JP2014023526A - ヘアレス動物の眼瞼状態の変化方法 - Google Patents
ヘアレス動物の眼瞼状態の変化方法 Download PDFInfo
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Abstract
【解決手段】ヘアレス動物の眼瞼の状態を変化させる方法、その方法により得られる眼瞼疾患の治療又は予防効果を評価するためのモデル動物、そのモデル動物の製造方法、そのモデル動物を利用したスクリーニング方法及びそのスクリーニング方法により選択される眼瞼疾患の治療又は予防効果を有する物質、ならびに、当該物質を有効成分として含有する眼瞼疾患の治療又は予防剤。
【選択図】なし
Description
(1)ヘアレス動物に対して脂質及び/又はミネラルの摂取量を制限することによるヘアレス動物の眼瞼の状態を変化させる方法。
本発明のヘアレス動物の眼瞼状態の変化方法は、ヘアレス動物に対して脂質及び/又はミネラルの摂取量を制限することによってヘアレス動物の眼瞼の状態を変化させることを特徴とする。本発明のヘアレス動物の眼瞼状態の変化方法に利用される「ヘアレス動物」とは、毛のない哺乳動物であり(ただし、ヒトは除く)、具体例としては、へアレスマウス、へアレスラット、へアレスハムスター、ヘアレスモルモット、ヘアレスウサギ等が挙げられ、へアレスマウス、ヘアレスラットが好ましく、Hos:HR−1系ヘアレスマウスが特に好ましい。Hos:HR−1系ヘアレスマウスは、株式会社星野試験動物飼育所により生産されている。へアレス動物の雌雄、週齢、体重については、特に制限はない。
(給餌した飼料)
・通常飼料給餌群:CRF−1飼料(オリエンタル酵母工業株式会社製)
・HR−AD飼料給餌群:HR−AD飼料(日本農産工業株式会社製)
(実験方法)
5週齢の雄性Hos:HR−1系ヘアレスマウスを通常飼料給餌群、HR−AD飼料給餌群に群分けし(各群6匹)、それぞれに通常飼料、HR−AD飼料を給餌し、自発的に摂取させた。給餌開始後、14日目、28日目、42日目に、スリットランプを用いて、マイボーム腺開口部ならびにその周辺を観察し、上眼瞼の中央8個のマイボーム腺開口部の中で、閉塞している開口部の数を計測した。この実験では、「閉塞している」状態として、マイボーム腺開口部が白濁して盛り上がった状態を確認した。また、上眼瞼のマイボーム腺開口部と開口部の間を走行する拡張した毛細血管の本数を計測した。ここで、「拡張した毛細血管」とは、血管径が拡大した結果、通常視認できない毛細血管が確認できる状態にある毛細血管をいう。
マイボーム腺開口部の閉塞数についての結果を表1、拡張毛細血管本数についての結果を表2に示す。
(給餌した飼料)
・通常飼料給餌群:CRF−1飼料(オリエンタル酵母工業株式会社製)
・HR−AD飼料給餌群:HR−AD飼料(日本農産工業株式会社製)
(実験方法)
6週齢の雄性Hos:HR−1系ヘアレスマウスを通常飼料給餌群(6匹)、HR−AD飼料給餌群(12匹)に群分けし、それぞれに通常飼料、HR−AD飼料を給餌し、自発的に摂取させた。給餌開始後28日目に、HR−AD飼料給餌群のマイボーム腺開口部をスリットランプを用いて観察し、マイボーム腺開口部の閉塞数の平均値のばらつきが小さくなるように、生理食塩液投与群とAzaSite(登録商標)点眼液(1% azithromycin)投与群に群分けした(各群6匹)。給餌開始後29日目より、生理食塩液、AzaSite(登録商標)点眼液を28日間点眼した(2μL/眼、投与開始1日目および2日目は1日2回、3日目以降は1日1回)。給餌開始後、42日目、56日目に、スリットランプを用いて、マイボーム腺開口部を観察し、上眼瞼の中央8個のマイボーム腺開口部の中で、閉塞している開口部の数を計測した。
結果を表3に示す。
Claims (21)
- ヘアレス動物に対して脂質及び/又はミネラルの摂取量を制限することによるヘアレス動物の眼瞼の状態を変化させる方法。
- 眼瞼の状態の変化が、マイボーム腺開口部の閉塞及び/又はマイボーム腺開口部周辺毛細血管の拡張である請求項1に記載の方法。
- へアレス動物がへアレスマウス又はヘアレスラットである、請求項1又は2に記載の方法。
- へアレス動物がHos:HR−1系ヘアレスマウスである、請求項1又は2に記載の方法。
- 摂取量を制限する脂質が必須脂肪酸である、請求項1〜4のいずれかに記載の方法。
- 摂取量を制限する必須脂肪酸がリノール酸又はα−リノレン酸である、請求項5に記載の方法。
- 摂取量を制限するミネラルがマグネシウムである、請求項1〜6のいずれかに記載の方法。
- 脂質の摂取量を3mg/kg/日以下に制限する、請求項1〜7のいずれかに記載の方法。
- マグネシウムの摂取量を0.15mg/kg/日以下に制限する、請求項7に記載の方法。
- HR−AD飼料を与えることにより脂質及び/又はミネラルの摂取量を制限する、請求項1〜9のいずれかに記載の方法。
- 脂質及び/又はミネラルの摂取量を制限する期間が3日間以上である、請求項1〜10のいずれかに記載の方法。
- 請求項1〜11のいずれかに記載の方法により得られる眼瞼疾患の治療又は予防効果を評価するためのモデル動物。
- 眼瞼疾患がマイボーム腺開口部の閉塞及び/又はマイボーム腺開口部周辺毛細血管の拡張を伴う疾患である、請求項12に記載のモデル動物。
- 眼瞼疾患が眼瞼炎、眼瞼縁炎、マイボーム腺機能不全、マイボーム腺炎又はマイボーム腺梗塞である、請求項12に記載のモデル動物。
- 請求項1〜11のいずれかに記載の方法による眼瞼疾患の治療又は予防効果を評価するためのモデル動物の製造方法。
- 請求項12〜14のいずれかに記載のモデル動物に被験物質を投与し、その眼瞼の状態を測定することを特徴とする、眼瞼疾患の治療又は予防効果を有する物質のスクリーニング方法。
- 眼瞼の状態がマイボーム腺又はその周辺の状態である、請求項16に記載のスクリーニング方法。
- マイボーム腺及びその周辺の状態がマイボーム腺開口部の閉塞及び/又はマイボーム腺開口部周辺毛細血管の拡張である、請求項17に記載のスクリーニング方法。
- 被験物質を点眼投与する、請求項16〜18のいずれかに記載のスクリーニング方法。
- 請求項16〜19のいずれかに記載のスクリーニング方法により選択される眼瞼疾患の治療又は予防効果を有する物質。
- 請求項20に記載の物質を有効成分として含有する眼瞼疾患の治療又は予防剤。
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WO2014142146A1 (ja) | 2013-03-13 | 2014-09-18 | 参天製薬株式会社 | マイボーム機能不全の治療剤 |
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EP3689348A1 (en) | 2013-03-13 | 2020-08-05 | Santen Pharmaceutical Co., Ltd. | Therapeutic agent for meibomian gland dysfunction |
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WO2013191167A1 (ja) | 2013-12-27 |
EP2862439A1 (en) | 2015-04-22 |
HK1204864A1 (en) | 2015-12-11 |
US20210011004A1 (en) | 2021-01-14 |
EP2862439A4 (en) | 2016-04-13 |
US20150125394A1 (en) | 2015-05-07 |
JP6324671B2 (ja) | 2018-05-16 |
US20180246081A1 (en) | 2018-08-30 |
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