JP2017519496A - 角膜血管新生および角膜拡張性疾患の動物モデル、製造方法、およびその使用方法 - Google Patents
角膜血管新生および角膜拡張性疾患の動物モデル、製造方法、およびその使用方法 Download PDFInfo
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Abstract
Description
(i)非ヒト動物の少なくとも1つの眼の角膜に式(I)の芳香族化合物の有効量を適用することを含む方法によって、角膜血管新生または角膜拡張性疾患の非ヒト動物モデルを調製すること:
(iii)上記の少なくとも1つの眼における角膜での血管成長および角膜の構造的歪みの少なくとも1つに対する上記試験化合物の効果を判定することを含み、
Rは、ヒドロキシル、ハロゲン、アルキル、アルコキシおよびアミノからなる群から選択され、nは0、1、2、3、4、5、または6である上記方法に関する。
(i)非ヒト動物の少なくとも1つの眼の角膜に試験物質を適用すること;および
(ii)角膜における血管成長および角膜の構造的歪みの少なくとも1つに対する試験物質の影響を測定することを含む。
(i)非ヒト動物の少なくとも1つの眼に有効量の式(I)の芳香族化合物を適用することを含む、角膜血管新生または角膜拡張性疾患の非ヒト動物モデルを調製すること;
(ii)試験化合物を上記非ヒト動物モデルの上記の少なくとも1つの眼に投与すること;および
(iii)角膜における血管成長および角膜の構造的歪みの少なくとも1つに対する上記試験化合物の効果を判定することを含む。
本明細書に記載の方法のいずれかを使用して、本発明の化合物をスクリーニングする方法における使用のための非ヒト動物モデルを製造することができる。
(i)非ヒト動物の少なくとも1つの眼の角膜に試験物質を適用すること;および
(ii)角膜における血管成長および角膜の構造的歪みの少なくとも1つに対する上記試験物質の影響を測定することを含む。
角膜血管新生または円錐角膜のような角膜拡張性疾患を誘発する化合物または物質は、ヒトの健康に有害であり得る。「人の健康に有害な」物質は、有毒であり、致命的な疾病(例えば、癌)の発生率を増加させるか、または刺激、発疹などの他の有害生物反応を引き起こすものである。したがって、本発明の方法により角膜血管新生および角膜拡張性疾患に対する効果のために化合物をスクリーニングすることにより、健康に有害であるか、またはヒトなどの哺乳動物に重大な健康リスクをもたらす物質を同定することができる。
Claims (20)
- 角膜血管新生の非ヒト動物モデルを製造する方法であって、非ヒト動物の少なくとも1つの眼に有効量の式(I)の芳香族化合物を適用することを含む方法;
- 投与される式(I)の芳香族化合物の有効量が、約1μmol〜約70μmolである請求項1に記載の方法。
- 式(I)の芳香族化合物が、ベンゼン(nが0)またはフェノール(Rがヒドロキシルであり、nが1である)である請求項1に記載の方法。
- 前記非ヒト動物がげっ歯類である請求項1に記載の方法。
- 式(I)の芳香族化合物が、水性ビヒクルとして投与される請求項1に記載の方法。
- 少なくとも1つの眼に麻酔薬を投与することをさらに含む請求項1に記載の方法。
- 請求項1に記載の方法により調製された角膜血管新生の非ヒト動物モデルであって、角膜に実質的に線維症を有していない前記非ヒト動物モデル。
- 角膜拡張性疾患の非ヒト動物モデルを製造する方法であって、非ヒト動物の少なくとも1つの眼に有効量の式(I)の芳香族化合物を適用することを含む方法;
- 投与される式(I)の芳香族化合物の有効量が、約30μmol〜約85μmolである請求項8に記載の方法。
- 式(I)の芳香族化合物が、ベンゼン(nが0)またはフェノール(Rがヒドロキシルであり、nが1である)である請求項8に記載の方法。
- 前記非ヒト動物がげっ歯類である請求項8に記載の方法。
- 式(I)の芳香族化合物が、水性ビヒクルとして投与される請求項8に記載の方法。
- 前記角膜拡張性疾患が円錐角膜である請求項8に記載の方法。
- 請求項8に記載の方法により調製された角膜拡張性疾患の非ヒト動物モデル。
- 前記の少なくとも1つの眼の角膜が丸い形状から円錐形状となる変化を特徴とする構造的歪みを含む請求項14に記載の非ヒト動物モデル。
- 角膜血管新生または角膜拡張性疾患を調節するための化合物をスクリーニングする方法であって、
(i)非ヒト動物の少なくとも1つの眼の角膜に式(I)の芳香族化合物の有効量を適用することを含む方法によって、角膜血管新生または角膜拡張性疾患の非ヒト動物モデルを調製すること:
(iii)前記角膜での血管成長および前記角膜の構造的歪みの少なくとも1つに対する前記試験化合物の効果を判定することを含み、
Rは、ヒドロキシル、ハロゲン、アルキル、アルコキシおよびアミノからなる群から選択され、nは0、1、2、3、4、5、または6である前記方法。 - 前記試験化合物が、式(I)の芳香族化合物の適用の前に、同時に、または後に投与される請求項16に記載の方法。
- 式(I)の芳香族化合物が、ベンゼン(nが0)またはフェノール(Rがヒドロキシルであり、nが1である)である請求項16に記載の方法。
- ヒトの健康に有害な物質を同定する方法であって、
(i)非ヒト動物の少なくとも1つの眼の角膜に試験物質を適用すること;および
(ii)前記角膜における血管成長および前記角膜の構造的歪みの少なくとも1つに対する前記試験物質の影響を判定することを含む方法。 - 前記試験物質が、食品、医薬品およびエレクトロニクスからなる群より選択される産業での製造に用いられる化合物または材料である請求項19に記載の方法。
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