JP7374455B2 - 心不全非ヒト霊長類モデル動物の製造方法 - Google Patents
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Description
項2.前記アントラサイクリン系抗腫瘍剤が、ドキソルビシン又はその薬理学的に許容される塩である、項1に記載の製造方法。
項3.アントラサイクリン系抗腫瘍剤の一日当たりの投与量が、0.1~2.0 mg/kg体重である、項1又は2に記載の製造方法。
項4.アントラサイクリン系抗腫瘍剤の一日当たりの投与量の1段階目が0.6~1.0 mg/kg体重であり、2段階目が1.1~1.5 mg/kg体重である、項1~3のいずれか一項に記載の製造方法。
項5.前記非ヒト霊長類が、オナガザル科マカク属に属するものである、項1~4のいずれか一項に記載の製造方法。
項6.項1~5のいずれか一項に記載の製造方法により製造された心不全非ヒト霊長類モデル動物に被験物質を投与する工程を含む、心不全の治療又は予防活性を有する物質の評価方法。
項7.非ヒト霊長類に対し、アントラサイクリン系抗腫瘍剤を総投与量が400~1000 mg/m2体表面積となるように段階的に増量しながら投与することにより製造された、心不全非ヒト霊長類モデル動物。
3匹のカニクイザルに対して、0.6~1.2 mg/kg体重でドキソルビシン(LC Laboratories社:D-4000)を1日1回3日間静脈投与し、11日間休薬を反復施行した(実施例1~3)。具体的には、2 mg (0.6 mg/kg体重)静注を3日間連続して行い、11日間休薬(1クール14日間)で開始し、その後、全身状態や心臓超音波装置(HITACHI社:ARIETTA60、L441プローブを使用)で心機能を観察しながら、ドキソルビシン1回投与量を2 mg (0.6 mg/kg体重)→3 mg (0.9 mg/kg体重)→4 mg (1.2 mg/kg体重)へと増量した。実施例1~3の投薬は図1下に示されるように行われた。心臓超音波法での左室駆出率(%)は、下記の式で求められた。
ここで左室拡張末期容積(Vd)又は左室収縮末期容積(Vs)は、心臓超音波装置で測定される左室拡張末期径(Dd)又は左室収縮末期径(Ds)をそれぞれ用いて、Teichholz法により下記の計算式で求められた。
Vd = {7.0/(2.4+Dd)}×Dd3
Vs = {7.0/(2.4+Ds)}×Ds3
これらの計算は心臓超音波装置に搭載されているコンピュータにより自動的に行われた。
Claims (6)
- 非ヒト霊長類に対し、アントラサイクリン系抗腫瘍剤を一日当たりの投与量が0.1~2.0 mg/kg体重であって、総投与量が400~1000 mg/m2体表面積となるように段階的に増量しながら投与する工程を含む、心不全非ヒト霊長類モデル動物の製造方法。
- 前記アントラサイクリン系抗腫瘍剤が、ドキソルビシン又はその薬理学的に許容される塩である、請求項1に記載の製造方法。
- アントラサイクリン系抗腫瘍剤の一日当たりの投与量の1段階目が0.6~1.0 mg/kg体重であり、2段階目が1.1~1.5 mg/kg体重である、請求項1又は2に記載の製造方法。
- 前記非ヒト霊長類が、オナガザル科マカク属に属するものである、請求項1~3のいずれか一項に記載の製造方法。
- 請求項1~4のいずれか一項に記載の製造方法により製造された心不全非ヒト霊長類モデル動物に被験物質を投与する工程を含む、心不全の治療又は予防活性を有する物質の評価方法。
- 非ヒト霊長類に対し、アントラサイクリン系抗腫瘍剤を一日当たりの投与量が0.1~2.0 mg/kg体重であって、総投与量が400~1000 mg/m2体表面積となるように段階的に増量しながら投与することにより製造された、心不全非ヒト霊長類モデル動物。
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HERMAN, E. H. et al.,Animal models of anthracycline cardiotoxicity:Basic mechanisms and cardioprotective activity,Progress in Pediatric Cardiology,8(2),1998年,pp.49-58,ISSN.1058-9813 |
SIEBER, S. M. et al.,Cardiotoxic and possible leukemogenic effects of adriamycin in nonhuman primates,Pharmacology,20(1),1980年,pp.9-14 |
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