JP2006117566A - Saccharometabolism-ameliorating agent - Google Patents

Abstract

<P>PROBLEM TO BE SOLVED: To provide a drug or food/drink promoting GLP-1 production in digestive tract tissue and in its turn, effective for preventing/treating obesity and hyperglycemia through utilizing living body-regulating function inherent in a yeast-derived mannan, in view of the fact that active ingredients need to be found from food or matter corresponding to food in preventing/treating obesity/arteriosclerosis that will threaten citizens' health. <P>SOLUTION: A saccharometabolism-ameliorating agent having the activity of promoting the production or secretion of glucagon-like peptide-1 (GLP-1) in digestive tract tissue is provided, containing as active ingredient mannan that is obtained from the cells or culture liquid of Saccharomyces yeast. <P>COPYRIGHT: (C)2006,JPO&NCIPI

Description

The present invention relates to a sugar metabolism-improving agent obtained from Saccharomyces yeast and having an action of promoting production / secretion of glucagon-like peptide-1 (GLP-1) in gastrointestinal tissue, and its use.

In recent years, the obesity tendency of the people is gradually progressing due to high fat and high calorie diet. Upper body obesity, impaired glucose tolerance, high triglycerides, and hypertension are called “death quartets”. When they overlap, the rate of arteriosclerosis and heart disease increases at an accelerated rate and is considered life-threatening. The manifestation of such physiological abnormalities is greatly related to genetic factors and environmental factors such as dietary habits, so it is sometimes necessary to change lifestyle habits to prevent or improve, and it is difficult to sustain. You may be forced to self-regulate. A simple means of preventing and improving obesity and arteriosclerosis that anyone can accept is desired.

In recent years, various useful substances have been found in foods or natural products equivalent thereto, and functional foods taking advantage of their physiological functions are becoming a boom. Functional foods are expected to improve blood lipids, blood sugar levels, blood pressure, etc. when taken by a semi-healthy person on a daily basis, and can provide simple means for promoting health and preventing diseases.

Baker's yeast and beer yeast are included in the “genus Saccharomyces” and have been used for food production and alcoholic brewing for a long time. Saccharomyces yeast is effectively used even after it has been used for fermentation and brewing of foods and alcoholic beverages. Widely used in feed microorganisms. In recent years, dietary fiber has attracted attention as a nutrient, but yeast contains indigestible polysaccharides composed of mannose and glucose, and has a particularly high content in the cell wall. The cell wall of yeast is composed of insoluble polysaccharides mainly composed of glucan in the inner layer and polysaccharides mainly composed of mannan in the outer layer (surface layer). Mannan can be collected from yeast cells by water / solvent extraction. (Patent Document 1, Patent Document 2). Yeast mannan is water-soluble and has an advantage that it is easy to use for the production of foods and the like as compared with insoluble yeast cells, cell walls, and glucan fractions in cell walls.

Mannan, a water-soluble dietary fiber, has been found to have various functionalities such as intestinal regulation, sugar absorption inhibition, lipid absorption inhibition, immune function improvement, mineral absorption promotion, etc. It is used as a raw material for many functional foods and health foods. Among them, with regard to the absorption inhibition of sugars and lipids, water-soluble dietary fibers suppress the activity of digestive enzymes by changing the physical properties of digestive tract contents, or water-soluble dietary fibers themselves are essential for lipid and lipid absorption It is said that adsorbing the bile acid, which is the above, promotes excretion into feces and is greatly related to the exertion of physiological action. Consumption of water and dietary fiber leads to the prevention and improvement of obesity because the calorie absorbed into the body decreases due to the continuous action of absorption of sugars and lipids.

On the other hand, the metabolism of nutrients and energy in the body is strongly controlled by insulin produced by pancreatic β cells. The most important function of insulin is to regulate blood sugar levels, and it acts on tissues and cells to promote glucose uptake from the blood. However, when the sensitivity of tissues and cells to insulin decreases due to continuous high-calorie food intake and aging, an increase in blood glucose level and excessive production of insulin proceed in parallel, and eventually the function of β cells in the pancreas decreases. Serious diabetes and obesity. Insulin production and β-cell function are regulated by various hormones. Among them, the role of Glucagon-1ike peptide-l (GLP-l) produced in gastrointestinal tissues has attracted attention. ing. GLP-1 is a peptide hormone having a molecular weight of about 4000, which is mainly produced in L cells of the small intestine. 1. Promotion of insulin production / secretion from β cells; 2. Suppresses gastric peristalsis and moderates digestion and absorption. 3. The effect of suppressing appetite and preventing overeating. It has been clarified that it has an effect of promoting the differentiation and proliferation of β-cells and has the effect of preventing the diabetes and obesity by maintaining normal sugar metabolism by adjusting the functions of β-cells and insulin. Furthermore, it is known that the ability to produce GLP-1 decreases due to diabetes or obesity, and if the production of GLP-1 can be stimulated in these pathologies, it will lead to prevention of diabetes and obesity development and improvement of symptoms. Be expected. Production of GLP-1 in L cells is promoted by ingestion of various nutrients such as sugars, lipids, and proteins, but reports on the GLP-1 production promoting action of specific food components are limited to fructooligosaccharides, olive oil, and the like. There have been examples of mannan obtained from Saccharomyces yeast cells or cultures as a diabetes control agent so far (Patent Document 3), but research reports and examples utilized as GLP-1 secretion promoters are currently available. I can't find it.

JP-A-2-286057 JP-A-4-58893 JP-A 61-167622

In the future, in order to prevent and treat obesity and arteriosclerosis, which will threaten the health of the people, it is necessary to find an active ingredient from foods or similar foods. The present invention uses a bioregulatory function of yeast-derived mannan to promote the production of GLP-1 in the gastrointestinal tissue, and thus to provide a drug or food or drink effective for the prevention and treatment of obesity and hyperglycemia. With the goal.

The present invention has been made to achieve the above object, and it has been confirmed by animal experiments that mannan obtained from Saccharomyces yeast cells or culture has a physiological activity that has not been known so far. The present invention has been completed.
That is, the present invention has an effect of promoting production or secretion of glucagon-ike peptide-1 (GLP-1) in gastrointestinal tissues using mannan obtained from Saccharomyces yeast cells or culture solution as an active ingredient. Is a sugar metabolism-improving agent. In addition, this sugar metabolism improving agent has a preventive or improving action against obesity or hyperglycemia. Further, the Saccharomyces yeast is a yeast used for brewing beer. This sugar metabolism improving agent is provided as a pharmaceutical or a food or drink.

According to the present invention, a substance having an action to improve obesity and hyperglycemia could be obtained using mannan of Saccharomyces yeast as a raw material. Furthermore, it could be easily used as a material for medicines and foods and drinks.

Mannan of Saccharomyces yeast may be extracted from yeast cells or recovered from the culture supernatant. In the case of extraction from yeast cells, Saccharomyces yeast cells are used as raw materials, regardless of whether they are live or dead, whether they contain water or are dried. Further, mannan may be prepared from a yeast extract prepared from yeast or a cell wall. In this case, you may use a commercial item for a yeast extract or a cell wall. Typical yeasts of the genus Saccharomyces include baker's yeast and beer yeast, but the yeast to be used is not limited to these.

When mannan is extracted from the cells of Saccharomyces yeast, water or an organic solvent is used, and a mixture thereof may be used. A preferred extraction solvent is acidic or alkaline water. Extraction is performed by room temperature extraction, heating extraction, or pressure extraction (processing such as autoclave). Generally, it is performed at room temperature to 121 ° C. After the extraction process, the solid content and the liquid are separated by centrifugation or the like to obtain only the liquid part. In order to remove unnecessary low-molecular components such as salts from this solution, a low-molecular fraction may be removed by membrane treatment, or ethanol or the like may be added to precipitate soluble carbohydrates and recovered. The obtained mannan fraction can be concentrated by vacuum concentration or the like, if necessary, or powdered by vacuum drying, freeze drying or the like. An appropriate excipient may be added during powdering. Mannan obtained by the above method is generally occupied by 40% mannose residues.

The obtained mannan can be used as a pharmaceutical product as an oral product, and can be mixed with a food material to make a food or drink. The properties are solid or liquid, and pharmaceuticals are in the form of tablets, capsules, granules, syrups and the like as oral preparations.
When administered to the human body as a pharmaceutical, the amount of 1-1000 mg (dry weight) / kg body weight per dose, preferably 1-100 mg (dry weight) / kg body weight, is orally administered once to several times a day To do.
In the case of a food or drink, the food material mixed therewith may be any of solids (powder, flakes, lumps, etc.), semi-solids (jelly, syrup, etc.), or liquids. The content per gram of food or drink is preferably 1 to 300 mg (dry weight).
The pharmaceuticals and foods and drinks containing yeast mannan according to the present invention comprise a glucose metabolism-improving agent having an action of promoting production or secretion of glucagon-ike peptide-1 (GLP-1) in gastrointestinal tissues. It has a preventive or ameliorating action against obesity or hyperglycemia.
Hereinafter, the present invention will be described more specifically with reference to examples, but the present invention is not limited thereto.

(Mannan preparation from Saccharomyces yeast) Commercial beer yeast cell wall (Asahi Food & Healthcare) 100 g was suspended in a small amount of distilled water, and further distilled water was added to make a 1 L suspension. Sodium hydroxide was added to adjust the pH to 9.0, followed by boiling at 100 ° C. for 4 hours. After cooling to room temperature, the mixture was centrifuged at 5000GG for 15 minutes to recover the supernatant (A). Hydrochloric acid was added to (A) to adjust to pH 6.0, half of the amount was recovered, concentrated at 30 to 40 ° C. under reduced pressure of 100 to 200 mmHg, and freeze-dried to obtain 10 g of soluble saccharide powder (crude mannan). It was. The remaining half of (A) was put into a dialysis tube with a molecular weight cut off of 10,000 and dialyzed to recover the solution remaining in the tube. This solution was concentrated under reduced pressure of 100 to 200 mmHg at 30 to 40 ° C., and then lyophilized to obtain 7.5 g of a soluble carbohydrate powder (purified mannan). As a result of analysis by sulfuric acid hydrolysis and high performance liquid chromatography, the ratio of mannose in the crude mannan and the purified mannan was 40% (w / w) and 94% (w / w), respectively.

(Tablets and capsules)
Crude mannan 10.0g
Lactose 75.0g
Magnesium stearate 15.0g
Total 100. g
The above respective parts by weight were uniformly mixed, and tablets and capsules were prepared according to a conventional method.

(Powder, granule)
Crude mannan 20.0g
Starch 30.0g
Lactose 50.0g
Total 100.0g
Each said weight part was mixed uniformly, and it was set as the powder and the granule according to the conventional method.

(candy)
Sucrose 20.0g
Chickenpox (75% solids) 70.0g
9.5g of water
Coloring material 0.45g
Perfume 0.045g
Crude mannan 0.005g
Total 100.0g
Using each component of each of the above parts by weight, it was made into a candy according to a conventional method.

(juice)
Concentrated tangerine juice 15.0 g
Fructose 5.0g
Citric acid 0.2g
Fragrance 0.1g
0.15 g of color
Sodium ascorbate 0.048g
Crude mannan 0.002g
79.5g of water
Total 100.0g
Using each component of the above-mentioned parts by weight, juice was prepared according to a conventional method.

(cookie)
Soft flour 32.0g
Whole egg 16.0g
16.0g butter
Sand sugar 25.0g
10.8 g of water
Baking powder 0.198g
Crude mannan 0.002g
Total 100.0g

(Tablets and capsules)
Purified mannan 5.0 g
Lactose 80.0g
Magnesium stearate 15.0g
Total 100.0g
The above respective parts by weight were uniformly mixed, and tablets and capsules were prepared according to a conventional method.

(Powder, granule)
Purified mannan 10.0g
Starch 40.0g
Lactose 50.0g
Total 100.0g
Each said weight part was mixed uniformly, and it was set as the powder and the granule according to the conventional method.

(candy)
Sucrose 20.0g
Chickenpox (75% solids) 70.0g
9.502 g of water
Coloring material 0.45g
Perfume 0.045g
0.003 g of purified mannan
Total 100.0g
Using each component of each of the above parts by weight, it was made into a candy according to a conventional method.

(juice)
Concentrated tangerine juice 15.0 g
Fructose 5.0g
Citric acid 0.2g
Fragrance 0.1g
0.15 g of color
Sodium ascorbate 0.049g
0.001 g of purified mannan
79.5g of water
total
100.0g
Using each component of the above-mentioned parts by weight, juice was prepared according to a conventional method.

(cookie)
Soft flour 32.0g
Whole egg 16.0g
16.0g butter
Sand sugar 25.0g
10.8 g of water
Baking powder 0.199g
0.001 g of purified mannan
Total 100.0g
Using each component of the above-mentioned parts by weight, a cookie was prepared according to a conventional method.

(Mannan promotes GLP-1 secretion, anti-obesity, and improves hyperglycemia)
After orbital blood collection from 3-week-old male ICR mice (Japan SLC), divided into 2 test groups consisting of 8 animals per group, 2% purified feed (AIN-93G: control group) or 2% purified mannan The added purified feed (mannan group) was allowed to freely ingest for 4 months. Blood was collected from the mouse again and then necropsied, and fat around the genital organ was removed and weighed. For blood collected at the start and end of the test, the blood glucose level and plasma GLP-1 concentration were measured.

Table 1 GLP-1 concentrations in the blood festival of each test group


Test group GLP-1 concentration ng / ml: GEOMEAM value)
At the start of the study (all cases, 4 weeks old) 1.39
Teru (5 months old) 0.73
Mannan group (5 months old) 2.81

As Table 1 shows, the GLP-1 concentration in blood purple decreased to about 1/2 in the control group by breeding for 4 months, but in the mannan group, the GLP-1 concentration doubled and was significantly higher than the control group. It was overpriced. p <0.05

Table 2 Weight of each test group
Test group Body weight (g: mean ± standard error)
At the start of the test (all cases, 4 weeks old) 10.5 ± 0.1
Control group (5 months old) 59.2 ± 2.1
Mannan group (5 months old) 53.2 ± 2.6

As Table 2 shows, the weight of the Mannan group after 4 months of breeding was 10% lower than the control group.

Table 3 Perigenital fat weight in each test group
Test group Fat weight (g: mean ± standard error)
Control group (5 months old) 2.6 ± 0.5
Mannan group (5 months old) 2.0 ± 0.4

As Table 3 shows, the perigenital fat weight of the mannan group after 4 months of breeding was 23% lower than that of the control group.

Table 4 Blood glucose levels in each test group
Test group Blood glucose level (mg / dL: mean ± standard error)

Test start (all cases, 4 weeks old) 94 ± 5
Control group (5 months old) 136 ± 6
Mannan group (5 months old) 124 ± 5

As shown in Table 4, the blood glucose level of the control group increased by 45% by breeding for 4 months, but only increased by 32% in the mannan group.

From the above results, yeast-derived mannan is 1. 1. GLP-1 production promoting action; 2. Inhibition of overweight and fat accumulation; It was confirmed that there is an inhibitory effect on hyperglycemia.

Claims (4)

Glucose metabolism having an action of promoting the production or secretion of glucagon-1ike peptide-1 (GLP-1) in gastrointestinal tissues using mannan obtained from Saccharomyces yeast cells or culture solution as an active ingredient Improver. The sugar metabolism-improving agent according to claim 1, which has an effect of preventing or improving obesity or hyperglycemia. The sugar metabolism-improving agent according to claim 1 or 2, wherein the Saccharomyces yeast is a yeast used for brewing beer. Food-drinks containing the sugar metabolism improving agent of any one of Claims 1-3.