JP2020105094A - Blood glucose level rise inhibiting and/or blood triglyceride rise inhibiting composition - Google Patents

Abstract

To provide a novel postprandial blood glucose level rise inhibiting and/or postprandial blood triglyceride rise inhibiting composition.SOLUTION: A postprandial blood glucose level rise inhibiting and/or postprandial blood triglyceride rise inhibiting composition, containing tea flower extract, mulberry leaf extract, and chitosan as active ingredients.SELECTED DRAWING: Figure 2

Description

The present invention relates to a composition for suppressing an increase in postprandial blood glucose level and/or suppressing an increase in blood triglyceride, which comprises a tea flower extract, a mulberry leaf extract, and chitosan as active ingredients.

Obesity is high after middle age, and statistical results have shown that 30% or more of men in their 40s and 70s and 20-30% of women are obese. Obesity has been identified as increasing the risk of these diseases, including the three major causes of death of cancer, heart disease and cerebrovascular disease. Obesity is caused by excessive intake of carbohydrates and increased intake of greasy sweets and sweet drinks. Although "dietary guidelines" and "dietary balance guides" have been established for the purpose of improving such eating habits, it is difficult to change eating habits.
Therefore, diet supplements are widely used as dietary supplements. Examples of active ingredients to be added to diet supplements include chitosan, which has a glucose absorption inhibitory effect for the purpose of suppressing postprandial blood glucose elevation, and mulberry extract, which suppresses the decomposition of sugars such as starch.

Patent Document 1 describes a diet food containing mulberry leaf extract and chitosan as useful components. Mulberry leaf extract inhibits the rise of blood glucose by inhibiting α-glucosidase in the digestive tract and inhibiting the decomposition of starch into glucose. Chitosan is known to have an α-glucosidase inhibitory action and an α-amylase inhibitory action in addition to suppressing the absorption of sugars by adhering to the mucosa in the digestive tract.

In recent years, the action of tea flower extract has been attracting attention as a useful component of diet. The tea flower extract contains flavonoid glycosides peculiar to tea flowers and improves fat metabolism (Patent Document 2).

Patent Document 3 describes a technique for extracting tea saponin from tea flowers. Further, saponin contained in tea flowers has antiallergic activity (Patent Document 4), neutral fat absorption suppression/gastric mucosal protection/sugar absorption suppression (Patent Document 5) intestinal motility enhancing action, intestinal obstruction or constipation prevention/improvement action. Various pharmacological actions such as pancreatic lipase activity inhibitory action/free fatty acid production inhibitory action (Patent Document 6) and gastric emptying function inhibitory action (Patent Document 7) are known.

JP, 2004-194635, A JP, 2011-051950, A JP, 2005-166326, A JP, 2008-024654, A JP, 2006-070018, A JP, 2009-057365, A JP, 2009-249374, A

The present inventors have found a composition having three components of mulberry leaf extract, chitosan, and tea flower extract, which has a strong inhibitory effect on postprandial blood glucose increase and an inhibitory effect on blood triglyceride increase, which have not been heretofore found, and made the present invention. ..

That is, an object of the present invention is to provide a novel composition for suppressing an increase in postprandial blood glucose and a composition for suppressing an increase in blood triglyceride.

The main configuration of the present invention is as follows.
(1) A composition for suppressing an increase in postprandial blood glucose level and/or suppressing an increase in postprandial blood triglyceride, which comprises tea flower extract, mulberry leaf extract, and chitosan as active ingredients.
(2) The composition according to (1), which contains 2 to 4 parts by mass of dried mulberry leaf extract and 1 to 2 parts by mass of chitosan per 1 part by mass of dried tea flower extract.
(3) The composition according to (1) or (2), which is to be taken just before eating a meal.
(4) A composition for suppressing an increase in postprandial blood glucose level and/or suppressing an increase in postprandial blood triglyceride, comprising 25 to 500 mg of a dried tea flower extract, 50 to 1000 mg of a dried product of mulberry leaf extract, and 25 to 1000 mg of chitosan.

INDUSTRIAL APPLICABILITY The present invention provides a novel composition for suppressing an increase in postprandial blood glucose, and tablets and foods and drinks containing the same. The composition of the present invention exerts the action and effect of lowering the blood glucose level that rises after meals. In humans, it also suppresses postprandial blood triglyceride elevation. Therefore, it can be used as a diet supplement or the like.

It is a graph which shows the time-dependent change of the blood glucose level of the test animal in an animal test. It is a graph which shows the time-dependent change of the blood glucose level of the test animal in an animal test. It is a graph which shows AUC of the blood glucose level of the test animal in an animal test. It is a graph which shows (DELTA)AUC of the blood glucose level of the test animal in an animal test. It is a graph which shows a time course of blood glucose level in a human clinical test (1). It is a graph which shows the time-dependent change of the blood insulin level in a human clinical test (1). It is a graph which shows the time-dependent change of the blood triglyceride (TG) value in a human clinical test (2).

The present invention is an invention of a composition for suppressing an increase in postprandial blood glucose, which contains tea flower extract, mulberry leaf extract, and chitosan as active ingredients, a tablet for suppressing an increase in postprandial blood sugar, and a food or drink containing the composition.
In the present invention, the tea flower used is a flower part of tea (Camellia sinensis, also known as Thea sinensis) belonging to the camellia genus Camellia L., that is, pistil, stamen, petal, calyx, bract leaf. , A flower axis, a so-called flower including a floral pattern, a flower bud and a bud.
In the present invention, tea flowers can be used as they are, as they are collected, or after dried, or after being made into tea by a method known to those skilled in the art.

(Tea extract)
The tea flower extract as used in the present invention refers to an extract obtained by extracting the above-mentioned tea flowers with water or an aqueous organic solvent and then removing the solvent, or an extract obtained by partitioning and extracting the same with an aqueous solvent.

As the extraction technique for producing a tea flower extract, the methods disclosed in Patent Documents 3 to 7 can be used. Specifically, it is as described below.
Regarding the extraction solvent used for producing the tea flower extract of the present invention, lower alcohol is preferable as the above-mentioned aqueous organic solvent. Examples of the lower alcohol include alcohols having 1 to 4 carbon atoms. Specific examples thereof include methanol, ethanol, n-propanol, isopropanol, n-butanol, isobutanol or t-butanol, a mixed solution thereof, and a hydrous alcohol in any proportion thereof. Water or ethanol is preferably used. More preferably, water or about 80% ethanol is used, but in the present invention, the amount of ethanol of hydrous ethanol is not particularly limited to 80%.
These extraction solvents are used in an amount of about 1 to 50 times (volume), preferably about 2 to 10 times (volume) of the extraction material.

The extraction can be carried out hot or at room temperature, and the extraction temperature can be arbitrarily set between room temperature and the boiling point of the solvent. In the case of hot extraction, it is carried out, for example, by immersing the inflorescence part of the tea flower in the above extraction solvent at a temperature of 50° C. to the boiling point of the extraction solvent with or without shaking (or stirring) or under reflux. Is appropriate. When the extraction material is dipped under shaking, it is suitable to carry out for 30 minutes to 5 hours, and when it is dipped under non-shaking, it is suitable for about 1 hour to 20 days. Moreover, when extracting under reflux of the extraction solvent, it is preferable to heat and reflux for 30 minutes to several hours.

It is also possible to immerse and extract at a temperature lower than 50°C, but in that case, it is preferable to immerse for a longer time than the above time. The extraction operation may be performed only once for the same material, but it is preferable to repeat the extraction operation a plurality of times, for example, about 2 to 5 times, from the viewpoint of extraction efficiency.

The extract obtained by filtering the solid matter after filtration is concentrated by an ordinary method to obtain an extract. Concentration is preferably performed under reduced pressure. Concentration may be performed until the extract is dried.
The extract may be used as it is for preparing the composition of the present invention, or may be used in the present invention as a powdery or lyophilized dry extract product. As a method for making these solids, a method known in the art can be adopted.

The tea flower extract in the present invention includes a concentrated dried product or a lyophilized product.
Further, in the present invention, the extract obtained by concentrating the tea flower extract is subjected to partition extraction with a solvent, that is, partition extraction using water and a non-hydratable organic solvent, once or multiple times to obtain an organic solvent-soluble fraction. And water-soluble fraction.

Examples of the non-hydratable organic solvent include ethyl acetate, n-butanol, hexane, chloroform and the like, among which ethyl acetate is preferable.
That is, the extract obtained by concentrating the water or hydrous lower alcohol extract of tea flowers is distributed using ethyl acetate and water as necessary to obtain an ethyl acetate-soluble fraction and a water-soluble fraction. You can

The water-soluble fraction obtained above can be further subjected to partition extraction using water and a non-hydratable organic solvent to separate it as an organic solvent-soluble fraction and a water-soluble fraction.
Examples of the non-hydratable organic solvent in this case include n-butanol, hexane, chloroform and the like, and among them, n-butanol is preferable.
That is, the water-soluble fraction obtained after the partition between ethyl acetate and water is directly subjected to partition with n-butanol, or the residue obtained by concentrating the water-soluble fraction is further mixed with water and n-butanol. Then, the n-butanol fraction and the water-soluble fraction can be obtained.

Tea extract is also commercially available as a raw material for supplements, and this commercially available tea extract can be used for the purpose of the present invention. As such a commercially available tea flower extract, "tea flower dry extract (manufactured by Japan Medicinal Food Research Institute Co., Ltd.)" can be exemplified.
As the tea flower extract used in the present invention, it is preferable that the tea flower extract contains tea flower saponins in an amount of 1.5% by mass or more as a total saponin.
The tea extract is blended as a dry extract so that the composition of the present invention contains 25 to 500 mg, preferably 50 to 250 mg, per person.

(Mulberry leaf extract)
Mulberry leaves are leaves of the mulberry genus of the mulberry family, and have been used for a long time as tea as well as for feeding silkworms. Typical examples of plants generally called mulberry are Yamaguchi (M. bombycis), Nagamiguwa (M. laevigata), and Kegwa (M. tiliaefolia). In the present invention, the mulberry leaf extract may be a commercially available product, and is commercially available from Nippon Shinyaku Co., Ltd., Toyoda Fragrance Co., Ltd., etc.

The mulberry leaf extract is preferably a hot water extract or a hydrous ethanol extract. For example, the raw or dried leaves of mulberry leaves are shredded, extracted in hot water for 15 minutes or more, and then concentrated and dried to obtain a powder. In the present invention, the mulberry leaf extract is not limited to the above powdery substance, and a concentrated liquid substance obtained without drying and a liquid extract obtained without concentration can be used.
The mulberry leaf extract is added as an extract dried product so that the composition of the present invention contains 50 to 1000 mg, preferably 100 to 500 mg, per person.

(Chitosan)
Chitosan is a kind of polysaccharide and is poly-β1→4-glucosamine. It is a linear polysaccharide, a 1,4-polymer of glucosamine, which is a high molecular substance having a molecular weight of several thousand to several hundred thousand.
Examples of chitosan used in the present invention include those obtained from cell walls such as crab, shrimp carapace, insect crust, squid, mushrooms and filamentous fungi. Those obtained from the crust of shrimp and shrimp are preferable. Chitosan is composed of glucosamine and acetylglucosamine and is soluble in acidic water. The average molecular weight is usually 10,000 or more, but preferably the average molecular weight is 100,000 or more and the rotational viscosity is 20 mPa·s or more. And more preferably, the average molecular weight is 800,000 or more and the rotational viscosity is 100 mPa·s or more. The particle size of chitosan is not particularly limited, but is preferably 30 mesh pass or less, more preferably 80 mesh pass or less. Chitosan is commercially available as a raw material for diet foods, and for example, a product of Nippon Kayaku Food Techno Co., Ltd. can be used.
Chitosan is added to the composition of the present invention in an amount of 25 to 1000 mg, preferably 50 to 500 mg, per person.

The composition of the present invention is blended so as to contain 2 to 4 parts by mass of dried mulberry leaf extract and 1 to 2 parts by mass of chitosan per 1 part by mass of dried tea flower extract. With such a blending ratio, an effective postprandial blood glucose elevation suppressing effect is exhibited.
In addition, when evaluated by the present inventors by an animal test, the known combination of mulberry leaf extract and chitosan exhibits a postprandial blood glucose level elevation-inhibiting effect at a level known in the prior art. Further, when the inventors of the present invention tested a tea flower extract known to have an inhibitory effect on blood glucose elevation, it did not exhibit an inhibitory effect on postprandial blood glucose elevation in an animal test. However, the composition containing the three components of the tea flower extract, mulberry leaf extract, and chitosan showed an excellent postprandial blood glucose elevation suppressing effect. Therefore, the composition containing the three components of the tea flower extract, mulberry leaf extract, and chitosan exerts an unprecedented strong postprandial blood glucose increase suppressing effect.

Further, the composition of the present invention may be blended with foods and beverages, and it is preferable to take it at the timing of eating.

The composition of the present invention can be incorporated into health foods or supplement tablets as it is or as a formulation.
Upon formulation, excipients and other active ingredients can be used within a range that does not impair the purpose of the composition of the present invention. Specifically, cyclodextrin, hemicellulose, lignin, guar gum, konjac mannan, isagole, alginic acid, agar, carrageenan, chitin, carboxymethyl cellulose, thickeners such as polydextrose, edible oil, calcium, iron, Minerals such as sodium, zinc, copper, potassium, phosphorus, magnesium, iodine, manganese, and selenium; fat-soluble or water-soluble vitamins A, vitamin C, vitamin D, vitamin E, vitamin K, niacin, folic acid, pantothenic acid, etc. Vitamin group, glycerin fatty acid ester, sucrose fatty acid ester, sorbitan fatty acid ester, propylene glycol fatty acid ester, phospholipid, gum arabic, xanthan gum, tragacanth gum, emulsifier and dispersant such as locust bean gum, extender, excipient, preservative・Antioxidants, flavor modifiers and flavors, flavorings such as sodium chloride, sodium glutamate, glycine, succinic acid, sodium lactate, etc., sourness such as citric acid, sodium citrate, acetic acid, adipic acid, fumaric acid, malic acid, etc. And low-calorie sweeteners such as maltitol, aspartame, and colorants.

Hereinafter, the present invention will be further described by showing test examples using the composition of the present invention.
<1. Animal test for confirming postprandial blood glucose elevation control>
1. Animals to be used ddy mice, 8 weeks old at the start of the test, 40 males were purchased, and their weights were measured, and each group was divided into 5 groups, with 8 mice per group. After carrying in the animals, about one week was used as a habituation period, and the animals were fasted for 12 hours or more from the evening of the last day of the acclimation period.

2. Administration test Under fasting conditions, the test substance was forcibly orally administered in a solution of the test substance dissolved in distilled water at 5 mL/kg, and then, a sugar (sucrose) was similarly orally administered at 2 g/5 mL/kg.

3. Test substance The test substance administration groups and doses are as follows.
(1) Control (distilled water 5 mL/kg)
(2) Chitosan 66.6 mg/kg+mulberry leaf extract (described as “mulberry” in the figure) 133.44 mg/kg
(3) Tea flower extract (described as "Chaka" in the figure) 39.96 mg/kg
(4) Chitosan 66.6 mg/kg+mulberry leaf extract 133.44 mg/kg+tea flower extract 39.96 mg/kg
(5) Positive control (Posicon) Acarbose 10 mg/kg
Acarbose, which was used as a positive control, is a therapeutic drug for diabetes that inhibits digestive enzymes required for digesting carbohydrates, especially α-glucosidase secreted by the small intestine and α-amylase secreted by the pancreas, and suppresses postprandial blood glucose elevation. Is known to do.
The above-mentioned amounts of chitosan, mulberry leaf extract and tea flower extract were calculated and set so as to correspond to three times the human equivalent capacity (human body weight 53 kg) shown in Table 1 below.

4. Postprandial blood glucose measurement On the day of the test, about 30 μL of blood was collected from the tail vein before administration of the test substance.
Approximately 30 μL of blood was collected at 30, 60, 90, 120 and 180 minutes after administration of sucrose in the same manner as above. Plasma was obtained from the collected blood, frozen and stored, and the plasma glucose concentration was measured at a later date.
As the statistical processing of the results, Tukey test was performed from the average value and the standard deviation, and a significant difference was determined at a risk rate of P<0.05.

5. Test results (1) Time-dependent change of blood glucose level Based on the results of time-dependent measurement of blood glucose level, the time-dependent change of blood glucose level and blood glucose level at each measurement time-blood glucose level before administration of test substance = Δ time-dependent change were obtained, and blood glucose was plotted respectively. A variation graph was created. The time course of blood glucose (FIG. 1) and the time course of Δ (FIG. 2) are shown.
As shown in FIG. 1 and FIG. 2, the composition of the present invention suppressed the increase in blood glucose almost in the same manner as the pharmaceutical product acarbose. Interestingly, unlike the known prior art information, tea flower extract (Chaka) showed almost no suppression of blood glucose elevation. This can be confirmed more clearly in the graph of Δ change with time.
Moreover, the postprandial blood glucose elevation was remarkably suppressed by blending the three components of the tea flower extract, mulberry leaf extract, and chitosan.

(2) Absorption of sugar In order to confirm the absorption amount of sugar, AUC and ΔAUC were calculated from graphs of changes over time, and shown in FIGS. 3 and 4. As is clear from AUC and ΔAUC, the composition of the present invention remarkably suppressed the absorption of sugars in the same manner as acarbose as a drug.
Interestingly, tea flower extract (Chaka) did not suppress the absorption of sugar, unlike the known prior art information. However, as shown in FIGS. 3 and 4, the incorporation of the three components of the tea flower extract, mulberry leaf extract, and chitosan markedly suppressed the absorption of sugar.

<2. Human clinical trial (1)>
The inhibitory effect on postprandial blood glucose elevation of the composition of the present invention was tested in a human clinical test.
・Test method 1. Subjects (1) Selection criteria 1) Japanese adult males and females aged 20 to less than 65 (age is the date of consent acquisition)
2) Person with a fasting blood glucose level of 125 (mg/dL) or less 3) Person with a blood glucose level of 140 (mg/dL) or more 30 minutes or 60 minutes after ingestion of the loaded food 4) 120 minutes after ingestion of the loaded food Subjects with blood glucose level of 199 (mg/dL) or less 40 adult men and women who satisfied the above conditions were used as subjects.
In addition, 40 subjects were randomly divided into A group and B group (1 group: 20 persons, 2 groups).

2. Test meal (1) Test meal Tablets formed by tablet compression (CAL)
(1 dose 3 tablets) Mulberry leaf extract (dry matter) 200mg
Chitosan 100mg
Tea flower extract (dry product) 60mg
Is compounded.
The following ingredients were added as excipients to produce other tablets.
Cellulose, starch, hydroxypropyl cellulose, silicon dioxide, calcium stearate, shellac, uncalcined shell calcium, colorant (placebo only), cellulose, starch, calcium monohydrogen phosphate, calcium stearate, shellac.

(2) Placebo food tablet-formed tablets (P)
Only the above excipients were tabletted.

3. Carbohydrate load A subject ingests 200 g of retort cooked rice (trade name of "Sato no rice") as a sugar load after ingesting a test meal or a placebo. The nutritional components of cooked rice are as follows.

For the carbohydrate load, after fasting blood sampling, the test food was ingested with 150 mL of water, and 10 minutes later, 200 g of “sato no mai” was ingested with 150 mL of water for 10 minutes. Blood is collected at 30, 60, and 120 minutes after starting to eat cooked rice. The test was divided into stage I and stage II, and the test subject was a crossover test in which both the test diet and the placebo were ingested (a blank period of 4 days or more was set). The blood samples collected were measured for blood glucose level and insulin level.

-Test results FIG. 5 shows a graph of blood glucose measurement results, and FIG. 6 shows a graph of insulin measurement results.
When the test food (CAL) was ingested, the blood glucose level after 30 minutes, 60 minutes after the loading of rice, and the AUC up to 120 minutes after administration of the placebo (P) were significantly lower. Similar results were obtained with insulin. Therefore, it was confirmed that the composition of the present invention suppresses postprandial blood glucose elevation in humans.

<3. Human clinical trial (2)>
A human clinical test was conducted to test the inhibitory effect on postprandial blood triglyceride elevation of the composition of the present invention.
-Test method As with the postprandial blood glucose elevation inhibitory effect test, a lipid tolerance test was performed to measure postprandial blood triglyceride. As the lipid-loaded food, a food having the following composition was prepared.

(1) Preparation of lipid-laden foods Corn cream soup (butter (yotsuba butter, salt-free, yotsuba dairy Co., Ltd.) 20.0 g and lard (lard, Snow Brand Megmilk Co., Ltd.) 13.9 g are corn potage (corn A mixture (200.0 g of cream potage, Nagoya Dairy Co., Ltd.) dissolved and mixed (total lipid amount of 40.0 g) was prepared, and this was used as a lipid-loaded food.

-Test result Fig. 7 shows a graph of the measurement result of triglyceride.
When the test food (CAL) was ingested, the blood triglyceride level after 2, 3, 4, 6 hours after lipid loading and the AUC up to 6 hours after administration of the placebo (P) were significantly lower. Therefore, it was confirmed that the composition of the present invention suppresses postprandial blood glucose elevation in humans.
In addition, in the clinical tests (1) and (2), there was no problem in the health of the subject.

The main configuration of the present invention is as follows.
(1) Camellia extract, mulberry leaf extract, and a postprandial blood glucose increase inhibition containing chitosan as an active ingredient and / or postprandial blood triglyceride rise suppression composition.
(2) The composition according to (1), which contains 2 to 4 parts by mass of dried mulberry leaf extract and 1 to 2 parts by mass of chitosan per 1 part by mass of dried tea flower extract.
(3) The composition according to (1) or (2), which is to be taken just before eating a meal.
(4) Camellia 25~500mg as extract dry matter, 50 to 1000 mg as a mulberry leaf extract dry matter, for the postprandial blood glucose increase inhibition containing chitosan 25~1000mg and / or postprandial blood triglyceride rise suppression composition.

Claims (4)

A composition for suppressing an increase in postprandial blood glucose level and/or suppressing an increase in postprandial blood triglyceride, which comprises tea flower extract, mulberry leaf extract, and chitosan as active ingredients. The composition according to claim 1, which comprises 2 to 4 parts by mass of dried mulberry leaf extract and 1 to 2 parts by mass of chitosan per 1 part by mass of dried tea flower extract. The composition according to claim 1 or 2, which is to be taken immediately before ingestion of a meal. A composition for suppressing an increase in postprandial blood glucose and/or suppressing an increase in postprandial blood triglyceride, comprising 25 to 500 mg of a dried tea flower extract, 50 to 1000 mg of a dried product of mulberry leaf extract, and 25 to 1000 mg of chitosan.