JP6615277B2 - R−ケタミンおよびその塩の医薬品としての応用 - Google Patents
R−ケタミンおよびその塩の医薬品としての応用 Download PDFInfo
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- JP6615277B2 JP6615277B2 JP2018126684A JP2018126684A JP6615277B2 JP 6615277 B2 JP6615277 B2 JP 6615277B2 JP 2018126684 A JP2018126684 A JP 2018126684A JP 2018126684 A JP2018126684 A JP 2018126684A JP 6615277 B2 JP6615277 B2 JP 6615277B2
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Classifications
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- A61P25/18—Antipsychotics, i.e. neuroleptics; Drugs for mania or schizophrenia
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- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
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- A61P25/00—Drugs for disorders of the nervous system
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- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
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Description
R(−)−およびS(+)−ケタミン塩酸塩は、RS(±)−ケタミン(Ketalar(登録商標)、ケタミン塩酸塩、第一三共株式会社、東京、日本)から、D(−)−およびL(+)−酒石酸をそれぞれ使用して、既報(特許文献2)に記載の方法で調製した(図1)。これら異性体の純度は、高速液体クロマトグラフィー(CHIRALPAK(登録商標) IA、カラムサイズ:250×4.6mm、移動相;n−ヘキサン/ジクロロメタン/ジエチルアミン(75/25/0.1)、S(+)−ケタミンの保持時間=6.99分、R(−)−ケタミンの保持時間=10.56分、株式会社ダイセル、東京、日本)により確認した。
新生仔期にDEX暴露したマウスでは、正常マウスと比較して、TSTおよびFSTにおける無動時間に有意な増加が認められ、また、SPTにおいてショ糖消費嗜好性の低下が認められた。一方、LMTでは、DEX処理マウスと正常マウスの間で自発運動量に差異はなかった。
R(−)−およびS(+)−ケタミン塩酸塩は、RS(±)−ケタミン(Ketala
r(登録商標)、ケタミン塩酸塩、第一三共株式会社、東京、日本)から、D(−)−およびL(+)−酒石酸をそれぞれ使用して、既報(特許文献2)に記載の方法で調製した
(図1)。これら異性体の純度は、高速液体クロマトグラフィー(CHIRALPAK(
登録商標) IA、カラムサイズ:250×4.6mm、移動相;n−ヘキサン/ジクロ
ロメタン/ジエチルアミン(75/25/0.1)、S(+)−ケタミンの保持時間=6
.99分、R(−)−ケタミンの保持時間=10.56分、株式会社ダイセル、東京、日
本)により確認した。
社会的敗北ストレスマウスでは、正常マウスと比較して、TSTおよびFSTにおける無動時間に有意な増加が認められ、また、SPTにおいてショ糖消費嗜好性の有意な低下が認められた。一方、LMTでは、社会的敗北ストレスマウスと正常マウスの間で自発運動量に差異はなかった。
R(−)−およびS(+)−ケタミン塩酸塩の調製および純度の確認は、実施例2に記載の方法で実施した。
両ケタミン異性体の投与後の運動量測定において、S(+)−ケタミン(10mg/kg、20mg/kg)を投与したマウスは、生理食塩水を投与した正常マウスと比較して運動量の有意な増加が投与10分および20分後に認められた。S(+)−ケタミン(10mg/kg、20mg/kg)の運動量亢進は、一過性で、投与30分後には正常値まで戻った。一方、R(−)−ケタミン(5、10、20mg/kg)の投与は、運動量には影響を与えなかった(図4)。
Claims (28)
- 大うつ病性障害、強迫性障害又は心的外傷後ストレス障害の予防若しくは治療のための、R(−)−ケタミンまたはその薬理学的に許容される塩、及び薬理学的に許容される担体を含む、医薬組成物であって、該医薬組成物がS(+)−ケタミンまたはその薬理学的に許容される塩を実質的に含まない、医薬組成物。
- 非経口投与のために製剤化されてなる、請求項1に記載の医薬組成物。
- 静脈投与、筋肉投与、皮下投与、経鼻投与、経口投与、直腸投与、若しくは経皮投与のために製剤化されてなる、請求項1に記載の医薬組成物。
- 静脈投与、経鼻投与、経口投与のために製剤化されてなる、請求項3に記載の医薬組成物。
- 液体、溶液、懸濁液、粉末、錠剤、コーテイング錠、カプセル、トローチ、クリーム、座薬、塗布薬(リニメント)、パッチ薬、噴霧剤、若しくはゲルの剤型である、請求項1に記載の医薬組成物。
- 前記非経口投与が、R(−)−ケタミンまたはその薬理学的に許容される塩の約0.01〜1000mg/人/日又は約0.1〜500mg/人/日での投与を含む、請求項2に記載の医薬組成物。
- 前記経口投与が、R(−)−ケタミンまたはその薬理学的に許容される塩の約0.01〜500mg/人/日又は約0.1〜100mg/人/日での投与を含む、請求項3に記載の医薬組成物。
- R(−)−ケタミンの薬理学的に許容される塩が、R(−)−ケタミン塩酸塩である、請求項1に記載の医薬組成物。
- S(+)−ケタミンまたはその薬理学的に許容される塩を実質的に含まない医薬組成物が、S(+)−ケタミンまたはその薬理学的に許容される塩を含まない、請求項1に記載の医薬組成物。
- S(+)−ケタミンまたはその薬理学的に許容される塩を実質的に含まない医薬組成物が、S(+)−ケタミンまたはその薬理学的に許容される塩の副作用が生じないような量を含む、請求項1に記載の医薬組成物。
- 副作用が、精神病症状惹起作用である、請求項10に記載の医薬組成物。
- 大うつ病性障害、強迫性障害又は心的外傷後ストレス障害の治療のためであって、該治療がその必要とする対象に医薬組成物の治療的有効量を投与することを含む、R(−)−ケタミンまたはその薬理学的に許容される塩を含む医薬組成物であって、該医薬組成物がS(+)−ケタミンまたはその薬理学的に許容される塩を実質的に含まない、医薬組成物。
- その必要とする対象が、子供である、請求項12に記載の医薬組成物。
- その必要とする対象が、大人である、請求項12に記載の医薬組成物。
- その必要とする対象が、高齢者である、請求項14に記載の医薬組成物。
- その必要とする対象が、うつ病若しくはうつ症状と診断された対象である、請求項12に記載の医薬組成物。
- S(+)−ケタミンまたはその薬理学的に許容される塩を実質的に含まない医薬組成物が、S(+)−ケタミンまたはその薬理学的に許容される塩を含まない、請求項12に記載の医薬組成物。
- S(+)−ケタミンまたはその薬理学的に許容される塩を実質的に含まない医薬組成物が、S(+)−ケタミンまたはその薬理学的に許容される塩の副作用が生じないような量を含む、請求項12に記載の医薬組成物。
- 副作用が、精神病症状惹起作用である、請求項18に記載の医薬組成物。
- 非経口投与のために製剤化されてなる、請求項12に記載の医薬組成物。
- 前記非経口投与が、R(−)−ケタミンまたはその薬理学的に許容される塩の約0.01〜1000mg/人/日又は約0.1〜500mg/人/日での投与を含む、請求項20に記載の医薬組成物。
- 経口投与のために製剤化されてなる、請求項12に記載の医薬組成物。
- 前記経口投与が、R(−)−ケタミンまたはその薬理学的に許容される塩の約0.01〜500mg/人/日又は約0.1〜100mg/人/日での投与を含む、請求項22に記載の医薬組成物。
- R(−)−ケタミンまたはその薬理学的に許容される塩が、対象への投与後24時間治療的に有効である、請求項12に記載の医薬組成物。
- R(−)−ケタミンまたはその薬理学的に許容される塩が、対象への投与後48時間治療的に有効である、請求項12に記載の医薬組成物。
- R(−)−ケタミンまたはその薬理学的に許容される塩が、対象への投与後少なくとも6日間治療的に有効である、請求項12に記載の医薬組成物。
- R(−)−ケタミンまたはその薬理学的に許容される塩が、対象への投与後少なくとも7日間治療的に有効である、請求項12に記載の医薬組成物。
- R(−)−ケタミンまたはその薬理学的に許容される塩が、さらに、薬理学的に許容される担体を含む、医薬組成物として投与される、請求項12に記載の医薬組成物。
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PT3043785T (pt) * | 2013-09-13 | 2021-11-05 | Univ Chiba Nat Univ Corp | Aplicação de r-cetamina e seu sal como medicamentos |
CA2936809A1 (en) | 2014-01-14 | 2015-07-23 | Children's Hospital Medical Center | Compositions comprising ketamine for treating an autism spectrum disorder |
US10098854B2 (en) | 2014-08-13 | 2018-10-16 | Janssen Pharmaceutica Nv | Method for the treatment of depression |
EP3085366A1 (en) | 2015-04-22 | 2016-10-26 | Institut du Cerveau et de la Moelle Epiniere-ICM | Nmda antagonists for the treatment of mental disorders with occurrence of aggressive and/or impulsive behavior |
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JPWO2019160057A1 (ja) | 2018-02-15 | 2021-02-04 | 国立大学法人千葉大学 | 炎症性疾患若しくは骨疾患の予防又は治療剤及び医薬組成物 |
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EP3968979A4 (en) | 2019-05-15 | 2023-03-01 | Bexson Biomedical, Inc. | KETAMINE FORMULATION FOR SUBCUTANEOUS INJECTION |
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DK3043785T3 (da) | 2021-11-15 |
JP2021073310A (ja) | 2021-05-13 |
ES2897453T3 (es) | 2022-03-01 |
LT3043785T (lt) | 2021-12-10 |
HUE056378T2 (hu) | 2022-02-28 |
EP3964203A1 (en) | 2022-03-09 |
JP6842206B2 (ja) | 2021-03-17 |
US20160220513A1 (en) | 2016-08-04 |
PL3043785T3 (pl) | 2022-02-28 |
JP2020015766A (ja) | 2020-01-30 |
WO2015037248A1 (en) | 2015-03-19 |
PT3043785T (pt) | 2021-11-05 |
JP7398836B2 (ja) | 2023-12-15 |
JP2023011027A (ja) | 2023-01-20 |
US9872841B2 (en) | 2018-01-23 |
US20180177745A1 (en) | 2018-06-28 |
JP2015078181A (ja) | 2015-04-23 |
CA2923685C (en) | 2022-03-08 |
RS62516B1 (sr) | 2021-11-30 |
US11207279B2 (en) | 2021-12-28 |
EP3043785A1 (en) | 2016-07-20 |
SI3043785T1 (sl) | 2022-02-28 |
JP2018145207A (ja) | 2018-09-20 |
CA2923685A1 (en) | 2015-03-19 |
JP2024009274A (ja) | 2024-01-19 |
US20190343781A1 (en) | 2019-11-14 |
CA3143962A1 (en) | 2015-03-19 |
JP6366439B2 (ja) | 2018-08-01 |
HRP20211629T1 (hr) | 2022-02-04 |
CY1125290T1 (el) | 2023-03-24 |
EP3043785B1 (en) | 2021-08-25 |
US20220071929A1 (en) | 2022-03-10 |
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