JP5547654B2 - 精神神経系障害の治療のための、医薬組成物並びにd−アミノ酸及び抗酸化物を利用する方法 - Google Patents
精神神経系障害の治療のための、医薬組成物並びにd−アミノ酸及び抗酸化物を利用する方法 Download PDFInfo
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Description
本発明の好適な実施形態では、D−アミノ酸がD−セリン、D−アラニン、D−システイン、D−ホモシステイン、またはD−トレオニンからなる群から選択される。
本発明の他の好適な実施形態では、グルタチオン前駆体はL−システインまたはN−アセチル−L−システイン及びこれらのラセミ体或いはこれらの組合せからなる群から選択される。
本発明の他の好適な実施形態では、抗酸化物はビタミンEであり、一方で他の好適な実施形態では抗酸化物はビタミンCである。
好適には、D−アミノ酸及び抗酸化物は1:10〜10:1の間のモル比で存在する。
本発明の好適な実施形態では、精神神経系障害は統合失調症、統合失調症様障害、精神障害NOS、または統合失調症の前駆症状である。
本発明の好適な実施形態では、精神神経系障害はアルツハイマー病である。
本発明はまた、減弱されたNMDAの神経伝達を特徴とする精神神経系障害を患者で治療するための方法を供し、当該方法は、精神神経系障害に罹患していると診断された患者に、ビタミンE、ビタミンC、グルタチオンまたはこの前駆体からなる群から選択される抗酸化物と組合され、治療効果のある量のD−アミノ酸を含んでなる経口医薬組成物を投与することを含んでなる。
ここで使用する用語アミノ酸は、アミノ酸はアミン及びカルボキシル官能基どちらも含む分子であることを意味する。生化学では、この用語は一般式H2NCHRCOOHを有するαアミノ酸を示し、式中Rは有機置換基である。αアミノ酸において、アミノ及びカルボキシレート基は同一の炭素に結合し、この炭素はα炭素と呼ばれる。αアミノ酸は様々に相違し、式中側鎖(R基)はこれらのα炭素に結合する。これらは、サイズの点で、単にグリシン中の水素原子から、アラニン中のメチル基を含め、トリプトファン中の大きな複素環基まで変化することができる。
ここで使用する用語「腎毒性(nephrotoxicity)」或いは「腎毒性(renal toxicity)」は、腎臓への薬物誘発の障害そして、特に、尿細管の壊死を意味する。このような損傷は、アミノグリコシド、シスプラチン、静脈内の造影剤、及びD−アミノ酸を含む多くの腎毒性薬剤のいずれかによって生じるかもしれない。
群B: 4:3:1の割合で、D−セリン、L−システイン及びN−アセチルシステイン;
群C: 2:1:1の割合で、D−セリン、L−システイン及びN−アセチルシステイン;
群D: 1:0:1の割合で、D−セリン、L−システイン及びN−アセチルシステイン;
及び群E: 1:1:0の割合で、D−セリン、L−システイン及びN−アセチルシステイン。
腎毒性を2つの方法で評価した: 1つ目、クレアチニンレベルによって、そして2つ目、剖検での病理組織診断によって。
本発明は、経口で活性を有する抗酸化物と組合せてD−アミノ酸を含有する組成物を含んでなる、D−アミノ酸での経口治療の間に、腎毒性の危険性を軽減するための方法を記載する。本発明はまた、NMDA受容体を経由した神経伝達の欠如を有する精神神経系障害に罹患している、と診断されD−セリンの治療が望ましいかもしれない患者を治療するための改善された方法を記載する。本発明は、D−セリンでの治療の間の腎毒性の危険性、或いは他の精神神経系疾病を軽減する効果を有する。
あるいは、医薬組成物を、チューイングガム、棒付キャンディー等として製剤化することができる。
Amirzadeh A, McCotter C (2002): アセトアミノフェン過剰投与の治療のための、静脈内での経口アセチルシステイン (ムコミスト)の使用。Archives of internal medicine 162:96-97.
Arfsten DP, Johnson EW, Wilfong ER, Jung AE, Bobb AJ (2007): スプラーグドーリーラットにおける、経口胃管栄養法による単回投薬及び反復投薬の後の放射標識されたN−アセチル−L−システインの分布及びグルタチオン代謝に対するその効果。Cutaneous and ocular toxicology 26:113-134.
Atkuri KR, Mantovani JJ, Herzenberg LA, Herzenberg LA (2007): システイン/グルタチオン欠乏症のための、N−アセチルシステインの安全な解毒剤。Current opinion in pharmacology 7:355-359.
Azmus AD, Gottschall C, Manica A, Manica J, Duro K, Frey M, et al (2005): 造影剤腎症の予防におけるアセチルシステインの有効性。The Journal of invasive cardiology 17:80-84.
Betten DP, Cantrell FL, Thomas SC1 Williams SR, Clark RF (2007): 急性アセトアミノフェン中毒の治療のための、短縮経路の経口N−アセチルシステインの予測評価。Annals of emergency medicine 50:272-279.
Dickey DT1 Muldoon LL, Doolittle ND, Peterson DR, Kraemer DF1 Neuwelt EA (2007):ラットモデルでの、シスプラチン−誘発毒性に対するに対する化学防御上のN−アセチルシステインの投与経路の影響。Cancer Chemother Pharmacol.
Dilger RN, Baker DH (2007): 経口N−アセチル−L−システインは安全でありそして効果的なシステインの前駆体である。Journal of animal science 85: 1712-1718.
Goldenberg I, Shechter M, Matetzky S, Jonas M1 Adam M1 Pres H1 et al (2004):冠血管造影の後の造影剤誘発性腎症の予防のための生理的食塩水(saline hydration)への補助剤としての経口アセチルシステイン。任意に選択された対照試験及び最新文献の再考。European heart journal 25:212-218.
Javitt DC (2000): 陰性症状及び認知症状のD−セリンでの治療。In: USPTO editor. USA.
Kaltenbach JP, Ganote CE, Carone FA (1979): 構造上D−セリンに関連する化合物によって誘発される腎尿細管壊死。Exp Molec Pathol 30:209-214.
Kanter MZ (2006): アセトアミノフェン中毒の治療における、経口及び静脈内アセチルシステインの比較。Am J Health Syst Pharm 63:1821-1827.
Krug AW, Volker K, Dantzler WH, Silbernagl S (2007): なぜD−セリンは腎毒性があり、そしてαアミノイソ酪酸は保護作用があるのか?American journal of physiology 293.F382-390.
Lawlor DK, Moist L1 DeRose G, Harris KA, Lovell MB, Kribs SW, et al (2007): 血管手術患者における造影剤誘発性腎症の予防。Annals of vascular surgery 21 :593-597.
Maekawa M, Okamura T, Kasai N, Hori Y, Summer KH, Konno R (2005): D−アミノ酸オキシダーゼは、D−セリン誘発性腎毒性に関与する。Chemical research in toxicology 18:1678-1682.
Orozco-lbarra M1 Medina-Campos ON, Sanchez-Gonzalez DJ, Martinez-Martinez CM, Floriano-Sanchez E, Santamaria A1 et al (2007): D−セリン誘発性腎毒性の酸化ストレス評価。Toxicology 229: 123-135.
Sandhu C, Belli AM, Oliveira DB (2006): 造影剤誘発腎毒性の予防におけるN−アセチルシステインの役割。Cardiovascular and interventional radiology 29:344-347.
Shalansky SJ, Pate GE, Levin A, Webb JG (2005): 放射性造影剤誘発性腎毒性の予防のためのN−アセチルシステイン: 投与用量及び投与経路の重要性。Heart (British Cardiac Society) 91 :997-999.
Stacul F, Adam A1 Becker CR, Davidson C, Lameire N, McCullough PA, et al (2006): 造影剤誘発性腎症のリスクを軽減するための戦略。The American journal of cardiology 98:59K-77K.
Tsai GE (2001): 精神神経系障害の治療のための方法。
Williams RE1 Lock EA (2005): ラットにおいて、安息香酸ナトリウムによってD−セリン誘発性腎毒性が抑制される。Toxicology 207:35-48.
Claims (15)
- グルタチオンまたはこの前駆体からなる群から選択される抗酸化物と組合された、D−アミノ酸を含んでなる経口投与のための医薬組成物であって、
上記前駆体が、L−システインまたはN−アセチル−L−システイン及びこれらのラセミ体或いはこれらの組合せからなる群から選択される、医薬組成物。 - 前記D−アミノ酸が、D−セリン、D−アラニン、D−システイン、D−ホモシステイン、またはD−トレオニンからなる群から選択される、請求項1記載の医薬組成物。
- 前記D−アミノ酸及び抗酸化物が1:10〜10:1の間のモル比で存在する、請求項1又は2に記載の医薬組成物。
- 減弱されたNMDA神経伝達を特徴とする精神神経系障害を治療するための、請求項1〜3のいずれか1項に記載の医薬組成物。
- 前記精神神経系障害が、統合失調症、統合失調症様障害、精神障害NOS、または統合失調症の前駆症状である、請求項4記載の医薬組成物。
- 前記精神神経系障害がアルツハイマー病である、請求項4記載の医薬組成物。
- 前記精神神経系障害が自閉症である、請求項4記載の医薬組成物。
- 前記精神神経系障害がうつ病である、請求項4記載の医薬組成物。
- 前記精神神経系障害が良性健忘症である、請求項4記載の医薬組成物。
- 前記精神神経系障害が幼児期学習障害である、請求項4記載の医薬組成物。
- 前記精神神経系障害が注意欠陥障害である、請求項4記載の医薬組成物。
- 前記精神神経系障害が閉鎖性頭部外傷である、請求項4記載の医薬組成物。
- 前記精神神経系障害が運動性疾患である、請求項4記載の医薬組成物。
- 前記運動性疾患がパーキンソン病、ハンチントン舞踏病、ウィルソン病、トゥレット症候群、チック障害、または強迫性障害である、請求項13記載の医薬組成物。
- 減弱されたNMDA神経伝達を特徴とする精神神経系障害に罹患していると診断された患者における精神神経系障害の治療における使用のための経口医薬組成物であって、グルタチオンまたはこの前駆体からなる群から選択される抗酸化物と組合された、D−アミノ酸の治療上有効量を含んでなり、
上記前駆体が、L−システインまたはN−アセチル−L−システイン及びこれらのラセミ体或いはこれらの組合せからなる群から選択される、経口医薬組成物。
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IL188681A IL188681A0 (en) | 2008-01-09 | 2008-01-09 | Pharmaceutical compositions and methods utilizing a d-amino acid |
PCT/IL2009/000008 WO2009087615A1 (en) | 2008-01-09 | 2009-01-08 | Pharmaceutical compositions and methods utilizing a d-amino acid and an antioxidant for treating neuropsychiatric disorders |
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BR112012016869A2 (pt) * | 2010-01-08 | 2015-09-01 | President And Fellows Harvard College | Método e revestimentos para tratar biofilmes. |
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US20220313640A1 (en) * | 2019-05-29 | 2022-10-06 | Dario Doller | Deuterated analogs of d-serine and uses thereof |
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US20170157066A1 (en) | 2017-06-08 |
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US20190240169A1 (en) | 2019-08-08 |
US20090176715A1 (en) | 2009-07-09 |
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CA2711675C (en) | 2016-10-18 |
WO2009087615A1 (en) | 2009-07-16 |
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