JP2009539826A - イノシトールリン脂質による免疫系の調節 - Google Patents
イノシトールリン脂質による免疫系の調節 Download PDFInfo
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Abstract
【選択図】なし
Description
下記実施例1及び2は、イン ビトロ(in vitro)条件下で、イノシトールリン脂質の免疫抑制効果を示し、一方、実施例3は、免疫障害用の動物モデルにおいてIPLのイン ビボ(in vivo)効果を記載する。全てのイン ビボ(in vivo)実験は、エラスムス大学(ロッテルダム、オランダ)の実験動物委員会によって、動物実験のための倫理規約に従って行なわれた。使用された物質は、シグマ社から入手されたホスファチジルイノシトール(PI)(ウシ肝臓PI;シグマ社カタログ番号P 8443)、ベクトン・ディッキンソンから入手されたI-イノシトール/ミオイノシトールを含む。
0日目において、T84D細胞(CD1dで形質転換されたヒト上皮細胞株)が、aGalCer(10mg/ml)とともに一晩インキュベートされた。各種量のPIが、各時点でT84D細胞に添加された。次に、T84D細胞がPBSで1回洗浄され、そしてDN32細胞(ネズミの1.1倍陽性NKT細胞株)が添加され(T84D: DN32 = 1:10)、そして24時間共培養された。上清が集められ、そして(T細胞活性化を反映する)DN32によるIL-2サイトカイン生産が、ELISAによって決定された。該結果が、図1に示される。
PIの粘膜投与のための組成物の調製:
2mgのウシ肝臓PI(アヴァンティ・ポーラー・リピッズ;カタログ番号830042)が窒素の流下で乾燥され、そして上下に数回ピペッティングすることによって1 mlの生理食塩水(0.9% NaCl)中に懸濁された。2 mg/mlのこの貯蔵溶液が生理食塩水中に10倍に希釈されて、0.2 mg/mlの懸濁液を得た。
0日目において、オスの7〜10週齢野生型black/6マウス(チャールス・リバー)が、100%エタノール中150μlの3% 4-エトキシメチレン-2-フェニルオキサゾリン-5-オン(オキサゾロン;シグマ社)で経皮的に感作された。5日目で、マウスは、ケタミン(80 mg/kg)及びキシラジン(10 mg/kg)の麻酔下で、水性エタノール(50%)中100μlの2%オキサゾロンの直腸投与によって試験された。試験20分前に、マウスが100μlの食塩水(対照)又はPI(2 mg/ml)で直腸内に処理された。3つの全ての群は、8匹のマウスを含んだ。マウスは、5、6、7及び8日目に体重測定され、そして8日目に犠牲にされた。
マウスにおいてハプテン誘発された大腸炎の誘発前に結腸投与を介したPIでの局所処理は、減少した体重減少及び増加した生存を生じた。図5に示されているように、IPLでのマウスの直腸内処理は、腸のT細胞をエクス ビボ(ex-vivo)刺激するとIL-2生産を抑制した。これらのデータは、IPLがヒト炎症性腸疾患、例えば潰瘍性大腸炎の予防又は治療として使用されうることを示す。
0日目において、8匹のオスの7〜10週齢野生型Blab/cマウス(チャールス・リバー)が、2.25 mgのミョウバン(AlumImuject;ピアス)中に乳化された20μgのOVA(シグマ社)の腹腔内(i.p.)注射によって感作された。15、16及び17日目において、マウスが落ち着かせられ、そしてPI(0μg/ml、200μg/ml又は200mg/ml)の3つの溶液のうちの1つの80μlを気管内に(i.t.)受け取った。引き続き、該マウスは、OVA(1%食塩水中)を含む60μlのエアロゾルに、20分の吸入暴露によって試験された。3つの全ての群は、8匹のマウスを含んだ。マウスは、18日目に犠牲にされた。
気道過敏反応性のためのこのモデルは、PIでの気管内処理が喘息に関連付けられる好酸球の典型的な流入を強く阻害することを示す。該肺の分析は、PIがこのモデルに特徴的である組織病理学的変化を減らすことを裏付けた。これらのデータは、IPLがヒトの喘息の予防又は治療のために適切に使用されうることを示す。
Claims (24)
- 活性成分としてイノシトールリン脂質(IPL)、及び医薬的に許容される担体又は希釈剤を含む粘膜投与のために適合された医薬組成物。
- 前記IPLのイノシトール頭部基が、リン酸基以外の残基に共役されていない、請求項1に記載の組成物。
- 前記IPLが天然起源である、請求項1又は2に記載の組成物。
- 前記IPLがジアシルグリセロールホスファチジルイノシトールである、請求項1〜3のいずれか一項に記載の組成物。
- 前記IPL中に存在する飽和対不飽和脂肪酸の比が、少なくとも1.0、好ましくは少なくとも1.1である、請求項1〜4のいずれか1項に記載の組成物。
- 前記IPLが、哺乳動物組織、好ましくは肝臓、より好ましくはウシの肝臓から得られる、請求項1〜5のいずれか1項に記載の組成物。
- 前記組成物が非リポソーム組成物である、請求項1〜6のいずれか1項に記載の組成物。
- 前記少なくとも1つのIPLが、生理学的に許容される水性担体中に、好ましくは生理食塩水中に、懸濁された形態で前記組成物中に存在する、請求項1〜7のいずれか1項に記載の組成物。
- 前記少なくとも1つのIPLが、前記組成物の乾燥重量の50%未満、好ましくは30%未満、より好ましくは25%未満を成す、請求項1〜8のいずれか1項に記載の組成物。
- 前記組成物が、直腸投与のために適合されている、請求項1〜9のいずれか1項に記載の組成物。
- 前記組成物が、例えばネブライザ又はエアロゾルの形態で、肺内投与のために適合されている、請求項1〜9のいずれか1項に記載の組成物。
- 肺サーファクタントポリペプチドを含まない、請求項11に記載の組成物。
- 活性成分として少なくとも1つのIPLを含む医薬組成物を調製するための方法であって、水性の生理学的に許容される担体中で、好ましくは食塩水中で前記少なくとも1つのIPLの非リポソーム懸濁液を調製することを含む、前記方法。
- 哺乳動物における喘息状態の治療又は予防のための医薬品の製造のためにIPLを使用する方法。
- 前記医薬品が肺サーファクタントポリペプチドを含まない、請求項13に記載の方法。
- 哺乳動物における炎症性腸疾患、好ましくは潰瘍性大腸炎の治療のための医薬品の製造のためにIPLを使用する方法。
- 少なくとも1つのIPL、好ましくはPI、より好ましくはジアシルグリセロールPIを強化された食品又は食品サプリメント。
- 炎症性疾患、特にアレルギー性喘息又は潰瘍性大腸炎を予防することが可能な食品又は食品サプリメントの製造のためにIPLを使用する方法。
- 健康な対象において炎症性疾患、特にアレルギー性喘息又は潰瘍性大腸炎の発生を予防するための方法であって、IPL又はその前駆体、誘導体若しくは医薬的に許容されるその塩の高められたレベルを有する食事を前記対象に与えることを含む、前記方法。
- 健康な対象において炎症性疾患、特にアレルギー性喘息又は潰瘍性大腸炎の発生を予防するための方法であって、請求項1〜12のいずれか1項に記載の医薬組成物を前記対象に投与することを含む、前記方法。
- 炎症性疾患、特にアレルギー性喘息又は潰瘍性大腸炎を患う対象を治療するための方法であって、請求項1〜12のいずれか1項に記載の医薬組成物の治療的に有効な量をその必要がある対象に投与することを含む、前記方法。
- 炎症性疾患、特にアレルギー性喘息又は潰瘍性大腸炎の予防及び/又は治療のために、IPL又はその前駆体若しくは誘導体の高められた量を有する食品を使用する方法。
- 炎症性疾患、特にアレルギー喘息又は潰瘍性大腸炎の治療及び/又は予防のための食品中にIPL又はその前駆体若しくは誘導体の高められた量を有する食品を使用する方法。
- 炎症性疾患、特にアレルギー性喘息又は潰瘍性大腸炎の予防及び/又は治療のために、請求項1〜12のいずれか1項に記載に従う医薬組成物を使用する方法。
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WO2013081452A1 (en) | 2011-11-30 | 2013-06-06 | Erasmus University Medical Center Rotterdam | Phosphatidylinositol |
CN102978160A (zh) * | 2012-12-13 | 2013-03-20 | 上海柯莱逊生物技术有限公司 | 一种体外诱导扩增nkt细胞的方法 |
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- 2006-06-09 JP JP2009514221A patent/JP2009539826A/ja not_active Ceased
- 2006-06-09 EP EP06747568A patent/EP2035010B1/en not_active Not-in-force
- 2006-06-09 CN CNA2006800555634A patent/CN101505763A/zh active Pending
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WO2016185816A1 (ja) * | 2015-05-18 | 2016-11-24 | 不二製油グループ本社株式会社 | IL-1β産生抑制作用を有する食品添加用組成物 |
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Also Published As
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EP2035010B1 (en) | 2012-10-03 |
EP2382978A2 (en) | 2011-11-02 |
AU2006344178A1 (en) | 2007-12-13 |
CN101505763A (zh) | 2009-08-12 |
EP2382978A3 (en) | 2012-01-18 |
EP2035010A1 (en) | 2009-03-18 |
CA2654631A1 (en) | 2007-12-13 |
WO2007142510A1 (en) | 2007-12-13 |
US20090176741A1 (en) | 2009-07-09 |
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