JP2010520155A - グルタミン残基を含む炭水化物系腹膜透析液 - Google Patents
グルタミン残基を含む炭水化物系腹膜透析液 Download PDFInfo
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- JP2010520155A JP2010520155A JP2009551077A JP2009551077A JP2010520155A JP 2010520155 A JP2010520155 A JP 2010520155A JP 2009551077 A JP2009551077 A JP 2009551077A JP 2009551077 A JP2009551077 A JP 2009551077A JP 2010520155 A JP2010520155 A JP 2010520155A
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- Prior art keywords
- glutamine
- peritoneal dialysis
- glutaminyl
- hsp
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- Granted
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- QNAYBMKLOCPYGJ-REOHCLBHSA-N L-alanine Chemical compound C[C@H](N)C(O)=O QNAYBMKLOCPYGJ-REOHCLBHSA-N 0.000 description 1
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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
- A61K38/00—Medicinal preparations containing peptides
- A61K38/04—Peptides having up to 20 amino acids in a fully defined sequence; Derivatives thereof
- A61K38/05—Dipeptides
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- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K31/00—Medicinal preparations containing organic active ingredients
- A61K31/185—Acids; Anhydrides, halides or salts thereof, e.g. sulfur acids, imidic, hydrazonic or hydroximic acids
- A61K31/19—Carboxylic acids, e.g. valproic acid
- A61K31/195—Carboxylic acids, e.g. valproic acid having an amino group
- A61K31/197—Carboxylic acids, e.g. valproic acid having an amino group the amino and the carboxyl groups being attached to the same acyclic carbon chain, e.g. gamma-aminobutyric acid [GABA], beta-alanine, epsilon-aminocaproic acid or pantothenic acid
- A61K31/198—Alpha-amino acids, e.g. alanine or edetic acid [EDTA]
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- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K38/00—Medicinal preparations containing peptides
- A61K38/04—Peptides having up to 20 amino acids in a fully defined sequence; Derivatives thereof
- A61K38/06—Tripeptides
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- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
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- A61K38/04—Peptides having up to 20 amino acids in a fully defined sequence; Derivatives thereof
- A61K38/07—Tetrapeptides
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- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K38/00—Medicinal preparations containing peptides
- A61K38/04—Peptides having up to 20 amino acids in a fully defined sequence; Derivatives thereof
- A61K38/08—Peptides having 5 to 11 amino acids
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- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61M—DEVICES FOR INTRODUCING MEDIA INTO, OR ONTO, THE BODY; DEVICES FOR TRANSDUCING BODY MEDIA OR FOR TAKING MEDIA FROM THE BODY; DEVICES FOR PRODUCING OR ENDING SLEEP OR STUPOR
- A61M1/00—Suction or pumping devices for medical purposes; Devices for carrying-off, for treatment of, or for carrying-over, body-liquids; Drainage systems
- A61M1/14—Dialysis systems; Artificial kidneys; Blood oxygenators ; Reciprocating systems for treatment of body fluids, e.g. single needle systems for hemofiltration or pheresis
- A61M1/28—Peritoneal dialysis ; Other peritoneal treatment, e.g. oxygenation
- A61M1/287—Dialysates therefor
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- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P13/00—Drugs for disorders of the urinary system
- A61P13/12—Drugs for disorders of the urinary system of the kidneys
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- A—HUMAN NECESSITIES
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- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P35/00—Antineoplastic agents
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- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P7/00—Drugs for disorders of the blood or the extracellular fluid
- A61P7/08—Plasma substitutes; Perfusion solutions; Dialytics or haemodialytics; Drugs for electrolytic or acid-base disorders, e.g. hypovolemic shock
Landscapes
- Health & Medical Sciences (AREA)
- Life Sciences & Earth Sciences (AREA)
- Veterinary Medicine (AREA)
- Public Health (AREA)
- General Health & Medical Sciences (AREA)
- Animal Behavior & Ethology (AREA)
- Pharmacology & Pharmacy (AREA)
- Chemical & Material Sciences (AREA)
- Medicinal Chemistry (AREA)
- Engineering & Computer Science (AREA)
- Epidemiology (AREA)
- Bioinformatics & Cheminformatics (AREA)
- Proteomics, Peptides & Aminoacids (AREA)
- Immunology (AREA)
- Gastroenterology & Hepatology (AREA)
- Urology & Nephrology (AREA)
- Heart & Thoracic Surgery (AREA)
- Emergency Medicine (AREA)
- Hematology (AREA)
- Organic Chemistry (AREA)
- General Chemical & Material Sciences (AREA)
- Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
- Chemical Kinetics & Catalysis (AREA)
- Vascular Medicine (AREA)
- Anesthesiology (AREA)
- Biomedical Technology (AREA)
- Diabetes (AREA)
- Medicines That Contain Protein Lipid Enzymes And Other Medicines (AREA)
- Acyclic And Carbocyclic Compounds In Medicinal Compositions (AREA)
- Medicinal Preparation (AREA)
Abstract
−グルタミン,好ましくはL−グルタミン,
−グルタミン,L−グルタミンを遊離形で放出しうるジペプチドであって,好ましくはグルタミニル−グリシン,グリシニル−グルタミン,グルタミニル−アラニン,アラニル−グルタミンからなる群より選択されるジペプチド,
−2から7個のグルタミン,好ましくはL−グルタミン残基から構成されるオリゴペプチド,および
−これらの混合物
からなる群より選択される化合物を含む炭水化物系腹膜透析液に関する。本発明の腹膜透析液は,腹膜透析治療を受けている人における技術的障害の抑制に有用である。
Description
−グルタミン,好ましくはL−グルタミン,
−グルタミン,好ましくはL−グルタミンを遊離形で放出しうるジペプチドであって,好ましくはグルタミニル−グリシン,グリシニル−グルタミン,グルタミニル−アラニンおよびアラニル−グルタミンからなる群より選択されるジペプチド,
−2から7個のグルタミン,好ましくはL−グルタミン残基から構成されるオリゴペプチド
−これらの混合物
からなる群より選択される化合物を含む炭水化物系腹膜透析液により解決される。
−グルタミン,好ましくはL−グルタミン,
−グルタミン,好ましくはL−グルタミンを遊離形で放出しうるジペプチドであって,好ましくはグルタミニル−グリシン,グリシニル−グルタミン,グルタミニル−アラニンおよびアラニル−グルタミンからなる群より選択されるジペプチド,
−2から7個のグルタミン,好ましくはL−グルタミン残基から構成されるオリゴペプチド,および
−これらの混合物
からなる群より選択される化合物であって,炭水化物系腹膜透析液を用いる腹膜透析治療における技術的障害を抑制する特定の用途のための化合物により解決される。
−グルタミン,好ましくはL−グルタミン,
−グルタミン,好ましくはL−グルタミンを遊離形で放出しうるジペプチドであって,,好ましくはグルタミニル−グリシン,グリシニル−グルタミン,グルタミニル−アラニンおよびアラニル−グルタミンからなる群より選択されるジペプチド,
−2から7個のグルタミン,好ましくはL−グルタミン残基から構成されるオリゴペプチド,および
−これらの混合物
からなる群より選択される,技術的障害を抑制するための特定の用途のための化合物を含む炭水化物系腹膜透析液により解決される。
−グルタミン,好ましくはL−グルタミン,
−グルタミン,好ましくはL−グルタミンを遊離形で放出しうるジペプチドであって,好ましくはグルタミニル−グリシン,グリシニル−グルタミン,グルタミニル−アラニンおよびアラニル−グルタミンからなる群より選択されるジペプチド,
−2から7個のグルタミン,好ましくはL−グルタミン残基から構成されるオリゴペプチド,および
−これらの混合物
からなる群より選択される化合物の,技術的障害を抑制するための炭水化物系腹膜透析液の製造における使用に関する。
PDのインビトロモデル(出典:文献5)
不死化ヒト中皮細胞(Met5A,ATCC CRL−9444)は,100ユニット/mlのペニシリン,100μg/mlのストレプトマイシンおよび10%FCSを補充したM199/MCDB105培地(1:1)で培養した。培養物は75cm2組織培養フラスコ(Falcon,Becton Dickinson,Oxnard,California)で37℃,5%CO2で維持し,定期的にトリプシン処理することにより継代した。培地は2〜3日ごとに交換した。平均して6−7日後にコンフルエントに達した。次に,コンフルエントの培養物を,1.5%無水デキストロース(pH5.5)を含む標準的なグルコースモノマーおよび酸性の乳酸系PDF(Fresenius 2,Bad Homburg,Germany)に,細胞保護化合物(4〜20mMのグルタミン)を添加してまたは添加せずに,120分間暴露し,通常の成長培地で16時間回復させた。対照培養物は通常の培地で37℃で維持し,"シャム培地交換"を行った,すなわち,PDFへの暴露と平行して対照培地に暴露した。
実験は,成人雄近交系スプラグドーリーラット(平均体重310g)を用いて行った。動物を麻酔した後(100mg/kgのケタミンおよび5mg/kgのキシラジン,筋肉内),加熱小動物手術台に置いた。小さい腹部正中切開を通して滅菌カテーテルを腹腔内に挿入し,35mlの試験液体(4〜10mMのL−グルタミンを添加または添加しないPDF)を45〜60秒間かけてゆっくり注入した。動物を静かに動かし,少量の腹膜液体を吸引し,カテーテルを抜去し,腹部を縫合した。動物は処置から20分以内に覚醒し,餌および水道水を自由に摂取させた。腹腔内注入の4時間後,動物を再び麻酔し,さらに別の少量の腹膜液体を吸引し,動物を心臓穿刺および放血により犠牲死させた。その後,正中切開により開腹し,腹膜内液体すべてを静かに回収した。回収した液体の容量を記録し,総細胞数および2つの時点(0および4時間)における数の相違を,ギムザ染色後に手動で,およびクールターカウンターで機械的に測定した。次に,各ラットについて,剥離した中皮細胞の総数を計算した。選択された動物においては,4時間ドウェル後,腹膜を0.1%のトリプシンおよび0.1%のEDTAを含む20mLのリン酸緩衝化食塩水(PBS)で20分間洗浄することにより,腹腔中の中皮細胞内膜を回収した。
ウエスタンブロッティング:中皮細胞回収物の蛋白質含量をブラッドフォード・アッセイ(BioRad)により測定し,等量の蛋白質サンプル(5μg/レーン)をPharmacia Multiphore IIユニットを用いる標準的なSDS−PAGEにより分離した。サイズ分画した蛋白質を,Pharmacia Multiphore II Novablotユニットで半乾燥移動によりPVDF膜に移した。膜をTBS−Tween(10mMTris,150mMNaCl,0.05%Tween20,pH8.0)中5%ドライミルクでブロッキングした。膜をHSP−72抗体(SPA810,Stressgen,B.C.,Canada)とともにインキュベーションした。検出は,ECLウエスタンブロッティング分析システムおよびプロトコル(Renaissance,NEN−Life Science Products,Boston,MA,USA)を用いて,ペルオキシダーゼ結合二次抗体(Sigma,USA)および強化化学発光(ECL)とともにインキュベーションすることにより行った。密度測定は画像分析ソフトウエア(Molecular Analyst software,Bio−Rad,USA)を用いて行った。HSP−72の発現差異は,内部標準に対して正規化した蛋白質/シグナル強度相関の直線範囲における特異的シグナルの比率から求め,平行実験間で比較した。
L−グルタミンの細胞保護効果
インビトロ実験により,L−グルタミンをPDFに加えた後,中皮細胞におけるHSP媒介性細胞保護が示された。
細胞保護PDFの原理の証明としてグルタミンについて記載された急性回復実験設定は,PDFの初期毒性効果の最も優れた代表物である。これは主として,低いpHおよび乳酸のためである。代替モデル,例えば,通常の培地で1:1に希釈した未使用PDFに長期暴露するモデルは,臨床的PDにおいて生ずるような,より長期のPDFへの暴露の際に腹膜において生ずる細胞プロセスを評価するための,よく受け入れられているツールである。
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Claims (7)
- −グルタミン,好ましくはL−グルタミン,
−グルタミン,好ましくはL−グルタミンを遊離形で放出しうるジペプチドであって,好ましくはグルタミニル−グリシン,グリシニル−グルタミン,グルタミニル−アラニンおよびアラニル−グルタミンからなる群より選択されるジペプチド,
−2から7個のグルタミン,好ましくはL−グルタミン残基から構成されるオリゴペプチド,および
−これらの混合物,
からなる群より選択される化合物を含む,炭水化物系腹膜透析液。 - −グルタミン,好ましくはL−グルタミン,
−グルタミン,好ましくはL−グルタミンを遊離形で放出しうるジペプチドであって,好ましくはグルタミニル−グリシン,グリシニル−グルタミン,グルタミニル−アラニンおよびアラニル−グルタミンからなる群より選択されるジペプチド,
−2から7個のグルタミン,好ましくはL−グルタミン残基から構成されるオリゴペプチド,および
−これらの混合物,
からなる群より選択される化合物であって,
炭水化物系腹膜透析液を用いる腹膜透析治療における技術的障害を抑制する特定の用途のための化合物。 - −グルタミン,好ましくはL−グルタミン,
−グルタミン,好ましくはL−グルタミンを遊離形で放出しうるジペプチドであって,好ましくはグルタミニル−グリシン,グリシニル−グルタミン,グルタミニル−アラニンおよびアラニル−グルタミンからなる群より選択されるジペプチド,
−2から7個のグルタミン,好ましくはL−グルタミン残基から構成されるオリゴペプチド,
および
−これらの混合物,
からなる群より選択される化合物を含む炭水化物系腹膜透析液であって,
技術的障害を抑制する特定の用途のための炭水化物系腹膜透析液。 - 前記オリゴペプチドは,アラニル−グルタミンおよびグルタミニル−アラニンからなる群より選択される,請求項1−3のいずれかに記載の腹膜透析液および/または化合物。
- 液体中の前記化合物の濃度は0.3mMから300mM,好ましくは2mMから25mMである,請求項1−4のいずれかに記載の腹膜透析液および/または化合物。
- 前記透析液はグルコース系である,請求項1−5のいずれかに記載の腹膜透析液および/または化合物。
- −グルタミン,好ましくはL−グルタミン,
−グルタミン,好ましくはL−グルタミンを遊離形で放出しうるジペプチドであって,好ましくはグルタミニル−グリシン,グリシニル−グルタミン,グルタミニル−アラニン,アラニル−グルタミンからなる群より選択されるジペプチド,
−2から7個のグルタミン,好ましくはL−グルタミン残基から構成されるオリゴペプチド,および
−これらの混合物,
からなる群より選択される化合物の,技術的障害を抑制するための炭水化物系腹膜透析液の製造における使用。
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AT3402007 | 2007-03-02 | ||
ATA340/2007 | 2007-03-02 | ||
PCT/AT2008/000072 WO2008106702A1 (en) | 2007-03-02 | 2008-03-03 | Carbohydrate-based peritoneal dialysis fluid comprising glutamine residue |
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EP (1) | EP2129370B1 (ja) |
JP (1) | JP5433424B2 (ja) |
CA (1) | CA2679452C (ja) |
DK (1) | DK2129370T3 (ja) |
ES (1) | ES2400001T3 (ja) |
HK (1) | HK1139311A1 (ja) |
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DK2129370T3 (da) | 2007-03-02 | 2013-02-11 | Zytoprotec Gmbh | Kulhydratbaseret peritonealdialysevæske indeholdende glutaminrest |
WO2024008684A1 (en) * | 2022-07-08 | 2024-01-11 | Zytoprotec Gmbh | Peritoneal dialysis fluid |
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JP2015506930A (ja) * | 2011-12-27 | 2015-03-05 | シュトプロテック ゲーエムベーハー | Gsk−3阻害剤を含む腹膜透析液 |
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WO2008106702A1 (en) | 2008-09-12 |
CA2679452C (en) | 2013-05-21 |
EP2129370B1 (en) | 2012-11-21 |
DK2129370T3 (da) | 2013-02-11 |
EP2129370A1 (en) | 2009-12-09 |
JP5433424B2 (ja) | 2014-03-05 |
CA2679452A1 (en) | 2008-09-12 |
US20140142051A1 (en) | 2014-05-22 |
HK1139311A1 (en) | 2010-09-17 |
US11534475B2 (en) | 2022-12-27 |
ES2400001T3 (es) | 2013-04-04 |
US20200113965A1 (en) | 2020-04-16 |
US9931369B2 (en) | 2018-04-03 |
US20100099628A1 (en) | 2010-04-22 |
PL2129370T3 (pl) | 2013-04-30 |
US20180177838A1 (en) | 2018-06-28 |
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