JP2022071083A - うつ病を予防または治療するための安息香酸またはその塩および誘導体 - Google Patents
うつ病を予防または治療するための安息香酸またはその塩および誘導体 Download PDFInfo
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- JP2022071083A JP2022071083A JP2022031267A JP2022031267A JP2022071083A JP 2022071083 A JP2022071083 A JP 2022071083A JP 2022031267 A JP2022031267 A JP 2022031267A JP 2022031267 A JP2022031267 A JP 2022031267A JP 2022071083 A JP2022071083 A JP 2022071083A
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- benzoic acid
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Abstract
Description
(実施例)
この研究は、MDDの治療のための安息香酸ナトリウムの検証を目的とする8週間のパイロット試験であった。患者に、徹底的な医学的および神経学的精密検査を行った後、研究精神科医により評価された。診断のために、DSM-IVの構造的臨床面接(strucured clinical interview for DSM-IV、以下、SCIDとも称する)(アメリカ精神医学会、1994)を行い、DSM-IV(アメリカ精神医学会、1994b)によりMDDと診断された適格患者を採用した。全ての患者は、プラセボ群または安息香酸ナトリウム群(250~1500mg/日、例えば、250mg/日、500mg/日、750mg/日、1000mg/日、1250mg/日または1500mg/日)の二つの群にランダムに割り当てられた。臨床評価に基づいて、試験薬の投与量を調整した。
MDDの治療に対する安息香酸ナトリウムの有効性は、2、4、6および8週目の終わりに、HAMD-17、PSSおよびGAFにより評価された。
データ分析は、治療意図解析の原則(intent-to-treat principle)に基づいた。最後の観測結果は、サンプル全体から利用可能な全てのデータを分析するために使用された(すなわち、完全なデータと不完全なデータがあるケース)。統計的有意性の全ての分析は、タイプIのエラーの0.05レベル(両側値)を採用した。人口統計的特性、ベースラインおよびエンドポイントの症候学は、連続変数についてのT検定(またはマン・ホイットニーのU検定)およびカテゴリー変数についてのカイ二乗検定(またはフィッシャーの正確確率検定)により、二つの群の間で比較された。
下記の表1に示すように、安息香酸ナトリウム群とプラセボ群とは、人口統計データおよび教育レベルが類似しており(p>0.05)、また、エンドポイントでの安息香酸ナトリウムの平均投与量は775.0±213.1であった。
[1]有効量の安息香酸またはその塩および誘導体と、
薬学的に許容される賦形剤と
を含み、
必要のある対象におけるうつ病を予防または治療するための、組成物。
[2]前記うつ病は、大うつ病性障害(MOD)、老年期うつ病、晩年うつ病または高齢者うつ病である、[1]に記載の組成物。
[3]前記治療は、対象の認知を改善する、[1]に記載の組成物。
[4]前記安息香酸またはその塩および誘導体は、安息香酸ナトリウム、安息香酸カリウム、安息香酸カルシウム、安息香酸マグネシウム、2-アミノベンゾアート、3-アミノベンゾアート、4-アミノベンゾアート、4-ヒドロキシ安息香酸エチル、4-ヒドロキシ安息香酸エチルナトリウム、4-ヒドロキシ安息香酸プロピル、4-ヒドロキシ安息香酸プロピルナトリウム、4-ヒドロキシ安息香酸メチルまたは4-ヒドロキシ安息香酸ナトリウムである、[1]に記載の組成物。
[5]前記安息香酸の塩は、安息香酸ナトリウムである、[1]に記載の組成物。
[6]前記安息香酸またはその塩および誘導体は、100mg/日~2500mg/日の量で対象に投与される、[1]に記載の組成物。
[7]前記安息香酸またはその塩および誘導体は、250mg/日~1500mg/日の量で対象に投与される、[6]に記載の組成物。
[8]前記安息香酸またはその塩および誘導体は、500mg/日~1000mg/日の量で対象に投与される、[7]に記載の組成物。
[9]前記薬学的に許容される賦形剤は、充填材、結合剤、防腐剤、崩壊剤、潤滑剤、懸濁剤、湿潤剤、溶媒、界面活性剤、酸、香味剤、ポリエチレングリコール(PEG)、アルキレングリコール、セバシン酸、ジメチルスルホキシド、アルコール、およびこれらの任意の組合せからなる群から選ばれる、[1]に記載の組成物。
[10]前記安息香酸またはその塩および誘導体は、組成物におけるうつ病を予防または治療するための唯一の有効成分として機能する、[1]に記載の組成物。
[11]前記安息香酸またはその塩および誘導体は、うつ病を予防または治療するための追加の有効成分と組み合わされる、[1]に記載の組成物。
[12]前記追加の有効成分は、デュロキセチン(duloxetine)、レボミルナシプラン(levomilnacipran)、ベンラファキシン(venlafaxine)、デスベンラファキシン(desvenlafaxine)、シタロプラム(citalopram)、エスシタロプラム(escitalopram)、フルオキセチン(fluoxetine)、フルボキサミン(fluvoxamine)、パロキセチン(paroxetine)、セルトラリン(sertraline)、アミトリプチリン(amitriptyline)、アモキサピン(amoxapine)、クロミプラミン(clomipramine)、デシプラミン(desipramine)、ドキセピン(doxepin)、イミプラミン(imipramine)、ノルトリプチリン(nortriptyline)、プロトリプチリン(protriptyline)、トリミプラミン(trimipramine)、マプロチリン(maprotiline)、ブプロピオン(bupropion)、ビラゾドン(vilazodone)、ネファゾドン(nefazodone)、トラゾドン(trazodone)、ボルチオキセチン(vortioxetine)、イソカルボキサジド(isocarboxazid)、フェネルジン(phenelzine)、セレギリン(selegiline)、トラニルシプロミン(tranylcypromine)、ミルタザピン(mirtazapine)、オランザピン(olanzapine)、クエチアピン(quetiapine)、アリピプラゾール(aripiprazole)、スルピリド(sulpiride)、フルペンチキソール(flupentixol)、メリトラセン(melitracen)、アゴメラチン(agomelatine)、モクロベミド(moclobemide)、セイヨウオトギリソウ(St.John’s wort)、S-アデノシルメチオニン(S-adenosyl-L-methionine)、およびこれらの任意の組合せからなる群から選ばれる、[11]に記載の組成物。
[13]前記安息香酸またはその塩および誘導体の投与は、うつ病のための追加の療法と組み合わされる、[1]に記載の組成物。
[14]前記追加の療法は、心理療法、電気けいれん療法(ECT)、脳部刺激療法、光療法、およびこれらの任意の組合せからなる群から選ばれる、[13]に記載の組成物。
[15]前記脳部刺激療法は、脳深部刺激、侵襲的迷走神経刺激、経頭蓋磁気刺激、経頭蓋直流電気刺激、経頭蓋交流電気刺激、電気けいれん治療、磁気発作療法、経頭蓋電気刺激または非侵襲的迷走神経刺激である、[14]に記載の組成物。
・American Psychiatric Association (1994) “Structured Clinical Interview for DSM-IV.” American Psychiatric Press: Washington, DC.
・Banerjee, S., J. Hellier, et al. (2011) “Sertraline or mirtazapine for depression in dementia (HTA-SADD): a randomised, multicentre, double-blind, placebo-controlled trial.” Lancet 378(9789): 403-411.
・Bartlett, G. R. (1948) “The inhibition of d-amino acid oxidase by benzoic acid and various monosubstituted benzoic acid derivatives.” J. Am. Chem. Soc. 70(3): 1010.
・Beneyto, M. and J. H. Meador-Woodruff (2008) “Lamina-specific abnormalities of NMDA receptor-associated postsynaptic protein transcripts in the prefrontal cortex in schizophrenia and bipolar disorder.” Neuropsychopharmacology 33(9): 2175-2186.
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Claims (14)
- 有効量の安息香酸またはその塩および誘導体と、
薬学的に許容される賦形剤と
を含み、
必要のある対象におけるうつ病を予防または治療すると同時に前記対象の認知障害を改善するための、組成物であって、
前記うつ病は、大うつ病性障害(MDD)であり、
前記安息香酸またはその塩および誘導体は、安息香酸ナトリウム、安息香酸カリウム、安息香酸カルシウム、安息香酸マグネシウム、2-アミノベンゾアート、3-アミノベンゾアート、4-アミノベンゾアート、4-ヒドロキシ安息香酸エチル、4-ヒドロキシ安息香酸エチルナトリウム、4-ヒドロキシ安息香酸プロピル、4-ヒドロキシ安息香酸プロピルナトリウム、4-ヒドロキシ安息香酸メチルまたは4-ヒドロキシ安息香酸ナトリウムである、組成物。 - 前記うつ病は、晩年うつ病(late-life depression)である、請求項1に記載の組成物。
- 前記安息香酸の塩は、安息香酸ナトリウムである、請求項1に記載の組成物。
- 前記安息香酸またはその塩および誘導体は、100mg/日~2500mg/日の量で対象に投与される、請求項1に記載の組成物。
- 前記安息香酸またはその塩および誘導体は、250mg/日~1500mg/日の量で対象に投与される、請求項4に記載の組成物。
- 前記安息香酸またはその塩および誘導体は、500mg/日~1000mg/日の量で対象に投与される、請求項5に記載の組成物。
- 前記薬学的に許容される賦形剤は、充填材、結合剤、防腐剤、崩壊剤、潤滑剤、懸濁剤、湿潤剤、溶媒、界面活性剤、酸、香味剤、ポリエチレングリコール(PEG)、アルキレングリコール、セバシン酸、ジメチルスルホキシド、アルコール、およびこれらの任意の組合せからなる群から選ばれる、請求項1に記載の組成物。
- 前記安息香酸またはその塩および誘導体は、組成物におけるうつ病を予防または治療するための唯一の有効成分として機能する、請求項1に記載の組成物。
- 前記安息香酸またはその塩および誘導体は、うつ病を予防または治療するための追加の有効成分と組み合わされる、請求項1に記載の組成物。
- 前記追加の有効成分は、デュロキセチン(duloxetine)、レボミルナシプラン(levomilnacipran)、ベンラファキシン(venlafaxine)、デスベンラファキシン(desvenlafaxine)、シタロプラム(citalopram)、エスシタロプラム(escitalopram)、フルオキセチン(fluoxetine)、フルボキサミン(fluvoxamine)、パロキセチン(paroxetine)、セルトラリン(sertraline)、アミトリプチリン(amitriptyline)、アモキサピン(amoxapine)、クロミプラミン(clomipramine)、デシプラミン(desipramine)、ドキセピン(doxepin)、イミプラミン(imipramine)、ノルトリプチリン(nortriptyline)、プロトリプチリン(protriptyline)、トリミプラミン(trimipramine)、マプロチリン(maprotiline)、ブプロピオン(bupropion)、ビラゾドン(vilazodone)、ネファゾドン(nefazodone)、トラゾドン(trazodone)、ボルチオキセチン(vortioxetine)、イソカルボキサジド(isocarboxazid)、フェネルジン(phenelzine)、セレギリン(selegiline)、トラニルシプロミン(tranylcypromine)、ミルタザピン(mirtazapine)、オランザピン(olanzapine)、クエチアピン(quetiapine)、アリピプラゾール(aripiprazole)、スルピリド(sulpiride)、フルペンチキソール(flupentixol)、メリトラセン(melitracen)、アゴメラチン(agomelatine)、モクロベミド(moclobemide)、セイヨウオトギリソウ(St.John’s wort)、S-アデノシルメチオニン(S-adenosyl-L-methionine)、およびこれらの任意の組合せからなる群から選ばれる、請求項9に記載の組成物。
- 前記安息香酸またはその塩および誘導体の投与は、うつ病のための追加の療法と組み合わされる、請求項1に記載の組成物。
- 前記追加の療法は、心理療法、電気けいれん療法(ECT)、脳部刺激療法、光療法、およびこれらの任意の組合せからなる群から選ばれる、請求項11に記載の組成物。
- 前記脳部刺激療法は、脳深部刺激、侵襲的迷走神経刺激、経頭蓋磁気刺激、経頭蓋直流電気刺激、経頭蓋交流電気刺激、電気けいれん治療、磁気発作療法、経頭蓋電気刺激または非侵襲的迷走神経刺激である、請求項12に記載の組成物。
- 少なくとも2ヶ月にわたって毎日投与される、請求項1に記載の組成物。
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