JPH04124140A - Angiotensin-transforming enzyme inhibitor - Google Patents

Abstract

PURPOSE:To obtain the subject enzyme inhibitor effective for therapy of hypertension, containing a fraction derived from the extract of a food with water, surfactant or an organic solvent. CONSTITUTION:The objective enzyme inhibitor contains a fraction derived from the extract of a food selected from pomegranate, Japanese plum, lemon, Japanese nutmeg, 'KYOHO' (name of a species of grape) and Chinese quince with water, or the extract of a food selected from tomato, pholiota nameko, cinnamon, grapefruit, pomegranate, kiwi fruit, Japanese plum, 'Sordam' (name of a species of plum), lemon, fruit of gardenia, Japanese nutmeg, pineapple, Delaware (a species of grape), neo-muscat, KYOHO (name of large grape), 'KABOSU' (a sort of citron), citron and Chinese quince with a solution of surfactant or an organic solvent (e.g. alcohols, esters, ethers or ketones), as an activating component. The extraction is performed with an extracting solvent in an amount of 2-5 times weight to raw material in a range of 0-100 deg.C for about 10min-24hr, and the resultant extracted solution is subjected to solid-liquid separation to remove a solid component, then concentrated, as necessary.

Description

DETAILED DESCRIPTION OF THE INVENTION (Field of Industrial Application) The present invention relates to angiotensin-converting enzyme inhibitors, and particularly to substances effective in treating hypertension.

(Prior art) Hypertension includes essential hypertension and secondary hypertension.
Essential hypertension and secondary hypertension (renal hypertension) are closely related to diseases such as endocrine hypertension. 8CE acts on T-tongiotensin I, and dipebutyM (ll+5
-Leu) and produce angiotensin (2), which has blood pressure increasing activity. Therefore, if we inhibit this enzyme,
It is possible to suppress increases in blood pressure. Searches for inhibitors have actually been conducted from this perspective, and various proline derivatives have been developed and put into practical use as pharmaceuticals. However, since they are synthetic products, they are not accepted by society as non-medicinal products, and have poor marketability for general consumers such as health foods. Among natural products, the inhibitory ability of green tea, soybeans, and soba noodles has been reported. However, the ACE of these natural products
The inhibitory ability is weaker than that of synthetic products).

(Problems to be Solved by the Invention) The present inventor faced the above-mentioned situation and investigated the possibility of using ACE inhibitors in natural food products. Surfactant extracts include tomato, nameko, nnamon, grapefruit, pomegranate, kiwifruit, plum, soldum, lemon, garden fruit, kayanomi, pineapple, prawea, neomuscat, and kyoho. The present invention was completed based on the discovery that there is a component that strongly inhibits ACE in fruits such as kabosu, yuzu, and quince.

Therefore, the present invention provides an enzyme inhibitor that can be used to lower blood pressure by inhibiting the activity of ACH induced in essential hypertension and secondary hypertension such as renal hypertension or endocrine hypertension. The purpose is to provide.

Foods are commonly ingested orally in Japan, and their safety is clear. Regarding ACE inhibition in foods, there have been reports on protease-degrading peptides from soybeans, corn, etc. (Japan Society of Agricultural Chemistry 1990 Conference Abstracts, ρ
247). In addition, Ehon et al. have reported on A-oral inhibition of water-soluble components of foods (Takeo Ehon et al.: Stratification, 57.1
143 (19g3)). However, no search for inhibition of 〇ε in undigested foods containing poorly water-soluble components has been made. Therefore, the present inventors have conducted extensive research to search for substances that exhibit a blood pressure lowering effect by inhibiting ACE, not only from water extracts but also from surfactant extracts, and have found that certain food extracts have the ability to inhibit ACE. They discovered that there is, and completed the present invention.

The present invention provides ACE inhibitors of food ingredients.

Foods used in the present invention include pomegranates, plums, lemons, oyster mushrooms, and giant I! foods containing water-soluble inhibitory ingredients. Foods containing li, quince, and poorly water-soluble inhibitory ingredients include tomatoes, nameko mushrooms, cinnamon, grapefruit, pomegranates, kiwifruit, plums, soldum, lemons, garden nuts, pineapple, pineapple, telaware, neomuscat, kyoho, kabosu, yuzu, One type or a mixture of two or more types of quince can be used as a starting material.

In the present invention, the extraction of active ingredients from foods is claimed in claim 2.
The food according to claim 4 uses water, and the food according to claim 4 uses a surfactant solution and an organic solvent.

In order to perform extraction using one or more of the foods described in claim 2 as starting materials, the extraction is carried out using the food as it is or after it has been crushed or dried and smoked by a conventional method. Extraction conditions are not particularly limited, but it is preferable to carry out the extraction at a temperature in the range of 0°C to 100°C for about 10 minutes to 24 hours.

The amount of water used during extraction is ~1 times that of the starting material.
It is preferably about 50 times (by weight), and preferably about 2 to 5 times.

Next, the obtained extract is subjected to solid-liquid separation to remove solid content, and then, if necessary, concentrated to obtain an extracted substance.

The surfactant used for food component extraction according to claim 4 includes a wide variety of substances, and the following may be exemplified.

Anionic surfactants such as taurocholic acid sodium salts, cationic surfactants, amine salts, quaternary ammonium salts, etc. The organic solvent used for extraction includes a wide variety of substances, and examples thereof include those listed below.

Alcohols (anhydrous or water-containing) Ethanol, methanol, propatool, etc. Esters Methyl acetate, ethyl acetate, etc. Ethers Diethyl ether, dipropyl ether, etc. Ketones Acetone, diethyl ketone, etc. Hydrocarbons Tetrahydrofuran, benzene, etc. Chlorinated hydrocarbons Chloroform These surfactants and organic solvents may be used alone or as a mixture of two or more. In order to extract one or more kinds of foods using the above-mentioned solvents as starting materials, extraction is performed on the foods as they are or on crushed or dried foods by a conventional method. Extraction conditions are not particularly limited, but 0°C to 1
It is preferable to carry out the treatment at a temperature of 00°C for about 10 minutes to 24 hours.

The amount of surfactant, organic solvent, etc. used during extraction is as follows:
It is best to use 1 to 50 times (by weight) of the starting material.
About 5 times is preferable.

Next, the obtained extract is subjected to solid-liquid separation to remove solid content, and then, if necessary, concentrated to obtain an extracted substance.

(Enzyme activity measurement method) To measure ACE inhibitory ability, a substrate (formerly ρ-formerly 5-Leu) was added to the test sample solution and ACE solution, and the resulting dipeptide (tlis-Leu) was shaken at 37t for 1 hour. After fluorescing with phthaldialdehyde, the fluorescence intensity was measured (E
X, 340%m Em, 455%m) L, ACE
Enzyme activity was calculated. Specifically, AC”ε solution (106 m
tl/5 ng) 20μi, 5mM substrate solution (pH
8,3) A 240 µm acetate was added and the reaction was carried out in the following conventional manner. Let S be the fluorescence intensity in the test sample solution, A be the fluorescence intensity when water and TCA solution are added instead of the sample, B be the fluorescence intensity when water is added instead of the enzyme, and (S-B) / By AX 100 (%), AC [
E enzyme activity was calculated. It is 100% when the enzyme is not inhibited at all, and 0% when it is completely inhibited.

Next, by showing examples of the present invention, the effects of the present invention will become clearer.

(Examples) Example 1 Water and surfactant extracts of foods were prepared, and the ability of water-soluble components and poorly water-soluble components of foods to inhibit ACE was examined.

First, crush 5 mg of the raw material dry food, and add 1 mfl of water and surfactant solution! Extract overnight at 5°C. 10.000
For the supernatant centrifuged for 10 minutes at 5°C, AC
E inhibition ability was measured. A 5mM taurocholic acid solution (hereinafter abbreviated as TCA) was used as a surfactant solution.

The results of the ACE inhibition test for water and TC^ extracts are shown in Table 1. Foods that were effective with aqueous extracts, that is, contained water-soluble inhibitory substances, were pomegranates, plums, lemons, oyster mushrooms, kyoho grapes, and quince.

Foods that are effective on TC8, that is, contain poorly water-soluble inhibitory substances, include tomatoes, nameko mushrooms, cinnamon, grapefruit, pomegranates, kiwifruit, plums, soldum, lemons, garden berries, pine nuts, pineapple, praware, They were Neomuscat, Kyoze, Kabosu, Yuzu, and Karin.

Example 2 Among foods, 10 mg of dried fruit pulp of pineapple, quince, lemon, and plum was mixed with water and various organic solvents (methanol,
Ethyl acetate, acetone, tetrahydrofuran, n-hexane, diethyl ether, chloroform) 2m! was added, extracted overnight at 5°C, and filtered through a 0.5 μm filter. 1 ml of the extract was concentrated under reduced pressure and dissolved in TCAlmf.
ACE inhibition ability was measured.

The results are shown in Table 2. Inhibition was shown not only in the aqueous extract used as a control but also in the organic solvent extract. Among the seven organic solvents, methanol, ethyl acetate, acetone, tetrahydrofuran, diethyl ether, and chloroform extracts were effective.

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(Effects of the Invention) As described above, the ACε inhibitor according to the present invention exhibits a strong inhibitory effect, and since it is extracted from food, which is a natural product, it is possible to provide a safe and highly effective antihypertensive agent. It becomes possible.

that's all

Claims (1)

[Scope of Claims] 1. An angiotensin converting enzyme inhibitor containing a fraction obtained by extracting food with water as an active ingredient. 2. The enzyme inhibitor according to claim 1, wherein the food is a mixture containing one or more components selectively extracted from pomegranate, plum, lemon, kayanomi, kyoho, and quince. 3. An angiotensin converting enzyme inhibitor containing a fraction obtained by extracting food with a surfactant solution or an organic solvent as an active ingredient. 4. Foods include tomatoes, nameko mushrooms, cinnamon, grapefruit, pomegranates, kiwifruit, plums, soldum, lemons, garden nuts, pine nuts, pineapples,
The enzyme inhibitor according to claim 3, which is a mixture containing one or more components selectively extracted from Delaware, neomuscat, Kyoho, kabosu, yuzu, and quince. 5. The enzyme inhibitor according to claim 3, wherein the organic solvent is one or a mixture of two or more selected from the group consisting of alcohols, esters, ethers, and ketones. 6. Surfactants include anionic surfactants, cationic surfactants,
Enzyme inhibitor according to claim 3, selected from amphoteric active agents and nonionic active agents.