JP2018530517A - 一酸化窒素レベルを急激に上昇させるための組成物および方法 - Google Patents
一酸化窒素レベルを急激に上昇させるための組成物および方法 Download PDFInfo
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Abstract
Description
1つの実施形態において、本明細書中に示したのは:対象において一酸化窒素レベルを急激に上昇させるための組成物であって、有効量の一酸化窒素のNOS依存性源と、有効量の一酸化窒素のNOS非依存性源と、有効量のミエロペルオキシダーゼ阻害剤とを有し、前記組成物は、前記組成物の投与に先立っての対象における一酸化窒素の利用可能な源によって提供されたレベルを超えて前記対象における一酸化窒素レベルを急激に上昇させる組成物である。
以下に示される2つのNO−生成配合物を試験して、通常の血漿中濃度のADMAを持つ対象において、それらの、NOバイオマーカー、唾液中のNO2の急激な増強された生合成を評価した。
前記表2に記載されたように、処方1および2をそれらの相乗的活性について試験した。F1およびF2の追加の試料を、アセトン:水(1:1)溶液中の100mg/mLの初期濃度で調製し、10分毎に、渦巻かせつつ氷浴中で60分間音波処理し、3000rpmにおいて雰囲気温度で5分間遠心した。上清液体を新しい試験管に移し、13,300rpmにおいて、雰囲気温度で10分間再度遠心した。最終上清画分を新しい試験管に移し、分析するまで−80℃で保存した。
[1/予測されたIC50]=[Fa/IC50A]+[Fb/IC50B]+...+[Fn/IC50N]
Fa=組合せ中の成分Aのモル分率およびFn=n番目の成分組合せのモル分率、ここに、Fa+Fb+...+Fn=1であって、IC50A=成分Aの観察されたIC50等である。
以下に示される液状クロロフィリン/スペアミント油を試験して、ADMAの通常の血漿中濃度を持つ対象における唾液中でのNOバイオマーカーNO2の急激な生合成を評価した。
10成分植物複合体を、MPOのイン・ビトロ阻害における相乗作用について試験した。全ての化学物質、方法、試料、分析、および計算は実施例2に記載されたように行った。
PC10処方の臨床的安全性および有効性を、非盲検観察臨床試験で判断した。実験の集団は、以下の脂質変数:血清中トリグリセリド≧150mg/dlおよび/または血清中低密度リポ蛋白質コレステロール(計算)≧150mg/dlを呈する18歳から72歳の間の男性および女性を含んだ。12週間の実験の間、対象を、各々、500、750、または1000mgのPC10を受ける3つの群のうちの1つに割り当てて、夕食と共に毎日1回2、3、または4個のカプセル剤を摂取してもらった。
試験を行って、MPOのイン・ビトロ阻害において相乗効果を呈する9成分植物複合体(PC9p)の能力を評価した。全ての化学物質、方法および計算は実施例2に記載されたように行った。
それらの成分の比のみが異なる2つの4成分植物複合体を、MPOのイン・ビトロ阻害における相乗効果を呈することにつき試験した。全ての化学物質、方法および計算は実施例2に記載したように行った。
推定NO生成活性を含有する市販の製品を摂取した後に、健康な対象における唾液中亜硝酸塩生産レベルを評価した。実験においては、18歳から72歳の間の8人の対象が、唾液中NO2の彼らのベースラインレベルを決定するために、朝早く、Berkeley Test(登録商標)一酸化窒素バイオマーカーストリップ(NOBS)試験を行った。もしベースラインスコアが目視スケールで5未満であれば、対象を進めて、表11にリストされた被験物質のうちの1つを摂取させた。被験物質の消費後に、NOBSを30、60、90、120および240分に発生させた。
示された結果に基づき、以下の配合物は、PA9−PWまたはProArgi9P1と同程度に効果的に働くと予測されるであろう。
Claims (87)
- 対象において一酸化窒素レベルを急激に上昇させるための組成物であって、
有効量の一酸化窒素のNOS依存性源と、
有効量の一酸化窒素のNOS非依存性源と、
有効量のミエロペルオキシダーゼ阻害剤と
を有し、前記組成物は、前記組成物の投与前の前記対象における利用可能な一酸化窒素の源によって提供されるレベルを超えて、前記対象における一酸化窒素レベルを急激に上昇させる、組成物。 - 請求項1記載の組成物において、前記組成物の投与後の前記対象における一酸化窒素レベルは、同等量の前記一酸化窒素のNOS依存性源、前記一酸化窒素のNOS非依存性源、または前記ミエロペルオキシダーゼ阻害剤のうちのいずれか1つによって提供される量よりも多い、組成物。
- 請求項1記載の組成物において、前記一酸化窒素のNOS依存性源は、前記組成物の約1重量%〜約80重量%を構成する、組成物。
- 請求項1記載の組成物において、前記一酸化窒素のNOS依存性源は、L−アルギニン、L−シトルリン、オルニチン、またはそれらの組合せから成る群から選択されるメンバーを有する、組成物。
- 請求項4記載の組成物において、前記一酸化窒素のNOS依存性源はL−アルギニンを有する、組成物。
- 請求項5記載の組成物において、前記組成物中のL−アルギニンは約1重量%〜約80重量%の範囲である、組成物。
- 請求項4記載の組成物において、前記一酸化窒素のNOS依存性源はL−シトルリンを有する、組成物。
- 請求項7記載の組成物において、前記組成物中のL−シトルリンは約1重量%〜約80重量%の範囲である、組成物。
- 請求項7記載の組成物において、前記L−シトルリンの源はスイカ抽出物を有する、組成物。
- 請求項1記載の組成物において、前記一酸化窒素のNOS依存性源はL−アルギニンおよびL−シトルリンを有する、組成物。
- 請求項10記載の組成物において、前記L−アルギニンおよび前記L−シトルリンは、各々、前記組成物の約1重量%〜約80重量%を構成する、組成物。
- 請求項10記載の組成物において、前記L−アルギニンおよびL−シトルリンは、各々、約1:1〜約5:1の範囲の重量パーセント濃度で前記組成物に存在する、組成物。
- 請求項12記載の組成物において、前記L−アルギニンおよびL−シトルリンは、各々、約2:1の重量パーセント濃度比で前記組成物に存在する、組成物。
- 請求項1記載の組成物において、前記一酸化窒素のNOS非依存性源は、ビート根抽出物、ビタミンB1、コラードの若葉抽出物、ナッツ粉末、ホウレンソウ抽出物、ブロッコリー抽出物、レタス抽出物、セロリ、ケール、クレソン、ニンジン、ルッコラ、マスタードグリーン、またはそれらの組合せから成る群から選択されるメンバーを有する、組成物。
- 請求項14記載の組成物において、前記一酸化窒素のNOS非依存性源は、ビート根抽出物、ビタミンB1、またはそれらの組合せを有する、組成物。
- 請求項15記載の組成物において、前記一酸化窒素のNOS非依存性源は、ビート根抽出物およびビタミンB1を有する、組成物。
- 請求項16記載の組成物において、前記ビート根抽出物は前記組成物の約5重量%〜約90重量%を構成し、前記ビタミンB1は前記組成物の約0.01重量%〜約80重量%を構成する、組成物。
- 請求項16記載の組成物において、前記ビート根抽出物およびビタミンB1は、各々、約50:1〜約10:1の範囲の重量パーセント濃度比で前記組成物に存在する、組成物。
- 請求項1記載の組成物において、前記ミエロペルオキシダーゼ阻害剤は、約1重量%〜約90重量%を構成する、組成物。
- 請求項1記載の組成物において、前記ミエロペルオキシダーゼ阻害剤は、ザクロ果実抽出物、赤ブドウポリフェノール、リンゴ抽出物、ブルーベリー抽出物、唐辛子抽出物、ブドウ抽出物、緑茶抽出物、オリーブ抽出物、ベルガモット抽出物、マンゴスチン抽出物、またはそれらの組合せから成る群から選択されるメンバーを有する、組成物。
- 請求項1記載の組成物において、前記ミエロペルオキシダーゼ阻害剤は、ザクロ果実抽出物、赤ブドウポリフェノール、またはそれらの組合せから成る群から選択されるメンバーを有する、組成物。
- 請求項21記載の組成物において、前記ミエロペルオキシダーゼ阻害剤は、ザクロ果実抽出物および赤ブドウポリフェノールを有する、組成物。
- 請求項22記載の組成物において、前記ザクロ果実抽出物は前記組成物の約1重量%〜約80重量%を構成し、前記赤ブドウポリフェノールは前記組成物の約1重量%〜約80重量%を構成する、組成物。
- 請求項1記載の組成物において、前記ミエロペルオキシダーゼ阻害剤は、リンゴ抽出物、ブドウ抽出物、緑茶抽出物、およびオリーブ抽出物を有する、組成物。
- 請求項24記載の組成物において、前記リンゴ抽出物、ブドウ抽出物、緑茶抽出物、およびオリーブ抽出物は、合計で、前記組成物の約1重量%〜約80重量%を構成する、組成物。
- 請求項26記載の組成物において、前記リンゴ抽出物は前記組成物の約0.01重量%〜約80重量%を構成し、前記ブドウ抽出物は前記組成物の約0.01重量%〜約80重量%を構成し、前記緑茶抽出物は前記組成物の約0.01重量%〜約80重量%を構成し、前記オリーブ抽出物は前記組成物の約0.01重量%〜約80重量%を構成する、組成物。
- 請求項24記載の組成物において、前記リンゴ抽出物、ブドウ抽出物、緑茶抽出物、およびオリーブ抽出物は、約1:1:1:1の重量比で前記組成物に存在する、組成物。
- 請求項24記載の組成物において、前記リンゴ抽出物、ブドウ抽出物、緑茶抽出物、およびオリーブ抽出物は、約6:1:3:1の重量比で前記組成物に存在する、組成物。
- 請求項24記載の組成物において、前記リンゴ抽出物、前記ブドウ抽出物、前記緑茶抽出物、および前記オリーブ抽出物のうちの少なくとも1つは、異なる量で前記組成物に存在する、組成物。
- 請求項24記載の組成物において、前記ブドウ抽出物は、ブドウ種子抽出物およびブドウ皮抽出物を有する、組成物。
- 請求項24記載の組成物において、前記ミエロペルオキシダーゼ阻害剤はザクロ果実抽出物をさらに有する、組成物。
- 請求項24記載の組成物であって、さらに、ブルーベリー果実抽出物、唐辛子果実抽出物、およびウコン根抽出物を有する、組成物。
- 請求項32記載の組成物において、前記ブルーベリー果実抽出物は前記組成物の約0.01重量%〜約80重量%を構成し、前記唐辛子果実抽出物は前記組成物の約0.01重量%〜約80重量%を構成し、前記ウコン根抽出物は前記組成物の約0.01重量%〜約80重量%を構成する、組成物。
- 請求項32記載の組成物において、前記リンゴ抽出物、前記ブドウ抽出物、前記緑茶抽出物、前記オリーブ抽出物、前記ブルーベリー果実抽出物、前記唐辛子果実抽出物、および前記ウコン根抽出物は、約1:1:1:1:1:1:1の重量比で前記組成物に存在する、組成物。
- 請求項32記載の組成物であって、さらに、ウコン地下茎抽出物、およびマンゴスチン抽出物を有する、組成物。
- 請求項33記載の組成物において、前記ウコン地下茎抽出物は前記組成物の約0.01重量%〜約80重量%を構成し、前記マンゴスチン抽出物は前記組成物の約0.01重量%〜約80重量%を構成する、組成物。
- 請求項35記載の組成物において、前記リンゴ抽出物、前記ブドウ抽出物、前記緑茶抽出物、前記オリーブ抽出物、前記ブルーベリー果実抽出物、前記唐辛子果実抽出物、前記ウコン根抽出物、前記ウコン地下茎抽出物、および前記マンゴスチン抽出物は、約1:1:1:1:1:1:1:1:1の重量比で前記組成物に存在する、組成物。
- 請求項35記載の組成物において、前記マンゴスチン抽出物は、マンゴスチン果実抽出物、マンゴスチン果皮抽出物、またはそれらの組合せを有する、組成物。
- 請求項35記載の組成物において、前記製剤はベルガモット果実抽出物をさらに有する、組成物。
- 請求項39記載の組成物において、前記ベルガモット果実抽出物は前記組成物の約0.01重量%〜約80重量%を構成する、組成物。
- 請求項39記載の組成物において、前記リンゴ抽出物、前記ブドウ抽出物、前記緑茶抽出物、前記オリーブ抽出物、前記ブルーベリー果実抽出物、前記唐辛子果実抽出物、前記ウコン根抽出物、前記ウコン地下茎抽出物、前記マンゴスチン抽出物、および前記ベルガモット果実抽出物は、約1:1:1:1:1:1:1:1:1:1の重量比で前記組成物に存在する、組成物。
- 請求項1記載の組成物において、前記ミエロペルオキシダーゼ阻害剤は、ナトリウム銅クロロフィリン、スペアミント油、またはそれらの組合せを有する、組成物。
- 請求項1記載の組成物において、前記一酸化窒素のNOS依存性源は、L−アルギニン、L−シトルリン、またはそれらの組合せから成る群から選択されるメンバーを有し、前記ミエロペルオキシダーゼ阻害剤は、赤ブドウ種子抽出物およびザクロ果実抽出物を有する、組成物。
- 請求項1記載の組成物において、前記組成物は、d−リボース、葉酸、リンゴ酸、ビタミンB6、ビタミンB12、ビタミンD3、酸化マグネシウム、カルシウム、イヌリン、チコリー根抽出物、サクランボ抽出物、またはそれらの組合せから成る群から選択されるメンバーをさらに有する、組成物。
- 請求項1記載の組成物において、前記組成物は医薬的に許容される担体をさらに有する、組成物。
- 請求項45記載の組成物において、前記組成物は、甘味剤、保存剤、フレーバリング、またはそれらの組合せから成る群から選択されるメンバーをさらに有する、組成物。
- 請求項1記載の組成物において、前記組成物は経口投与製剤である、組成物。
- 請求項47記載の組成物において、前記経口投与形態は、カプセル剤、錠剤、散剤、飲料、シロップ、懸濁剤、または食品を有する、組成物。
- 請求項48記載の組成物において、前記経口投与形態は、約5mg〜約1,000mgの前記一酸化窒素のNOS依存性源、約5mg〜約1,000mgの前記一酸化窒素のNOS非依存性源、および約5mg〜約1,000mgの前記ミエロペルオキシダーゼ阻害剤を有する、組成物。
- 請求項47記載の組成物において、前記経口投与形態は、所定の投薬計画に従って、前記対象への投与のために調製される、組成物。
- 請求項50記載の組成物において、前記経口投与形態は、前記対象に1日当たり1回投与される、組成物。
- 請求項1記載の組成物において、前記組成物は、一酸化窒素の生合成生産を増強させることによって、前記対象において一酸化窒素レベルを急激に上昇させる、組成物。
- 請求項1記載の組成物において、前記組成物は、ミエロペルオキシダーゼ活性を阻害することによって、前記対象において一酸化窒素レベルを急激に上昇させる、組成物。
- 請求項1記載の組成物において、前記組成物は、一酸化窒素への変換用の亜硝酸塩/硝酸塩源を提供することによって、前記対象において一酸化窒素レベルを急激に上昇させる、組成物。
- 対象において一酸化窒素レベルを急激に上昇させる方法であって、
治療上有効量の請求項1〜54のいずれかに記載の組成物を前記対象に投与する工程を有する、方法。 - 一酸化窒素療法に対して応答性である疾患または障害について対象を治療する方法であって、
同時に、一酸化窒素の生合成を増加させ、硝酸塩/亜硝酸塩レベルを増加させ、およびミエロペルオキシダーゼ活性を阻害することによって、対象において一酸化窒素レベルを急激に上昇させる工程を有する、方法。 - 請求項56記載の方法において、前記疾患または障害は一酸化窒素関連病変である、方法。
- 請求項57記載の方法において、前記一酸化窒素関連病変は、アルツハイマー病、狭心症、喘息、鬱血性障害、クローン病、深部静脈血栓症、認知症、糖尿病(1、2および3型)、糖尿病性足障害、減少した運動能力、内皮機能不全、内毒血症、勃起機能不全、線維筋痛症、心臓発作、心不全、高血圧、炎症性腸疾患、腸管壁浸漏、黄斑変性、単球−媒介動脈プラーク形成、運動機能障害、多発性硬化症、肥満、LDLの酸化、歯周病、末梢動脈病、血小板粘性、門脈圧亢進症日、妊娠/子癇前症、早漏、肺性高血圧、レイノー病、腎不全、睡眠時無呼吸、平滑筋細胞増殖、発作、および血管炎から成る群から選択されるメンバーを有する、方法。
- 請求項56記載の方法において、前記疾患または障害は心血管代謝障害である、方法。
- 請求項59記載の方法において、前記心血管代謝障害は、アルツハイマー病、狭心症、喘息、鬱血性障害、クローン病、深部静脈血栓症、認知症、糖尿病(1、2および3型)、糖尿病性足障害、減少した運動能力、内皮機能不全、内毒血症、勃起機能不全、線維筋痛症、心臓発作、心不全、高血圧、炎症性腸疾患、腸管壁浸漏、黄斑変性、単球−媒介動脈プラーク形成、運動機能障害、多発性硬化症、肥満、LDLの酸化、歯周病、末梢動脈病、血小板粘性、門脈圧亢進症、妊娠/子癇前症、早漏、肺性高血圧、レイノー病、腎不全、睡眠時無呼吸、平滑筋細胞増殖、発作、および血管炎から成る群から選択されるメンバーを有する、方法。
- 請求項59記載の方法において、前記心血管代謝障害は、高血圧、心血管機能不全、神経変性、関節炎、喘息、および敗血症性ショックから成る群から選択されるメンバーを有する、方法。
- 請求項59記載の方法において、前記心血管代謝障害は動脈プラークの形成の予防を有する、方法。
- 請求項59記載の方法において、前記対象の治療は予防的である、方法。
- 請求項56記載の方法において、前記疾患または障害はミエロペルオキシダーゼ関連病変である、方法。
- 請求項64記載の方法において、前記ミエロペルオキシダーゼ関連病変は、アルツハイマー病、狭心症、喘息、全身鬱血性障害、クローン病、深部静脈血栓症、認知症、糖尿病(1、2および3型)、糖尿病性足障害、減少した運動能力、内皮機能不全、内毒血症、勃起機能不全、線維筋痛症糸球体腎炎、心臓発作、心不全、高血圧、免疫不全、炎症性腸疾患、腸管壁浸漏、黄斑変性、単球−媒介動脈プラーク形成、運動機能障害、多発性硬化症、肥満、LDLの酸化、歯周病、末梢動脈病、血小板粘性、門脈圧亢進症、妊娠/子癇前症、早漏、肺性高血圧、レイノー病、腎不全、睡眠時無呼吸、平滑筋細胞増殖、発作、血管炎、および遅い創傷治癒、皺、および老化の早期兆候などの皮膚に関連する病気である、方法。
- 請求項64記載の方法において、前記ミエロペルオキシダーゼ関連病変は、増加した酸化LDLコレステロールを有する、方法。
- 請求項64記載の方法において、前記ミエロペルオキシダーゼ関連病変は、代謝症候群、1型糖尿病、2型糖尿病、3型糖尿病、またはそれらの組合せを有する、方法。
- 請求項64記載の方法において、前記ミエロペルオキシダーゼ関連病変は、腸管壁浸漏、内毒血症、炎症性腸疾患、またはそれらの組合せを有する、方法。
- 請求項64記載の方法において、前記ミエロペルオキシダーゼ関連病変は、遅い創傷治癒、皺、日焼けによるシミ、および老化の早期兆候を含む皮膚の病変(dermatopic pathology)を有する、方法。
- 請求項64記載の方法において、前記対象の治療は予防的である、方法。
- 請求項56記載の方法において、前記疾患または障害は陰茎機能不全である、方法。
- 請求項56記載の方法において、前記対象における一酸化窒素レベルの急激な上昇は、内皮機能を増強させ、単球媒介性動脈プラーク形成を減少させ、末梢動脈病の発生を減少させ、またはそれらの組合せを行い、増加または減少は、前記治療上有効な組合せの投与前の前記対象におけるレベルを参照する、方法。
- 請求項56記載の方法において、前記対象はヒトである、方法。
- 請求項56記載の方法において、前記対象の治療は予防的である、方法。
- 請求項56記載の方法において、前記対象における一酸化窒素レベルの急激な上昇は、前記治療上有効な組合せの投与前のレベルと比較して、前記対象における唾液中亜硝酸塩のレベルを超えて前記対象における唾液中亜硝酸塩レベルを上昇させる工程を有する、方法。
- 対象において一酸化窒素レベルを急激に上昇させるためのシステムであって、
有効量の一酸化窒素のNOS依存性源と、
有効量の一酸化窒素のNOS非依存性源と、
有効量のミエロペルオキシダーゼ阻害剤と
を有する、システム。 - 請求項76記載のシステムにおいて、前記一酸化窒素のNOS依存性源、前記一酸化窒素のNOS非依存性源、および前記ミエロペルオキシダーゼ阻害剤のうちの少なくとも1つは、相互に離されている、システム。
- 請求項76記載のシステムにおいて、前記一酸化窒素のNOS依存性源、前記一酸化窒素のNOS非依存性源、および前記ミエロペルオキシダーゼ阻害剤のうちの少なくとも1つは、別々の製剤中に存在する、システム。
- 請求項76記載のシステムにおいて、前記組成物の投与後の前記対象における一酸化窒素のレベルは、同等量の前記一酸化窒素のNOS依存性源、前記一酸化窒素のNOS非依存性源、または前記ミエロペルオキシダーゼ阻害剤のうちのいずれか1つによって提供される量よりも多い、システム。
- 請求項79記載のシステムにおいて、一酸化窒素のレベルは、同等量の前記一酸化窒素のNOS依存性源、前記一酸化窒素のNOS非依存性源、または前記ミエロペルオキシダーゼ阻害剤のうちの少なくとも1つの添加量よりも多い、システム。
- 請求項76記載のシステムにおいて、前記システムはキットとして処方される、システム。
- 対象において一酸化窒素レベルを急激に上昇させるための組成物であって、
有効量のナトリウム銅クロロフィリン、スペアミント油、またはそれらの組合せを有する、組成物。 - 請求項82記載の組成物において、ナトリウム銅クロロフィリンおよびスペアミント油を有する、組成物。
- 請求項83記載の組成物において、スペアミント油に対するナトリウム銅クロロフィリンの重量比は、約1:1〜約10:1の範囲である、組成物。
- 請求項82記載の組成物において、前記組成物はスペアミント油を有し、前記スペアミント油は、気中部分、根、葉、花、またはそれらの組合せに由来する、組成物。
- 一酸化窒素療法に対して応答性である疾患または障害について対象を治療する方法であって、
ミエロペルオキシダーゼ活性を阻害する工程を有する、方法。 - 請求項86記載の方法において、治療上有効量のナトリウム銅クロロフィリン、スペアミント油、またはそれらの組合せを前記対象に投与する工程を有する、方法。
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2016
- 2016-08-28 US US15/756,548 patent/US11241406B2/en active Active
- 2016-08-29 WO PCT/US2016/049306 patent/WO2017040421A1/en active Application Filing
- 2016-08-29 CN CN201680061891.9A patent/CN108778306A/zh active Pending
- 2016-08-29 EP EP16842766.4A patent/EP3341003A4/en not_active Withdrawn
- 2016-08-29 CA CA2996627A patent/CA2996627A1/en not_active Abandoned
- 2016-08-29 JP JP2018503486A patent/JP2018530517A/ja active Pending
- 2016-08-29 KR KR1020187002380A patent/KR20180043251A/ko unknown
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2022
- 2022-02-07 US US17/666,305 patent/US20220296552A1/en active Pending
Cited By (2)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
JP2020182384A (ja) * | 2019-04-26 | 2020-11-12 | 健商株式会社 | 経口組成物およびこれを含有する食品 |
WO2022202403A1 (ja) * | 2021-03-23 | 2022-09-29 | 花王株式会社 | 口腔内ナイセリア・ムコサ増加剤 |
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US20220296552A1 (en) | 2022-09-22 |
EP3341003A1 (en) | 2018-07-04 |
US11241406B2 (en) | 2022-02-08 |
US20180263944A1 (en) | 2018-09-20 |
CA2996627A1 (en) | 2017-03-09 |
KR20180043251A (ko) | 2018-04-27 |
CN108778306A (zh) | 2018-11-09 |
WO2017040421A1 (en) | 2017-03-09 |
EP3341003A4 (en) | 2019-04-03 |
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