JPH11217336A - Antiallergic agent and agent for removing active oxygen - Google Patents

Abstract

PROBLEM TO BE SOLVED: To obtain an antiallergic agent useful for treating various allergic diseases such as bronchial asthma, atopic dermatitis and allergic rhinitis, and providing a little side effect by making the agent include a hydrophilic solvent extract of a mushroom. SOLUTION: This antiallergic agent contains a hydrophilic solvent extract of a mushroom. To obtain the hydrophilic solvent extract of the mushroom, selection of a grown mushroom is desirable, and the whole fruit body can be used but especially stem and ferrule parts are effective. The extraction of an effective component from the mushroom fruit body is preferably carried out by slicing the fruit body in a fresh state without browning or the one obtained by freezing the fruit body in the state, and rapidly inserting the sliced fruit body into a hot extraction solvent. The extraction solvent is preferably water, ethanol or a mixed solvent of the water and the ethanol. The daily dose is generally 0.01-50 g, especially 0.1-5 g.

Description

DETAILED DESCRIPTION OF THE INVENTION

[0001]

The present invention relates to an antiallergic agent and an active oxygen scavenger.

[0002]

2. Description of the Related Art Various allergic diseases such as atopic dermatitis, bronchial asthma and allergic rhinitis are mainly caused by a type I allergic reaction, and it is not uncommon for them to develop as adults. Many patients with atopic dermatitis suffer from intense pruritus and have been said to be on an increasing trend in recent years. Type I allergy is processed by macrophages (macrophages) when the allergen invades, and the information is transmitted to T cells made in the thoracic line and B cells made in the bone marrow. Produces specific IgE antibodies upon stimulation from T cells. This IgE is associated with receptors on the surface of mast cells on the skin and mucous membranes, and the sensitization process is established. Next, when the same allergen invades again, the allergen is associated with IgE on mast cells, and calcium ion influx occurs,
Activation of various enzymes results in the explosive induction of the synthesis and release of leukotrienes, prostaglandins and cytokines, including the release of various chemical mediators that cause allergic inflammation, namely histamine It is known.

[0003] As therapeutic agents for allergic diseases, sodium cromoglycate, tranilast, oxatomide and the like have also been developed, but these agents may have side effects on the digestive system and central system. In the treatment of atopic dermatitis, corticosteroids, corticosteroids and the like are often used, but they have side effects such as susceptibility to infection.

[0004]

SUMMARY OF THE INVENTION Accordingly, an object of the present invention is to provide an antiallergic agent having less side effects. Another object of the present invention is to provide an active oxygen-scavenging agent having few side effects.

[0005]

SUMMARY OF THE INVENTION The present invention provides an antiallergic agent containing a hydrophilic solvent extract of mushroom as an active ingredient, and an active oxygen eliminating agent containing a hydrophilic solvent extract of mushroom as an active ingredient. Things. The antiallergic agent of the present invention contains a hydrophilic solvent extract of mushrooms as an active ingredient, and has a remarkable effect on various allergic diseases such as bronchial asthma, atopic dermatitis and allergic rhinitis. The hydrophilic solvent extract of mushroom used as an active ingredient of the antiallergic agent and active oxygen scavenger of the present invention is disclosed in Japanese Patent Application Laid-Open No. 2-27745.
No. 6 (U.S. patent application Ser. No. 08/107333, EP 038055). Mushrooms are foods themselves and their hydrophilic solvent extracts are not toxic.

[0006] The components of the mushroom fruit body differ depending on its maturity and its location. In order to obtain the hydrophilic solvent extract used in the present invention, it is preferable to select the mushrooms that have grown, and to select the extraction method according to the site. Although the active ingredient is also contained in the mycelium in the compost, it cannot be obtained for oral ingestion due to the low extraction rate and the large amount of impurities from the compost at the time of extraction. The mushroom fruiting bodies normally used for edible use are those that are growing during the period when the umbrella does not open. However, in the present invention, it is preferable to use the fruiting bodies at this time because there are fewer problems such as coloration. As the site to be used, the whole fruit body can be used, but a site with a stem or stone is particularly effective.

In order to extract the active ingredient from the fruit body of the mushroom, it is preferable to slice a fresh substance which does not turn brown or a substance frozen at that time into a hot extraction solvent quickly. The cut mushrooms will brown in a short time due to the action of phenol oxidase, causing the decomposition of the active ingredient. Therefore, immersion or spraying in 0.1% or more of an organic or inorganic acid solution is also effective in preventing browning. As an extraction solvent, a hydrophilic solvent such as methanol, ethanol, isopropyl alcohol and acetone, or a mixed solvent thereof can be used in addition to water, but particularly for medical use and edible use, there is no problem even if it remains. Water or ethanol or a mixed solvent of water / ethanol is preferred. The extraction solvent may be generally added 2 to 10 times (weight ratio) to the material 1. In the case of water, the extraction temperature and time
The time is preferably 0 minutes or more and 2 hours or more at 80 ° C.

[0008] A mixed solvent with water is preferable to extraction with an alcohol or acetone solvent alone. Further, an organic acid or a sugar can be added to the solvent, and in this case, the extraction of the components is performed more effectively. As the organic acid, citric acid, malic acid, acetic acid, and ascorbic acid are preferable. The addition amount is suitably 0.05 to 2% by weight with respect to the solvent, and the pH is preferably adjusted to a range of 3.0 to 5.0. As sugar, fructose, glucose, sucrose, maltose and the like can be used. An appropriate amount of addition is 0.5 to 5% by weight. In this case, the osmotic pressure allows more effective extraction of the active ingredient in the cell wall of the fruit body.

[0009] Further, about 0.01 to 0.1% by weight of cellulase or amylase is added to water, and 25 ° C to 40 ° C.
, The reaction may be carried out for 2 to 24 hours to decompose the cell wall or protein before extracting. Further, once the mushroom is frozen and then thawed, the tissue (cell wall) is destroyed, and the active ingredient can be efficiently extracted. It is known that a hydrophilic solvent extract of mushroom has an excellent deodorizing effect, but it is not known at all that it has an antiallergic effect or an active oxygen eliminating effect. The administration form of the hydrophilic solvent extract of mushrooms is not particularly limited, but oral administration is the simplest. The dose should be appropriately increased or decreased depending on the condition of the patient, age, gender, disease state, etc., but is generally 0.01 to 5 per day.
0 g, especially 0.1 to 5 g, is suitable and is administered continuously or intermittently, preferably for a maximum of 3 months, while observing the symptoms.

[0010] The hydrophilic solvent extract of mushrooms may be administered as it is, but may be taken as various foods, for example, foods such as drinks, gums, candy, tablets, soups, miso soup, and gruel. It may be. The concentration of the hydrophilic solvent extract of mushrooms in such foods is not particularly limited, but may be a concentration suitable for ingesting the above-mentioned daily intake of 0.01 to 50 g, particularly 0.1 to 5 g. do it.

[0011]

The antiallergic agent of the present invention has excellent effects on leukotriene release inhibitory action and active oxygen scavenging action, and has allergic diseases such as bronchial asthma, atopic dermatitis, and release of chemical mediators. Allergic rhinitis, allergic dermatitis, food allergies,
It is effective in preventing and treating diseases such as inflammation. The antiallergic agent and active oxygen scavenger of the present invention are medical products,
It can be used in the form of quasi-drugs, cosmetics, foods and the like.

[0012]

Next, the present invention will be described by way of examples. Production Example 1 To 10 kg of fresh mushrooms, 20 kg of a 1% by weight aqueous solution of malic acid was added and extracted at 70 ° C. for 70 minutes. 20 kg of the extract was concentrated 10 times to obtain 2 kg of a concentrate. To 2 kg of this concentrate, 1.64 kg of dextrin was added,
Spray drying was performed to obtain 2 kg of powder. These concentrates and powders are commercially available from Ricom Corporation under the trade name “Champignon Extract” (registered trademark). Example 1 An antiallergic agent comprising the extract (concentrate) of Production Example 1. Example 2 An antiallergic agent comprising the powder of Production Example 1. Example 3 1 g of the powder of Production Example 1, 0.2 g of whey calcium, 0.2 g of isomaltooligosaccharide and 0.1 g of cellulose were mixed,
An anti-allergic agent in the form of a health food that is mixed with granule sachets. Example 4 An active oxygen eliminating agent comprising the extract (concentrate) of Production Example 1. Example 5 An active oxygen scavenging agent comprising the powder of Production Example 1. Example 6 1 g of the powder of Production Example 1, 0.2 g of whey calcium, 0.2 g of isomaltooligosaccharide and 0.1 g of cellulose were mixed,
An active oxygen scavenging agent in the form of a health food compounded in a granular package.

Test Example 1 (Test of leukotriene release inhibitory effect of extract of Production Example 1) Wistor rats of 7 to 8 weeks of age are exsanguinated after decapitation, and cold Tyrode's solution is injected intraperitoneally by a known method. Mast cells were isolated and prepared in PBS to a cell suspension of 1 × 10 ⁷ cells / ml. Add the cell suspension to the sample solution,
Incubated at 37 ° C for 5 minutes. This solution was placed in calcium ionophore A23187 (an antibiotic taking up calcium ions), incubated at 37 ° C. for 10 minutes, cooled PBS was added, and centrifugation was performed.
This supernatant was subjected to column chromatography (Isolute C ₁₈ (E
C)) and eluted with 3 ml each of water, 40% methanol and methanol. The fraction eluted with methanol was evaporated to dryness under reduced pressure and dissolved in methanol. HPLC [column: Capcell pak UG-120A (4.6 id × 250 mm), mobile phase:
0.2 mM CH ₃ COONa / CH ₃ CN / CH ₃ OH / TFA (55/30/22 / 0.04),
Flow rate: 1 ml / min, detection: ultraviolet ray, 280 nm]. From these results, the inhibition rate was calculated by the following equation. Table 1 shows the results. Inhibition rate (%) = (1-A / B) × 100 A: The amount of leukotriene released by calcium ionophore A23187 in the presence of the extract of Preparation Example B: The amount of leukotriene released by calcium ionophore A23187

[0014]

[Table 1] In comparison with the rat peritoneal mast cells of the extract of Production Example 1
Leukotriene (LT) inhibitory effect (%) ──────────────────────────────────── Sample LTB ₄ LTC ₄ LTD ₄ LTE ₄  Dose of the extract of Production Example 1 (μg / ml) 0.1 16.9 10.6 22.5 25.8 1 22.9 21.2 44.8 42.4 10 46.9 22.2 52.3 52.5 100 78.2 53.3 76.6 72.6 1000 90.0 65.8 84.8 88.3Hydrocortisone dose (0.25 mM / ml) 72.5 70.1 62.5 70.5 Test Example 2 (Reactive oxygen scavenging action test) The experiment was partially modified by Oyanagi's method (Anal. Biochem., 142,
 290-296 (1984)).

0.1 mM xanthine (0.2 ml), 0.1 mg /
After adding a sample or water to a mixture of 1 ml of hydroxylamine-O-sulfonic acid and 1 mM hydroxylamine hydrochloride and 7 mM borate buffer (pH 8.3), 6.3 × 10
^After adding ² U / ml xanthine oxidase (XOD) or water and incubating at 37 ° C. for 30 minutes, a mixed solution of 2 mM sulfanilic acid solution, 20 μM N-1-naphthylethylenediamine and 16.7% acetic acid was added, and the mixture was added at room temperature for 30 minutes.
After standing for a minute, OD 550 nm was measured. Also, superoxide dismutase (SOD) prepared from bovine erythrocytes
Was used as a positive control. The inhibition rate was calculated by the following equation. Table 2 shows the results. Inhibition rate (%) = (1-A / B) × 100 A: (OD when XOD was added) − (O when no XOD was added)
D) B: (OD when control XOD was added)-(OD when control XOD was not added)

[0016]

[Table 2] Active oxygen inhibitory effect of the extract of Production Example 1 ───────────────────────Dose (μg / mL) Inhibition rate (%) 1 37 3 44 10 51 30 78 100 100 83

Claims (2)

[Claims] 1. An antiallergic agent comprising a mushroom hydrophilic solvent extract as an active ingredient. 2. An active oxygen-scavenging agent comprising a mushroom hydrophilic solvent extract as an active ingredient.