JP2007008838A - Thromboxanthin B2 regulator, food and drink containing the same, food additive, medicine and cosmetics - Google Patents

Abstract

PROBLEM TO BE SOLVED: To provide a TXB ₂ modulator capable of enhancing the vascular endothelial function improving action by regulating TXB ₂ production amount, which is safe and effective even when continuously used, and foods and drinks and foods containing the same Additives, medicines and cosmetics are provided.
[Solution]
(1) A TXB ₂ regulating agent comprising an apple extract as an active ingredient.
(2) The TXB ₂ regulating agent according to (1), wherein the apple extract is an apple-derived polyphenol.
(3) The TXB ₂ regulating agent according to (2), wherein the apple-derived polyphenol has a content of procyanidins in the total polyphenol of 20 to 100% by weight.
(4) A food or drink containing the TXB ₂ regulating agent according to any one of (1) to (3).
(5) A food additive containing the TXB ₂ regulating agent according to any one of (1) to (3).
(6) A medicament comprising the TXB ₂ modulating agent according to any one of (1) to (3).
(7) A cosmetic containing the TXB ₂ regulating agent according to any one of (1) to (3).
[Selection figure] None

Description

The present invention relates to a TXB ₂ modulator that improves vascular endothelial function by regulating the amount of thromboxane xin B ₂ (hereinafter abbreviated as “TXB ₂ ”), foods and drinks containing the same, food additives, pharmaceuticals, and cosmetics About.

  In recent years, in Japan, as the lifestyle has become westernized, the population that should be called obese and pre-obese groups has increased, and thrombosis and arteriosclerosis associated with obesity, hyperlipidemia, diabetes, etc. have become major problems.

TXB ₂ is a stable metabolite of local hormone (ortachoid) thromboxanthin A ₂ (hereinafter “TXA ₂ ”) biosynthesized mainly from arachidonic acid (hereinafter abbreviated as “AA”) in platelets. TXA ₂ has the property of antagonizing prostacyclin (PGI ₂ ) produced mainly from vascular endothelial cells from the same AA, and exhibits platelet aggregation inducing action and vascular smooth muscle contraction action. In order for the vascular system to work properly, a balanced production of TXA ₂ and PGI ₂ is necessary, and if this goes wrong, it triggers various diseases such as thrombosis, which improves vascular endothelial function. It has attracted a lot of attention. However, half-life in vivo of TXA ₂ is very short, since it is metabolized into TXB ₂ in about 30 seconds, typically the TXB ₂ is stable metabolite are measured.

  Some antihyperlipidemic drugs and the like can be mentioned as those having an effect of improving vascular endothelial function, but side effects must be taken into account along with their efficacy. For vascular lesions, which are chronic and asymptomatic conditions, prevention with foods that can be safely ingested for a long time is considered to be more important, and development of foods having an effect of improving vascular endothelial function is expected.

However, Patent Document 1 discloses a “thrombogenic inhibitor and functional food” containing proanthocyanidins, but does not mention anything about improving vascular endothelial function by regulating the amount of TXB ₂ produced. .

  In the “Composition and method for the prevention and treatment of vascular degenerative diseases (Patent Document 2)”, the prevention and treatment of vascular degenerative diseases may be achieved only by a combination of cocoa polyphenol and chondroitin sulfate. It is disclosed.

  Also in “Cocoa component, edible product having increased polyphenol content, production method thereof, and medical use method (Patent Document 3)”, a medical use method limited to only cocoa polyphenol is disclosed.

  Furthermore, “a product containing polyphenol and L-arginine to promote the production of nitrogen oxide (Patent Document 4)” discloses that the production of nitrogen oxide is promoted only by a combination of procyanidin and arginine. Yes.

As described above, the patent literature discloses that proanthocyanidins or polyphenols are derived from grape seeds, pine bark, and the like, and there is no description that they are derived from apples. Thus, none of the patent document, discloses that has the effect of apple extract to adjust the TXB ₂ production amount is not been made, from adjusting the TXB ₂ production amount, increasing the vascular endothelial function improving action Therefore, there has been a long-awaited demand for simple and safe foods, food additives, medicines and cosmetics.
Kobayashi Takemaru, Japanese Clinical, 43, 1985.1086-1089. JP 2004-238289 A Special table 2001-511153 JP2003-204758 Special table 2001-505864

An object of the present invention is to provide a TXB ₂ modulator capable of enhancing the vascular endothelial function improving action by regulating the amount of TXB ₂ production, which is safe and effective even when continuously used, and a food and drink containing the same It is to provide products, food additives, medicines and cosmetics.

As a result of intensive studies to solve the above problems, the present inventor found that the apple extract has a TXB ₂ regulating action, and has completed the present invention.

That is, the present invention has the following contents.
(1) A TXB ₂ regulating agent comprising an apple extract as an active ingredient.
(2) The TXB ₂ regulating agent according to (1), wherein the apple extract is an apple-derived polyphenol.
(3) The TXB ₂ regulating agent according to (2), wherein the apple-derived polyphenol has a content of procyanidins in the total polyphenol of 20 to 100% by weight.
(4) A food or drink containing the TXB ₂ regulating agent according to any one of (1) to (3).
(5) A food additive containing the TXB ₂ regulating agent according to any one of (1) to (3).
(6) A medicament comprising the TXB ₂ modulating agent according to any one of (1) to (3).
(7) A cosmetic containing the TXB ₂ regulating agent according to any one of (1) to (3).

The TXB ₂ regulator comprising the apple extract of the present invention as an active ingredient can regulate TXB ₂ with very few side effects.

Moreover, food / beverage products, food additives, medicines and cosmetics containing the above-mentioned TXB ₂ regulating agent as an active ingredient can regulate TXB ₂ with very few side effects.

The TXB ₂ regulating agent in the present invention refers to an agent that regulates TXB ₂ production and improves vascular endothelial function.

  The apple extract in the present invention is obtained by extraction from a fruit of a Rosaceae apple genus plant, for example, cultivars such as Fuji, Mutsu, Tsugaru, Starking Delicious, and original apples by a known extraction means.

  As the fruit, both a mature fruit and a young fruit can be used, but a young fruit is particularly preferable because it contains more polyphenol compounds and contains a large amount of various active ingredients having a wide range of physiological actions.

The apple-derived polyphenol in the present invention contains polyphenol as an active ingredient in an apple extract. The TXB ₂ regulator in the present invention may be either an apple extract or an apple-derived polyphenol, but is preferably an apple-derived polyphenol. Apple-derived polyphenols with a high degree of purification have high processing applicability, such as being less likely to cause turbidity and turbidity when added to foods and drinks, and also capable of suppressing the influence of flavor on foods and drinks themselves.

In the apple-derived polyphenol of the present invention, the procyanidins content in the total polyphenol is preferably 20 to 100% by weight, more preferably 30 to 90% by weight, and particularly preferably 20 to 65% by weight. When the ratio of procyanidins in the total polyphenol is lower than 20% by weight, the effect of regulating TXB ₂ is lowered. That the content of procyanidins is lower than 20% by weight means that the proportion of the monomer (catechin) in the apple-derived polyphenol is 80% by weight or more, and the proportion of the monomer is 80% by weight or more. This is because it is difficult to obtain the effect of TXB ₂ adjustment.

  The apple-derived polyphenol contained in the apple extract of the present invention consists of a clarified fruit juice obtained from the juice of apple fruit or juvenile fruit, or a polyphenol fraction purified from the extract. The fraction is purified by treating the juice juice and extract with an adsorbent, and the fraction adsorbed on the adsorbent (hereinafter referred to as the adsorbed fraction) contains polyphenol. The adsorbent is not particularly limited as long as it adsorbs polyphenol. For example, hydrophilic vinyl polymer resin (“Toyopearl HW40” manufactured by Tosoh Corporation), styrene-divinylbenzene resin (“Separbeads SP-850” manufactured by Mitsubishi Chemical Corporation). ) And gel type synthetic resin (“Diaion HP-20” manufactured by Mitsubishi Chemical Corporation).

  The polyphenol fraction is purified by eluting the adsorbed fraction adsorbed on the adsorbent with an alcohol solvent such as water-containing ethanol. The polyphenol fraction can then be concentrated to obtain a liquid formulation as an apple extract, and further, a powder formulation can be obtained by spray drying or freeze-drying the liquid formulation.

  As an extraction method of an apple extract as a raw material for apple-derived polyphenols, for example, the washed raw material is crushed at pH 3.2 to 4.6, preferably pH 3.5 to 4.3, and pectinase is added to the obtained fruit juice. Clarified by adding 10 to 100 ppm, more preferably 20 to 30 ppm at ˜75 ° C., preferably 30 to 60 ° C., and centrifuging at 5 to 75 ° C., preferably 15 to 25 ° C. after centrifugation. Silica 300S "(manufactured by Chuo Silica Co., Ltd.) is further clarified by filtration to obtain clarified juice. Alternatively, partitioning and filtration with an organic solvent such as hexane and chloroform can be performed to obtain apple juice as a clarified extract.

  In order to obtain apple-derived polyphenol from apple juice, the clarified extract is then used at 0 to 40 ° C., preferably 15 to 25 ° C., pH 1.5 to 4.2, preferably pH 3.0 to 4.0. The solution is passed through a packed adsorption column (trade name “Diaion HP-20”, manufactured by Mitsubishi Chemical Corporation) to adsorb polyphenols. Subsequently, pure water is passed through to remove non-adsorbing substances (saccharides, organic acids, etc.) in the column, and then the adsorbed fraction is eluted with 10 to 90%, preferably 30 to 80% ethanol. Ethanol is distilled off from the obtained adsorbed fraction under reduced pressure at 25 to 100 ° C., preferably 35 to 90 ° C., and the concentrated solution may be used as it is as a liquid apple-derived polyphenol. Or powder auxiliary agents, such as dextrin, may be added, spray-drying or freeze-drying may be carried out, and it may be set as the extraction powder product of an apple origin polyphenol.

The daily dose for adults to obtain the effect of regulating TXB ₂ with the TXB ₂ modulator of the present invention is 100 to 2500 mg as an apple extract or apple-derived polyphenol, preferably 150 to 1500 mg, More preferably, it is 150-1000 mg, It is especially preferable that it is 150-750 mg.

When using the TXB ₂ regulator of the present invention, the blood concentration of polyphenols is higher when taking the amount of apple extract per day or the amount of polyphenol derived from apples in a smaller number of times from the point of absorption of polyphenols, It is easy to develop the action of polyphenols.

The TXB ₂ regulator of the present invention can be used by adding it as a food additive in general, including beverages, such as soups, beverages (juice, mineral water, coffee, tea, non-alcoholic beer, etc.), confectionery Suitable for beverages (gum, candy, chocolate, snacks, jelly, etc.), noodles (soba, udon, ramen, etc.), alcoholic beverages (beer, sparkling liquor, cocktail, chuhai, shochu, sake, whiskey, brandy, wine, etc.) Used.

The pharmaceutical dosage form containing the TXB ₂ modulator of the present invention is not particularly limited, but for example, solid preparations such as tablets, powders, fine granules, granules, capsules, pills, liquid preparations, suspensions, syrups And oral administration agents such as liquids such as emulsions. This orally administered agent includes excipients, disintegrants, binders, lubricants, surfactants, alcohols, water, water-soluble polymers, sweeteners, flavoring agents, It can be produced by a commonly used method by adding a sour agent, a pharmaceutical carrier and the like.

  Moreover, you may mix | blend apple origin polyphenol with cosmetics. The cosmetic product in the present invention means a series of products to be applied to the human body such as cosmetics, body cleaning agents, oral preparations, bathing agents and the like. Examples of cosmetics include skin lotion, cosmetic cream, milky lotion, foundation, funny, lipstick, hair styling agent, hetonic hair restoration agent, hair rinse and the like. Examples of body cleansing agents include face wash, shampoo, body soap and the like. Examples of the oral preparation include toothpaste and tip liquid. In the case of preparing a cosmetic product, it can be produced by appropriately blending those used as normal cosmetic raw materials.

(Example)
The present invention will be specifically described below with reference to examples and test examples.

(Production Example 1)
300 kg of apple fruit from Aomori Prefecture was crushed and pressed to obtain 210 kg of fruit juice. The obtained fruit juice was clarified with 30 ppm of pectinase, and after centrifugation, clarification was performed by filtration through diatomaceous earth (silica 300S, manufactured by Chuo Silica Co., Ltd.) to obtain a clarified fruit juice. The clarified fruit juice was passed through an adsorption column (Diaion HP-20, manufactured by Mitsubishi Chemical Corporation) to adsorb polyphenols. Subsequently, pure water was passed through to remove non-adsorbed substance chambers (saccharides, organic acids, etc.) in the column, and then eluted with 80% alcohol. Alcohol was concentrated under reduced pressure from the obtained fraction to prepare about 2 kg of an extracted powder product. When the extracted powder was measured by reversed-phase high performance liquid chromatography, chlorogenic acids (about 20%), fluorethylene glycosides (about 5%), flavonols (about 15%), proanthocyanidins (about 50%) And other components (about 10%). Furthermore, as a result of analysis with a matrix-assisted laser ionization-time-of-flight mass spectrometer (MALDI-TOF / MS, manufactured by Applied Biosystems), this protosiadinin is a two-component compound composed of catechins and shrimp catechins that are flavanols. It was confirmed to be an oligomer or polymer from the body to the 15-mer (M. Ohnishi-kameyama et al. Mass Spectrometry, 11, 31, -36, 1997).

(Example 1) Tablet 150 g of apple-derived polyphenol obtained in Production Example 1, 90 g of lactose and 17 g of corn starch were mixed, and this mixture was granulated with a paste prepared in advance from 70 g of corn starch. 1 g of magnesium stearate was added to the obtained granules and mixed well, and the mixture was tableted with a tableting machine to produce 1000 tablets.

Comparative Example 1 Tablet Lactose 140 g and corn starch 17 g were mixed, and the mixture was granulated with a paste prepared in advance from corn starch 70 g. 1 g of magnesium stearate was added to the obtained granules and mixed well, and the mixture was tableted with a tableting machine to produce 1000 tablets.

(Test Example 1) TXB ₂ regulatory action of apple-derived polyphenols (human)
Next, TXB ₂ regulatory action of apple-derived polyphenols was examined by clinical trials.

(Method)
1) Subjects High blood glucose levels (fasting blood glucose levels) in a preliminary test conducted within 4 weeks before the start of the study among Japanese males over 40 years old and BMI 24 or older who volunteered to participate in this study. Of 110-140 mg / dl) and high blood pressure (systolic blood pressure 130-159 mmHg or diastolic blood pressure 85-99 mmHg). However, those who have been treated with antihyperlipidemic drugs or blood glucose-improving drugs that may affect vascular endothelial function, those who have a history of food allergies, and other health examinations and drugs before the start of the study Those who were judged to be inappropriate for participation by the investigator in the usage survey were excluded. Seven subjects who fulfilled these conditions were subjects, and subject to study in accordance with the purpose of the Declaration of Helsinki (adopted in 1964, revised in '75, '83, '89, '96, 2000, revised in 2002)) We fully explained the methods, etc., and obtained the written consent.

2) Test meal This test meal consists of tablets containing apple-derived polyphenols produced in Example 1 (150 mg / 1 tablet) and control meals not containing polyphenols produced in Comparative Example 1 (placebo tablets). did. In addition, before conducting the test, the investigator confirmed that there was no distinction between the test beverage and the placebo tablet due to sensory aspects such as flavor and aroma and packaging.

3) Ingestion method and schedule The study used a double-blind method with crossover. The intake period was set to 1 week, the rest period was set to 2 weeks, the intake period was set to 1 week, and the post-observation period was set to 1 week. The test subject ingested the test tablet by the following method.
・ Apple-derived polyphenol-containing test tablets (150 mg / tablet): 4 tablets at dinner, the following: Apple-derived polyphenol intake: placebo tablets (150 mg / tablet): 4 tablets at dinner, the following: placebo During this period, subjects were instructed to take a daily life that was consistent with their daily diet, alcohol consumption, and exercise. Furthermore, in order to clarify the effect of the test food, the intake of apples and apple products was prohibited during the test period.

4) Blood test In all subjects, TXB ₂ , Na, Ca, Cl, K, GPT (ALT), LDH, γ-GTP, GOT on the start date of intake, 1 week after intake (end of intake), and after observation Measurement items of total protein, urea nitrogen, Cre, TC, TG, ALB, blood glucose, IRI, blood cell components (white blood cell, red blood cell, hemoglobin content, hematocrit value, MCV, MCH, MCHC, platelet count) were carried out. In order to avoid external effects such as food and exercise, all tests were fasted for 12 hours or longer, maintained at rest for 10 minutes or more after visiting the hospital, and blood was collected in the sitting position.

(result)
The results are shown in Table 1. In this test subject considered to have strong vascular endothelial dysfunction, TXB ₂ decreased after intake of apple-derived polyphenols compared to before intake (p <0.10). In addition, no abnormality was observed from various blood tests. During the intake period, no complaining complaints were found.

(Example 2) External preparation
Oil phase components of 30 g of petroleum jelly, 20 g of liquid paraffin, 7 g of paraffin and 4 g of lanolin are mixed and dissolved by heating at 75 ° C. Meanwhile, 4 g of sorbitan sesquioleate, 2.5 g of propylene glycol, 0.2 g of magnesium sulfate, 0.2 g of methyl parahydroxybenzoate,
31.7 g of the water phase component of purified water was mixed and dissolved by heating at 75 ° C., and 0.2 g of fragrance was added thereto, and dispersed uniformly with a homomixer. The oil phase component was added to the aqueous phase component and emulsified with a homomixer. Cooling was started after the emulsification was completed, and the component of 0.2 g of polyphenol derived from apple obtained in Example 1 was added at 40 ° C. and mixed uniformly.

(Example 3) ポ リ Apple-derived polyphenol 5.0 g
Sucrose 15.0 g
Chickenpox (75% solids) 70.0g
9.5g of water
Coloring agent (Daiwa Kasei High Orange W-150) 0.05g
Fragrance (Hasegawa Fragrance Co., Ltd. Orange Flavor AH-11444) 0.45g
Total 100.0g
Using each component of each of the above parts by weight, it was made into a candy according to a conventional method.

(Example 4) Juice Apple-derived polyphenol 2.5g
Concentrated tangerine juice 15.0g
Fructose 2.5g
Citric acid 0.2g
Fragrance (Takasago Fragrance Co., Ltd. Orange Flavor) 0.1g
Pigment (Saneigen Orange Color Base) 0.15g
Sodium ascorbate 0.05g
79.5g of water
Total 100.0g
Using each component of the above-mentioned parts by weight, juice was prepared according to a conventional method.

(Example 5) Cookie Apple-derived polyphenol 5.0 g
Soft flour 32.0g
Whole egg 16.0g
16.0g butter
20.0g sugar
10.8g of water
Baking powder 0.2g
Total 100.0g
Using each component of the above-mentioned parts by weight, a cookie was prepared according to a conventional method.

The present invention, since the TXB ₂ modifier composition capable of modulating the TXB ₂ production amount was obtained, high safety can improve endothelial function food products, food additives, are available in the pharmaceutical and cosmetics such .

Claims (7)

A thromboxanthin B ₂ regulator comprising an apple extract as an active ingredient. Thromboxane xanthine B ₂ modulating agent according to claim 1, wherein the apple extract is from apple polyphenol. The apple-derived polyphenol, thromboxane xanthine B ₂ modulating agent according to claim 2, wherein the content of procyanidins in the total polyphenols is 20 to 100% by weight. Food or drink containing the thromboxane xanthine B ₂ modulating agent according to any one of claims 1 to 3. Food additives containing thromboxane xanthine B ₂ modulating agent according to any one of claims 1 to 3. A medicament containing the thromboxane xanthine B ₂ modulating agent according to any one of claims 1 to 3. Cosmetics containing the thromboxane xin B ₂ regulator according to any one of claims 1 to 3.