JP2021505673A - 代謝性疾患の治療のための組成物および方法 - Google Patents
代謝性疾患の治療のための組成物および方法 Download PDFInfo
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Abstract
Description
(a)滅菌水溶液中に少なくとも1つの医薬品グレードの酸を含有する静脈内緩衝液を含む第1のバイアル;
(b)滅菌水溶液中に少なくとも1つの医薬品グレードのpH緩衝剤を含む第2のバイアル、ここで、2つのバイアルの内容物は、組み合わされた場合、静脈内緩衝液を形成し、ここで、緩衝液中の医薬品グレードの酸および医薬品グレードのpH緩衝剤の濃度は、対象に投与したときに60mmol/L〜3000mmol/Lの滴定可能な全酸含量を提供するのに十分であり、ならびに医薬品グレードの酸および医薬品グレードのpH緩衝剤の選択は、4〜7.7の緩衝液pHを提供するのに有効である;ならびに
(c)使用説明書
を含むキットを提供する。
本発明の一実施形態では、本発明の組成物は、対象への静脈内投与に適するように製剤化された安定な治療用組成物である。組成物は、少なくとも1つの医薬品グレードの酸、および少なくとも1つの医薬品グレードのpH緩衝剤を含有する静脈内緩衝液を含む。医薬用途への適合性を確保するために、酸および緩衝液は滅菌水溶液中に存在する。緩衝液中の医薬品グレードの酸および医薬品グレードのpH緩衝剤の濃度は、対象に投与したときに60mmol/L〜3000mmol/Lの滴定可能な全酸含量を提供するのに十分である。酸および塩基は、それらが一緒になって、4〜7.7のpHを有する緩衝液を提供できるように選択される。
別の態様では、本開示は治療方法を提供する。本発明の方法は、本発明の組成物を、それを必要とする対象に投与することを含む。
本発明の一実施形態は、本開示の安定な治療用組成物を対象に投与するためのキットを含む。この実施形態では、キットは、単一のバイアルまたは複数のバイアル中に組成物を含み得る。バイアルは、好ましくは、バイアルから溶液を引き出すためにシリンジを挿入するのに適した膜を備える注射バイアル、またはソフトI.V.注入バッグであり得る。本発明の組成物は、滅菌水溶液中でバイアルに含まれる。溶液は、投与の前に希釈剤が添加される濃縮溶液として提供され得る。希釈剤は滅菌水であり得る。キットは、希釈剤を含む予め充填された容器をさらに含み得る。好ましい実施形態では、ソフト注入バッグには希釈剤が予め充填されている。あるいは、組成物バイアルは、希釈せずに注射に適した濃度の溶液を含むことができる。好ましくは、注射用の溶液は等張性である。すなわち、溶液は、塩、グルコースなどの糖質、NaHCO3またはグリシンなどのアミノ酸を含むことができ、血漿と等張である。他の例では、溶液は、より迅速な細胞内取り込みを促進するように低張性であり得るか、またはより緩やかな細胞内取り込みを促進するように高張性であり得る。
本明細書で説明する実験は、治療目的で血流のpHを酸性にシフトする緩衝酸性溶液を使用することの主要な態様を検証するために設計された。具体的には、いくつかの態様が例示されている:(1)血液は、生理的pHおよび緩衝能を有する溶液として概念化され得る酸塩基特性を有する。さらに、投与時に血液pHをシフトするように設計された治療組用組成物は、標的pHおよび緩衝能を有する溶液として概念化され得る。(2)血流の酸性状態へのpHシフトは、酸性溶液の静脈内または動脈内投与を介して達成することができる。(3)より高濃度の緩衝液成分を有する代替製剤は、血流pHの生理的状態への回復を妨げる能力が高められている。(4)状態が所与のpHでの平衡からより低いpHレベルにシフトすると、石灰化ミネラル形態のより速い溶解が達成できる。
生理的基準状態では、血液は一般に7.41に近いpH値を有すると認識されている。これは、その中の様々な酸(主にHCl)および様々な緩衝剤(主に重炭酸塩)の存在に起因する。血液の酸塩基特性を模倣する代理物を開発するために、HClおよびHCO3を含む水ベースの溶液を調製した。HClおよびHCO3は、血液中の主要な酸および緩衝剤種であるので、この代理物のために選択した。この血液代理物では、5,000mlの水溶液中の0.0024M HClを0.025MのNaHCO3で緩衝し、7.41のpHを生成した(表3)。この代理物は、大気に曝露したままにしておいた場合、CO2の損失が経時的にpHに影響を及ぼすため、実施されたそれぞれの試験用に新たに調製した。
試験は、治療用組成物を3頭のウマに投与することによって実施した。以下の材料を試験のために調製した:
1.対象1−牝馬、34歳、ウェールズクロス、739ポンド、前糖尿病、クッシング病を伴う蹄葉炎、およびライム病の病歴。
a.100mlのA−バイアルAS*溶液(アスコルビン酸、塩酸、および塩化ナトリウムと水を含有する水性溶媒を含む)、または
100mlのA−バイアルASVM**溶液(アスコルビン酸、デヒドロアスコルビン酸、塩酸、チアミンHCl、硫酸マグネシウム、シアノコバラミン結晶、ナイアシンアミド、ピロキシジンHCl、リボフラビン5’リン酸塩、D−パントテン酸カルシウム、および塩化ナトリウムと水を含有する水性溶媒を含む)
b.100mlのB−バイアル重炭酸塩溶液(重炭酸ナトリウムおよび塩化ナトリウムと水を含有する水性溶媒を含む)
c.IV用バッグ中の1000mlの生理食塩水、またはIV用バッグ中の2000mlの生理食塩水
*AS−グレード供給の酸シフト組成物
**ASVM−選択ビタミンとミネラルをさらに含むグレード供給の酸シフト組成物。
治療用組成物の投与は以下のように管理した:
Aバイアル製品は使用前に40°Fで冷蔵し、Bバイアル製品は70°Fで保存した。Aバイアル製品100mlを生理食塩水IVバッグに入れ、次にBバイアル製品100mlをIVバッグに入れた。IVバッグは、注入点の18インチ上の高所から吊り下げた。カテーテルを対象の頸静脈に挿入した。治療前の静脈血試料を、IDEXX分析(血液学、化学、内分泌学および血清学)ならびに血液ガス分析(酸/塩基状態、オキシメトリ、電解質、代謝物)のために患者から採取した(T=−5分)。5分後(T=0分)、IVバッグをカテーテルに接続し、点滴を開いて注入を開始した。45分後(T=45分)、注入が完了するように点滴速度を調整した。治療中、治療開始後15分(T=15分)および30分(T=30分)に静脈血試料を対象から採取した。治療後の静脈血試料を、治療開始後60分(T=60分)および120分(T=120分)に採取した。治療後の試料を血液ガス分析(酸/塩基状態、オキシメトリ、電解質および代謝物)に供した。
結果セクション1:血液g¥ガスおよび酸塩基応答:
対象2 AS 投与1およびASVM 投与4および5−観察された応答:血液pH、血液HCO3−、およびオキシメトリを、表8に示すように、投与開始の5分前(T=−5)、投与開始後20分(T=20)、および投与完了後5分(T=45で投与完了、T=50で測定)の時間間隔で観察した。
図6に示すように、静脈のpHは、7.392の境界アシドーシスの開始時からT=20でアルカリ性へと上昇し、その後T=50で酸性に向かって低下することが観察された。AS溶液は血流を酸性にシフトするはずであるが、おそらくT=20での観察点は、腎代償過程が既に酸塩基状態を管理し始めた後であったために、これは観察されなかった。同時に、静脈のHCO3−は、最初に、クッシング病と一致する、33.2mmol/Lという高い値を有することが測定された。治療の間に、細胞内または腎抽出への流れと一致して、他の時点で値は31mmol/Lに低下した。図7に示すように、静脈のsO2とpO2はこの時間中に、組織への酸素供給の増強と一致して、55%sO2および30mmHg pO2の低い開始レベルから上昇することが観察された。pCO2は、代謝の減少、血漿量の拡大、またはCO2へのヘモグロビン親和性の低下とO2への親和性の上昇と一致して、低下することが認められた。
図8に示すように、ASを使用した投与1と同様の応答で、静脈のpHはT=20でアルカリ性へと上昇し、その後T=50で酸性へと低下することが観察された。同時に、静脈のHCO3−は、クッシング病の解消と一致して、T=−5で26.7mmol/Lであることが観測され、観察期間を通じてほとんど変化しなかった。図9に示すように、静脈のsO2とpO2は、pCO2の減少と共に、薬物投与中に上昇することが再び観察された。
図10に示すように、投与5は、投与1および4とは異なって応答を誘発し、静脈のpHは、観察枠を通じて酸性に向かって低下することが観察された。これは、血流に対するよりアルカリ性の開始バイアスに起因する可能性があった。同時に、静脈のHCO3−は、やはりクッシング病の解消と一致して、T=−5で29.4mmol/Lであることが観察された。上昇または変化しないままである代わりに、血流のHCO3−は、細胞内への流れと一致して、観察期間を通じて低下した。図11に示すように、静脈のsO2とpO2は、組織への酸素供給増強のより耐久性のある回復と一致して、73%sO2および37mmHg pO2のより高い開始レベルを有することが観察された。sO2およびpO2は、薬物投与中にさらに上昇することが再び観察された。pCO2はほとんど変化しないままであった。投与1および4と比較して、投与5での挙動の違いは、酸/塩基状態に関するホメオスタシスの増強の達成と一致する。
対象2と実質的に類似しており、提示していない。
図12に示すように、投与5は対象2での投与5と同様の応答を誘発し、静脈のpHは、観察枠を通じて酸性に向かって低下することが観察された。同時に、静脈のHCO3−は、やはりクッシング病の解消と一致して、T=−5で27.7mmol/Lであることが観察された。上昇または変化しないままである代わりに、血流HCO3−は、細胞内への流れと一致して、観察期間を通じて低下した。図13に示すように、静脈のsO2とpO2は、治療前のレベルと比較して、組織への酸素供給の増強へのバイアスと一致して、70%sO2および34mmHg pO2の比較的高い開始レベルを有することが観察された。AS製品を使用した対象2の投与5の応答とは対照的に、sO2とpO2は、薬物投与中に低下することでAS製品の注入に応答し、これは、肝臓からのEPO放出を刺激してRBC貯蔵の補充を促進する可能性があると認識されている刺激である。この応答の違いは、AS構成とASVM構成の製剤の違いによって引き起こされた可能性がある。この時間中、pCO2はそれに対応して上昇した。
対象2 AS投与1およびASVM投与4および5−観察された応答:血液電解質、ヘモグロビン(Hb)、グルコース(Glu)および乳酸(Lac)を、表7に示すように、投与開始の5分前(T=−5)、投与開始後20分(T=20)、および投与完了後5分(T=45で投与完了、T=50で測定)の時間間隔で観察した。
3頭のウマでの4回の投与を含む1日目から8日目の間に観察された応答:血液学、化学、内分泌学、および血清学を1日目、投与1の前、および8日目、投与5の前に観察し、したがってASVM、または一部の投与例ではASの4回の投与を含んだ。表8に示すように、以下の作用をデータで認めることができる。
Claims (54)
- 滅菌水溶液中に少なくとも1つの医薬品グレードの酸および少なくとも1つの医薬品グレードのpH緩衝剤を含有する静脈内緩衝液を含む、対象への静脈内投与用に製剤化された安定な治療用組成物であって、
ここで、前記緩衝液中の前記医薬品グレードの酸および前記医薬品グレードのpH緩衝剤の濃度が、対象に投与したときに60mmol/L〜3,000mmol/Lの滴定可能な全酸含量を提供するのに十分であり、ならびに
前記医薬品グレードの酸および前記医薬品グレードのpH緩衝剤の選択が、4〜7.7の緩衝液pHを提供するのに有効である、
組成物。 - 前記医薬品グレードの酸が、塩酸、アスコルビン酸、酢酸、(他の生理学的に許容される酸)、またはそれらの組合せである、請求項1に記載の組成物。
- 前記少なくとも1つのpH緩衝剤が、重炭酸ナトリウム、リン酸緩衝液、水酸化ナトリウム、有機酸、有機アミン、アンモニア、クエン酸緩衝液、特定のアルカリ条件を創出する合成緩衝液(例えばトリス−ヒドロキシメチルアミノメタン)、(他の生理学的に許容される緩衝液)、またはそれらの組合せである、請求項1に記載の組成物。
- ビタミン、塩、酸、アミノ酸またはその塩、および安定化された酸化種からなる群より選択される1つ以上の成分をさらに含む、請求項1に記載の組成物。
- アスコルビン酸をさらに含む、請求項4に記載の組成物。
- デヒドロアスコルビン酸をさらに含む、請求項4に記載の組成物。
- トコフェロール(aTCP)、補酵素Q10(Q)、シトクロムc(C)およびグルタチオン(GSH)などの非酵素化合物、ならびにマンガンスーパーオキシドジスムターゼ(MnSOD)、カタラーゼ(Cat)、グルタチオンペルオキシダーゼ(GPX)、リン脂質ヒドロペルオキシドグルタチオンペルオキシダーゼ(PGPX)、グルタチオンレダクターゼ(GR)、ペルオキシレドキシン(PRX3/5)、グルタレドキシン(GRX2)、チオレドキシン(TRX2)およびチオレドキシンレダクターゼ(TRXR2)を含む酵素成分を含む、他の広く認められている抗酸化防御化合物をさらに含む、請求項4に記載の組成物。
- ナトリウム塩、マグネシウム塩、カリウム塩、およびカルシウム塩の1つ以上をさらに含む、請求項4に記載の組成物。
- Bビタミン、ビタミンC、およびビタミンKの1つ以上をさらに含む、請求項4に記載の組成物。
- 前記組成物が、静脈内、ボーラス、皮膚、経口、耳、坐剤、バッカル、眼、または吸入送達用に製剤化されている、請求項1に記載の組成物。
- 前記組成物が、局所液体、ゲル、またはペーストとして製剤化されている、請求項1に記載の組成物。
- 前記組成物が、点眼剤の形態での眼投与用に製剤化されている、請求項1に記載の組成物。
- 低張、等張、または高張形態に製剤化された、請求項4に記載の組成物。
- 前記静脈内投与がボーラス送達である、請求項1に記載の組成物。
- 前記組成物が凍結乾燥または凍結されている、請求項1に記載の組成物。
- 前記組成物がスペクトル遮断バイアルに保存される、請求項1に記載の組成物。
- 前記組成物が、2つ以上のバイアルからの成分を組み合わせることによって形成される、請求項1に記載の組成物。
- 対象への静脈内投与用に製剤化された安定な治療用組成物であって、医薬品グレードの、
900±90mgのL−アスコルビン酸;
63.33±6.33mgのチアミンHCl;
808±80.8mgの硫酸マグネシウム;
1.93±.193mgのシアノコバラミン;
119±11.9mgのナイアシンアミド;
119±11.9mgの塩酸ピリドキシン;
2.53±.253mgのリボフラビン5’リン酸塩;
2.93±.293mgのD−パントテン酸カルシウム;
840±84mgの重炭酸ナトリウム;
4.5±.45mMのHCl;および
20mLの最終組成物容量を得るための量の水
を含有する、組成物。 - 100±10mgのデヒドロアスコルビン酸をさらに含む、請求項18に記載の組成物。
- 対象におけるアシドーシスを治療または改善する方法であって、滅菌水溶液中に少なくとも1つの医薬品グレードの酸および少なくとも1つの医薬品グレードのpH緩衝剤を含有する静脈内緩衝液を含む安定な治療用組成物を前記対象に投与することを含み、
ここで、前記緩衝液中の前記医薬品グレードの酸および前記医薬品グレードのpH緩衝剤の濃度が、対象に投与したときに60mmol/L〜3,000mmol/Lの滴定可能な全酸含量を提供するのに十分であり、ならびに
前記医薬品グレードの酸および前記医薬品グレードのpH緩衝剤の選択が、4〜7.7の緩衝液pHを提供するのに有効である、
方法。 - 対象における塩基過剰を治療または改善する方法であって、滅菌水溶液中に少なくとも1つの医薬品グレードの酸および少なくとも1つの医薬品グレードのpH緩衝剤を含有する静脈内緩衝液を含む安定な治療用組成物を前記対象に投与することを含み、
ここで、前記緩衝液中の前記医薬品グレードの酸および前記医薬品グレードのpH緩衝剤の濃度が、対象に投与したときに60mmol/L〜3,000mmol/Lの滴定可能な全酸含量を提供するのに十分であり、ならびに
前記医薬品グレードの酸および前記医薬品グレードのpH緩衝剤の選択が、4〜7.7の緩衝液pHを提供するのに有効である、
方法。 - 対象における血中酸素を高める方法であって、滅菌水溶液中に少なくとも1つの医薬品グレードの酸および少なくとも1つの医薬品グレードのpH緩衝剤を含有する静脈内緩衝液を含む安定な治療用組成物を前記対象に投与することを含み、
ここで、前記緩衝液中の前記医薬品グレードの酸および前記医薬品グレードのpH緩衝剤の濃度が、対象に投与したときに60mmol/L〜3,000mmol/Lの滴定可能な全酸含量を提供するのに十分であり、ならびに
前記医薬品グレードの酸および前記医薬品グレードのpH緩衝剤の選択が、4〜7.7の緩衝液pHを提供するのに有効である、
方法。 - 対象における静脈血中のpO2を上昇させることを含む、請求項22に記載の方法。
- ミトコンドリア障害、代謝障害、糖尿病に関連する疾患または心血管機能不全を、その治療または改善を必要とする対象において治療または改善する方法であって、滅菌水溶液中に少なくとも1つの医薬品グレードの酸および少なくとも1つの医薬品グレードのpH緩衝剤を含有する静脈内緩衝液を含む安定な治療用組成物を前記対象に投与することを含み、
ここで、前記緩衝液中の前記医薬品グレードの酸および前記医薬品グレードのpH緩衝剤の濃度が、対象に投与したときに60mmol/L〜3,000mmol/Lの滴定可能な全酸含量を提供するのに十分であり、ならびに
前記医薬品グレードの酸および前記医薬品グレードのpH緩衝剤の選択が、4〜7.7の緩衝液pHを提供するのに有効である、
方法。 - 前記代謝障害が、糖尿病、インスリン抵抗性、耐糖能異常、高血糖症、高インスリン血症、肥満、高脂血症、または高リポタンパク血症である、請求項24に記載の方法。
- 前記糖尿病に関連する疾患が、高血圧症、高脂血症、脂肪肝疾患、腎症、神経障害、腎不全、網膜症、糖尿病性潰瘍、白内障、インスリン抵抗性症候群および悪液質である、請求項24に記載の方法。
- 前記心血管機能不全が、冠状動脈性心疾患、脳血管疾患、高血圧症、末梢動脈疾患、閉塞性動脈疾患、狭心症、リウマチ性心疾患、先天性心疾患、心不全、心機能不全、動悸、上室性頻拍、細動、失神、めまい、疲労、片頭痛、高レベルの総血中コレステロールおよび/またはLDLコレステロール、低レベルのHDLコレステロール、高レベルのリポタンパク質、心臓炎および心内膜炎などの心臓の感染症、糖尿病性潰瘍、血栓性静脈炎、レイノー病、神経性食欲不振症、跛行、壊疽、アテローム性動脈硬化症ならびに末梢動脈疾患である、請求項24に記載の方法。
- 前記ミトコンドリア障害が、神経変性障害、心血管疾患、メタボリックシンドローム、自己免疫疾患、神経行動疾患もしくは精神疾患、胃腸障害、疲労病、慢性筋骨格疾患、または慢性感染症である、請求項24に記載の方法。
- 前記組成物がデヒドロアスコルビン酸をさらに含む、請求項24に記載の方法。
- マグネシウムイオン源、カリウムイオン源、およびカルシウムイオン源の1つ以上をさらに含む、請求項24に記載の方法。
- Bビタミン、ビタミンC、およびビタミンKの1つ以上をさらに含む、請求項24に記載の方法。
- トコフェロール(aTCP)、補酵素Q10(Q)、シトクロムc(C)およびグルタチオン(GSH)などの非酵素化合物、ならびにマンガンスーパーオキシドジスムターゼ(MnSOD)、カタラーゼ(Cat)、グルタチオンペルオキシダーゼ(GPX)、リン脂質ヒドロペルオキシドグルタチオンペルオキシダーゼ(PGPX)、グルタチオンレダクターゼ(GR)、ペルオキシレドキシン(PRX3/5)、グルタレドキシン(GRX2)、チオレドキシン(TRX2)およびチオレドキシンレダクターゼ(TRXR2)を含む酵素成分を含む、他の広く認められている抗酸化防御化合物をさらに含む、請求項24に記載の方法。
- 低張、等張、または高張形態に製剤化される、請求項24に記載の方法。
- 前記組成物が、静脈内に、ボーラスによって、経皮的に、経口的に、光学的に、坐剤によって、口腔に、または吸入によって投与される、請求項24に記載の方法。
- 前記投与が約1分〜約1時間の期間にわたる注入によって前記組成物を導入することを含み、前記注入が約1日〜約1年から選択される期間にわたって必要に応じて繰り返される、請求項24に記載の方法。
- 対象の代謝を変更する方法であって、滅菌水溶液中に少なくとも1つの医薬品グレードの酸および少なくとも1つの医薬品グレードのpH緩衝剤を含有する静脈内緩衝液を含む安定な治療用組成物を前記対象に投与することを含み、
ここで、前記緩衝液中の前記医薬品グレードの酸および前記医薬品グレードのpH緩衝剤の濃度が、対象に投与したときに60mmol/L〜3,000mmol/Lの滴定可能な全酸含量を提供するのに十分であり、ならびに
前記医薬品グレードの酸および前記医薬品グレードのpH緩衝剤の選択が、4〜7.7の緩衝液pHを提供するのに有効である、
方法。 - 中枢神経系障害の治療を必要とする対象において中枢神経系障害を治療する方法であって、滅菌水溶液中に少なくとも1つの医薬品グレードの酸および少なくとも1つの医薬品グレードのpH緩衝剤を含有する静脈内緩衝液を含む安定な治療用組成物を前記対象に投与することを含み、
ここで、前記緩衝液中の前記医薬品グレードの酸および前記医薬品グレードのpH緩衝剤の濃度が、対象に投与したときに60mmol/L〜3,000mmol/Lの滴定可能な全酸含量を提供するのに十分であり、ならびに
前記医薬品グレードの酸および前記医薬品グレードのpH緩衝剤の選択が、4〜7.7の緩衝液pHを提供するのに有効である、
方法。 - 対象の慢性創傷を治療する方法であって、滅菌水溶液中に少なくとも1つの医薬品グレードの酸および少なくとも1つの医薬品グレードのpH緩衝剤を含有する静脈内緩衝液を含む安定な治療用組成物を前記対象に投与することを含み、
ここで、前記緩衝液中の前記医薬品グレードの酸および前記医薬品グレードのpH緩衝剤の濃度が、対象に投与したときに60mmol/L〜3,000mmol/Lの滴定可能な全酸含量を提供するのに十分であり、ならびに
前記医薬品グレードの酸および前記医薬品グレードのpH緩衝剤の選択が、4〜7.7の緩衝液pHを提供するのに有効である、
方法。 - 対象の精神的または身体的能力を高める方法であって、滅菌水溶液中に少なくとも1つの医薬品グレードの酸および少なくとも1つの医薬品グレードのpH緩衝剤を含有する静脈内緩衝液を含む安定な治療用組成物を前記対象に投与することを含み、
ここで、前記緩衝液中の前記医薬品グレードの酸および前記医薬品グレードのpH緩衝剤の濃度が、対象に投与したときに60mmol/L〜3,000mmol/Lの滴定可能な全酸含量を提供するのに十分であり、ならびに
前記医薬品グレードの酸および前記医薬品グレードのpH緩衝剤の選択が、4〜7.7の緩衝液pHを提供するのに有効である、
方法。 - 乳酸負荷の低減を必要とする対象において乳酸負荷を低減する方法であって、滅菌水溶液中に少なくとも1つの医薬品グレードの酸および少なくとも1つの医薬品グレードのpH緩衝剤を含有する静脈内緩衝液を含む安定な治療用組成物を前記対象に投与することを含み、
ここで、前記緩衝液中の前記医薬品グレードの酸および前記医薬品グレードのpH緩衝剤の濃度が、対象に投与したときに60mmol/L〜3,000mmol/Lの滴定可能な全酸含量を提供するのに十分であり、ならびに
前記医薬品グレードの酸および前記医薬品グレードのpH緩衝剤の選択が、4〜7.7の緩衝液pHを提供するのに有効である、
方法。 - 前記乳酸負荷が、アシドーシス、敗血症、または多系統萎縮症(MSA)である、請求項40に記載の方法。
- 前記乳酸負荷が身体運動の結果である、請求項40に記載の方法。
- 低酸素ストレスの解消または改善を必要とする対象において低酸素ストレスを解消または改善する方法であって、滅菌水溶液中に少なくとも1つの医薬品グレードの酸および少なくとも1つの医薬品グレードのpH緩衝剤を含有する静脈内緩衝液を含む安定な治療用組成物を前記対象に投与することを含み、
ここで、前記緩衝液中の前記医薬品グレードの酸および前記医薬品グレードのpH緩衝剤の濃度が、対象に投与したときに60mmol/L〜3,000mmol/Lの滴定可能な全酸含量を提供するのに十分であり、ならびに
前記医薬品グレードの酸および前記医薬品グレードのpH緩衝剤の選択が、4〜7.7の緩衝液pHを提供するのに有効である、
方法。 - 対象の動脈から血管プラークを除去し、それによってCa2+増加から生じる代謝危機を解消する方法であって、滅菌水溶液中に少なくとも1つの医薬品グレードの酸および少なくとも1つの医薬品グレードのpH緩衝剤を含有する静脈内緩衝液を含む安定な治療用組成物を前記対象に投与することを含み、
ここで、前記緩衝液中の前記医薬品グレードの酸および前記医薬品グレードのpH緩衝剤の濃度が、対象に投与したときに60mmol/L〜3,000mmol/Lの滴定可能な全酸含量を提供するのに十分であり、ならびに
前記医薬品グレードの酸および前記医薬品グレードのpH緩衝剤の選択が、4〜7.7の緩衝液pHを提供するのに有効である、
方法。 - 前記対象がヒトまたは獣医学的対象である、請求項20〜44のいずれか一項に記載の方法。
- 前記緩衝液が、対象の生理的血流のpHを0.01〜1.1だけ低下させるのに十分である、請求項20〜44のいずれか一項に記載の方法。
- 前記緩衝液が、前記対象の生理的血流のpHの低下を1分〜1週間維持するのに十分な緩衝能を有する、請求項46に記載の方法。
- 前記緩衝液が、対象の生理的血流のpHを0.15〜0.75だけ低下させるのに十分である、請求項46に記載の方法。
- 前記緩衝液が、対象の生理的血流のpHを0.15〜0.5だけ低下させるのに十分である、請求項46に記載の方法。
- 前記緩衝液が、前記対象の生理的血流のpHの低下を1分〜1時間維持するのに十分な緩衝能を有する、請求項46に記載の方法。
- 前記緩衝液が、前記対象の生理的血流のpHの低下を1時間〜1日間維持するのに十分な緩衝能を有する、請求項46に記載の方法。
- 前記緩衝液が、前記対象の生理的血流のpHの低下を1日〜1週間維持するのに十分な緩衝能を有する、請求項46に記載の方法。
- a.滅菌水溶液中に少なくとも1つの医薬品グレードの酸および少なくとも1つの医薬品グレードのpH緩衝剤を含有する静脈内緩衝液を含む安定な治療用組成物を含む第1のバイアル、
ここで、前記緩衝液中の前記医薬品グレードの酸および前記医薬品グレードのpH緩衝剤の濃度は、対象に投与したときに60mmol/L〜3,000mmol/Lの滴定可能な全酸含量を提供するのに十分であり、および
前記医薬品グレードの酸および前記医薬品グレードのpH緩衝剤の選択は、4〜7.7の緩衝液pHを提供するのに有効である;ならびに
b.使用説明書
を含むキット。 - a.滅菌水溶液中に少なくとも1つの医薬品グレードの酸を含有する静脈内緩衝液を含む第1のバイアル;ならびに
b.滅菌水溶液中に少なくとも1つの医薬品グレードのpH緩衝剤を含む第2のバイアル、
ここで、2つのバイアルの内容物は、組み合わされた場合、静脈内緩衝液を形成し、ここで、前記緩衝液中の前記医薬品グレードの酸および前記医薬品グレードのpH緩衝剤の濃度は、対象に投与したときに60mmol/L〜3,000mmol/Lの滴定可能な全酸含量を提供するのに十分であり、および
前記医薬品グレードの酸および前記医薬品グレードのpH緩衝剤の選択は、4〜7.7の緩衝液pHを提供するのに有効である;ならびに
c.使用説明書
を含むキット。
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Citations (6)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
JPH07503010A (ja) * | 1992-01-06 | 1995-03-30 | ヘルス・メインテナンス・プログラムズ,インコーポレイテッド | 薬学活性酸化防止剤含有組成物並びに該組成物を使用する血管形成後の再狭窄予防および治療方法 |
JP2004514650A (ja) * | 2000-05-19 | 2004-05-20 | プロジェニクス・ファーマスーティカルズ・インコーポレイテッド | デヒドロアスコルビン酸処方物およびその使用 |
JP2005179200A (ja) * | 2003-12-16 | 2005-07-07 | Terumo Corp | ビタミンb1類配合輸液剤 |
WO2011138973A1 (ja) * | 2010-05-07 | 2011-11-10 | 味の素株式会社 | ビタミン配合末梢静脈投与用栄養輸液 |
JP2013532661A (ja) * | 2010-07-22 | 2013-08-19 | リベン ファーマシューティカルズ インコーポレイテッド | 磁気双極子安定化溶液の使用を含む疾患を処置または改善する方法および行動を向上させる方法 |
US20150079201A1 (en) * | 2008-07-25 | 2015-03-19 | Reven Pharmaceuticals, Inc. | Compositions and methods for the prevention and treatment of cardiovascular diseases |
Family Cites Families (26)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
US5080886A (en) * | 1990-01-05 | 1992-01-14 | Sterling Drug Inc. | Pharmaceutical compositions for the prevention and treatment of oxidant injuries |
JPH0959150A (ja) * | 1995-08-11 | 1997-03-04 | Roussel Morishita Kk | 経静脈用輸液製剤 |
FR2740686B1 (fr) | 1995-11-03 | 1998-01-16 | Sanofi Sa | Formulation pharmaceutique lyophilisee stable |
US20030190307A1 (en) * | 1996-12-24 | 2003-10-09 | Biogen, Inc. | Stable liquid interferon formulations |
CA2371728C (en) | 1999-06-11 | 2009-06-02 | Neorx Corporation | High dose radionuclide complexes for bone marrow suppression |
US20040110684A1 (en) | 1999-08-02 | 2004-06-10 | Universite Catholique De Louvain | Novel pharmaceutical compositions for modulating angiogenesis |
US7122210B2 (en) * | 2002-01-11 | 2006-10-17 | Baxter International Inc. | Bicarbonate-based solutions for dialysis therapies |
WO2005044176A2 (en) | 2003-11-10 | 2005-05-19 | Lipogen Ltd. | Compositions containing phosphatidic acid, methods of use thereof, methods of manufacture thereof, and articles of manufacture containing same |
WO2005084660A1 (ja) * | 2004-03-05 | 2005-09-15 | Morishige, Fumie | ミトコンドリア病予防と対策 |
DE102004023828A1 (de) * | 2004-05-13 | 2005-12-08 | Fresenius Medical Care Deutschland Gmbh | Lösung für die Peritonealdialyse |
CU23432B6 (es) * | 2005-11-02 | 2009-10-16 | Ct Ingenieria Genetica Biotech | Formulaciones estabilizadas que contienen a los interferones gamma y alfa en proporciones potenciadoras |
JP4615470B2 (ja) | 2006-03-29 | 2011-01-19 | 卓郎 簑和田 | 大脳の認知力を用いた疾患治療・予防の方法および医薬 |
US7282225B1 (en) | 2006-09-27 | 2007-10-16 | Occular Technologies, Inc. | Composition and methods for improving retinal health |
CN101209344B (zh) * | 2006-12-28 | 2012-07-04 | 赵超英 | 高渗液组合物在制备促进伤口愈合的药物中的应用 |
EP2336120B1 (en) | 2007-01-10 | 2014-07-16 | MSD Italia S.r.l. | Combinations containing amide substituted indazoles as poly(adp-ribose)polymerase (parp) inhibitors |
WO2009152374A2 (en) * | 2008-06-12 | 2009-12-17 | Medtronic Xomed, Inc. | Method for treating chronic wounds |
WO2011011092A1 (en) | 2009-07-22 | 2011-01-27 | University Of Massachusetts | Methods and compositions to reduce oxidative stress |
WO2011013138A1 (en) * | 2009-07-29 | 2011-02-03 | Strides Arcolab Limited | Stable multi- vitamin formulations |
ES2457641T3 (es) * | 2009-10-15 | 2014-04-28 | Purecircle Sdn Bhd | Procedimiento para preparar rebaudiósido D de pureza elevada |
EP2324832B2 (de) * | 2009-11-09 | 2016-11-30 | Biogena Naturprodukte GmbH & Co KG | Nahrungsergänzungsmittel bei Einnahme von hormonellen Kontrazeptiva |
WO2012009171A2 (en) * | 2010-07-15 | 2012-01-19 | The Schepens Eye Research Institute, Inc. | Compositions and methods of treatment of corneal endothelium disorders |
KR20130021958A (ko) * | 2011-08-24 | 2013-03-06 | 울산대학교 산학협력단 | 인공 수액 |
WO2014028945A1 (en) * | 2012-08-17 | 2014-02-20 | The Regents Of The University Of California | Systems, methods and compositions for improved treatment of acidosis |
ES2795982T3 (es) | 2013-08-07 | 2020-11-25 | Yeda Res & Dev | Péptidos capaces de reactivar mutantes de p53 |
CN106924744A (zh) * | 2015-12-30 | 2017-07-07 | 钟术光 | 一种供注射或口服用的药物载体(或制剂) |
WO2017143446A1 (en) * | 2016-02-23 | 2017-08-31 | Mitronite Inc. | Compositions and methods for improving mitochondrial function |
-
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- 2023-07-14 JP JP2023115774A patent/JP2023134671A/ja active Pending
Patent Citations (6)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
JPH07503010A (ja) * | 1992-01-06 | 1995-03-30 | ヘルス・メインテナンス・プログラムズ,インコーポレイテッド | 薬学活性酸化防止剤含有組成物並びに該組成物を使用する血管形成後の再狭窄予防および治療方法 |
JP2004514650A (ja) * | 2000-05-19 | 2004-05-20 | プロジェニクス・ファーマスーティカルズ・インコーポレイテッド | デヒドロアスコルビン酸処方物およびその使用 |
JP2005179200A (ja) * | 2003-12-16 | 2005-07-07 | Terumo Corp | ビタミンb1類配合輸液剤 |
US20150079201A1 (en) * | 2008-07-25 | 2015-03-19 | Reven Pharmaceuticals, Inc. | Compositions and methods for the prevention and treatment of cardiovascular diseases |
WO2011138973A1 (ja) * | 2010-05-07 | 2011-11-10 | 味の素株式会社 | ビタミン配合末梢静脈投与用栄養輸液 |
JP2013532661A (ja) * | 2010-07-22 | 2013-08-19 | リベン ファーマシューティカルズ インコーポレイテッド | 磁気双極子安定化溶液の使用を含む疾患を処置または改善する方法および行動を向上させる方法 |
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