WO2005082390A1

WO2005082390A1 - Fat accumulation inhibitors

Info

Publication number: WO2005082390A1
Application number: PCT/JP2005/003178
Authority: WO
Inventors: Tomomasa Kanda; Manabu Sami; Youko Akazome; Kyouichi Osada
Original assignee: Asahi Breweries, Ltd.
Priority date: 2004-03-02
Filing date: 2005-02-25
Publication date: 2005-09-09
Also published as: JPWO2005082390A1

Abstract

[PROBLEMS] To provide fat accumulation inhibitors which originate from natural products and exhibit an effect of inhibiting fat accumulation per body weight without harmful effects on the human body. [MEANS FOR SOLVING PROBLEMS] The invention relates to fat accumulation inhibitors containing as the active ingredient fruit polyphenols originating from plants such as rosaceous plants, particularly from ripe or unripe apple fruit, specifically proanthocyanidins such as procyanidins; and to foods, drinks, food additives, drugs, quasi drugs and feeds, containing the same.

Description

Specification

Fat accumulation inhibitor

Technical field

The present invention relates to a fat accumulation inhibitor containing, as an active ingredient, a plant, preferably a Rosaceae plant, particularly a fruit polyphenol derived from apple fruit or immature fruit, and more particularly, polyphenol is a proanthocyanin, particularly A procyadine, a fat accumulation inhibitor having the effects of suppressing in-situulin elevation in the living body, suppressing lebutin elevation, and inhibiting fat accumulation per body weight, and foods, beverages, food additives, pharmaceuticals, and pharmaceuticals containing the same. Regarding quasi-drugs and feed. Background art

[0002] In recent years, not only European and American meals but also Japanese meals have been remarkably westernized, and high-fat diets and high calorie diets have been advanced. In particular, excessive intake of lipids and carbohydrates causes excessive accumulation of fat, and the number of people suffering from obesity and increased body fat is increasing calories. Body fat is the sum of subcutaneous fat and visceral fat, but a positive correlation has been obtained between visceral fat mass and body fat, and it is known that visceral fat mass reflects body fat.

In addition, obesity and increased body fat are considered to be risk factors for ischemic heart disease, stroke, diabetes, etc. soon after complicating hypertension and hyperlipidemia. It is.

To date, most methods of preventing and treating obesity are dietary restrictions and dietary diets, but dietary restriction is accompanied by mental difficulties and, if improper, causes pathological symptoms such as malnutrition and anorexia nervosa. There is also danger. Also, unreasonable dieting and inhibition of digestive enzymes reduce the body's supply of nutrients, causing rebound after dieting.

On the other hand, various drugs are also administered, but the side effects as well as the efficacy must be considered.

[0003] Here, polyphenols widely existing in the plant kingdom have been confirmed to have various physiological functions by recent research, and polyphenols derived from rose fruits or immature fruits have been confirmed. Has also been found to have functions such as prevention of oxidization, anti-erosion, and suppression of allergy (Patent Document

1), however, has not been reported on the function of suppressing fat accumulation.

In addition, it has been reported that in vivo lipid metabolism is suppressed using fruit polyphenol as an active ingredient.

(Patent Document 2), reports on inhibition of in vivo lipid oxidization, improvement of HDL (good cholesterol) Z total cholesterol ratio, and suppression of cholesterol absorption; fruit polyphenol procyanidin and fat accumulation With regard to the relationship, it is completely mentioned, what ,.

In addition, although the prevention of obesity by procyadine has been reported (Patent Document 3), examples show that weight gain due to eating disorders or digestive enzyme inhibition and suppression of serum lipids and blood glucose elevation are suppressed. There is no mention of body fat mass (visceral fat mass). Patent Document 1: Japanese Patent Application Laid-Open No. 7-285876

Patent Document 2: Japanese Patent Application Laid-Open No. H10-330278

Patent Document 3: JP-A-9-291039

Disclosure of the invention

Problems to be solved by the invention

[0004] As described above, a fat accumulation inhibitor having the effect of suppressing the rise of insulin in the living body and the rise of lebutin, especially the effect of suppressing the accumulation of fat per body weight, without affecting the weight gain, increases the body fat percentage. It is expected to prevent and prevent hypertension, hyperlipidemia, ischemic heart disease, stroke, diabetes and the like!

Therefore, an object of the present invention is to provide a fat accumulation inhibitor that satisfies these properties and is derived from natural products and has no harmful effect on the human body.

Means for solving the problem

[0005] The present inventors have conducted intensive studies to find a natural product that has a fat accumulation inhibitory action and is safe in a high-fat diet system. As a result, polyphenol phenols derived from apple fruits or immature fruits were obtained. The present inventors have found that they have an inhibitory action on insulin rise in the body and an inhibitory action on lebutin increase, and in particular, have an inhibitory action on fat accumulation per body weight, and have reached the present invention. That is, according to the present invention, there is provided a fat accumulation inhibitor characterized by containing a polyphenol derived from fruit or immature fruit as an active ingredient.

In addition, the fat accumulation inhibitor of the present invention suppresses an increase in insulin in vivo and an increase in lebutin. It suppresses fat accumulation per body weight by suppression or the like.

Further, as the fat accumulation inhibitor of the present invention, it is preferable to use a polyphenol derived from a rose plant, especially an apple fruit or an unripe fruit among plants.

Further, the fat accumulation inhibitor of the present invention can be used by being contained in foods, beverages, food additives, pharmaceuticals, quasi-drugs, and feeds.

The invention's effect

[0006] According to the present invention, a fat characterized by containing, as an active ingredient, an apple extract or polyphenol or procyadine as an active ingredient, which is also extracted and purified from solanaceous plants, particularly apple fruit or immature fruit. An accumulation inhibitor is provided, and the function of the fat accumulation inhibitor to suppress visceral fat accumulation, hyperinsulinemia, hyperlebutinemia, and the like can suppress fat accumulation.

Furthermore, the fat accumulation inhibitor of the present invention can be used for foods and beverages, food additives, pharmaceuticals, quasi-drugs for those who are concerned about increased body fat, obesity, hyperlipidemia, arteriosclerosis, diabetes, etc. And animal feed.

Brief Description of Drawings

FIG. 1 is a graph showing the effect of suppressing the mesenteric fat accumulation by an animal experiment using apple polyphenol.

FIG. 2 is a graph showing the effect of suppressing the total visceral fat accumulation by an animal experiment using apple polyphenol.

FIG. 3 is a graph showing the inhibitory effect of apple polyphenol on an increase in blood insulin concentration in animal experiments.

FIG. 4 is a graph showing the effect of suppressing the increase in blood lebutin concentration in animal experiments using apple polyphenol.

BEST MODE FOR CARRYING OUT THE INVENTION

[0008] The polyphenol used in the present invention is a fruit or immature fruit extract that is a purified polyphenol fraction. The polyphenol fraction is firstly a juice of raw material fruit or water or ethanol. An extract obtained by using the above organic solvent can be used. The juice from which the squeezed juice or the organic solvent has been removed can be used as it is, but through steps such as centrifugation and filtration, a clear juice or extract can be obtained, and the polyphenol fraction can be obtained. Is further purified by ion-exchange resin / synthetic adsorption resin, or an adsorbent such as silica gel or a gel filtration agent.

The polyphenol fraction can then be concentrated to obtain a liquid preparation, and further, the concentrate can be spray-dried or freeze-dried to obtain a powder preparation.

Auxiliaries such as organic solvents such as ethanol and organic acids such as citric acid can be used for liquid preparations, and dextrins and saccharides can be used as excipients for powder preparations. In the present invention, a fruit, preferably a fruit of a Rosaceae plant, specifically, an apple, a pear, a peach, a rice cake, or the like can be used as a raw material. .

In addition, immature fruits are particularly preferable because they contain more polyphenols than can be used for both mature fruits and immature fruits, and contain many active ingredients having a wide range of physiological functions.

The dose of the fat accumulation inhibitor described in the present invention, and the insulin elevation inhibitor and the lebutin elevation inhibitor used as an oral agent vary depending on the purpose of administration and the gender, age, weight, and health status of the administration subject. Force can be administered in the range of lmg Zkg body weight to lOOmg Zkg body weight as the weight of the dry polyphenol fraction.

The apple-derived polyphenol of the present invention is a fruit used as a raw material in food, so there is no problem in terms of safety.However, the acute toxicity test, the chronic toxicity test, and the mutation Various safety tests such as a safety test are conducted to confirm the safety.

The polyphenol fraction obtained as described above includes flavonols such as caffeic acid derivatives (esters) such as chlorogenic acid, P-tamaric acid derivatives, flavan 3-ols (catechins) and quercetin glycoside, and phloretin. It is composed of chalcones such as glycosides and polyphenols such as procyadins such as procyadine B-2. Inhibition of elevation, suppression of mutagenicity, allergy It has already been confirmed that it has physiological functions such as unisex suppression, pile caries, deodorization, and control of lipid metabolism in vivo (JP-A-7-285876, JP-A-10-330278).

[0009] Thereafter, as a result of further intensive studies by the present inventors, it was confirmed that the polyphenol had the following new physiological functions.

First, it was confirmed that the polyphenol had a function of suppressing the accumulation of visceral fat. That is, polyphenols containing the above-mentioned procyazines as main components are extremely effective in suppressing body fat accumulation.

Second, it was confirmed that the polyphenol had a function of suppressing an increase in insulin. That is, the polyphenols containing the above-described procyazines as main components are extremely effective in improving hyperinsulinemia.

Third, it was confirmed that the polyphenol had a function of suppressing the rise of lebutin. That is, polyphenols containing the above-described procyazines as main components are extremely effective in improving hyperleptinemia.

Next, the present invention will be described in more detail based on examples, but the present invention is not limited to these examples.

Example 1

[0010] Three-week-old male Sprauge-Dawley (SD) rats were pre-fed for 1 week on a commercial solid diet, and then fed a high-fat diet based on the diet composition of obesity and diabetes-inducing diet (the control was low-fat). (Fat feed) was fed a diet containing 1.0% of the polyphenol (no control group). In addition, since the intake of polyphenol-containing feed temporarily decreases at the beginning of administration due to the inherent bitterness, six animals per group are required to ensure that the intake is finally the same in all groups. (Table 1). After breeding, blood was collected from the abdominal artery under ether anesthesia, blood was collected and various tissues were collected, and various fat and tissue weights and various parameters of lipid metabolism system of liver and serum were measured.

[0011] [Table 1] Composition of each feed ingredient (%)

Adipose tissue weight: After breeding, peri-kidney (retroperitoneal), peri-testis (epitestis) and mesenteric adipose tissues were collected and weighed.

Measurement of Serum Insulin and Leptin: Serum insulin and leptin levels were measured as indicators related to obesity using a commercially available ELISA kit (insulin: ELISA kit from Mercodia; leptin: Yanaihara Institute ELISA kit).

Statistical processing: All the obtained results were shown by the standard error of the mean, and the significance test between each group was performed using Duncan's new multiple range test. The level of significance was set at p <0.05.

As a result, as shown in Table 2, body weight gain and food consumption increased significantly in the high-fat diet group compared to the control group, while the body weight gain and food consumption increased significantly. No significant difference was observed between the phenol groups. As shown in Table 3 and FIGS. 1 and 2, visceral fat mass was significantly suppressed.

Looking at the fat accumulation rate (total visceral fat increase ÷ control group total visceral fat), the high-fat diet group had (7.36-4.94) ÷ 4.94 x 100 = 49.0%. On the other hand, in the high-fat diet + polyphenol group (5.99-4.94) ÷ 4.94 × 100 = 21.2%, the fat accumulation rate was suppressed, and the change in body fat percentage (total Visceral fat increase ÷ weight gain x 100) The fat diet group (7.36-4.94) ÷ 424.7 X 100 = 0.56%, while the high fat diet + polyphenol group (5.99-4.94) ÷ 432. At 7 X 100 = 0.24%, the body fat percentage is also reduced.

[Table 2]

[0014] [Table 3]

*: Significantly different from the high-fat diet group at p <0.05

[0015] As a result of the measurement, as shown in Figs. 3 and 4, the serum insulin concentration and serum lebutin concentration were significantly higher in the high-fat diet group than in the normal diet control group. It was observed that the addition of apple-derived polyphenol suppressed the increase.

Example 2

(Production Example) 300 kg of Aomori apple fruit was crushed and pressed to obtain 210 kg of fruit juice. The resulting juice was subjected to clarification with 30 ppm of actinase, and after centrifugation, clarification was performed by filtration through diatomaceous earth (Silica 300S, manufactured by Chuo Silica Co., Ltd.) to obtain a clarified juice. The clarified juice was passed through an adsorption column (Senose HP-20, manufactured by Mitsubishi Chemical Corporation) to adsorb polyphenols. Subsequently, pure water is passed through the column to remove non-adsorbed substances (sugars, organic acids, etc.) from the column. Eluted with alcohol. The resulting fractional alcohol was concentrated under reduced pressure to prepare about 2 kg of an extracted powder product. When the extracted powder was assayed by reversed-phase high-performance liquid chromatography, it was found that chlorogenic acids (about 20%), phlorethylene glycosides (about 5%), flavonols (about 15%), proanthocyanin (about 50%) and other browning substances (about 10%). In addition, this protociadinin liability is composed of a matrix-assisted laser ionization-time-of-flight mass spectrometer (MALDI-TOFZMS, manufactured by Applied Biosystems Inc.). Oligomers and polymers ranging from dimers to 15-mers were confirmed. (M. Ohnishi-kameyama et al. Mass spectrometry, 11, 31-36, 1997)

(Comparative Example) Tablets 140 g of ratatose and 17 g of corn starch were mixed, and the mixture was granulated together with a paste prepared from 70 g of corn starch in advance. Magnesium stearate lg was added to the obtained granules and mixed well, and the mixture was tableted with a tableting machine to produce 1,000 tablets.

(Practical example) Tablets 150 g of the apple polyphenol obtained in Production Example 1, 90 g of ratatose and 17 g of corn starch were mixed, and the mixture was granulated together with a paste prepared from 70 g of corn starch. Magnesium stearate (lg) was added to the obtained granules and mixed well, and the mixture was tableted with a tableting machine to produce 1,000 tablets.

(Test Example) Fat accumulation suppression effect of apple polyphenol (human)

Next, a clinical study was conducted to examine the effect of apple polyphenol on inhibiting fat accumulation.

[0018] (Method)

Target

In a preliminary study conducted four weeks before the start of the study, 50 male and female volunteers who were voluntary volunteers to participate in the study and who showed a body mass index of 22 and a BMI ≤ 30 were volunteer volunteers. Selected. However, if you are taking medicines or health foods that may affect lipid metabolism, have a history of food allergy, or 200ml within 1 month or 400ml within 3 months Blood samples that exceed the threshold (such as those who donated blood or those judged by the investigator to be unsuitable for study participation) were excluded from the study. Results (blood, physical examination) and Age, weight, height, body mass index, blood pressure, triglyceride, total fat area (TFA), visceral fat area (VFA) and subcutaneous fat area (SFA) We divided them into two groups so that the backgrounds, such as West Z Hips, could be aligned. This study was conducted in accordance with the purpose of the Helsinki Declaration, with the subject fully explained about the contents and methods of the study, and with the written consent.

[0019] Test meal

This test meal was prepared by mixing a tablet containing apple polyphenol (150 mg Zl tablet) manufactured in a practical example and a polyphenol manufactured in a comparative example, and was used as a control food (placebo tablet). Before the test, the investigator confirmed that the test drink and the placebo tablet were indistinguishable due to the sensory surface such as flavor and aroma, and the package. Ingestion method and schedule

The study was a parallel two-group comparative study employing a double-blind method by random assignment. The study period was set for a total of 20 weeks: 4 weeks of early observation, 12 weeks of ingestion, and 4 weeks of observation after ingestion. The subjects were divided into two groups and consumed test tablets in the following manner.

Group A: 4 tablets each of apple polyphenol-containing test tablets (150 mg Zl tablets) before dinner (total 4 tablets Z days), the following groups of apple polyphenol test tablets

Group B: 4 placebo tablets (150 mg Zl tablets) each before dinner (4 tablets Z days), below placebo tablets

The subjects were instructed not to change their daily eating habits, smoking and exercising, except for taking test tablets daily.

[0020] CT examination

All subjects underwent abdominal fat analysis by CT scan. The analysis was performed using an L4ZL5 abdominal CT tomography image of the intervertebral disc, and a total fat area (TFA) using the PC software "Fat Scan" (manufactured by N2 System Co., Ltd.). The visceral fat area (VFA) was determined.

The administration was conducted twice, starting with the intake and 12 weeks after the intake (end of the intake). In principle, the test should be performed within 4 days before and after the test.The test date should be at least 4 hours after fasting and 2 hours after fasting. 查 was carried out.

Result

Table 4 shows the results. As a result of two-way analysis of variance, changes in total fat area (TFA), visceral fat area (VFA), and subcutaneous fat area (SFA) in all subjects were 12 weeks after ingestion in the placebo tablet group in TFA Although there was an increasing trend (p <0.1), no fluctuation tendency was observed in the group receiving the apple polyphenol test tablets.

[Table 4]

Note +: p <0.1 (ANOVA)

Note †: p <0.1 (paired t-test)

[0022] Regarding VFA, no fluctuation tendency was observed in the group receiving the placebo tablet, whereas a significant decreasing tendency was observed 12 weeks after ingestion in the group receiving the apple polyphenol test tablet (P. 1). As a result of the change in the amount of change, there was a tendency that there was a difference between the group receiving the placebo tablet and the group receiving the apple polyphenol test tablet (P <0.1).

The above results indicate that apple polyphenol has an effect of reducing body fat

Claims

The scope of the claims

[1] A fat accumulation inhibitor characterized by containing a polyphenol derived from fruit or immature fruit as an active ingredient.

[2] The fat accumulation inhibitor according to claim 1, wherein the fruit is a Rosaceae plant.

[3] The fat accumulation inhibitor according to claim 2, wherein the Rosaceae plant is an apple.

[4] The fat accumulation inhibitor according to claim 1, wherein the polyphenol is proanthocyanin.

[5] The fat accumulation inhibitor according to claim 4, wherein the proanthocyanin is procyadine.

[6] The method according to claim 15, which has an action of suppressing an increase in insulin or an increase in lebutin in a living body.

V. The fat accumulation inhibitor according to any one of the above items.

[7] The fat accumulation inhibitor according to any one of claims 15 to 15, which suppresses a fat accumulation rate.

[8] The fat accumulation inhibitor according to any one of claims 15 to 15, which reduces a body fat percentage.

[9] A food containing the fat accumulation inhibitor according to any one of claims 11 to 8.

[10] A beverage containing the fat accumulation inhibitor according to any one of claims 11 to 8.

[11] A food additive comprising the fat accumulation inhibitor according to any one of claims 11 to 8.

[12] A drug containing the fat accumulation inhibitor according to any one of claims 11 to 8.

[13] A quasi-drug containing the fat accumulation inhibitor according to any one of claims 11 to 8.

[14] An animal feed containing the fat accumulation inhibitor according to any one of claims 11 to 8.