JP2010209084A - Angiotensin-converting enzyme inhibitor - Google Patents

Abstract

<P>PROBLEM TO BE SOLVED: To provide an angiotensin-converting enzyme inhibitor able to be easily produced, more safely and easily ingested and absorbed in high efficiency. <P>SOLUTION: The angiotensin-converting enzyme inhibitor contains L-serine or its salt as an active ingredient. Forms of the inhibitor are not particularly limited, and a powder, tablet, liquid form dissolved in a proper medium and the like are cited. Objects for administering the inhibitor are animals such as mammals including humans, routes of administration are not particularly limited, and the inhibitor is preferably administered perorally. <P>COPYRIGHT: (C)2010,JPO&INPIT

Description

The present invention relates to an angiotensin converting enzyme (ACE) inhibitors.

  Conventionally, it is known that peptides having a specific sequence have various physiological activities. For example, Patent Documents 1 to 3 and Non-Patent Documents 1 to 3 describe that some peptides have ACE inhibitory activity. These peptides have a strong ACE inhibitory activity, have been shown to have a strong antihypertensive action in spontaneously hypertensive rats (SHR), and to have an antihypertensive effect on hypertensive patients.

  However, ACE inhibitory peptides with specific sequences that have been proposed in the past can be obtained mainly by enzymatic degradation or fermentation, but the yield is extremely low, and there is a concern about safety when chemically synthesized. Is done. Accordingly, there is a need for an ACE inhibitor that can be more easily produced, can be safely and easily ingested, and is absorbed at a high rate.

JP-A-4-28239 JP-A-6-40944 JP-A-6-197786

J. Dairy Sci. 1995, 78: 777-783 J. Dairy Sci. 1995, 78: 1253-1257 Am. J. Clin. Nutr. 1996, 64: 767-771

An object of the present invention can be easily produced, it can be taken more safely and easily, and to provide an ACE inhibitor which is absorbed at a high rate.

According to the present invention, an angiotensin converting enzyme inhibitor characterized by containing as L- serine or a salt thereof as an active ingredient is Ru are provided.

Since the ACE inhibitor of the present invention contains the specific amino acid component as an active ingredient, the ACE inhibitor can be easily produced, and can be safely and easily ingested, and is absorbed at a high rate. Useful as .

2 is a graph showing measurement results of ACE inhibitory activity (inhibition rate) of each amino acid in Example 1. FIG.

The present invention will be described in detail below.
The ACE inhibitor of the present invention contains L-serine or a salt thereof as an active ingredient .
What is the known ACE-inhibitory peptides are also known high ACE inhibitory activity than amino acids, amino acid is rich in dietary experience, does not adversely affect the living body even when a relatively large amount ingested Therefore, ACE inhibitory activity can be safely used by ingesting a large amount.

The content ratio of the specific amino acid in the ACE inhibitor of the present invention can be usually 1 to 100% (w / w).
Forms of ACE inhibitors of the present invention is not particularly limited, the specific amino acid or Ranaru powder, tablet, or include a suitable solvent liquid was dissolved in like. Further, in addition to the specific amino acid as an active ingredient, it may contain other ACE inhibitors, various nutritional ingredients and various additives for food or medicine as long as the effects of the present invention are not impaired. good.

The subject of administration of the ACE inhibitor of the present invention can be animals such as mammals including humans. The administration route is not particularly limited, but can be preferably administered orally.
The dosage of the ACE inhibitor of the present invention can be appropriately determined according to the type of active ingredient, dosage form, etc., when the active ingredient is only the specific amino acid or when it contains other ACE inhibitors. . For example, when it contains only the specific amino acid as an active ingredient by oral administration, the specific amino acid amount can be 10 mg to 10000 mg, preferably 50 mg to 5000 mg.

The method for preparing the ACE inhibitor of the present invention is not particularly limited, and specifically, for example, the specific amino acid is obtained by microbial fermentation, enzymatic degradation of protein or peptide, chemical synthesis, etc. Ru can be prepared by blending with other components.

EXAMPLES Hereinafter, although this invention is demonstrated in detail with reference to an Example, this invention is not limited to these.
Example 1
The ACE inhibitory activity of various amino acids (L form, purchased from Wako Pure Chemical Industries, Ltd.) was measured by the following procedure.

(a) ACE derived from bovine lung (manufactured by Wako Pure Chemical Industries, Ltd.) was dissolved in pH 8.3, 0.1 M borate buffer so as to be 0.1 U to obtain an ACE solution. On the other hand, 20 mg of amino acids dissolved in pH 8.3 and 0.1 M borate buffer were prepared at 10 mg / ml (final concentration of 2.7 mg / ml. Each amino acid solution was put in a test tube with 80 μl. 200 μl of hippuryl histidyl leucine (final concentration 5 mM, containing NaCl 300 mM) was added, and 20 μl of the ACE solution was further added, and the mixture was reacted for 30 minutes at 37 ° C. Thereafter, 250 μl of 1N hydrochloric acid was added to react. After stirring, 1.7 ml of ethyl acetate was added, and after stirring, 1.4 ml of the ethyl acetate layer was collected in a test tube and evaporated to dryness at 120 ° C. for about 60 minutes. Water was added and the absorbance at 228 nm of hyprilic acid extracted into ethyl acetate was measured.

(b) As a control, (b-1) The same as (a) except that the amino acid solution was not added, (b-2) The same as (a) except that the ACE solution was not added Absorbance was measured for the engineered product and (b-3) the same procedure as in (a) except that the amino acid solution and the ACE solution were not added.

From the absorbance measured in (a) and (b), ACE inhibitory activity was determined as an inhibition rate (%) by the following formula (1). The results are shown in FIG. In the measurement of this example, the value of A below was 0.35.
Inhibition rate (%) = (A−B) × 100 / A (1)
A: (Absorbance at (b-1))-(Absorbance at (b-3))
B: (Absorbance at (a))-(Absorbance at (b-2))

As a reference example amino acid solution, pH 8.3, 0.1 μl borate buffer solution containing L-cysteine at a predetermined concentration (100, 50, 25, 10 and 1.0 μg / ml) or L-histidine at a predetermined concentration (10 , 5.0, 2.5, 1.0 and 0.5 mg / ml) ACE inhibitory activity was measured in the same manner as in Example 1 except that the dissolved ones were prepared. From these measurement results, the concentration at which the inhibition rate was 50% was determined as the IC50 value. As a result, the IC50 value of L-cysteine was 33 μM, and the IC50 value of L-histidine was 1030 μM.

Claims (1)

An angiotensin converting enzyme inhibitor comprising L-serine or a salt thereof as an active ingredient.

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