JP6633173B1 - Composition for suppressing increase in blood sugar level and suppressing increase in blood triglyceride - Google Patents

Abstract

An object of the present invention is to provide a novel composition for suppressing a postprandial increase in blood glucose level and / or for suppressing a postprandial increase in blood triglyceride. A composition for suppressing an increase in postprandial blood sugar level and / or for suppressing an increase in postprandial blood triglyceride, comprising tea flower extract, mulberry leaf extract, and chitosan as active ingredients. [Selection diagram] FIG.

Description

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

Obesity has been increasing since middle age, with statistics indicating that more than 30% 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 so-called three leading causes of cancer, heart disease and cerebrovascular disease. Obesity is caused by an overdose of carbohydrates and an increased intake of greasy sweets and sweet drinks. "Eating habits guidelines" and "dietary balance guides" have been formulated for the purpose of improving such eating habits, but it is difficult to change eating habits.
Therefore, dietary supplements are widely used as health supplements. Examples of the active ingredient to be added to the dietary supplement include chitosan, which has an action of suppressing glucose absorption for the purpose of suppressing an increase in postprandial blood glucose, and a mulberry extract, which suppresses the decomposition of saccharides such as starch.

  Patent Literature 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 inhibit the absorption of carbohydrates by adhering to the mucous membrane in the digestive tract, and to inhibit α-glucosidase and α-amylase.

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

  Patent Literature 3 describes a technique for extracting tea saponin from tea flowers. In addition, saponin contained in tea flowers has anti-allergic activity (Patent Document 4), inhibition of neutral fat absorption, protection of gastric mucosa, and inhibition of sugar absorption (Patent Document 5). Various pharmacological actions such as a pancreatic lipase activity inhibitory action / free fatty acid production inhibitory action (Patent Document 6) and a gastric emptying function inhibitory action (Patent Document 7) are known.

JP 2004-194635 A JP 2011-051950 A JP 2015-166326 A JP 2008-024654 A JP 2006-070018 A JP 2009-057365 A JP 2009-249374 A

  Means for Solving the Problems The present inventors have found an unprecedented strong postprandial blood glucose increase inhibitory effect and blood triglyceride increase inhibitory effect on a composition containing mulberry leaf extract, chitosan, and tea flower extract, and made the present invention. .

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

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), comprising 2 to 4 parts by mass of the dried mulberry leaf extract and 1 to 2 parts by mass of chitosan per 1 part by mass of the dried tea flower extract.
(3) The composition according to (1) or (2) for drinking immediately before ingesting 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.

  According to the present invention, there is provided a new composition for suppressing postprandial blood glucose elevation, and tablets, foods and drinks containing the same. The composition of the present invention exerts an effect of lowering the blood glucose level which rises after a meal. In humans, it also suppresses postprandial blood triglyceride elevation. Therefore, it can be used for dietary supplements and the like.

It is a graph which shows the time-dependent change of the blood glucose concentration of the test animal in an animal test. It is a graph which shows (DELTA) time-dependent change of the blood glucose concentration 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 concentration of the test animal in an animal test. It is a graph which shows a blood glucose level temporal change 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 postprandial blood glucose increase, comprising a tea flower extract, a mulberry leaf extract, and chitosan as active ingredients, a tablet for suppressing postprandial blood glucose increase, and a food or drink containing the composition.
In the present invention, the tea flowers used are the flower parts of tea (Camellia sinensis, also known as Thea sinensis) belonging to the Camellia L., a plant of theaceaceae (Theaceae) plant, that is, pistils, stamens, petals, calyxes and bracts. , Flower buds, buds, etc., including flower axes, floral patterns and the like.
In the present invention, tea flowers can be used as they are, as they are, or dried, or made by using a method known to those skilled in the art.

(Tea flower extract)
The tea flower extract as referred to 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 using an aqueous solvent.

As an extraction technique for producing the tea 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 extract of the present invention, a lower alcohol is preferable as the aqueous organic solvent. Examples of the lower alcohol include alcohols having 1 to 4 carbon atoms. Specific examples include methanol, ethanol, n-propanol, isopropanol, n-butanol, isobutanol or t-butanol, a mixed solution thereof, or a hydrated alcohol in any ratio thereof. Preferably, water or ethanol is used. More preferably, water or about 80% ethanol is used, but in the present invention, the ethanol content of the water-containing 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 performed 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, the extraction is carried out, for example, by immersing the flower portion of tea flower in the above-mentioned extraction solvent at a temperature of 50 ° C. to the boiling point of the extraction solvent under shaking (or stirring), without shaking or under reflux. Is appropriate. When the extraction material is immersed under shaking, it is suitably performed for about 30 minutes to 5 hours, and when immersed under non-shaking, it is suitably performed for about 1 hour to 20 days. In addition, when extracting under reflux of the extraction solvent, it is preferable to reflux under heating for 30 minutes to several hours.

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

The extract obtained by filtering the solid after extraction is concentrated by a conventional method to obtain an extract. The concentration is preferably performed under reduced pressure. The concentration may be performed until the extract is dried.
The extract may be used as it is to prepare the composition of the present invention, or may be used in the present invention as a powdery or lyophilized dry extract. A method known in the art can be used as a method for forming these solids.

The tea 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 one or more times of partition extraction using a solvent, that is, partition extraction using water and a non-hydratable organic solvent, and the organic solvent soluble fraction is used. And a 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 water-containing 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. Can be.

In addition, 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 after the above-mentioned distribution of ethyl acetate and water is directly subjected to distribution with n-butanol, or the residue obtained by concentrating the water-soluble fraction is further treated with water and n-butanol. To obtain an n-butanol fraction and a water-soluble fraction.

Tea flower extract is also commercially available as a raw material for supplements, and this commercially available tea flower extract can be used for the purpose of the present invention. An example of such a commercially available tea flower extract is “tea flower dried extract (manufactured by Japan Medical Food Research Institute Co., Ltd.)”.
As the tea extract used in the present invention, a tea extract containing 1.5% by mass or more of tea saponin as a total saponin is preferable.
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 human dose.

(Mulberry leaf extract)
Mulberry leaves are the leaves of the mulberry plant of the mulberry family, and have been used for a long time as tea in addition to feeding on silkworms. Plants generally called mulberry are representative of M. bombycis, M. laevigata, Kegwa (M. tiliafolia) and the like. In the present invention, a commercially available mulberry leaf extract can be used, and is commercially available from Nippon Shinyaku Co., Ltd., Toyoda Perfume Co., Ltd. and the like.

The mulberry leaf extract is preferably a hot water extract or a water-containing ethanol extract. For example, fresh or dried mulberry leaves are shredded and extracted in hot water for 15 minutes or more, and then concentrated and dried to form a powder. In the present invention, as the mulberry leaf extract, not only the above-mentioned powdery substance but also a concentrated liquid substance obtained without drying, a liquid extract obtained without concentration, and the like can be used.
The mulberry leaf extract is blended as a dry extract so that the composition of the present invention contains 50 to 1000 mg, preferably 100 to 500 mg, per human dose.

(Chitosan)
Chitosan is a kind of polysaccharide and refers to poly-β1 → 4-glucosamine. It is a 1,4-polymer of glucosamine, a linear polysaccharide, and a high molecular substance having a molecular weight ranging from thousands to hundreds of thousands.
Examples of the chitosan used in the present invention include crabs, shrimp shells, insect shells, squid, mushrooms, fungi and the like obtained from cell walls. Preferably, those obtained from crab and shrimp shells are good. Chitosan is composed of glucosamine and acetylglucosamine and is soluble in acidic water. The average molecular weight is usually 10,000 or more. Preferably, the average molecular weight is 100,000 or more, and the rotational viscosity is 20 mPa · s or more. Yes, 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 passes or less, more preferably 80 mesh passes or less. Chitosan is commercially available as a raw material for diet foods. For example, a product of Nippon Kayaku Food Techno Co., Ltd. can be used.
Chitosan is blended with the composition of the present invention so that the ingestion amount per human is 25 to 1000 mg, preferably 50 to 500 mg.

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. By setting such a mixing ratio, an effective postprandial blood glucose increase inhibitory effect is exhibited.
In addition, when the present inventors evaluated by the animal test, the combination of the well-known mulberry leaf extract and chitosan shows the postprandial blood glucose level elevation inhibitory effect of the level known in the prior art. In addition, when the present inventors tested a tea extract which is known to have a blood sugar rise inhibitory effect, it did not exhibit a postprandial blood sugar rise inhibitory effect in animal tests. However, the composition containing the three components of the tea flower extract, the mulberry leaf extract, and chitosan showed an excellent postprandial blood glucose increase inhibitory action. Therefore, the composition containing the three components of the tea flower extract, the mulberry leaf extract, and chitosan exhibits an unprecedented strong postprandial blood glucose elevation inhibitory effect.

  Further, the composition of the present invention may be incorporated into foods and beverages, and is preferably taken according to the timing of eating.

The composition of the present invention can be used as it is or in the form of a formulation and blended into health foods or supplement tablets.
Upon formulation, excipients and other active ingredients can be used within a range that does not interfere with the purpose of the composition of the present invention. Specifically, dietary fibers and thickeners such as cyclodextrin, hemicellulose, lignin, guar gum, konjac mannan, isagole, alginic acid, agar, carrageenan, chitin, carboxymethyl cellulose, polydextrose, edible oil, calcium, iron, Minerals such as sodium, zinc, copper, potassium, phosphorus, magnesium, iodine, manganese and selenium; fat-soluble or water-soluble such as vitamin A, vitamin C, vitamin D, vitamin E, vitamin K, niacin, folic acid, pantothenic acid Emulsifiers and dispersants such as vitamins, glycerin fatty acid ester, sucrose fatty acid ester, sorbitan fatty acid ester, propylene glycol fatty acid ester, phospholipid, gum arabic, xanthan gum, tragacanth gum and locust bean gum; Weighting agents, excipients, preservatives / antioxidants, flavor modifiers and flavors, flavoring agents such as sodium chloride, sodium glutamate, glycine, succinic acid, sodium lactate, citric acid, sodium citrate, acetic acid, adipic acid , Fumaric acid, malic acid and the like, low calorie sweeteners such as maltitol and aspartame, coloring agents and the like.

The present invention will be further described below by showing test examples using the composition of the present invention.
<1. Animal test to confirm postprandial blood glucose elevation inhibitory effect>
1. Animals used ddy mice, 8 weeks old at the start of the test, males, 40 males were purchased, their body weights were measured, and they were divided into 5 groups of 8 animals per group so that there was no weight variation between groups. Approximately one week after the introduction of the animals was set as the acclimatization period, and the animals were fasted for at least 12 hours from the evening of the last day of the acclimation period.

2. Administration Test Under fasting conditions, mice were gavaged with a test substance dissolved in distilled water at 5 mL / kg by oral gavage, and then carbohydrate (sucrose) was similarly gavage-administered at 2 g / 5 mL / kg.

3. Test substance The administration groups and doses of the test substance are as follows.
(1) Control (distilled water 5mL / kg)
(2) Chitosan 66.6 mg / kg + mulberry leaf extract (described as “mulberry” in the figure) 133.44 mg / kg
(3) Tea 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 10mg / kg
Acarbose, used as a positive control, is a drug for the treatment of diabetes that inhibits digestive enzymes required for carbohydrate digestion, especially α-glucosidase secreted from the small intestine and α-amylase secreted from the pancreas, and suppresses postprandial blood glucose elevation. It is known to
The amounts of the chitosan, mulberry leaf extract and tea flower extract were calculated and set so as to be equivalent to three times the human equivalent capacity (human body weight of 53 kg) 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 30, 60, 90, 120 and 180 minutes after sucrose administration in the same manner as described above. Plasma was obtained from the collected blood, stored frozen, and the plasma glucose concentration was measured at a later date.
In the statistical processing of the results, a Tukey test was performed from the average value and the standard deviation, and a significant difference was determined at a risk ratio of P <0.05.

5. Test results (1) Time-dependent change in blood sugar level Based on the result of the time-dependent measurement of the blood sugar level, the time-dependent change in the blood sugar level and the blood sugar level at each measurement time−the blood sugar level before the administration of the test substance = Δ change over time were determined, and the blood sugar level was plotted and plotted. A fluctuation 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 rise of blood sugar almost in the same manner as the pharmaceutical acarbose. Interestingly, tea flower extract (chaka), unlike known prior art information, showed little suppression of blood glucose elevation. This can be more clearly confirmed in the graph of Δ change over time.
In addition, the postprandial increase in blood glucose was remarkably suppressed by adding the three components of tea flower extract, mulberry leaf extract, and chitosan.

(2) Absorption of sugar In order to confirm the amount of sugar absorbed, AUC and ΔAUC were calculated from the graph of the change over time, and are shown in FIGS. As is clear from AUC and ΔAUC, the composition of the present invention remarkably suppressed the absorption of saccharide almost in the same manner as the acarbose drug.
Interestingly, tea flower extract (chaka) did not inhibit sugar absorption, unlike known prior art information. However, as shown in FIG. 3 and FIG. 4, the absorption of sugar was remarkably suppressed by mixing the three components of the tea flower extract, the mulberry leaf extract, and chitosan.

<2. Human clinical trial (1)>
The postprandial blood glucose elevation inhibitory effect of the composition of the present invention was tested by a human clinical test.
-Test method 1. Subjects (1) Selection criteria 1) Japanese adult men and women aged between 20 and 65 (age is the date of consent)
2) fasting blood sugar level of 125 (mg / dL) or less 3) blood sugar level of 140 (mg / dL) or more 30 minutes or 60 minutes after ingestion of load food 4) 120 minutes after ingestion of load food Subjects with a blood glucose level of 199 (mg / dL) or less 40 adult men and women meeting the above conditions were used as subjects.
The 40 subjects were randomly divided into groups A and B (20 per group, 2 groups).

2. Test food (1) Test food Tablet-formed tablets (CAL)
(Per 3 tablets per serving) Mulberry leaf extract (dry) 200mg
Chitosan 100mg
Tea extract (dry) 60mg
Is blended.
In order to produce other tablets, the following ingredients were blended as excipients.
Cellulose, starch, hydroxypropylcellulose, silicon dioxide, calcium stearate, shellac, shell calcined calcium, coloring (placebo only), cellulose, starch, calcium monohydrogen phosphate, calcium stearate, shellac

(2) Placebo meal tableted tablet (P)
Only the above excipients were tableted.

3. Carbohydrate load After ingestion of a test meal or placebo, the subject ingests 200 g of retort cooked rice (trade name of "Sato no rice") as a carbohydrate load. The nutritional components of cooked rice are as follows.

  The carbohydrate load is such that the test food is taken together with 150 mL of water after fasting blood sampling, and 10 minutes later, 200 g of “rice of sugar” is taken together with 150 mL of water for 10 minutes. Blood is sampled at 30, 60, and 120 minutes after the start of eating rice. The test was divided into stage I and stage II, and the subjects were a crossover test in which the test food was ingested with both the test food and placebo (with a blank period of 4 days or more). The blood samples collected were measured for blood glucose level and insulin level.

-Test results Fig. 5 shows a graph of the measurement results of the blood glucose level, and Fig. 6 shows a graph of the measurement results of the insulin.
Compared with the placebo (P) intake, the test food (CAL) intake had significantly lower blood glucose levels at 30 minutes and 60 minutes after the rice load and AUC up to 120 minutes after the rice load. Similar results were obtained with insulin. Therefore, it was confirmed that the composition of the present invention suppressed the increase in postprandial blood glucose in humans.

<3. Human clinical trial (2)>
The inhibitory effect of the composition of the present invention on postprandial blood triglyceride elevation was tested by a human clinical test.
-Test method Similar to the test of the effect of suppressing postprandial blood glucose elevation, a lipid tolerance test was performed to measure postprandial blood triglyceride. In addition, the lipid-loaded food prepared the food of the following composition.

(1) Preparation of lipid-loaded food Corn cream soup (butter (yotsuba butter, salt-free, yotsuba dairy) Co., Ltd.) 20.0 g and lard (lard, Megmilk Snow Brand Megmilk Co., Ltd.) 13.9 g of corn potage (corn) Cream potage (Nagoya Seiyaku Co., Ltd.) dissolved and mixed in 200.0 g (total lipid amount: 40.0 g) to prepare a lipid-loaded food.

-Test results Fig. 7 shows a graph of the measurement results of triglycerides.
Blood triglyceride levels at 2, 3, 4, and 6 hours after lipid loading and AUC up to 6 hours after lipid loading were significantly lower when the test food (CAL) was ingested than when placebo (P) was ingested. Therefore, it was confirmed that the composition of the present invention suppressed the increase in postprandial blood glucose in humans.
In both clinical tests (1) and (2), there was no problem with the health of the subjects.

Claims (4)

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.   The composition according to claim 1, comprising 2 to 4 parts by mass of the dried mulberry leaf extract and 1 to 2 parts by mass of chitosan per 1 part by mass of the dried tea flower extract.   The composition according to claim 1 or 2 for drinking immediately before eating a meal. 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.