JP2007197398A - Oral composition for preventing/treating allergic symptom - Google Patents

Abstract

<P>PROBLEM TO BE SOLVED: To provide an oral composition for preventing/treating allergic symptom, having effects higher than single intake of isoflavone. <P>SOLUTION: The oral composition for preventing/treating the allergic symptom is an extract from a soybean raw material, and contains 2-70 wt.% isoflavone and 2-80 wt.% soybean saponin based on the dry weight of the extract by purification. The oral composition has the effects for treating and preventing various kinds of allergic symptoms associated with IgE such as pollinosis and dermatitis because of having strong IgE production-inhibiting effects. <P>COPYRIGHT: (C)2007,JPO&INPIT

Description

  The present invention relates to an oral composition for preventing / treating allergic symptoms.

  At present, an increase in allergic diseases such as hay fever is a social problem. Furthermore, it is known that chemical mediators such as leukotrienes play a major role in reactions in allergic diseases such as asthma and atopic dermatitis. Allergic reactions are caused by the binding of immunoglobulin (IgE) antibodies to high affinity IgE receptors on the cell membrane surface of mast cells. IgE-bound mast cells release chemical mediators and cause various allergic diseases.

  With regard to allergic diseases, research on the effects of various plant-derived components is progressing for the purpose of prevention and treatment. Among them, some studies on the effects of intake of isoflavones such as daidzein and genistein in legumes such as soybeans and red clover are reported on allergic symptoms. Non-patent documents 1 to 3, Patent documents 1 to 4).

  All of the above documents show the possibility that a single component of isoflavone can alleviate allergic symptoms, but the anti-allergic effect of isoflavone alone is not sufficient, and it has a stronger anti-allergic effect. It is preferable to show.

(References)
WONG WS Fred et al., "Effects of Tyrosine Kinase Inhibitors on Antigen Challenge of Guinea Pig Lung In Vitro", THE JOURNAL OF PHARMACOLOGY AND EXPERIMENTAL THERAPEUTICS, Vol.283, No.1, 131-137, 1997. PARK Kwanha et al., "Anti-asthmatic compound with leukotriene D4 antagonism isolated from Pueraria radix", J. Korean Soc. Agric. Chem. Biotechnol., Vol.44, No.1, 38-39, 2001. ATLURU Durgaprasadarao et al., "Genistein, a Selective Protein Tyrosine Kinase Inhibitor, Inhibits Interleukin-2 and Leukotriene B4 Production from Human Mononuclear Cells", Clinical Immunology and Immunopathology, Vol.59, No.3, 379-387, 1991. JP-T-2002-530346 (International Publication WO00 / 30664) JP 2003-28111 A International Publication WO03 / 097037 JP 2004-26733 A

  It is an object of the present invention to provide an oral composition for preventing / treating allergic symptoms that is more effective than taking isoflavone alone.

  As a result of repeated studies to solve the above problems, the present inventors orally administered a mixture containing isoflavone and soy saponin to a cedar pollen-sensitized mouse, resulting in a stronger blood IgE concentration than when isoflavone alone was administered. The present invention has been completed by finding that it is suppressed.

That is, the present invention for solving the above problems
1. An oral composition for preventing / treating allergic symptoms, characterized by comprising isoflavones and soy saponins;
2. The isoflavone and soybean saponin added in the oral composition are added as an extract from the soybean raw material as described in 1. above. An oral composition for the prevention / treatment of allergic symptoms,
3. 2. The extract added to the oral composition is one obtained by concentrating the content of isoflavone or soybean saponin by purification. An oral composition for the prevention / treatment of allergic symptoms,
4). 2. The extract added to the oral composition contains 2 to 70% by weight of isoflavone and 2 to 80% by weight of soybean saponin per dry weight. An oral composition for the prevention / treatment of allergic symptoms,
5). The extract added to the oral composition is 15 to 95% by weight of malonyl isoflavone glycoside and 0 to 50% by weight of isoflavones other than malonyl isoflavone glycoside, based on the total amount of isoflavone and soybean saponin. And 5 to 60% by weight of soybean saponin. An oral composition for the prevention / treatment of allergic symptoms,
6). 1. The ratio of group A saponin in soybean saponin added to the oral composition is 30% or more. An oral composition for the prevention / treatment of allergic symptoms,
7). 1. The oral composition is a food, drug or feed. An oral composition for the prevention / treatment of allergic symptoms,
8). Use of an isoflavone and soy saponin-containing extract for the manufacture of an oral composition for the prevention / treatment of allergic symptoms.

  Since the oral composition provided by the present invention has a strong IgE production inhibitory effect, it is useful for the treatment and prevention of various allergic conditions involving IgE such as hay fever and dermatitis.

  The oral composition for preventing / treating allergic symptoms disclosed in the present invention is characterized in that isoflavones and soybean saponins are added. The present invention also discloses a method for using an extract containing isoflavone and soybean saponin for the production of an oral composition for preventing / treating allergic symptoms. Hereinafter, the present invention will be described in detail.

  The isoflavone added to the oral composition of the present invention refers to a group of compounds having a 3-phenylchromone skeleton present in beans such as soybeans, kuzu, red clover, clover, and the like. Specifically, daidzein, genistein and aglycone With glycitein as a basic structure, their free glycosides, daidzin, genistin and glycitin; their malonyl glycosides, 6 ″ -O-malonyldaidine, 6 ″ -O-malonylgenistin and 6 ″ -O— Malonyl glycitin; their acetylisoflavone glycosides 6 ″ -O-acetyldidine, 6 ″ -O-acetylgenistin, 6 ″ -O-acetylglycitin, and their metabolites equol and others Biocanin A, formononetin, cumestrol and the like contained in clovers and the like are included.

  The soybean saponin added to the oral composition of the present invention is a general term for saponins contained in soybean raw materials, and is contained in, for example, about 2 to 4% by weight in soybean hypocotyls. Group A saponin, which is a bisdesmoside saponin in which sugar chains are ether-bonded at positions C-3 and C-22 of aglycone, with “Soyasapogenol A” as an aglycone skeleton, and “Soyasapogenol B” as an aglycone skeleton. It is classified into a group B saponin, which is a monodesmoside saponin having a sugar chain ether-linked at the 3-position. In addition, saponins in which the sugar chain part is acetylated have also been reported.

  The isoflavones and soybean saponins added to the oral composition of the present invention are preferably added as extracts from soybean raw materials. Examples of soybean raw materials include whole soybeans, moulted soybeans, moulted and detached hypocotyl soybeans, defatted soybeans, soybean hypocotyls, concentrated soybean protein, and okara. Extracts from soybeans include soy whey that replicates during the production of isolated soy protein, acid cleaning solutions and alcohol cleaning solutions that replicate during the manufacture of concentrated soy protein, and water soaking solutions of soybean that replicate during manufacturing of tofu and soy milk included. There is no particular limitation as to which extract is selected, but it is preferable to use a soybean hypocotyl having a high isoflavone content and a high ratio of group A saponin in soybean saponin.

  The solvent used for the extraction of isoflavones and soybean saponins is not particularly limited, and may be extracted by a known method, preferably an aqueous solvent, more preferably water or alcohols such as methanol, ethanol or propanol alone or mixed. Can be used. For example, an extract containing both isoflavones and soybean saponins can be obtained with good flavor and at low cost by extracting soybean hypocotyls as a raw material with an aqueous solvent or the like. The extract can be made into a state suitable for food, as it is, or can be processed into a concentrated solution by concentration, or processed as a dry powder by spray drying to obtain an extract.

  The isoflavone and soybean saponin-containing extract may be further enriched by isoflavone or soybean saponin content by purification. The purity of the isoflavones can be 2 to 70% by weight, further 4 to 60% by weight, and further 4 to 55% by weight per dry weight. The purity of soy saponin can be 2 to 80% by weight, and further 5 to 70% by weight, based on dry weight.

The purification can be performed by resin treatment such as column chromatography, liquid-liquid distribution method using an organic solvent, or the like. In particular, the method of adsorbing the extract on a synthetic adsorbent and eluting isoflavones and soybean saponins with an appropriate concentration of hydrous alcohol can purify isoflavones and soybean saponins with higher purity by a simple method.
Examples of usable synthetic adsorbents include non-polar synthetic adsorbents such as styrenedivinylbenzene such as Diaion (Mitsubishi Chemical), Sepabeads (Mitsubishi Chemical), and Amberlite (Sumitomo Chemical). . This can be put into a production tank, or packed into a column and brought into contact with an extract to adsorb isoflavones or soybean saponins.
After washing away non-adsorbed components, the adsorbed fraction is eluted with, for example, 20 to 80% by volume of water-containing ethanol, whereby a highly pure isoflavone and soybean saponin-containing composition can be obtained efficiently.

When providing the oral composition of this invention in a liquid form, it is preferable that the isoflavone and soybean saponin containing extract added have a water-soluble property. In this case, a known technique for making the extract water soluble can be used. For example, a method using an additive such as cyclodextrin or an emulsifier can be used. In particular, isoflavone and saponin in an extract containing soy saponin have a specific composition by a purification method described in International Publication WO 2004/57983. It is preferable to do. That is, it is preferable that isoflavones are composed mainly of malonyl isoflavone glycosides. More specifically, the malonyl isoflavone glycoside is 15 to 95% by weight based on the total amount of isoflavone and soybean saponin in the extract, and isoflavones other than malonyl isoflavone glycoside (isoflavone aglycone, free isoflavone glycoside) , And the total amount of acetylisoflavone glycosides) may be 0 to 50% by weight and soy saponin may be 5 to 60% by weight.
Thus, as a method of obtaining an extract whose main component of isoflavone is malonyl isoflavone glycoside, the concentration of hydrous alcohol when eluting isoflavone and soybean saponin from a synthetic adsorbent is set to a relatively low concentration. A method of eluting with a solvent having a higher value is preferred. That is, as described in International Publication WO2004 / 57983, a method of eluting with a hydrous alcohol having an alcohol concentration of about 15 to 40% by weight is preferable.

  In the above isoflavone and soybean saponin-containing extract, the soybean saponin contained is preferably a group A saponin as a main component. That is, the ratio of group A saponin is preferably 30% by weight or more, and more preferably 50% by weight or more. In order to prepare an extract having such a composition, soybean hypocotyls may be selected as soybeans as an extraction raw material.

  By ingesting the oral composition to which the isoflavone and soybean saponin of the present invention are added, the IgE concentration in the blood can be lowered to a high level, and the IgE concentration is higher than that of the oral composition containing isoflavone alone. The effect of lowering is shown. Therefore, as a disease that can be prevented or treated, a high improvement effect is expected for allergic symptoms such as hay fever, skin diseases such as atopic dermatitis, asthma, further itching and swelling.

  The content of isoflavone and soybean saponin in the oral composition of the present invention varies depending on the form and amount of the oral composition and can be appropriately set. Usually, the content in the oral composition can be set by those skilled in the art so that isoflavones and soy saponins can take an effective amount per day. For example, when the intake amount of isoflavone or soybean saponin per day is set to 50 mg, when the intake amount of the oral composition per day is 10 g, the content in the oral composition is 0.5 wt. %.

The oral composition of the present invention is provided, for example, as a drug, food, feed or the like.
When the oral composition of the present invention is provided as a drug, it can be prepared in various dosage forms. That is, in the case of oral administration, it can be administered in the form of solid preparations such as tablets, hard capsules, soft capsules, granules or pills, or liquid preparations such as solutions, emulsions or suspensions. In the case of parenteral administration, it is administered in the form of an injection solution or a suppository, but oral administration is desirable from the viewpoint of simplicity. In the preparation of these preparations, additives that are acceptable for formulation, such as excipients, stabilizers, preservatives, lubricants, emulsifiers, lubricants, sweeteners, colorants, fragrances, tonicity adjusters. , Buffering agents, antioxidants, pH adjusting agents, etc. can be used in combination.

  When the oral composition of the present invention is provided as a food, it is a common food form of cream, margarine, soft drink, dairy product, soy milk, fermented soy milk, soy protein drink, tofu, natto, fried chicken, deep fried Can be formulated into various foods such as candy, hamburger, hamburger, meatballs, fried chicken, nuggets, various prepared dishes, baked goods, cereals, rice cakes, gums and other confectionery, tablets, breads, and cooked rice. Furthermore, since the contents of isoflavones and soy saponins, which are active ingredients in foods, can be easily measured, the effect of the present invention is described in food packaging, commercial pamphlets and the like using these as active ingredients (components involved). It can be made into food for health use (food for specified health use, etc.).

  The oral composition of the present invention can also be provided as a feed. The type of feed is not particularly limited, but in recent years, hay fever of pets such as dogs and cats has become serious, and can be included in feeds such as pet food. By reducing the IgE concentration in feed, it is effective against diseases that can be prevented and treated.

  Polyphenols such as epigallocatechin gallate, epigallocatechin and epicatechin, flavonoids such as kaempferol, quercetin, myricetin, luteolin and the like which are said to be effective for allergy symptoms in the oral composition of the present invention A known synergistic effect can be obtained by adding known antiallergic ingredients.

  The effective intake amount of the obtained oral composition for prevention / treatment of allergic symptoms varies depending on the purpose of use, the target of use, and the form, but in the case of humans, usually about 10 to 100 mg of isoflavone and soybean saponin per day are consumed. What is necessary is just to divide and adjust once or several times so that it can do. The intake of more than the appropriate amount of many medicines may cause safety problems, whereas the active ingredient of the present invention can use natural plant-derived contents, so the intake from the viewpoint of safety The upper limit is almost never a problem.

  Examples are shown below, but the technical scope of the present invention is not limited by these examples.

(Analysis method)
The main analysis methods used in the present invention are as follows.
Analysis of isoflavone: A sample corresponding to 1-10 mg as isoflavone was accurately weighed, and 25 mL of 70% (v / v) ethanol was added thereto. After stirring and extracting at room temperature for 30 minutes, the mixture was centrifuged to obtain an extract. The residue was subjected to the same extraction operation twice more. A total of 3 times of the extract was made up to a volume of 100 mL with 70% (v / v) ethanol and filtered through a 0.45 μm PVDF filter as the test solution. There are 12 kinds of standard tests for isoflavones, namely daidzin, genistin, glycitin, daidzein, genistein, glycitein, malonyldaidine, malonylgenistin, malonylglycitin, acetyldidine, acetylgenistin, acetylglycitin (Wako Pure Chemical Industries, Ltd.) Was used to confirm approximately the same retention time peak. In the quantitative test, 12 kinds of isoflavone concentrations (Daidin equivalent values) were quantified using Daidine standard products, and the true isoflavone concentration was calculated by multiplying by the following quantitative coefficient. Quantitative coefficients of isoflavones: daidzin (1.000), genistin (0.814), glycitin (1.090), malonyl daidzine (1.444), malonyl genistin (1.095), malonyl glycitin (1.351), acetyl daidzin (1.094), acetylgenistin (1.064) The amount of isoflavone was determined from the sum of acetylglycitin (1.197), daidzein (0.583), genistein (0.528), glycitein (0.740) and various isoflavone concentrations. The HPLC conditions of the test solution and standard solution were as shown in Table 1.

(Table 1) HPLC conditions

Saponin quantification method: Methanol was added to soybean extract and reflux extraction was performed. The obtained extract was dried and hydrolyzed with hydrochloric acid methanol. Further, after partitioning with ethyl acetate, derivatization was performed with bis-trimethylsilyl trifluoroaceamide. This was subjected to gas chromatography and quantified from an internal standard (cholesterol caprate). Quantification was carried out by measuring the group A saponin content and the group B saponin content from the calibration curves of soyasapogenol A and soyasapogenol B, which are aglycones, and the total was taken as the total saponin content.

(Production Example 1) -Manufacture of isoflavones and soybean saponin extract-
To 500 g of the soy hypocotyl, 2.0 L of 75% hydrous ethanol was added and extracted with stirring. After the extract was separated by filtration, the extract was concentrated at 50 ° C. under reduced pressure.
The extract thus obtained was dissolved in water, and loaded on SV2 to a column (100 mL) packed with adsorption resin Diaion HP-20 (Mitsubishi Chemical Corporation).
Next, elution was carried out with 30% by volume of water-containing ethanol. This fraction was concentrated under reduced pressure and dried to obtain an extract containing isoflavone and soybean saponin. In the obtained extract, the isoflavone content per wet weight was 50%, and the soybean saponin content was 10%. And, the total amount of isoflavone and soybean saponin is 55% by weight of malonylisoflavone glycoside, and isoflavones other than malonylisoflavone glycoside (total amount of isoflavone aglycone, free isoflavone glycoside, acetylisoflavone glycoside) 29 wt% and soy saponin was 16 wt%. The proportion of group A saponin in soy saponin was 70%.

Example 1
As model animals, 18 4-week-old female BALB / C mice were used. After 1 week of preliminary breeding, the control group (6 animals), the test group (6 animals) and the comparison group (6 animals) were divided into groups so that the average body weights between the groups were almost equal. The cedar pollen extract was administered intranasally for 10 days to produce cedar pollen-sensitized mice. From 7 days before administration of cedar pollen, the control group is 0.5% carboxymethylcellulose (hereinafter CMC), the test group is the extract containing isoflavone and soybean saponin prepared in Production Example 1, and the comparative group is a commercially available high-purity isoflavone-containing extract. The product was suspended in CMC, and the test group and the control group were administered orally continuously for 1 month so that the isoflavone was 100 mg / kg / body weight.

(Table 2) Administration sample

After the administration, whole blood was collected from the orbital venous plexus. FIG. 1 shows the result of preparing serum according to a conventional method and measuring the amount of IgE in blood by ELISA.
As shown in FIG. 1, contrary to expectations from the conventional literature, no decrease in IgE amount was observed in the comparative group containing only isoflavone glycosides other than malonyl isoflavone glycosides. Surprisingly, in the test group to which malonyl isoflavone glycoside and soy saponin-containing extract containing a large amount of soy saponin were added, a decrease in blood IgE level was observed. From the above results, it was shown that a strong IgE production inhibitory effect can be obtained by ingesting the oral composition to which the isoflavone and soybean saponin-containing extract is added.

It is the graph which compared the influence which the oral composition formed by adding isoflavone and soybean saponin exerts on the blood IgE concentration.

Claims (8)

An oral composition for preventing / treating allergic symptoms, comprising isoflavone and soybean saponin added thereto. The oral composition for prevention / treatment of allergic symptoms according to claim 1, wherein the isoflavone and soybean saponin added to the oral composition are added as an extract from soybean ingredients. The oral composition for prevention / treatment of allergic symptoms according to claim 2, wherein the extract added to the oral composition is a product in which the content of isoflavone or soybean saponin is concentrated by purification. The oral composition for preventing / treating allergic symptoms according to claim 3, wherein the extract added to the oral composition contains 2 to 70% by weight of isoflavone and 2 to 80% by weight of soybean saponin per dry weight. object. The extract added to the oral composition is 15 to 95% by weight of malonyl isoflavone glycoside and 0 to 50% by weight of isoflavones other than malonyl isoflavone glycoside based on the total amount of isoflavone and soybean saponin. And an oral composition for preventing / treating allergic symptoms according to claim 4, wherein 5 to 60% by weight of soybean saponin is contained. The oral composition for preventing / treating allergic symptoms according to claim 1, wherein the ratio of group A saponin in soybean saponin added to said oral composition is 30% or more. 2. The oral composition for prevention / treatment of allergic symptoms according to claim 1, wherein the oral composition is a food, drug or feed. Use of an isoflavone and soy saponin-containing extract for the manufacture of an oral composition for the prevention / treatment of allergic symptoms.

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