JP2003081825A - Catechin-containing beverage - Google Patents

Abstract

PROBLEM TO BE SOLVED: To obtain a GLUT4 expression promoter and a bottled beverage containing the same, which control a blood sugar level by rapidly taking absorbed glucose in blood in cells not by blood sugar control by sucrose absorption suppression such as digestive enzyme inhibition of glucide and transportation route inhibition from the intestinal tract, can suppress a rapid rise of blood sugar after taking sugar even without taking the promoter or the beverage simultaneously with a meal and are useful for preventing and ameliorating diabetes. SOLUTION: This glucose transporter 4 expression promoter comprises catechins. This bottled beverage for preventing/ameliorating diabetes comprises dissolved catechins as nonpolymer constituents (A) non-epicatechin and (B) epicatechin in the ratio of component (A)/the component (B) (by weight) (A)/(B) of 0.25-9.0.

Description

Detailed Description of the Invention

[0001]

TECHNICAL FIELD The present invention relates to a glucose transporter 4 expression promoter, and diabetes containing the same,
The present invention relates to a packaged beverage containing a glucose transporter 4 expression promoter which is effective in preventing and improving hyperinsulinemia and insulin resistance.

[0002]

2. Description of the Related Art Regarding the metabolism of carbohydrates in the body, glucose uptake in muscle and adipose tissue is due to a glucose transporter (glucose transporter) on the cell membrane.
orter: GLUT), and the amount of glucose uptake is regulated by the amount of glucose transporter. The major glucose transporter in these tissues is glucose transporter 4 (GLUT4).
Although it is called inside the cell, it usually exists inside the cell, and is translocated to the cell membrane by insulin stimulation, and glucose is taken into the cell through the carrier. As a diabetes therapeutic agent focused on GLUT4, a method has been proposed in which the protein p72 of insulin signal transduction system is tyrosine phosphorylated to activate the translocation of GLUT4 (Japanese Patent Laid-Open No. H11 (1999) -111945).
-35485 gazette). In addition, it has been reported that transgenic mice in which GLUT4 is overexpressed even in a small amount are unlikely to have diabetes caused by a high-fat diet (Ikemot).
o, S. et al.:Proc. Natl. Acad. Sci. USA, 92: 3086-308
9, 1995), a material that promotes the expression of GLUT4 in tissues was considered to be effective in the prevention and cure of diabetes.

[0003]

The object of the present invention is not to control blood sugar by suppressing sugar absorption such as inhibition of digestive enzymes of carbohydrates and inhibition of transport pathways from the intestinal tract, but promptly intracellular glucose absorption in blood. It is possible to control the blood sugar level by taking it in and suppress a sharp rise in blood sugar after sugar intake even if it is not taken at the same time as meals,
It is intended to provide a GLUT4 expression promoter and a packaged beverage that are useful for preventing and improving diabetes.

[0004]

The present inventor has found that catechins have a GLUT4 expression promoting action and are useful for preventing and improving diabetes, hyperinsulinemia, insulin resistance, and impaired glucose tolerance. . The present invention provides a glucose transporter 4 expression promoter comprising catechins. Further, the present invention comprises the following non-polymer components (A) and (B): (A) non-epi catechins, (B) epi-catechins dissolved therein, (A) / (B) (Weight ratio) is (A) /
(B) = 0.25 to 9.0 The present invention provides a packaged beverage for diabetes prevention / improvement. Furthermore, the present invention comprises the following non-polymer components (A) and (B): (A) non-epi catechins, (B) epi-catechins dissolved therein, and (A) + (B ) Is 460 to 2500 m
g, (A) 90 to 2250 mg and (A) / (B) (weight ratio) is (A) / (B) = 0.25 to 9.0, hyperinsulinemia or insulin resistance prevention / improvement The present invention provides a packaged beverage for a container.

[0005]

BEST MODE FOR CARRYING OUT THE INVENTION In the present invention, catechins include non-epicatechins such as catechin, gallocatechin, catechin gallate, and gallocatechin gallate, and epicatechin, epigallocatechin, epicatechin gallate, epigallocatechin gallate, and the like. It is a generic term for epi-catechins.

The catechins used in the present invention are Camellia.
Genus, such as C. sinensis and C. assaimica, or tea made from tea leaves obtained from hybrids thereof, sencha, bancha,
Green teas such as gyokuro, tencha, and tea in a kettle, as well as iron Kannon, which is generally called Toryu-cha, color species, semi-fermented teas such as Golden Katsura, Wuyiwaiwa tea, and Darjeeling, Assam, Sri Lanka, etc. It is obtained by extracting the leaves of fermented tea with water or hot water.

Instead of extracting from tea leaves, the tea extract concentrate may be dissolved in water and used, or the extract from tea leaves and the tea extract concentrate may be used in combination. The concentrate of the tea extract as used herein is a concentrate of an extract obtained by extracting tea leaves with hot water or a water-soluble organic solvent, and is disclosed in JP-A-59-219384 and JP-A-4-20589. Japanese Patent Application Laid-Open No. 5-260907, Japanese Patent Application Laid-Open No. 5-30
It refers to one prepared by a method detailed in Japanese Patent No. 6279. Commercially available Mitsui Norin Co., Ltd. “Polyphenon”, ITO EN Co., Ltd. “Theafran”, Taiyo Kagaku Co., Ltd.
"Sunphenon", Suntory Co., Ltd. "Sanwoolong"
Etc. In addition, catechin can be used in other raw materials, column refined products and chemically synthesized products. Examples of the form of the tea extract concentrate include various forms such as solid, aqueous solution and slurry. Examples of the medium for dissolving the tea extract (hereinafter referred to as an extract) include water, carbonated water, teas containing commercially available levels of catechins, and the like.

In the tea extract, these catechins include non-polymerized ones which are dissolved and solid ones which are adsorbed and contained in fine tea powder. The catechins used in the present invention are obtained by dissolving an extract obtained by filtering a tea extract or the like and drying it.

In tea leaves, most of catechins exist as epi-forms, but they are transformed into non-epio-forms which are stereoisomers by treatment with heat, acid or alkali. Non-epi catechins can be obtained by, for example, converting an extract from a green tea, a semi-fermented tea or a fermented tea or a concentrate of a tea extract into an aqueous solution, for example, 4
It can be obtained by heat treatment at 0 to 140 ° C. for 0.1 minutes to 120 hours. Alternatively, a concentrate of tea extract having a high non-epicatechin content may be used. They may be used alone or in combination.

The GLUT4 expression promoting agent of the present invention is such a catechin, but the form of ingesting the GLUT4 expression promoting agent is not particularly limited as long as it can be taken orally. For example, beverages, tablets, capsules, powders, granules, as well as bread, cereals, noodles,
Processed foods such as rice, potatoes and corn, dairy products, processed agricultural products, confectionery, cakes, biscuits, cookies, gummy,
All types of foods such as jelly and oral medications are possible. For example, beverages, tablets, and capsules can be applied, but among them, easier beverages are preferable,
Further, a packaged beverage that can be carried is preferable.

When the GLUT4 expression promoting agent of the present invention is used as a packaged beverage for preventing or improving diabetes, non-epicatechins (component (A)) and epicatechins (component (B)) in catechins are included. ) Are both dissolved and contained in the beverage, and the content weight ratio thereof is (A) / (B) = 0.25 to 9.0, preferably 0.43 to 5.67, particularly 0.67 to 5 .67
Is preferred for promoting GLUT4 expression.

Further, the GLUT4 expression promoting agent of the present invention is
In the case of a packaged beverage for preventing / ameliorating hyperinsulinemia or insulin resistance, non-epicatechins (component (A)) and epicatechins (component (B)) are both dissolved in the beverage. Contained in the packaged beverage, the total amount of component (A) and component (B) is 460 to 25 per 500 mL of packaged beverage.
It is preferably contained in an amount of 00 mg, preferably 500 to 1300 mg, more preferably 600 to 1300 mg, and particularly preferably 640 to 800 mg. Within this range, the effect is excellent and the taste is also preferable. Further, from the viewpoint of stability, the component (A) is packed in a container 500
90 to 2250 mg per mL, preferably 140 to 225
It is preferable to contain 0 mg, particularly 140 to 1880 mg.
Further, the content weight ratio of the component (A) and the component (B) is (A) /
(B) = 0.25 to 9.0, preferably 0.43 to 5.
67, especially 0.67 to 5.67 is preferable.

Component (A) contained in the packaged beverage of the present invention
When component (B) and component (B) have such an amount of components, the effects are excellent, and the taste and stability are excellent, and the following are more preferable. If the content of catechins is 30 to 98% by weight, preferably 40 to 90% by weight, it is selected from epigallocatechin gallate, gallocatechin gallate, epigallocatechin, gallocatechin, and the taste as a beverage is obtained. It is more preferable, and it is preferable because it does not have any astringent property. Here, at least one epigallocatechin gallate, gallocatechin gallate, epigallocatechin, and gallocatechin is contained, but usually all are contained. Also, from the relationship with the taste of the green tea extract to be added, even if the catechin concentration is increased,
The combination of semi-fermented tea, Toryu tea, and fermented tea, black tea, is preferable because the astringency of catechins is alleviated and the palatability is excellent. The content of catechins in the total polyphenols in the packaged beverage was 10 after the production.
It is at least wt%, preferably at least 20 wt%.

The GLUT4 expression-enhancing agent of the present invention is such a catechin, but by combining it with other beverage components such as fruit juice, prevention and improvement of a wide range of diabetes, hyperinsulinemia and insulin resistance. It is possible to provide an effective packaged beverage containing catechins. For example, it may be appropriately added to soft drinks such as carbonated drinks, fruit extract-containing drinks, vegetable extract-containing juices, near-water, sports drinks, diet drinks and the like.

The pH of the beverage containing the GLUT4 expression promoter is
It is preferably 3 to 7, preferably 4 to 7, particularly 5 to 7 at 25 ° C. from the viewpoint of taste and chemical stability of catechins.

In the packaged beverage containing the GLUT4 expression promoting agent of the present invention, antioxidants, flavors, various esters, organic acids, organic acid salts, inorganic acids, inorganic acid salts are added as components which may be added in the formulation. , Pigments, emulsifiers, preservatives, seasonings, sweeteners, acidulants, fruit juice extracts, vegetable extracts, nectar extracts, pH adjusters, quality stabilizers and other additives alone,
Alternatively, they may be used in combination. Further, it may be used in combination with other components effective for preventing / ameliorating diabetes, preventing / ameliorating hyperinsulinemia, and preventing / ameliorating insulin resistance. In addition, as a pharmaceutical composition, in addition to raw materials used in beverages, foods, and pharmaceuticals, it is used in combination with other ingredients effective in preventing / ameliorating diabetes, preventing / ameliorating hyperinsulinemia, and preventing / ameliorating insulin resistance. May be. Further, the GLU of the present invention
A T4 expression promoter is used in combination with a sugar absorption inhibitor such as an amylase inhibitor, a glucosidase inhibitor, a sucrase inhibitor, or a glucose transport pathway inhibitor that suppresses postprandial hyperglycemia, or another sugar absorption inhibitor or dietary fiber. Good.

When used as a packaged beverage, the container to be used is a molded container containing polyethylene terephthalate as a main component (so-called PET bottle), a metal can, a metal foil or a plastic film, like a general beverage. It can be provided in a usual form such as a paper container, a bottle and the like. The term "packaged beverage" as used herein means one that can be drunk without dilution. In addition, the packaged beverage of the present invention is manufactured under the sterilization conditions stipulated by the Food Sanitation Act when it can be heat sterilized after being filled in a container such as a metal can. PET
For bottles and paper containers that cannot be sterilized by retort, the same sterilization conditions as above, such as high temperature short time sterilization using a plate heat exchanger, etc., is followed by cooling to a certain temperature and filling the container. Is adopted. Further, aseptically, another component may be mixed and filled in the filled container. Further, it is possible to carry out an operation such that after heat sterilization under acidic condition, pH is returned to neutral under aseptic condition, or after heat sterilization under neutral condition, pH is returned to acidic under sterile condition.

[0018]

Example 1 GLUT4 expression promoting effect of catechins C57BL / 6J mice (male, 7 weeks old, 5 mice in each group) containing 5% by weight of triglyceride, and 30% by weight of triglyceride and 13% by weight of sucrose The high-fat sucrose diet and the catechin-containing diet in which 0.5 wt% of the catechins of the composition of Table 1 was replaced with 0.5 wt% of the potato starch of the high-fat sucrose diet were freely ingested. One month later, the mouse was dissected, the coating was collected, total RNA was extracted as follows, and subjected to Northern blot.

[0019]

[Table 1]

Total RNA was purified using Isogen (Wako Pure Chemical Industries, Ltd.), and the resulting RNA (20 μg / lane) was subjected to agarose electrophoresis and then transferred to Hybond-N + (Amersham) nylon membrane and UV-fixed. A filter was produced. Then pre-hybridization solution (50 wt% formamide, 5
× SSPE, 0.5 wt% sodium dodecyl sulfate, 10 wt%
Denhardt's solution, 40mg / mL denatured salmon sperm DN
Pre-hybridization was performed in A) at 42 ° C. for 6 hours, and then ³² P-labeled GLUT4 probe was added, and hybridized at 42 ° C. for 15 to 18 hours. The filter was washed with 2 × SSC / 0.1 wt% sodium dodecyl sulfate at room temperature and then washed with 0.1 wt% SSC / 0.1 wt% sodium dodecyl sulfate at 50 ° C. The obtained filter was subjected to autoradiography using a BAS2000 bioimage analyzer (Fujifilm), and the radioactivity of each band was measured. Similarly, 36B4 RNA was also hybridized as a control gene, and the radioactivity of GLUT4 mRNA was corrected by the radioactivity of 36B4 RNA to obtain each expression level. The cDNA probe is GLUT4 (Gen
bankAB008453, nt 74-1122) and 36B4 (Genbank X15267,
nt 97-860) PCR-amplified product ready-to-go DNA labeling
The cells were labeled with beads (Amersham) and ³² P-dCTP (Amersham) before use.

The results are shown in Table 2. Catechins were excellent in promoting GLUT4 expression in muscle.

[0022]

[Table 2]

Example 2 Dietary obesity / diabetes model mouse (C57BL / 6J mouse:
Males, 7 weeks old, 5 animals in each group) were allowed to freely ingest the normal diet, high-fat sucrose diet and catechins-containing diet (containing 1.2% by weight of catechins based on sugar) used in Example 1 for 10 months. It was The glucose tolerance is evaluated by the oral glucose tolerance test (OGTT: Glucose to
lerance test). After fasting for 12 hours, glucose (3 mg / g body weight) was orally administered, and blood was collected from the tail vein over time to measure the blood glucose level. A simple blood glucose meter (glucose dehydrogenase / potentiometric method, manufactured by Roche Dianostic) was used for blood glucose measurement. Simultaneously with the blood glucose measurement, blood was collected from the tail vein using a heparin-treated hematocrit capillary tube (75 mm, DRUMMOND SCIENTIFIC CO.). Plasma was collected by centrifugation at about 11000 r / min for 5 minutes, and the insulin concentration was measured by the EIA method (insulin measurement kit: Morinaga Institute of Scientific Research).

The results are shown in FIGS. In the high-fat sucrose diet intake group, the blood glucose level after oral administration of glucose was significantly higher than that in the normal diet intake group up to 2 hours after the glucose load, and deterioration of glucose tolerance was observed. Moreover, the insulin level before oral administration of glucose was also significantly higher than that in the normal diet intake group, indicating hyperinsulinemia. On the other hand, in the catechins-containing food intake group, the increase in blood glucose level was significantly suppressed, and improvement in glucose tolerance was observed. At the same time, the hyperinsulinemia observed in the high-fat sucrose diet group was also improved, and the insulin resistance was improved.

It was confirmed by the following tests that this bait composition (containing 1.2% by weight of catechins with respect to sugar) does not have a sugar absorption inhibitory action due to digestive enzyme inhibition, absorption pathway inhibition and the like. C57BL / 6J mice (male, 9 weeks old, 5 mice in each group, fasted for 7 hours) were treated with catechins (Table 1) for sugar (starch 2.85 mg).
+ Sucrose 1.3 mg / g body weight) was orally administered simultaneously. The catechins were set to be 1.2% by weight with respect to the sugar.
Blood was collected from the tail vein before oral administration and after the administration, and blood glucose was measured using a simple blood glucose meter (glucose dehydrogenase / potentiometric method, manufactured by Roche Dianostic). The result is shown in FIG. As shown in FIG. 3, the food composition (1.2% by weight of catechins based on sugar) used for promoting GLUT4 expression and improving glucose tolerance did not have a sugar absorption suppressing effect.

Example 3 Effect of catechins on type 2 diabetes model mouse Genetic type 2 diabetes model mouse (C57BL / KsJ-db / db Jcl
Mice, females, 6 weeks old, 8 mice in each group), triglyceride 10
% Sucrose diet containing 13% by weight of sucrose, 0.5% by weight of potato starch of this high sucrose diet was 0.5% by weight of catechin group (Table 1) (1.0% by weight of catechins to sugar)
The high sucrose catechins diet replaced with (containing) was allowed to freely ingest for 4 weeks. Oral glucose tolerance test (OGTT)
I went there. After fasting for 12 hours, glucose (1 mg / g body weight) was orally administered, and heparinized hematocrit capillaries (75 mm, DRUMMOND SCIENTIFIC C
Blood was collected using O.). Plasma was collected by centrifugation at about 11000 rpm for 5 minutes, and glucose concentration in the plasma was measured by the Mutarose GOD method (Glucose II-Test Wako: Wako Pure Chemical Industries, Ltd.). The result is shown in FIG. As shown in FIG. 4, the high sucrose catechin dietary intake group was significantly suppressed in the increase in blood glucose level after oral administration of glucose, and was excellent in improving glucose tolerance.

It should be noted that, in the same manner as in Test Example 2, this bait composition (containing 1.0% by weight of catechins based on sugar) does not have a sugar absorption inhibitory action due to digestive enzyme inhibition, absorption pathway inhibition, etc. I confirmed as follows. C57BL / KsJ-db / db
Jcl mice (female, 9 weeks old, 5 mice in each group, fasted for 7 hours), catechins (Table 1) and carbohydrates (starch 2.85 mg + sucrose 1.3 mg / g)
(Body weight) was orally administered. Catechins are used for sugars 2.
It was set to be 4%. Heparinized hematocrit capillaries (75%) from the tail vein before and after oral administration
mm, DRUMMOND SCIENTIFIC CO.). About 1
Plasma was collected by centrifugation at 1000 r / min for 5 minutes, and the glucose concentration in the plasma was measured by the Mutarose GOD method (Glucose II-Test Wako: Wako Pure Chemical Industries, Ltd.). The result is shown in FIG. As shown in FIG. 5, 2.4% by weight of catechins relative to sugar, that is, 1.4 from the bait composition (containing 1.0% by weight of catechins relative to sugar) for promoting GLUT4 expression and improving glucose tolerance. No sugar absorption inhibitory effect was observed even with a high catechin concentration by weight.

Example 4 A packaged beverage having the composition shown in Table 3 was produced.

[0029]

[Table 3]

* 1 33 g of Choryu tea leaves were added to 1 kg of ion-exchanged water heated and held at 85 ° C, extracted for 8 minutes, and then filtered with a nel filter cloth while cooling with a heat exchanger. * 2 Tea extract concentrate A Catechins content 33% by weight, non-epi compound content 4% by weight (Mitsui Norin Co., Ltd.) B Catechins content 33% by weight, non-epi compound content 14% by weight C catechins content 30% by weight, non-epi compound content 3% by weight (manufactured by Mitsui Norin Co., Ltd.) D catechins content 30% by weight, non-epi compound content 14% by weight * 3 Inventions 1 and 2, Comparatives 1 and 2 were prepared with citric acid / disodium phosphate, invention 3 and comparison 3 with citric acid, invention 4 with sodium hydrogen carbonate. * 4 10 seconds (pass through degassing line before sterilization process)

The products 1 to 4 of the present invention have high palatability, and
It was a packaged beverage having a GLUT4 expression promoting effect.

Example 5 In a clean bench, 100 g of the tea leaves shown in Table 3 were extracted with 1000 g of distilled water at a temperature of 80 ° C. for 10 minutes to prepare a filtered tea extract. Next, the components in Table 4 were mixed, deaerated, heat-treated at 139 ° C. for 10 seconds, and then filled in a 500 mL PET bottle to produce a packaged beverage.

[0033]

[Table 4]

It was a packaged beverage which tasted good when drunk, was highly palatable, and had the effect of promoting GLUT4 expression.

Example 6 The packaged beverages shown in Table 5 were produced.

[0036]

[Table 5]

Five males (fasting blood glucose level 105 to 130 mg / dL) were allowed to drink 500 mL each day, and the effect of this beverage was measured after 3 months. As a result, 4 out of 5 people highly evaluated the drinking feeling of this beverage. In addition, the blood sugar level tended to decrease as a whole, and the beverage according to the present invention had a high palatability and was excellent in effectiveness.

[0038]

INDUSTRIAL APPLICABILITY The GLUT4 expression promoter of the present invention and a packaged beverage containing the same are not absorbed in blood by controlling blood sugar by suppressing sugar absorption such as inhibiting digestive enzymes of carbohydrates and transport pathways from the intestinal tract. It is possible to control the blood glucose level by promptly taking up glucose into cells, and it is possible to suppress a rapid increase in blood glucose after ingestion of sugar even if it is not taken at the same time as meals, which is useful for the prevention and improvement of diabetes.

[Brief description of drawings]

FIG. 1 is a graph showing changes in blood glucose level after oral administration of glucose.

FIG. 2 is a graph showing changes in plasma insulin concentration after oral administration of glucose.

FIG. 3 is a graph showing changes in blood glucose level after oral administration of sugar.

FIG. 4 is a graph showing changes in blood glucose level after oral administration of glucose.

FIG. 5 is a graph showing changes in blood glucose level after oral administration of sugar.

─────────────────────────────────────────────────── ─── Continuation of front page (51) Int.Cl. ⁷ Identification code FI theme code (reference) A61P 43/00 111 C07D 311/62 C07D 311/62 A23F 3/16 // A23F 3/16 A23L 2/00 F (72) Inventor Azumi Nagasawa 2606 Akabane, Akabane, Kaiga-cho, Haga-gun, Tochigi Prefecture, Kao Stock Company Research Institute (72) Inventor Tadashi Hase, 2606 Akabane, Kai-cho, Haga-gun, Tochigi Prefecture (72) Inventor, Ichiro Tokimitsu 2606 Akabane, Kaigamachi, Haga-gun, Tochigi Prefecture F-term in Kao Institute of Stock Companies (reference) 4B017 LC03 LE10 LG14 LK06 LP01 4B027 FB01 FB08 FB10 FB17 FC06 FK02 FK09 FP72 4C062 FF43 4C076 AA12 BB04 CC21 CC29 4C0 MA15AA01 AA01 ZC21 ZC35

Claims (5)

[Claims] 1. A glucose transporter 4 expression promoter comprising catechins. 2. A catechin is one of the following non-polymer components (A):
And (B): (A) non-epicatechins, (B) epicatechins, wherein (A) / (B) (weight ratio) is (A) / (B) =
The glucose transporter 4 expression promoter according to claim 1, which is dissolved in a beverage at a ratio of 0.25 to 9.0. 3. The following non-polymer components (A) and (B): (A) non-epi catechins, (B) epi catechins are dissolved and contained, and (A) / (B) ( (Weight ratio) is (A) /
(B) A packaged beverage for diabetes prevention / improvement, which is 0.25 to 9.0. 4. The following non-polymer components (A) and (B): (A) non-epi catechins and (B) epi catechins are dissolved and contained, and (A) + per 500 mL of a container. (B)
Is 460 to 2500 mg, (A) is 90 to 2250 mg, and (A) / (B) (weight ratio) is (A) / (B) = 0.25.
A packaged beverage for preventing / ameliorating hyperinsulinemia or insulin resistance, which is ˜9.0. 5. The content of catechins is 30 to 98% by weight.
Is epigallocatechin gallate, gallocatechin gallate, epigallocatechin and gallocatechin.
Alternatively, the packaged beverage according to item 5.