JP2006298802A - Ester-bonded chlorogenic acid derivative/alginine having vasorelaxing action and food supplement and cosmetic containing the same - Google Patents

Abstract

<P>PROBLEM TO BE SOLVED: To provide an ester-bonded chlorogenic acid derivative/alginine having little side effects and excellent vasorelaxing action and to provide an excellent food supplement and an excellent cosmetic each containing the ester-bonded product and having little side effects. <P>SOLUTION: The ester-bonded product having vasorelaxing action comprises chlorogenic acid or a chlorogenic acid derivative and alginic acid and contains any one member selected from among gamma-aminobutyric acid, an amino acid, a polyamine, an aminosugar, and a glucosamine. An ester-bonded product is provided which is obtained by adding alginine to leaves or root tubers of yacon of the family Compositae and reducing the extract with an alkali. The food and the cosmetic each comprises an ester-bonded chlorogenic acid derivative/alginic acid having vasorelaxing action. <P>COPYRIGHT: (C)2007,JPO&INPIT

Description

The present invention relates to an ester conjugate of a chlorogenic acid derivative having vasorelaxant action, blood pressure lowering action and anti-arteriosclerotic action and arginine, food preparation containing the same, and cosmetics.

Hypertension is one of the lifestyle-related diseases, and according to statistical data of the Ministry of Health, Labor and Welfare in 2002, hypertension accounts for the largest number of patients including hospitalization and outpatient as the estimated number of patients. Has been reported (for example, see Non-Patent Document 1).

According to the estimation of annual medical expenses by disease in 1999 created by the University of Tokyo, hypertensive diseases are the largest among Japanese patients, and the cost of treatment approaches 2 trillion yen (for example, Non-Patent Document 2). reference.). Considering the current situation in which the issue of financial resources for national health insurance and the increase in the burden of medical expenses on patients are issues, lifestyles and eating habits that prevent the development of hypertension are desired.

In addition, drugs that act via various mechanisms such as diuretics, angiotensin converting enzyme inhibitors, calcium antagonists, and sympathetic blockers have been developed as drugs that improve hypertension. Drugs synthesized in this way have side effects and are not suitable for long-term use. For example, kidney disorders and hearing impairments are recognized as side effects for diuretics, dry cough for angiotensin converting enzyme inhibitors, muscle disorders for calcium antagonists, and nausea and vomiting for sympathetic blockers.

On the other hand, coffee extracts, polyphenols, amino acids, peptides, and the like are known as substances for hypertension derived from natural products, but all have a problem that the effect is mild. For example, although caffeic acid derivatives such as chlorogenic acid and coumaric acid are present in the coffee extract, each angiotensin converting enzyme inhibitory action is very mild and transient.

In addition, nitric oxide produced from arginine, a kind of amino acid, is known as a substance that exhibits vasodilatory action, acts on smooth muscle cells of the vascular media and inhibits calcium uptake of the smooth muscle cells. Dilate blood vessels. In particular, the vasodilatory effect of nitric oxide is strongly expressed in arterioles, and nitric oxide is expected to dilate coronary arteries and basilar arteries to improve myocardial infarction and cerebral hemorrhage.

Although pharmaceutical compounds containing chlorogenic acid (for example, see Patent Document 1) and antihypertensive agents (for example, see Patent Document 2) have been invented, an ester conjugate of chlorogenic acid and arginine and its The action is not mentioned.

Furthermore, although a food containing arginine has been invented, a chlorogenic acid derivative targeting hypertension has not been reached (see, for example, Patent Document 3).
Special table 2002-541233 JP 2002-53464 A JP 2004-147630 A Created by the Ministry of Health, Labor and Welfare, major injuries by sex and age group, 2002. Created by the University of Tokyo Graduate School of Pharmaceutical Sciences, Department of Pharmaceutical Economics, Estimated Annual Medical Costs by Disease in 1999, 2000.

As described above, the chemically synthesized antihypertensive agent has a problem of side effects that adversely affect the kidneys, nerves, respiratory organs, and the like. In addition, the vasodilatory effect of chemically synthesized substances is difficult to sustain for a long time.

On the other hand, naturally-occurring substances have a problem that their effects are mild. Therefore, there is a demand for a substance derived from a natural product that has weak side effects and exhibits an excellent vasodilatory effect.

The present invention has been made paying attention to the problems existing in the prior art as described above. The object is to provide an ester conjugate of a chlorogenic acid derivative and arginine that has weak side effects and exhibits an excellent vasodilatory effect. Another object of the present invention is to provide an excellent food preparation and cosmetics which have a weak side effect containing an ester conjugate of a chlorogenic acid derivative exhibiting a vasodilating action and arginine.

In order to achieve the above object, the invention described in claim 1 relates to an ester conjugate of a chlorogenic acid derivative and arginine exhibiting a vasorelaxant activity represented by the following formula (1).

Ｘは、水素、ガンマ−アミノ酪酸、アミノ酸、ポリアミン、アミノ糖、グルコサミンから選択されるいずれか。

X is any one selected from hydrogen, gamma-aminobutyric acid, amino acid, polyamine, amino sugar, and glucosamine.

The invention according to claim 2 relates to an ester conjugate of a chlorogenic acid derivative exhibiting a vasorelaxant action according to claim 1 represented by the following formula (2), wherein X is hydrogen, and arginine.

請求項３に記載の発明は、Ｘがガンマ−アミノ酪酸である下記の式（３）で示される請求項１に記載の血管弛緩作用を呈するクロロゲン酸誘導体とアルギニンとのエステル結合体に関するものである。

The invention according to claim 3 relates to an ester conjugate of a chlorogenic acid derivative exhibiting a vasorelaxant action according to claim 1 represented by the following formula (3), wherein X is gamma-aminobutyric acid, and arginine. is there.

請求項４に記載の発明は、キク科ヤーコンの葉又は塊根を刈取り、アルギニン溶液に浸した後、５％〜４５％エタノール溶液により抽出した抽出液をアルカリ還元化して得られる請求項１又は請求項２又は請求項３に記載の血管弛緩作用を呈するクロロゲン酸誘導体とアルギニンとのエステル結合体に関するものである。

The invention according to claim 4 is obtained by cutting the leaves or tuberous roots of Asteraceae, soaking in arginine solution, and then alkali-reducing the extract extracted with 5% -45% ethanol solution. The present invention relates to an ester conjugate of a chlorogenic acid derivative exhibiting a blood vessel relaxing action according to Item 2 or Claim 3 and arginine.

Invention of Claim 5 is related with the foodstuff formulation which consists of the ester conjugate of the chlorogenic acid derivative which exhibits the blood vessel relaxation action of Claim 1, or Claim 2, or Claim 3 or Claim 4, and arginine. .

Invention of Claim 6 is related with the cosmetic formulation which consists of an ester conjugate of the chlorogenic acid derivative which exhibits the blood vessel relaxation action of Claim 1 or Claim 2 or Claim 3 or Claim 4, and arginine. .

Since this invention is comprised as mentioned above, there exist the following effects.
According to the ester conjugate of the chlorogenic acid derivative and arginine according to any one of claims 1 to 4, side effects are weak and an excellent vasodilatory effect is exhibited.

According to the food preparation of claim 5, side effects are weak and an excellent vasodilatory action is exhibited.

According to the cosmetic preparation of claim 6, side effects are weak and an excellent vasodilatory action is exhibited.

Hereinafter, embodiments embodying the present invention will be described in detail.

First, an ester conjugate of a chlorogenic acid derivative and arginine exhibiting a blood vessel relaxing action represented by the following formula (1) will be described.

Ｘは、水素、ガンマ−アミノ酪酸、アミノ酸、ポリアミン、アミノ糖、グルコサミンから選択されるいずれか。

X is any one selected from hydrogen, gamma-aminobutyric acid, amino acid, polyamine, amino sugar, and glucosamine.

The term “chlorogenic acid derivative” as used herein includes chlorogenic acid, that is, 3-caffeoylquinic acid, and chlorogenic acid derivatives include derivatives in which a mesoxy group is introduced into the side chain hydroxyl group of quinogenic acid of chlorogenic acid, quinaic acid. Also included are compounds in which ferulic acid is bonded to the 3-position of isochlorogenic acid, neochlorogenic acid and quinic acid in which caffeic acid is bonded to acid.

The ester conjugate of chlorogenic acid derivative and arginine here is a compound in which the carboxyl group of quinic acid in chlorogenic acid and the amino group at the alpha position of arginine are ester-bonded. X is a substance bonded to the carboxyl group side of the alpha position of arginine.
X is composed of any one selected from hydrogen, gamma-aminobutyric acid, amino acid, polyamine, amino sugar, and glucosamine.

Since the ester conjugate here is an ester, the fat solubility is increased. Since intestinal epithelial cells are made of a fat layer, they easily penetrate into the intestinal epithelial cell membrane, are familiar, absorbed and sustained.

Within the intestinal epithelial cells, this incorporated ester conjugate moves into the blood, infiltrates and acts on vascular smooth muscle cells, and exerts a vasodilating action.

In vascular smooth muscle cells, this ester conjugate inhibits L-type calcium channels on the cell membrane, where the portion of the chlorogenic acid derivative is involved in contraction, and suppresses neuronal N-type calcium channels. Inhibition of calcium channels suppresses excessive vascular smooth muscle contraction and relaxes blood vessels. Furthermore, the guanidyl group in the arginine side chain of the ester conjugate is metabolized to produce nitric oxide, which relaxes vascular smooth muscle. Two mechanisms are mainly based on the inhibition of calcium channel by the chlorogenic acid derivative and the production of nitric oxide by the guanidyl group in the arginine side chain.

In addition, this ester conjugate inhibits angiotensin converting enzyme and also inhibits peripheral sympathetic adrenergic receptors, thus relaxing the blood vessels by a different mechanism of action.

As mentioned above, there are mechanisms that inhibit calcium channels, nitric oxide production system, angiotensin converting enzyme inhibition and adrenergic receptors, complementing each other and helping each other that vascular smooth muscles eventually relax. It is done.

When X is hydrogen, the ester conjugate is an ester conjugate of chlorogenic acid and arginine. Such a configuration is preferable because production of nitric oxide from arginine is enhanced and a vasodilatory effect is exhibited.

When X is gamma-aminobutyric acid, the ester conjugate is an ester conjugate composed of chlorogenic acid, arginine, and gamma-aminobutyric acid. In this case, the carboxyl group at the alpha position of arginine and the amino group at the gamma position of gamma-aminobutyric acid are ester-bonded. By comprising in this way, in addition to the said vasorelaxation mechanism, it is preferable from the fact that gamma-aminobutyric acid acts as a neurotransmitter of the central nerve and lowers blood pressure.

When X is an amino acid, the ester conjugate is an ester conjugate composed of chlorogenic acid, arginine and an amino acid. In this case, the carboxyl group at the alpha position of arginine and the amino group at the alpha position of the amino acid are ester-bonded. Amino acids are all L-type amino acids. Among these, arginine is preferable because production of nitric oxide is enhanced and a vasodilatory effect is exhibited.

When X is a polyamine, the ester conjugate is an ester conjugate composed of chlorogenic acid, arginine, and polyamine. In this case, the carboxyl group at the alpha position of arginine and the amino group at the alpha position of polyamine are ester-bonded. Polyamines include putrescine, spermidine, spermine and the like. By comprising in this way, nitric oxide is produced | generated from the amino group of a polyamine, and since it exhibits a vasodilatory effect, it is more preferable.

When X is an amino sugar, the ester conjugate is an ester conjugate composed of chlorogenic acid, arginine, and amino sugar. In this case, the carboxyl group at the alpha position of arginine and the amino group of the amino sugar are ester-bonded. Examples of amino sugars include galactosamine, fructosamine, and glucosamine. By comprising in this way, since the production | generation of nitric oxide from the amino group of galactosamine is accelerated | stimulated and it exhibits a vasodilatory effect, it is preferable.

When X is glucosamine, the ester conjugate is an ester conjugate composed of chlorogenic acid, arginine, and amino sugar. In this case, the carboxyl group at the alpha position of arginine and the amino group of the amino sugar are ester-bonded. Examples of amino sugars include galactosamine, fructosamine, and glucosamine. By comprising in this way, since the production | generation of nitric oxide from the amino group of galactosamine is accelerated | stimulated and it exhibits a vasodilatory effect, it is preferable.

The ester conjugate of a chlorogenic acid derivative and arginine exhibiting the above-mentioned vasorelaxant action can be obtained by extraction from a natural material, chemically synthesized, or obtained by fermentation.
Natural materials include coffee, green tea leaves, cacao, yacon, and kikumo. These materials are obtained by adding an arginine solution, glucosamine, or amino acid, which are food additives, to stand and extracting.

In the case of chemical synthesis, it can be obtained by chemically esterifying a chlorogenic acid derivative and arginine as raw materials under a catalyst.

When obtained by a fermentation method, the chlorogenic acid derivative and arginine are used as raw materials, put in a fermentation tank, added with lactic acid bacteria, natto bacteria, brewer's yeast, etc., heated and aerated, and then extracted after stirring.

Hydrous ethanol is used for this extraction, and the concentration of this solution is preferably 5 to 15%. After extraction, it is filtered and the obtained filtrate is heated to obtain a solution, or this is freeze-dried to obtain a powder. The obtained ester conjugate is used as a pharmaceutical raw material, food raw material, cosmetic raw material, and animal feed.

Next, an ester conjugate of a chlorogenic acid derivative and arginine exhibiting a blood vessel relaxing action represented by the following formula (2) will be described.

このエステル結合体は、前記の構造体のうち、Ｘが水素になったものである。
ここでいうクロロゲン酸誘導体とは、クロロゲン酸、すなわち、３−カフェオイルキナ酸を含む。さらに、クロロゲン酸誘導体とは、クロロゲン酸のキナ酸の側鎖水酸基にメソキシ基が導入された誘導体、キナ酸にカフェ酸が結合したイソクロロゲン酸及びネオクロロゲン酸、キナ酸の３位にフェルラ酸が結合した誘導体である。

This ester bond is one in which X is hydrogen in the above structure.
The chlorogenic acid derivative here includes chlorogenic acid, that is, 3-caffeoylquinic acid. Furthermore, the chlorogenic acid derivative is a derivative in which a mesoxy group is introduced into the side chain hydroxyl group of quinogenic acid of chlorogenic acid, isochlorogenic acid in which caffeic acid is bonded to quinic acid, neochlorogenic acid, and ferulic acid at the 3-position of quinic acid. Is a derivative bound.

The ester conjugate herein is a compound in which the carboxyl group of quinic acid in chlorogenic acid and the amino group at the alpha position of arginine are ester-bonded.

Since the ester conjugate here is an ester, the fat solubility is increased. Since intestinal epithelial cells are made of a fat layer, they easily penetrate into the intestinal epithelial cell membrane and are familiar and absorbed.

Within the intestinal epithelial cells, this incorporated ester conjugate moves into the blood and infiltrates vascular smooth muscle cells. In vascular smooth muscle cells, this ester conjugate inhibits L-type calcium channels on the cell membrane, where the portion of the chlorogenic acid derivative is involved in contraction, and suppresses neuronal N-type calcium channels. Inhibition of calcium channels suppresses excessive vascular smooth muscle contraction and relaxes blood vessels. Furthermore, the guanidyl group in the arginine side chain of the ester conjugate is metabolized to produce nitric oxide, which relaxes vascular smooth muscle. Two mechanisms are mainly based on the inhibition of calcium channel by the chlorogenic acid derivative and the production of nitric oxide by the guanidyl group in the arginine side chain.

In addition, this ester conjugate inhibits angiotensin converting enzyme and also inhibits peripheral sympathetic adrenergic receptors, thus relaxing the blood vessels by a different mechanism of action.

As mentioned above, there are mechanisms that inhibit calcium channels, nitric oxide production system, angiotensin converting enzyme inhibition and adrenergic receptors, complementing each other and helping each other that vascular smooth muscles eventually relax. It is done.

The ester conjugate is an ester conjugate of chlorogenic acid and arginine. Such a configuration is preferable because production of nitric oxide from arginine is enhanced and a vasodilatory effect is exhibited.

The ester conjugate of a chlorogenic acid derivative and arginine exhibiting the above-mentioned vasorelaxant action can be obtained by extraction from a natural material, chemically synthesized, or obtained by fermentation.
Natural materials include coffee, green tea leaves, cacao, yacon, and kikumo. These materials are obtained by adding an arginine solution, glucosamine, or amino acid, which are food additives, to stand and extracting.

In the case of chemical synthesis, it can be obtained by chemically esterifying a chlorogenic acid derivative and arginine as raw materials under a catalyst.

When obtained by a fermentation method, the chlorogenic acid derivative and arginine are used as raw materials, put into a fermentation tank, added with lactic acid bacteria, natto bacteria, brewer's yeast, etc., heated, stirred and extracted.

Hydrous ethanol is used for this extraction, and the concentration of this solution is preferably 5 to 15%. After extraction, it is filtered and the obtained filtrate is heated to obtain a solution, or this is freeze-dried to obtain a powder. The obtained ester conjugate is used as a pharmaceutical raw material, food raw material, cosmetic raw material, and animal feed.

Next, an ester conjugate of a chlorogenic acid derivative, arginine, and gamma-aminobutyric acid that exhibits a vasorelaxant action represented by the following formula (3) will be described.

このエステル結合体は、前記の構造体のうち、Ｘがガンマ−アミノ酪酸になったものである。

This ester conjugate is one in which X is gamma-aminobutyric acid in the above structure.

The chlorogenic acid derivative here includes chlorogenic acid, that is, 3-caffeoylquinic acid. Furthermore, the chlorogenic acid derivative is a derivative in which a mesoxy group is introduced into the side chain hydroxyl group of quinogenic acid of chlorogenic acid, isochlorogenic acid in which caffeic acid is bonded to quinic acid, neochlorogenic acid, and ferulic acid at the 3-position of quinic acid. Is a derivative bound.

The ester conjugate herein is a compound in which the carboxyl group of quinic acid in chlorogenic acid and the amino group at the alpha position of arginine are ester-bonded.

Furthermore, the amino group of gamma-aminobutyric acid is bonded to the carboxyl group at the alpha position of arginine.

Since the ester conjugate here is an ester, the fat solubility is increased. Since intestinal epithelial cells are made of a fat layer, they easily penetrate into the intestinal epithelial cell membrane and are familiar and absorbed.

Within the intestinal epithelial cells, this incorporated ester conjugate moves into the blood and infiltrates vascular smooth muscle cells. In vascular smooth muscle cells, this ester conjugate inhibits L-type calcium channels on the cell membrane, where the portion of the chlorogenic acid derivative is involved in contraction, and suppresses neuronal N-type calcium channels. Inhibition of calcium channels suppresses excessive vascular smooth muscle contraction and relaxes blood vessels. Furthermore, the guanidyl group in the arginine side chain of the ester conjugate is metabolized to produce nitric oxide, which relaxes vascular smooth muscle. Two mechanisms are mainly based on the inhibition of calcium channel by the chlorogenic acid derivative and the production of nitric oxide by the guanidyl group in the arginine side chain.

In addition, this ester conjugate inhibits angiotensin converting enzyme and also inhibits peripheral sympathetic adrenergic receptors, thus relaxing the blood vessels by a different mechanism of action.

As mentioned above, there are mechanisms that inhibit calcium channels, nitric oxide production system, angiotensin converting enzyme inhibition and adrenergic receptors, complementing each other and helping each other that vascular smooth muscles eventually relax. It is done.

The ester conjugate is an ester conjugate composed of chlorogenic acid, arginine, and gamma-aminobutyric acid. In this case, in addition to the above-mentioned vasorelaxation mechanism, gamma-aminobutyric acid is preferable because it acts as a neurotransmitter of the central nervous system and lowers blood pressure.

The ester conjugate is obtained by extraction from a natural material, may be chemically synthesized, or can be obtained by a fermentation method. Natural materials include coffee, green tea leaves, cacao, yacon, and kikumo. An arginine solution and a gamma-aminobutyric acid solution, which are food additives, are added to these materials, and the mixture is left to stand and extracted.

In the case of chemical synthesis, it can be obtained by chemically esterifying a chlorogenic acid derivative, arginine and gamma-aminobutyric acid as raw materials under a catalyst.

When obtained by fermentation, use chlorogenic acid derivative, arginine and gamma-aminobutyric acid as raw materials, put them in a fermentation tank, add lactic acid bacteria, natto bacteria or brewer's yeast, etc. It is done.

Hydrous ethanol is used for this extraction, and the concentration of this solution is preferably 5 to 15%. After extraction, it is filtered and the obtained filtrate is heated to obtain a solution, or this is freeze-dried to obtain a powder. The obtained ester conjugate is used as a pharmaceutical raw material, food raw material, cosmetic raw material, and animal feed.

Next, the leaves or tuberous roots of the Asteraceae are harvested, soaked in an arginine solution, and then extracted with a 5% to 45% ethanol solution, which is obtained by alkali reduction. The ester conjugate of will be described.

The resulting ester conjugate of a chlorogenic acid derivative and arginine that exhibits vasorelaxant activity is the ester conjugate described above.

The Asteraceae Yacon used is a plant belonging to the family Asteraceae, which has the scientific name Semarantas Sonsiforius and is cultivated in South America, China, Japan, North America, Australia and Europe.

This yacon leaf or tuberous root is cut and soaked in an arginine solution. The concentration of the arginine solution is preferably 1 to 10%, more preferably 3 to 8%. The soaking time is preferably 6 to 48 hours, and more preferably 12 to 24 hours. 5-30 degreeC is preferable and, as for the temperature immersed, 10-20 degreeC is more preferable.

The extract is an ethanol solution, which is a solution obtained by diluting ethanol with water, and its concentration is 5% to 45%. When this ethanol concentration is less than 5%, there is a possibility that the target ester is not obtained by dissolution. Moreover, when this density | concentration exceeds 45%, there exists a possibility that the extracted ester body may become unstable and may be decomposed | disassembled.

The obtained extract is preferably filtered through a layer of diatomaceous earth, kaolin, silica, talc or the like. The obtained extract is alkali reduced. Alkaline reduction is performed by electrolysis apparatus having a platinum electrode, for example, chlorogenic acid derivative and arginine which are electrolyzed by a trim ion TI-8000, Pearl Water DX-7000, etc. and exhibit a desired blood vessel relaxation action from the cathode side. The ester conjugate with is obtained as a solution. The obtained ester conjugate is pulverized by lyophilization and used.

The obtained ester conjugate is used as various processed products such as pharmaceutical raw materials, quasi-drug raw materials, foods, and cosmetics.

Next, a food preparation composed of an ester conjugate of a chlorogenic acid derivative exhibiting the above-mentioned vasorelaxant action and arginine will be described. The food preparation here is used as a feed for animals, a feed for pets, or a supplement in addition to general foods and health foods taken by humans.

This food preparation contains, as an active ingredient, an ester conjugate of a chlorogenic acid derivative that exhibits the above-mentioned vasorelaxant action and arginine. The ratio of the ester conjugate of a chlorogenic acid derivative and arginine that exhibits a vasorelaxant action in food preparations is 0.1 to 30% by weight, preferably 0.3 to 20% by weight, and 0.5 to 15% by weight. More preferred.

When this ratio is less than 0.1% by weight, there is a possibility that sufficient action is not exhibited. Moreover, when this ratio exceeds 30 weight%, there exists a possibility that a form cannot be maintained as a food formulation.
In that case, by adding to various food materials or beverage materials, it is possible to obtain food preparations in the form of powder, tablets, liquids (drinks, etc.), capsules, and the like. Moreover, you may add a base material, an excipient | filler, an additive, a subsidiary material, a bulking agent, etc. suitably.

The food preparation is taken orally in several divided doses per day. The daily intake is preferably 0.1 to 10 g, more preferably 0.3 to 5 g, and even more preferably 0.5 to 3 g. If the daily intake is less than 0.1 g, sufficient effects may not be exhibited. If the daily intake exceeds 10 g, the cost may increase. In addition to the above, it can be used in the form of rice cake, rice crackers, cookies, beverages, powders and the like.

This food preparation has the feature that the ester conjugate is highly fat-soluble, so that it has excellent absorbability from the digestive tract and, when absorbed, binds to the cell membrane and has high durability. In addition, it is highly safe because it is degraded by enzymes such as esterases in the body.

The obtained food preparation is preferably used as a nutritional functional product or a food for specified health use as a health functional food.

When the obtained food preparation is used for pets, chlorogenic acid has a deodorizing action, which is preferable for faecal measures for animals kept in the home. Since the ester conjugate dilates blood vessels, it has a function of suppressing high blood pressure such as arteriosclerosis and diabetes and suppressing hypertension.

Next, a cosmetic product comprising an ester conjugate of a chlorogenic acid derivative exhibiting a vasorelaxant action and arginine will be described. The cosmetics referred to here are those used for pets and animals to improve their forms in addition to cosmetics used for humans. This cosmetic improves blood flow in skin blood vessels and is also used to activate skin cell turnover.

It can be used together with surfactants, solvents, thickeners, excipients and the like according to conventional methods as cosmetics. For example, it can be in the form of oil-soluble cream, hair gel, facial cleanser, cosmetic liquid, lotion and the like. The form of the cosmetic is arbitrary, and can be used as a solution, cream, paste, gel, gel, solid or powder.

As a cosmetic, it is applied, wiped or sprayed several times a day. The daily usage is preferably from 0.01 to 5 g, more preferably from 0.05 to 3 g, even more preferably from 0.1 to 1 g. If the daily usage is less than 0.01 g, sufficient effects may not be exhibited. If the daily usage exceeds 5 g, the cost may increase.

Since the obtained cosmetics dilate blood vessels in the skin, they are used in cosmetics for the purpose of activating fibroblasts in the dermis and subcutaneous tissue and enhancing collagen production. It is also used as a quasi drug.

Hereinafter, the embodiment will be specifically described with reference to examples and test examples.

1 kg of Japanese yacon leaves were cut and immersed in a 5% arginine solution in a room at 15 ° C. for 24 hours. This was transferred to an extraction tank, 10 L of a 25% ethanol solution was added, and the mixture was stirred with a mixer and pulverized. After stirring at 15 ° C. for 12 hours, the filtrate was obtained using a filter laid with diatomaceous earth and kaolin. The obtained filtrate was subjected to Pearl Water DX-7000 and electrolyzed to obtain a solution from the cathode side. This solution was heated to 50 ° C., ethanol was evaporated for 1 hour, and then freeze-dried with a freeze dryer (RLE-21, manufactured by Nissei Kogyo) to obtain 65 g of powder.
(Test Example 1)

  The obtained powder was analyzed by high performance liquid chromatography with a mass spectrometer (HPLC, Shimadzu Corporation) and analyzed by a nuclear magnetic resonance apparatus (NMR, manufactured by Bruker, AC-250). As a result, chlorogenic acid arginine ester was identified.

1 kg of Japanese yacon leaves were cut and immersed in a 4% arginine solution and a 1% gamma-aminobutyric acid solution in a 13 ° C. room for 20 hours. This was transferred to an extraction tank, 15 L of a 20% ethanol solution was added, and the mixture was stirred with a mixer and pulverized. After stirring at 13 ° C. for 10 hours, the filtrate was obtained using a filter with diatomaceous earth and kaolin spread. The obtained filtrate was subjected to Pearl Water DX-7000 and electrolyzed to obtain a solution from the cathode side. This solution was heated to 50 ° C. and ethanol was evaporated for 1 hour, followed by lyophilization with a freeze dryer (RLE-21, manufactured by Nissei Kogyo) to obtain 34 g of powder.
(Test Example 2)

  The obtained powder was analyzed by HPLC equipped with a mass spectrometer and analyzed by NMR. As a result, arginine chlorogenic acid-gamma-aminobutyric acid ester was identified.

Hereinafter, an intracellular calcium test using human skin-derived vascular smooth muscle cells will be described. This test is widely used as a method for observing a vasorelaxation response using changes in calcium channel function as an index.
(Test Example 3)

Normal human-derived vascular smooth muscle cells (coronary vascular smooth muscle cell culture product, Sanko Junyaku Co., Ltd.) were cultured in a dedicated culture solution. To this, 0.1 mg, 0.3 mg and 1 mg of the ester, chlorogenic acid and arginine obtained in Example 1 and Example 2, respectively, were added and cultured at 37 ° C. for 1 hour. A fluoro-3AM (Nacalai Tesque) 0.01% solution was added thereto, 0.01 mM isoproterenol was further added, and the intracellular calcium concentration was measured with a confocal laser fluorescence microscope. The change in calcium concentration relative to the solvent control was determined.

As a result, in 0.1 mg, 0.3 mg and 1 mg of the ester conjugate of Example 1, the intracellular calcium concentration relative to the solvent control group was 89%, 82% and 69%, respectively, which was significant compared to the control group. A significant decrease was observed. Furthermore, the intracellular calcium concentration of the ester conjugate of Example 2 with respect to the solvent control group was 0.1 mg, 0.3 mg, and 1 mg, which were 86%, 78%, and 70%, respectively, which was significant as compared with the control group. A significant decrease was observed. In addition, 1 mg of chlorogenic acid and arginine were 97% and 98%, respectively, compared with the value of the solvent control group. There was no change in the number of viable cells, and no toxicity to cells was observed.

The test for blood pressure using spontaneously hypertensive rats (SHR) will be described below. This SHR rat is widely used as a model of human vasoconstrictive hypertension, and there are abundant test examples, reflecting human results.
(Test Example 4)

Seven weeks old male SHR rats purchased from Nippon Charles River Co., Ltd. were preliminarily raised for 1 week, and then 1 mg / mg each of the ester conjugate, chlorogenic acid, arginine, and gamma-aminobutyric acid obtained in Examples 1 and 2. kg was orally administered for 28 days. After administration, tail blood pressure was measured using BP-38A manufactured by Softron and compared with the solvent control group.
As a result, the systolic blood pressures of the ester conjugate, chlorogenic acid, arginine, and gamma-aminobutyric acid obtained in Example 1 and Example 2 were 85% and 82%, respectively, compared with the values of the solvent control group. 95%, 99%, and 97%, and the ester conjugates of Example 1 and Example 2 clearly showed a blood pressure lowering effect.

Below, the Example of the foodstuff formulation which consists of ester conjugates is described.

In a ratio of 0.2 g of the ester conjugate obtained in Example 1 or Example 2, 0.2 g of propolis extract, 3 g of isomerized sugar, 1.8 g of edible cellulose, 0.01 g of ascorbic acid and 0.1 g of edible flavor. Mixed. This was tableted by a conventional method to obtain a triangular tablet having a diameter of 10 mm and a weight of 0.3 g.

Below, the Example of the cosmetics which consist of ester conjugates is described.

Polyethylene glycol monostearate, 1 g of lipophilic glyceryl monostearate, 2 g of horse oil ester and 3 g of oleic acid were heated and dissolved. To the obtained solution, 0.2 g of the ester conjugate obtained in Example 1 or Example 2, 2 g of propylene glycol, 0.1 g of dipotassium glycyrrhizinate, 0.1 g of α-tocopherol and 70 g of purified water were added. These were dissolved and then cooled to obtain an emulsion as a cosmetic.

The effects and side effects of the food preparation on hypertension were evaluated below.
(Test Example 5)

Twelve hypertensive patients with systolic blood pressure of 150 to 160 mmHg were ingested 3 tablets of the food preparation obtained in Example 3 three times a day for 28 days. The blood pressure and heart rate before and 28 days after ingestion were measured with a sphygmomanometer (manufactured by OMRON, HEM-1000). As a result, in the food preparation of Example 3 obtained in Example 1, the systolic blood pressure decreased by an average of 15 mmHg as compared with that before ingestion. The heart rate was 101%. In addition, in the food preparation of Example 3 obtained in Example 2, the systolic blood pressure decreased by an average of 17 mmHg as compared with that before ingestion. The heart rate was 98%. There was no change in the physical condition due to the intake of food preparations, and no side effects were observed in the blood test, blood biochemical test, and urinalysis test values.

Below, the test example evaluated about the effect and side effect of cosmetics is shown.
(Test Example 6)

10 mL of the emulsion obtained in Example 4 was applied to 10 healthy women aged 23 to 56 years on the right half of the face for 14 days. Before application and on the 14th day of application, the moisture retention power (manufactured by Integral, CM825) and skin elasticity (manufactured by Integral, shock wave measuring device, RVM600) were measured on the left and right sides of the face.

As a result, in the cosmetic product of Example 4 consisting of Example 1, both the moisture retention power and skin elasticity were improved by 112% and 134%, respectively, as compared to before application. Further, in the cosmetic product of Example 4 consisting of Example 2, the moisture retention power and skin elasticity were 115% and 139%, respectively, as compared to before application, and both values were improved.

In addition, no side effect was recognized in the physical condition and the skin state by any cosmetic application.

The ester conjugate of a chlorogenic acid derivative and arginine that exhibits an excellent vasorelaxant effect with weak side effects obtained in the present invention is caused by different mechanisms such as inhibition of calcium channels in vascular smooth muscle and vascular relaxation by nitric oxide. Therefore, a therapeutic effect is expected for various types of hypertension with different onset causes. Moreover, it can contribute to the treatment or prevention of hypertension, which is the most common disease in Japanese, and can improve QOL. It is a compound that can contribute not only to medical treatment but also to food and cosmetics in preventing blood pressure, and food preparations and cosmetics containing them. It is also expected to increase the marketability of natural yacon and increase the distribution of materials.

Claims (6)

An ester conjugate of a chlorogenic acid derivative represented by the following formula (1) and exhibiting a vasorelaxant action and arginine.

X is any one selected from hydrogen, gamma-aminobutyric acid, amino acid, polyamine, amino sugar, and glucosamine. The ester conjugate of a chlorogenic acid derivative exhibiting a vasorelaxant action and arginine according to claim 1 represented by the following formula (2), wherein X is hydrogen.

The ester conjugate of a chlorogenic acid derivative exhibiting a vasorelaxant action according to claim 1 represented by the following formula (3), wherein X is gamma-aminobutyric acid, and arginine.

The leaf or tuberous root of Asteraceae is harvested, immersed in an arginine solution, and then extracted with a 5% to 45% ethanol solution, which is obtained by alkali reduction. An ester conjugate of a chlorogenic acid derivative and arginine that exhibits a vasorelaxant action. A food preparation comprising an ester conjugate of a chlorogenic acid derivative exhibiting a vasorelaxant action according to claim 1 or claim 2, or claim 3 or claim 4 and arginine. Cosmetics comprising an ester conjugate of a chlorogenic acid derivative exhibiting a vasorelaxant action according to claim 1 or claim 2 or claim 3 or claim 4 and arginine.