JP2008511317A - Ace阻害乳漿加水分解物 - Google Patents
Ace阻害乳漿加水分解物 Download PDFInfo
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- JP2008511317A JP2008511317A JP2007529748A JP2007529748A JP2008511317A JP 2008511317 A JP2008511317 A JP 2008511317A JP 2007529748 A JP2007529748 A JP 2007529748A JP 2007529748 A JP2007529748 A JP 2007529748A JP 2008511317 A JP2008511317 A JP 2008511317A
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Classifications
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- C07K14/46—Peptides having more than 20 amino acids; Gastrins; Somatostatins; Melanotropins; Derivatives thereof from animals; from humans from vertebrates
- C07K14/47—Peptides having more than 20 amino acids; Gastrins; Somatostatins; Melanotropins; Derivatives thereof from animals; from humans from vertebrates from mammals
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- C12P—FERMENTATION OR ENZYME-USING PROCESSES TO SYNTHESISE A DESIRED CHEMICAL COMPOUND OR COMPOSITION OR TO SEPARATE OPTICAL ISOMERS FROM A RACEMIC MIXTURE
- C12P21/00—Preparation of peptides or proteins
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- C—CHEMISTRY; METALLURGY
- C12—BIOCHEMISTRY; BEER; SPIRITS; WINE; VINEGAR; MICROBIOLOGY; ENZYMOLOGY; MUTATION OR GENETIC ENGINEERING
- C12Y—ENZYMES
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- C12Y304/15001—Peptidyl-dipeptidase A (3.4.15.1)
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- C—CHEMISTRY; METALLURGY
- C12—BIOCHEMISTRY; BEER; SPIRITS; WINE; VINEGAR; MICROBIOLOGY; ENZYMOLOGY; MUTATION OR GENETIC ENGINEERING
- C12Y—ENZYMES
- C12Y304/00—Hydrolases acting on peptide bonds, i.e. peptidases (3.4)
- C12Y304/21—Serine endopeptidases (3.4.21)
- C12Y304/21026—Prolyl oligopeptidase (3.4.21.26), i.e. proline-specific endopeptidase
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- Pharmacology & Pharmacy (AREA)
- Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
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Abstract
【選択図】なし
Description
1.ACE阻害のイン ビトロ(in vitro)測定
ペプチド又は他の製品(例えば加水分解物)のACE阻害活性のイン ビトロ測定が、以下のように行なわれた:
・製品が、ホウ酸塩、塩化ナトリウムからなる測定バッファー(pH 8.3)中に溶解される。
・測定に使用される基質は、SigmaからのHippuryl-His-Leuである(H1635)。
・ACE酵素がまた、Sigmaから得られる(A6778)。
1.Domovictus 535(BDI);およそ35%のタンパク質を有するWPCであり、そのうちのおよそ85%がBLGである。
2.Hiprotal 580 (BDI);80%のタンパク質を有するWPCであり、そのうちの80%がBLGである。
3.カゼイン(Sigma)
4.Hiprotal 880 (BDI);80%のタンパク質を有するWPCであり、そのうちの50%がBLGである。
5.ベータ-ラクトグロブリン(Sigma)
6.アルファ-ラクトアルブミン(Sigma)
・CE90ACE (ACEを阻害すると疑われているDMV製品;www.dmv-international.comを参照)
・加水分解物DI 3065 (Arla) (79.8%タンパク質)
・加水分解物LE 80 BM (DMV) (81.7%タンパク質)
・加水分解物E 90 STL (DMV) (83.5%タンパク質)
・加水分解物CE90 CPP (DMV) (87.0%タンパク質)
1. Process for producing fermented milk containing angiotensin converting enzyme inhibitory peptide and process for producing milk serum; CALPIS CO., LTD.; 欧州公開特許EP 1142481A1号公報。
2. Process for producing fermented milk containing angiotensin converting enzyme inhibitory peptide and process for producing milk serum; CALPIS CO., LTD.; 欧州公開特許EP 1142481A4号公報。
3. HIGH YIELD PRODUCTION OF CURDS AND WHEY CONTAINING AN ACE INHIBITOR PEPTIDE(VAL-PRO-PRO AND/OR ILE-PRO-PRO) MADE UNDER STIRRING CONDITIONS; CALPIS CO.,LTD; ニュージーラン公開特許NZ 0513305A号公報。
4. Process for producing granules containing angiotensin-converting enzyme inhibiting peptides; CALPIS CO., LTD.; 米国特許US 6428812号公報。
5. GRANULES FOR ORAL ADMINISTRATION, PROCESS FOR PRODUCING THE SAME, AND TABLETS PRODUCED FROM THE GRANULES; CALPIS CO., LTD.; 国際公開WO 0041677A1号パンフレット。
6. GRANULATED MATERIAL, ITS PRODUCTION AND TABLET USING THE SAME; CALPIS CO., LTD.; 日本国公開特許JP 200020405A2号公報。
7. Method of purifying whey of lactic acid fermentation by electrodialysis; CALPIS CO.LTD; 米国特許US 6204362号公報。
8. Mullally等; Identification of a novel angiotensin-I-converting enzyme inhibitory peptide corresponding to a tryptic fragment of bovine β-lactoglobulin; FEBS Lett. 第402巻(1997年), 第99-101頁。
9. Abubakar等; Structural analysis of new antihypertensive peptides derived from cheese whey protein by proteinase K digestion; J. of Dairy Sci. 第81巻(1998年),第3131-3139頁。
10. Pihlanto-Leppala等; Angiotensin-I-converting enzyme inhibitory peptides derived from bovine milk proteins; Int. Dairy J. 第8巻(1998年), 第325-331頁。
11. Pihlanto-Leppala等; Angiotensin-I-converting enzyme inhibitory properties of whey protein digests: concentration and characterization of active peptides; J. of Dairy Res. 第67巻(2000年), 第53-64頁。
12. NEW PEPTIDE AND ITS UTILIZATION; SNOW BRAND CO. LTD.; 日本国公開特許JP 0829088A2号公報。
13. Human β-casein, process for producing it and use thereof; SYMBICOM AKTIEBOLAG; 米国特許US 5739407号公報。
14. GENE ENCODING A HUMAN BETA-CASEIN PROCESS FOR OBTAINING THE PROTEIN AND USE THEREOF IN AN INFANT FORMULA; SYMBICOM 欧州公開特許EP 0599978A1号公報。
15. GENE ENCODING A HUMAN BETA-CASEIN PROCESS FOR OBTAINING THE PROTEIN AND USE THEREOF IN AN INFANT FORMULA; SYMBICOM AKTIEBOLAG; WO 9304172A3号パンフレット。
16. GENE ENCODING A HUMAN BETA-CASEIN PROCESS FOR OBTAINING THE PROTEIN AND USE THEREOF IN AN INFANT FORMULA; SYMBICOM AKTIEBOLAG; 国際公開WO 9304172A2号パンフレット。
17. New peptide and angiotensin transferase inhibitor; NISSHIN FLOUR MILLING CO. LTD;日本国公開特許JP 04082898A2号公報。
18. Enzymatic treatment of whey proteins for the production of antihypertensive peptides, the resulting products and treatment of hypertension in mammals; DAVISCO; 国際公開WO 0185984号パンフレット。
19. Reducing cholesterol with hydrolyzed whey protein; DAVISCO; 国際公開WO 03/063778 A2号パンフレット。
20. Process for producing a product containing antihypertensive tripeptides; VALIO; 国際公開WO 01/32906号パンフレット。
Claims (16)
- アンギオテンシン転化酵素(ACE)阻害活性を有するタンパク質加水分解物を酵素的に生産するための方法であって、第1反応工程において広域スペクトルエンドプロテアーゼでベータ−ラクトグロブリン(BLG)含有基質を処理すること、引き続き第2反応工程においてプロリン特異的エンドプロテアーゼで処理することによって特徴付けられる方法。
- 前記基質が、乳漿タンパク質濃縮物(WPC)、好ましくはベータ−ラクトグロブリン(BLG)を富化されたWPCであることを特徴とする、請求項1に記載の方法。
- 前記基質が、少なくとも25%、好ましくは少なくとも35%、より好ましくは少なくとも60%のBLGを含むことを特徴とする、請求項1又は2に記載の方法。
- 広域スペクトルエンドプロテアーゼが、セリンプロテアーゼ、メタロプロテアーゼ又はアスパルテートプロテアーゼであることを特徴とする、請求項1〜3のいずれか一項に記載の方法。
- 広域スペクトルエンドプロテアーゼが、微生物プロテアーゼ、好ましくはバチルス・リケンフォルミス(Bacillus lichenformis)又はバチルス・スブチリス(Bacillus subtilis)から単離されたプロテアーゼであることを特徴とする、請求項1〜4のいずれか一項に記載の方法。
- プロリン特異的エンドプロテアーゼが、プロリン特異的エンドプロテアーゼ(PSE; EC 3.4.21.26)であることを特徴とする、請求項1〜5のいずれか一項に記載の方法。
- 第1反応工程が、約10〜約15%の加水分解の程度が到達されるまで行なわれる、請求項1〜6のいずれか一項に記載の方法。
- 第2反応工程が、少なくとも0.5時間、好ましくは少なくとも1時間、より好ましくは少なくとも2時間、最も好ましくは少なくとも3時間の間行なわれる、請求項1〜7のいずれか一項に記載の方法。
- 第2反応工程が、多くとも24時間、好ましくは多くとも16時間、より好ましくは多くとも10時間の間行なわれる、請求項1〜8のいずれか一項に記載の方法。
- アンギオテンシン転化酵素(ACE)阻害活性を有するタンパク質加水分解物であって、請求項1〜9のいずれか一項に記載の方法に従って得られうるタンパク質加水分解物。
- 請求項10に記載の加水分解物を含む組成物、好ましくは医薬組成物又は食品若しくはし好食料。
- 前記組成物が、液体製品、例えば乳製品若しくはフルーツジュース、又は固形製品、例えば粉末である、請求項11に記載の組成物。
- 哺乳動物、好ましくはヒト、より好ましくは高血圧又は高血圧の増加された危険を有するヒトにおけるACE活性を阻害するために請求項11又は12に記載の組成物を使用する方法。
- 哺乳動物におけるACE活性を阻害するための処置方法であって、ACE活性を阻害するために十分な量において及び投与間隔で、請求項11又は12に記載の組成物を投与する、好ましくは経口投与することを含む処置方法。
- 哺乳動物における高血圧の症状を減少するための処置方法であって、高血圧の症状を抑制するために十分な量において及び投与間隔で、請求項11又は12に記載の組成物を投与する、好ましくは経口投与することを含む処置方法。
- 哺乳動物におけるACE活性を阻害するための、血圧を下げるための及び/又は高血圧の発生を予防するための医薬品の調製のために請求項11又は12に記載の組成物を使用する方法。
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NL1026931A NL1026931C2 (nl) | 2004-08-31 | 2004-08-31 | ACE-remmende wei-hydrolysaten. |
PCT/NL2005/000622 WO2006025731A1 (en) | 2004-08-31 | 2005-08-29 | Ace-inhibitory whey hydrolysates |
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EP1967524A1 (en) * | 2007-03-06 | 2008-09-10 | Friesland Brands B.V. | Methods for producing ACE-inhibitory peptides from whey and peptides obtained thereby |
WO2009115331A2 (en) * | 2008-03-20 | 2009-09-24 | University Of Limerick | Protein product for modifying cardiovascular health |
DE102008032828A1 (de) | 2008-07-02 | 2010-01-07 | Technische Universität Dresden | Tryptophanhaltige Peptide aus alpha-Lactalbumin mit blutdrucksenkender und vasoprotektiver Wirkung für biofunktionelle Lebensmittel |
DE102011005288B4 (de) | 2011-03-09 | 2018-10-11 | Technische Universität Dresden | Verfahren zur Herstellung eines Proteinhydrolysats mit ACE-hemmenden tryptophanhaltigen Dipeptiden |
ES2394988B2 (es) * | 2011-06-15 | 2013-06-06 | Queizúar, S.L. | Procedimiento optimizado para la obtención de péptidos inhibidores de la actividad de la eca a partir de suero lácteo, péptidos inhibidores de la eca y alimento que los comprende. |
US20120322745A1 (en) * | 2011-06-15 | 2012-12-20 | Queizuar ,S.L. | Optimized method for obtaining ace activity inhibitory peptides from whey, ace inhibitory peptides and food comprising them |
CN103215333A (zh) * | 2013-04-16 | 2013-07-24 | 陕西科技大学 | 一种酶解羊乳酪蛋白制备ace抑制肽的方法 |
CN103215331A (zh) * | 2013-04-16 | 2013-07-24 | 陕西科技大学 | 一种复合酶解羊乳酪蛋白制备ace抑制肽的方法 |
CN112574294A (zh) * | 2020-12-30 | 2021-03-30 | 青海瑞肽生物科技有限公司 | 一种胶原蛋白肽及其制备方法和应用 |
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WO2002045524A2 (en) * | 2000-12-07 | 2002-06-13 | Dsm Ip Assets B.V. | Prolyl endoprotease from aspergillus niger |
WO2003007730A1 (en) * | 2001-07-18 | 2003-01-30 | Dsm Ip Assets B.V. | Process for the hydrolysis of milk proteins |
JP2004519204A (ja) * | 2000-05-08 | 2004-07-02 | ダビスコ フーズ インターナショナル インコーポレーテッド | 抗高血圧ペプチドの生成のための乳漿タンパク質の酵素処理、得られた産物、および哺乳動物における高血圧の処置 |
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WO2002045524A2 (en) * | 2000-12-07 | 2002-06-13 | Dsm Ip Assets B.V. | Prolyl endoprotease from aspergillus niger |
WO2003007730A1 (en) * | 2001-07-18 | 2003-01-30 | Dsm Ip Assets B.V. | Process for the hydrolysis of milk proteins |
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EP1794189B1 (en) | 2008-06-04 |
EP1794189A1 (en) | 2007-06-13 |
US20080070828A1 (en) | 2008-03-20 |
WO2006025731A1 (en) | 2006-03-09 |
PL1794189T3 (pl) | 2008-12-31 |
PT1794189E (pt) | 2008-09-10 |
NL1026931C2 (nl) | 2006-03-01 |
ES2308531T3 (es) | 2008-12-01 |
DE602005007365D1 (de) | 2008-07-17 |
ATE397623T1 (de) | 2008-06-15 |
DK1794189T3 (da) | 2008-09-15 |
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