JP5794911B2 - ペプチド、ペプチド模倣体及び他の胃腸内輸送タンパク質基質の吸収を増加する方法 - Google Patents
ペプチド、ペプチド模倣体及び他の胃腸内輸送タンパク質基質の吸収を増加する方法 Download PDFInfo
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Description
[0001]本出願は、その開示が参照により本明細書に組み込まれる、2008年3月27日出願の米国特許仮出願第61/072069号の優先権を主張する。
[発明の分野]
[0002]本発明は、全般に、動物による化合物の吸収増加方法に関し、具体的には、動物によるペプチド、ペプチド模倣体及び他の胃腸内輸送タンパク質基質の吸収増加のための5−メトキシ−N−アセチルトリプタミンなどのホルモンの使用に関する。
[0003]ペプチド輸送体タンパク質は、ジペプチド及びトリペプチド並びにさまざまなペプチド模倣体及び他の化合物の細胞内への取り込みを媒介する内在性膜タンパク質である。ペプチド輸送体タンパク質は、細菌、酵母、植物、無脊椎動物及び脊椎動物において認められる。脊椎動物において、それぞれPepT1及びPepT2と称される2種の輸送体タンパク質、ペプチド輸送体1及び2は、小腸の刷子縁膜(PepT1)、腎臓(PepT1及びPepT2)及び肺(PepT2)において主に発現される。PepT輸送体は、多数のジペプチド及びトリペプチド並びにβラクタム系抗生物質、選択されたアンジオテンシン変換酵素(ACE)阻害剤及びペプチダーゼ阻害剤などの広範囲の治療薬を輸送できるプロトン共役輸送体である。基質フラックスは、プロトン移動が、転移のための主な駆動力としての膜電位に伴う電気化学的プロトン勾配を下げるように共役すると考えられる。
[0011]したがって、本発明の目的は、動物において、ペプチド、ペプチド模倣体又は他の胃腸内輸送タンパク質基質の吸収、輸送、取り込み及び/又は同化を、増強、改善又は増加する方法を提供することである。
定義
[0015]「メラトニン」という用語は、5−メトキシ−N−アセチルトリプタミン及び5−メトキシ−N−アセチルトリプタミンと実質的に同じ生物活性を有するその誘導体又は類似体並びにそれらのインビボ前駆体を意味する。5−メトキシ−N−アセチルトリプタミンは、概日周期の間に量が変化する化合物である。この化合物は、松果腺、網膜、免疫細胞及び胃腸管により産生される。5−メトキシ−N−アセチルトリプタミンは、アミノ酸のトリプトファンからセロトニンの合成を介して天然に合成される。松果腺は、明と暗の日々のパターンについての情報を網膜から受け取り、それに応答してメラトニンを合成する。この化合物はさらに、コメなどのさまざまな植物及び細菌、原生動物、藻類及び他の生物によっても合成される。この用語は、PepT1及びPepT2などの胃腸内輸送タンパク質に対して、5−メトキシ−N−アセチルトリプタミンと実質的に同じ生物活性を有する任意の他のホルモンも意味する。
[0043]本発明は、ペプチド、ペプチド模倣体又は他の胃腸内輸送タンパク質基質、例えば、PepT1などのPTR2ファミリーのオリゴペプチド輸送体の基質の吸収、輸送、取り込み及び/又は同化の増強、改善又は増加に有用な組成物及び方法を提供する。この組成物及び方法は、胃腸の健康の支援及び/又は改善、動物の健康又はウェルネスの促進、吸収不良障害を有する動物への改善されたアミノ酸の栄養摂取の提供、胃腸内輸送タンパク質に対する基質である、又はこのような輸送タンパク質に対する基質となるように修飾された薬剤又はプロドラッグの送達、老齢動物又は激しい肉体的活動、例えば運動に供された動物中の筋肉量の改善又は維持に有益な用途を有する。この方法及び組成物は、最適なタンパク質及び/又はアミノ酸の栄養摂取又は同化が動物の総合的な健康の一因となる任意の状況においてさらに有用である。
[0084]低分子ペプチド及び/又はペプチド模倣体の吸収を改善する5−メトキシ−N−アセチルトリプタミン(実施例においてメラトニン)の能力を評価する研究を実施した。
[0089]メラトニン又はその前駆体の経口投与により、動物においてアミノ酸の吸収を増加させる方法。低分子ペプチド及び/又はペプチド模倣体薬剤の吸収を改善する、経口投与されたメラトニンの用量を滴定する研究を実施した。セファレキシンのようなペプチド模倣体薬剤及び低分子ペプチド(ジペプチド及びトリペプチド)は、単一の低分子腸内輸送タンパク質、ペプチド輸送体1により吸収される。
Claims (14)
- ヒトを除く動物において、ペプチド模倣体の吸収を改善する方法であって、動物において腸内輸送タンパク質を介するペプチド模倣体の吸収を改善するのに有効な量のメラトニンを投与するステップを含み、
前記動物がコンパニオンアニマルであり、
前記ペプチド模倣体が、ペニシリン、セファロスポリン、モノバクタム、カルバペネム、βラクタマーゼ阻害剤、これらの誘導体若しくはこれらの塩、又はこれらの組合せである、方法。 - 前記メラトニンを、ペプチド模倣体と併用して投与する、請求項1に記載の方法。
- 前記メラトニンを、食品組成物として投与し、前記食品組成物を、ペプチド模倣体と併用して投与する、請求項1に記載の方法。
- 投与するメラトニンの量が、少なくとも0.1mg/kgである、請求項1に記載の方法。
- 投与するメラトニンの量が、0.1mg/kg〜50/mg/kgである、請求項1に記載の方法。
- 前記腸内輸送タンパク質が、膜輸送体のPTR2ファミリーのメンバーである、請求項1に記載の方法。
- 前記腸内輸送タンパク質が、ペプチド輸送体1(PepT1)である、請求項1に記載の方法。
- 前記ペプチド模倣体が、栄養素又は薬剤である、請求項1に記載の方法。
- 前記動物が、吸収不良障害を有する、請求項1に記載の方法。
- 前記メラトニンが、1種又は複数種の刺激剤と併用して投与される、請求項1に記載の方法。
- メラトニンと、1種又は複数種のペプチド模倣体とを含み、前記ペプチド模倣体が、ペニシリン、セファロスポリン、モノバクタム、カルバペネム、βラクタマーゼ阻害剤、これらの誘導体若しくはこれらの塩、又はこれらの組合せである、ペプチド模倣体の吸収改善剤。
- 前記ペプチド模倣体が、抗生物質、降圧剤又は抗ウィルス性の薬剤若しくはプロドラッグを含む、請求項11に記載のペプチド模倣体の吸収改善剤。
- ヒトを除く動物において、抗生物質感受性微生物に対処するために必要とする抗生物質の量を減少させる方法であって、1種又は複数種の抗生物質を、胃腸内輸送タンパク質による抗生物質の吸収を改善するのに有効な量のメラトニンと併用して経口投与するステップを含み、
前記動物がコンパニオンアニマルであり、
前記抗生物質が、ペニシリン、セファロスポリン、モノバクタム、カルバペネム、βラクタマーゼ阻害剤、これらの誘導体若しくはこれらの塩、又はこれらの組合せである、方法。 - メラトニンが、少なくとも0.1mg/kgの量で投与される、請求項13に記載の方法。
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PCT/US2009/001937 WO2009120378A2 (en) | 2008-03-27 | 2009-03-26 | Methods for increasing absorption of peptides, peptidomimetics, and other gastrointestinal transport protein substrates |
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ZA201007646B (en) | 2012-04-25 |
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CN102046169A (zh) | 2011-05-04 |
BRPI0910039A2 (pt) | 2015-12-29 |
EP2257287B1 (en) | 2018-10-10 |
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WO2009120378A3 (en) | 2009-12-30 |
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