JP2008037785A - Antiallergic agent - Google Patents

Abstract

<P>PROBLEM TO BE SOLVED: To provide an antiallergic agent containing a novel antiallergic substance having strong inhibition of histamine release, and food and drink and a cosmetic which contain the antiallergic substance. <P>SOLUTION: The antiallergic agent has Scutellaria lateriflora or its extract as an active ingredient and the food and drink and the cosmetic contain Scutellaria lateriflora or its extract. The antiallergic agent, the food and drink, and the cosmetic have extremely strong inhibition of histamine release and are useful in preventing and treating atopic dermatitis caused by type I allergic reaction, allergic rhinitis, pollinosis, allergic asthma or the like. <P>COPYRIGHT: (C)2008,JPO&INPIT

Description

  The present invention relates to an antiallergic agent containing an antiallergic substance having a histamine release inhibitory action as an active ingredient, and a food and drink and a cosmetic containing the antiallergic substance.

  Allergic reactions such as hay fever and allergic rhinitis have become a major social problem in recent years. In this reaction, excessively produced IgE antibody by invasion of antigen binds to mast cells and basophils, and chemical mediators such as histamine are released by binding of the reinvaded antigen and IgE antibody, causing an inflammatory reaction It is. Therefore, it is possible to prevent allergic reactions by cutting off any of the above pathways.

  Several reports have been made on the antiallergic effects of Lamiaceae plant extracts. For example, an antiallergic cosmetic composition characterized by blending of Lamiaceae plants (see Patent Document 1), an antiallergic agent containing one of Lamiaceae perilla, mint, and weevil (Patent Document 2), Lamiaceae Anti-allergic agent including one of rosemary, thyme and melissa (see Patent Document 3), including one species of Miznata, L. mint, Peniloyl mint, Malba mint, Dutch mint and Bergamot mint An IgE production inhibitor (see Patent Document 4) and the like have been reported, but no plant having a remarkably high activity among Labiatae has been reported.

Japanese Patent Application Laid-Open No. 6-293652 Japanese Patent Laid-Open No. 1-102027 JP-A-8-333267 JP 2003-286182 A

  An object of the present invention is to provide an antiallergic agent containing a novel antiallergic substance having a strong inhibitory action on histamine release, and a food and drink and a cosmetic containing the antiallergic substance.

The present inventors searched for a novel antiallergic substance to search for an index effective for the treatment of allergic symptoms as histamine release inhibitory activity, and reported that it has histamine release inhibitory activity. Among the Labiatae plants, the skull cap (Scutellaria lateriflora) has high histamine release inhibitory activity, and the skull cap and its extract were found to be very useful as antiallergic substances.
The present invention has been made based on the above findings, and provides “an antiallergic agent containing a skullcap or an extract thereof as an active ingredient” and “a food or drink or a cosmetic containing the skullcap or an extract thereof”. This achieves the above object.

  ADVANTAGE OF THE INVENTION According to this invention, the antiallergic agent, food-drinks, and cosmetics which can suppress histamine release effectively and contain the highly safe antiallergic substance are provided.

First, the antiallergic agent of the present invention will be described.
The skull cap, which is an active ingredient of the antiallergic agent of the present invention, includes the whole, leaves, seeds, pericarp (including green skin and immature pericarp), mature fruit, immature fruit, pericarp, flower, material, bark, root, etc. The site can be used.

  The antiallergic agent of the present invention can be used as an antiallergic substance as an active ingredient after pulverizing the above-mentioned part of the skull cap.

  When obtaining an extract from the above-mentioned part of the skull cap, the skull cap may be used as it is, but it is preferable to dry and pulverize it and use it as a powder because the extraction efficiency is improved. Although there is no restriction | limiting in particular in the solvent used for extraction, Alcohols, such as water (hot water), methanol, ethanol, and propanol, Organic solvents, such as ether, hexane, chloroform, ethyl acetate, acetone, glycerol, propylene glycol, and mixtures thereof Those selected from the group consisting of can be used as the extraction solvent. However, considering that the skullcap extract is taken orally, it is desirable to extract using water, ethanol, hexane or a mixture thereof from the viewpoint of safety.

  When extracting a skull cap, it is desirable to add the said solvent as an extraction solvent and to perform extraction for about 0.5 to 48 hours at the temperature of 10-80 degreeC. Then, after the extraction solvent is distilled off from the extract, it can be used after being concentrated or lyophilized under reduced pressure. In addition, a product obtained by fractionating and purifying these extracts by organic solvent fractionation, column chromatography, or the like can also be used.

Skullcap and its extract have the action of suppressing histamine release in type I allergic reactions. Therefore, the antiallergic agent of the present invention comprising a skullcap or an extract thereof as an active ingredient is particularly useful for the prevention and treatment of atopic dermatitis, allergic rhinitis, hay fever or allergic asthma caused by type I allergic reaction. It is.

  The antiallergic agent of the present invention is useful as a prophylactic or therapeutic agent for various allergic diseases, an anti-inflammatory agent, and a histamine release inhibitor.

  As for the antiallergic agent of the present invention, the above-mentioned skull cap pulverized product or skullcap extract may be used as it is as an antiallergic agent, and if necessary, various pharmaceutically acceptable carriers, excipients, and other additives. It can be made an antiallergic agent by blending a preparation with other agents and other ingredients. The dosage form of this antiallergic agent is not particularly limited, and includes oral preparations such as tablets, powders, granules, capsules, and parenteral preparations such as ointments, lotions, gels, eye drops, and nasal drops. And can be formulated by a conventional method. As other components, other antiallergic components, anti-inflammatory drugs, various vitamins, herbal medicines, and minerals can be appropriately blended.

The content of the skull cap pulverized product or skull cap extract in the antiallergic agent of the present invention may be any amount as long as it can suppress histamine release. It can be appropriately changed depending on the type, symptom of the person who administers or ingests, age and sex. When the antiallergic agent of the present invention is orally administered, it is preferably contained so that the dose of the skull cap pulverized product or skull cap extract per person per day is 0.1 to 2500 mg. In the case of parenteral administration, it is preferable to contain the skull cap pulverized product or skull cap extract so as to be dropped, applied or sprayed onto the skin or mucous membrane within the range of 0.01 to 250 mg / cm ² .

Next, the food / beverage products and cosmetics of this invention are demonstrated.
The food / beverage products and cosmetics of this invention contain said skull cap ground material or skull cap extract, and have antiallergic properties.
Examples of the food and drink include, but are not limited to, beverages such as soft drinks, juices, and energy drinks, and confectionery such as breads, noodles, tablets, and candy.

  Examples of cosmetics include, but are not limited to, creams, lotions, essences, bathing agents, and the like. The cosmetics of the present invention usually contain ingredients used in cosmetics (for example, various herbal extracts, oily ingredients, moisturizing ingredients, thickeners, emulsifiers, horny layer release agents, preservatives, chelating agents, etc.). be able to. For example, examples of the oil component include hydrocarbons, various synthetic esters, waxes, fats and oils, higher fatty acids, higher alcohols, and silicones.

The timing of adding the above-mentioned skull cap pulverized product or skull cap extract to a food or drink or cosmetic is not particularly limited, and may be added during the manufacturing process of the food or drink or cosmetic. You may add to food-drinks or cosmetics.
The content of the skull cap pulverized product or skull cap extract in the food and drink and cosmetics of the present invention is not particularly limited and can be appropriately changed depending on the type of food and drink or cosmetics. In the case of foods and drinks, it is preferable to contain so that the intake of the skull cap pulverized product or skull cap extract per person is 0.1 to 2500 mg. In the case of cosmetics, the skull cap pulverized product Alternatively, it is preferable to contain the skull cap extract so as to be dripped, applied or sprayed onto the skin or mucous membrane within the range of 0.01 to 250 mg / cm ² .

  EXAMPLES Next, examples are given to describe the present invention more specifically, but the present invention is not limited to the following examples.

[Example 1]
1 L of 100% ethanol was added to 50 g of dried skull cap powder, extracted by stirring at room temperature for 45 hours, filtered and concentrated under reduced pressure to obtain a skull cap extract as an active ingredient of the antiallergic agent of the present invention. .

[Comparative Example 1]
Other than Skullcaps, Chilemendiso, Hyssop, Summer Savory, Catnip, Spearmint, Sage, Ogon, Rosemary, Peppermint, Thyme, Lemon Balm, Lavender, Basil powder and 1L of 100% ethanol at room temperature and 45 The extract of each Labiatae plant was obtained by carrying out stirring extraction for time, filtering, and concentrating under reduced pressure, respectively.

[Example 2]
1 L of water was added to 50 g of the dried skull cap powder, extracted at 100 ° C. for 1 hour, and the extract was freeze-dried to obtain a skull cap extract as an active ingredient of the antiallergic agent of the present invention.

[Comparative Example 2]
Add 1L of water to 50g powder of Chilemendiso, Hyssop, Summer Savory, Catnip, Spearmint, Sage, Ogon, Rosemary, Peppermint, Thyme, Lemon Balm, Lavender and Basil for 1 hour at 100 ° C. Extraction was carried out, and the extract of each Lamiaceae plant was obtained by freeze-drying the extract.

[Test Example 1]
Using the skull cap extract obtained in Example 1 and the extract of each Lamiaceae plant obtained in Comparative Example 1, the histamine inhibitory effect was examined.

  In this test, an antiallergic test using rat-derived basophil leukemia cells (RBL-2H3) was performed.

Test method
(1) Anti-degranulation test RBL-2H3 cells were pre-cultured with Dulbecco's modified Eagle medium (manufactured by Sigma) containing 10% fetal bovine serum (manufactured by JRH Bioscience) at a CO ₂ concentration of 5% at 37 ° C. Do. After pre-culture, the cells are detached using an EDTA / trypsin solution according to a conventional method, and the cells are collected by centrifugation. RBL-2H3 cells collected in a 24-well culture plate are seeded in each well to 2.0 × 10 ⁵ cells / well and cultured at 37 ° C. for 12 hours. After culturing, the medium is removed, 1 ml of 50 ng / ml anti-DNP-IgE antibody is added per well, and the cells are sensitized at 37 ° C. for 2 hours. The well is washed twice with a modified Tyrode solution (hereinafter referred to as MT), 1 ml of MT in which 600 μg of the test sample is dissolved is added thereto, and incubated at 37 ° C. for 10 minutes. As a control, 1 ml of MT containing no test sample is added and incubated at 37 ° C. for 10 minutes. DNP-HAS antigen (manufactured by Sigma) is added to these so as to be 50 ng / ml, and further cultured at 37 ° C. for 30 minutes, and then the culture supernatant is collected (hereinafter, the culture supernatant is referred to as the supernatant). Further, 100 μl of MT containing 0.1% Triton X-100 is added to the cells in the well to lyse the cells (hereinafter, this lysate is referred to as a cell solution).

(2) Measurement of the amount of histamine Add 100 μl of 0.1M hydrochloric acid to 100 μl each of the supernatant and the cell solution, and centrifuge at 15,000 rpm for 10 minutes at room temperature.
The obtained centrifuge supernatant is separated by HPLC, and the peak area of the obtained histamine is measured (the position of the histamine peak is confirmed by running a histamine sample).
The conditions of HPLC are as follows.
Column: shodex Asahipak ODP50 4E (4.6 x 250 mm, Showa Denko) guard column
Concatenated shodex Asahipak ODP50G 4A (Showa Denko) Mobile phase: Acetonitrile (180 ml), 50 mM sodium boride (820 ml),
o-Phthalaldehyde (134mg), N-acetylcysteine (215mg)
Flow rate: 0.5 ml / min Column temperature: 40 ° C
Detection: excitation wavelength 330 nm, measurement wavelength 430 nm

From the measured peak area of histamine, the histamine release rate (%) is calculated by the following formula.
[Supernatant liquid peak area / (cell liquid peak area + supernatant liquid peak area)] × 100
Based on the obtained histamine release rate, the histamine release inhibition rate (%) is calculated by the following formula.
[(Control release rate−Test product release rate) / Control release rate] × 100
The histamine release inhibition rate (%) thus obtained is shown in FIG.

  From the results of FIG. 1, some of the Lamiaceae plant ethanol extracts showed an inhibitory effect on histamine release, but the skullcap extract showed particularly high activity.

[Test Example 2]
The histamine inhibitory effect was examined in the same manner as in Test Example 1 using the skull cap extract obtained in Example 2 and the extract of each Lamiaceae plant obtained in Comparative Example 2 as samples.
The result is shown in FIG.

  From the results of FIG. 2, it was shown that some of the Lamiaceae plant hot water extracts have an inhibitory effect on histamine release, but the skull cap extract has particularly high activity.

Next, production examples of the antiallergic agent, food and drink, and cosmetics of the present invention are shown.
Example 3 (Tablet)
Skull cap extract obtained in Example 1 5 g
Corn starch 10 g
Lactose 40 g
Carboxymethylcellulose calcium 8 g
Microcrystalline cellulose 27 g
Polyvinylpyrrolidone 7 g
Magnesium stearate 3 g
Total 100 g
Corn skull, lactose, carboxymethylcellulose calcium and microcrystalline cellulose are mixed with the skullcap extract obtained in Example 1, and then an aqueous polyvinylpyrrolidone solution is added as a binder and granulated by a conventional method. To this, magnesium stearate as a lubricant is added and mixed, and then tableted into 100 mg tablets.

[Example 4] (Hard capsule)
10 g skull cap extract obtained in Example 1
Microcrystalline cellulose 55 g
Corn starch 25 g
Lactose 30 g
Polyvinylpyrrolidone 4 g
Magnesium stearate 1 g
Total 125 g
The above ingredients are granulated by a conventional method and then filled into gelatin hard capsules.

[Example 5] (Powder)
Skull cap extract obtained in Example 1 50 g
Microcrystalline cellulose 600 g
Corn starch 300 g
Polyvinylpyrrolidone 50 g
Total 1000 g
The skull cap extract obtained in Example 1 is mixed with microcrystalline cellulose, corn starch and polyvinylpyrrolidone, and powdered by a conventional method.

[Example 6] (Granule)
10 g skull cap extract obtained in Example 1
Lactose 130 g
Corn starch 87 g
Polyvinylpyrrolidone 8 g
L-menthol 15 g
Light anhydrous silicic acid 5 g
Total 255g
In the above formulation, the skull cap extract obtained in Example 1, lactose, corn starch and aqueous polyvinylpyrrolidone solution are mixed and heated and granulated with stirring in a granulator. After cooling, it is sieved to a particle size of 500 μm or less, L-menthol is added, silicic anhydride is added, mixed and packaged (1.0 g) to give granules.

[Example 7] (Candy)
50 g sugar
Minamata 33 g
Citric acid 2 g
Fragrance 0.2g
1.5 g skull cap extract obtained in Example 2
13.3 g of water
Total 100.0 g
Sugar, starch syrup and water are placed in a pan to boil and dissolve, and after the boiling temperature reaches 125 ° C., remove from the fire and add the fragrance, skull cap extract obtained in Example 2. The mixture is poured into a cooling plate with stirring, cooled to 80 ° C., then cut into an appropriate length in a bar shape, and 3.33 g of candy is produced per grain.

[Example 8] (roll bread)
Mix 150g of flour (strong flour) and 2g of dry yeast. Separately, 2 g of the skullcap extract obtained in Example 2, 20 g of sugar, 3 g of sodium chloride and 6 g of skim milk powder are dissolved in 70 g of hot water, and 1 egg is added and mixed well. Add this to the mixture of flour and dry yeast and knead well by hand, then add 40 g of butter and knead well by hand to make 8 dough rolls. Next, after fermenting, a beaten egg is applied to the surface and baked in an oven at 180 ° C. for about 15 minutes to produce a roll. This roll contains about 250 mg of the skullcap extract obtained in Example 2 per piece.

[Example 9] (Udon)
A mixture obtained by dispersing 10 g of the skullcap extract obtained in Example 2 and 15 g of sodium chloride in 150 g of water is mixed well with 300 g of wheat flour (medium flour) and then kneaded. Thereafter, the dough is stretched and cut into widths of about 5 mm to produce udon. When this was boiled with boiling water for about 10 minutes, the appearance, taste and texture were good. This udon contains about 1.2 g of the skullcap extract obtained in Example 2 per serving.

[Example 10] (Fruit juice jelly)
To 200 ml of orange juice, take 4.5 g of gelatin, 45 g of sugar, and 15 g of water, and put on a fire to dissolve the gelatin completely. After confirming that the gelatin is dissolved, 3 g of the skullcap extract obtained in Example 2 is thoroughly mixed and dissolved. Then, it is poured into 4 cups, cooled in a refrigerator for 2 hours or more and hardened to obtain orange juice jelly.

[Example 11] (Green juice)
15 g of the skull cap extract obtained in Example 2 and 585 g of organic green juice (manufactured by Nisshin Pharma) are mixed well, and thereafter, about 3 g of green juice in stick packaging per serving is obtained.

[Example 12] (Cream)
A Squalane 20 g
8 g olive oil
Refined beeswax 5 g
Glycerol monostearate 3 g
Cetostearyl alcohol 2 g
B Polyoxyethylene hydrogenated castor oil 3 g
Skull cap extract obtained in Example 1 2 g
Glycerin 10 g
Purified water Appropriate amount Solution A and solution B are heated to 80 ° C. Add B liquid to A liquid while stirring and emulsify until uniform to obtain a cream.

[Example 13] (Bathing agent)
Glycerol monostearate 10 g
Glycerin 50 g
Rice bran extract 10 g
10 g of skull cap extract obtained in Example 2
Fragrance 0.1g
0.1g of dye
20 g of purified water
Total 100.2g
All components are mixed and emulsified with a homomixer to prepare a bath agent.

6 is a graph showing test results of Test Example 1. 10 is a graph showing test results of Test Example 2.

Claims (2)

  An antiallergic agent containing skullcap or an extract thereof as an active ingredient. A food or drink or cosmetic containing a skullcap or an extract thereof.

Images