JPWO2019074131A1 - Anti-allergic agent containing ginseng extract extracted with silicate - Google Patents

Abstract

An object of the present invention is to provide an antiallergic agent containing a ginseng extract having few side effects and a high suppressive effect on allergic symptoms. Another object of the present invention is to provide an antiallergic food / drink composition, a feed composition, and a cosmetic composition having few side effects and high safety. The present invention is an antiallergic agent containing ginseng and silicate, an antiallergic agent containing ginseng extract extracted using silicate, and the like. Furthermore, the present invention is a food or drink composition, a feed composition, and a cosmetic composition containing the antiallergic agent. [Selection diagram] FIG. 11

Description

The present invention relates to an antiallergic agent containing a ginseng extract extracted with a silicate.

In recent years, allergic diseases such as atopic dermatitis have been increasing not only in infants but also in adults, and have become a serious social problem. There are various causes of atopic dermatitis, not only due to genetic factors, but also due to changes in the constitution itself due to westernization of eating habits, changes in living environment, sealing of housing structure, increased stress, etc. It is also said to be.

Therefore, many antiallergic agents have been developed so far, but in particular, since there are few side effects, a search from substances derived from natural products has been attempted, and among them, ginseng is atopic dermatitis. There is a report that it is effective for (Patent Document 1).

Ginseng contains a group of ginseno saponins called ginsenoside, and is known to have various functions such as antioxidant action, blood pressure promoting action, and anti-inflammatory action (Patent Document 2). ).

However, the effect is not sufficient for the prevention or treatment of allergic symptoms, and a drug capable of further suppressing allergic symptoms is required.

Special Table 2010-528109 Japanese Unexamined Patent Publication No. 2014-015462

An object of the present invention is to provide an antiallergic agent containing a ginseng extract having few side effects and a high suppressive effect on allergic symptoms.
Another object of the present invention is to provide an anti-allergic food / drink composition, a feed composition, and a cosmetic composition having few side effects and high safety.

As a result of intensive research to solve the above-mentioned problems, the present inventor has developed allergic symptoms by adding silicate to ginseng, especially by using ginseng extract extracted with an aqueous solution of silicate. I found that it can be alleviated. The present invention has been completed based on such findings.

That is, the present invention relates to the following antiallergic agents, pharmaceutical compositions, food and drink compositions, feed compositions, cosmetic compositions and the like.
Item 1.
An antiallergic agent containing ginseng and silicate.
Item 2.
An antiallergic agent containing ginseng extract extracted with silicate.
Item 3.
Item 2. The antiallergic agent according to Item 1 or 2, wherein the silicate is an alkali metal silicate or a hydrate thereof.
Item 4.
The antiallergic agent according to any one of Items 1 to 3, wherein the silicate is sodium silicate decahydrate.
Item 5.
The antiallergic agent according to any one of Items 1 to 4, for the purpose of preventing, suppressing, alleviating and / or treating the symptoms of atopic dermatitis.
Item 6.
Item 2. The antiallergic agent according to any one of Items 1 to 5, wherein the antiallergic agent is orally administered. Item 7.
Item 2. The antiallergic agent according to any one of Items 1 to 5, which is administered percutaneously. Item 8.
The ginsenoside extract is ginsenoside F1, ginsenoside F2, ginsenoside F5, ginsenoside Rb1, ginsenoside Rb2, ginsenoside Rc, ginsenoside Rd, ginsenoside Re, ginsenoside Rf, ginsenoside Rg1, ginsenoside Rg2 (S), ginsenoside Rg2 (S). Item 4. The antiallergic agent according to any one of Items 1 to 6, which contains at least one ginsenoside selected from the group consisting of ginsenoside Rh1 (R).
Item 9.
Item 2. The antiallergic agent according to any one of Items 1 to 8, wherein the ginseng extract is an extract of ginseng cultivated using a silicate fertilizer.
Item 10.
A pharmaceutical composition containing the antiallergic agent according to any one of the preceding paragraphs.
Item 11.
An antiallergic pharmaceutical composition containing the antiallergic agent according to any one of the preceding paragraphs.
Item 12.
A food or drink composition containing the antiallergic agent according to any one of the preceding paragraphs.
Item 13.
An anti-allergic food and drink composition containing the anti-allergic agent according to any one of the preceding paragraphs.
Item 14.
A feed composition containing the antiallergic agent according to any one of the preceding paragraphs.
Item 15.
An antiallergic feed composition containing the antiallergic agent according to any one of the preceding paragraphs.
Item 16.
A cosmetic composition containing the antiallergic agent according to any one of the preceding paragraphs.
Item 17.
An anti-allergic cosmetic composition containing the anti-allergic agent according to any one of the preceding paragraphs.
Item 18.
An IL-4 production inhibitor containing ginseng extract extracted with silicate.
Item 19.
An IL-6 production inhibitor containing ginseng extract extracted with silicate.
Item 20.
A TNFα production inhibitor containing ginseng extract extracted with silicate.
Item 21.
An INFγ production inhibitor containing ginseng extract extracted with silicate.
Item 22.
An IgE production inhibitor containing a ginseng extract extracted with a silicate.
Item 23.
A cytokine production inhibitor containing ginseng extract extracted with silicate.

According to the present invention, it is possible to provide an antiallergic agent capable of exerting an excellent effect in suppressing allergic symptoms.
Further, according to the present invention, it is possible to provide an anti-allergic food composition, a feed composition, and a cosmetic composition having few side effects and high safety.

FIG. 1 shows the ginseng of Example 1 cultivated with fertilizer for ginseng (Reference Examples 1 and 2) (day 25) and the ginseng of Comparative Example 1 obtained by the conventional cultivation method. It is a comparative photograph. The ginseng stalk A of Example 1 is characterized by being thicker and shorter than the ginseng stalk B of Comparative Example 1. FIG. 2 is a photograph of ginseng after being cultivated with the fertilizer of Comparative Example 1 in each cultivation period (50 days, 70 days, 90 days, and 115 days). FIG. 3 is a photograph of ginseng after being cultivated for 25 days with the fertilizer for ginseng for cultivating ginseng described in Example 1 (Reference Example 1). FIG. 4 is a schematic diagram of a cultivation system (isolated bed soil cultivation) for cultivating ginseng described in Example 1. FIG. 5 is a schematic diagram of a cultivation system (cultivation using ultrasonic spraying means) for cultivating ginseng described in Example 1. FIG. 6 is a schematic diagram of a cultivation system (cultivation using LED light irradiation means and ultrasonic spraying means) for cultivating ginseng described in Example 1. FIG. 7 is a graph showing the severity of skin symptoms of the antiallergic agent of the present invention (Example 1) and the silicon water of Comparative Example 1, respectively. FIG. 8 is a graph showing serum IgE concentrations of the antiallergic agent of the present invention (Example 1), the silicon water of Comparative Example 1 and the physiological saline (control), respectively. FIG. 9 is a graph showing the concentrations of the inflammatory cytokine INFγ in the results of tests using the antiallergic agent of the present invention (Example 1), the silicon water of Comparative Example 1 and the physiological saline (control). .. FIG. 10 is a graph showing the concentrations of the inflammatory cytokine IL-4 in the results of tests using the antiallergic agent of the present invention (Example 1), the silicon water of Comparative Example 1 and the physiological saline (control). Is. FIG. 11 is a photograph of the cell tissues of the ears of mice stained with respect to the results of tests using the antiallergic agent of the present invention (Example 1), ginsenoside F2 of Comparative Example 2 and physiological saline (control). .. FIG. 12 is a graph showing the serum IgE concentration of the results of the test using the antiallergic agent of the present invention (Example 1), ginsenoside F2 of Comparative Example 2 and physiological saline (control). FIG. 13 is a graph showing clinical scores for the antiallergic agent of the present invention (Example 1) and comparative extracts A to C (Examples 3 to 5). FIG. 14 is a graph showing the serum IgE concentration of the results of tests using the antiallergic agent of the present invention (Example 1) and comparative extracts A to C (Examples 3 to 5). FIG. 15 is a graph showing the serum INFγ concentration of the results of tests using the antiallergic agent of the present invention (Example 1) and comparative extracts A to C (Examples 3 to 5). FIG. 16 is a photograph (FIGS. 16a to 16f) of arms and hands before and after using the antiallergic agent of the present invention (Example 1) on an adult woman. FIG. 17 is a photograph (FIGS. 17a and 17b) of the hands before and after using the antiallergic agent of the present invention (Example 1) on an adult male. FIG. 18 is a photograph (FIGS. 18a-18e) of the face before and after using the antiallergic agent of the present invention (Example 1) on an adult male. FIG. 19 shows the results of measuring the cytokine IL-6 concentration in the cell culture solution by ELISA with or without TNFα stimulation of the antiallergic agent of the present invention (Examples 1, 6 and 7) and the test solution of Comparative Example 3. Is. FIG. 20 shows the results of measuring the IL-6 gene expression level by real-time PCR with and without TNFα stimulation of the antiallergic agent of the present invention (Examples 1, 6 and 7) and the test solution of Comparative Example 3. FIG. 21 shows the TNFα gene expression level measured by real-time PCR with and without TNFα stimulation of the antiallergic agent of the present invention (Examples 1, 6 and 7) and the test solution of Comparative Example 3. FIG. 22 shows the results of the residual rate of atopic dermatitis in mice of the antiallergic agent of the present invention (Examples 1, 6 and 7) and the test solution of Comparative Example 4.

Hereinafter, the antiallergic agent, pharmaceutical composition, food and drink composition, feed composition, cosmetic composition and the like of the present invention will be described in detail.

<Anti-allergic agent>
The antiallergic agent of the present invention contains ginseng and silicate. In addition, the antiallergic agent of the present invention contains ginseng extract extracted with silicate as an active ingredient. Here, the "Korean ginseng extract extracted using silicate" is an extract (or extract) obtained by extracting ginseng with a solution containing silicate or only silicate. ) Means. The Koryojin vine extract extracted using the silicate is the Koryojin 蔘 extract (hereinafter, also referred to as "Korean ginseng extract") extracted with silicon water, and the Koryojin 蔘 extract extracted with silicate. It can be paraphrased as a substance, a silicate extract of Koryojin, a silicon extract of Koryo ginseng, or an extract of Koryojin of the present invention.

In addition, the antiallergic agent containing ginseng and silicate includes not only a composition containing ginseng (for example, ginseng powder) before extraction with silicate and silicic acid, but also a composition containing ginseng. Also included are compositions containing ginseng extract (eg, ginseng extracted with water) and silicon. The antiallergic agent of the present invention can be paraphrased as an antiallergic composition, an antiallergic drug, or an antiallergic pharmaceutical composition.

The silicate silicate is not particularly limited, and examples thereof include an alkali metal silicate or a hydrate thereof; an alkaline earth metal silicate or a hydrate thereof and the like. Among them, as the silicate, a water-soluble silicate (sometimes referred to as water-soluble silicon) is preferable, an alkali metal silicate or a hydrate thereof is more preferable, and a hydrate of an alkali metal silicate is preferable. Is even more preferable.

The alkali metal silicate is not particularly limited as long as it is anhydrides, for _{example, Na 2 SiO 3, Na 4} SiO 4, Na 2 Si 2 O 5, sodium silicate, such as Na ₂ Si ₄ O _9; K _{2 SiO 3, K 4 SiO 4} , K 2 Si 2 O 5, K 2 Si 4 O 9 of potassium silicate such as _{formula: m (M 2 O) ·} n (SiO 2) (m in wherein, n Represents a positive integer and M represents an alkali metal atom.).

The number of hydrates of the alkali metal silicate is not limited, and the monohydrate, dihydrate, trihydrate, tetrahydrate, and water of the alkali metal silicate are not limited. Examples thereof include Japanese products, hexahydrates, heptahydrates, octahydrates, nine hydrates, pentahydrates, and 11 hydrates. Among them, sodium silicate decahydrate _{(Na 2 SiO 3 · 10H 2} O) are preferable.

Na ₂ SiO ₃ · 10H ₂ O is a commercially available product, or, for example, quartz (quartz) and high temperature (about 1,650 ° C. or higher) in the combustion dissolved over a period of 8 hours, the unnecessary components were decomposed crystals (KR10- 0361045 or crystals obtained by the method described in KR10-415594) can be used.

The alkaline earth metal silicate is not particularly limited as long as it is an anhydride, and examples thereof include calcium silicate such as the formula: 2CaO · xSiO ₂ (in the formula, 1 <x <2). ..

The number of hydrates of the alkali metal silicate earth metal salt is not limited, and the monohydrate, dihydrate, trihydrate, and tetrahydrate of the alkali metal silicate are used. Examples thereof include pentahydrate, hexahydrate, heptahydrate, octahydrate, nine hydrate, ten hydrate, and 11 hydrate.

The silicate can be used alone or in combination of two or more.

The silicate can be used in the form of a solid (crystal, granule, powder, etc.), or a solution (or aqueous solution) in which the solid is dissolved in a solvent such as water or ethanol can be used.

The concentration of the solution is not particularly limited, and examples thereof include a range of 0.001 to 20000 ppm. Specifically, a solid silicate can be dissolved in water to produce a concentrated solution type (for example, 5000 ppm to 20000 ppm), and the concentrated solution can be appropriately diluted with water or the like before use.

Ginseng Ginseng is a family Araliaceae ginseng perennial plant, used in medicinal or edible, ginseng (Panax ginseng), also referred to as a Stewartia ginseng (ginseng). The types of ginseng are not particularly limited, and examples thereof include ginseng (American ginseng), Panax notoginseng (Chinese ginseng), and ginseng (Japanese ginseng). In addition, these ginseng can produce processed products such as white ginseng, red ginseng, and black ginseng by a normal drying process.

As the ginseng, the processed product of ginseng can be used as it is. Examples of the treatment include crushing treatment, crushing treatment, heat treatment, drying treatment, extraction treatment, pressure treatment, enzyme treatment, decomposition treatment (for example, hydrolysis treatment), and a combination thereof.

Extraction method The antiallergic agent of the present invention uses ginseng and an extract extracted with a silicate as an active ingredient. Extraction using a silicate can easily enhance the effect of the present invention. As described above, the antiallergic agent of the present invention can be easily prepared and is highly effective, so that it is economically excellent.

The method for producing the silicate extract of ginseng used in the present invention will be described in detail. The site of ginseng used for extraction is not particularly limited, and for example, leaves, stems, roots and the like can be used. The silicate extract of ginseng of the present invention can be extracted using all or a part of the above-mentioned sites of ginseng (leaves, stems, and roots). Above all, it is preferable to extract the whole part of ginseng because it is easy to manufacture or contains many kinds of active ingredients. In addition, since it contains a large amount of an active ingredient as an antiallergic agent, it is possible to extract only the leaves of the ginseng site.

The extraction method is not particularly limited, and for example, Koryojin 蔘 or each part thereof is cut or crushed as it is, dried, crushed after drying, squeezed juice extracted by silicate, or the like. An extraction method that combines immersion, stirring, heating, etc. in a solvent in which is dissolved; a supercritical fluid extraction method and the like can be mentioned.

The solvent for dissolving the silicate is not particularly limited as long as it is a solvent generally used for obtaining an extract, and for example, water; lower alcohols such as ethanol, n-propyl alcohol, isopropyl alcohol, and n-butyl alcohol. Solvents: Organic solvents such as ester solvents such as methyl acetate, ethyl acetate, butyl acetate, isobutyl acetate and propyl acetate can be mentioned. As the solvent, these can be used alone or in combination of two or more kinds. When combined, the extraction operation can be performed using a mixture of a plurality of solvents, or the extraction operation can be performed in order in multiple steps with different solvents. When the above organic solvent is used, if necessary, the extract (extract) after extraction is solidified or liquid-concentrated by removing the organic solvent with an evaporator or the like and concentrating (or condensing). Can be done. After the immobilization or concentration, it can be solvated or diluted with the above water, ethanol or the like. As the solvent for producing the extract, water and ethanol are preferable, and water is particularly preferable, from the viewpoint of operability, safety and environmental friendliness. In the present invention, by using an aqueous silicate solution, the amount of ginseng extract can be increased and the extraction rate can be significantly improved.

The amount of the solvent for extraction is not particularly limited, and is, for example, 1 to 10000 parts by mass, preferably 5 to 1000 parts by mass, and more preferably 10 parts by mass with respect to 100 parts by mass of ginseng. ~ 500 parts by mass.

When an aqueous solution of silicate is used, the concentration of silicate is not particularly limited, and is, for example, 0.1 ppm to 200,000 ppm, preferably 1 ppm to 100,000 ppm, and more preferably 10 to 50,000 ppm.

The amount of silicate is not particularly limited, and is, for example, 1 to 10000 parts by mass, preferably 50 to 1000 parts by mass, and more preferably 100 to 500 parts by mass with respect to 100 parts by mass of ginseng. It is a mass part.

At the time of extraction, it can be extracted by heating or pressurizing / heating. When pressurizing, the pressure is not particularly limited, and is usually selected in the range of 1.01 to 5 MPa, for example. When heating, the temperature may be room temperature or higher, preferably 60 ° C. or higher, and more preferably 100 ° C. or higher.

The extraction time is not particularly limited, and is usually in the range of 1 to 24 hours, preferably 2 to 18 hours, and more preferably 3 to 12 hours.

Then, the mixture containing the extract and the residue is subjected to filtration, centrifugation or the like, if necessary, and the solid component which is the residue is removed to obtain an extract. The removed solid component can be subjected to the extraction operation again, and this operation can be repeated several times. In the present invention, the above extraction step can be performed once, but can also be divided into two or more times for extraction. When extracting two or more times, different extraction conditions can be used.

The extract (or extract) thus obtained may be used as it is, or if necessary, it may be dried by a method such as concentration, freeze-drying, or spray-drying, and used as a powder. Good.

Since the antiallergic agent of the present invention can exert a preventive or therapeutic effect on atopic dermatitis regardless of the use form by oral ingestion or administration or the use form by transdermal application, for example, beverages, foods and feeds. , Cosmetics, pharmaceuticals, etc. can be widely used.

Allergies In the present invention, allergies (allergic diseases) are not particularly limited, and are, for example, type I allergic diseases, type II allergic diseases, type III allergic diseases, type IV allergic diseases, and type V allergic diseases. Etc., and are preferably type I allergic diseases and type IV allergic diseases. The type I allergic disease is not particularly limited, and specifically, for example, urticaria, pollinosis, asthma, PIE syndrome, atopic dermatitis, allergic rhinitis, allergic conjunctivitis, food allergy, drug allergy. , Anaphylaxis, etc. Type IV allergies include inflammations such as contact dermatitis, thyroiditis, and allergic encephalitis, in addition to atopic dermatitis. The antiallergic agent of the present invention can be used for the prevention, suppression, alleviation and / or treatment of these diseases or symptoms. The Koryojin extract extracted using the silicate used in the present invention is not only an antiallergic agent but also has a skin inflammation inhibitory effect, and therefore is a skin inflammation inhibitor or a skin inflammation inhibitor. It can be a composition.

It is useful that the antiallergic agent of the present invention is applied to humans, animals other than humans, birds, fish and the like.

The effective application amount of the antiallergic agent of the present invention is appropriately set according to the form of the agent, the age of the subject, the sex thereof, the expected effect, the type of the active ingredient to be used, and the like. The effective amount (dry weight equivalent) of the antiallergic agent of the present invention is, for example, the effective amount (dry weight equivalent) of the agent per day for an adult (60 kg), which is usually extracted with a silicate. The total amount of the vine extract is 0.001 mg to 100 g, preferably 0.01 mg to 10 g, and more preferably 0.1 mg to 5 g.

In addition, for example, when the preventive or therapeutic agent for atopic dermatitis of the present invention is applied transdermally (externally), the dry weight is usually used as the effective amount of the agent per day for 1 cm ² of the affected area applied to adults. In terms of conversion, the total amount of the Koryojin extract extracted using the above silicate is 0.001 mg to 100 g, preferably 0.01 mg to 10 g, and more preferably 0.1 mg to 5 g. Be done.

The daily intake may be taken once or in several divided doses.

In addition, the antiallergic agent of the present invention includes pharmaceuticals or pharmaceutical compositions, foods and drinks (including functional foods, foods for specified health uses, health supplements, dietary supplements, sick foods, etc.) or food and drink compositions, feeds. Alternatively, it can be used in feed compositions, cosmetics, cosmetic compositions, and the like.

When the antiallergic agent of the present invention is used as a pharmaceutical composition, examples of the dosage form include tablets, capsules, granules, powders, syrups, dry syrups, liquids, suspensions and other oral preparations, inhalants, etc. Examples thereof include enteric preparations such as suppositories, ointments, creams, gels, external preparations for skin such as patches, infusions, and injections. Of these, oral preparations are preferable.

Such dosage forms are commonly used additives, such as excipients, disintegrants, binders, lubricants, surfactants, alcohols, for processed products of the active ingredient Koryojin. It can be produced according to a conventional method by blending water, a water-soluble polymer, a sweetener, a flavoring agent, an acidulant, etc. according to the dosage form. Liquid preparations such as liquid preparations and suspensions may be dissolved or suspended in water or other suitable media immediately before administration, and in the case of tablets and granules, they may be prepared by a well-known method. The surface may be coated.

The content of the processed ginseng product in the pharmaceutical composition varies depending on the dosage form, but is usually in the range of 0.001 to 99% by mass, preferably 0.01 to 80% by mass based on the dry mass. For example, it is desirable that the daily dose can be controlled so that the above-mentioned daily intake for adults can be taken.

<Food and drink composition or feed composition>
In the food and drink composition or feed composition of the present invention, the content ratio of the ginseng extract extracted by using silicate as an active ingredient is not particularly limited, and various food and drink compositions or feed compositions are not particularly limited. It can be set as appropriate according to the type of object.

When the antiallergic agent of the present invention is added to a food or drink composition or a feed composition, the form thereof is not particularly limited, and the antiallergic agent of the present invention can be used in addition to health foods, functional foods, foods for specified health uses and the like. All food and drink compositions or feed compositions that can be blended are included. The food and drink composition can be paraphrased as a food and drink, a beverage, a beverage composition, a food, a food composition and the like. In addition, the feed composition can be paraphrased as feed.

Specifically, it can be in various forms such as liquid foods such as tablets, chewable tablets, powders, capsules, granules, drinks, and tube-intestinal nutritional supplements. The food and drink composition in the form of a formulation can be produced in the same manner as the pharmaceutical composition. Further, the food and drink composition includes tea beverages such as green tea, oolong tea, and tea, soft beverages, jelly beverages, sports beverages, dairy beverages, carbonated beverages, fruit juice beverages, lactic acid bacteria beverages, fermented milk beverages, powdered beverages, cocoa beverages, and purified water. Beverages (juice), butter, jam, sprinkles, margarine and other spreads, mayonnaise, shortening, custard cream, dressings, breads, rice, noodles, pasta, miso soup, tofu, milk, yogurt, soup or sauce It may be prepared as a kind, a confectionery (for example, biscuits, cookies, chocolate, candy, cake, ice cream, chewing gum, tablet) and the like.

The food and drink composition according to the present invention also includes feeds for livestock, racehorses, ornamental animals, birds, farmed fish and the like, pet foods and the like. Since the feed can be used in almost the same composition and form as the food and drink composition, the description regarding the food and drink composition in the present specification can be applied to the feed composition as well.

Food and beverage compositions also include other food materials used in the manufacture of beverages, foods or feeds, various nutrients, various vitamins, minerals, amino acids, various fats and oils, various additives (eg, taste components, sweeteners, etc.) It can be produced according to a conventional method by blending an acidulant such as an organic acid, a surfactant, a pH adjuster, a stabilizer, an antioxidant, a pigment, a flavor) and the like. In addition, the food and drink composition according to the present invention can be produced by adding the antiallergic agent of the present invention to the food and drink that is normally eaten.

In the food and drink composition or feed composition according to the present invention, the content of the processed ginseng extract varies depending on the form of the food and drink composition or feed composition, but is usually based on the dry mass. , 0.001 to 50% by mass, preferably 0.05 to 20% by mass, more preferably 0.1 to 5% by mass. The daily intake may be taken once, or may be taken in several divided doses. It is preferable that the daily intake can be controlled so that the adult can eat and drink the daily intake as described above.

Known antihistamines, antiallergic substances, and immunomodulators can be combined with the antiallergic agent, food and drink composition, or feed composition of the present invention. Antihistamines include tea, perilla, fuki, polyphenols, diphenhydramine hydrochloride, diphenylpyraline hydrochloride, diphenylpyraline theocrate, cremastine fumarate, chlorpheniramine maleate, tripridine hydrochloride, cyproheptadine hydrochloride, promethazine hydrochloride, alienmemazine tartrate, Examples include dimenhidenat. Anti-allergic substances include tea, citrus tea, perilla, oligosaccharide, lactic acid bacterium, anlexanox, ibudilast, sodium cromoglycate, tazanolast, tranilast, pemirolast potassium, repilinast, evastin, azelastine hydrochloride, epinastine hydrochloride, olopatadine hydrochloride, cetirizine hydrochloride, Fexofenadine Hydrochloride, Levocabastine Hydrochloride, Oxatomid, Ketotiphen Fumarate, Emedastin Fumalate, Bepotastine Pesylate, Mequitadine, Loratadine, Ozagrel Hydrochloride, Ceratrodust, Ramatroban, Zafillucast, Prunlucast Hydrate, Montercast Sodium, Tosylate Splatast, etc. Can be mentioned. Immunomodulators include arabinoxylan, lactic acid bacteria, β-glucan, ginger, IL-1α, IL-1β, IL-2, IL-3, IL-4, IL-5, IL-6, IL-7, IL- 8, IL-9, IL-10, IL-11, IL-12, IL-13, IL-15, IL-21, TGF-β, GM-CSF, M-CSF, G-CSF, TNF-α, Examples thereof include TNF-β, LAF, TCGF, BCGF, TRF, BAF, BDG, MP, LIF, OSM, TMF, PDGF, INF-α, INF-β, INF-γ and the like.

Further, in addition to the above, the antiallergic agent, food and drink composition or feed composition of the present invention may include, for example, conjugated linoleic acid, taurine, glutathione, carnitine, creatine, coenzyme Q, glucuronic acid, glucuronolactone, and pepper extract. , Gourd extract, cacao extract, galana extract, garcinia extract, theanine, γ-aminobutyric acid, capsaicin, capsiate, various organic acids, flavonoids, polyphenols, catechins, xanthin derivatives, refractory oligosaccharides such as fructo-oligosaccharides, Polyvinylpyrrolidone and the like may be blended.

<Cosmetic composition>
The cosmetic composition of the present invention contains ginseng extract extracted with silicate. Here, the cosmetic composition can be paraphrased as a cosmetic, a cosmetic, a cosmetic composition, or the like. In the present invention, cosmetics include quasi-drugs in addition to cosmetics under the Pharmaceutical Affairs Law. The cosmetic composition of the present invention may be intended for humans, or may be intended for non-human animals, especially mammals.

In the cosmetic composition of the present invention, the content ratio of the ginseng extract extracted using silicate is not particularly limited and can be appropriately set according to the type of various cosmetic compositions. ..

Further, the method for obtaining the cosmetic composition of the present invention is not particularly limited, and the above active ingredient may be contained at an arbitrary method and timing in a known production method according to the type of various cosmetic compositions. do it.

The cosmetic composition of the present invention is not particularly limited, and is, for example, a lotion, lotion, essence, beauty essence, milky lotion, face wash cream, cream cosmetic, foundation, lipstick, gel, facial mask, toothpaste, hair styling product, etc. Known cosmetics such as soaps, detergents, shampoos and conditioners can be mentioned.

The cosmetic composition of the present invention allows consumers to use without worrying about the fear of various symptoms due to allergic reactions, or by reducing or suppressing the fear.

<Ginseng cultivated using silicate fertilizer>
As the antiallergic agent, food and drink composition, feed composition or cosmetic composition of the present invention, ginseng cultivated using silicate fertilizer can be used.

Ginseng in particular contains ginsenosides. Ginsenosides include ginsenoside F1, ginsenoside F2, ginsenoside F5, ginsenoside Rb1, ginsenoside Rb2, ginsenoside Rc, ginsenoside Rd, ginsenoside Re, ginsenoside Rf, ginsenoside Rg1, ginsenoside Rg2 (S), ginsenoside Rg2 (S), ginsenoside Rg2 (S) It contains at least one selected from the group consisting of R).

Ginseng cultivated using silicate fertilizer has at least the following A) to C)
A) Ginsenoside F2 content in the harvest is 0.1 mg or more / body weight 1 g,
B) Ginsenoside Rg2 (S) content in the harvest is 0.05 mg or more / body weight 1 g, C) Ginsenoside Rf content in the harvest is 0.05 mg or more / body weight 1 g There is.

The content of ginsenoside in ginseng can be increased by a cultivation system or cultivation method using the silicate fertilizer.

Ginsenoside is, for example, a group of peculiar saponins contained in ginseng, and there are more than 20 kinds of them, and it is known that they have various physiological activities such as antioxidant action and blood circulation promoting action. There is.

Examples of ginsenosides include protopanaxadiol-type ginsenosides [eg, Rb1, Rb2, Rc, Rd, (20R) Rg3, (20S) Rg3, Rh2], and protopanaxatriol-type ginsenosides [eg, Re, Rf, Rg1. , Rg2, Rh1], and oleanolic acid-type ginsenosides [eg, RO]. Among them, in the above fertilizer, cultivation system and cultivation method, ginsenoside F1, ginsenoside F2, ginsenoside F5, ginsenoside Rb1, ginsenoside Rb2, ginsenoside Rc, ginsenoside Rd, ginsenoside Re, ginsenoside Rf, ginsenoside Rg1 and ginsenoside Rg1 The content of at least one ginsenoside selected from the group consisting of (S), ginsenoside Rh1 (S), and ginsenoside Rh1 (R) can be increased. Ginseng (young shoots) cultivated with fertilizer containing silicate contains nutritional components (ginsenoside Rf, Rg2s, F2, etc.) that are not contained in shoots cultivated without silicate. .. For example, ginsenoside F2 is a component whose physiological activity such as the effect of preventing or treating atopic dermatitis has been attracting attention in recent years (Patent Document 2).

Fertilizers containing silicates can reduce ginseng stalk length or increase ginseng stalk thickness. Ginseng has underground parts such as roots and above-ground parts such as leaves, stems, and flowers, but according to the cultivation method using fertilizer containing silicate, ginseng is compared with the usual cultivation method. Can be cultivated with thick and short stems. It is presumed that the content of ginsenoside is increased due to such characteristics.

The fertilizer containing a silicate can be used alone or in combination of two or more of the above silicates (or hydrates thereof). The fertilizer containing a silicate may be composed of only the silicate (or its hydrate), but may contain a known fertilizer other than the silicate.

The known fertilizer is not particularly limited as long as it is a fertilizer component other than the above silicate, and examples thereof include fertilizers such as inorganic fertilizers (chemical fertilizers) and organic fertilizers.

Examples of the inorganic fertilizer include nitrogenous fertilizers (lime nitrogen; urea; inorganic acid ammonium salts such as ammonium sulfate, ammonium chloride and ammonium nitrate; alkali metal salts of nitrates such as sodium nitrate and potassium nitrate or alkaline earth metal salts); phosphoric acid. Quality fertilizer (lime perphosphate, lime perphosphate, fused phosphorus fertilizer, alkali metal salt of phosphoric acid such as calcined phosphorus fertilizer or alkaline earth metal salt); potash fertilizer (potassium carbonate, potash chloride, potash sulfate) , Potassium silicate, etc.); Complex potassium phosphate fertilizer (eg, monopotassium phosphate, dipotassium phosphate, etc.); Silica fertilizer (eg, calcium silicate, etc.); Magnesium fertilizer (eg, magnesium sulfate, magnesium chloride, etc.); Zinc fertilizer (eg zinc sulfate, zinc, etc.); Calcium fertilizer (eg, fresh lime, slaked lime, calcium carbonate, etc.); Manganese fertilizer (eg, manganese sulfate, magnesium sulfate, etc.); Boron fertilizer (eg, magnesium sulfate, etc.) Boron, boric acid, borate, etc.); Iron-containing fertilizer (eg, chelated iron (ethylenediamine tetraacetate complex: EDTA-Fe), steel slag, etc.); Copper fertilizer (eg, copper sulfate, etc.); Molybdenum fertilizer (eg, eg, copper sulfate) Examples include ordinary fertilizers (including compound fertilizers) specified in the Fertilizer Control Law such as sodium molybdenate.

The organic fertilizer may be, for example, one containing organic nitrogen such as protein or its decomposition product, amino acid, and ammonia. Specific examples of the organic fertilizer include organic fertilizers such as compost, green manure, blurred fertilizer, and deciduous leaves; food residues such as fish meal, oil cake, okara, kitchen waste, and rice bran, or extracts or concentrates obtained from these; livestock manure, Examples include organic waste such as green manure and waste water containing these organic substances. Known fertilizers can be used alone or in admixture of two or more.

When a known fertilizer is added to a fertilizer containing a silicate, the amount of the known fertilizer is not particularly limited. For example, it is usually 0.001 to 10000 parts by mass, preferably 0.001 to 10000 parts by mass with respect to 100 parts by mass of the silicate. It is about 0.01 to 1000 parts by mass, more preferably 0.1 to 500 parts by mass.

Further, the fertilizer containing silicate includes physiologically active substances (for example, growth regulators such as growth promoters and growth inhibitors), microbial material extracts, pesticides to the extent that the effects of the present invention are not impaired. (For example, herbicides, insecticides, bactericides, acaricides, nematodes, etc.), surfactants (eg, nonionic surfactants, anionic surfactants, carboxylic acid-based surfactants, sulfonic acids Surfactants, sulfate ester surfactants, phosphate ester surfactants, amphoteric surfactants, etc.), vitamins (eg, vitamin B1, vitamin B6, nicotinic acid amide, choline salts, etc.), antiseptic agents (For example, sodium benzoate, sorbic acid, propionic acid, etc.), chelating agent (for example, ethylenediamine tetraacetic acid or a salt thereof; citric acid or a salt thereof (for example, sodium salt, potassium salt, etc.)), pH adjuster, precipitation prevention Other ingredients such as agents, spreading agents, colorants and the like can be added.

When other components are used, the amount used is usually 0.001 to 10000 parts by mass, preferably 0.01 to 1000 parts by mass, and more preferably 0.1 to 500 parts by mass with respect to 100 parts by mass of silicate. It is about a mass part.

Other components may be used alone or in admixture of two or more.

The content of silicate ions in the fertilizer containing silicate is not particularly limited, and is, for example, 20% by mass or less in terms of SiO ₂ , preferably 10% by mass, and more preferably 5% by mass. Further, as the lower limit of the content of the silicate ion, 0.001% by mass is preferable, 0.01% by mass is more preferable, and 0.1% by mass is further preferable.

Cultivation system Ginseng is provided with means for using the above-mentioned silicate-containing fertilizer for ginseng, and can also be provided with ultrasonic spraying means and / or light irradiation means. In addition, known cultivation means used in a plant factory can be adopted for the above cultivation system.

Ultrasonic spraying means The ultrasonic spraying means is not particularly limited, and a known or commercially available ultrasonic spraying device can be used. The conditions such as the spray amount per spray time of the liquid fertilizer, the spray time, and the spray interval are not particularly limited.

The light irradiation means is not particularly limited, and examples thereof include (1) means for irradiating purple illumination light and / or (2) means for irradiating red irradiation light.

Among them, (1) means for irradiating purple light and (2) means for irradiating red light are provided, and (2) the intensity of the red light is 3 to 3 with respect to (1) the intensity of purple light 1. It is preferably in the range of 30.

The peak wavelength of the violet illumination light is substantially 380 to 450 nm, preferably 400 to 445 nm, and more preferably 420 to 440 nm.

The peak wavelength of the red irradiation light is substantially 620 to 750 nm, preferably 700 to 740 nm, and more preferably 710 to 730 nm.

As the light irradiation means, it is preferable that the purple illumination light and the red irradiation light are simultaneously irradiated. The wavelengths of purple light and red light can be changed within the above wavelength range.

Light intensity (intensity)
The amount (intensity) of the violet light and the red light is not particularly limited. For example, the photosynthetic photon Flux Density (PPFD) is 1 to 1000 μmol / m ² s, preferably 10 to 500 μmol / m, respectively. It is about ² s, particularly preferably about ^{20 to} 250 μmol / m ² s. As the PPFD, the amount of light at a distance of about 30 cm from the light source can be measured using a general photon meter.

The light intensity (intensity) ratio of the purple light illumination light and the red light illumination light is, for example, 1: 3 to 30 for "purple: red", preferably 1: 3.2 to 10, and more preferably 1: 3. It is in the range of 5-8, particularly preferably 3.8-4.2. The amount of violet light and red light can be changed within the above range.

Irradiation time
The maximum LED light irradiation time is the entire cultivation period. Further, the shortest time can be arbitrarily set as long as the effect of the present invention is exhibited.

The light irradiation unit includes a light source that emits purple light or red light. Conventionally known light sources can be used alone or in combination as the light sources for violet light and red light.

As the light source, it is preferable to use an optical semiconductor element such as a light emitting diode (LED) or a laser diode (LD) that emits light in which the wavelength can be easily selected and the ratio of light energy in the effective wavelength range is large. When electroluminescence (EL) is used as the light source, the EL may be organic or inorganic.
The opto-semiconductor element is small and has a long life, emits light at a specific wavelength depending on the material, and has no unnecessary heat radiation, so that it is energy efficient, and even if a plant is irradiated in close proximity, no trouble such as leaf burning occurs. Therefore, by using the optical semiconductor element as the light source, it is possible to cultivate the light source at a lower power cost and in a smaller space as compared with other light sources.

Cultivation method Fertilizer containing silicate can be used for the method of cultivating ginseng (hereinafter, also referred to as "cultivation method"). Further, the cultivation method can include an ultrasonic spraying step and / or a light irradiation step. A process can be rephrased as a step.

The form (shape) of the fertilizer containing the silicate is not particularly limited, and any form of generally known fertilizer such as powder, granular, paste, slurry, suspension, and solution can be used. It can be used. Above all, the fertilizer is preferably diluted with an agriculturally acceptable solvent or carrier to a desired concentration to obtain a liquid fertilizer.

Agriculturally acceptable solvents include water (including sterilized water, deionized water, and ultrapure water) or other agriculturally acceptable aqueous solutions. Examples of the aqueous solution include a buffer such as a phosphate buffer solution and a liquid medium.

Examples of the agriculturally acceptable carrier include the above-mentioned other components and the like. When the fertilizer containing the silicate is an aqueous solution, the concentration of the silicate in the aqueous solution is not particularly limited, and is usually 0.001 to 200,000 ppm, preferably 0.01 to 150,000 ppm, and more. It is preferably 0.1 to 100,000 ppm.

The method of applying the fertilizer containing the silicate is not particularly limited, and the same method as the general method of applying the fertilizer can be used. For example, when the fertilizer is a liquid fertilizer, a method of spraying or irrigating the liquid fertilizer on the soil; a method of spraying the liquid fertilizer on the leaf surface of a crop or the like; a method of drip irrigation of the liquid fertilizer; A method of cultivating; a method of spray cultivating the liquid fertilizer can be mentioned.

According to the cultivation system or cultivation method used in the present invention, the cultivation cost in the cultivation of ginseng can be suppressed. In particular, in an artificial medium cultivation method such as hydroponics or a spray cultivation method, an inexpensive cultivated plant can be provided by suppressing the power cost and the fertilizer cost.

The cultivation method includes a step of applying the fertilizer containing the silicate to ginseng. The application method can be appropriately selected depending on the type of soil, ginseng, and the like. For example, fertilizer can be applied to the cultivated soil, preferably the corresponding part of the main root group area of the target crop, by mixing, spraying, irrigation or the like. The cultivation method is not particularly limited, and for example, the fertilizer can be applied to isolated bed soil cultivation, hydroponics, open field cultivation and the like.

In the present specification, "isolated bed soil cultivation" means that culture soil (bed soil, Masa soil, bark, coconut culture soil, peat moss, pearlite, etc.) is added to an isolated cultivation container (bed), and a nutrient solution is instilled. Alternatively, it is a method of irrigating and cultivating crops.

In the present specification, "hydroponics" is a cultivation method in which all or part of the roots of a cultivated plant is immersed in a hydroponic solution, and is, for example, a bottom irrigation method, a bubbling method, or a spray (mist) method. And so on. The bottom irrigation method is a method in which water or nutrient solution is supplied to plants for cultivation by filling the bottom surface of the reincubator with water or nutrient solution. The bubbling method is a method in which water or nutrient solution containing air bubbles is supplied to the underground part of a plant for cultivation. The spraying method is a method of cultivating by spraying water or nutrient solution on the underground part of the plant.

In the present specification, "spray hydroponics" includes, for example, a method of spraying in the form of mist. Examples of such a spraying method include a spraying type using a high-pressure gas, ultrasonic spraying (ultrasonic mist), and the like. The ultrasonic spray is not particularly limited as long as it is a known ultrasonic spray used in plant cultivation.

As the spray hydroponics, the ultrasonic spray method is preferable in that a specific component in ginseng is increased or the growth of ginseng is promoted.

As the cultivation method, an LED light irradiation step can be further provided. The cultivation method can be applied to plant factories, especially fully controlled plant factories. Here, a "fully controlled plant factory" means that in a closed space such as inside a building, weather conditions such as light, humidity, and temperature, supply or replacement of media, etc. are completely systematized, and computer control is performed. It means a factory that grows plants in an artificial environment. In a plant factory, a hydroponic cultivation form is generally adopted from the viewpoints of management, hygiene, labor and the like.

In normal hydroponics, it is cultivated only in hydroponics, but in hydroponics as used herein, the hydroponics can be filled with a support as a scaffold for plants. Supports include, for example, inorganic materials such as urethane, rock wool, sand, gravel, vermiculite, and perlite; Natural organic materials such as; or a combination thereof can also be used.

As for the cultivation conditions such as the light / dark time (light irradiation time and dark time), the weather conditions including the temperature and humidity, and the growing period in the plant factory, the conditions known in the art can be applied to the cultivated plants. Above all, the cultivation method preferably includes the above-mentioned ultrasonic spraying step and LED light irradiation step.

Hereinafter, the present invention will be specifically described with reference to Examples, Comparative Examples, Reference Examples and Test Examples, but the present invention is not limited thereto.

Light source of light irradiation means The following LEDs were used as the light source for the light environment of this test example.
-Purple LED (center wavelength: 430 nm): Red LED (center wavelength: 720 nm)
-A light source having a red light intensity of about 4 with respect to a purple light intensity of 1 was used.
・ PPFD: 220 μmol / m ² sec (distance from light source 30 cm)
・ Working voltage: 24V / 28.8W
・ 600mA constant current method / 30W class high output LED

The following LEDs were used as the light source used in Reference Comparative Example 1.
-LED (center wavelength: 450 nm): LED (center wavelength: 660 nm)
-A light source having a red light intensity of about 2 with respect to a purple light intensity of 1 was used.
・ PPFD: 200 μmol / m ² sec (distance from light source 30 cm)
・ Working voltage: 24V / 28.8W
・ 600mA constant current system / 30W class high output LED.

Cultivation system: Isolation bed soil cultivation method The isolation bed soil cultivation system is as shown in Fig. 4. Pipe (FRP or iron), 2. Prop pipe, 3. Non-woven fabric, 4. Polyethylene (PE) film tunnel, 5. Cultivation bed, 6. Intravenous hose, 7. Seedlings, 8. Black PE film, 9. Straw foam bed, 10. Horticultural floor soil, 11. Rice husks, 12. Black PE film, 13. Drainage ditch, and 14. It has a coaster pipe.

Cultivation system: Spray-cultivation method In spray-cultivation, rhizosphere oxygen is insufficient, and ultrasonic spray-cultivation is useful as a means to solve it.

The ultrasonic spray hydroponics system is as shown in FIG. Pipe (FRP or iron), 16. Non-woven fabric, 17. Vinyl tunnel, 18. Iron support, 19. Cultivation bed, 20. Seedling, 21. Fixing sponge, 22. Bed top plate, 23. Supply pipe, 24. Drainage ditch, 25. Injection nozzle (manufactured by M-Tech Win Co., Ltd., product name: MH-106A (6 wards), humidification method ultrasonic type, power consumption: 240 W, maximum spray amount: 2,800 ± 200 (about 3000 cc) / hr, water method: Automatic water supply system, water pressure used: 0.2 to 6.8 bar, area used about 30 tsubo, external dimensions: 516 (horizontal) x 270 (vertical) x 284 (height)), and 26, 27. It has a non-woven fabric.

As shown in FIG. 6, the cultivation system using the light irradiation means using the LED and the ultrasonic spraying means is 27. LED, 28. Fog injection nozzle, 29. Vinyl cover, 30. Ginseng, 31. Cultivation bed top plate, 32. Cultivation bed, and 33. It has an ultrasonic spray pump.

Conditions for HPLC analysis Ultra-high performance liquid chromatography equipment: LaChromUltra L-2000 U series (manufactured by Hitachi High-Technologies Corporation)

The device is equipped with an eluent reservoir, an HPLC pump (L-2160U), an automatic injection system (L-2200U) and an ultraviolet detector (L-2400U).

Columns: LaChromUltra C18 short-length column (2mm id, 50mm L, 2μm; manufactured by Hitachi High-Technologies Corporation), LaChromUltra C18 middle-length column (2mm id, 100mm L, 2μm; manufactured by Hitachi High-Technologies Corporation)
Eluent A: 20% aqueous acetonitrile solution, eluent B: 80% aqueous acetonitrile solution Column temperature: 30 ° C
Detection: Varian 380-LC
Injection volume: 5.0 μL
Granant: A / B = 100/0 → 0/100 (10min); Flow rate: 0.2mL / min.

<Reference example 1>
Crystal 500g (KOSIBIO Co., Ltd. Ltd) silicon water silicate _{(Na 2 SiO 3 -10H 2 O} ) was dissolved in water 50 liters, an aqueous solution of silicate 1 (10,000 ppm) (hereinafter "silicon It is also called "water".) Was prepared.

<Reference example 2>
Liquid fertilizer A
Liquid fertilizer 1 (500 ml, DAEYU Co., Ltd) containing 1 to 4 below.
1. 1. Calcium nitrate 20g
2. 2. Saltpeter 30g
3. 3. Chelated iron 2.5g
4. Water about 470cc

Liquid fertilizer B
Liquid fertilizer 2 (100 ml, DAEYU Co., Ltd) containing the following 1 to 8.
1. 1. 1st Magnesium Phosphate 4.5g
2. 2. Magnesium sulfate 12.5g
3. 3. Boron or boric acid 150mg
4. Manganese 100mg
5. Zinc 10mg
6. Copper 5mg
7. Sodium molybdate 1 mg
8. Water about 93cc

Liquid fertilizer C
The above liquid fertilizer A (500 g), liquid fertilizer B (100 g) and water (50 L) were mixed together and stirred well to prepare liquid fertilizer C (50600 g) containing the following components 1 to 10.
1. 1. Calcium nitrate _{(Ca (NO 3) 2 ·} 4H 2 O) 4g,
2. 2. Potassium Nitrate (KNO ₃ ) 6g,
3. 3. Chelated iron (ethylenediaminetetraacetic acid complex: EDTA-Fe) 0.5 g,
4. Ammonium dihydrogen phosphate (NH ₄ · H ₂ PO ₄ ) 0.9 g,
5. Magnesium sulfate _{(MgSO 4 · 4H 2 O)} 2.5g,
6. Boron (B) or boric acid (H ₃ BO ₃ ) 0.03g,
7. Manganese _{(MnSO 4 · 4 H2 O)} 0.02g,
8. Zinc _{(ZnSO 4 · 4H 2 O)} 0.005g,
9. Copper _{(CuSO 4 · 5H 2 O)} 0.002g,
10. Sodium molybdate _{(NaMoO 4 · 2H 2 O)} 0.001g.

Silicon water mixed liquid fertilizer Sodium silicate aqueous solution (50 g) and the above liquid fertilizer C (50600 g) were mixed together to prepare fertilizer 2 (50650 g).

<Reference comparison example 1>
Comparative fertilizer 1
The liquid fertilizer C was used as the comparative fertilizer 1.

[Test Example 1 (hydroponics; spray cultivation method)]
The annual seedlings of ginseng were placed at equal intervals (about 4 cm) on the cultivation top plate bed, and the ultrasonic spray spray was placed in the basement and the LED lamp was placed in the aboveground (Fig. 6). Using the above-mentioned silicon water-mixed liquid fertilizer and the reference comparison fertilizer 1, the Koryojin 蔘 was cultivated by the ultrasonic spray cultivation method under each of the above LED light irradiations.

The components of ginseng cultivated in Test Example 1 were analyzed, and the results of the amounts of each component of ginsenoside are shown in Table 1.

<Cultivation result>
Comparative fertilizer 1 usually requires a cultivation period of about 60 to 90 days from implantation to collection of ginseng, whereas silicon water mixed liquid fertilizer should be grown quickly in a cultivation period of 25 days. The production efficiency has improved dramatically.

In addition, as is clear from the results in Table 1, ginseng cultivated using a fertilizer containing silicic acid has a higher ginsenoside content than ginseng cultivated using the conventional comparative fertilizer 1. It has increased significantly. As shown in FIG. 1, the ginseng stalk A cultivated using a fertilizer containing silicic acid has a shorter stalk and is shorter than the ginseng stalk B cultivated using the conventional comparative fertilizer 1. Due to its thickness, fertilizer containing silicic acid was able to harvest ginseng, which is said to be of high quality.

[Test Example 2 (soil cultivation; isolated bed cultivation method)]
The annual seedlings of ginseng were planted at equal intervals (about 4 cm) in the soil of the isolation bed (Fig. 4). Using the above silicon water and the comparative fertilizer 1, the ginseng was cultivated by the soil cultivation method under each of the above LED light irradiations.

The components of ginseng cultivated in Test Example 2 were analyzed, and the results of each component amount of ginsenoside are shown in Table 2.

<Cultivation result>
The fertilizer of the comparative example usually requires a cultivation period of about 60 to 90 days from implantation to collection of ginseng, whereas even a fertilizer containing only silicon water grows quickly in a cultivation period of 25 days. This made it possible to dramatically improve production efficiency.

Further, as is clear from the results in Table 2, the ginsenoside content of ginseng cultivated using the fertilizer containing silicic acid is higher than that of the ginseng cultivated using the conventional comparative fertilizer 1. It has increased significantly. As shown in FIG. 1, the ginseng stalk A cultivated using a fertilizer containing silicic acid has a shorter stalk and is shorter than the ginseng stalk B cultivated using the conventional comparative fertilizer 1. Because it is thick, we were able to harvest ginseng, which is said to be of high quality.

Example 1 (Manufacturing method of ginseng silicon water extract 1)
The Koryojin 蔘 obtained by the cultivation system or cultivation method of Test Example 1 was dried at 90 ° C. for 10 hours, and 60 g of the dried product (water content 12-14%), 100 g of sodium silicate tetrahydrate crystals, And 3 L of water was placed in a pressure cooker and heated at 85 ° C. to 125 ° C. for about 6 hours to obtain a dark brown Koryojin silicon water extract (2970 g, Koryojin vine concentration 2%). About 100 to 120 g of solid components are precipitated in the ginseng silicon water extract. It was found that the extraction speed was faster when the aqueous solution of sodium silicate tetrahydrate was used than when the extraction was performed with water. In addition, ginseng obtained by the cultivation system or cultivation method of Test Example 1 in the same manner as in Example 1 above, except that 100 g of sodium silicate tetrahydrate crystals are not added, is mixed with only 3 L of water. Extraction was performed, but the extraction did not work. Therefore, it was found that it is important to use silicon water.

Example 2 (Manufacturing method of ginseng silicon water extract 2)
60 g of dried ginseng obtained by the cultivation system or cultivation method of Test Example 1 is placed in a pressure cooker, and 3 L of an aqueous sodium silicate tetrahydrate solution (10000 ppm) obtained in Reference Example 1 is further added. , 85 ° C.-125 ° C. for about 6 hours to obtain a dark brown ginseng silicon aqueous extract 2 (2970 g, ginseng concentration 2%). It was found that the extraction speed was faster when the aqueous solution of sodium silicate tetrahydrate was used than when the extraction was performed with water.

Comparative Example 1 (Silicon water)
Crystal 500g (KOSIBIO Co., Ltd. Ltd) silicate _{(Na 2 SiO 3 -10H 2 O} ) in the dissolved with water 50 liters, was prepared silicon water (10,000 ppm).

Comparative Example 2 (F2)
Ginsenoside F2 was purchased from Abcam.

[Test Example 3. Examination of dermatitis symptom relief effect in NC / Ng mice]
(Purpose)
The effect of the ginseng silicon water extract 1 (test object 1) obtained in Example 1 on skin inflammation will be examined.

(Method)
Animals and dosing samples
For NC / Nga mice, 20 5-week-old male mice were purchased from Nippon SLC Co., Ltd. After purchase, the mice were bred in the SPF (specific pathogen free) environment on the 5th floor of the Animal Experiment Resources Division, The University of Tokushima. Next, from 6 weeks of age, 200 μl of the silicon water of Comparative Example 1 in the control group or 200 μl of ginseng extract (10% concentration of ginseng) by extracting the silicon water of Example 1 in the intervention group per day. It was performed once by oral sonde administration.

(Induction of dermatitis and clinical evaluation of dermatitis)
The chest and abdomen of 6-week-old NC / Nga mice were coated with 5% picryl chloride, which induces dermatitis. Then, 1% picryl chloride was applied to the ears of the mice every week. Dermatitis in the ear is classified into 4 severity scores of 0 (asymptom), 1 (mild), 2 (moderate), and 3 (severe), and the average value of the scores of both ears is the clinical symptom. It was quantified as.

(Serum IgE concentration)
Mice were subjected to 1% picryl chloride application for 10 weeks, and then heart blood was collected at 16 weeks of age to obtain serum. Using this, IgE was measured according to the protocol using the Mouse IgE quantitation kit (Bethyl Laboratories Inc.).

(Cytokine concentration)
Cytokine concentration in mouse serum was measured using Mouse INFγ ELISA Kit (R & D systems Inc) and Mouse IL-4 ELISA Kit (R & D systems Inc) according to the attached protocol.

(Statistical analysis)
As a comparison between the two groups, GraphPad Prism 5 was used and analyzed by unpaired T-test, and p <0.05 was considered to be a significant difference.

[result]
Allergy was induced by applying 1% picryl chloride to the ears once a week for 10 weeks from the age of 6 weeks in NC / Nga mice. During this period, the body weight and food intake were measured once a week, and the body weight and food intake were measured between the silicon water administration group of Comparative Example 1 and the Koryojin 蔘 silicon water extract administration group (intervention group) of Example 1. No difference in food intake was observed.

Comparison of Severity of Skin Symptoms The skin symptoms (severity score) of mice were evaluated in both ears. The results are shown in Table 3 and FIG.

[result]
As shown in Table 3 and FIG. 7 (mean score), skin allergic symptoms were apparent in the silicon water administration group of Comparative Example 1, whereas the Koryojin 蔘 silicon water extract administration group of Example 1 was found. Relief of symptoms was observed in (intervention group). Shows the average score. The control group scored an average of 2.3, while the intervention group had a significantly lower mean of 0.5 (p <0.05).

[結果]
表４及び図８に示すように、実施例１の高麗人蔘ケイ素水抽出物投与群（介入群）では、生理食塩水群（コントロール）及び比較例１のケイ素水投与群に比べて、有意にIgEが低値であった（p＜0.05）。 Comparison of Serum IgE Concentration Serum IgE concentration was measured to compare allergic reactions. The results are shown in Table 4 and FIG.

[result]
As shown in Table 4 and FIG. 8, the Koryojin 蔘 silicon water extract administration group (intervention group) of Example 1 was significantly more than the physiological saline group (control) and the silicon water administration group of Comparative Example 1. IgE was low (p <0.05).

[結果]
表５、表６、図９及び図１０に示すように、生理食塩水群（コントロール）及び比較例１のケイ素水投与群では皮膚炎の誘導によりサイトカイン産生が認められるが、実施例１の高麗人蔘ケイ素水抽出物投与群（介入群）では有意に抑制されていることが示唆された（p＜0.05）。 Comparison of cytokine concentrations The inflammatory cytokines INFγ and IL-4 were measured. The results are shown in Tables 5, 6, 9, and 10.

[result]
As shown in Tables 5, 6, 9 and 10, cytokine production was observed by induction of dermatitis in the physiological saline group (control) and the silicon water-administered group of Comparative Example 1, but Koryo of Example 1 It was suggested that it was significantly suppressed in the human silicon aqueous extract administration group (intervention group) (p <0.05).

[Test Example 4. Examination of the effect on immune response in TNP-IgE mice]
(Purpose)
The effect of the ginseng silicon water extract (test object 1) obtained in Example 1 on the immune response in TNP-IgE mice will be examined. Among the ginseng used in the present invention, the ginseng obtained by using the specific cultivation method or cultivation system described in Test Example 1 above has a higher amount of ginsenoside F2 than other ginseng. It was found that there were many (Tables 1 and 2). In addition, since ginsenoside F2 is known to have an effect of improving immunity, it is considered that the effect shown in Test Example 3 described above may also be due to F2, and ginsenoside F2 alone was administered to the ginseng. Compared with the effect of silicon water extract.

(Method)
As for the mice, 6-week-old TNP-IgE mice were purchased from Japan Claire Co., Ltd. and bred at the Animal Experiment Facility of the University of Tokushima. After 1 week of break-in, 200 μl of extract was administered once daily to the Koryojin group (Example 1) and 2.5 mg / kg BW to the F2 group (Comparative Example 2) from 7 weeks of age. Once a day, 200 μl of physiological saline was administered to the control group (control), which was continued for 7 days, and then allergic inflammation was induced by TNP administration. An autopsy was performed 4 days after the administration, the cell tissue of the ear was observed, and the blood sample was analyzed. Serum IgE was measured according to the protocol using the Mouse IgE quantitation kit (Bethyl Laboratories Inc.). In the administration of ginsenoside F2 alone, an amount equivalent to the literature was administered.

[result]
The results of staining the cell tissue of the mouse ear are shown in FIG. Although it is difficult to quantify, ear swelling was improved in the F2 group (Comparative Example 2) than in the control group (control) and in the ginseng group (Example 1) than in the F2 group (Comparative Example 2). It was suggested that there was.

Furthermore, the results of measuring the IgE concentration of serum are shown in Table 7 and FIG.

[result]
As a result, the IgE concentration was lower in the F2 group (Comparative Example 2) and the ginseng silicon water extract group (Example 1) as compared with the control group (control). In addition, the IgE of the ginseng group (Example 1) was lower than that of the F2 group (Comparative Example 2).

That is, ginsenoside F2 alone was found to have an improving effect on the immune response compared to the physiological saline group (control), but the ginseng silicon water extract obtained in Example 1 was more effective. It was. That is, the effect on the immune response may be due to the involvement of components other than sodium silicate tetrahydrate, and also due to the synergistic effect of the components contained in the Koryojin silicon water extract and the silicate. Conceivable.

As described above, the ginseng silicon water extract (test object 1) obtained in Example 1 can suppress atopic dermatitis as compared with the F2 group (Comparative Example 2) and the control group (Control). It was clear that

[Test Example 5. Comparison with other companies' ginseng]
(Purpose)
For the antiallergic agent (Korean ginseng extract) of the present invention, it was confirmed whether the ginseng itself used in this test is important, or whether the extraction method using both ginseng and silicon water is important. ..

Examples 3-5
(Method)
The following ginseng A, B, and C were prepared.
・ Ginseng A: (manufactured by Haeung Insan Processing Co., Ltd., 6-year-old root, open-field cultivation)
・ Ginseng B: Ginseng (made by Haeung Insan Processing Co., Ltd., 4-year-old root, open-field cultivation)
・ Ginseng C: Ginseng (manufactured by Happy and Joy, 1 year root, hydroponics (50 days cultivation))
Comparative extract A (Example 3) and comparative extract B in the same manner as in Example 1 except that ginseng A to C were used in place of the ginseng used in Example 1. (Example 4) and comparative extract C (Example 5) were obtained.

As the mouse, a TNP-IgE mouse was used. The detailed test method is the same as that of Test Example 4, and the ginseng silicon water extract obtained in Example 1 and the comparative extracts A to C obtained in Examples 3 to 5 above were used in mice. The test was performed and the clinical scores of inflammation of the forelimbs, hindlimbs, and ears were evaluated up to 6 points. The results are shown in Table 8 and FIG.

[result]
As a result, as shown in Table 8 and FIG. 13, the ginseng silicon water extract obtained in Example 1 showed the history of the lowest score. In addition, for one week (up to 7 days) after the onset induction, the extracts of Example 1 and the comparative extracts A, B, and C of Examples 3 to 5 all contain silicates to prevent allergies. It showed an effect. In particular, the ginseng silicon water extract obtained in Example 1 showed a high anti-allergic effect.

[結果]
表９、表１０、図１４及び１５に示すように、血清IgE及び血清INFγについても、実施例１で得られた高麗人蔘ケイ素水抽出物が、最も低い値を示した。また、発症誘導後１週間（７日まで）の間、実施例１の抽出物、実施例３〜５の比較抽出物A、B及びCは何れも、ケイ酸酸塩を含むことで抗アレルギー効果を示した。特に、実施例１で得られた高麗人蔘ケイ素水抽出物が高い抗アレルギー効果を示した。 The inflammatory cytokines IgE and INFγ were measured. The results are shown in Table 9, Table 10, FIG. 14 and FIG.

[result]
As shown in Tables 9, 10, 14 and 15, the ginseng silicon water extract obtained in Example 1 also showed the lowest values for serum IgE and serum INFγ. In addition, for one week (up to 7 days) after the onset induction, the extracts of Example 1 and the comparative extracts A, B, and C of Examples 3 to 5 all contain silicates to prevent allergies. It showed an effect. In particular, the ginseng silicon water extract obtained in Example 1 showed a high anti-allergic effect.

[Test Example 6. Tests for humans (female)]
A few drops (2 mg) of ginseng extract (2% concentration of ginseng) extracted with silicon water was applied to the arm of an adult woman (about 50 kg) three times a day for one week. In addition, ginseng extract (Korean ginseng concentration 2%) extracted with silicon water was applied to the hands of a woman (about 50 kg) in several drops (2 mg) three times a day for 2 months. After using the above ginseng extract, the condition of the skin of the arms and hands was visually observed.

[result]
As a result, the symptoms of atopic dermatitis of the hands and arms (FIGS. 16b, 16d, and 16f) after using the ginseng extract were higher than those before the use (FIGS. 16a, 16c, and 16e). Clearly improved. In addition, the itching symptoms of the subjects were significantly improved.

[Test Example 7. Tests on humans (males)]
The ginseng extract (Korean ginseng concentration 2%) by silicon water extraction used in Example 1 was diluted 100-fold, and 500 mg was orally administered to an adult male (about 65 kg) four times a day. In addition, several drops (2 mg) of ginseng extract (2% concentration of ginseng) extracted with silicon water were applied to the face and hands three times a day. After using the above ginseng extract, the condition of the skin of the hands and skin was visually observed based on the following judgment. The results are shown in Table 11.

(Judgment)
3: Symptoms of allergic dermatitis improved significantly.
2: The symptoms of allergic dermatitis improved.
1: The symptoms of allergic dermatitis were terrible.

[result]
As a result of continuous oral administration for 3 months, the symptoms of atopic dermatitis on the hands and face (Fig. 17b, Fig. 18c and Fig. 18d) after using the ginseng extract (Fig. 1) before its use (Fig. Compared with 17a, FIG. 18a and FIG. 18b), the condition of the skin became clearer and clearly improved. Furthermore, as a result of continuous oral administration for 6 months (9 months in total), the symptoms of atopic dermatitis on the face (FIG. 18e) after using the Koryojin 蔘 extract of Example 1 (after use 2) are as described above. Compared with 3 months after the administration (FIGS. 18c and 18d), the condition of the skin became clearer and the atopic (allergic) symptom could be remarkably suppressed. In addition, the itching symptoms of the subjects were significantly improved.

[Test Example 8. Culture and stimulation experiments of human skin fibroblasts]
Human skin fibroblasts (NHDF: Normal Human Dermal Fibroblasts) were obtained from Cell research.
NHDF was cultured in DMEM (Dulbecco's Modified Eagle Medium) / 10% FBS (fetal bovine serum) and subcultured into 6-well plates.
Then, at 80% confluence (very close and dense), Example 1 (stock solution), Example 6 (concentration of the stock solution diluted to 1/10 with water), Example, with respect to 2 ml DMEM. 7 (concentration of undiluted solution diluted to 1/100 with water) and 20 μl of test solution of Comparative Example 3 (untreated group; water) were added.
Eight hours after the addition, stimulation was performed with TNFα, and 16 hours later, cells were recovered from the medium with a TRIzol (registered trademark) reagent, and RNA was extracted.

<IL-6 concentration with and without TNFα stimulation>
The cytokine IL-6 concentration (pg / ml) in the cell culture medium with and without TNFα stimulation was measured by ELISA (Enzyme-Linked ImmunoSorbent Assay). The results are shown in Table 12 and FIG.

[result]
As a result of Table 12, by treating the cells after stimulating the test solutions of Examples 1, 6 and 7 of the present invention with TNFα, the IL-6 concentration was higher than that of the untreated group (water) of Comparative Example 3. Was clearly reduced.

<Expression levels of IL-6 and TNFα genes with and without TNFα stimulation>
RNA extracted from the cell fraction was converted to cDNA and real-time PCR was performed using the Step One ^TM real-time PCR System (Applied Biosystems). Fast SYBR® Green master Mix (Applied Biosystems) 10 μl, cDNA 2 μl, Primer (final concentration 0.4 μM) was stirred in the plate (95 ° C x 20 seconds, 95 ° C x 3 seconds, 60 ° C x 30). The seconds were set to 40 cycles, 95 ° C. × 15 seconds, 60 ° C. × 1 minute, 95 ° C. × 15 seconds). Quantitative analysis of IL-6 and TNFα was performed. Primers were prepared using Primer3Plus based on the reported cDNA sequence. The expression of each gene was corrected by GADPH as an internal control and shown as a relative value based on the control group. The results are shown in Table 13, Table 14, FIG. 20 and FIG.

[result]
As a result of Table 13, the test solutions of Examples 1, 6 and 7 of the present invention were treated with cells after stimulating TNFα, as compared with the untreated group (water) of Comparative Example 3. The IL-6 concentration was clearly reduced.

[result]
As a result of Table 14, by treating the cells after stimulating TNFα with the test solutions of Examples 1, 6 and 7 of the present invention, the TNFα concentration was increased as compared with the untreated group of Comparative Example 3. Obviously decreased.

[Test Example 9. Experiments on mouse atopic dermatitis]
4% SDS (Sodium Dodecyl Sulfate) was applied to the back of NC / Nga mice at a rate of 100 mg / animal twice a week. The onset of dermatitis began to be observed after 3 to 4 applications, and up to 80% of the cases were confirmed by the 6 to 8 applications. The area of dermatitis after 8 times of application was measured and set to 100%. Then, 200 μl of the sample of Example 1 (stock solution), 200 μl of the sample of Example 6 (concentration of 1/10 of the stock solution), and the sample of Example 7 (concentration of 1/100 of the stock solution). 200 μl per animal and 200 μl of Comparative Example 4 (water) were applied daily for 14 days each. Table 15 and FIG. 22 show the percentage of the area of dermatitis on the back after 2 weeks with respect to 100%.

[result]
As a result of Table 15, the test solutions of Examples 1, 6 and 7 of the present invention clearly reduced the residual rate of atopic dermatitis in mice as compared with the water of Comparative Example 4 alone.

An example of the method for producing the antiallergic agent (pharmaceutical composition) of the present invention is described below.
Formulation Example 1 Tablets A tablet having the following composition was produced according to a conventional tablet method.

Formulation amount per tablet (mg)
Ginseng Silicon Water Extract Produced in Example 1 73.1
Theanine 16.0
Rice germ oil containing ceramide glycolipid 1.6
(Contains 37.5% by weight of ceramide glycolipid)
Powder reduced maltose 100.0
Starch 0.28
Calcium carbonate 2.1
Dextrin 56.5
Crystalline cellulose 34.42
Sucrose fatty acid ester 15.0
Total amount per tablet (mg) 300.0

Formulation Example 2 Ointment An ointment having the following composition was produced according to a conventional method.

Blending ratio (% by weight)
Ginseng Silicon Water Extract 3 Produced in Example 1
White petrolatum 25
Stearyl alcohol 22
Propylene glycol 12
Sodium lauryl sulfate 15
Methyl paraoxybenzoate 0.02
Propyl paraoxybenzoate 0.015
Purified water Appropriate amount 100% by weight

An example of the method for producing the food composition of the present invention is described below.
A candy having the following composition was produced according to a conventional method.
Prescription example 3 (candy)
(weight%)
Ginseng Silicon Water Extract Produced in Example 1 0.5
Sugar 47.5
Syrup 49.0
Fragrance 1.0
Water 2.0

Prescription example 4 (soft drink)
(weight%)
Ginseng Silicon Water Extract Produced in Example 1 0.5
Fructose-glucose solution 20
Liquid yogurt 30
Emulsifier 0.5
Sodium hyaluronate (molecular weight 50,000 to 150,000) 0.5
Rotgenic acid 0.001
Fragrance Appropriate amount Purified water 100 in total

(Prescription example 5) Tablet-type health food
(weight%)
Ginseng Silicon Water Extract 3 Produced in Example 1
Chondroitin sulfate 2
Hyaluronic acid 0.5
N-Acetylglucosamine 40
Collagen extract powder 7.5
Rotgenic acid 0.001
Crystalline cellulose 9
Sucrose fatty acid ester 3
Fine silicon oxide 2
Make the total amount of maltitol 100

The method for producing the antiallergic agent (cosmetic composition) of the present invention is described below.
Prescription example 6 (toner)
(weight%)
Panax ginseng silicon water extract produced in Example 1 2.0
Nicotinamide 2.0
1,3-butylene glycol 3.0
Concentrated glycerin 2.0
Polyoxyethylene / methylpolysiloxane copolymer 0.3
Ethanol 7.0
Preservatives Appropriate amount Fragrances Appropriate amount
pH adjuster Appropriate amount of purified water Residual total 100% by weight

Prescription example 7 (essence)
(weight%)
Panax ginseng silicon water extract produced in Example 1 3.0
Dipropylene glycol 5.0
Concentrated glycerin 3.0
Sodium hyaluronate 0.2
Xanthan gum 0.2
Polyoxyethylene hardened castor oil 0.3
Ethanol 5.0
Preservatives Appropriate amount Fragrances Appropriate amount
pH adjuster Appropriate amount of purified water Residual total 100% by weight

1. 1. Pipe (FRP or iron), 2. Prop pipe, 3. Non-woven fabric, 4. PE film tunnel, 5. Cultivation bed, 6. Intravenous hose, 7. Seedlings, 8. Black PE film, 9. Straw foam bed, 10. Horticultural floor soil, 11. Rice husks, 12. Black PE film, 13. Drainage ditch, 14. Coaster pipe, 15. Pipe (FRP or iron), 16. Non-woven fabric, 17. Vinyl tunnel, 18. Iron support, 19. Cultivation bed, 20. Seedling, 21. Fixing sponge, 22. Bed top plate, 23. Supply pipe, 24. Drainage ditch, 25. Injection nozzle, 26. Nonwoven fabric, 27. LED, 28. Fog injection nozzle, 29. Vinyl cover, 30. Ginseng, 31. Cultivation bed top plate, 32. Cultivation bed, 33. Ultrasonic spray pump

Claims (12)

An antiallergic agent containing ginseng and silicate. An antiallergic agent containing ginseng extract extracted with silicate. The antiallergic agent according to claim 1 or 2, wherein the silicate is an alkali metal silicate or a hydrate thereof. The antiallergic agent according to any one of claims 1 to 3, wherein the silicate is sodium silicate tetrahydrate. The antiallergic agent according to any one of claims 1 to 4, for the purpose of preventing, suppressing, alleviating and / or treating the symptoms of atopic dermatitis. The antiallergic agent according to any one of claims 1 to 5, wherein the antiallergic agent is orally administered. The antiallergic agent according to any one of claims 1 to 5, which is characterized by being administered transdermally. The ginsenoside extract is ginsenoside F1, ginsenoside F2, ginsenoside F5, ginsenoside Rb1, ginsenoside Rb2, ginsenoside Rc, ginsenoside Rd, ginsenoside Re, ginsenoside Rf, ginsenoside Rg1, ginsenoside Rg2 (S), ginsenoside Rg2 (S). The antiallergic agent according to any one of claims 1 to 7, which contains at least one ginsenoside selected from the group consisting of ginsenoside Rh1 (R). The antiallergic agent according to any one of claims 1 to 8, wherein the ginseng extract is an extract of ginseng cultivated using a silicate fertilizer. A food or drink composition containing the antiallergic agent according to any one of claims 1 to 9. A feed composition containing the antiallergic agent according to any one of claims 1 to 9. A cosmetic composition containing the antiallergic agent according to any one of claims 1 to 9.

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