JP2006241020A - Immune system activating agent - Google Patents

Abstract

<P>PROBLEM TO BE SOLVED: To provide an immune system activating agent useful for preventing/treating adult disease, given by utilizing a function of enhancing phagocytic ability of a neutrophilic leukocyte inherent in mannan which is extracted from a cell wall of yeast, for the purpose of finding out an active ingredient even in a food or a product corresponding to the food, in preventing/treating cancer or infectious disease of which the morbidity rate is estimated that it continues to rise even in the future, to provide a pharmaceutical having an immune system activating function, and to provide food and drink. <P>SOLUTION: An immune system activating substance contains the mannan derived from the yeast as the active ingredient and has action of enhancing the phagocytic ability of the neutrophilic leukocyte. The pharmaceutical and the food and drink contain the substance, respectively. <P>COPYRIGHT: (C)2006,JPO&NCIPI

Description

The present invention relates to an immune system activator obtained from yeast-derived mannan and uses thereof.

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. Among them, the “yeast cell wall” is characterized by containing a high concentration of soluble and insoluble dietary fibers mainly composed of glucose and mannose.

Currently, the three major causes of death in Japan are cancer, cerebrovascular disease, and heart disease, and these prevalences are expected to increase further in the future due to the progress of an aging society. Among them, the growth rate of cancer mortality is remarkable, and it is now one cause of death for every three people. In addition, the prevalence of various infectious diseases is also increasing due to aging, and the wonders as complications of the above three major diseases are only increasing. Our bodies have immune functions and protect our bodies from the onset of cancer and infectious diseases, but these immune functions are largely related to genetic factors and environmental factors such as dietary habits. Are known. In order to enhance immune function, it is sometimes necessary to change lifestyle habits, and self-regulation that is difficult to sustain may be forced. A simple means for improving immune function that anyone can accept is desired.

The main dietary fibers contained in the cell wall of Saccharomyces yeast are glucan, which is a polymer of glucose, and mannan, which is a polymer of mannose. Some of these dietary fibers reach the large intestine in the digested or undigested state by the action of digestive enzymes, and are assimilated by bifidobacteria and lactic acid bacteria in the intestine to be metabolized into low molecular weight fatty acids. While low molecular weight fatty acids stimulate the intestinal tract, the dietary fiber itself increases stool bulk and fluidity, thereby improving the flow of stool, and the so-called “digestive effect of dietary fiber” is exhibited.

In recent years, it has been proposed that dietary fiber materials enhance systemic immune function by the following mechanism. (1) Excretion of harmful substances with immunosuppressive action and carcinogenicity is promoted by the intestinal regulating effect, and absorption into the body is inhibited. (2) The number of “good bacteria” such as bifidobacteria and lactic acid bacteria in the intestine increases, and these bacteria and dietary fibers themselves directly stimulate intestinal lymphoid tissues such as Peyer's patches and intestinal exudate lymphocytes. , "Gastrointestinal immunity function", and further systemic immune function is enhanced.

In animal studies and clinical studies conducted so far, the following facts have been revealed about the effect of oral administration of dietary fiber on immune function. That is, (1) enhancement of lymphocyte cytokine production, (2) enhancement of lymphocyte cytotoxicity, (3) enhancement of phagocytosis of neutrophils / macrophages, and (4) enhancement of IgA production in the gastrointestinal tract. Among them, the neutrophil (3) is a phagocytic cell occupying 35 to 75% of peripheral blood leukocytes, and works to eliminate them at the early stage of pathogen infection or tumor cell proliferation. That is, neutrophils are immunocompetent cells that first function to protect the living body from foreign substances, and increasing the function of neutrophils leads to prevention and early treatment of infections and cancer.

In recent years, interest in useful substances in foods has increased, and health foods that have no side effects and can be consumed with peace of mind are becoming a boom. Particularly for elderly people, pregnant women, infants, children, etc., there is a desire for a method of treatment and prevention using a food-derived component that has no side effects.

The yeast cell wall and its extracted fraction are known to exhibit an immunostimulatory effect when ingested by humans and animals, but there are few reports that mention the effect on the function of neutrophils. It has been introduced that the phagocytic ability of neutrophils was increased when fish was given protein components extracted from yeast cells with alkali and protein components extracted from yeast cells with enzymes (see Patent Documents 1 and 2). ). However, there is no finding that mannan obtained from yeast cells or yeast cell walls enhances human neutrophil function at present.
JP-A-8-283175 JP-A-8-113539

As described above, in order to prevent and treat cancer and infectious diseases whose morbidity is expected to continue to increase in the future, it is necessary to find an active ingredient from foods or similar foods. The present invention provides an immune system activator effective for prevention and treatment of adult diseases, a pharmaceutical product having an immune system activation function, and a food and drink, utilizing the neutrophil phagocytic enhancement function of mannan extracted from the yeast cell wall The purpose is to do.

The present invention was made in order to achieve the above-mentioned object, and the present inventors completed the present invention by confirming by a clinical test that the mannan on the yeast cell wall has a physiological activity that has not been known so far. .
That is, the present invention provides an immune system stimulating substance having an action of enhancing the phagocytic ability of neutrophils using mannan derived from yeast as an active ingredient, and pharmaceuticals and foods and drinks containing the same.

The present invention is characterized by the use of physiological functions of mannan derived from yeast, and as a raw material for pharmaceuticals, foods and drinks, yeast cells containing mannan, yeast strains enriched with mannan as compared to bacterial cells Either a body extract or a yeast culture supernatant containing mannan released from yeast cells or secreted from yeasts may be used. Whether the yeast cells are live or dead, it is desirable that the content of mannan is 5% (w / w) or more in the analysis in a dry state. Saccharomyces beer yeast and baker's yeast are known as yeast containing mannan. In addition, the yeast cell extract and culture supernatant preferably have a mannan content of 25% (w / w) or more in the analysis in a dry state.

According to the present invention, a substance having an action of enhancing the phagocytic ability of neutrophils and improving immune function can be obtained using yeast-derived mannan as a raw material. Furthermore, it could be easily used as a material for foods and drinks and pharmaceuticals.

When preparing cell extracts for the purpose of concentrating mannan, it is preferable to use yeast cells of the genus Saccharomyces as raw materials, whether they are live or dead, whether they contain water or are dried. Absent. Further, mannan may be further extracted from a yeast extract prepared other than for the purpose of concentrating mannan, or a yeast cell wall obtained as an insoluble residue when the yeast extract is produced. In this case, you may use a commercial item for a yeast extract or a cell wall. Examples of yeasts belonging to 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 or concentrated from the cells of Saccharomyces yeast, water, an organic solvent, or the like 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-containing extract solution 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. In addition, in the case of precipitation by addition of ethanol or the like, the precipitate may be washed with hydrous ethanol or the like and dried or powdered as it is, or ethanol or the like may be removed to form a solution. After extraction by the above method, mannose or a polymer thereof occupies 50% or more of the mannan-containing extract obtained by membrane treatment or ethanol precipitation.

When handling the culture supernatant of yeast, the content of mannan can be increased by performing molecular weight fractionation by membrane treatment, ethanol precipitation, or the like, similar to the treatment of yeast cell extract.
Purified yeast mannan, or yeast cells characterized by the inclusion of mannan, extracts, and culture supernatant concentrates can be used as pharmaceuticals as oral products, and mixed with food materials to make food and drink be able to. The properties are solid or liquid, and pharmaceuticals are in the form of tablets, capsules, granules, syrups and the like as oral preparations.

When it is administered to the human body as a pharmaceutical, it is orally administered once to several times a day in an amount of 1 to 500 mg (dry weight) / kg body weight, preferably 2 to 100 mg (dry weight) / kg body weight. 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 500 mg (dry weight).
Since the pharmaceuticals and foods and drinks containing yeast mannan of the present invention improve the immune function of the living body by enhancing the phagocytic ability of neutrophils, they are effective for the prevention and treatment of infectious diseases and cancer.
Hereinafter, the present invention will be described more specifically with reference to examples, but the present invention is not limited thereto.

(Preparation of yeast mannan from Saccharomyces yeast)
1000 g of beer yeast cell walls (Asahi Food & Healthcare) were suspended in distilled water, adjusted to pH 11.0 by adding sodium hydroxide, and then boiled at 90 ° C. for 12 hours. The supernatant was recovered by centrifugation and adjusted to pH 4.0 by adding hydrochloric acid. After high-pressure sterilization, heat coagulated substances and the like were removed, and sodium hydroxide was added to the obtained supernatant to adjust the pH to 5 or more. By freeze-drying, 15 g of yeast mannan fraction was obtained. As a result of analysis by sulfuric acid hydrolysis / high performance liquid chromatography, the ratio of mannose in the yeast mannan fraction was 77% (w / w).

(Tablets and capsules)
Yeast mannan 10.0g
Lactose 75.0g
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)
Yeast 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 10.0g
Chickenpox (75% solids) 60.0g
9.5g of water
0.455g of coloring agent
Perfume 0.045g
Yeast mannan 20g
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)
150g concentrated orange juice
Fructose 50g
Citric acid 2g
1g fragrance
1.5g
Sodium ascorbate 0.5g
Yeast mannan 10g
785 g of water
Total 1000g
Using each component of the above-mentioned parts by weight, juice was prepared according to a conventional method.

(barley tea)
Barley tea 5.0g
2995 g of water
Total 3000g
Using each component of each of the above parts by weight, after extracting barley tea components according to a conventional method,
Sodium ascorbate 1.8g
Yeast mannan 40g
To make barley tea.

(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
Yeast mannan 0.002g
Total 100.0g
Using each component of the above-mentioned parts by weight, a cookie was prepared according to a conventional method.

(Improvement of neutrophil phagocytosis in humans)
Five healthy adults were allowed to drink 3 soft drinks with 2 g or 3 g yeast mannan per 190 g per can, 3 per day for 2 weeks. That is, 6 g or 9 g of yeast mannan was ingested daily with meals for 2 weeks. Blood was collected immediately before the start of drinking (0 week) and the day after the end of drinking (2 weeks), and the phagocytic ability of neutrophils in peripheral blood was measured.
As shown in Table 1, neutrophil phagocytic ability was improved in all subjects by ingestion of yeast mannan.

以上の結果から、酵母マンナンがヒトの好中球貪食能を高める作用を有することが確認された。

From the above results, it was confirmed that yeast mannan has an action of enhancing human neutrophil phagocytic ability.

Claims (6)

An immune system activator having a phagocytic ability-improving action of neutrophils, comprising a mannose polymer or mannan derived from yeast cells as an active ingredient. 2. The immune system activator according to claim 1, wherein the yeast belongs to the genus Saccharomyces. The immune system activator according to claim 2, wherein the yeast is a yeast for brewing beer. 4. The immune system stimulating substance according to claim 3, which has a liquid form and contains 100 mg to 2 g of mannose per 100 mL. A pharmaceutical product utilizing immune system sputum comprising the immune system stimulating substance according to any one of claims 1 to 4. A food or drink containing the immune system activator according to any one of claims 1 to 4.