JP3510639B2 - Functional food or health food with a function to regulate interleukin production - Google Patents

Description

Detailed Description of the Invention

[0001]

The present invention relates to interleukin human cells (hereinafter, IL hereinafter) production capacity, more particularly <br/> of human cell IL-2 and / or IL-3 Sanseino enhance, inhibit IL-6 production ability necessary IL-producing ability
The present invention relates to a functional food or a health food that has a function of regulating the.

[0002]

2. Description of the Related Art Conventionally, fermented milk has been enhanced in natural killer cell (NK cell) activity, macrophage activity,
It is known to have actions such as enhancement of antibody production, enhancement of gamma-interferon production, and enhancement of cell proliferation ability [Toshiaki Takano, Journal of the Brewing Society of Japan, 85 (7), 438-444 (199).
0), and Perdigon, G., Nader de Macias et al., J. Dair.
yRes. 57 (2), 255-264 (1990)]. However, it is not known that fermented milk has an IL production ability-regulating action, and conversely, it is shown in the literature that yogurt has no IL-2 production ability-enhancing effect. Namely Simone, CD _E et al, Nutrit
According to ion Reports International, 33 (3), 419-433 (1986), human peripheral blood lymphocytes were stimulated with concanavalin A as mitogen in the presence of yogurt.
Although the ability to produce γ-interferon was enhanced, IL-2
The productivity was not enhanced (particularly Table 3 in the literature and its preamble). IL is a kind of cytokine that is a humoral factor produced by cells, and includes many kinds [References on IL in general: Immunology, Medical Review, pp. 57-73 (March 1991). , Literature on IL-2: History of Medicine, 126 (5), 381-386, 394-400, 401.
-408 (1983), literature on IL-3: Medical Immu.
nology 11 (6), 671-681, (1986), literature on IL-6: clinical immunity 21 (8), 1225-1241 (1989)].

Among these, since IL-2 is a T cell growth factor, it has a function of promoting reactions involving T cells in various immune reactions in vivo. In particular, it is considered to be useful for enhancing antibody production and activating cytotoxic T cells when a foreign substance enters the body. It is also possible to activate the immune system against cancer. In fact, IL-2 has been attracting attention as a therapeutic drug for cancer and infectious diseases. Since IL-3 is a growth and differentiation factor for hematopoietic stem cells, it is considered to have a function of supplementing it when the living body is infected with a virus, a microorganism, cancer or the like and the number of differentiated cells of the hematopoietic system is insufficient.
For example, when a virus that attacks T cells and enters a function is invaded, peripheral T cells may be killed and the antibody production system may stop working, but this is supplemented by differentiation and proliferation from stem cells. It is possible that I
L-6 is known as a multifunctional factor. For example, it promotes the differentiation of B cells into antibody-producing cells, increases the cytotoxicity of T cells, promotes the differentiation and proliferation of hematopoietic stem cells, and promotes the differentiation and proliferation of epidermal basal layer keratinocytes. . In addition, it is known to have effects on cells of the liver and kidneys. However, nowadays, if you have a disease such as lymphoma or AIDS, IL in blood
It is known that the amount of −6 is higher than that of the normal amount. This is because it is attempting to protect IL-6 by producing high levels of IL-6 against abnormalities in the living body, and it is considered that such high production is unnecessary in normal cases. On the contrary, when the amount of IL-6 is large, the amount of antibody produced is increased, and the amount of unnecessary antibody is increased in blood, which is considered to be an unfavorable situation.
Therefore, it is considered that the IL-6 producing ability does not need to be so high in a normal state.

[0004]

OBJECTS OF THE INVENTION It is therefore an object of the present invention is to modulate IL-producing ability of the human, for example, IL-2
And / or enhances IL-3 production ability, and if necessary IL
Ru can be suppressed -6-producing ability is to provide a functional food or health food have a function of adjusting the I L-producing ability.

[0005]

According to the present invention, a lactic acid bacterium of the genus Lactobacillus and the genus Saccharomyces is added to a milk medium containing at least one selected from the group consisting of whole animal milk, skim milk and reconstituted milk. yeast and / or Candida yeasts and lactic acid bacteria and fermented milk obtained by symbiotic fermentation was inoculated with yeast consists, interleukin production ability of the cells of human containing the concentrate treated or dried as an active ingredient
Functional foods or health foods that have the function of regulating
Be served . According to the invention, whole milk animal milk, a milk medium containing at least one selected from the group consisting of skim milk and reconstituted milk, a lactic acid bacteria of the genus Lactobacillus, and Saccharomyces yeast and / or Candida genus yeasts A fermented milk co-fermented by inoculating lactic acid bacteria and yeast consisting of , a concentrated processed product thereof or a dried processed product thereof as an active ingredient,
Human cell interleukin-2-producing ability, and / or interleukin interleukin production functional food capacity have a function of adjusting the or Ken enhancing Kin -3 production ability of
Kang food is provided . Further according to the present invention, whole milk of animal milk, a milk medium containing at least one selected from the group consisting of skim milk and reconstituted milk, Lactobacillus lactic acid bacteria,
And Saccharomyces yeast and / or Candida genus yeasts
Lactic acid bacteria and fermented milk obtained by symbiotic fermentation was inoculated with yeast consists, contains the concentrate treated or dried as an active ingredient, interleukin-2 production ability of human cells and / or interleukin-3 Increase productivity,
And a functional food having a function of controlling interleukin-producing ability that suppresses interleukin-6 producing ability, or
Health food Ru is provided.

[0006] Fermented milk, whole milk animal milk, a milk medium containing at least one selected from the group consisting of skim milk and reconstituted milk, a lactic acid bacteria of the genus Lactobacillus, and Saccharomyces yeast and / or Candida genus yeasts It is obtained by inoculating lactic acid bacteria and yeast consisting of Lactobacillus lactic acid bacteria include Lactobacillus bulgaricus ( Lactobacillus bulgaricus ), Lactobacillus helveticus (L. helveticus ), Lactobacillus
L. casei , Lactobacillus acidophilus
(L. acidophilus ), Lactobacillus fermentum
Lactic acid-producing bacteria belonging to (L. fermentum) and the like are used. Specifically, Lactobacillus bulgaricus ATCC 11842,
Lactobacillus helveticus ATCC 15009, Lactobacillus helveticus ss Eugleti (jugurt
i) ATCC 521, Lactobacillus casei ATCC 393, Lactobacillus acidophilus JCM 1132, Lactobacillus fermentum ATCC 14937, etc. are used.
As yeast, strains belonging to the genus Saccharomyces or the genus Candida are essentially used, and the yeast imparts an aroma to the fermented milk. More specifically, strains belonging to Saccharomyces cerevisiae , Candida utilis, etc. are used.
Specifically, Saccharomyces cerevisiae ATCC 2565,
Candida Uchiris ATCC 8205 etc. are used.

One or more of the above- mentioned lactic acid bacteria and one or more of the above-mentioned yeast are combined and cultured in a medium. The medium may be whole milk, a medium consisting of one or more of milk components, and yeast extract, vitamins (ascorbic acid, etc.), amino acids (cysteine, etc.), salts (secondary components) thereto. It may be a medium in which saccharides (such as sodium chloride), sugars (such as sucrose, raffinose, stachyose, and other oligosaccharides), stabilizers (gelatin, etc.), flavors and the like are appropriately added. Fermentation is usually by static culture at a temperature of 25 to 45 ° C., preferably 37 ° C., initial pH
Performed at 6.0 to 7.0, the number of bacteria is 10 ⁷ cells / ml or more, p
The culture is stopped at the time when it becomes H5.5 or less. The fermented milk obtained is heated (for example, 80 ° C) even if the bacteria used are still alive.
It may be sterilized by the final temperature). As fermented milk concentrate treated with concentrated intact or <br/> other under reduced pressure concentration or the like, or lyophilized, dried powder or the like and dried by spray drying or the like
It can be used as an active ingredient of the present modifier as objects. At the time of pulverization, an excipient such as dextrin can be added to facilitate pulverization.

[0008] In the present invention, the fermented milk or a Japanese
Constant of the workpiece may be a pharmaceutical composition comprising further comprise a normal least one pharmaceutical adjuvant. The pharmaceutical group
Narubutsu is orally administered to humans. The orally administered drug is formulated into a form suitable for absorption by the gastrointestinal tract. Tablets, capsules, granules, fine granules and powders are commonly used pharmaceutical auxiliaries such as binders (syrup, gum arabic, gelatin, sorbitol, tragacanth, polyvinylpyrrolidone, hydroxypropylcellulose), excipients (lactose). , Dextrin, sucrose, corn starch, calcium phosphate, sorbitol, glycine, etc.), lubricants (magnesium stearate, talc, polyethylene glycol, silica, etc.), disintegrants (potato starch, carboxymethyl cellulose, etc.), wetting agents (sodium lauryl sulfate, etc.) )
Can be included. The tablets can be coated by a conventional method. The oral liquid preparation can be an aqueous solution or a dry product. Such oral solutions may contain conventional additives such as preservatives (methyl or propyl p-hydroxybenzoate, sorbic acid, etc.). The amount of fermented milk or its concentrated or dried product in the present regulator can be variously changed, but usually 5 to 100% (w / w), particularly 10 to 60% (w / w) is suitable. is there. When administered to humans, the dose of this regulator is
Dried product of fermented milk which is an active ingredient, for example, 100 mg / kg / day or more as a freeze-dried product, for example, 100 to 3000 mg /
kg / day, especially about 500 mg / kg / day is suitable.

[0009] Fermented milk or JP used in the present invention
Since a certain treated product has an advantage that it does not adversely affect the living body even if it is ingested in a large amount, a function of regulating the IL-producing ability as it is, or by adding various nutrients or the like, or by including it in food or drink, In particular IL-2 producing ability and / or I
It can also be ingested as a functional food or a health food having an ability to enhance L-3 production and, if necessary, a function to suppress IL-6 production. As a specific embodiment, in the present invention
Sugars fermented milk to be used, and / or the like is added to the flavor used directly as yoghurt-like food, the onset
Sugar and / or protein in fermented milk used in Ming
And / or lipid, and / or vitamins, and / or minerals, and / or used as a dietary supplement material by adding flavors or the like; perform powdered as in Example, instead of skim milk added to the food; perform powdered as in example, it is possible embodiment of such use as health supplements material. Such functional food, the content of the active ingredient in the present regulator as a health food,
The intake amount may be the same as the content and dose in the above pharmaceutical composition, respectively.

[0010]

EXAMPLES Next, the present inventionIn the exampleExplain moreIs the present invention
Is not limited to these. Example 1 <Production of fermented milk and dried product thereof> Lactobacillus helveticus ss Eugleti A
TCC 521 and Candida Uchiris ATCC 8205 85
3 to skim milk sterilized to reach ℃ (solid content: about 9% by weight)weight%
Inoculate and perform co-cultivation at 37 ℃ for 24 hours to fermented milk (lactic acid
Number of bacteria 10⁹/ ml, pH 3.2) was obtained. This fermented milk 10k
g (containing about 900 g of solid content) with dextrin
After adding 900g and stirring well, lyophilize,
Fermented milk was made into powder (fermented milk-derived solid content of about 50weight
%).<Enhancement of IL-2 productivity> Got Fermented milk powder is used as a basic feed for mice and rats (Funabashi
Farm-made MF) (water content 7.4%, crude protein 19.6)
%, Crude fat 4.8%, crude fiber 2.4% and crude ash 4.0
%) Added to about 2.5% by weight to promote 6-week-old female aging
Mouse (hereinafter referred to as SAM) -P / 2 [SAM-P / 2
Is a relatively short-lived strain, and the cause of death is often infectious diseases and cancer.
Therefore, it is considered that the immune function is lowered. Fact IL
-2 productivity is significantly lower than that of normal mice (Futami Akira
Basic aging research,12(2): 107-108, (1988). ] About 10
Can be ingested ad libitum for a week and splenocytes are concanavalin A (CoA)
IL-2 productivity when stimulated with J. Watson, J. Exp. M
ed.150, 1510-1519 (1979) and S. Gillis et al., J. of
 Immunology120(6), 2027-2032 (1976).
I investigated by the method. As a result, the amount of IL-2 produced was
305.4 + 41.1 (standard error (S.E.)) μg / ml
On the other hand, on the other hand, in the group that received only basic feed (target group)
Is 190.1 + 34.7 (S.E.) μg / ml, and IL-2
Productivity was significantly increased at a risk rate of 5%.<Enhancement of IL-3 productivity> Obtained above Fermented milk powder as a basic feed for mice and rats
Add about 2.5% by weight to (MF manufactured by Funabashi Farm), 6 weeks old
SAM-P / 2 for free for about 10 weeks,
Poke weed mitog
en) and IL-3 production ability and IL-6 production
Noh and S. Koyasu et al., J. of Immunology134(5), 3
130-3136 (1985) and N. Tohyama et al., J. Exp. Med.
171, 389-400 (1990).
It was The number of animals used is based on the group using basic feed containing fermented milk powder (fermentation)
8 in the milk powder addition group, in the basic feed use group (target group)
Was 5 animals. The results are shown in Tables 1 and 2. Tables 1 and 2
The unit of numbers is units / ml.

[0012]

[Table 1]

[0013]

[Table 2] As is clear from Tables 1 and 2, in the fermented milk powder-added group, the IL-3 production amount was significantly increased on the 7th day at a risk rate of 5%, and the IL-6 production amount was decreased, as compared with the control group. There was a tendency.

Example 2 Lactobacillus helveticus ss was added to a milk medium consisting of 15% by weight reduced skim milk heat-sterilized at 85 ° C. for 30 minutes.
3% by weight of a starter obtained by co-culturing Eugleti ATCC521 and Saccharomyces cerevisiae ATCC2565 in the same medium as above was inoculated, and cultured at 35 ° C. for 24 hours to obtain fermented milk. 60 kg of this fermented milk has 10 kg of honey,
Vitamin A 5g, Vitamin C 20g, Vitamin E 2
0 g, pectin 0.4 kg, and water 29.4 kg were added and homogenized by a homogenizer and sterilized at a temperature of 85 ° C.
0 kg was obtained.

[0015]

The functional food or health food of the present invention is
Adjust the IL-producing capacity of cells bets, in particular, of human cells I
It is possible to enhance L-2 production ability and / or IL-3 production ability, and further suppress IL-6 production ability.

Continued front page    (72) Inventor Toshiaki Takano               2-4-1 Ebisu Minami, Shibuya-ku, Tokyo               Research and Development Center, Lupis Food Industry Co., Ltd.               -In                (56) Reference JP-A-2-219538 (JP, A)                 JP-A-52-128207 (JP, A)                 JP-A-64-47338 (JP, A)

Claims (3)

(57) [Claims] 1. A lactic acid bacterium of the genus Lactobacillus, a yeast of the genus Saccharomyces and / or a milk medium containing at least one selected from the group consisting of whole animal milk, skim milk and reconstituted milk.
Or Candida yeasts and lactic acid bacteria and fermented milk obtained by symbiotic fermentation was inoculated with yeast consists, the concentrate treated product or the ability to modulate interleukin production ability of the cells of human containing the dried product as an active ingredient Functional food
Product or health food . 2. A lactic acid bacterium of the genus Lactobacillus, a yeast of the genus Saccharomyces and / or a milk medium containing at least one selected from the group consisting of whole animal milk, skim milk and reconstituted milk.
Or Candida yeasts and lactic acid bacteria and fermented milk obtained by symbiotic fermentation was inoculated with yeast consists, contains the concentrate treated or dried as an active ingredient, human cell interleukin-2-producing ability and / Or regulate interleukin-producing ability that enhances interleukin-3 producing ability
Functional foods or health foods with the function to do . 3. A lactic acid bacterium of the genus Lactobacillus, a yeast of the genus Saccharomyces and / or a milk medium containing at least one selected from the group consisting of whole milk of animal milk, skim milk and reconstituted milk.
Or Candida yeasts and lactic acid bacteria and fermented milk obtained by symbiotic fermentation was inoculated with yeast consists, contains the concentrate treated or dried as an active ingredient, human cell interleukin-2-producing ability and / Alternatively, the function of enhancing the interleukin-3 producing ability and suppressing the interleukin-6 producing ability is regulated.
Functional foods or health foods .