JP2016505057A - 非糖尿病の哺乳動物における雌性不妊症の治療のためのタングステン(vi)塩の使用 - Google Patents
非糖尿病の哺乳動物における雌性不妊症の治療のためのタングステン(vi)塩の使用 Download PDFInfo
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- A—HUMAN NECESSITIES
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- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K33/00—Medicinal preparations containing inorganic active ingredients
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- A61P1/00—Drugs for disorders of the alimentary tract or the digestive system
- A61P1/16—Drugs for disorders of the alimentary tract or the digestive system for liver or gallbladder disorders, e.g. hepatoprotective agents, cholagogues, litholytics
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- A61P15/08—Drugs for genital or sexual disorders; Contraceptives for gonadal disorders or for enhancing fertility, e.g. inducers of ovulation or of spermatogenesis
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Abstract
Description
IRS2−/−マウスモデルは、Irs2遺伝子ノックアウトマウスモデルである(Burks et. al., "IRS-2 pathways integrate female reproduction and energy homeostasis", Nature, 2000, vol. 407, pp. 377-382)。Irs2遺伝子欠失は、生殖能力及び糖代謝に関連する明確な性的二型へと翻訳する。
A.動物
6週齢〜8週齢の10匹のIRS2−/−雌性マウス。
6週齢〜8週齢の6匹の「野生型」(IRS2wt)雄性マウス。
前処理段階
順応期間の後、IRS2−/−雌性マウスを1つのケージ当たり4匹〜6匹のマウス群で飼育した。前処理段階(2週間)の間、動物にタングステン酸塩不含飲用水を投与した。
前処理段階(治療0日目)後から動物を屠殺する4週間前まで、蒸留水中、タングステン酸ナトリウム二水和物(Carlo Erbaにより販売される)の2mg/ml溶液を用いた飲用水(任意)においてタングステン酸ナトリウムを投与した。マウスにより摂取されたタングステン酸ナトリウムの1日当たりの用量は体重1kg当たり約180mgである。
治療の最初の3週間の後、IRS2−/−雌性マウスをIRS2wt雄性マウスと継続的につがいでケージにおいて飼育した。
この期間の経過後、雌性マウスを屠殺し、妊娠の兆候を求めて生検を行った。
排卵調査の結果
前処理期間中及び治療の最初の3週間の間、−8日目、−5日目、−2日目、−1日目、7日目、8日目、14日目、15日目及び22日目に無作為に選択した6匹の雌性マウスにおいて膣垢検査を行い、それらのマウスの発情周期の段階を求めた。
50体積%アルコール中に10回出し入れ、
ハリスヘマトキシリン溶液中に3分間浸漬、
流水ですすぐ、
酸アルコール(1%塩酸)中に10回出し入れ、
流水ですすぐ、
95体積%アルコール中に10回出し入れ、
OG−6溶液中に30秒間浸漬、
96体積%アルコール中に10回出し入れ、
エオシン溶液中に1分間浸漬、
96体積%アルコール中に10回出し入れ、
86体積%アルコール中に10回出し入れ、及び、
キシロール中に10回出し入れ。
B欄の方法の交配期間が経過した後、雌性マウスを屠殺し、妊娠の兆候を求めて生検を行った。
A.動物
6週齢〜8週齢の6匹のIRS2−/−雌性マウス。
治療段階
順応期間の後、前処理段階(治療0日目)後に、及び12日間に亘り、蒸留水中、タングステン酸ナトリウム二水和物(Carlo Erbaにより販売される)の2mg/ml溶液を用いた飲用水(任意)においてタングステン酸ナトリウムを投与した。
治療期間の0日目、2日目、5日目、7日目、9日目及び12日目に体重をモニターし、上述の日の各々において6時間の絶食の後、尾静脈からの採血及びグルコースセンサー(ドイツ国マンハイムのRoche AccuTrend Glucose Sensor)により血中グルコースを求めた。
Claims (15)
- 非糖尿病の哺乳動物において雌性不妊症を治療する医薬品の調製のための薬学的若しくは獣医学的に許容可能なカチオン基を有する治療的有効量のタングステン(VI)塩、又はその溶媒和物の使用。
- 前記哺乳動物がヒトである、請求項1に記載の使用。
- 前記カチオン基がアルカリカチオン又はアルカリ土類カチオンである、請求項1又は2に記載の使用。
- 前記カチオン基が、ナトリウム、カリウム、マグネシウム及びカルシウムからなる群より選択される、請求項3に記載の使用。
- 前記タングステン(VI)塩がタングステン(VI)のナトリウム塩である、請求項4に記載の使用。
- 前記溶媒和物が二水和物である、請求項1〜5のいずれかに記載の使用。
- 前記雌性不妊症の治療が排卵を回復することを含む、請求項1〜6のいずれかに記載の使用。
- 前記雌性不妊症の治療が、子宮壁における接合体の着床を増加することを含む、請求項1〜7のいずれかに記載の使用。
- 雌性不妊症が、視床下部下垂体軸における変化に伴って起こる、請求項1〜8のいずれかに記載の使用。
- 前記視床下部下垂体軸における変化が、多嚢胞性卵巣症候群、メタボリックシンドローム、高プロラクチン血症、子宮内膜症、摂食障害、肥満、甲状腺機能低下症、多発性硬化症、関節リウマチ、紅斑性狼瘡、肝硬変、小児脂肪便症、慢性腎不全、及び特発性の原因からなる群より選択される、請求項9に記載の使用。
- 前記視床下部下垂体軸における変化が特発性の原因による、請求項10に記載の使用。
- 摂食障害が拒食症及び過食症から選択される、請求項10に記載の使用。
- 前記タングステン(VI)塩又はその溶媒和物が、薬学的又は獣医学的に許容可能な賦形剤又は担体を更に含む、医薬組成物又は動物用医薬組成物の一部である、請求項1〜12のいずれかに記載の使用。
- 前記医薬組成物又は動物用医薬組成物が経口投与用組成物である、請求項13に記載の使用。
- 前記経口投与用組成物が液体組成物である、請求項14に記載の使用。
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ES201330071A ES2478790B1 (es) | 2013-01-22 | 2013-01-22 | Uso de sales de tungsteno (VI) para el tratamiento de la infertilidad femenina en mamíferos no diabéticos |
PCT/EP2014/051141 WO2014114644A1 (en) | 2013-01-22 | 2014-01-21 | Use of tungsten (vi) salts for the treatment of female infertility in non-diabetic mammals |
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