JP6872201B2 - 認知症の予防及び/又は治療のための薬剤 - Google Patents
認知症の予防及び/又は治療のための薬剤 Download PDFInfo
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- JP6872201B2 JP6872201B2 JP2018518213A JP2018518213A JP6872201B2 JP 6872201 B2 JP6872201 B2 JP 6872201B2 JP 2018518213 A JP2018518213 A JP 2018518213A JP 2018518213 A JP2018518213 A JP 2018518213A JP 6872201 B2 JP6872201 B2 JP 6872201B2
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- dementia
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- cilostazol
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- A61K31/435—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having six-membered rings with one nitrogen as the only ring hetero atom
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- A61K31/35—Heterocyclic compounds having oxygen as the only ring hetero atom, e.g. fungichromin having six-membered rings with one oxygen as the only ring hetero atom
- A61K31/352—Heterocyclic compounds having oxygen as the only ring hetero atom, e.g. fungichromin having six-membered rings with one oxygen as the only ring hetero atom condensed with carbocyclic rings, e.g. methantheline
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- A61P25/28—Drugs for disorders of the nervous system for treating neurodegenerative disorders of the central nervous system, e.g. nootropic agents, cognition enhancers, drugs for treating Alzheimer's disease or other forms of dementia
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Description
を併用して投与する、ことを特徴とする。
を併用して投与するものである。
換言すれば、「カルボスチリル誘導体又はその塩と、ジヒドロケルセチン又はその塩と、を有する薬剤」は、例えば、以下の形態が該当する。
・有効成分のカルボスチリル誘導体又はその塩と、有効成分のジヒドロケルセチン又はその塩とを、同時に若しくは別々に、又は逐次的に投与する形態。
・有効成分のカルボスチリル誘導体又はその塩と、有効成分のジヒドロケルセチン又はその塩とを含む形態。
8ヶ月齢の通常餌投与APPSwDI遺伝子改変マウス(n=5)、シロスタゾール含有餌投与APPSwDI遺伝子改変マウス(n=5)、タキシフォリン含有餌投与APPSwDI遺伝子改変マウス(n=6)、シロスタゾール及びタキシフォリン含有餌(本実施例にかかる薬剤含有餌)投与APPSwDI遺伝子改変マウス(n=6)の計22匹で解析を行った。シロスタゾール含有餌、タキシフォリン含有餌、及びシロスタゾール及びタキシフォリン含有餌は4週齢から8ヶ月齢まで投与した。シロスタゾール含有餌におけるシロスタゾール濃度は0.3wt%で、タキシフォリン含有餌におけるタキシフォリン濃度は3wt%であった。シロスタゾール及びタキシフォリン含有餌におけるシロスタゾール濃度、タキシフォリン濃度は、それぞれ0.3wt%、3wt%であった。APPSwDI遺伝子改変マウスは全てホモ接合体雄性マウスを使用した。なお、4週齢のAPPSwDI遺伝子改変マウスは脳血管にAβが蓄積する初期段階、即ち脳アミロイド血管症の初期段階と考えられ、脳内の神経細胞の壊死はさほど進行していない段階と考えられる。
2.炭酸ガス吸入試験
12ヶ月齢の通常餌投与C57BL/6Jマウス(n=4)、通常餌投与APPSwDI遺伝子改変マウス(n=10)、シロスタゾール含有餌投与APPSwDI遺伝子改変マウス(n=4)、タキシフォリン含有餌投与APPSwDI遺伝子改変マウス(n=5)、シロスタゾール及びタキシフォリン含有餌投与APPSwDI遺伝子改変マウス(n=7)の計30匹で解析を行った。シロスタゾール、タキシフォリン、もしくはシロスタゾール及びタキシフォリン含有餌は4週齢から12ヶ月齢まで投与した。シロスタゾール含有餌におけるシロスタゾール濃度は0.3wt%で、タキシフォリン含有餌におけるタキシフォリン濃度は3wt%であった。APPSwDI遺伝子改変マウスは全てホモ接合体雄性マウスを使用した。
3.水迷路試験
8ヶ月齢のC57BL/6Jマウス(n=15)、通常餌投与APPSwDI遺伝子改変マウス(n=17)、シロスタゾール含有餌投与APPSwDI遺伝子改変マウス(n=10)、タキシフォリン含有餌投与APPSwDI遺伝子改変マウス(n=10)、シロスタゾール及びタキシフォリン含有餌投与APPSwDI遺伝子改変マウス(n=9)の計61匹で水迷路試験を行った。シロスタゾール含有餌、タキシフォリン含有餌、並びに、シロスタゾール及びタキシフォリン含有餌は4週齢から8ヶ月齢まで投与した。シロスタゾール含有餌におけるシロスタゾール濃度は0.3wt%で、タキシフォリン含有餌におけるタキシフォリン濃度は3wt%であった。シロスタゾール及びタキシフォリン含有餌におけるシロスタゾール濃度、タキシフォリン濃度は、それぞれ0.3wt%、3wt%であった。APPSwDI遺伝子改変マウスは全てホモ接合体雄性マウスを使用した。
4.生存曲線
2014年4月1日から2015年11月30日に誕生した通常餌投与APPSwDI遺伝子改変マウス(n=40)、シロスタゾール含有餌投与APPSwDI遺伝子改変マウス(n=65)、タキシフォリン含有餌投与APPSwDI遺伝子改変マウス(n=33)、シロスタゾール及びタキシフォリン含有餌投与APPSwDI遺伝子改変マウス(n=33)について、マウスの生存曲線を作成し、解析した。マウスの死亡に、動物実験実施に伴う屠殺は含めていない。
Aは通常餌投与APPSwDI遺伝子改変マウス群、Bはシロスタゾール含有餌投与APPSwDI遺伝子改変マウス群、Cはタキシフォリン含有餌投与APPSwDI遺伝子改変マウス群、Dはシロスタゾール及びタキシフォリン含有餌投与APPSwDI遺伝子改変マウス群を示している。
5.脱毛スコア
マウスはファイティング(けんか)が生じると、脱毛が生じる。そのため、各マウスの脱毛の程度をGrade:0〜3の4段階で記述し、脱毛スコアとした。ほぼ正常な状態をGrade:0とし、ほぼ全身にわたった脱毛が見られる状態をGrade:3とした。全体表の50%未満と50%以上でGrade:1とGrade:2に分類した。
6.Y迷路試験
13ヶ月齢のC57BL/6Jマウス(n=4)、通常餌投与APPSwDI遺伝子改変マウス(n=14)、タキシフォリン含有餌投与APPSwDI遺伝子改変マウス(n=7)、シロスタゾール及びタキシフォリン含有餌投与APPSwDI遺伝子改変マウス(n=14)の計39匹でY迷路試験を行った。シロスタゾール含有餌、タキシフォリン含有餌、並びに、シロスタゾール及びタキシフォリン含有餌は4週齢から13ヶ月齢まで投与した。シロスタゾール含有餌におけるシロスタゾール濃度は0.3wt%で、タキシフォリン含有餌におけるタキシフォリン濃度は3wt%であった。シロスタゾール及びタキシフォリン含有餌におけるシロスタゾール濃度、タキシフォリン濃度は、それぞれ0.3wt%、3wt%であった。APPSwDI遺伝子改変マウスは全てホモ接合体雄性マウスを使用した。
Claims (4)
- 前記カルボスチリル誘導体が、6−[4−(1−シクロへキシル−1H−テトラゾ一ル−5−イル)ブトキシ]−3,4−ジヒドロカルボスチリルである、請求項1又は2に記載の薬剤。
- 前記認知症が、アルツハイマー型認知症、レビー小体型認知症、前頭側頭型認知症、脳血管性認知症、パーキンソン病、ダウン症、又は、ハンチントン病である、請求項1乃至3の何れか1項に記載の薬剤。
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