JP2009274969A - Serum triglyceride concentration-reducing agent - Google Patents

Abstract

<P>PROBLEM TO BE SOLVED: To provide an effective preparation not only heightening body weight-reducing effects from the initial period by promoting the burning of abdominal fat, but also reducing a serum triglyceride concentration at fasting time and a free fatty acid concentration. <P>SOLUTION: The serum triglyceride concentration-reducing agent at the fasting time contains (A) non-polymerized catechins which may be a tea extract or a concentrate thereof, and (B) theanine as active ingredients. The agent may further contain amino acids other than the theanine, e.g. (C) aspartic acid and (D) arginine from the view points of further reducing the serum triglyceride concentration at the fasting time and the free fatty acid concentration. <P>COPYRIGHT: (C)2010,JPO&INPIT

Description

  The present invention relates to a serum triglyceride concentration lowering agent.

  Fat is an important nutrient together with protein and carbohydrate, and is particularly useful as an energy source. However, fat is high in calories (9 kcal / g), and thus promotes obesity and causes problems such as lifestyle-related diseases. Diets that use a lot of fat are delicious, and modern people are accustomed to such diets, which is a national problem in advanced countries that are in a fed state, coupled with increased medical costs. . Against this background, in recent years, interest in maintenance and promotion of health and prevention and treatment of diseases has increased, and many studies have been conducted on the relationship between fat and obesity and lifestyle-related diseases.

For example, Patent Document 1 reports that a packaged beverage containing a specific amount of non-polymer catechins and containing a non-epimer and an epimer in a specific ratio significantly promotes the burning of accumulated fat. Yes. Patent Document 2 reports that a container-packed beverage in which sodium ions and potassium ions are combined at a specific ratio with non-polymer catechins increases the body fat reduction effect by combining exercise habits. . Among these documents, the serum triglyceride concentration is measured in Patent Document 1, but a significant effect of reducing the serum triglyceride concentration has not been confirmed.
On the other hand, Patent Document 3 proposes a packaged beverage combining non-polymer catechins with theanine and glutamic acid or a salt thereof. This container-packed beverage aims to improve the flavor by suppressing bitterness and astringency, and has not been studied at all for reducing body fat and serum triglyceride concentrations.
As described above, the actual situation is that the effect of the combined use of non-polymer catechins and specific amino acids on specific components of serum has not been sufficiently studied.

JP 2002-326932 A JP 2006-158379 A JP 2008-63321 A

  Therefore, an object of the present invention is to provide a preparation effective for reducing serum triglyceride concentration.

  The present inventors have found that a combination of non-polymer catechins and a specific amino acid is effective in reducing serum triglyceride concentration.

  That is, the present invention provides a fasting serum triglyceride concentration-reducing agent containing (A) non-polymer catechins and (B) theanine as active ingredients.

  In the present invention, combining non-polymer catechins and specific amino acids not only enhances the weight loss effect from the initial stage by promoting the burning of abdominal fat, but also the serum triglyceride concentration and free fatty acids during fasting The concentration can be reduced. Such an effect can be further enhanced by combining the intake of non-polymer catechins and specific amino acids with exercise load.

The fasting serum triglyceride concentration-lowering agent (hereinafter, also referred to as “formulation”) of the present invention is characterized by containing (A) non-polymer catechins and (B) theanine as active ingredients.
In the present invention, (A) non-polymer catechins are non-epimeric catechins (hereinafter also referred to as “non-epimers”) consisting of catechin, gallocatechin, catechin gallate, gallocatechin gallate, epicatechin, epigaro It is a collective term for epi-catechins consisting of catechin, epicatechin gallate, and epigallocatechin gallate (hereinafter also referred to as “epi-form”), and the concentration of non-polymer catechins is based on the total amount of the above eight types. Defined. Here, the ratio of epimer in non-polymer catechins (hereinafter also referred to as “(E) epimer ratio”) is the total mass of these four epimers and the sum of eight non-polymer catechins. It is a numerical value expressed as a percentage of the mass.

  In addition, (A) non-polymer catechins include gallate bodies composed of epigallocatechin gallate, gallocatechin gallate, epicatechin gallate and catechin gallate, and non-gallate bodies composed of epigallocatechin, gallocatechin, epicatechin and catechin. is there. Here, the ratio of the gallate body in the non-polymer catechins (hereinafter also referred to as “(F) gallate body ratio”) is the total mass of these four types of gallate bodies and the total of the eight non-polymer catechins. It is a numerical value expressed as a percentage of the mass.

Further, the epimer ratio in the (E) non-polymer catechins contained in the preparation of the present invention is preferably 40 to 95% by mass, more preferably 50 to 90% by mass, particularly preferably 55 to 90% by mass. is there. Thereby, taste becomes much more excellent, and there is little astringent taste that pulls behind, which is preferable.
Further, the gallate content in the (F) non-polymer catechins contained in the preparation of the present invention is preferably 20 to 90% by mass, more preferably 30 to 90% by mass, particularly preferably 40 to 90% by mass. is there. Thereby, taste becomes much more excellent, and there is little astringent taste that pulls behind, which is preferable.

The preparation of the present invention contains (B) theanine as an active ingredient, but may contain other amino acids. From the viewpoint of reducing the serum triglyceride concentration and free fatty acid concentration during fasting, for example, ( C) Aspartic acid and (D) arginine are preferred.
These amino acids can use any isomers of L-form, D-form and DL-form, but L-form is preferred from the viewpoint of existing in nature. As amino acids, commercially available products may be used, or amino acids produced or extracted by known methods may be used.

The preparation of the present invention, when taken in combination with exercise load, not only promotes abdominal fat burning and further enhances the weight loss effect from the initial stage, but also increases the serum triglyceride concentration and free fatty acid concentration during fasting. It can be significantly reduced. That is, the combination of the present invention with the exercise habit increases not only the body fat reduction action, but also enhances the effect of reducing fasting serum triglyceride concentration and free fatty acid concentration. Preferably, the administration period is 2 weeks or longer.
The exercise load may be low to moderate, such as walking or jogging. Specifically, the intensity of exercise load is 5 (MET-hours of activity per week) or more, particularly 5-30 (MET- hours of activity per week) is preferred. “MET-hours of activity per week” is a unit that is a measure of the amount of exercise required, and exercise equivalent to the value obtained by dividing each exercise metabolism by the resting metabolism (MET) for one week. Measured at the time taken. For example, cycling and underwater exercise correspond to 4METS, and if this exercise is performed for 1 hour every day, it corresponds to 28 MET hour of activity per week. In addition, the preparation of the present invention can be taken freely without particular limitation such as at meals, between meals, before and after exercise, but it is preferable to take the prescribed amount per day in about 30 minutes.

The amount of (A) non-polymer catechins administered as an active ingredient in the preparation of the present invention is preferably 400 mg or more per day for an adult, more preferably 500 mg or more, still more preferably 550 mg or more, particularly preferably 600 mg. That's it. The upper limit is preferably 3000 mg, more preferably 2500 mg, and particularly preferably 2000 mg.
The dose of (B) theanine is preferably 25 mg or more per day for an adult, more preferably 27 mg or more, and particularly preferably 29 mg or more. The upper limit is preferably 139 mg, more preferably 116 mg, and particularly preferably 93 mg.
Further, the mass ratio [(C) / (B)] of (B) theanine and (C) aspartic acid in the preparation of the present invention is preferably 0.2 or less, more preferably 0.1 or less, particularly Preferably it is 0.05 or less. The lower limit is preferably 0.001, more preferably 0.01, and particularly preferably 0.02.
Furthermore, the preparation of the present invention may further contain (D) arginine, and the dose of (D) arginine is preferably 2.6 mg or more, more preferably 2.8 mg or more, particularly preferably 3. 0 mg or more. The upper limit is preferably 114 mg, more preferably 120 mg, particularly preferably 96 mg.
By setting it as such a dosage, while abdominal fat combustion is accelerated | stimulated, the serum triglyceride density | concentration and free fatty acid density | concentration at the time of an empty stomach can be reduced significantly.

Since the (A) non-polymer catechins used in the present invention are generally contained in a tea extract extracted from tea leaves, a concentrate thereof or a purified product thereof, those obtained from these are preferred, Specifically, a tea extract, a concentrate thereof or a purified product thereof is blended.
Extraction from tea should be carried out by stirring or extracting tea leaves made from tea leaves selected from the genus Camellia, such as C. sinensis and C. assamica, Yabuki species or their hybrids, using water or hot water Can do. The tea leaves produced include green teas such as Sencha, Bancha, Gyokuro, Tencha, Kabusecha, etc .; Iron Kannon, which is collectively called Oolong tea, color types, semi-fermented teas such as golden katsura, wushuiwa tea; Examples include fermented teas such as darjeeling, uba, and key man. Of these, green teas are preferred from the viewpoint that high concentrations of (A) non-polymer catechins are readily available. Moreover, you may add an extraction aid to the water or hot water used at the time of extraction, and organic acid, such as ascorbic acid, or its salt (for example, sodium salt) can be used as an extraction aid.

  Concentration of the tea extract can be performed by removing a part of the water from the tea extract extracted from the tea leaves. For example, JP-A-59-219384, JP-A-4-20589, The methods exemplified in JP-A-5-260907, JP-A-5-306279 and the like can be employed. Examples of the commercially available products include “Polyphenone”, Mitsui Norin Co., Ltd., “Theafranc”, ITO EN Co., Ltd., “Sunphenon”, Taiyo Chemical Co., Ltd., “Sunwoolon”, etc. The tea extract can be purified by removing precipitates and the like using a solvent and a column. Various forms such as solids, aqueous solutions, slurries, etc., can be used as the form of concentrate and purified product of tea extract.

(A) Non-polymer catechins used in the present invention are obtained by suspending a tea extract or a concentrate thereof in water or an aqueous organic solvent solution and filtering the resulting precipitate from activated carbon, acidic clay and activated clay. Those derived from a purified tea extract obtained by adding and purifying at least one selected are preferred, and purification of the tea extract obtained by adding and purifying activated carbon and acid clay or activated clay What originates in a thing is especially preferable.
The order in which the tea extract or its concentrate is brought into contact with activated carbon, acidic clay and activated clay is not particularly limited. For example, after the tea extract or its concentrate is dispersed or dissolved in water or an aqueous organic solvent solution, activated carbon is used. And a method of contacting with acid clay or activated clay is preferably employed.

Examples of the organic solvent used for the purification include alcohols such as methanol and ethanol, ketones such as acetone, and esters such as ethyl acetate. Is preferred. Examples of water include ion-exchanged water, distilled water, tap water, natural water, and the like, and ion-exchanged water is particularly preferable from the viewpoint of taste.
The ratio of the tea extract or its concentrate to water or the organic solvent aqueous solution is 10 to 40 parts by mass of the tea extract or its concentrate (in terms of dry mass) with respect to 100 parts by mass of the water or organic solvent aqueous solution, In particular, it is preferable to add 10 to 30 parts by mass for the processing efficiency.
It is preferable to provide an aging time of about 10 to 180 minutes for the contact treatment, and these treatments can be carried out at 10 to 60 ° C., more preferably 10 to 50 ° C., particularly preferably 10 to 40 ° C.
The mass ratio of the organic solvent and the water in the aqueous organic solvent solution is 99/1 to 70/30, particularly 97/3 to 75/25, from the viewpoint of improving the concentration of non-polymer catechins and removing the flavor component derived from tea. Is preferred.

As the activated carbon used for the contact treatment, commercially available products can be used. For example, ZN-50 (made by Hokuetsu Carbon Co., Ltd.), Kuraray Coal GLC, Kuraray Coal PK-D, Kuraray Coal PW-D (made by Kuraray Chemical Co., Ltd.) White birch AW50, white birch A, white birch M, white birch C (manufactured by Takeda Pharmaceutical Company Limited), and the like. The pore volume of the activated carbon is preferably 0.01 to 0.8 mL / g, particularly preferably 0.1 to 0.8 mL / g. The specific surface area is preferably in the range of 800 to 1600 m ² / g, particularly 900 to 1500 m ² / g. These physical property values are values based on the nitrogen adsorption method.
The amount of activated carbon used is 0.5 to 8 parts by mass, particularly 0.5 to 3 parts by mass, based on 100 parts by mass of water or an organic solvent aqueous solution, because the purification efficiency and the cake resistance in the filtration step are small. preferable.

Both the acid clay and the activated clay used for the contact treatment contain SiO ₂ , Al ₂ O ₃ , Fe ₂ O ₃ , CaO, MgO, etc. as general chemical components, but SiO ₂ / Al ₂ O. _{3 A} ratio of 3 to 12, particularly 4 to 9 is preferred. Further, Fe ₂ O ₃ 2 to 5 wt%, the CaO 0 to 1.5 wt%, preferably from compositions containing MgO 1 to 7% by weight.
The specific surface area of the acid clay or the activated clay is preferably 50 to 350 m ² / g, and the pH (25 ° C., 5 mass% suspension) is 2.5 to 8, particularly 3.6 to 7. For example, as the acid clay, commercially available products such as Mizuka Ace # 600 (manufactured by Mizusawa Chemical Co., Ltd.) can be used.
The ratio of the activated carbon to the acid clay and the activated clay is preferably 1 to 10 with respect to the activated carbon 1 in terms of mass ratio, and is preferably activated carbon: acid clay and activated clay = 1: 1 to 1: 6.

  Whether the preparation used in the present invention is a combination of at least two selected from tea extracts, concentrates thereof, and purified products thereof so that the non-polymer catechins and specific amino acids have a predetermined concentration. Or by using at least one selected from tea extracts, concentrates thereof and purified products thereof, and adding amino acids as necessary to adjust the non-polymer catechins and specific amino acids to a predetermined concentration. can get.

As described above, the combination of the non-polymer catechins of the present invention and the amino acids exhibits not only an excellent body fat reduction effect, but also an effect of reducing serum triglyceride concentration and free fatty acid concentration at the time of fasting. It is useful not only as a serum triglyceride concentration lowering agent, but also as a free fatty acid concentration lowering agent, a fat metabolism promoter, etc. during fasting.
That is, such a combination can be provided in the form of a pharmaceutical product or quasi drug. Examples of pharmaceuticals and quasi drugs include oral preparations such as solid preparations such as powders, granules, capsules, pills and tablets, and liquid preparations such as liquids, suspensions and emulsions. Oral administration agents are produced by adding excipients, disintegrants, binders, lubricants, surfactants, alcohols, water, water-soluble polymers, sweeteners, flavoring agents, acidulants and the like, for example. It is possible.

  Moreover, the combination of the non-polymer catechins of the present invention and the amino acids can be used as food. Specific examples of such foods include bakery foods such as bread, cakes and cookies, confectionery such as chocolate and candy, sauces, soups, dressings, mayonnaises and creams. The daily intake of active ingredients in these foods is the same as the dosage of the above preparation.

Measurement of non-polymer catechins Beverage filtered through a membrane filter (0.8 μm), packed column for octadecyl group-introduced liquid chromatograph L-column TM ODS (4.6 mmφ × 250 mm, manufactured by Chemical Substances Evaluation Research Organization) Was performed by a gradient method at a column temperature of 35 ° C. using a high performance liquid chromatograph (model SCL-10AVP, manufactured by Shimadzu Corporation) equipped with The mobile phase A solution was a distilled aqueous solution containing 0.1 mol / L of acetic acid, the B solution was an acetonitrile solution containing 0.1 mol / L of acetic acid, the sample injection amount was 20 μL, and the UV detector wavelength was 280 nm. .

Measurement of Amino Acid Sample preparation was performed by quantifying 1 mL of 0.2 mM hydrochloric acid in a 10 ml volumetric flask, and adding 9 mL of sample to make up the volume. After filtration with a membrane filter (0.45 μm), 1 mL was transferred to a vial and used as a measurement sample. The measurement was performed by a protein hydrolyzate analysis method, which is an official method described in the manual of this measuring apparatus, using a Hitachi L-8800A type high-speed amino acid analyzer.

Test example Randomly extract the catechin group and the control group from 132 subjects, and specify the intake time of each test subject (preparation) 500 mL or control substance 500 mL shown in Table 1 for 12 weeks. Without ingesting within 30 minutes. During the test, subjects were required to have habitual energy intake and exercise of 5 (MET-hours of activity per week) or more, and prohibited to take caffeine-containing beverages more than once a day.
The composition of the subjects is as follows.
Age: Men and women aged 21-65 years (average age: 47 years for catechin group, 49 years for control group)
Girth: Women over 87 cm, men over 90 cm Total cholesterol: 200 mg / dL or more BMI: 25-39.99 Kg / m ²

  During the 12-week test period, weak to medium intensity exercise was performed with a goal of 180 minutes / week. At least three exercises per week were carried out under supervised exercises in gyms. The fasting body weight and waist circumference were measured every other week.

(1) Measurement of fasting serum triglyceride concentration and total cholesterol level Using a Roche reagent (Roche Modular), the serum triglyceride concentration and total cholesterol level were measured. The results are shown in Table 2.

(2) Measurement of free fatty acid concentration on an empty stomach The free fatty acid concentration was measured using WACO (Dalton). The results are shown in Table 2.

(3) Measurement of fasting body weight and waist circumference After exhaling normally, the waist circumference is measured on a level surface at the height of the iliac crest using a non-stretchable body measuring tape, and the body weight is also measured. did. The difference in body weight (ΔKg) in each week relative to week 0 is shown in FIG.

(4) Measurement of fasting body composition and fat distribution Body composition was measured by a dual energy X-ray absorption measurement method (DEXA), and abdominal fat area was measured by abdominal computer cross-sectional photography. Whole body DEXA scans were performed with LUNAR (GE). Body composition (fat and lean mass) was analyzed using software (version 9.30) manufactured by Prodigy Advance DXA System. Abdominal computer cross-sectional imaging was performed using Somaton (manufactured by Seimens Co., Ltd.), and a 3-slice abdominal CT scan was performed with the subject lying on his back, with a slice thickness of 7 mm or less and a height of 4-5 calculus in the waist. The measurement protocol and CT scan data were read using a standard protocol manufactured by BioImaging Technologies. The result is shown in FIG.

(5) Statistical analysis The comparison between week 0 and week 12 was evaluated by SAS version 9.1.1, and the obtained numerical values were shown as mean value ± standard deviation.

From the results in Table 2, the serum triglyceride concentration was significantly decreased in the catechin group, and the effect of reducing the serum triglyceride concentration by the combination of non-polymer catechins and specific amino acids was confirmed. In addition, serum triglyceride concentration is one of the indicators of metabolic syndrome, and a decrease in this indicates that lipid metabolism is improved.
In addition, a significant decrease in plasma free fatty acid concentration was observed in the catechin group, whereas a slight increase was confirmed in the control group.
In the catechin group, the body weight decreased more significantly in the 2nd to 8th weeks after the start of the test, and the decrease in body weight was also confirmed in the 12th week.
As shown in FIG. 2, a significant reduction was observed in the total abdominal fat area and the abdominal subcutaneous fat area, and a similar reduction was also confirmed in the visceral fat area.
From these results, the combination of the non-polymer catechins of the present invention and specific amino acids not only exerts a weight loss effect from the initial stage by promoting the burning of abdominal fat, but also the serum triglyceride concentration and release during fasting It was confirmed that the fatty acid concentration was significantly reduced.

Production example (purified green tea extract)
100 g of a commercially available concentrate of green tea extract (polyphenone HG, manufactured by Mitsui Norin Co., Ltd.) is dispersed in 490.9 g of 95% by mass ethanol, 20 g of activated carbon Kuraray Coal GLC (manufactured by Kuraray Chemical Co., Ltd.) and acidic clay Mizuka Ace # 600 ( After adding 50 g of Mizusawa Chemical Co., Ltd., stirring was continued for about 10 minutes. And 409.1g of 95 mass% ethanol aqueous solution was dripped over 10 minutes, Then, the stirring process for about 30 minutes was continued with room temperature. Thereafter, the activated carbon and the precipitate were filtered with No. 2 filter paper, and further filtered with a filter paper having a pore size of 0.2 μm. Finally, 350 mL of water was added and concentrated under reduced pressure to obtain a purified product of green tea extract. The concentration of non-polymer catechins in the purified product of this green tea extract is 15.5% by mass, (C) the mass ratio of aspartic acid / (B) theanine, and (D) the mass of arginine / (B) theanine. Both ratios were 0.034.

It is a figure which shows the change of the body weight in the catechin group and control group which ingested the formulation of this invention. It is a figure which shows the change of fat distribution in the fasting 12 weeks after in the catechin group and control group which ingested the formulation of this invention.

Claims (8)

  A fasting fasting agent for serum triglycerides containing (A) non-polymer catechins and (B) theanine as active ingredients.   The serum triglyceride concentration-lowering agent according to claim 1, further comprising (C) aspartic acid as an active ingredient.   The serum triglyceride concentration-lowering agent according to claim 1 or 2, which is for ingestion in combination with an exercise load having an exercise load intensity of 5 (MET-hours of activity per week) or more.   (A) The serum triglyceride concentration-lowering agent according to any one of claims 1 to 3, wherein the dose of non-polymer catechins is 400 mg or more per day.   (B) The serum triglyceride concentration-lowering agent according to any one of claims 1 to 4, wherein the dose of theanine is 25 mg or more per day.   The serum triglyceride concentration-lowering agent according to any one of claims 2 to 5, wherein the mass ratio [(C) / (B)] of (C) aspartic acid and (B) theanine is 0.2 or less.   The serum triglyceride concentration-lowering agent according to any one of claims 1 to 6, further comprising (D) arginine as an active ingredient, wherein the dose of (D) arginine is 2.6 mg or more per day.   (A) A non-polymer catechin is prepared by suspending a tea extract or a concentrate thereof in water or an organic solvent aqueous solution and bringing it into contact with at least one selected from activated carbon, acidic clay and activated clay, and purifying the tea extract. The serum triglyceride concentration-lowering agent according to any one of claims 1 to 7, which is obtained from a purified product.

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