JP7470791B2 - 眼疾患の予防または治療用点眼組成物 - Google Patents
眼疾患の予防または治療用点眼組成物 Download PDFInfo
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- JP7470791B2 JP7470791B2 JP2022529470A JP2022529470A JP7470791B2 JP 7470791 B2 JP7470791 B2 JP 7470791B2 JP 2022529470 A JP2022529470 A JP 2022529470A JP 2022529470 A JP2022529470 A JP 2022529470A JP 7470791 B2 JP7470791 B2 JP 7470791B2
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- pyrazol
- pyridin
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- A61K31/00—Medicinal preparations containing organic active ingredients
- A61K31/33—Heterocyclic compounds
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Description
[化学式I]
3-フェニル-4-プロピル-1-(ピリジン-2-イル)-1H-ピラゾール-5-オール塩酸塩(APX-115)を含む組成物を下記表1の通り可溶化剤および緩衝剤を添加して製造した。
下記表2に基づいて、APX-115および可溶化剤を含み、pHの異なる点眼液を製造した。
下記表3に基づいて、APX-115および可溶化剤を含み、pHの異なる点眼液を製造した。
下記表4に基づいて、APX-115および可溶化剤を含み、pHが7.2である0.5w/v%APX-115点眼液を製造した。
下記表5に基づいて、APX-115および可溶化剤を含み、pHが6.0である0.5w/v%APX-115点眼液を製造した。
実施例10~22の組成物と成分は同一でpHは異なる組成物を製造するために、下記表6に示す通りAPX-115を含む組成物を製造した。
前記実施例および比較例で製造した溶液を40℃/75%RH条件下で保管した。4週間後にAPX-115分解産物中の最大未知の類縁物質の生成量を下記条件のHPLC法で測定した。
<分析条件>
-カラム:Kromasil C18(4.6×150mm,5μm)
-カラム温度:30℃
-移動相:20mM Ammonium Formate(pH3.0)/アセトニトリル=20/80(v/v)
-波長:293nm
-注入量:10μl
体重2.0~2.7kgのニュージーランドホワイト種ウサギの両眼に、前記実施例10~14、比較例1~4の組成物をそれぞれ50μLずつ1回点眼した後、実験動物の行動を観察した。実施例10~14を試験群とし、比較例1~4を比較群とし、市販の点眼剤であるジクアス(登録商標)を陽性対照群として用いた。薬物の投与直後に、各ウサギの行動を観察し、下記表に示した。
本発明の組成物を注射で投与せずに点眼投与だけで後眼部に薬物が送達されて治療効果を示すか確認するため、試験例3の試験によって後眼部組織のうち網膜/脈絡膜に隣接している硝子体内の有効成分濃度を確認した。また、先行した安定性研究(試験例1)から、組成物のpHによって組成物の安定性に差があることを確認し、pHによる有効成分のイオン化傾向が変わってくるため、組成物のpHによって後眼部組織に送達される有効成分の量を評価するために、各pH別にPK分布試験を行った。
<分析条件>
-カラム:Waters Acquity UPLC BEH C18(50×2.1mm,1.7mm)
-カラム温度:40℃
-移動相:アセトニトリル/0.1% formic acid=70/30(v/v)
-注入量:5μl
-流量:0.2mL/分
先行した眼組織分布試験(試験例3)から、一実施形態による各pH別の点眼組成物を投与した際に後眼部組織である網膜に隣接している硝子体にまで有効成分が分布していることを確認した。その後、本発明の点眼組成物(実施例13)の脈絡膜血管新生(choroidal neovasculariation,CNV)抑制効果を確認するために、本発明の組成物を試験物質とし、プラセボ物質を陰性対照物質(G1)とし、市販の注射剤アイリーア(Eylea(登録商標))を陽性対照物質(G2)として、CNVモデルマウスにおける効力を評価した。
試験例4と同様の方法により、組成は同一であるがpHが異なる各点眼組成物の有効性評価を行った。
Claims (7)
- 下記化学式Iで表される3-フェニル-4-プロピル-1-(ピリジン-2-イル)-1H-ピラゾール-5-オールまたはその薬学的に許容される塩を有効成分として0.1w/v%~2.0w/v%含み、
可溶化剤および緩衝液を含むpH範囲が3.5~8.5である、脈絡膜血管新生(CNV)の予防または治療用点眼剤。
[化学式I]
- 下記化学式Iで表される3-フェニル-4-プロピル-1-(ピリジン-2-イル)-1H-ピラゾール-5-オールまたはその薬学的に許容される塩を有効成分として0.1w/v%~2.0w/v%含み、
可溶化剤および緩衝剤を含み、pH範囲が4.5~8.5である、脈絡膜血管新生(CNV)の予防または治療用点眼剤。
[化学式I]
- 前記薬学的に許容される塩は、塩酸塩である、請求項1又は2に記載の点眼剤。
- 前記可溶化剤の濃度は、0.1w/v%~25.0w/v%である、請求項1又は2のいずれか1項に記載の点眼剤。
- 前記可溶化剤は、界面活性剤、溶剤、およびこれらの混合物からなる群から選択される1種以上を含むものである、請求項1又は2に記載の点眼剤。
- 前記可溶化剤は、1種以上の界面活性剤を含むものである、請求項1又は2に記載の点眼剤。
- 脈絡膜血管新生(CNV)の予防または治療用点眼剤の製造のための、下記化学式Iで表される3-フェニル-4-プロピル-1-(ピリジン-2-イル)-1H-ピラゾール-5-オールまたはその薬学的に許容される塩を有効成分として0.1w/v%~2.0w/v%含み、可溶化剤および緩衝剤を含み、3.5~8.5のpH範囲を有する点眼組成物の使用。
[化学式I]
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JP2013082751A (ja) | 2002-04-08 | 2013-05-09 | Lion Corp | 眼科用組成物、及び眼科製剤用防腐組成物 |
KR101821593B1 (ko) | 2017-02-23 | 2018-01-25 | 압타바이오 주식회사 | 안질환 치료제 |
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ES2362604B1 (es) * | 2009-12-22 | 2012-06-28 | Bcn Peptides, S.A. | Formulación tópica oftálmica de péptidos. |
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Lu, Guang W. et al.,Recent Patents on Drug Delivery & Formulation,2010年,Vol.4, No.1,p.49-57 |
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