ANGIOTENSIN I-CONVERTING ENZYME ACTIVITY INHIBITOR

Abstract

Provided is an ACE activity inhibitor that can be integrated into easy-to-take daily food and drink. The ACE activity inhibitor of the present invention contains an amber extract wherein an extraction solvent thereof is hydrous ethanol (moisture content: 1 mass % to 60 mass %).

Claims

1. An angiotensin I-converting enzyme activity inhibitor comprising an amber extract wherein an extraction solvent thereof is hydrous ethanol (moisture content: 1 mass % to 60 mass %).

2. An oral administration composition for inhibiting an angiotensin I-converting enzyme activity prepared by blending the angiotensin I-converting enzyme activity inhibitor according to claim 1.

3. The oral administration composition for inhibiting an angiotensin I-converting enzyme activity according to claim 2, wherein an aspect is a pharmaceutical product, a quasi-drug, a food and drink or a food additive.

Description

BRIEF DESCRIPTION OF DRAWINGS

[0026] FIG. 1 is a graph showing inhibition of angiotensin I-converting enzyme activity by the amber extract of Production Example 1.

[0027] FIG. 2 is a graph showing diastolic blood pressure and systolic blood pressure by intake of the amber extract of Production Example 2.

DESCRIPTION OF EMBODIMENTS

[0028] <The Amber Extract of the Present Invention>

[0029] The ACE activity inhibitor according to the present invention contains an amber extract as an active ingredient. The amber extract herein refers to, e.g., amber itself, processed amber such as crushed or chopped amber, an amber extract with a solvent added to amber or processed amber, a solvent-free amber extract obtained by removing the solvent from the amber extract, and purified products of these. Of them, an amber extract or a solvent-free amber extract is particularly preferable. Also, the amber to be used in the present invention is not particularly limited by the production area; however, taking production and reserve thereof into consideration, amber produced in Kaliningrad of Russia is preferable.

[0030] Examples of the solvent for the amber extract include water, an alcohol such as methanol, ethanol, 1,3-butanediol, propylene glycol and glycerin; an ester such as ethyl acetate and methyl formate; a nitrile such as acetonitrile; an ether such as diethyl ether and tetrahydrofuran; a halogenated hydrocarbon such as chloroform and methylene chloride; and a ketone such as acetone and methyl ethyl ketone. These solvents may be used singly or as a mixture (of two or more). Of these solvents, water or an alcohol is preferable and hydroalcoholic solution is more preferable. As the alcohol, ethanol having a water content of 1 mass % to 60 mass %, and preferably 10 mass % to 50 mass % can be used. If the water content deviates from the upper lower end of the range mentioned above, extraction efficiency may deteriorate.

[0031] An extraction method is as follows. For example, to crushed amber, a solvent in a volume 2 to 20 times of the amber is added. If the extraction is carried out at room temperature, the crushed amber may be soaked for several days; whereas, if the extraction is carried out at about the boiling point, the crushed amber may be soaked for several hours. Thereafter, the resultant extract is subjected to filtration to remove insoluble matter. The filtrate may be concentrated under vacuum. The concentrate may be purified by column chromatography using a column packed with silica gel, octadecylsilyl silica gel or ion exchange resin.

[0032] <Production Example 1<

[0033] Powder (100 g) of amber produced in Kaliningrad of Russia was extracted with 50% ethanol (ethanol having a water content of 50%), concentrated under vacuum and lyophilized to obtain a 8 g of a 50% ethanol extract

[0034] Examples of drinks containing the extract of the present invention include tea drinks, coffee drinks, soft drinks, alcohol drinks, milk drink, carbonated drinks, healthy drinks, nutrition drinks, sports drinks and concentrated stock solutions of these and preparation powders. Examples of food include gums, candies, jellies, tablets, healthy food, nutritional supplementary food and supplements.

[0035] When the extract of the present invention is used as a medicine such as a prophylactic agent for hypertension, the extract is provided in the dosage form of a powder, a granule, a tablet, a capsule, a liquid and an injection. The extract of the present invention can be orally administered directly or as a dilution of the extract with water. Alternatively, the extract of the present invention may be prepared into a preparation in combination with a pharmaceutical carrier known in the art. More specifically, the extract of the present invention can be administered as an oral liquid preparation such as a syrup or as an oral solid preparation, such as tablets, capsules, granules and powders, which is prepared by processing the extract of the present invention into a liquid extract or a powder and blending the liquid extract or power with a pharmaceutically acceptable carrier. As the pharmaceutically acceptable carrier, an organic or inorganic carrier substance ordinarily used as preparation material is used and blended as an excipient, a lubricant, a binder and a disintegrant in a solid preparation, and as a solvent, an excipient, a suspending agent and a binder in a liquid preparation. If necessary, additives such as a preservative, an antioxidant, a coloring and a sweetener can be used in the preparations.

[0036] In a food and drink or a pharmaceutical composition containing the extract of the present invention, the extract of the present invention can be added in any concentration. The extract of the present invention is preferably added in a concentration of 0.01 to 50 mass % and more preferably 0.05 to 20 mass % of the total amount of a food and drink or a pharmaceutical composition.

[0037] The effective dosage can be appropriately determined depending on the age and body weight of a patient, the type and severity of the disease, and the administration route.

[0038] Now, the present invention will be more specifically described by way of Examples below; however, the present invention is not limited to these Examples.

EXAMPLES

Example 1

ACE Activity Inhibition Test

[0039] ACE activity was measured in accordance with the following procedure by using ACE Kit-WST (trade name, manufactured by DOJINDO LABORATORIES):

[0040] (1) The amber extract (10 mg) of Production Example 1 was dissolved in dimethyl sulfoxide (1 ml). After centrifugation, the supernatant was diluted serially with pure water 5 times. The individual dilutions were used as sample solutions.

[0041] (2) The sample solutions (sample) or pure water (blank 1, blank 2) were added to individual wells of a 96 well plate each in an amount of 20 μl.

[0042] (3) To individual wells, a substrate buffer was added in an amount of 20 μl.

[0043] (4) To the well of blank 2, pure water was added each in an amount of 20 μl.

[0044] (5) To each of the wells to which the sample solution was added and the well of blank 1, the enzyme solution (20 μl) was added. The plate was subjected incubation to be performed at 37° C. for 60 minutes.

[0045] (6) To each well, a color-producing liquid was added in an amount of 200 μl, and the plate was subjected incubation to be performed at room temperature for 10 minutes.

[0046] (7) Absorbance at 450 nm was measured by a plate reader.

[0047] (8) ACE inhibitory activity (inhibition rate %) is calculated in accordance with the following expression.

ACE inhibitory activity value (inhibition rate %)=[(A.sub.blank1−A.sub.sample)/(A.sub.blank1−A.sub.blank2)]×100

[0048] From the results shown in FIG. 1, it was confirmed that the amber extract of the present invention inhibits ACE activity in a concentration dependent manner.

Example 2

Effect of Amber Extract on Blood Pressure

[0049] The subjects (10 persons) having high blood pressure were allowed to take an amber extract (100 mg) of Production Example 1 once a day for four weeks. Blood pressure (systolic phase and diastolic phase) were measured before intake (0 W), 2 weeks (2 W) after intake and 4 weeks (4 W) after intake.

[0050] From the results of FIG. 2, it was confirmed that the amber extract of the present invention facilitates a decrease of both systolic blood pressure and diastolic blood pressure.