範囲に属
するものとする。
110 細胞保護剤アミフォスチン
120 ポリ(エチレングリコール)−b−ポリ(グルタミン酸)
130 塩化第一鉄
Claims (6)
- アミフォスチンとポリ(エチレングリコール)−b−ポリ(グルタミン酸)と塩化第一
鉄を含む原料を提供する工程と、
該原料を緩衝液に投入して連続的に混合する工程を備え、
アミフォスチンとポリ(エチレングリコール)−b−ポリ(グルタミン酸)は第一鉄イ
オンを介して配位結合によって自己組織化することを特徴とするキレート化複合ミセルを
有する医薬組成物の製造方法。 - 前記アミフォスチンの重量は0.1〜10mgの範囲にあり、ポリ(エチレングリコー
ル)−b−ポリ(グルタミン酸)の重量は0.1〜100mgの範囲にあり、塩化第一鉄
の重量は0.01〜50mgの範囲にあることを特徴とする請求項1に記載のキレート
化複合ミセルを有する医薬組成物の製造方法。 - 前記アミフォスチンの濃度は0.01〜10mg/mLの範囲にあることを特徴とする請求項1に記載のキレート化複合ミセルを有する医薬組成物の製造方法。
- 前記緩衝液は4−(2−ヒドロキシエチル)−1−ピペラジンエタンスルホン酸であることを特徴とする請求項1に記載のキレート化複合ミセルを有する医薬組成物の製造方法。
- 前記緩衝液のpH値は6.5〜7.5の範囲にあることを特徴とする請求項1に記載のキレート化複合ミセルを有する医薬組成物の製造方法。
- 前記混合する工程は4〜40℃の温度で行うことを特徴とする請求項1に記載のキレート化複合ミセルを有する医薬組成物の製造方法。
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US201161562663P | 2011-11-22 | 2011-11-22 | |
US61/562,663 | 2011-11-22 |
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JP2016132358A Active JP6224776B2 (ja) | 2011-11-22 | 2016-07-04 | キレート化複合ミセルを有する薬物キャリア及びその応用 |
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EP (1) | EP2783679B1 (ja) |
JP (3) | JP2015507605A (ja) |
KR (2) | KR101815030B1 (ja) |
CN (1) | CN103127521B (ja) |
AU (1) | AU2012343239B2 (ja) |
CA (1) | CA2856501C (ja) |
IL (1) | IL232729B (ja) |
IN (1) | IN2014MN00936A (ja) |
TW (1) | TWI568453B (ja) |
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WO2014079020A1 (en) * | 2012-11-22 | 2014-05-30 | Original Biomedicals Co., Ltd. | Pharmaceutical composition used for reducing damage caused by free radicals |
BR112014013184A2 (pt) * | 2012-08-28 | 2017-06-13 | Original Biomedicals Co Ltd | método de liberação controlada para manipulação de liberação de fármaco e método de liberação controlada que usa micelas complexas quelantes |
WO2015020240A1 (ko) * | 2013-08-06 | 2015-02-12 | 동국제약 주식회사 | 엔테카비어 미립구 및 이를 포함하는 비경구투여용 약제학적 조성물 |
CN104627958B (zh) * | 2015-01-30 | 2016-03-16 | 四川大学 | 一种稳定性增强的改性纳米粒子及其制备方法 |
CN104693433B (zh) * | 2015-02-04 | 2017-06-06 | 国家纳米科学中心 | 一种聚乙二醇化氨磷汀、制备方法及其用途 |
WO2017087668A1 (en) * | 2015-11-17 | 2017-05-26 | The Burlington Hc Research Group, Inc. | Methods for improved protection and delivery of aminothiols and analogs thereof |
EP3505154B1 (en) | 2017-12-26 | 2022-04-06 | Industrial Technology Research Institute | Composition for improving the solubility of poorly soluble substances, use thereof and complex formulation containing thereof |
KR102206913B1 (ko) | 2018-12-04 | 2021-01-26 | 한국생산기술연구원 | 기능성 물질 전달용 조성물 및 이의 제조 방법 |
CN109970987B (zh) * | 2019-04-11 | 2021-09-17 | 中国医学科学院放射医学研究所 | Mof材料、纳米载药材料、药物组合物及其应用 |
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