Angiotensin-converting-enzyme inhibiting dipeptide

A sequence, tryptophan technology, applied in the field of 15 kinds of dipeptides and peptide compositions containing them, can solve problems and other problems

Inactive Publication Date: 2015-04-29
YAMAKI CO LTD
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  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

AI Technical Summary

Problems solved by technology

However, in the case of pharmaceuticals, it is also true that dry cough, which is confirmed as a side effect by taking it, has problems in terms of QOL
In addition, it is known that drug withdrawal will rebound

Method used

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  • Angiotensin-converting-enzyme inhibiting dipeptide
  • Angiotensin-converting-enzyme inhibiting dipeptide
  • Angiotensin-converting-enzyme inhibiting dipeptide

Examples

Experimental program
Comparison scheme
Effect test

Embodiment 1

[0108] [(a) Industrial production of peptide composition having ACE inhibitory activity (1)]

[0109] Add 10,000 L of water to 1,000 kg of bonito knuckle protein, heat treatment (95°C, 35 minutes), remove amino acids and water-soluble proteins, add 2,884 L of water to the obtained hot water extraction residue 1,153 kg (576 kg of protein), and adjust the pH to 7 with 6N caustic soda. Protein NY100 (Amano enzyme) enzyme 2.0wt% (per protein enzyme amount) was added, and it was made to react at 50 degreeC for 20 hours, stirring. After the reaction, add caustic soda to adjust the pH to 6.8, and heat at 98°C for 15 minutes to inactivate the enzyme. Thereafter, the undecomposed protein was removed by a vibration filter, a Delaval centrifuge, and a centrifuge, and the supernatant was filtered and clarified with celite to obtain a decomposed liquid (200 kg of protein). ACE inhibitory activity IC 50 The value is 0.136 mg / ml (protein).

[0110] 200 kg of this peptide was loaded to the...

Embodiment 2

[0199] [(a) Industrial production of peptide composition having ACE inhibitory activity]

[0200] Add 10,000L of water to 1,000kg of skipjack protein, heat treatment (95°C, 35 minutes), remove amino acids and water-soluble proteins, add 4,436L of water to the obtained hot water extraction residue 1,774kg (886kg of protein), and adjust the pH to 7 with 6N caustic soda 1.0 wt% (per protein enzyme amount) of THERMOASE PC10F (Yamato Kasei) enzyme was added and reacted at 50° C. for 17 hours while stirring. After the reaction, add caustic soda to adjust the pH to 6.8, and heat at 98°C for 15 minutes to inactivate the enzyme. Thereafter, the undecomposed protein was removed by a vibrating filter, a Delaval centrifuge, and a centrifuge, and the supernatant was filtered with diatomaceous earth to obtain an enzymatic decomposition solution (200 kg of protein). ACE inhibitory activity IC 50 The value is 0.204 mg / ml (protein).

[0201] 200 kg of this peptide was loaded to the hydropho...

Embodiment 3

[0260] Synthesis of Peptides by Synthesis:

[0261] Using the automatic peptide synthesizer (ABI 430 model) of Applied Biosystems, according to the program, the peptide chain was extended from the C-terminus by the BOC method to synthesize the target protected peptide resin.

[0262] After the construction of the peptide on the resin is completed, the peptide resin is dried to protect it. Deprotection of the resulting protected peptide and cleavage of the peptide from the resin support were performed by anhydrous hydrogen fluoride treatment (HF / p-Creso18: 2 v / v, 60 minutes). The resulting crude peptide was extracted with 90% acetic acid and obtained as a powdered solid by lyophilization. Furthermore, the obtained crude peptide was loaded on a high performance liquid chromatography using an ODS column and purified to obtain the target peptide.

[0263] Column: YMC-Pack ODS-A (30mmID×250mmL, YMC)

[0264] Mobile layer: Buffer A: 5% CH 3 CN, 0.1% TFA

[0265] Buffer B: 40% C...

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Abstract

[Problem] To provide a useful dipeptide-containing composition derived from dried bonito flakes and the like, having an angiotensin-converting-enzyme inhibiting activity that imparts a blood pressure reducing function. [Solution] A composition containing a dipeptide derived from a fish meat protein having an angiotensin-converting-enzyme inhibiting activity. The composition is characterised by containing: at least one type of dipeptide selected from the group consisting of a dipeptide consisting of a tryptophan-leucine amino acid sequence, a dipeptide consisting of a leucine-tryptophan amino acid sequence, a dipeptide consisting of a tryptophan-isoleucine amino acid sequence, a dipeptide consisting of a valine-triptophan sequence, a dipeptide consisting of a tryptophan-tyrosine sequence, a dipeptide consisting of a tryptophan-methonine sequence, a dipeptide consisting of a serin-triptophan sequence, and a dipeptide consisting of an asparagine-triptophan sequence; and / or an acid addition salt of said dipeptide(s).

Description

【Technical field】 [0001] The present invention relates to useful 15 kinds of dipeptides having the activity of inhibiting angiotensin-converting enzyme (ACE), thereby exhibiting a blood pressure lowering effect, and peptide compositions containing them. The method for obtaining the dipeptide and peptide composition of the present invention is to absorb the dipeptide obtained by enzymatically hydrolyzing the protein NY100 (Amano Enzyme) with the insoluble protein remaining as a residue during hot water extraction of fish meat proteins, especially bonito knuckles. After the hydrophobic resin is detached from the water-containing alcohol and then passed through the ultrafiltration membrane (molecular weight: 1000), this highly active ACE-inhibiting fraction can be used as an active ingredient of an angiotensin-converting enzyme inhibitor and a blood pressure lowering agent. The dipeptide with high ACE inhibitory activity and the peptide composition containing the dipeptide of the...

Claims

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Application Information

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Patent Type & Authority Applications(China)
IPC IPC(8): C07K5/062A23L1/305A61K38/00A61P9/12A61P43/00C07K5/072C07K5/078
CPCA23L2/66A23L33/18A61K38/05A61P9/12A61P43/00C07K5/06026C07K5/06034C07K5/06043C07K5/06052C07K5/0606C07K5/06069C07K5/06078C07K5/06104C07K5/06121C07K5/06156A23V2002/00A23V2200/326A61K38/00C07K5/06C07K5/06113
Inventor 关英治朝田仁
Owner YAMAKI CO LTD
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