JP2016147857A - 眼疾患処置薬 - Google Patents
眼疾患処置薬 Download PDFInfo
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Abstract
【解決手段】本発明は、有効成分としての分岐鎖アミノ酸(BCAA)を含む眼疾患の処置および/または予防剤を提供する。本発明は、また、BCAAを有効成分として含有する網膜の細胞の変性および/または細胞死の抑制剤を提供する。本発明は、さらに、BCAAを有効成分として含有する視機能低下の抑制剤を提供する。本発明は、さらに、BCAAを有効成分として含有する、眼疾患のリスクの低減、または、視機能の維持もしくは改善用の食品を提供する。
【選択図】図1
Description
以下の実施例において、ロイシン、イソロイシン及びバリンを2:1:1.2の割合で含む分岐鎖アミノ酸の混合物をBCAAとして使用した。BCAAはγ-シクロデキストリン水溶液(CAVAMAX W8, Wacker fine chemicals)への溶解後に投与した。
網膜色素変性モデルとして、rd12マウス(The Jackson Laboratory)(Pang, J.J., Chang, B., Hawes, N.L., et al. 2005. Retinal degeneration 12 (rd12): a new, spontaneously arising mouse model for human Leber congenital amaurosis (LCA). Molecular vision 11, 152-162)を用いた。このマウスモデルでは、ゆっくりと視細胞の細胞死が進行する。13か月齢のrd12マウス34匹を、BCAA投与群(17匹)および対照群(17匹)の2群に分けた。13か月齢からBCAA群ではBCAA7.5g/lを含む水の自由飲水により、BCAAを経口投与した(約1.6kg/kg/日)。対照群には、同じ方法で水のみを与えた。
進行が遅い正常眼圧緑内障のマウスモデルであるGLAST欠損(ヘテロ+/-)マウス(The Journal of Clinical Investigation, Volume 117, Number 7, July 2007)をマウスB6.Cg-Tg (Thy 1-CFP) 23Jrs/Jと交配し、GLAST欠損(+/-)・Thy 1-CFPマウスを得、正常眼圧緑内障のモデルマウスとして使用した。4週齢のモデルマウス30匹を、対照群(15匹)およびBCAA投与群(15匹)の2群に分けた。BCAA群では、4週齢から8週齢にわたり、0.375g/kg/日のBCAAを週5日、腹腔内投与し、8週齢以降はBCAA7.5g/lを含む水の自由飲水により、BCAAを経口投与した(約1.7g/kg/日)。対照群には、4週齢から8週齢にわたり、生理食塩水を週5日、腹腔内投与し、8週齢以降は自由飲水によりBCAAを含まない水を与えた。
加齢黄斑変性のモデルとして、CCR2(単球走化活性化因子(MCP−1)受容体)欠損マウス(The Jackson Laboratory)(Nat Med. 2003 Nov;9(11):1390-7. Epub 2003 Oct 19. An animal model of age-related macular degeneration in senescent Ccl-2- or Ccr-2-deficient mice. Ambati J1, Anand A, Fernandez S, Sakurai E, Lynn BC, Kuziel WA, Rollins BJ, Ambati BK)を用いた。9か月齢のCCR2欠損マウス34匹を、対照群(24匹)およびBCAA投与群(10匹)の2群に分けた。CCR2欠損マウスに対して、9か月齢から、γ−シクロデキストリン水溶液に溶解したBCAA(7.5g/l)を含む水の自由飲水により、BCAAを経口投与した。対照マウスには、同じ方法で水のみを与えた。
2か月齢のCCR2欠損マウス37匹を、BCAA投与群(11匹)および対照群(26匹)の2群に分けた。CCR2欠損マウスに対して、2か月齢から、γ−シクロデキストリン水溶液に溶解したBCAA(7.5g/l)を含む水の自由飲水により、BCAAを投与した。対照マウスには、同じ方法で水のみを与えた。
網膜色素変性モデルとして、rd10マウス(B6.CXB1-Pde6brd10/J(Jackson Laboratory (Bar Harbor, ME)より購入、Chang B. et al; Vision Res (2007))を用いた。このマウスモデルでは、2か月齢までに急速に視細胞が変性する。7日齢のrd10マウス35匹を、BCAA投与群(17匹)および対照群(18匹)の2群に分けた。BCAA群では、7日齢から23日齢まで、1.5g/kg/日のBCAAを腹腔内投与し、24日齢以降はBCAA7.5g/lを含む水の自由飲水により、BCAAを経口投与した(約1.7g/kg/日)。対照群には、7日齢から23日齢まで生理食塩水を腹腔内投与し、24日齢以降は自由飲水によりBCAAを含まない水を与えた。
Claims (15)
- イソロイシン、ロイシンおよびバリンからなる群から選択される少なくとも1種を有効成分として含有する、眼疾患の処置および/または予防剤。
- イソロイシンを有効成分として含有する、請求項1に記載の眼疾患の処置および/または予防剤。
- イソロイシンを有効成分として含有し、かつロイシンおよびバリンを有効成分として含有しない、請求項1または請求項2に記載の眼疾患の処置および/または予防剤。
- イソロイシン、ロイシンおよびバリンを有効成分として含有する、請求項1に記載の眼疾患の処置および/または予防剤。
- イソロイシン、ロイシンおよびバリンの重量比が、1:1.5〜2.5:0.8〜1.7である、請求項4に記載の眼疾患の処置および/または予防剤。
- 眼疾患が、緑内障、網膜色素変性または加齢黄斑変性である、請求項1ないし請求項5のいずれかに記載の眼疾患の処置および/または予防剤。
- 眼圧降下剤と併用される、請求項1ないし請求項6のいずれかに記載の眼疾患の処置および/または予防剤。
- 抗VEGF剤と併用される、請求項1ないし請求項6のいずれかに記載の眼疾患の処置および/または予防剤。
- イソロイシン、ロイシンおよびバリンからなる群から選択される少なくとも1種を有効成分として含有する、網膜の細胞の変性および/または細胞死の抑制剤。
- 網膜の細胞が、視細胞、網膜色素上皮細胞および網膜神経節細胞からなる群から選択される、請求項9に記載の網膜の細胞の変性および/または細胞死の抑制剤。
- イソロイシン、ロイシンおよびバリンからなる群から選択される少なくとも1種を有効成分として含有する、視機能低下の抑制剤。
- イソロイシン、ロイシンおよびバリンからなる群から選択される少なくとも1種を有効成分として含有する、眼疾患のリスクの低減、または、視機能の維持もしくは改善用の食品。
- イソロイシン、ロイシンおよびバリンを有効成分として含有する、請求項12に記載の眼疾患のリスクの低減、または、視機能の維持もしくは改善用の食品。
- イソロイシン、ロイシンおよびバリンの重量比が、1:1.5〜2.5:0.8〜1.7である、請求項13に記載の眼疾患のリスクの低減、または、視機能の維持もしくは改善用の食品。
- 眼疾患が、緑内障、網膜色素変性または加齢黄斑変性である、請求項12ないし請求項14のいずれかに記載の眼疾患のリスクの低減、または、視機能の維持もしくは改善用の食品。
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