JP6859313B2 - 軟骨破壊における使用のための組成物 - Google Patents
軟骨破壊における使用のための組成物 Download PDFInfo
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- JP6859313B2 JP6859313B2 JP2018230353A JP2018230353A JP6859313B2 JP 6859313 B2 JP6859313 B2 JP 6859313B2 JP 2018230353 A JP2018230353 A JP 2018230353A JP 2018230353 A JP2018230353 A JP 2018230353A JP 6859313 B2 JP6859313 B2 JP 6859313B2
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- oleuropein
- cartilage destruction
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Description
本発明をさらに詳細に考察する前に、以下の用語及び表記法を最初に定義する。
オレウロペインは、炎症及び骨代謝に有益な効果を有することが以前に示されているポリフェノールである。ヒドロキシチロソールは関連する化合物であり、オレウロペインの代謝産物であり、また、それらの効果を有することが示されている。本発明者らは、本発明において、驚くべきことに、オレウロペイン及びヒドロキシチロソールは、各々が軟骨破壊に対して有益な効果を有することも示している。
主な生理活性化合物:
オレウロペイン、ヒドロキシチロソール、クルクミン、及びケルセチンは本発明による主な生理活性分子である。それらは任意の適切な供給源由来であり得る。好ましい実施形態において、オレウロペイン、ヒドロキシ、クルクミン、及びケルセチンは植物供給源から得られる。オレウロペイン及びヒドロキシチロソールは例えばオリーブ植物から得られる。
本発明による使用のための組成物はまた、少なくとも1種のさらなる生理活性化合物、例えば、抗酸化剤、抗炎症化合物、グリコサミノグリカン、プレバイオティクス、繊維、プロバイオティクス、脂肪酸、ミネラル、微量元素、及び/又はビタミンからなる群から選択される化合物を含み得る。
抗炎症化合物との組み合わせ:
本発明は、一態様において、軟骨破壊を防止又は治療するための使用のための組成物に関する。
グリコサミノグリカンは、健康な軟骨中に存在する、大きな、強く荷電した分子である。グリコサミノグリカンの例はグルコサミン及びコンドロイチン硫酸である。
一部の実施形態において、本発明による使用のための組成物は1種又は複数種のプレバイオティクスを含む。プレバイオティクスの非限定的な例は、アカシアガム、アルファグルカン、アラビノガラクタン、ベータグルカン、デキストラン、フラクトオリゴ糖、フコシルラクトース、ガラクトオリゴ糖、ガラクトマンナン、ゲンチオオリゴ糖、グルコオリゴ糖、グアーガム、イヌリン、イソマルトオリゴ糖、ラクトネオテトラオース、ラクトスクロース、ラクツロース、レバン、マルトデキストリン、ミルクオリゴ糖、部分加水分解グアーガム、ペクチンオリゴ糖、難消化性デンプン、老化デンプン、シアロオリゴ糖、シアリルラクトース、ダイズオリゴ糖、糖アルコール、キシロオリゴ糖、それらの加水分解物、又はそれらの組み合わせを含む。
本発明による使用のための組成物は繊維を含み得る。繊維は、可溶性繊維、不溶性繊維、又はそれらの組み合わせであり得る。可溶性繊維は、例えば、フラクトオリゴ糖、アカシアガム、イヌリン、寒天、アルギン酸塩、イナゴマメ、カラギーナン、アラビアガム、グアーガム、カラヤガム、ペクチン又はキサンタンガムなどを含み得るが、これらの可溶性繊維は加水分解又は非加水分解の形態である。不溶性繊維は、例えば、エンドウ豆の外側繊維を含み得る。
本発明による使用のための組成物は1種又は複数種のプロバイオティクスを含み得る。プロバイオティクスの非限定的な例は、アエロコッカス属(Aerococcus)、アスペルギルス属(Aspergillus)、バクテロイデス属(Bacteroides)、ビフィドバクテリウム属(Bifidobacterium)、カンジダ属(Candida)、クロストリジウム属(Clostridium)、デバリオマイセス属(Debaromyces)、エンテロコッカス属(Enterococcus)、フゾバクテリウム属(Fusobacterium)、ラクトバチルス属(Lactobacillus)、ラクトコッカス属(Lactococcus)、ロイコノストック属(Leuconostoc)、メリッソコッカス属(Melissococcus)、ミクロコッカス属(Micrococcus)、ムコール属(Mucor)、オエノコッカス属(Oenococcus)、ペディオコッカス属(Pediococcus)、ペニシリウム属(Penicillium)、ペプトストレプトコッカス属(Peptostrepococcus)、ピキア属(Pichia)、プロピオニバクテリウム属(Propionibacterium)、シュードカテニュレイタム属(Pseudocatenulatum)、リゾプス属(Rhizopus)、サッカロミセス属(Saccharomyces)、ブドウ球菌属(Staphylococcus)、連鎖球菌属(Streptococcus)、トルロプシス属(Torulopsis)、ワイセラ属(Weissella)、非複製性微生物、及びそれらの組み合わせを含む。
本発明による組成物中に含まれ得るミネラル及び微量元素の例は、ミネラル元素及び微量元素、例えば、カルシウム、マグネシウム、ナトリウム、カリウム、リン、銅、亜鉛、鉄、セレン、クロミウム、及びモリブデン、並びにそれらの組み合わせを含む。
本発明による使用のための組成物はまた、ビタミンA、ビタミンD、ビタミンE、ビタミンK、ビタミンC、葉酸、チアミン、リボフラビン、ビタミンB6、ビタミンB12、ナイアシン、ビオチン、及びパントテン酸から選択される1種又は複数種のさらなるビタミンを含み得る。
本発明による使用のための組成物は、主な生理活性成分であるオレウロペイン、ヒドロキシチロソール、クルクミン及びケルセチンを、各々、1食当たり0.01mg〜約1g、好ましくは0.1mg〜1g、さらに好ましくは1mg〜約1gの量で含み得る。
本発明による使用のための組成物は栄養組成物又は医薬組成物であり得、また、ヒト又は動物用のものであり得る。
タンパク質源:
一実施形態において、本発明による使用のための組成物はタンパク質の供給源を含む。タンパク質源は、動物性タンパク質(例えば、乳タンパク質、食肉タンパク質、又は卵タンパク質)、植物性タンパク質(例えば、ダイズタンパク質、コムギタンパク質、米タンパク質、及びエンドウマメタンパク質)、又はそれらの組み合わせを含む(但し、これらに限定されない)食物タンパク質であり得る。一実施形態において、タンパク質は、乳清、チキン、トウモロコシ、カゼイン、コムギ、アマ、ダイズ、イナゴマメ、エンドウマメ、又はそれらの組み合わせからなる群から選択される。
一実施形態において、組成物は炭水化物の供給源を含む。デンプン、ショ糖、乳糖、ブドウ糖、果糖、コーンシロップ固形物、マルトデキストリン、加工デンプン、アミロースデンプン、タピオカデンプン、トウモロコシデンプン、キシリトール、ソルビトール、又はそれらの組み合わせを含む(但し、これらに限定されない)任意の適切な炭水化物が本発明の組成物中で使用され得る。
一実施形態において、組成物は脂肪の供給源を含む。脂肪の供給源は、任意の適切な脂肪又は脂肪混合物を含み得る。例えば、脂肪源は、植物性脂肪(例えば、オリーブ油、トウモロコシ油、ヒマワリ油、高オレイン酸ヒマワリ油、ナタネ油、キャノーラ油、ヘーゼルナッツ油、ダイズ油、パーム油、ココナッツ油、クロフサスグリ種子油、ボラージ油、レシチン)、及び動物性脂肪(例えば乳脂肪)、又はそれらの組み合わせを含む(但し、これらに限定されない)。脂肪の供給源は、また、上に列挙する脂肪のあまり精製されていない形態(例えば、ポリフェノール含量についてのオリーブ油)であり得る。
さらに、本発明による使用のための組成物は、天然又は人工の香味料、例えば、バナナ、オレンジ、モモ、パイナップル、ラズベリーなどの果実香味料、又はバニラ、ココア、コーヒーなどの他の植物香味料も含み得る。
栄養組成物は、主な生理活性成分及び任意のさらなる生理活性成分以外に、任意選択で、1種又は複数種のタンパク質、炭水化物及び脂肪源、従来の食品添加物(合成又は天然)、例えば、1種又は複数種の酸味料、追加の増粘剤、pH調整用の緩衝剤又は薬剤、キレート剤、着色剤、乳化剤、賦形剤、香味剤、ミネラル、浸透剤、薬学的に許容される担体、保存剤、安定剤、糖、甘味料、テクスチャライザー、及び/又はビタミンを含む任意の数の任意選択の追加の食品成分を含み得る。任意選択の成分は任意の適切な量で添加することができる。
本開示の栄養組成物は、ヒトへの投与のため、特に、胃腸管の任意の部分における投与のための適切な任意の手段により投与され得る。腸内投与、経口投与、及びチューブ又はカテーテルを介した投与のすべてが本開示の対象となる。栄養組成物はまた、経口、直腸、舌下、唇下、口腔内、局所などから選択される手段により投与され得る。
本発明の組成物は、特に関節軟骨において、軟骨の破壊を減少させることが示されている。
本発明の組成物は軟骨破壊を防止することができることが本明細書に示されている。
オレウロペインは、コラーゲンの分解生成物の出現を減少させることが本明細書に示されている(例えば図8A)。すなわち、オレウロペインは軟骨中のコラーゲン分解を抑制又は減少させるように作用する。
本発明による使用のための組成物はタンパク質分解活性を抑制又は減少させることが示されている。
オレウロペイン、クルクミン及びケルセチンを含む本発明による組成物、又はヒドロキシチロソール、クルクミン及びケルセチンを含む本発明による組成物の両方が、軟骨破壊に関連するプロテアーゼを強く下方制御する。
オレウロペイン及び/又はヒドロキシチロソールと、さらにクルクミン及びケルセチンのうちの少なくとも1種と、を含む本発明の組成物は、軟骨破壊において活性であるプロテアーゼを下方制御し、また、炎症マーカーを下方制御することが示されている。
さらなる実施形態において、本発明は、オレウロペイン及び/又はヒドロキシチロソールを含み、さらに、クルクミン、ケルセチンからなる群から選択される少なくとも1種を含む、本発明による使用のための組成物に関する。
本発明による使用のための組成物の標的集団は、軟骨破壊を呈する任意の哺乳動物であり得る。これは、例えば、任意の哺乳動物は、本明細書で言及される軟骨破壊を含む病的状態のうちの1種又は複数種に罹患するからである。軟骨破壊は、視覚的手段、例えばX線撮影などにより検出され得る。あるいは、軟骨の破壊生成物の検出は体液中で検出され得る。例えば、1種又は複数種のコラーゲンIIエピトープ(Col2−1、Col2−1 NO、CTX−IIなど)は、血漿サンプル又は尿サンプルなどのサンプル中で検出され得る。
本発明は、さらなる態様において、本発明による使用のための栄養組成物を製造する方法であって、
栄養組成物用の成分とオレウロペインを用意し、栄養組成物がオレウロペインを含むように混合するステップ
を含む方法に関する
栄養組成物用の1種又は複数種の成分、オレウロペイン及び/又はヒドロキシチロソール、及び任意選択でさらにクルクミン及びケルセチンのうちの1種又は複数種を用意し、それらを混合するステップ
を含む方法に関する。
さらなる実施形態において、本発明は、本発明による軟骨破壊を抑制又は防止するための使用のための組成物であって、医薬組成物である組成物に関する。
本発明はまた、軟骨破壊、例えば、軟骨破壊が生じる病的状態、又は軟骨破壊に関連する外傷の防止又は治療の方法であって、それを必要とする個体に有効量の本方法による組成物を投与することを含む方法に関する。例えば、本方法は有効量のオレウロペインの投与を含む。他の例において、本発明の方法は、有効量の、オレウロペイン及び/又はヒドロキシチロソールのうちの1種又は複数種を投与することを含む。好ましい実施形態において、治療方法は、オレウロペイン及び/又はヒドロキシチロソールと、1種又は複数種のさらなるポリフェノール、例えば、クルクミン、ケルセチン及びルチンからなる群から選択される1種又は複数種のさらなるポリフェノールと、を含む有効量の本発明による使用のための組成物を投与することを含む。
本発明の態様の1つの状況において記載される実施形態及び特徴は本発明の他の態様にも適用されることに留意されたい。
実施形態1:
軟骨破壊を防止又は治療するための使用のための、オレウロペイン及び/又はヒドロキシチロソールを含む組成物。
実施形態2:
クルクミンをさらに含む、実施形態1に記載の使用のための組成物。
実施形態3:
ケルセチンをさらに含む、実施形態1又は2に記載の使用のための組成物。
実施形態4:
抗酸化剤、抗炎症化合物、グリコサミノグリカン、プレバイオティクス、繊維、プロバイオティクス、脂肪酸、ミネラル、微量元素、及び/又はビタミンからなる群から選択される少なくとも1種の化合物をさらに含む、実施形態1〜3のいずれかに記載の使用のための組成物。
実施形態5:
少なくとも1種の抗炎症化合物をさらに含む、実施形態4に記載の使用のための組成物。
実施形態6:
前記少なくとも1種の抗炎症化合物は植物抽出物である、実施形態4又は5に記載の使用のための組成物。
実施形態7:
前記植物抽出物は、デビルズクロー(ハルパゴフィツム・プロクムベンス(Harpagophytum procumbens))、ロスマリヌス・オフィキナリス(Rosmarinus officinalis)、ヒソップ、ショウガ(ジンギベル・オフィキナレ(Zingiber officinale))、ウコン(クルクマ・ロンガ(Curcuma longa))、アルニカモンタナ(Arnica montana)、ヤナギの樹皮、ザクロ(プニカ・グラナトゥム(Punica granatum))、緑茶(カメリア・シネンシス(Camellia sinensis))、キャッツクロー(ウンカリア・トメトサ(Uncaria tometosa)及びウンカリア・ギアネンシス(Uncaria guianensis))、インディアン・オリバナム(ボスウェリア・セラータ(Boswelia serrata))、及びパイナップルブロメライン(アナナス・コモスス(Ananas comosus))、ブラックシード(ニゲラ・サティバ(Nigella sative))、セイヨウオトギリソウ、ヒペルフォリン、ゴールデンシール、ジャーマンカモミール(マトリカリア・レクティタ(Matricaria recutita))からなる群から選択される1種又は複数種の植物からの抽出物である、実施形態6に記載の使用のための組成物。
実施形態8:
少なくとも1種の抗酸化剤をさらに含む、実施形態4〜7のいずれかに記載の使用のための組成物。
実施形態9:
前記少なくとも1種の抗酸化剤は、アスタキサンチン、カロテノイド、コエンザイムQ10(「CoQ10」)、フラボノイド、グルタチオン、ゴジ(クコ)、ヘスペリジン、ラクトウルフベリー、リグナン、ルテイン、リコピン、ポリフェノール、セレン、ビタミンA、ビタミンC、ビタミンE、ゼアキサンチンからなる群から選択される、実施形態8に記載の使用のための組成物。
実施形態10:
栄養組成物である、実施形態1〜9のいずれかに記載の使用のための組成物。
実施形態11:
医薬組成物である、実施形態1〜9のいずれかに記載の使用のための組成物。
実施形態12:
前記栄養組成物はメディカルフードである、実施形態10に記載の使用のための組成物。
実施形態13:
前記使用は軟骨におけるコラーゲンの分解を抑制又は減少させるためのものである、実施形態1〜12のいずれかに記載の使用のための組成物。
実施形態14:
実施形態1〜13のいずれかに記載の使用のための栄養組成物を製造する方法であって、栄養組成物用の1種又は複数種の成分、オレウロペイン及び/又はヒドロキシチロソール、及び任意選択でさらにクルクミン及びケルセチンのうちの1種又は複数種を用意するステップと、それらを混合するステップと、を含む方法。
実施形態15:
軟骨の破壊を防止又は治療する方法であって、それを必要とする個体に有効量の実施形態1〜13のいずれかに記載の組成物を投与することを含む方法。
本発明は、以下の非限定的な実施例においてさらに詳細に説明される。
材料及び方法:
オレウロペイン: 十分に精製されたオレウロペイン(>98%)をExtrasynthese(Genay,France)から購入した。
ヒドロキシチロソール: 十分に精製されたヒドロキシチロソール(>98%)をExtrasynthese(Genay,France)から購入した。オレウロペインの代謝産物。
ケルセチン: 十分に精製されたケルセチン(>97%)をHWI Analytik GmbH(Ruelzheim,Germany)から購入した。ルチンの代謝産物。
ルチン: 十分に精製されたルチン(>94%)をSigma−Aldrich(Buchs,Switzerland)から購入した。
クルクミン: 十分に精製されたルチン(>70%)をSigma−Aldrich(Buchs,Switzerland)から購入した。
若牛の足を洗浄し、土を除去した。皮膚を足から除去した。関節を横方向に開いた。関節内靭帯を切除した。開いた関節を、リン酸緩衝生理食塩水で洗浄した。外科用メスの刃で軟骨の全層スライスを切り開き、10mM hepes及び1%ペニシリン−ストレプトマイシンを含むDMEM高グルコース中に回収した。軟骨の切片を10mM hepes及び1%ペニシリン−ストレプトマイシンを含むDMEM高グルコース中で洗浄した。
全RNAを40個のビーズのプールから単離し、QiagenからのRNeasyキットを使用して単離した。cDNAはTakaraからのPrimescript 1st strand cDNA Synthesisキットを用いて、RNAの逆転写により得た。ADAMTS−5、COX−2、MMP−13、及びGAPDHのmRNA発現を、リアルタイムPCR(SYBR Green)において定量化した。
図1〜3は、3日間の培養後のGAPDH mRNA発現量により標準化されたADAMTS−5、COX−2及びMMP−13のmRNA発現量を示す。データは、陰性対照(完全培地中で培養された細胞)と比較した遺伝子発現量の変化倍率(fold change)として表した。結果は2−ΔΔCT法に従って算出した。
CTL−: 陰性対照
OLP: オレウロペイン
HTY: ヒドロキシチロソール
QRC: ケルセチン
CUR: クルクミン
IL1a: インターロイキン1アルファ 10ng/ml
動物及び処置:
3週齢の65匹の雄HartleyモルモットをCharles River Laboratories(Paris)から入手した。動物を平底ケージにおいて1ケージ当たり5匹を収容し、ビタミンC(1mg/g)及びビタミンD3(3.4IU/g)を含む標準モルモット食、並びに水を不断給餌した。すべての動物を、オレウロペイン、ルチン、及び/又はクルクミンの投与前に、1週間にわたって収容条件に順応させた。PVCパイプをケージに加えて収容条件を改善し、ストレスを最小限にした。
A群(n=15)には、31週間、1日用量のオレウロペインが与えられた。
B群(n=15)には、31週間、標準食が与えられた(対照)。
C群(n=15)には、31週間、1日用量のルチンが与えられた。
D群(n=15)には、31〜5週間、1日用量のルチン及びクルクミンが与えられた。
E群(n=5、参照群)は、組み入れ時に安楽死させ、いずれの介入も受けなかった。
6時間の断食後の血液を、午前中に、ケタミン/キシラジンによる鎮静作用下、耳の表在静脈で得た。これを、6週間毎に、すなわちW4(=T0)、W10、W16、W22及びW28に行った。W35において、全身麻酔下、安楽死の直前に心臓内穿刺により血液を採取した。
秤量後、動物の安楽死をペントバルビタールナトリウム100mg/kgの心臓内血液穿刺後に実施した。主な重要臓器が観察され、異常(心臓、消化管及び尿管、副腎)が検出された。肝臓及び副腎を秤量した。各動物からの右膝関節を4%緩衝パラホルムアルデヒド中で24時間固定し、続いてパラフィン包埋の前、4℃、4時間のHCl酸(DC2,Labonord,ベルギー)中での脱灰が行われる。
OARSIにより推奨されるように、パラフィンを包埋した右膝を、Cushin面に従って、メニスカスによりカバーされていない中央領域において、6μm切片にミクロトーム(Leica)で切開した。
PGE2を、競合ELISAキット(Arbor Assays,USA)を使用してモルモットの血清中で測定した。
結果(平均±SD)を各パラメータについて算出した。正規性検定に続き、ダネットのポスト検定又はピアソン相関を用いたパラメトリックANOVAをすべての実験で実施した。*p<0.05;**<0.01;***p<0.001。
対照 W35 B群(n=15)には、31週間、標準食が与えられた。
A W35 A群(n=15)には、31週間、1日用量のオレウロペインが与えられた。
C W35 C群(n=15)には、31週間、1日用量のルチンが与えられた。
D W35 D群(n=15)には、31週間、1日用量のルチン及びクルクミンが与えられた。
Claims (16)
- 軟骨破壊を抑制又は減少させるための組成物であって、オレウロペインを含む組成物。
- 外傷又は変形性関節症において生じる軟骨破壊を抑制又は減少させるための組成物であって、オレウロペインを含む組成物。
- クルクミンをさらに含む、請求項1又は2に記載の組成物。
- ケルセチンをさらに含む、請求項1〜3のいずれか一項に記載の組成物。
- グリコサミノグリカン、プレバイオティクス、繊維、プロバイオティクス、脂肪酸、ミネラル、微量元素、及び/又はビタミンからなる群から選択される少なくとも1種の化合物をさらに含む、請求項1〜4のいずれか一項に記載の組成物。
- 少なくとも1種の抗炎症化合物をさらに含む、請求項1〜5のいずれか一項に記載の組成物。
- 前記少なくとも1種の抗炎症化合物は植物抽出物である、請求項6に記載の組成物。
- 前記植物抽出物は、デビルズクロー(ハルパゴフィツム・プロクムベンス(Harpagophytum procumbens))、ロスマリヌス・オフィキナリス(Rosmarinus officinalis)、ヒソップ、ショウガ(ジンギベル・オフィキナレ(Zingiber officinale))、ウコン(クルクマ・ロンガ(Curcuma longa))、アルニカモンタナ(Arnica montana)、ヤナギの樹皮、ザクロ(プニカ・グラナトゥム(Punica granatum))、緑茶(カメリア・シネンシス(Camellia sinensis))、キャッツクロー(ウンカリア・トメトサ(Uncaria tometosa)及びウンカリア・ギアネンシス(Uncaria guianensis))、インディアン・オリバナム(ボスウェリア・セラータ(Boswelia serrata))、及びパイナップルブロメライン(アナナス・コモスス(Ananas comosus))、ブラックシード(ニゲラ・サティバ(Nigella sative))、セイヨウオトギリソウ、ヒペルフォリン、ゴールデンシール、ジャーマンカモミール(マトリカリア・レクティタ(Matricaria recutita))からなる群から選択される1種又は複数種の植物からの抽出物である、請求項7に記載の組成物。
- 少なくとも1種の抗酸化剤をさらに含む、請求項1〜8のいずれか一項に記載の組成物。
- 前記少なくとも1種の抗酸化剤は、アスタキサンチン、カロテノイド、コエンザイムQ10(「CoQ10」)、フラボノイド、グルタチオン、ゴジ(クコ)、ヘスペリジン、ラクトウルフベリー、リグナン、ルテイン、リコピン、ポリフェノール、セレン、ビタミンA、ビタミンC、ビタミンE、ゼアキサンチンからなる群から選択される、請求項9に記載の組成物。
- 栄養組成物である、請求項1〜10のいずれか一項に記載の組成物。
- 医薬組成物である、請求項1〜10のいずれか一項に記載の組成物。
- 前記栄養組成物はメディカルフードである、請求項11に記載の組成物。
- 軟骨におけるコラーゲンの分解を抑制又は減少させるための組成物である、請求項1〜13のいずれか一項に記載の組成物。
- 個体の活動性及び/又は可動性を維持又は改善するための組成物である、請求項1〜14のいずれか一項に記載の組成物。
- 関節痛を減少させるための組成物である、請求項1〜15のいずれか一項に記載の組成物。
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EP3003338A1 (en) * | 2013-05-29 | 2016-04-13 | Nestec S.A. | Compositions for use in cartilage breakdown |
JP6588013B2 (ja) * | 2013-10-14 | 2019-10-09 | ソシエテ・デ・プロデュイ・ネスレ・エス・アー | 滑膜炎の治療及び予防のための抗炎症植物性栄養素 |
JP6497675B2 (ja) * | 2015-01-22 | 2019-04-10 | 国立研究開発法人産業技術総合研究所 | 活動量の低下及び/又は不安の改善用組成物 |
US20180139997A1 (en) * | 2015-06-15 | 2018-05-24 | Gexnano S.R.L. | Food supplement for use in a process of metabolic rebalancing |
ITUB20154001A1 (it) * | 2015-09-15 | 2017-03-15 | Scotto Dabusco Anna | Metodo di integrazione dietetica e uso per la preparazione di prodotti per l'integrazione personalizzata. |
WO2018027128A1 (en) | 2016-08-04 | 2018-02-08 | Performance Labs PTE. LTD. | Multivitamin capable of beneficial gene regulation through microrna (mirna) |
IT201600124013A1 (it) * | 2016-12-06 | 2018-06-06 | Solarpharm Srl | Prodotto alimentare a base di astaxantina |
CN106727652A (zh) * | 2016-12-30 | 2017-05-31 | 福建中医药大学 | 一种用于缓解骨关节炎疼痛的分子中药缓释片及其制备方法 |
GR1009331B (el) * | 2017-03-14 | 2018-07-31 | Ευαγγελια Παναγιωτη Λαγου | Λαδι με βοτανα που ανακουφιζει τους ταλαιπωρημενους μυς |
CA3078317A1 (en) * | 2017-11-08 | 2019-05-16 | Societe Des Produits Nestle S.A. | Bioconversion of oleuropein |
US20200360409A1 (en) * | 2017-11-08 | 2020-11-19 | Societe Des Produits Nestle S.A. | Bioconversion of oleuropein |
WO2019092069A2 (en) | 2017-11-08 | 2019-05-16 | Nestec S.A. | Homovanillyl alcohol (hva), hva isomer, methods of making compositions comprising such compounds, and methods using such compounds |
EP3706760B1 (en) | 2017-11-08 | 2023-08-02 | Société des Produits Nestlé S.A. | Method of selecting a probiotic |
CN108686119A (zh) * | 2018-06-27 | 2018-10-23 | 陶燃 | 一种治疗痛风的药物组合物及其应用 |
CN115023150B (zh) * | 2019-12-17 | 2024-04-26 | 三得利控股株式会社 | 硫酸软骨素合成促进用组合物 |
CN111286205A (zh) | 2019-12-17 | 2020-06-16 | 陕西科技大学 | 一种具有抗氧化活性及沙门氏菌检测能力的羟基酪醇鲟鱼鱼皮明胶薄膜及其制备方法 |
JP2023548903A (ja) * | 2020-11-18 | 2023-11-21 | ソシエテ・デ・プロデュイ・ネスレ・エス・アー | 軟骨変性における使用のための、オレウロペイン及びケルセチンの組み合わせを使用した組成物及び方法 |
CN113475624A (zh) * | 2021-06-10 | 2021-10-08 | 云南农业大学 | 一种菲牛蛭配合饲料 |
WO2023222704A1 (en) * | 2022-05-17 | 2023-11-23 | Société des Produits Nestlé S.A. | Compositions and methods using a combination of oleuropein and fisetin for use in cartilage degeneration |
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US6887497B2 (en) * | 2002-12-19 | 2005-05-03 | Vitacost.Com, Inc. | Composition for the treatment and prevention of osteoarthritis, rheumatoid arthritis and improved joint function |
FR2853549B1 (fr) * | 2003-04-11 | 2007-11-09 | Agronomique Inst Nat Rech | Composition nutritionnelle ou therapeutique contenant le compose oleuropeine ou l'un de ses derives |
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US20130115202A1 (en) * | 2005-08-31 | 2013-05-09 | Theta Biomedical Consulting & Development Co., Inc | Anti-inflammatory compositions for treating neuro-inflammation |
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JP5175481B2 (ja) * | 2006-10-23 | 2013-04-03 | エーザイフード・ケミカル株式会社 | 軟骨再生促進剤 |
WO2008115783A1 (en) * | 2007-03-19 | 2008-09-25 | Metaproteomics, Llc | Methods and compositions for promoting bone and joint health |
EP1982706A1 (en) * | 2007-04-18 | 2008-10-22 | DSMIP Assets B.V. | Use of hydroxytyrosol for the treatment of cartilage injury |
GB0807673D0 (en) * | 2008-04-28 | 2008-06-04 | Bio Actor Bcba | Polyphenolic extract |
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EP3003339A1 (en) | 2016-04-13 |
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AU2014273185A1 (en) | 2015-11-05 |
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CN105263505A (zh) | 2016-01-20 |
BR112015029611B1 (pt) | 2023-01-17 |
AU2014273185B2 (en) | 2019-04-18 |
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JP2019110899A (ja) | 2019-07-11 |
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US20160120891A1 (en) | 2016-05-05 |
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EP3003339B1 (en) | 2023-03-22 |
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