JP6480640B2 - イマチニブを有効成分として含む眼球乾燥疾患予防及び治療用薬学組成物 - Google Patents
イマチニブを有効成分として含む眼球乾燥疾患予防及び治療用薬学組成物 Download PDFInfo
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- JP6480640B2 JP6480640B2 JP2018518557A JP2018518557A JP6480640B2 JP 6480640 B2 JP6480640 B2 JP 6480640B2 JP 2018518557 A JP2018518557 A JP 2018518557A JP 2018518557 A JP2018518557 A JP 2018518557A JP 6480640 B2 JP6480640 B2 JP 6480640B2
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- A—HUMAN NECESSITIES
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Description
ただし、下記の実施例は本発明を例示するものに過ぎず、本発明の内容が下記の実施例に限定されるわけではない。
乾性角結膜炎モデルにおいてイマチニブ点眼剤の角膜上皮保護効果
乾燥性角膜上皮損傷に対する実験のために乾性眼(dry eye)動物モデルを製作した。動物は、白ねずみ(sd rat、8週齢、オリエントバイオ社)を使用し、乾性角結膜炎の誘導は、1%硫酸アトロピン(1% atropine sulfate、アルコン社)に0.1%塩化ベンザルコニウム(0.1% benzalkonium chloride、シグマアルドリッチ社)が含まれた点眼液を1日に2回ずつ2週間点眼して誘導した。
乾性角結膜炎においてイマチニブ点眼剤の角膜変性保護効果
乾性角結膜炎(Keratoconjunctivitis sicca)に対する実験のために実施例1と同じ乾性眼(dry eye)動物モデルを製作して実験した。動物は、白ねずみ(sd rat)を使用し、乾性角結膜炎の誘導は、1%硫酸アトロピン(1% atropine sulfate)と0.1%塩化ベンザルコニウム(0.1% benzalkonium chloride)を1日に2回ずつ2週間点眼して誘導した。
イマチニブ点眼剤の乾性角結膜炎において特定炎症細胞の侵入抑制効果
実施例1の動物モデルと同じ投与方法で実験した後、角膜に侵入した特定炎症細胞に対するイマチニブの炎症抑制効果を確認した。
Claims (9)
- イマチニブ(Imatinib)を有効成分として含む、眼球乾燥症又は眼球乾燥症関連眼科疾患予防及び治療用薬学組成物であって、
点眼投与のためのものである、薬学組成物。 - 上記眼球乾燥症は、水性涙液欠乏性眼球乾燥症又は蒸発性眼球乾燥症であることを特徴とする、請求項1に記載の組成物。
- 上記眼球乾燥症関連眼科疾患は、乾性角結膜炎、乾性による角膜潰瘍、眼瞼炎(瞼炎症)、眼の充血及び角膜新生血管生成からなる群から選ばれるいずれか一つであることを特徴とする、請求項1に記載の組成物。
- 上記組成物は角膜の変性を抑制し、炎症細胞の数を減少させることを特徴とする、請求項1に記載の組成物。
- 上記イマチニブ(Imatinib)の含量は組成物全重量を基準に0.005〜5重量%であることを特徴とする、請求項1に記載の組成物。
- イマチニブ(Imatinib)を有効成分として含む、眼球乾燥症又は眼球乾燥症関連眼科疾患の予防及び治療用点眼剤。
- 上記点眼剤は、水溶液を含む担体をさらに含み、液状であることを特徴とする、請求項6に記載の点眼剤。
- 上記水溶液を含む担体は、蒸留水、リン酸緩衝液、平衡塩類溶液及び生理食塩水からなる群から選ばれる一つ以上の薬学的に許容される担体であることを特徴とする、請求項7に記載の点眼剤。
- イマチニブの眼球乾燥症又は眼球乾燥症関連眼科疾患治療剤の製造のための使用であって、前記治療剤が点眼投与のためのものである、使用。
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KR1020150088701A KR101778004B1 (ko) | 2015-06-22 | 2015-06-22 | 이마티닙을 유효성분으로 포함하는 안구 건조 질환 예방 및 치료용 약학 조성물 |
KR10-2015-0088701 | 2015-06-22 | ||
PCT/KR2016/006616 WO2016208961A1 (ko) | 2015-06-22 | 2016-06-22 | 이마티닙을 유효성분으로 포함하는 안구 건조 질환 예방 및 치료용 약학 조성물 |
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KR101386697B1 (ko) | 2012-06-18 | 2014-04-18 | 아주대학교산학협력단 | 이매티닙 또는 이의 약학적으로 허용되는 염을 유효성분으로 포함하는 혈관 투과성 관련 질환의 치료 또는 예방용 조성물 |
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