WO2010035675A1

WO2010035675A1 - Immunopotentiator or antiallergic agent

Info

Publication number: WO2010035675A1
Application number: PCT/JP2009/066203
Authority: WO
Inventors: Fumitaka Ueda; Chihaya Kakinuma; Yuriko Serizawa
Original assignee: Fujifilm Corp
Current assignee: Fujifilm Corp
Priority date: 2008-09-24
Filing date: 2009-09-10
Publication date: 2010-04-01
Anticipated expiration: 2011-03-24
Also published as: JP2010077039A

Abstract

An immunopotentiator or antiallergic agent includes: a pulverized product or extract of a plant belonging to the genus Salacia.

Description

DESCRIPTION

Title of Invention IMMUNOPOTENTIATOR OR ANTIALLERGIC AGENT

Technical Field

This invention relates to an immunopotentiator or antiallergic agent, which comprises a pulverized product or extract of a plant belonging to the genus Salacla.

Background Art

In recent years, allergic symptoms typified by pollinosis, bronchial asthma, atopic dermatitis and the like are one of the diseases having most high morbidity rate in advanced nations . Particularly, it is said that the number of patients of pollinosis adds up to about twenty million even in Japan alone, thus posing a great social problem.

It is known that an allergen-specific IgE antibody excessively produced from the B cell, histamine and leukotriene released from the mast cell and basophilic leukocyte and inclination of the Thl/Th2 balance to Th2 side are directly concerned in pollinosis. The allergen advanced into the living body is incorporated into natural immunity system cells and thereby decomposed, and a part of the information is presented to the T cell via MHC class II. The T cell which received antigen presentation is differentiated and activated into Th2 cell and thereby allows IL-4 or the like cytokine to act upon the B cell. The IgE antibody is produced from the B cell that received stimulation by the Th2 cell and binds to an Fc receptor which is present on the surface of the mast cell and basophilic leukocyte. When the allergen again breaks into the living body and binds to the IgE antibody on the surface of mast cell and basophilic leukocyte, the cells undergo degranulation and thereby release a large amount of histamine and the like chemical mediators and, at the same time, leukotriene and the like are synthesized on the surface of cells. These various substances cause nasal congestion by accelerating vascular permeability and generate airway contraction by contracting smooth muscle. Thus, it has been revealed by degrees that inclination of the Thl/Th2 balance to the Th2 side due to changes in the life style and dietary life, and the like, in the recent years is one of the causes of the increasing tendency of allergic diseases.

At present, a method for lessening chances of contacting with pollen by using a mask, a goggle or an air cleaner, a method for ingesting an antihistaminic or a food having degranulation inhibiting ability or leukotriene synthesis inhibiting ability, such as sweet tea, beefsteak plant leaf and the like, a desensitization therapy which induces tolerance by periodically injecting an allergen itself, and the like are known as the methods for improving symptoms of pollinosis, and their improving effect can be expected to a certain degree (cf., "Supplement Health Bible (written in Japanese) " edited by Japan Supplement Association, p. 74 (2004) and "Pollinosis (written in Japanese)" edited by H. Otsuka, published by Hoken Dojin Sha (1999), and JP-A-2000-041639 and JP-A-2004-217604) .

However, the method for lessening chances of contacting with pollen has a technical limitation, and the antihistaminic and desensitization therapy have a problem regarding their side effects and it cannot be said that there are sufficient effects in the existing functional food, so that these methods are not decisive.

Accordingly, while daily cleaning is recommended at least for preventing exposure to pollen on the one hand, concern has been directed on the other hand toward a functional food which exerts a composite effect of improving allergic constitution by returning the Th2- inclination type immune system to the normal state, while alleviating symptoms of pollinosis and the like by inhibiting release of histamine and the like. On the other hand, the root and trunk of a plant of the genus Salacia have been used as a natural drug by a traditional medical science, aayurveda, in India and Sri Lanka. It has been handed down in Sri Lanka that the root skin of Salacia reticulata is effective in treating rheumatism, gonorrhea and a skin disease and is also used in the treatment of initial stage diabetes mellitus. In India, the root of Salacia oblonga is used in similar treatments and it is said that Salacia chinensis is also used in the treatment of diabetes mellitus, and it has been reported that its action mechanism is the sugar absorption suppressing action based on the α-glucosidase activity inhibition (FOOD Style 21, vol. 6, no. 5, pp. 72 - 78) .

Summary of Invention

The problem that the invention is to solve is to provide a food or pharmaceutical preparation which is safe even when internally used for a prolonged period of time, because it is derive from a natural material and therefore shows fewer side effects, and can prevent pollinosis, atopy and the like allergic symptoms and carcinogenesis based on its immune balance adjusting and immunopotentiation actions.

The present inventors have conducted intensive examinations on the influences of ingestion of Salacia on blood, and as a result, have found for the first time that Salacia has an immunopotentiation action and also has the effect to alleviate allergy by adjusting immune balance.

The invention consists illustratively of the following constitutions.

<1> An immunopotentiator, which comprises: a pulverized product or extract of a plant belonging to the genus Salacia.

<2> The immunopotentiator as described in <1> above, wherein the plant belonging to the genus Salacia is at least one species of plant selected from the group consisting of Salacia reticulata, Salacia oblonga and Salacia chinensis.

<3> The immunopotentiator as described in <1> or <2> above, wherein the pulverized product or extract of a plant belonging to the genus Salacia shows a sucrase 50% inhibition concentration (IC₅₀ value) of from 10 μg/ml to 1,000 μg/ml.

<4> The immunopotentiator as described in any one of <1> to <3> above, which further comprises: a substance capable of binding with a Toll-like receptor.

<5> The immunopotentiator as described in any one of <1> to <4> above, wherein the substance capable of binding with a Toll-like receptor is at least one species selected from the group consisting of a glucopolysaccharide, a lipopolysaccharide and hyaluronic acid, or a degradation product thereof.

<6> A food or pharmaceutical preparation, which comprises : the immunopotentiator as described in any one of <1> to <5> above.

<7> An antiallergic agent, which comprises: a pulverized product or extract of a plant belonging to the genus Salacia.

<8> The antiallergic agent as described in <7> above, wherein the plant belonging to the genus Salacia is at least one species of plant selected from the group consisting of Salacia reticulata, Salacia oblonga and Salacia chinensis .

<9> The antiallergic agent as described in <7> or <8> above, wherein the pulverized product or extract of a plant belonging to the genus Salacia shows a sucrase 50% inhibition concentration (IC₅₀ value) of from 10 μg/ml to 1,000 μg/ml.

<10> The antiallergic agent as described in any one of <7> to <9> above, which further comprises: a substance capable of binding with a Toll-like receptor.

<11> The antiallergic agent as described in any one of <7> to <10> above, wherein the substance capable of binding with a Toll-like receptor is at least one species selected from the group consisting of a glucopolysaccharide, a lipopolysaccharide and hyaluronic acid, or a degradation product thereof.

<12> A food or pharmaceutical preparation, which comprises : the antiallergic agent as described in any one of <7> to <11> above.

Description of Embodiments

The immunopotentiator or antiallergic agent of the invention includes a pulverized product or extract of a plant belonging to the genus Salacia.

The plant belonging to the genus Salacia is a plant of the family Celastraceae growing naturally mainly in Sri Lanka, India and Southeast Asia regions, and more illustratively, one species or more of plants selected from Salacia reticulata, Salacia oblonga, Salacia prinoides, Salacia chinensis, Salacia latifolia, Salacia burunoniana, Salacia grandiflora and Salacia macrosperma are used, of which at least one species of plant selected from Salacia reticulata, Salacia oblonga and Salacia chinensis is desirable.

The pulverized product or extract of a plant belonging to the genus Salacia means a pulverized product, dried product, extract or dried powder (extract powder) or the like of a root, trunk, leaf, flower, fruit or the like edible part. One or more kinds of parts may be used by mixing them. More desirably, an extract powder extracted from a root or trunk is used.

Said extract powder is a product prepared by drying an extract obtained by a solvent extraction from the aforementioned edible part or the like. As the extraction solvent, it may be selected from water, or alcohols including methanol and ethanol, or mixed solvents of water with alcohols or acetone and the like ketones. Preferably, water, an alcohol or an aqueous alcohol is used. More preferably, hot water or ethanol or an aqueous alcohol is used. Regarding the alcohol concentration of the aforementioned aqueous alcohol, those having a concentration of from 30 to 90% by mass, preferably from 40 to 70% by mass, may be used. (In this specification, mass ratio is equal to weight ratio.)

As the drying method, spray drying, freeze drying and the like can be exemplified, though not limited thereto.

It is desirable that the pulverized product or extract of a plant belonging to the genus Salacia, to be used in the invention, has a sucrase 50% inhibition concentration (IC₅₀ value) of from 10 μg/ml to 1,000 μg/ml. When the inhibitory activity is within this range, the action to inhibit absorption of glucose from the digestive tract can be sufficiently obtained, and the feeling of abdominal swelling and generation of gas can also be suppressed. The sucrase 50% inhibition concentration of the extract of a plant belonging to the genus Salacia is more preferably from 10 μg/ml to 600 μg/ml, further preferably from 100 μg/ml to 450 μg/ml.

The sucrase 50% inhibition concentration (IC_5O value) is measured by the following method. [Test method 1] Measurement of sucrase IC_5O value

Preparation of sample solution: A 2 mg portion of a sample (a pulverized product or extract of a plant belonging to the genus Salacia) is weighed and put into a tube and thoroughly suspended in 2 ml of water added thereto, thereby preparing a sample solution having a concentration of 1 mg/ml. This is diluted with water to respective concentrations of 0, 50, 100, 250 and 500 μg/ml .

Preparation of substrate liquid: Sucrose is dissolved in 0.2 M maleate buffer (pH 6.0) to a sucrose concentration of 100 mM, and this is used as the substrate liquid.

Preparation of crude enzyme liquid: A I g portion of intestinal acetone powder rat (mfd. by SIGMA) is suspended in 10 ml of physiological saline and then centrifuged (3,000 rpm, 4°C, 5 min) . The thus obtained supernatant is separated and used as the crude enzyme liquid.

A 400 μl portion of the substrate liquid is added to 500 μl of each of the aforementioned sample solution having respective concentrations and preliminarily heated at 37°C for 5 minutes in a water bath. A 100 μl portion of the crude enzyme liquid is added to each of them and allowed to undergo the reaction at 37°C for 60 minutes. After completion of the reaction, the reaction is terminated by deactivating the enzyme through heating at 95°C for 2 minutes. Determination of concentration of the thus formed glucose is carried out using a commercially available kit for mutarotase glucose oxidase method (Glucose CII Test Wako, mfd. by Wako Pure Chemical Industries) .

Preparation of blank: A 200 μl portion of the substrate liquid and 50 μl of the crude enzyme liquid are added to 250 μl of each of the aforementioned sample solution having respective concentrations and immediately heated at 95°C for 2 minutes to effect thermal deactivation of the enzyme, to be used as blank data.

By preparing a calibration curve from the thus obtained values, the concentration which inhibits 50% of the enzyme activity (IC₅₀ value) is calculated.

When a daily dose or standard daily dose of an immunopotentiator or antiallergic agent is set, the amount of a pulverized product or extract of a plant belonging to the genus Salacia in the daily dose of the immunopotentiator or antiallergic agent is, in the case of using an extract of a plant belonging to the genus

Salacia having an IC₅₀ value of 50 μg/ml for example, preferably from 10 to 600 mg, more preferably from 40 to 450 mg, particularly preferably from 50 to 350 mg.

Desirable amount of a plant belonging to the genus Salacia in the immunopotentiator or antiallergic agent can be optionally calculated from the above-mentioned desirable daily dose. For example, when a tablet having a daily dose of 3 tablets are prepared, it is desirable that it contains 1/3 of the daily dose per tablet. That is, it contains preferably from 3 to 200 mg, more preferably from 13 to 150 mg, particularly preferably from 17 to 117 mg of a pulverized product or extract of a plant belonging to the genus Salacia.

In addition, it is preferable that the value calculated by the following formula 1 is 0.5 or more, more preferably 0.8 or more, particularly preferably 1.7 or more .

The IC₅₀ value the pulverized product or extract as a whole is preferably from 0.1 to 7.5, more preferably from 0.15 to 4.50, particularly preferably from 0.3 to 3.75, as the value calculated by a formula 2.

[Formula 1]

Extract of a plant belonging to the genus Salacia in daily dose of immunopotentiator or antiallergic agent

(mg) /IC50 value (μg/ml) [Formula 2] Mass of immunopotentiator or antiallergic agent

(mg) /IC50 value (μg/ml)

It is preferable that the aforementioned pulverized product or extract of a plant belonging to the genus Salacia contains 0.8% by mass or more, more preferably from 1 to 30% by mass or more, particularly from 3.0 to 11% by mass or more of mangiferin based on the total amount of the extract. In addition, the mangiferin content of the immunopotentiator or antiallergic agent of the invention is preferably 1 mg or more, more preferably from 1.8 to 54 mg, particularly preferably from 5.5 to 19 mg, based on the daily dose.

Mangiferin can be measured by a test method 2.

[Test method 2] Measurement of the mangiferin content

The mangiferin content is measured by the following method using HPLC.

Column: Capcellpack C18 UG120 (4.6 φ x 250 mm, mfd. by Shiseido)

Column temperature: 40°C

Detection: UV 360

Flow rate: 1.0 ml/itiin

Solvent A: 1.0% acetic acid, Solvent B: methanol

Linear gradient (%B) : 15% (0 min) -> 25% (20 min)

A sample is prepared by dissolving it in 50% methanol and then removing the insoluble matter using a syringe filter.

The content is calculated from the detected peak area of mangiferin using a calibration curve of an authentic sample. <Substance capable of binding with a Toll-like receptor>

It is desirable that the iπununopotentiator or antiallergic agent of the invention further contains a substance which can bind and react with a Toll-like receptor (TLR) presenting on the surface of macrophage in the living body.

As such a substance, a substance capable of binding and reacting with TLR 2 and a substance capable of binding and reacting with TLR 4 are desirable, and containment of both of them is further desirable.

As the substance capable of binding and reacting with TLR 2, β glucan and the like glucopolysaccharide or yeasts, lactic acid bacteria, lipopeptides, lipoteichoic acid, riboarabinomannan and the like can be cited, of which β glucan (βl, 3-glucan) is more desirable. Origins of the β glucan, such as plant-derived, fungi-derived, bacteria-derived and the like ones, are not particularly limited, but those which are derived from fungi such as mushrooms (e.g., Agaricus blazei, reishi mushroom and Fomes yucatensis) , yeasts (e.g., baker's yeast and beer yeast) and the like are more desirable.

As the substance capable of binding and reacting with TLR 4, hyaluronic acid or a degradation product thereof, a hyaluronic acid oligomer, a lipopolysaccharide or a Gram-negative bacterium containing the same, mannans and the like can be cited.

It is known that macrophage is activated when a substance capable of binding with a Toll-like receptor binds to a TLR, such as production of cytokine (interferon or TNF-α) , surface expression increase of CD 40, CD 80, CD 86, MHC class II, and the like.

It is desirable that the substance capable of binding with a Toll-like receptor is at least one species selected from a glucopolysaccharide, a lipopolysaccharide and hyaluronic acid, or a degradation product thereof.

It is desirable that the substance capable of binding with a Toll-like receptor is dispersed to a nano scale order. Illustratively, an emulsion or suspension having an average particle diameter of from 1 nm to 1,000 nm is desirable, and the average particle diameter is more preferably from 5 nm to 200 nm.

In addition, the "high concentration emulsion" according to the invention means an emulsion having 0.1% by mass or more of the content of the substance capable of binding with a Toll-like receptor. It is desirable that the high concentration emulsion of the invention has an average particle diameter of 200 nm or more, more desirably from 300 to 10,000 nm or more.

Particle diameter of the emulsion can be measured by a particle size distribution analyzer or the like. The emulsion can be prepared by a conventionally known emulsion preparation method which is described for example in "Techniques for Emulsification and Solubilization (written in Japanese)" (edited by Tsuji, published by Kogyo Tosho) , pp. 65 - 66 and pp. 92 - 105, and both of the flocculation method and dispersion method can be suitably used. In addition, as described in "Emulsifiers for Food Use (written in Japanese) second edition" (edited by Hidaka, published by Saiwai Shobo) , pp. 88 - 90, any on of the methods classified into (1) self emulsification method, (2) soap forming method, (3) simple emulsification method, (4) transfer emulsification method and (5) surfactant method emulsification method is preferable, but when a high concentration emulsion is prepared, the simple emulsification method or surfactant method emulsification method is desirable, and the surfactant method emulsification method is particularly desirable. It is desirable that the emulsion of a substance capable of binding with a Toll-like receptor is prepared via the high concentration emulsion of the invention. Regarding the suspension, it is desirable to prepare it by a crushing method such as shearing, high pressure pulverization and the like, or a method which is effected through the mediation of an enzymatic degradation, thermal degradation, hydrolysis, emulsion polymerization or the like reaction.

When it is prepared via the high concentration emulsion of the invention by the surfactant method emulsification method, it can be prepared by adding the high concentration emulsion, while stirring, to a solution to be used as the emulsion composition. The dilution ratio of this case is preferably from 5 to 1,000 times, more preferably from 10 to 200 times.

Molecular weight of the substance capable of binding with a Toll-like receptor is preferably from 100 to 8,000,000. The molecular weight is more preferably from 1,000 to 1,000,000, further preferably from 3,000 to 300,000.

It is desirable to ingest the substance capable of binding with a Toll-like receptor as a daily dose of generally from 1 to 2,000 mg, further preferably from 50 mg to 1,000 mg.

It is desirable that the substance capable of binding with a Toll-like receptor is contained in the immunopotentiator or antiallergic agent in an amount of from 0.1% by mass to 95% by mass, more preferably from 0.5% by mass to 70% by mass, further preferably from 1% by mass to 50% by mass.

As the substance capable of binding with a Toll-like receptor, various articles on the market may be used, or those which were synthesized by a general method may be used.

<0ther components>

The immunopotentiator or antiallergic agent of the invention may further contain other components, for example, it may contain a lactic acid bacterium, a mineral yeast, a flavonoid, a polyphenol and the like.

It is desirable that the lactic acid bacteria can be orally administered to mammals including human and are bacteria which exert useful actions in the digestive tracts of the living body.

More illustratively, desirable are those which are harmless for their hosts, are relatively resistance to the gastric acid and bile acid, produce lactic acid by settling in the intestines of the living body and have an action to regulate intestinal microbial flora. As such useful lactic acid bacteria, for example, an acidophilus lactobacillus {Lactobacillus acidophilus) , a bifidobacterium (Bifidobacterium longum or the like) , a faecalis bacterium (Streptococcus faecalis) a reuteri lactobacillus (Lactobacillus reuteri) , a casei lactobacillus (Lactobacillus casei) , a plantarum lactobacillus (Lactobacillus plantarum) , a fermentum lactobacillus (Lactobacillus fermentum) , a rhamnosus lactobacillus (Lactobacillus rhamnosus) , an agilis -Lactobacillus {Lactobacillus agilis) , a gasseri lactobacillus [Lactobacillus gasseri) , a mesentericus {Bacillus mesentericus) , a butyric acid bacterium {Clostridium butyricum) or subspecies and the like thereof, and the like can be exemplified, of which the acidophilus lactobacillus {Lactobacillus acidophilus) , the bifidobacterium {Bifidobacterium longum or the like) and the faecalis bacterium {Streptococcus faecalis) are preferred, and these lactic acid bacteria can be used alone or as an optional combination of two or more species .

Obtained origins of these lactic acid bacteria are not particularly limited so far as they are intact strains, and for the sake of convenience, commercially available counterparts can be broadly used.

When a daily dose or standard daily dose of an immunopotentiator or antiallergic agent is set, the amount of the lactic acid bacteria to be used in the invention is preferably from ten million to one hundred billion, more preferably from fifty million to fifty billion, particularly preferably from one hundred million to ten billion, as the number of viable cells of lactic acid bacteria in daily dose of the immunopotentiator or antiallergic agent.

The mineral yeast means a yeast containing minerals. As the minerals, 16 metallic elements of sodium (Na) , potassium (K) , chlorine (Cl) , calcium (Ca) , magnesium (Mg) , phosphorus (P) , sulfur (S) and so-called trace elements iron (Fe) , zinc (Zn) , cupper (Cu) , manganese (Mn), cobalt (Co), chromium (Cr), iodine (I), molybdenum (Mo) and selenium (Se) can be cited. As the mineral yeast to be used in the invention, chromium yeast which contains chromium is desirable. Though kinds of the yeast are not particularly limited, baker' s yeast or beer yeast is desirable.

The chromium content of chromium yeast is preferably from 0.01 to 5 parts by mass, more preferably from 0.05 to 1 part by mass, particularly preferably from 0.1 to 0.3 part by mass, based on 100 parts by mass of the chromium yeast.

The chromium yeast content in an immunopotentiator or antiallergic agent is preferably from 0.5 to 50 parts by mass, more preferably from 1 to 10 parts by mass, particularly preferably from 3 to 5 parts by mass, based on 100 parts by mass of the immunopotentiator or antiallergic agent.

When a daily dose or standard daily dose is set, the amount of the chromium yeast in the daily dose of the immunopotentiator or antiallergic agent is preferably from 5 to 500 mg, more preferably from 10 to 100 mg, particularly preferably from 30 to 50 rag. The amount of chromium in the daily dose of the immunopotentiator or antiallergic agent is preferably from 20 to 200 μg, more preferably from 40 to 150 μg, particularly preferably from 60 to 100 μg.

Flavonoid is a general term for the pigment components distributing in all organs of plants, which is contained mainly in fruits and vegetables and is present particularly in the form of glycosides in green and white vegetables and skins of citrus fruits.

According to the invention, the flavonoid is a general term for the pigment components broadly distributing in plants, and particularly, it means flavan derivatives frequently contained in vegetables and fruits .

As the flavonoid, flavonols, isoflavones and catechins are preferable. Flavonols are known as polyphenols .

Flavonoid is a substance ingested into the body, but is generally hard to be absorbed. However, since flavonoid is effective even at a small amount and is a strong antioxidant, it is known that it suppresses the activity of carcinogens and has blood circulation accelerating action and anti-thrombus action.

According to the invention, flavonoid can be obtained from tea, grape, onion and the like respective origins. In this case, the origins mean those which are extracted from at least a part of an organism. For example, the above-mentioned method for preparing an extract of a plant of the genus Salacia can be employed for the extraction, and the form of the extract can also be the same as described in the above; for example, it may be any one of the filtrate after extraction as such, or its concentrated or diluted state or in the form of its dried powder, or a mixture thereof.

The tea extract containing catechins is prepared from a tea plant which is an evergreen tree belonging to the family Theaceae. As the tea plant, both of the assamica cultivated in India, Sri Lanka and Southeast Asia and Camellia sinensis cultivated in China and Japan can be used. In general, water, an alcohol or a hydrous alcohol is preferably used in the extraction. More preferably, hot water or ethanol or hydrous ethanol is used as the extraction solvent. Regarding the alcohol concentration of the aforementioned hydrous alcohol, those which having a concentration of from 30 to 90% by mass, preferably from 40 to 70% by mass, may be used. As the drying method, spray drying, freeze drying and the like can be exemplified, though not limited thereto.

Polyphenol, catechins and the like antioxidants are contained in the tea extract. It is desirable that catechin, epicatechin, gallocatechin, epigallocatechin, catechin gallate, epicatechin gallate, gallocatechin gallate or epigallocatechin gallate is contained therein, and it is particularly desirable that epigallocatechin gallate is contained therein.

It is preferable that the immunopotentiator or antiallergic agent of the invention contains said tea extract in an amount of from 0.1 to 40% by mass, more preferably from 0.5 to 35% by mass, particularly preferably from 1.0 to 30% by mass.

Also, the flavonols as one of the flavonoid eliminate active oxygen and thereby show anti-oxidation actions such as suppression of arteriosclerosis and improvement of blood circulation. Among the flavonols, resveratrol as one of the polyphenol has been drawing attention as an antioxidant. Resveratrol is constituted from the stilbene backbone and contained in a large amount in the rind of grapes so that it is also contained in red wine produced from grapes .

It is desirable that the invention comprises a grape extract or grape wine concentrate which contains said flavonols as a component.

It is preferable that the immunopotentiator or antiallergic agent of the invention contains the grape extract in an amount of from 0.1 to 30% by mass, more preferably from 0.1 to 10% by mass.

It has been revealed that resveratrol has the actions to burn fat, to prevent a blood vessel system disease, arteriosclerosis, to exert anti-cancer action and to prevent shortening of DNA caused by cell division, and has the effect to prolong life of cells similar to the case of carrying out calorie control, so that it has the excellent effect as a material for preventing life style-related diseases.

The resveratrol content in the immunopotentiator or antiallergic agent of the invention is preferably from 0.0001 to 5.00% by mass, more preferably from 0.001 to 2.00% by mass.

In addition, among the flavonols, quercetin as a polyphenol has been drawing attention as an antioxidant. Quercetin has the flavan structure and is contained in a large amount in onion skins.

Vitamin C absorption support, anti-oxidation action, immune action and the like physiological actions of quercetin have been reported, and it has been revealed that it is effective in suppressing fat absorption and it has been revealed also that it has the excellent effect as a material for preventing life style-related diseases.

The quercetin content in the immunopotentiator or antiallergic agent of the invention is preferably from 0.001 to 15% by mass, more preferably from 0.05 to 10% by mass, further preferably from 0.1 to 5.0% by mass.

It is preferable that the immunopotentiator or antiallergic agent of the invention contains catechin in an amount of particularly from 1 to 50% by mass. As the catechin, a green tea-derived one or the like is particularly desirable.

In addition, it is preferable that the immunopotentiator or antiallergic agent of the invention contains a polyphenol having lipase activity inhibitory effect in an amount of from 2 to 80% by mass. As the polyphenol having lipase activity inhibitory effect, those which are derived from Oolong tea, derived from grape, derived from apple, derived from Lychee, derived from pine bark, derived from kanka and the like are particularly desirable. Applications and pharmaceutical preparations>

The immunopotentiator or antiallergic agent of the invention is intended for mammals including human and orally administered to said mammals. The immunopotentiator or antiallergic agent of the invention may be food (including drinks) , food materials, quasi drugs, pharmaceutical preparations, medicinal materials or quasi drug materials. As other components, various types of carriers pharmaceutically or food sanitarily acceptable as oral preparations, such as fillers, lubricants, stabilizers, dispersing agents, binders, diluents, spices, sweeteners, flavors, colorants and the like, can be exemplified.

The shape of the immunopotentiator or antiallergic agent of the invention is not particularly limited with the proviso that it exerts the effect of the invention, and its examples include tablets, pills, granules, fine subtilaes, chewable preparations, capsules (those which are filled in hard capsules or soft capsules), solutions, chewable tablets, drinks and the like. It may be shapes of other food.

These administration shapes can be prepared using commonly used methods generally known in said field.

In this connection, in the case of tablets, pills and granules, they can be made into certain dosage forms to which commonly use coatings are applied as occasion demands, such as sugar coated tablets, gelatin coated preparations, enteric coated preparations, film coated preparations and the like, and the tablets can also be made into double layer tablets and the like multiple layer tablets.

In addition to the above, vitamins, vitamin-like substances, proteins, amino acids, oils and fats, organic acids, carbohydrate, plant-derived materials, animal- derived materials, microorganisms, food additives, pharmaceutical additives and the like orally ingestible components can be optionally contained in the immunopotentiator or antiallergic agent of the invention. By the ingestion of the immunopotentiator or antiallergic agent of the invention, IFN-γ in the serum is increased and the immune balance therefore is improved. In addition, mass of the blind gut having an intestinal tract immune organ is increased and the number of lymphocytes in the blind gut epithelial cells is increased so that the immune system is activated. Accordingly, alleviation of pollinosis, atopy and the like allergic symptoms, prevention of a cold and prevention of cancer development are expected.

Since the immunopotentiator or antiallergic agent of the invention is derived from an edible natural source, a plant belonging to the genus Salacia, it is safe even when ingested for a prolonged period of time and shows fewer side effects.

Examples

The following describes the invention using examples, but the invention is not limited to the following examples. (Test Example 1)

Parts of the roots and trunks of Salacia reticulata (S. reticulata) and Salacia oblonga (S. oblonga) were pulverized, mixed in equal weights and then subjected to a hot water extraction step at 98⁰C, and the thus obtained liquid was spray-dried to obtain a Salacia extract powder 1. Sucrase IC50 value of the Salacia extract powder 1 was 41.

Wistar male rats (6 weeks of age, about 200 g in body weight) were preliminarily reared for 7 days and then reared by dividing them into the administration groups shown in Table 1, in 5 animals per group. The administration of each aqueous solution (100 mg/ml liquid) was carried out using a stomach tube, and the same volume of water was administered to the control.

In Table 1, the dose was shown by the daily dose to be administered per 1 kg body weight. "Pure White" manufactured by ALPRON CO., LTD. was used as the β glucan, and an article manufactured by NAKAHARA CO., LTD. as a low molecular weight hyaluronic acid (molecular weight 100,000 or less).

Abdominal section was carried out under ether anesthesia after 8 weeks of the rearing, and blood was collected from the ventral aorta to measure IFN-γ as an immunological index (rat IFN-γ ELISA mfd. by COSMO BIO CO . , LTD . was used) .

In addition, by carrying out pathologic autopsy, mass measurement and histopathological examination of each organ were carried out.

Based on the compared results of the respective administration groups, results of IFN-γ, blind gut mass and the number of lymphocytes in blind gut epithelial cells, which showed large differences, are shown in Table 1. In this case, the values were shown as relative values of average values of 5 animals for each group when the control group was regarded as 100.

Table 1 Rat administration groups

Co o

As a result of Test Example 1, the IFN-γ in serum was significantly increased in the inventive examples of the invention in comparison with the comparative examples, thus showing that immune balance was improved. In addition, since mass of the blind gut having an intestinal tract immune organ was increased and the number of lymphocytes in the blind gut epithelial cells was significantly increased in comparison with the control group, it was found that there is an immunopotentiator effect.

In this connection, a difference in body weight was not found among respective groups during the testing period, and abnormalities of liver function, renal function and the like were not found too.

(Test Example 2)

Parts of the roots and trunks of Salacla chinensis were pulverized and then subjected to an extraction step by an aqueous ethanol (30% by volume of ethanol) of 40°C, and the thus obtained liquid was mixed with dextrin and spray-dried to obtain a Salacia extract powder 2 (the dextrin content 30% by mass) .

Powders having the formulations of the samples 1 to 8 of Table 1 were prepared using this Salacia extraction powder, and sucrase IC₅₀ value per 1 sample tablet was measured by the method described in "Test method 1". Using these, the formulation components shown in the following Table 2 were made into tablets to prepare the samples 7 to 12.

The dose for the persons to be tested was set to 3 tablets/day for each sample of Table 2. "Pure White" manufactured by ALPRON CO., LTD. was used as the β glucan, and an article manufactured by NAKAHARA CO., LTD. as a low molecular weight hyaluronic acid (molecular weight 100,000 or less), and "CEOLUS FD-IOl" manufactured by ASAHI KASEI CHEMICALS as crystalline cellulose.

After carrying out sufficient informed consent for 30 patients of whole year allergic rhinitis, one tablet of each of the samples 7 to 12 was orally ingested within 30 minutes after each meal every day by each group of 5 members, and this was repeated for 30 days. After completion of the ingesting period, effects were evaluated by them regarding the rhinitis symptoms, and average value of the results was calculated for each group .

Point Evaluation criteria

0 Almost no change in symptoms

1 Symptoms were slightly improved

2 Symptoms were improved

3 Symptoms were fairly improved The results are shown in Table 2. Table 2

ω

to

From the results of Test Example 2, significant improvement of rhinitis symptoms was found in the inventive examples of the invention in comparison with comparative examples. It was found that this effect is significant when the sucrase IC₅₀ value is smaller than 1,000, and that the effect is further increased by the concomitant use of β glucan.

(Test Example 3) (Tablets which used Salacia extract powder)

Based on the formulation shown in Table 3, a supplement was prepared by preparing tablets and applying shellac coating thereto. The material prepared in Test Example 1 was used as the Salacia extract powder 1, and the following substances as the other respective components .

^• Green tea extract: Sunphenon 100s (contains 55% by mass of catechin) manufactured by Taiyo Kagaku Co., Ltd.

^■ Onion skin extract: manufactured by TAIHO CO., LTD.

• Hematococcus algal pigment: ASTOTS-S (the content of astaxanthins; 20% by mass) , manufactured by TAKEDA SHIKI CO., LTD.

^• Chromium yeast: LALLEMAND BIO-INGREDIENTS (contains 0.2% by mass or more of chromium), manufactured by LALLEMAND Inc. ^• Sucrose lauric acid ester: Ryoto® Sugar Ester L- 1695, manufactured by Mitsubishi-kagaku Foods Corporation ■ Carnitine: manufactured by ILS Inc.

Table 3 Tablet formulation example using the Salacia extract powder of the invention

In February just before the scattering of Japanese cedar pollen (place: Odawara) , after carrying out sufficient informed consent for 10 adults having past history of cedar pollinosis, one tablet of Table 3 was orally ingested within 30 minutes after each meal every day by them, and this was repeated for 60 days to examine its influences after the scattering of Japanese cedar pollen.

As a result, the effect shown by Inventive Example 2 was obtained also by ingestion of the tablet of this formulation. In addition, "constipation was cured", ^Nλmy body became lighter", "it became hard to catch cold" and the like reports were obtained from the ingested volunteers .

(Test Example 4) (A drink which used Salacia extract powder 2)

A drinking liquid was prepared by mixing and dissolving the components of Table 4. This was filled in 50 cc portions in bottles, sterilized by heating at 85°C for 10 minutes and then cooled to room temperature to be used as a drink.

In February just before the scattering of Japanese cedar pollen (place: Odawara) , after carrying out sufficient informed consent for 10 adults having past history of cedar pollinosis, one bottle of the drink of Table 4 was orally ingested within 30 minutes after each meal every day by them, and this was repeated for 60 days to examine its influences after the scattering of Japanese cedar pollen.

The same materials as in the above-mentioned Test Examples 1 to 3 were used as the respective components. Table 4 Drink formulation example using the Salacia extract powder of the invention

The effect shown by Inventive Example 2 was obtained also by ingestion o.f the drink of this formulation. In addition, "girth of the abdomen was reduced", "my body became lighter", "it became hard to have a hangover" and the like reports were obtained from the ingested volunteers .

Industrial Applicability

An immunopotentiator, an antiallergic agent and a food or pharmaceutical preparation, which are safe even when internally used for a prolonged period of time, because they are derive from a natural material and therefore show fewer side effects, are provided by the invention. By internally using them, pollinosis and the like allergic symptoms are alleviated and immune index is improved so that preventive effects for cancers and the like can be expected.

This application is based on Japanese patent application JP 2008-244869, filed on September 24, 2008, the entire content of which is hereby incorporated by reference, the same as if set forth at length.

Claims

1. An immunopotentiator, which comprises: a pulverized product or extract of a plant belonging to the genus Salacia.

2. The immunopotentiator according to claim 1, wherein the plant belonging to the genus Salacia is at least one species of plant selected from the group consisting of Salacia reticulata, Salacia oblonga and Salacia chinensis .

3. The immunopotentiator according to claim 1 or 2, wherein the pulverized product or extract of a plant belonging to the genus Salacia shows a sucrase 50% inhibition concentration (IC₅₀ value) of from 10 μg/ml to 1,000 μg/ml.

4. The immunopotentiator according to any one of claims 1 to 3, which further comprises: a substance capable of binding with a Toll-like receptor.

5. The immunopotentiator according to any one of claims 1 to 4, wherein the substance capable of binding with a Toll-like receptor is at least one species selected from the group consisting of a glucopolysaccharide, a lipopolysaccharide and hyaluronic acid, or a degradation product thereof.

6. A food or pharmaceutical preparation, which comprises : the immunopotentiator according to any one of claims 1 to 5.

7. An antiallergic agent, which comprises: a pulverized product or extract of a plant belonging to the genus Salacia.

8. The antiallergic agent according to claim 7, wherein the plant belonging to the genus Salacia is at least one species of plant selected from the group consisting of Salacia reticulata, Salacia oblonga and Salacia chinensis.

9. The antiallergic agent according to claim 7 or 8, wherein the pulverized product or extract of a plant belonging to the genus Salacia shows a sucrase 50% inhibition concentration (IC₅₀ value) of from 10 μg/ml to 1,000 μg/ml.

10. The antiallergic agent according to any one of claims 7 to 9, which further comprises: a substance capable of binding with a Toll-like receptor.

11. The antiallergic agent according to any one of claims 7 to 10, wherein the substance capable of binding with a Toll-like receptor is at least one species selected from the group consisting of a glucopolysaccharide, a lipopolysaccharide and hyaluronic acid, or a degradation product thereof.

12. A food or pharmaceutical preparation, which comprises : the antiallergic agent according to any one of claims 7 to 11.