JP2002080355A - Preventing and treating agent for hypertension - Google Patents

Abstract

PROBLEM TO BE SOLVED: To provide a preventing and treating agent for hypertension capable of suppressing the increase of blood pressure and improving hypertension, and usable as a medicine or a food for preventing and treating hypertension. SOLUTION: (a) A compound selected from a group consisting of coffeic acid, chlorogenic acid and ferulic acid, esters of the compounds, and pharmaceutically permissible salts of the compounds, and (b) a preventing and treating agent for hypertension containing a sugar alcohol.

Description

DETAILED DESCRIPTION OF THE INVENTION

[0001]

TECHNICAL FIELD The present invention relates to an agent for preventing and treating hypertension.

[0002]

2. Description of the Related Art Heart diseases such as angina pectoris, myocardial infarction, and heart failure or cerebrovascular diseases such as cerebral infarction, cerebral hemorrhage, and subarachnoid hemorrhage are very closely related to hypertension. Occupies second and third place. According to the Ministry of Health and Welfare Basic Survey on Human Life (1998), the number of patients who visit the hospital for hypertension is 64 per 1,000 in Japan, which is the leading cause of the disease. As measures against hypertension, diuretics,
Antihypertensive drugs, such as sympathomimetic drugs, vasodilators, and angiotensin exchange enzyme inhibitors, are mainly applied to patients with severe hypertension. On the other hand, general therapies aimed at improving lifestyle, such as diet, exercise, and restricting drinking and smoking, are widely applied to hypertensive patients from mild to severe. Is recognized. Above all, it is said that improving eating habits is important, and there are many foods that are said to have a blood pressure lowering effect as a tradition. In addition, search for food-derived blood pressure lowering materials has been actively conducted, and many active ingredients having blood pressure lowering action have been separated and identified.

[0003]

However, many of the pharmaceuticals currently used for the purpose of countermeasures against hypertension are satisfactory in terms of efficacy, but because of the side effects such as tachycardia and bradycardia which are not a little present. The burden on the patient is great. In addition, foods that are said to have a blood pressure lowering action or active ingredients thereof are not always satisfactory in their effectiveness, and many require a long period of time to develop a blood pressure lowering effect.

[0004] Accordingly, an object of the present invention is to provide a food and drink, a food for specified health use, and the like, which are excellent in safety for daily consumption, do not burden daily intake, and have a higher antihypertensive effect.
An object of the present invention is to provide quasi-drugs and pharmaceuticals.

[0005]

According to the present invention, there is provided a compound selected from the group consisting of (a) caffeic acid, chlorogenic acid, ferulic acid, esters thereof and pharmaceutically acceptable salts thereof, and (b) It is intended to provide a prophylactic / therapeutic agent for hypertension containing a sugar alcohol.

[0006]

BEST MODE FOR CARRYING OUT THE INVENTION As the component (a) used in the present invention, an extract of a natural product (particularly, a plant) containing the same can be used. Plants include, for example, coffee, onion, radish, lemon, moloheiya, senkyu, touki, pine, spinach, agi, sweet potato, corn, barley,
Rice and the like.

The caffeic acid and chlorogenic acid may be those extracted from plants such as green coffee beans, leaves of southern sky, immature apples, and the like. For example, coffee of the family Rubiaceae (Coffea arabic)
a LINNE) is preferably obtained by extraction with hot ascorbic acid, aqueous citric acid solution or hot water from seeds of LINNE).

The ferulic acid used in the present invention is a natural product such as rice or barley, particularly a compound contained in plants, and can be obtained as a purified product from plants or a synthetic product obtained industrially. . Ferulic acid ester, for example, rice bran oil obtained from rice bran,
After partitioning with aqueous ethanol and hexane at room temperature under weak alkalinity, the aqueous ethanol fraction is obtained. Ferulic acid can be obtained by hydrolyzing the ferulic acid ester obtained in the above step with sulfuric acid under pressure and heat and purifying it, or by obtaining bacteria (P
seudomonas) in the family Myrtaceae (Syzygium ar
omaticum MERRILL et PERRY) from buds and leaves of steam-distilled clove oil or a culture solution containing eugenol obtained by refining clove oil, and separating and purifying the culture solution. Can be.

When ferulic acid is prepared by chemical synthesis, it can be produced, for example, by a condensation reaction between vanillin and malonic acid (Journal of American Chemic).
al Society, 74, 5346, 1952). In addition, caffeic acid, chlorogenic acid, ferulic acid, or a pharmaceutically acceptable salt thereof has a stereoisomer, and in the present invention, a pure stereoisomer or a mixture thereof can be used.

Esters of caffeic acid, chlorogenic acid or ferulic acid are natural products, especially those originally contained in plants, those converted by chemical treatment upon extraction or fractionation, and those subjected to chemical modification. And others are included. Specific examples include ferulic acid esters. Specific examples of the ferulic acid ester include, for example, an ester with an alcohol having 1 to 40 carbon atoms,
An ester compound of linear or branched alkyl or alkenyl alcohol, allyl alcohol, terpene alcohol, sterol, or trimethyl sterol with ferulic acid may be mentioned. The present invention also includes those obtained by replacing ferulic acid in these ferulic acid esters with caffeic acid or chlorogenic acid.

The use of caffeic, chlorogenic and ferulic acids in the form of pharmaceutically acceptable salts improves water solubility and increases physiological effectiveness. Examples of the base substance for salt formation of these pharmaceutically acceptable salts include hydroxides of alkali metals or alkaline earth metals, for example, lithium hydroxide, sodium hydroxide, potassium hydroxide, magnesium hydroxide, Inorganic bases such as calcium hydroxide or ammonium hydroxide, arginine, lysine, histidine, basic amino acids such as ornithine, or monoethanolamine, diethanolamine, organic bases such as triethanolamine are used. Alkali metal or alkaline earth metal hydroxides may be mentioned. After preparing these salts, the salts may be added to the product of the present invention, or the salt-forming components may be separately added to the product of the present invention and reacted in a formulation system.

As the component (a), two or more kinds may be used in combination.

The component (b) sugar alcohol used in the present invention is a natural product, especially one originally contained in a plant, one converted by a chemical treatment at the time of extraction or fractionation, and subjected to chemical modification. And others are included. Specifically, monosaccharides, oligosaccharides, polysaccharides, and the like, in which the carbonyl group is reduced to alcohol are used. As a specific example of the monosaccharide alcohol, glucose is selected by fermenting and decomposing glucose with yeast. Erythritol, a sugar alcohol of sugar,
Pentose xylitol, hexose sorbitol, mannitol and the like are specific examples of oligosaccharides. Disaccharide alcohol palatinit (reduced palatinose), maltitol (reduced maltose), lactitol, branched oligosaccharide alcohols and the like are polysaccharide alcohols. Specific examples include reduced dextrin used as reduced starch syrup and the like.

Of the component (b), erythritol, xylitol, maltitol, palatinit, reduced dextrin, and branched oligosaccharide alcohol are preferred. As the component (b), two or more kinds may be used in combination.

When the agent for preventing or treating hypertension of the present invention is used as a medicine, a pharmaceutically acceptable carrier can be added to the above-mentioned active ingredient to prepare an oral or parenteral composition. Examples of the oral composition include tablets, granules, fine granules, pills, powders, capsules (including hard capsules and soft capsules), troches, chewables, and liquids (drinks). . Examples of the parenteral composition include intravenous preparations such as injections, suppositories, and external preparations for skin.

When the agent for preventing or treating hypertension of the present invention is used as a food, liquid foods such as drinks and soups, milky or pasty foods such as milk and curry, semi-solid foods such as jelly, gummy and jam, gums , Solid foods such as tofu, powdered foods, foods containing fats and oils such as margarine, mayonnaise, and dressings, and alternative forms of sugar substitutes.

The content of the component (a) in the preparation is 0.005 to 5% by weight (hereinafter simply referred to as%),
Preferably, it is 0.01 to 1%, and the component (b) is 0.1 to 1%.
It is 1-70%, preferably 1-50%.

An adult (body weight 6) of the component (a) used in the present invention.
0kg) The effective daily dose is 0.001 to
Preferably, it is such that it consumes 10 g, especially 0.005 to 5 g. In addition, an adult (body weight 6) of the component (b)
0 kg) The effective daily dose is 0.1 to 50
g, especially 1-20 g.

[0019]

Example 1 Evaluation of Suppression of Elevated Blood Pressure in Rats (1) Animal used Seven-week-old male spontaneously hypertensive rats (SHR) were prepared for 7 consecutive days in advance using a commercially available non-invasive blood pressure measuring device for rats ( By measuring blood pressure using Softlon Co., Ltd.)
After the rats were sufficiently familiarized with the blood pressure measurement operation, an evaluation test was started. All rats had a temperature of 25 ± 1 ° C., a relative humidity of 55 ± 10%, and an illumination time of 12 hours (7:00 am to 7 pm)
H) (bred room in the rat area).

(2) Administration method and dosage In the control group, a 1% aqueous sugar solution was used as drinking water, and a commercially available solid feed was freely ingested. In test plot 1, an aqueous solution containing 0.1% ferulic acid (manufactured by Wako Pure Chemical Industries, Ltd.) and 1% sugar was used as drinking water, and a commercially available solid feed was freely ingested. Test plot 2
In the present invention, an aqueous solution containing 0.1% ferulic acid and 1% erythritol (manufactured by Wako Pure Chemical Industries, Ltd.) was used as drinking water, and a commercially available solid feed was freely ingested.

(3) Test method SHR was used in 8 animals per group, and after 4 weeks, systolic blood pressure of the tail artery was measured.

(4) Statistical processing method The obtained test results are expressed as an average value and a standard error.
A t's t-test was performed and the significance level was set to 5% or less.

Table 1 shows the systolic blood pressure before administration and 4 weeks after administration. As is clear from Table 1, the ingestion of the product of the present invention in Test Section 2 showed a remarkable blood pressure increase suppressing effect.

[0024]

[Table 1]

Example 2 Evaluation of Hypotension in Rats (1) Animals Used Male 14-week-old male spontaneously hypertensive rats (SHR) were preliminarily bred in the same manner as in Example 1. (2) Administration method and dosage In the control group, a 1% aqueous solution of sugar was orally administered. In test group 1, an aqueous solution containing 0.2% ferulic acid and 1% sugar was orally administered. In Test Group 2, an aqueous solution containing 0.2% ferulic acid and 1% erythritol was orally administered. The dose was 15 mL / kg. (C) Test method Six SHRs were used per group, and the systolic blood pressure of the tail artery 1 hour after administration was measured.

Table 2 shows the systolic blood pressure before administration and 1 hour after administration, which were statistically treated in the same manner as in Example 1. As is evident from Table 2, a significant decrease in blood pressure was observed upon ingestion of the composition.

[0027]

[Table 2]

Example 3 Soft Capsules 50 mg of chlorogenic acid (manufactured by Wako Pure Chemical Industries, Ltd.) and 450 mg of maltitol (manufactured by Wako Pure Chemical Industries, Ltd.) were placed in a soft capsule skin (oval type, weight 150 mg). Filling was performed by a conventional method to produce a soft capsule. It showed a good blood pressure lowering effect.

Example 4 Beverage Skim Milk Powder 3.5% Lemon Extract 3.5 Palatinit (Wako Pure Chemical Industries, Ltd.) 9.0 Sodium Ferulate (Wako Pure Chemical Industries, Ltd.) 0.1 Citric Acid 1 Ascorbic acid 0.1 Flavor 0.1 Water 83.6 The storage stability of the beverage having the above composition was high, and the flavor was also good.

Example 5 Cookies Rapeseed oil 12% Corn starch 12 Orange extract 5 Flour 40 Butter 5 Reduced dextrin (manufactured by Wako Pure Chemical Industries, Ltd.) 14 Cycloartenol ferulate (manufactured by Wako Pure Chemical Industries, Ltd.) 1 Salt 0.5 Baking soda 0.5 water 10 A cookie having the above composition was baked. It was delicious.

[0031]

EFFECT OF THE INVENTION The increase in blood pressure is suppressed and hypertension is improved, so that it can be used as a medicament and food for preventing and treating hypertension.

Continued on the front page (51) Int.Cl. ⁷ Identification symbol FI Theme coat II (Reference) A23L 1/30 A23L 1/30 Z 4C206 2/52 C07H 13/04 C07H 13/04 A23L 2/00 F (72) Invention Person Ichiro Tokitsu 2606 Akabane, Kakaicho, Haga-gun, Tochigi Prefecture F-term in the Kao Corporation Research Laboratories (reference) 4B017 LC03 LK06 LK12 LL09 4B018 LB01 LB08 MD09 MD10 MD32 ME04 4B032 DB21 DK07 DK12 DL20 4C057 HH02 4C086 AA03 MA02A42A14 AA01 AA02 DA21 DB20 DB41 MA02 MA03 MA05 NA14 ZA42

Claims (1)

[Claims] 1. Hypertension comprising (a) a compound selected from the group consisting of caffeic acid, chlorogenic acid, ferulic acid, esters thereof and pharmaceutically acceptable salts thereof, and (b) a sugar alcohol. Prophylactic and therapeutic agents.