JP4189039B2 - Antibody-producing cell inhibitor - Google Patents

Description

【００３１】
【発明の効果】
本発明によれば、抗体産生細胞の抗体産生を抑制し、自己免疫疾患の改善及び予防に有益な抗体産生細胞抑制剤及び食品組成物が提供できる。[0001]
BACKGROUND OF THE INVENTION
The present invention relates to an antibody-producing cell inhibitor useful for the treatment or prevention of autoimmune diseases.
[0002]
[Prior art]
In recent years, autoimmune diseases such as atopic dermatitis, systemic lupus erythematosus, bronchial asthma, and allergic rhinitis have been greatly affected by sudden changes in the living environment and dietary habits. . At present, for these autoimmune diseases, inflammation is only symptomatically suppressed by administration of non-steroidal or steroidal anti-inflammatory agents.
[0003]
In such autoimmune diseases, the existence of various autoantibodies and autoantigen-sensitized lymphocytes is known, and autoantibodies alone, complement dependency, phagocytic antibody properties, and killer cell dependency It has also been confirmed experimentally that it is causing trouble. However, the specific mechanism has not been elucidated, and therefore, attempts to reduce autoimmunity often cause immunodeficiency, so there is currently no curative treatment method. That is, there has been a demand for a drug that suppresses autoantibody-producing cells and antibody-producing cells such as the spleen.
[0004]
On the other hand, it has not been known at all that yeast protease degradation products, or solvent extracts or fractions thereof are useful for inhibiting antibody-producing cells and preventing or improving autoimmune diseases.
[0005]
[Problems to be solved by the invention]
The present invention has been made in view of such a situation, and an object thereof is to provide a substance that suppresses antibody-producing cells such as the spleen.
[0006]
[Means for Solving the Problems]
In view of such a situation, the present inventors have intensively studied for a substance that suppresses antibody-producing cells, and as a result, found that the protease degradation product of yeast has such an action and completed the invention. It was. Hereinafter, the present invention will be described in detail.
[0007]
(1) Antibody-producing cell inhibitor of the present invention The antibody-producing cell inhibitor of the present invention comprises a yeast protease degradation product, or a solvent extract or a fraction thereof. Specifically, a part or all of a protein or peptide constituting yeast is enzymatically decomposed with a protease such as pepsin, trypsin, chymotrypsin, cathepsin, papain, promeline, ficin, or a solvent extract or fraction thereof. Examples include purified products. Furthermore, the yeast is not particularly limited as long as it is a fungus that passes through most of the life cycle as a single cell, and examples thereof include yeasts of the yeast fungus, protozoan fungus, and protozoan basidiomycete incomplete generation. Of these, preferred bacterial species are those belonging to the genus Saccharomyces, and among these, baker's yeast and brewer's yeast are more preferred, and brewer's yeast is even more preferred. These can be manufactured as follows.
[0009]
(1 1) 2 protease hydrolyzate yeast or the workpiece is dispersed in a solvent such as water, to which pepsin, trypsin, chymotrypsin, cathepsin, papain, Puromerin, at a temperature in the region of the protease was added 40 ° C. such as ficin What is necessary is just to decompose for 72 hours. A microorganism-derived protease such as a yeast-derived protease may be used. What is necessary is just to use pH optimal for protease. Among these enzyme groups, pepsin is readily available. After the enzymatic decomposition, the protease may be inactivated by heating or the like to remove undigested material, and then the solvent may be distilled off.
[0011]
( 1-2 ) Solvent extract The solvent extract may be obtained by adding a solvent to the above protease decomposition product , immersing for several hours if the temperature is near the boiling point, and for several days if it is room temperature, and distilling off the solvent. The solvent is preferably a polar solvent, for example, water, alcohols such as ethanol and methanol, ketones such as acetone and methyl ethyl ketone, ethers such as diethyl ether and tetrahydrofuran, halogenated hydrocarbons such as chloroform and carbon tetrachloride, Nitriles such as acetonitrile can be mentioned. These may use only 1 type and may mix and use 2 or more types. Particularly preferred among such solvents is a mixture of water and alcohol, which is excellent in safety and extraction efficiency.
[0012]
( 1-3 ) Fraction As a fraction, the above protease degradation product or solvent extract is subjected to liquid-liquid extraction in a two-phase solvent system such as diethyl ether-water, chloroform-water, hexane-hydrated alcohol, water-butanol or the like. And a fraction obtained by column chromatography using a carrier such as silica gel, ODS, ion exchange resin, gel filtration, etc., a fraction obtained by dialysis membrane, and the like. Of these, ion exchange resin column chromatography and gel filtration are preferred.
[0013]
(2) Antibody-producing cell inhibitor of the present invention The antibody-producing cell inhibitor of the present invention comprises the above-mentioned yeast protease degradation product, or a solvent extract or fraction thereof . The antibody-producing cell inhibitor referred to in the present invention has the action of suppressing antibody production activity of antibody-producing cells and reducing the amount of antibody production. Since the yeast-related polymer is excellent in the action of suppressing antibody-producing cells such as the spleen and decreasing the amount of antibody production as shown in the examples below, it is excellent in the improvement and prevention of autoimmune diseases, in particular, atopic dermatitis. . In particular, for atopic dermatitis that develops depending on the season, it is possible to administer the antibody-producing cell inhibitor in a timely manner before the immune reaction flares up, so a high preventive effect can be expected.
[0014]
(3) Food composition Food Compositions of the Invention The present invention is characterized by containing the antibody-producing cell inhibitor singly or in combination. The type of the food composition of the present invention, a food composition for improving or preventing the autoimmune disease. These food compositions can contain optional components commonly used in these food compositions in addition to the antibody-producing cell inhibitor of the present invention. Examples of such optional components, wear colorants, thickeners, flavoring agents, stabilizers, emulsifiers, preservatives, Ru is like oxidation stabilizers. Food composition of these invention can be prepared by conventional methods. The preferred content of the antibody-producing cell inhibitor of the present invention in these food compositions is 0 . 1 to 80% by weight is preferred, 1 to 70% by weight is more preferred, and 5 to 50% by weight is even more preferred . Apply the amount of the food composition of the present invention, an adult per day, it can be taken once to several times a 1 ~500g. Since the antibody-producing cell inhibitor of the present invention is excellent in safety as shown in Examples below, such a large amount of administration is possible.
[0015]
DETAILED DESCRIPTION OF THE INVENTION
The embodiments of the present invention will be described in detail below with examples, but it goes without saying that the present invention is not limited to these examples.
[0016]
Example 1 (Production example)
100 g of beer yeast was dried and pulverized, dispersed in 500 ml of hot water at 39 ° C., 1 g of pepsin was added thereto, stirred at 39 ° C. for 72 hours, and treated at 100 ° C. for 1 hour to inactivate pepsin. After filtration, the filtrate was lyophilized to obtain 92 g of antibody-producing cell inhibitor 1.
[0017]
Example 2 (Production example)
10 g of the antibody-producing cell inhibitor 1 was taken, and 100 ml of 50% ethanol aqueous solution was added thereto, heated under reflux for 2 hours, filtered, and concentrated under reduced pressure to obtain 3.6 g of antibody-producing cell inhibitor 2.
[0022]
Example 3 (Formulation example: Candy )
Candy was prepared according to the following prescription. That is, the prescription ingredients were heated and mixed at 120 ° C., poured into a mold and molded into a candy.
Antibody-producing cell inhibitor 1 10 parts by weight Chickenpox 30 parts by weight Sorbite 60 parts by weight
Example 4 (Formulation example: Candy )
Candy was prepared according to the following prescription. That is, the prescription ingredients were heated and mixed at 120 ° C., poured into a mold and molded into a candy.
Antibody producing cell inhibitor 2 10 parts by weight Minamata 30 parts by weight Sorbite 60 parts by weight
【Example】
Example 1
Acute toxicity The acute toxicity of the antibody-producing cell inhibitors 1 and 2 of the present invention was examined using 5 ICR mice per group. That is, the antibody-producing cell inhibitors 1 and 2 of the present invention were each dispersed or solubilized in physiological saline and orally administered in an amount of 2 g / Kg. On the 14th day after administration, the animals were confirmed to be alive or dead, and all animals were alive. This shows that the LD50 value of the antibody-producing cell inhibitor of the present invention is larger than 2 g / Kg, and the safety is high.
[0029]
Example 2
Antibody-producing cell inhibitory action The antibody-producing cell inhibitory action was performed by identifying and counting antibody-producing cells of splenocytes by plaque formation according to the hemolytic plaque method (Science, 140, 405, 1963) developed by Jern et al. . That is, six ddy male mice per group were sensitized by dispersing SRBC (sheep erythrocytes) in phosphate buffered saline at a concentration of 4 × 10 ⁸ cells / ml from the tail vein and administering 0.25 ml. Samples were dispersed or solubilized in physiological saline at doses of 500 and 1000 mg / Kg for 4 consecutive days from the SRBC administration day. 24 hours after the end of the final administration, the spleen was taken out, and antibody-producing cells were counted by the method of Jerun. That is, it was divided into spleen cells, incubated with SRBC on an agar medium, and further incubated with guinea pig serum to count plaque-forming cells. The results are shown in Table 1. Thus, it can be seen that the antibody-producing cell inhibitor of the present invention is excellent in antibody-producing cell inhibitory action.
[0030]
[Table 1]

[0031]
【The invention's effect】
ADVANTAGE OF THE INVENTION According to this invention, the antibody production cell inhibitor and food composition which suppress the antibody production of an antibody producing cell, and are useful for the improvement and prevention of an autoimmune disease can be provided.

Claims (1)

An antibody-producing cell inhibitor comprising a protease degradation product of a yeast protein , or a solvent extract or fraction thereof.