JP5558475B2 - ニワトコ抽出物とl.パラカゼイ、l.カゼイ、l.ブルガリクスまたはs.サーモフィルスの菌株との組合せを含む組成物 - Google Patents
ニワトコ抽出物とl.パラカゼイ、l.カゼイ、l.ブルガリクスまたはs.サーモフィルスの菌株との組合せを含む組成物 Download PDFInfo
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- JP5558475B2 JP5558475B2 JP2011531498A JP2011531498A JP5558475B2 JP 5558475 B2 JP5558475 B2 JP 5558475B2 JP 2011531498 A JP2011531498 A JP 2011531498A JP 2011531498 A JP2011531498 A JP 2011531498A JP 5558475 B2 JP5558475 B2 JP 5558475B2
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- 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
- A61K35/74—Bacteria
- A61K35/741—Probiotics
- A61K35/744—Lactic acid bacteria, e.g. enterococci, pediococci, lactococci, streptococci or leuconostocs
- A61K35/747—Lactobacilli, e.g. L. acidophilus or L. brevis
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K36/00—Medicinal preparations of undetermined constitution containing material from algae, lichens, fungi or plants, or derivatives thereof, e.g. traditional herbal medicines
- A61K36/18—Magnoliophyta (angiosperms)
- A61K36/185—Magnoliopsida (dicotyledons)
- A61K36/35—Caprifoliaceae (Honeysuckle family)
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P29/00—Non-central analgesic, antipyretic or antiinflammatory agents, e.g. antirheumatic agents; Non-steroidal antiinflammatory drugs [NSAID]
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P31/00—Antiinfectives, i.e. antibiotics, antiseptics, chemotherapeutics
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P31/00—Antiinfectives, i.e. antibiotics, antiseptics, chemotherapeutics
- A61P31/12—Antivirals
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P31/00—Antiinfectives, i.e. antibiotics, antiseptics, chemotherapeutics
- A61P31/12—Antivirals
- A61P31/14—Antivirals for RNA viruses
- A61P31/16—Antivirals for RNA viruses for influenza or rhinoviruses
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P37/00—Drugs for immunological or allergic disorders
- A61P37/02—Immunomodulators
- A61P37/04—Immunostimulants
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- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P43/00—Drugs for specific purposes, not provided for in groups A61P1/00-A61P41/00
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- A—HUMAN NECESSITIES
- A23—FOODS OR FOODSTUFFS; TREATMENT THEREOF, NOT COVERED BY OTHER CLASSES
- A23V—INDEXING SCHEME RELATING TO FOODS, FOODSTUFFS OR NON-ALCOHOLIC BEVERAGES AND LACTIC OR PROPIONIC ACID BACTERIA USED IN FOODSTUFFS OR FOOD PREPARATION
- A23V2002/00—Food compositions, function of food ingredients or processes for food or foodstuffs
Description
a)ニワトコ抽出物とL.パラカゼイ、L.カゼイ、L.ブルガリクスまたはS.サーモフィルスの少なくとも1つの菌株との組合せを調製し、
b)本発明による組成物に対する前記組合せを添加すること
を含む方法により調製することができる。
好ましくは、本発明による組成物は、食品、栄養補助食品、医薬またはOTC(Over The Counter)製品である。
限外濾過:予め希釈されたジュースを、続けて有機または無機膜により1kDaと20kDaとの間の、好ましくは3kDaと10kDaとの間のカットオフ閾値で一極集中させることに基づく透析濾過ステップ(Girard B. and Fukumoto L. R. Membrane processing of fruit juices and beverages: a review. Critical Reviews in Food Science and Nutrition, 2000, 40(2):91−157);
Amberliteタイプの吸収剤ポリマー性樹脂XADのカラムに通す;
水性アルコール(任意の比率の水とC1からC4までのアルコールとの混合物)または酸性pH水溶液による抽出(Bronnum−Hansen K. and Flink J.M. Anthocyanin colorants from elderberry (Sambucus nigra L.) IV. Further studies on production of liquid extracts, concentrates and freeze dried powders. Int. J. Food Sci Tech 1986, 21(2):605−614; Lee J. and Wrolstad R.E. Extraction of Anthocyanins and polyphenolics from blueberry processing waste. J. Food Sci. 2004, 69(7):564−573)。この抽出は、好ましくは、乾燥して粉砕された果粒または新鮮果粒からの裏ごしに直接行うことができる。
好ましくは、毎日の投与計画は1日当たり2単位の用量である。
100mgから1g、好ましくは150mgから500mg、有利には150mgから300mg、およびより好ましくは200mgから250mgのニワトコ固体;および
1×107から1×1011のL.パラカゼイ、L.カゼイ、L.ブルガリクスまたはS.サーモフィルス;
を含む。
3mgから200mg、好ましくは10から100mgおよびより好ましくは20mgから50mgのニワトコアントシアン;
2mgから100mg、好ましくは10mgから20mgのニワトコタンパク質;および
1×107から1×1011のL.パラカゼイ、L.カゼイ、L.ブルガリクスまたはS.サーモフィルス;
を含む。
それと共に、有利なことに相乗効果が記録されている。
これらの《冬の病気》は、我々の免疫防御の弱体化に関連する。
添付図を参照して説明する:
ニワトコ抽出物は、アントシアンを富化したニワトコ果粒ジュースから得て、マルトデキストリンに加えて乾燥する。富化は下記の方法による膜濾過工程を使用して実施した:26リットルの清澄化されたニワトコジュースを284リットルの水(1容量のジュース当たり11容量の水)で希釈する。生じた310リットルを攪拌して45℃に加熱し、次にジュース1容量当たり7容量の水(即ち181L)を添加しながら第1の5kDa膜で透析濾過する。続いて透析透過液を限外濾過により5kDa膜(5.8m2の単位表面積を有する5/10kDのパイロット膜)で濃縮する。限外濾過濃縮水を真空下に50℃を超えない温度で加熱濃縮し、次にマルトデキストリン支持体にマルトデキストリンの量が30%(w/w)以下になるように加えて微細化する。生じる抽出物の特性は:
アントシアン含有率:抽出物の固体含有率を基準にして10〜14重量%(J Agric Food Chem 2004、52、7846−7856)に記載されたHPLC法によりシアニジン−3−グルコシドとして表される)
タンパク質含有率:抽出物の固体含有率を基準にして5〜7重量%(ケルダール法によるN×6.25)。
末梢血単核細胞(PBMC)は、健常被験者から単離して再懸濁し、24ウェルのプレート中に0.5×l06細胞/ウェルで分配する。これらのPBMCを、種々の濃度のニワトコ抽出物(3、10、30、100μg/mlのPBMC細胞培養上清)と共に、ある量のL.パラカゼイ(PBMC1細胞当たり4.5細胞のL.パラカゼイ)を存在させ若しくは存在させずに、またはこれとは別に異なるL.パラカゼイ:PBMC比(0.5:1、1:1、2:1、4.5:1)でニワトコ抽出物を10μg/ml(PBMC細胞培養上清)で存在させ若しくは存在させずにのいずれかで、終夜37℃でインキュベートする。
図1および2は得られた結果を示す:
− 図1は、単独のまたは4.5:1の比のL.パラカゼイ:PBMCと組み合わせたニワトコ抽出物により誘発されたIL−10産生を示す。
− 図2は、単独のまたは10μg/mlのニワトコ抽出物と組み合わせたL.パラカゼイより誘発されたIFN−γ産生を示す。
ニワトコ抽出物とL.パラカゼイCNCM I−1518(DN−114 001)とは非特異的免疫応答に対して相乗的に作用し、したがってヒト免疫系細胞を感染性侵襲または病的炎症性過程に対して、より反応しやすくする。
材料および方法
末梢血単核細胞(PBMC)は健常被験者から単離し、再懸濁して24ウェルプレート中に0.5×l06細胞/ウェルで分配した。これらのPBMCを、異なった菌株:PBMC比(0.5:1、1:1、2:1、4.5:1)で、ニワトコ抽出物を10μg/ml(PBMC細胞培養上清)で存在させまたは存在させずに、終夜37℃でインキュベートする。
ニワトコ抽出物/菌株の組合せが相乗効果を生じるかを決定するために、Etievant C.らの報告(上記を参照されたい)に記載された方法を使用した。この報告は、理論曲線のプロットと比較して実験結果の比較および解釈を教示する。
図3から7は得られた結果を示す:
− 図3は、L.パラカゼイ単独または10μg/mlのニワトコ抽出物との組合せにより誘発されたIL−6の産生(10μg/mlの濃度のニワトコ抽出物で得られたサイトカイン濃度は7.7ng/mlである)を表し;
− 図4は、L.カゼイ単独または10μg/mlのニワトコ抽出物との組合せにより誘発されたIL−6の産生(10μg/mlの濃度のニワトコ抽出物で得られたサイトカイン濃度は2.2ng/mlである)を表し;
− 図5は、L.ブルガリクス単独または10μg/mlのニワトコ抽出物との組合せにより誘発されたIL−6の産生(10μg/mlの濃度のニワトコ抽出物で得られたサイトカイン濃度は2.0ng/mlである)を表し;
− 図6は、S.サーモフィルス単独または10μg/mlのニワトコ抽出物との組合せにより誘発されたIL−6の産生(10μg/mlの濃度のニワトコ抽出物で得られたサイトカイン濃度は2.4ng/mlである)を表し;
− 図7は、L.ブレビス単独または10μg/mlのニワトコ抽出物との組合せにより誘発されたIL−6の産生(10μg/mlの濃度のニワトコ抽出物で得られたサイトカイン濃度は6.0ng/mlである)を表す。
ニワトコ抽出物とL.パラカゼイとは非特異的免疫応答に対して相乗的に作用し、したがってヒト免疫系細胞を感染性侵襲または病的炎症性過程に対して、より反応しやすくすることが確認された。
序
実施例2および3で示したように、ニワトコ果粒抽出物およびL.パラカゼイDN−114 001などのプロバイオティクスはインビトロにおいて、増大したサイトカイン産生を生じるように相乗的に作用する。この検討の目的は免疫機能に対する完全剤形のインビボでの効果を評価して、その活性を各成分群:
− L.パラカゼイ+乳製ミックス;
− ニワトコ果粒抽出物;
− ビタミンおよび無機塩のミックス=ビタミン+ミネラル;
と比較することであった。
完全剤形は以下の成分の組合せ、すなわちL.パラカゼイ+乳製品ミックス、ニワトコ果粒抽出物、ビタミンと無機塩と賦形剤とのミックスである。成分の3群の各成分についての投与量は、完全剤形中に存在する成分の対応する量に等しい。
動物および処置
7週齢のBALB/c雌マウスを、5群の1群に無作為に割り当てた:
第1群→担体(滅菌水)
第2群→完全剤形(1500mg/kg)
第3群→L.パラカゼイDN−114 001+乳製品ミックス(393mg/kg)
第4群→ニワトコ果粒抽出物(296mg/kg)
第5群→ビタミン+ミネラル(282mg/kg)
標的に対する細胞溶解活性はCytoTox 96非放射性細胞傷害性アッセイを使用して決定した。脾細胞をマウスから捕集して、YAC−1細胞(マウスTリンパ腫細胞ライン)を標的細胞として、適当なエフェクター対標的細胞の計数比で、96ウェルV底プレート中で共培養した。37℃で4時間インキュベートした後、放出された乳酸デヒドロゲナーゼ(LDH)の量を上清中で測定した。放出されたLDH量はLDH基質を使用して測定し、490nmで評価した。各マウスについて、3通りのエフェクター/標的比(100:1、50:1、および25:1)における平均のNKの細胞傷害性(%)を以下の式を使用して決定した:
[A490実験放出−(A490エフェクター細胞自発放出+A490標的細胞自発放出)×100]/(A490標的細胞最大放出−A490標的細胞自発放出)。
統計分析はWindows用のSigmaStat3.5パッケージを使用して実施した。結果は一元配置分散分析を用いて、続いてHolm−Sidak法を使用する多重比較群(multiple comparison group)により評価した。前例において、P<0.05で統計的に有意と見なした。
完全剤形または各成分を投与されたマウスの脾細胞の細胞傷害活性を研究した。完全剤形で免役されたマウスの脾細胞は、担体(水)を投与されたマウスに比較して、YAC−1標的細胞に対して有意に増大した細胞傷害活性を発揮した(図8)。対照的に、個々の成分で免役されたマウスは、YAC−1標的細胞に対する細胞傷害活性を増大することはなかった。
これらのデータは、NK細胞の活性化に対して個々では効率の悪い成分の組合せが、適当な量で組み合わされると十分有効になることを明確に示す。
1.Di Santo, J.P. Natural killer cell developmental pathways: a question of balance. Annu. Rev. Immunol. 24, 257−286 (2006)
2.Vivier, E., Tomasello, E., Baratin, M., Walzer, T. & Ugolini, S. Functions of natural killer cells. Nat. Immunol. 9, 503−510 (2008)
3.Lodoen, M. B. & Lanier, L.L. Natural killer cells as an initial defense against pathogens. Curr. Opin. Immunol. 18, 391−398 (2006)
如何なるタイプの栄養補助食品も考慮に入れることができた。例として、単位用量は1gのカプセルまたは2gの錠剤にすることができた。一般的組成物は以下の通りである:
ニワトコ固体(実施例1による) 30%
L.パラカゼイDN−114 001を含む発酵乳粉末 40%
ビタミンミックス(ビタミンC、EおよびB6) 24〜27%
グルコン酸亜鉛(亜鉛) 2〜5%
セレン酸ナトリウム(セレン) 0.1〜0.5%
それ故、調製工程の終了時の錠剤またはカプセルのL.パラカゼイDN−114 001の個体数は、2×1010CFUである。
単位用量は100mlの発酵乳製品に相当する。しかしながら、例えば、100gのActimel(登録商標)は、考慮されるレシピが低カロリーかまたは標準かに依存して94〜97mlの製品に相当することは注意すべきである。
− L.パラカゼイDN−114 001菌株(CNCM I−1518)(Actimel(登録商標)タイプの製品)により、およびラクトバチルス・ブルガリクスおよびストレプトコッカス・サーモフィルスの市販の菌株により発酵した95%の乳製品;
− 実施例1に記載したような濃縮されたニワトコ抽出物ジュースを5%含有する、5%の伝統的な赤色フルーツ製剤;
を含有する。
− 標準的スキムミルク77%(乳タンパク質3.64%)
− 低温殺菌されたクリーム9.6%
− 濃縮されたスキムミルク5.7%
− スキムミルクタンパク質0.6%
− スクロース6.6%
− デキストロ−ス(Cargill)0.5%
− DN−114 001(CNCM I−1518)発酵物:108〜109CFU/ml
− 全体的に107CFU/mlから108CFU/mlの個体数のL.ブルガリクスおよびS.サーモフィルスの数種の市販の菌株からなる発酵物。
この製品100g当たり250mgのニワトコ固体、即ち単位用量に対して、単位用量の固体重量を基準にして1.47重量%のニワトコ固体である。
L.パラカゼイ個体数:100mlの発酵製品に対して108CFU/mlである。
Claims (12)
- ニワトコ抽出物と、ラクトバチルス・パラカゼイ、ラクトバチルス・カゼイ、ラクトバチルス・ブルガリクスまたはストレプトコッカス・サーモフィルスの少なくとも1つの菌株との組合せを含み、キャッツクロー、パウダルコ、スクテラリア・バイカレンシスおよびアルテミシニンの混合物を含まない、食品、栄養補助食品または医薬である、組成物。
- ニワトコ抽出物と、ラクトバチルス・パラカゼイの少なくとも1つの菌株との組合せを含む、請求項1に記載の組成物。
- ニワトコ抽出物が、該抽出物の固形分を基準にして0.5重量%と25重量%との間のアントシアン、および抽出物の固形分を基準にして2重量%と10重量%との間のタンパク質を含有する、請求項1または2に記載の組成物。
- 1×107CFU/単位用量と1×1011CFU/単位用量との間の量のL.パラカゼイ、L.カゼイ、L.ブルガリクスまたはS.サーモフィルスを含有する、請求項1〜3のいずれか一項に記載の組成物。
- 前記食品が、乳製品、発酵乳製品、ヨーグルト、発酵乳、乳幼児用ミルク、散剤、トローチ剤、野菜ジュース、飲料およびそれらの混合物からなる群から選択される、請求項1〜4のいずれか一項に記載の組成物。
- 前記食品が、新鮮な乳製品、果物および/または野菜ジュース、およびフルーツピューレからなる群から選択される、請求項1〜5のいずれか一項に記載の組成物。
- 内服用錠剤、チュアブル錠、発泡錠、カプセル剤、トローチ剤、丸薬、散剤、顆粒剤、経口液剤または懸濁剤、ならびに、舌下およびバッカルの投与形態からなる群から選択される生薬の形態である栄養補助食品または医薬である、請求項1〜4のいずれか一項に記載の組成物。
- 単位用量当たり150mgと300mgとの間のニワトコ固形分、および単位用量当たり1×107CFUと1×1011CFUとの間のL.パラカゼイ、L.カゼイ、L.ブルガリクスまたはS.サーモフィルスを含有する、請求項1〜7のいずれか一項に記載の組成物。
- 単位用量当たり200mgと250mgとの間のニワトコ固形分、および単位用量当たり1×10 7 CFUと1×10 11 CFUとの間のL.パラカゼイ、L.カゼイ、L.ブルガリクスまたはS.サーモフィルスを含有する、請求項1〜8のいずれか一項に記載の組成物。
- 医薬として用いられる、請求項1〜9のいずれか一項に記載の組成物。
- 免疫を刺激しおよび/または免疫防御を増強しおよび/または抗感染性および/または抗炎症応答を促進するための、請求項1〜9のいずれか一項に記載の組成物。
- インフルエンザウイルスによる感染によって引き起こされるインフルエンザ病態の症状の治療および/または予防に用いられる、請求項1〜11のいずれか一項に記載の組成物。
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Application Number | Priority Date | Filing Date | Title |
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FR0857102 | 2008-10-17 | ||
FR0857102A FR2937252B1 (fr) | 2008-10-17 | 2008-10-17 | Association d'un extrait de sureau et d'une souche de l. paracasei. |
PCT/EP2009/063534 WO2010043696A1 (en) | 2008-10-17 | 2009-10-16 | Composition comprising a combination of an elder extract and a strain of l. paracasei, l. casei, l. bulgaricus or s. thermophilus |
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JP2011531498A Active JP5558475B2 (ja) | 2008-10-17 | 2009-10-16 | ニワトコ抽出物とl.パラカゼイ、l.カゼイ、l.ブルガリクスまたはs.サーモフィルスの菌株との組合せを含む組成物 |
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US (1) | US8734784B2 (ja) |
EP (1) | EP2349294B1 (ja) |
JP (1) | JP5558475B2 (ja) |
CN (1) | CN102186486B (ja) |
AR (1) | AR073890A1 (ja) |
CA (1) | CA2740560C (ja) |
ES (1) | ES2433209T3 (ja) |
FR (1) | FR2937252B1 (ja) |
RU (1) | RU2537185C2 (ja) |
TW (1) | TW201021816A (ja) |
WO (1) | WO2010043696A1 (ja) |
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US20130121976A1 (en) | 2010-03-12 | 2013-05-16 | Agusti Montserrat Carreras | Lactic Acid Bacteria for Coeliac Disease |
WO2011141762A1 (en) | 2010-05-12 | 2011-11-17 | Compagnie Gervais Danone | Synergistic fermentation of lactobacillus rhamnosus and lactobacillus paracasei subsp paracasei |
DE102010055170A1 (de) * | 2010-12-20 | 2012-06-21 | Maria Clementine Martin Klosterfrau Vertriebsgesellschaft Mbh | Verfahren zur Herstellung alkoholfreier Zusammensetzungen auf pflanzlicher Basis sowie auf diese Weise hergestellte Zusammensetzungen und deren Verwendung |
WO2014038929A1 (en) | 2012-09-07 | 2014-03-13 | N.V. Nutricia | Probiotics for producing antiviral factors |
EP2710901A1 (en) * | 2012-09-20 | 2014-03-26 | Symrise AG | Dietary supplement compositions |
FR3004109B1 (fr) * | 2013-04-09 | 2016-01-01 | Pf Medicament | Composition comprenant une association d'un extrait de sureau et d'une souche de lactobacillus rhamnosus |
MA42041A (fr) * | 2015-05-07 | 2018-03-14 | Gervais Danone Sa | Fabrication de produits laitiers fermentés égouttés |
CN105639385A (zh) * | 2016-02-02 | 2016-06-08 | 南京通孚轻纺有限公司 | 一种婴儿舒适水及其制备方法 |
WO2018220416A1 (en) * | 2017-05-31 | 2018-12-06 | Compagnie Gervais Danone | Lactobacillus paracasei strain capable of improving the immune response to a viral-bacterial coinfection |
TWI797780B (zh) * | 2021-10-15 | 2023-04-01 | 大江生醫股份有限公司 | 接骨木莓磁場發酵物之製備方法及其用於製備促進硬骨生成、增強免疫力或抗氧化的組合物之用途 |
CN113861303B (zh) * | 2021-10-21 | 2023-04-21 | 华南理工大学 | 一种从德氏乳杆菌和嗜热链球菌发酵酸奶中分离出的胞外多糖及其应用 |
CN113995015A (zh) * | 2021-11-17 | 2022-02-01 | 合肥工业大学 | 一种控制酸奶后酸化的方法 |
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DK32788D0 (da) * | 1988-01-25 | 1988-01-25 | Hansens Lab A S Chr | Fremgangsmaade til fremstilling af en drik |
ES2126962T3 (es) | 1995-01-02 | 1999-04-01 | Gervais Danone Co | Fermento lactico, y su uso para la preparacion de productos antidiarreicos. |
EP1151673A3 (en) * | 2000-05-03 | 2002-01-02 | Societe Des Produits Nestle S.A. | Confectionery product having a filling |
FR2809312B1 (fr) * | 2000-05-25 | 2002-07-12 | Gervais Danone Sa | Utilisation de l. casei dans des compositions immunostimulantes |
FR2863828B1 (fr) | 2003-12-23 | 2007-02-02 | Gervais Danone Sa | Produit alimentaire liquide comprenant des granules de bacteries lactiques |
US20060233895A1 (en) * | 2005-04-15 | 2006-10-19 | Brown Paul R | Herbal remedy for treating Lyme disease |
IL173207A0 (en) * | 2006-01-17 | 2006-06-11 | Healthcare Brands Internat Ltd | Treatment of avian flu with black elderberry extract |
DE602007001324D1 (de) * | 2006-10-13 | 2009-07-30 | Gervais Danone Sa | Neue Zusammensetzung zur Verbesserung des Hautzustandes und Verfahren zu ihrer Herstellung |
FR2912657B1 (fr) | 2007-02-16 | 2009-04-17 | Gervais Danone Sa | Utilisation de lactobacillus casei pour renforcer la protection induite par la vaccination anti-grippale. |
DE202007008818U1 (de) * | 2007-06-21 | 2008-07-24 | Maria Clementine Martin Klosterfrau Vertriebsgesellschaft mit beschränkter Haftung | Zusammensetzung zur Behandlung von Infekten |
CN101253923A (zh) * | 2008-02-06 | 2008-09-03 | 周波 | 一种冷冻饮品 |
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Publication number | Publication date |
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US8734784B2 (en) | 2014-05-27 |
FR2937252A1 (fr) | 2010-04-23 |
RU2537185C2 (ru) | 2014-12-27 |
CA2740560C (en) | 2017-01-31 |
EP2349294B1 (en) | 2013-08-28 |
CN102186486B (zh) | 2013-07-24 |
CN102186486A (zh) | 2011-09-14 |
WO2010043696A1 (en) | 2010-04-22 |
AR073890A1 (es) | 2010-12-09 |
ES2433209T3 (es) | 2013-12-09 |
RU2011115977A (ru) | 2012-11-27 |
JP2012505862A (ja) | 2012-03-08 |
US20110262409A1 (en) | 2011-10-27 |
CA2740560A1 (en) | 2010-04-22 |
TW201021816A (en) | 2010-06-16 |
FR2937252B1 (fr) | 2011-05-20 |
EP2349294A1 (en) | 2011-08-03 |
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