JP6837442B2 - 乳酸菌を活性化する方法 - Google Patents
乳酸菌を活性化する方法 Download PDFInfo
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- JP6837442B2 JP6837442B2 JP2017555837A JP2017555837A JP6837442B2 JP 6837442 B2 JP6837442 B2 JP 6837442B2 JP 2017555837 A JP2017555837 A JP 2017555837A JP 2017555837 A JP2017555837 A JP 2017555837A JP 6837442 B2 JP6837442 B2 JP 6837442B2
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- citrate
- bacteria
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- lyophilized
- bacterium
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Classifications
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- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K35/00—Medicinal preparations containing materials or reaction products thereof with undetermined constitution
- A61K35/66—Microorganisms or materials therefrom
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Description
したがって、本発明はまた、以下を含む調製物を提供する:
(i)クエン酸塩を外部電子受容体として利用する能力を有する生細菌、特に乳酸菌;および
(ii)クエン酸塩。
またさらなる側面において、本発明は、本明細書中に記載されるように、本発明のそのようなクエン酸塩活性化細菌または本発明の調製物の治療的使用を提供する。
これに関して、発酵は、糖からエネルギーを放出し、酸素または電子輸送鎖を必要としないプロセスである。代わりに、有機分子が電子受容体として使用され、解糖の間に生成されたNAD(P)Hの再酸化を行う。ほとんどの場合、この有機分子は、ピルビン酸塩であり、エムデン・マイヤーホフ経路(EMP)の最終生成物、最も一般的なタイプの解糖系である。
他の好ましい対象は、NECを有する対象またはNEC発症のリスクがある対象であり、未熟児に一般的であり得る状態である。
「人工腸基板」におけるラクトバチルス・ロイテリ(Lactobacillus reuteri)の増殖
糖および電子受容体の異なる組み合わせについてラクトバチルス・ロイテリ(L.reuteri)DSM17983の増殖を「人工腸基板」(SIS)で評価した。
糖−電子受容体対としてのラクトースおよびクエン酸塩を有するSISにおいてラクトバチルス・ロイテリ(Lactobacillus reuteri)DSM17938の増殖は、GOSおよび電子受容体としてのクエン酸について上記のような同じ方法で評価される。上記基質(SIS)が使用される。ラクトバチルス・ロイテリ(Lactobacillus reuteri)DSM17938は、GOS−クエン酸塩の組み合わせと同様に、ラクトース−クエン酸塩で効率的に増殖している(データを示さす)。
本明細書中で本発明を使用して、NECを発症するリスクのある未熟児をチューブ給餌で使用するのに適した生成物の処方
本明細書中の本発明を使用して、NECを発症するリスクのある未熟児をチューブ給餌する際に使用されるのに適切な生成物の処方
凍結保護剤へのクエン酸塩の添加は、凍結保護剤へのクエン酸塩の添加は、凍結乾燥されたラクトバチルス・ロイテリ(Lactobacillus reuteri)DSM17938の活性化時間を短縮する。
培養:
9mlの増殖培地を有するファルコンチューブ(表1参照)に凍結ストックからのラクトバチルス・ロイテリ(Lactobacillus reuteri)DSM17938を接種した。前培養物を、37℃で16時間インキュベートした。この後に、第1の前培養物の5mlを45mlの新鮮な培地に添加する第2の前培養ステップを行った。第2の前培養物は、≧13の光学密度(600nm)に到達するようにした(約24時間)。
凍結乾燥前に、細菌懸濁液を1mlの体積でゴム栓付きの5mlのフリーズドライバイアル中に等分した。以下の凍結乾燥プログラムを実行した:
細菌の定量のためのサンプルを2つの部分に分配する前の培養物から取り出した。生存率を決定するために、これらの結果を後で、凍結乾燥サンプルの分析と比較した。
DNeasy(登録商標)Blood & Tissue Handbook(カタログ番号69504)(プロトコル:グラム陽性菌の前処理によるわずかに変更)
プライマー:DSM17f2 (TACGGGGAACGAGTTATTGC)およびDSM17r2 (GGACGGCTTAACAAAACAGC);生成物サイズ216bp
プライマーを有するMastermix 反応ごとの体積
水(PCR品質) 3.0μl
プライマー, forw. (10 pmol/μl) 1.0μl
プライマー, rev. (10 pmol/μl) 1.0μl
BSA (最終濃度 0.1 μg/μl) 2.5μl
DreamTaq 12.5μl
凍結乾燥DSM17938の2つの変異体(CおよびN)の人工腸培地(STMmod 3、表4参照)における活性化時間を、経時的な濁りの変化を測定するコンピュータ制御インキュベータ/リーダー/シェーカー(BioScreen C MBR)を使用して分析した。培地STMmod 3を使用して、腸内の状態を模倣した。
PCR:
DSM17938特異的プライマーを用いたPCRを、発酵槽培養物上のDNA抽出について行い、正確な細菌が培養されたことを確認した。結果は実際に、DSM17938が発酵槽で培養されたことを示す(図2)。
凍結乾燥後のDSM17938の生存率は、クエン酸塩ありで凍結乾燥された細菌(C)で約13%およびクエン酸塩なしで凍結乾燥された細菌(N)で12%であることが決定された(表5参照)。
濁度実験の結果は、DSM17938のフリーズドライされた培養物が、凍結保護剤がクエン酸塩を含む場合、より短い時間でOD中3%上昇に達したことを明らかにした(図3参照)。
Claims (13)
- 休眠後のより速い活性を有する再構成された生ラクトバチルス・ロイテリ(Lactobacillus reuteri)DSM17938細菌の投与から恩恵を受ける状態の新生児、未熟児、または乳児の治療における使用のための、クエン酸塩を含む調製物にラクトバチルス・ロイテリ(Lactobacillus reuteri)DSM17938細菌を曝露することを含む活性化されたラクトバチルス・ロイテリ(Lactobacillus reuteri)DSM17938細菌を調製する方法であって、
ここで、前記ラクトバチルス・ロイテリ(Lactobacillus reuteri)DSM17938細菌は、外部電子受容体としてクエン酸塩を利用する能力を有し、
前記調製物中の前記細菌は、凍結、凍結乾燥又はフリーズドライされ、
前記クエン酸塩は、凍結、凍結乾燥又はフリーズドライされた調製物中に存在し;および/または前記クエン酸塩は、前記新生児、未熟児、または乳児への投与のための最終処方中に存在し、
前記凍結、凍結乾燥又はフリーズドライされた調製物は、前記新生児、未熟児、または乳児への投与前に最終処方として再構成され、並びに
前記新生児、未熟児、または乳児は、口からの摂食が困難であるか、或いは授乳又は口からの摂食が不可能である、
上記方法。 - 休眠後のより速い活性を有する再構成された生ラクトバチルス・ロイテリ(Lactobacillus reuteri)DSM17938細菌の投与から恩恵を受ける状態の新生児、未熟児、または乳児の治療において使用するための、(i)クエン酸塩を外部電子受容体として利用する能力を有する生ラクトバチルス・ロイテリ(Lactobacillus reuteri)DSM17938細菌、および(ii)クエン酸塩を含む調製物であって、
前記調製物中の前記細菌は、凍結、凍結乾燥又はフリーズドライされ、
前記クエン酸塩は、凍結、凍結乾燥又はフリーズドライされた調製物中に存在し;および/または前記クエン酸塩は、前記新生児、未熟児、または乳児への投与のための最終処方中に存在し、
前記凍結、凍結乾燥又はフリーズドライされた調製物は、前記新生児、未熟児、または乳児への投与前に最終処方として再構成され、並びに
前記新生児、未熟児、または乳児は、口からの摂食が困難であるか、或いは授乳又は口からの摂食が不可能である、
上記調製物。 - 休眠後のより速い活性を有する再構成された生ラクトバチルス・ロイテリ(Lactobacillus reuteri)DSM17938細菌の投与から恩恵を受ける状態の新生児、未熟児、または乳児の治療において使用するためのクエン酸塩活性化ラクトバチルス・ロイテリ(Lactobacillus reuteri)DSM17938細菌を含む調製物であって、
前記調製物中の前記細菌は、凍結、凍結乾燥又はフリーズドライされ、
前記クエン酸塩は、凍結、凍結乾燥又はフリーズドライされた調製物中に存在し;および/または前記クエン酸塩は、前記新生児、未熟児、または乳児への投与のための最終処方中に存在し、
前記凍結、凍結乾燥又はフリーズドライされた調製物は、前記新生児、未熟児、または乳児への投与前に最終処方として再構成され、並びに
前記新生児、未熟児、または乳児は、口からの摂食が困難であるか、或いは授乳又は口からの摂食が不可能である、
上記調製物。 - クエン酸塩の前記利用は、前記細菌の改善された増殖速度をもたらす、請求項2又は3に記載の調製物。
- 前記細菌が糖に曝露される、請求項2〜4のいずれか一項に記載の調製物。
- 前記糖がラクトースである、請求項5に記載の調製物。
- 前記クエン酸塩は、0.01mg/ml〜10mg/mlの濃度で前記調製物中に存在する、請求項2〜6のいずれか一項に記載の調製物。
- 前記クエン酸塩は、0.1mg/ml〜2.0mg/mlの濃度で前記調製物中に存在する、請求項2〜6のいずれか一項に記載の調製物。
- 前記調製物は、クエン酸塩/ラクトース比 1:10〜1:600で含む、請求項6〜8のいずれか一項に記載の調製物。
- 前記調製物は、クエン酸塩/ラクトース比 1:60〜1:600又は1:30〜1:300で含む、請求項6〜8のいずれか一項に記載の調製物。
- 前記新生児、未熟児、または乳児は、腸内で栄養素を欠いている若しくは栄養素が限られている対象であるか、又は腸内の栄養素の量が医学的理由により意図的に制限されている対象であるか、又は非経口若しくは静脈栄養を必要とする対象である、請求項2〜10のいずれか一項に記載の調製物。
- 前記新生児、未熟児、または乳児は、壊死性腸炎(NEC)を有する対象であるか、又はNECを発症するリスクがある、請求項2〜11のいずれか一項に記載の調製物。
- 前記新生児、未熟児、または乳児が、ヒトである、請求項2〜12のいずれか一項に記載の調製物。
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FR2967070B1 (fr) * | 2010-11-05 | 2013-07-05 | Oreal | Acide gras monoinsature pour prevenir et/ou traiter les imperfections du teint de la peau |
EP2408171A1 (en) * | 2010-07-16 | 2012-01-18 | Research In Motion Limited | Application programming interface for mapping application |
CA2822660C (en) * | 2010-12-31 | 2021-09-07 | Abbott Laboratories | Synbiotic combination of probiotic and human milk oligosaccharides |
JP5622110B2 (ja) * | 2011-02-21 | 2014-11-12 | 株式会社農 | 新規乳酸菌 |
JP6051112B2 (ja) * | 2013-06-05 | 2016-12-27 | 公立大学法人大阪府立大学 | 白金族金属の回収方法 |
CN104206539A (zh) * | 2014-08-14 | 2014-12-17 | 澳优乳业(中国)有限公司 | 一种益生菌婴幼儿奶粉 |
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CY1126127T1 (el) | 2023-11-15 |
WO2016113363A1 (en) | 2016-07-21 |
CN107427461B (zh) | 2021-04-13 |
ES2952585T3 (es) | 2023-11-02 |
EP3244903A1 (en) | 2017-11-22 |
PL3244903T3 (pl) | 2023-08-14 |
EP3244903C0 (en) | 2023-06-07 |
AU2016208007A1 (en) | 2017-07-06 |
US20170304376A1 (en) | 2017-10-26 |
EP3244903B1 (en) | 2023-06-07 |
JP2018503684A (ja) | 2018-02-08 |
HK1247561A1 (zh) | 2018-09-28 |
CN107427461A (zh) | 2017-12-01 |
AU2016208007B2 (en) | 2021-09-09 |
CL2017001722A1 (es) | 2018-04-06 |
RS64392B1 (sr) | 2023-08-31 |
HUE062482T2 (hu) | 2023-11-28 |
BR112017014192A2 (pt) | 2018-03-06 |
BR112017014192B1 (pt) | 2022-02-01 |
CA2972963C (en) | 2023-03-14 |
HRP20230639T1 (hr) | 2023-09-29 |
MX2017009247A (es) | 2017-10-12 |
CA2972963A1 (en) | 2016-07-21 |
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