JP6684632B2 - Anti-type I allergy suppression enhancer and anti-type I allergy suppression enhancer food - Google Patents

Description

The present invention relates to an anti-type I allergy suppression enhancer that contains an extract component extracted from a plant body as an anti-allergic active ingredient, and a method for using the anti-type I allergy suppression enhancer.

In recent years, the number of people showing allergic symptoms such as hay fever, allergic rhinitis, food allergies, contact dermatitis, atopic dermatitis, and bronchial asthma has been increasing, becoming a major social problem. Allergies are an example of an excessive immune response, and are classified into types I to IV. Allergic diseases such as hay fever and atopic dermatitis, which have attracted a lot of social attention, are type I allergies.

Type I allergy develops through the following process:
(1) When allergens such as pollen and mold enter the body, IgE (immunoglobulin E) type antibodies corresponding to the allergens are produced in excess by B cells.
(2) The produced IgE antibodies bind to the high-affinity IgE receptor (FcεRI) expressed on the surface of mast cells (also called mast cells) and basophil cells (sensitization), creating a state in which the body is primed for an allergic reaction (sensitized state).
(3) The allergen again invades the body and cross-links the IgE antibodies on the surface of sensitized cells (antigen-antibody reaction).
(4) This stimulation causes the release of chemical mediators such as histamine and leukotrienes (degranulation).
(5) Chemical mediators induce allergic symptoms such as inflammation and increased vascular permeability in the surrounding tissues.

Patients who have developed such type I allergies are usually administered drugs such as antihistamines and steroids. Although these drugs are highly effective, they have side effects such as drowsiness, dry mouth, and gastrointestinal disorders. Furthermore, since long-term medication is required to improve allergic symptoms, it is desirable to have an anti-allergy drug that is highly safe and can be used continuously, rather than a drug that may have side effects. Anti-allergy drugs derived from natural sources are considered to be safer than the above-mentioned drugs. For example, Patent Documents 1 to 6 report anti-allergy drugs derived from plants.

Patent Document 1 describes that extracts of plants of the genus Helichrysum have anti-allergic effects such as inhibitory activity against interleukin 4 signaling (inhibitory activity against IgE class switching), reducing activity against FcεRI expression, and inhibitory activity against histamine release.
Patent Document 2 describes an antiallergic agent containing as an active ingredient the plant body of Momordica napus or Shell Ginger, or an extract obtained by extracting the plant body with water or an organic solvent alone, or a mixture of these.
Patent Document 3 describes an antiallergic composition which contains as an active ingredient an extract or extract obtained by extracting a Citrullus plant with a lower aliphatic alcohol or a water-containing product thereof.
Patent Document 4 describes an antiallergic agent that contains rice-derived polyphenol as an active ingredient.
Patent Document 5 describes an antiallergic agent that contains at least one of rose plant, rose extract, and a fermented product obtained by fermenting and culturing these, and α-cyclodextrin.
Patent Document 6 describes an antiallergic agent that contains the active ingredient of purslane.

JP 2009-96761 A JP 2006-117562 A JP 2006-206520 A JP 2007-45755 A JP 2007-176797 A JP 2008-247779 A

In Patent Documents 1 to 6, antiallergic agents are prepared from various plants such as Helichrysum plants, Momordica charantia, Shell Ginger, Citrullus plants, Rice, Rose plants, and Portulaca oleracea. It is desirable to prepare as many types of plants as possible that can produce safe antiallergic agents that can be used continuously, not only for the prevention and treatment of allergic symptoms, not limited to type I allergies. Furthermore, it is desirable that such plant-derived antiallergic agents can be prepared for drinking, eating, application, etc., so that they can be easily taken in as many ways as possible, so that they can be adapted to the preferences of the person who takes them.
To extract an ingredient effective against allergies from the leaves of a plant, for example, the leaves of the plant are processed into tea and extracted with a solvent. The extract obtained at this time can be consumed as an antiallergic agent containing an ingredient effective against allergies.

The leaves of trees other than tea plants are rarely used for drinking. For example, in the case of figs, apart from eating the fruit, in a very small number of regions the only use is to process fig leaves into drinking tea. As a result, most parts of the plant other than the fruit are discarded and are not used effectively. Fig leaves are known to contain functional ingredients such as polyphenols, but because most of the fig leaves were discarded, research has not progressed and it is believed that they still contain many unidentified ingredients.

As described above, when B cells produce IgE antibodies specific to the invading allergen, the IgE antibodies enter the bloodstream and bind to FcεRI expressed by mast cells and basophil cells, sensitizing these cells.
Cross-linking between IgE antibodies in mast cells or basophil cells via allergens plays an important role in inducing type I allergy. That is, it is believed that the binding of monomeric IgE antibodies to FcεRI alone (sensitized state) is not enough to induce a response sufficient to cause systemic type I allergic symptoms.

Therefore, for example, if the sensitized state of mast cells and basophil cells can be eliminated at the stage where they are in preparation for an allergic reaction (sensitized state), it is thought that the onset of type I allergy can be suppressed.

As mentioned above, when an extract containing ingredients effective against allergies from plant leaves is taken as an anti-allergy drug, if the extract has a high concentration of the active ingredients or if the extract is taken frequently, it is believed that the effect of the anti-allergy drug can be fully expected.

On the other hand, there are cases where users of the anti-allergy agent find it convenient to consume an extract that is consumed less frequently or is low cost. Therefore, in order to reduce the burden on such users, it would be desirable to enhance the allergy suppression effect of the anti-allergy agent, particularly the anti-type I allergy suppressing component.

The object of the present invention is therefore to provide an anti-type I allergy suppression enhancer that can easily enhance the allergy suppression effect of an anti-type I allergy suppression component, and a method for using said anti-type I allergy suppression enhancer.

The first characteristic feature of the anti-type I allergy suppression enhancing agent according to the present invention for achieving the above object is an anti-type I allergy suppression component containing, as an active ingredient, an antibody dissociation composition having an effect of dissociating IgE antibodies against sensitized mast cells or basophil cells;
The antibody dissociating composition contains an allergy suppression enhancing component extracted from a plant different from the plant from which the antibody dissociating composition was extracted, and the antibody dissociating composition is an extract extracted from the leaves of any one of fig, loquat, rooibos, or senna using an extraction solvent of hot water, and the allergy suppression enhancing component comprises a composition extracted from onion using hot water, or the antibody dissociating composition is an extract extracted from fig leaves using an extraction solvent of hot water, and the allergy suppression enhancing component comprises a composition extracted from ginger using hot water, and the hot water has a temperature of 80 to 100°C .

In general, the following measures can be considered to suppress type I allergies: (1) suppressing the overproduction of antibodies, (2) suppressing sensitization, (3) suppressing the degranulation reaction, and (4) suppressing allergic symptoms after degranulation, such as inflammation and edema. Of these, existing anti-allergy technologies are classified as (3) and (4). In addition, by suppressing the sensitization state as in (2), type I allergies can be suppressed.
The anti-type I allergy suppressing component does not suppress sensitization, but rather relieves the sensitized state of sensitized mast cells and basophil cells, thereby suppressing the onset of type I allergy.

In other words, when mast cells or basophil cells that have been sensitized by an allergen are contacted with an anti-type I allergy suppressing component that contains as an active ingredient an antibody dissociating composition that has the effect of dissociating IgE antibodies, the IgE antibodies bound to the surface of the mast cells or basophil cells are dissociated, and the mast cells or basophil cells can be returned to the state before they were sensitized. Even if an allergen again invades in this state, an antigen-antibody reaction does not occur in the mast cells or basophil cells that are not sensitized, and therefore a series of reactions such as the release of chemical mediators does not occur, and the onset of allergic symptoms can be prevented in advance.

In this configuration, in addition to the anti-type I allergy suppressing component that contains the above-mentioned antibody dissociation composition as an active ingredient, it contains an allergy suppression enhancing component extracted from a plant different from the plant from which the antibody dissociation composition was extracted.

In this way, the anti-type I allergy suppression enhancing agent of the present invention contains an anti-type I allergy suppression component containing an antibody dissociation composition as an active ingredient and the allergy suppression enhancing component, and thus can enhance the type I allergy suppression effect obtained when only the anti-type I allergy suppression component containing an antibody dissociation composition as an active ingredient is used.

Therefore, the anti-type I allergy suppression enhancer of the present invention can easily enhance the allergy suppression effect of the anti-type I allergy suppression component without increasing the amount of the antibody dissociation composition, and is therefore considered to be highly effective in preventing and treating type I allergies.

Furthermore, with an anti-type I allergy suppression enhancer with enhanced suppressive effect against type I allergy, as in the present invention, the effect as an anti-allergy agent can be expected to be sufficient even if the frequency of ingestion is reduced, thereby reducing the burden and stress on the user.

In the present invention, the antibody dissociation composition is an extract extracted from the leaves of any one of fig, loquat, rooibos, and senna using hot water , and the allergy suppression enhancing component includes a composition extracted from onion using hot water, or the antibody dissociation composition is an extract extracted from fig leaves using hot water, and the allergy suppression enhancing component includes a composition extracted from ginger using hot water, and the temperature of the hot water is 80 to 100°C.

As a result of intensive research, the present inventors have found that figs, loquat, rooibos, and senna contain antibody dissociation compositions. Therefore, the anti-type I allergy suppressive component contained in the anti-type I allergy suppressive enhancer of the present invention can be an anti-type I allergy suppressive component that contains a plant-derived component as an anti-allergic active ingredient, so the anti-type I allergy suppressive enhancer of the present invention is highly safe and can be used continuously.

In addition, in order to obtain an extract composition containing an antibody dissociation composition from a plant, fig leaves, loquat leaves, etc. are used . Considering the current situation where most parts other than the fruit are discarded, the plant bodies of figs, loquats, etc. can be effectively utilized.
In this embodiment, the extraction solvent is hot water at 80 to 100° C., so that the anti-type I allergy suppressing component can be obtained by a method similar to that used for preparing a general tea extract .
Therefore, according to the present invention, the anti-type I allergy suppression component can be obtained simply and easily, and therefore the anti-type I allergy suppression enhancer can be easily produced.

In this configuration, the allergy suppression enhancing component is a composition extracted from onion or ginger, which are easily available, so that the allergy suppression effect of the anti-type I allergy suppressing component can be easily and inexpensively enhanced, and the cost burden on users is unlikely to increase.

The characteristic configuration of the anti-type I allergy suppression enhancing food of the present invention is that it contains an anti-type I allergy suppression ingredient containing as an active ingredient an antibody dissociation composition having the effect of dissociating IgE antibodies against sensitized mast cells or basophil cells, and an allergy suppression enhancing ingredient extracted from a plant different from the plant from which the antibody dissociation composition was extracted, wherein the antibody dissociation composition is an extract extracted with hot water from the leaves of any one of fig, loquat, rooibos, and senna, and the allergy suppression enhancing ingredient includes a composition extracted from onion with hot water, or the antibody dissociation composition is an extract extracted with hot water from fig leaves, and the allergy suppression enhancing ingredient includes a composition extracted from ginger with hot water, and the hot water has a temperature of 80 to 100°C .

In this configuration, the antibody dissociation composition extracted from the leaves of any one of fig, loquat, rooibos, or senna, and the allergy suppression enhancing component extracted from a plant different from the plant from which the antibody dissociation composition was extracted, can be used as an anti-type I allergy suppression enhancing food to enhance the effect of alleviating, suppressing, and preventing allergic symptoms.
That is, the food contains the antibody dissociating composition as an active ingredient and is capable of enhancing the type I allergy suppression effect obtained when only the anti-type I allergy suppressing ingredient is used.
The food with enhanced suppression of anti-type I allergy can be provided in the form of food or drink as a health food, functional food, or feed, and can therefore be easily ingested in a form that meets the diverse tastes of consumers.

FIG. 1 is a diagram showing an outline of the treatment steps when an antibody dissociation composition is extracted with hot water. FIG. 1 shows the results of immunoblotting. 1 is a graph showing the results of determining the relative intensity of the amount of dissociated IgE antibodies. This is a graph showing the relative intensity of dissociation of IgE antibodies from sensitized cells when extracts extracted from fig, loquat, senna, and rooibos were added to the sensitized cells. This is a graph showing the evaluation results of the β-Hex release amount (anti-allergic effect) of fig tea, loquat tea, senna tea and rooibos tea. 1 is a graph showing the results of an investigation into how the allergy suppression effect of an anti-type I allergy suppressing ingredient changes when an allergy suppression enhancing ingredient (onion skin powder) is added. This is a graph showing the results of an investigation into how the allergy suppression effect of the anti-type I allergy suppressing ingredient changes when an allergy suppression enhancing ingredient (ginger powder) is added. This is a graph showing the results of an investigation into how the allergy suppressing effect of the anti-type I allergy suppressing ingredient changes when 28 types of comparative materials are added. 1 is a graph showing the results of an investigation into how the allergy suppression effect changes when the mixing ratio of fig tea and onion peel powder is changed.

Hereinafter, an embodiment of the present invention will be described with reference to the drawings.
The present invention relates to an anti-type I allergy suppression enhancer having a naturally derived, particularly plant-derived, extract component capable of enhancing the allergy suppression effect of an anti-type I allergy suppression component alone, and a method for using the same.

Allergies are an example of an excessive immune response, and plant-derived extracts have been shown to have anti-allergic effects. The anti-type I allergy suppression enhancer of the present invention contains an anti-type I allergy suppression component that contains as an active ingredient an antibody dissociation composition that has the effect of dissociating IgE antibodies against sensitized mast cells or basophil cells, and an allergy suppression enhancer extracted from a plant different from the plant from which the antibody dissociation composition was extracted.

Among types I to IV allergies, the present invention is particularly applicable to type I allergies such as hay fever, acute urticaria, and food allergies, but is not limited to these.

The antibody dissociation composition is an extract component extracted from a plant body, such as fig, loquat, rooibos, or senna, using an extraction solvent such as water, hot water, alcohol, or hydroalcohol.

Figs are plants of the genus Ficus in the family Moraceae, and in this embodiment, the use of Ficus carica L. is described. As figs, for example, the major cultivars cultivated in Japan, Masui Dauphine, Temari fig, Dalmatia, Plecos Ronde de Bordeaux, and Negrone are preferred, but are not limited to these.

The fig plant used in the present invention may be the entire plant, from the roots to the tips of the leaves, but it is preferable to use the leaves. Of the leaves, it is particularly preferable to use young leaves at the tips of new shoots.

A new shoot is a newly grown branch, also called a current year's branch.
Young leaves refer to leaves that have just grown. For example, in the case of figs, it is preferable to use leaves that are about 14 days old after leaf emergence and are located from the tip of the shoot to about the fifth node. When young leaves from the tip of the shoot are used, extraction with an extraction solvent is easy, and an antibody dissociation composition can be obtained efficiently.
The plant body may be fresh or dried. The size (degree of crushing) of the plant body used for extracting the antioxidants is not particularly limited, but it is preferably in a powder state or a roughly chopped state, for example.

Loquat is a plant of the Rosaceae family, and examples of the loquat include, but are not limited to, Mogi and Tanaka varieties, which are major cultivars in Japan. The loquat leaves are preferably used.
Rooibos is a species of the genus Aspalathus in the subfamily Fabaceae, and is preferably, but not limited to, Aspalathus linearis. Rooibos is preferably used in the form of leaves.
Senna is a legume, and is preferably, but not limited to, for example, Cinnamon senna or Alexandria senna. Senna is preferably used in the form of a stem.

In this specification, for example, the whole plant or parts of fig, loquat, rooibos, and senna are referred to as "plant bodies."

The extraction solvent may be water, hot water, or an organic solvent. Hot water may be, for example, at 1 atmospheric pressure and at a temperature of 80 to 100° C. When extraction is performed with hot water, the following method may be used.
That is, the process includes a heating process A in which a Ficus plant is steamed, a kneading process B in which the heat-treated plant body is kneaded, a drying process C in which the kneaded plant body is dried, and an extraction process D in which hot water, which serves as an extraction solvent, is added to the dried plant body to obtain an extract composition containing an antibody dissociation composition (Figure 1).

Heat treatment is a process that inactivates enzymes in a plant body by heat, and is carried out, for example, by exposing the plant body to steam at 100°C. The heating temperature is not limited to 100°C as long as it is a temperature at which the enzyme is inactivated, and may be, for example, in the range of 80 to 100°C, and preferably 95 to 100°C. The heat treatment time may be set to a time that reliably inactivates the enzyme activity, and may be, for example, about 0.5 to 10 minutes. Heat treatment is carried out in a rotatable cylinder or steamer, but is not limited to these.

The kneading process is carried out to transfer moisture so that the tea leaves dry evenly, and to make it easier to extract the antibody dissociation composition from the plant body. For example, the kneading process involves kneading the tea leaves for 25 to 40 minutes at a temperature of 35 to 60°C. It is believed that the moisture content of the plant body is reduced to about 13 to 30% after the kneading process.

The drying process is carried out to improve the shelf life of the plant body. Preferably, the plant body is dried so that the moisture content is 4-5%. The drying process is carried out, for example, at 55-65°C for 2-5 hours.

When obtaining the antibody dissociation composition described above, it is advisable to use the plant body immediately after harvesting, or to use the plant body that has been stored under specified conditions. For example, the storage may involve packaging the plant body in a resin film bag and storing it at low temperature for a specified period of time as a low-temperature storage treatment. The resin film bag may be, for example, a low-density polyethylene bag with a thickness of about 0.02 to 0.04 mm, the temperature conditions may be, for example, about 0 to 8°C, and the specified period may be, for example, 10 days or more.

The organic solvent that can be used as the extraction solvent is preferably either alcohol or water-containing alcohol. The alcohol is preferably a linear or branched saturated alcohol having 1 to 8 carbon atoms, preferably 1 to 4 carbon atoms. Specific examples of the alcohol include methanol, ethanol, and n-butanol, and among these, methanol and ethanol are preferred.
The alcohol concentration of the water-containing alcohol is 20 to 80% by weight, preferably 50 to 75% by weight. For example, water-containing alcohol with an alcohol concentration of 50% by weight means that 50 parts by weight of alcohol and 50 parts by weight of water are weighed separately, then placed in a container and thoroughly mixed.

When using either alcohol or hydrous alcohol, the temperature during extraction is usually in the range of room temperature to 90°C, preferably 50 to 80°C. More preferably, the temperature is such that the hydrous alcohol refluxes at normal pressure. In this case, the extractor may be an open or closed system. The extraction time depends on the raw material and extraction temperature, but is usually 0.5 to 10 hours, preferably 1 to 4 hours.

For example, when extraction is performed with aqueous alcohol, the following method can be used.
That is, in the case of a Ficus plant, a crushing process is performed in which the Ficus plant is crushed, a solvent addition process is performed in which a hydrous alcohol is added, a shaking process is performed in which the plant is shaken after the solvent is added, and a recovery process is performed in which the plant is centrifuged after the shaking process to recover the supernatant.

The crushing process is carried out using a crusher capable of crushing freeze-dried fig leaves. The solvent addition process involves adding an appropriate amount of hydrous alcohol, which is an extraction solvent, to the crushed fig leaves. The shaking process involves, for example, shaking in a circular motion at 120 revolutions per minute for 3 hours at room temperature. The recovery process involves recovering the supernatant by, for example, centrifuging at 12,000 revolutions per minute for 10 minutes. The residue after recovering the supernatant may be subjected to repeated solvent addition, shaking, and recovery processes as necessary.

The water or alcohol used as the extraction solvent may be used in the form of a buffer solution containing various acids, alkalis, salts, etc.

As described above, the antibody dissociation composition can be extracted using hot water or an organic solvent, and then, for example, it can be subjected to an appropriate treatment such as concentration, dilution, or drying, either as is with insoluble matter still present or after removing the insoluble matter.

The anti-type I allergy suppression enhancing agent of the present invention may contain not only an antibody dissociation composition extracted from a plant of the Ficus genus, but also an antibody dissociation composition extracted from other plants such as loquat, rooibos, and senna.

The anti-type I allergy suppression enhancing agent of the present invention contains the above-mentioned antibody dissociation composition and an allergy suppression enhancing component extracted from a plant different from the plant from which the antibody dissociation composition is extracted.

"Plants different from the plant from which the antibody dissociation composition is extracted" refers to plants other than fig, loquat, rooibos, and senna. In this embodiment, "plants different from the plant from which the antibody dissociation composition is extracted" refers to onion or ginger, but is not limited thereto.

"Allergy suppression enhancing ingredient" refers to an ingredient that, when added in an effective amount, can enhance the allergy suppression effect more than the anti-type I allergy suppression ingredient alone, which contains an antibody dissociation composition as an active ingredient.

In other words, the anti-type I allergy suppression enhancing agent of the present invention may contain an allergy suppression enhancing component in addition to the antibody dissociation composition.

Onions are plants of the Allium genus in the Amaryllidaceae family. For example, the main cultivars cultivated in Japan, such as Tarzan, Momiji 3gou, Satsuki, Sapporoki, Satsuo, and Sarara, are preferred, but are not limited to these. For onions, the pericarp is preferably used, but is not limited to these. When extracting an allergy suppression enhancing component from onions, an extraction solvent such as water, hot water, alcohol, or hydroalcohol may be used, but is not limited to these. In this embodiment, a case where a hot water solution of onion pericarp powder is used will be described.

The onion skin powder can be obtained by a normal method such as drying the onion skin naturally or with a dryer. The onion skin powder solution in hot water can be obtained by dissolving the powder obtained by drying the onion skin in hot water at, for example, about 80 to 100°C.

Ginger is a plant of the Zingiberaceae family, and examples of the main cultivars grown in Japan, such as Yanaka ginger, Otafuku ginger, Indo ginger, Tosaichi ginger, and Kintoki ginger, are preferred, but are not limited to these. Grated ginger or dried powder is preferably used, but are not limited to these. When extracting the allergy suppression enhancing component from ginger, an extraction solvent such as water, hot water, alcohol, or hydrous alcohol may be used, but are not limited to these. In this embodiment, a case where a hot water solution of ginger powder is used will be described.

Ginger powder can be obtained by conventional methods, such as drying grated ginger naturally or in a dryer. Ginger powder dissolved in hot water can be obtained by dissolving ginger powder in hot water at, for example, about 80 to 100°C.

As described above, the anti-type I allergy suppression enhancing agent of the present invention means an agent containing an anti-type I allergy suppression component containing the above-mentioned antibody dissociation composition as an active ingredient, and an allergy suppression enhancing component extracted from a plant different from the plant from which the antibody dissociation composition was extracted. That is, the anti-type I allergy suppression enhancing agent can be used in the form of a pharmaceutical product such as a solid preparation or liquid preparation, or in the form of a food or drink. When used in the form of a pharmaceutical product, a medicamentally acceptable pharmaceutical additive may be added to the active ingredient. When used in the form of a food or drink, the food or drink becomes an anti-type I allergy suppression enhancing food containing an anti-type I allergy suppression component containing an antibody dissociation composition as an active ingredient that has the effect of dissociating IgE antibodies against sensitized mast cells or basophil cells, and an allergy suppression enhancing component extracted from a plant different from the plant from which the antibody dissociation composition was extracted, that is, a food with enhanced anti-type I allergy prevention effect.

When producing solid preparations such as tablets, powders, and granules, pharmaceutical additives that can be used include excipients (e.g., sugars, starches, celluloses, magnesium aluminometasilicate, calcium phosphate, etc.), lubricants (e.g., magnesium stearate, talc, polyethylene glycol, etc.), binders (e.g., mannitol, sugars, crystalline cellulose, polyvinylpyrrolidone, hydroxypropylmethylcellulose, etc.), disintegrants (e.g., starches, celluloses, cross-linked polyvinylpyrrolidone, etc.), colorants, and flavoring agents.

Liquid preparations can be provided in the form of, for example, aqueous or oily suspensions, solutions, emulsions, syrups, or elixirs. Pharmaceutical additives that can be used when producing liquid preparations include solvents (e.g., oily solvents, hydrophilic solvents, etc.), solubilizing agents (e.g., polyethylene glycol, cholesterol, etc.), emulsifiers (e.g., surfactants, etc.), suspending agents (polyvinyl compounds, hydrophilic polymers, surfactants, etc.), preservatives (e.g., parabens, sorbic acid, etc.), colorants, and flavoring agents.

When the anti-type I allergy suppression enhancer of the present invention is used in the form of a medicine, it is configured to contain an anti-type I allergy suppression component containing an effective amount of an antibody dissociation composition to alleviate, suppress, or prevent type I allergy symptoms, and an effective amount of an allergy suppression enhancer extracted from at least one of onion and ginger to enhance the effect of the anti-type I allergy suppression component. The anti-type I allergy suppression enhancer prepared in this manner is administered to humans or animals who are the subjects of allergy symptoms to be alleviated, suppressed, or prevented. Administration can be performed, for example, orally using oral preparations such as powders, fine granules, granules, tablets, capsules, suspensions, emulsions, syrups, extracts, and pills, or parenterally using parenteral preparations such as injections, external liquids, ointments, suppositories, and eye drops.

In addition to the antibody dissociation composition and the allergy suppression enhancing component, the oral preparation can contain excipients such as sodium alginate, starch, corn starch, white sugar, lactose, glucose, mannitol, carboxymethylcellulose, dextrin, polyvinylpyrrolidone, crystalline cellulose, soybean lecithin, sucrose, fatty acid esters, talc, magnesium stearate, polyethylene glycol, magnesium silicate, anhydrous silicic acid, or synthetic aluminum silicate, binders, disintegrants, surfactants, lubricants, flow promoters, diluents, preservatives, colorants, fragrances, flavorings, stabilizers, moisturizers, preservatives, or antioxidants. That is, the oral preparation is an anti-type I allergy suppression enhancing agent that contains the antibody dissociation composition and the allergy suppression enhancing component.

In addition to the antibody dissociation composition and the allergy suppression enhancing component, the parenteral preparation can contain, for example, a water-soluble solvent such as physiological saline or Ringer's solution, a water-insoluble solvent such as vegetable oil or fatty acid ester, an isotonic agent such as glucose or sodium chloride, a solubilizing agent, a stabilizer, a preservative, a suspending agent, or an emulsifier. In other words, the parenteral preparation is an anti-type I allergy suppression enhancing agent that contains the antibody dissociation composition and the allergy suppression enhancing component.

When used in the form of food or beverage, it can be provided in the form of food or beverage as a health food (preferably functional food) or feed. Examples of such food or beverage include confectionery, soft drinks, tea, nutritional drinks, soups, etc. The antibody dissociation composition and the allergy suppression enhancing component can be added by mixing, applying, spraying, etc. during the manufacturing process of these foods and beverages, or to the final product, to make them into health foods. When used in the form of food or beverage, it is also preferable to include an anti-type I allergy suppression component containing an effective amount of the antibody dissociation composition to alleviate, suppress, or prevent type I allergy symptoms, and an effective amount of an allergy suppression enhancing component extracted from at least one of onion and ginger to enhance the effect of the anti-type I allergy suppression component.

In other words, whether the anti-type I allergy suppression enhancing agent of the present invention is used in the form of a pharmaceutical product or in the form of a food or beverage product, a method for enhancing the type I allergy prevention (suppression) can be provided that can enhance the type I allergy suppression effect obtained when only the anti-type I allergy suppression component containing the antibody dissociation composition as an active ingredient is used. Therefore, for example, even if the frequency of use is reduced, the effect as an anti-allergy agent can be fully expected, thereby reducing the burden and stress on the user.

When using the anti-type I allergy suppression enhancer of the present invention, the dosage (effective intake amount, maximum intake amount per day) can be appropriately determined depending on the type of allergy, the age, sex, weight, and severity of symptoms of the subject, the method of administration, etc.

The anti-type I allergy suppression enhancer of the present invention can be an anti-allergy suppression component that contains a plant-derived component as an anti-allergy active ingredient, so it is highly safe and can be used continuously as a medicine or food or drink.

Example 1
An experiment using cultured cells was conducted to investigate whether extracts extracted from fig leaves (fig tea) etc. have anti-type I allergy properties. The commercially available fig tea "Rinshizuku" (manufactured by Suwaen and sold by Kawanishi City Chamber of Commerce and Industry) was used as the fig leaves. The raw fig variety used was Masui Dauphin. First, it was investigated whether fig tea etc. has an anti-type I allergy suppressing ingredient that contains an antibody dissociating composition that has the effect of dissociating IgE antibodies as an active ingredient.

The tea leaves were prepared and the tea extract was prepared according to the heating, rolling, drying, and extraction processes described above. In the extraction process, 100 mL of ultrapure water (temperature 80°C) was added per gram of tea leaves, and the mixture was left to stand for 3 minutes, after which it was filtered through a 0.45 μm membrane filter to prepare the tea extract.

Similar experiments were also conducted to examine whether loquat tea, senna tea, and rooibos tea have anti-type I allergy properties. For loquat, looibos tea (Yoso Sabo) was used, for rooibos, rooibos tea (Marumo Co., Ltd.) was used, and for senna, senna tea (Honzo Pharmaceutical Co., Ltd.) was used. 100 mL of ultrapure water (temperature 80°C) was added per 1 g of each tea leaf, and the mixture was left to stand for 3 minutes, after which it was filtered through a 0.45 μm membrane filter to prepare tea extracts.

The cultured cells were the peripheral blood-derived mast cell line RBL-2H3 (JCRB0023) from basophilic leukemia rats. The culture medium used was Earle's minimal essential medium (MEM medium: containing 10% fetal bovine serum (FBS), 100 units/mL penicillin, and 100 μg/mL streptomycin), and the culture conditions were stationary culture at 37° C. and 5% CO ₂ .

Cells (final concentration ^4x105 cells/well) suspended in 400μL of culture medium were seeded on a 24-well culture plate and cultured at 37℃ and 5% _CO2 for 1 hour, after which 1/10 volume of tea extract (final concentration 1mg/mL in tea leaf equivalent) was added. As a negative control, phosphate buffered saline (containing no calcium chloride or magnesium chloride; hereafter referred to as PBS(-)) was added.
Next, mouse monoclonal anti-DNP-IgE antibody was added at a final concentration of 0.45 μg/mL, and the cells were cultured for 1 hour at 37° C., _CO2 concentration 5%, and stationary conditions to sensitize the cells. After that, the culture medium was removed, washed twice with PBS(-) solution, and then cultured in MEM medium to which the sample had been added for a certain period of time (24 hours or 6 hours) at 37° C., and only the MEM medium was collected. The IgE antibody contained in the MEM medium was selectively collected by immunoprecipitation, and the amount of the IgE antibody was detected by immunoblotting using an IgE-specific antibody. In the immunoprecipitation method, a biotin-bound anti-IgE antibody and a streptavidin carrier (manufactured by GE Healthcare Japan) were used to form a complex with the IgE antibody and collected. The results of the immunoblotting method are shown in FIG. 2. The relative intensity (control is set to 1) obtained as a result is also shown in FIG. 3.

In Figure 2, the CBB staining shows that all proteins in the MEM medium are stained, but in detection by immunoblotting using an IgE-specific antibody, bands thought to be IgE antibodies were observed in lane 2 (treated for 24 hours) and lane 3 (treated for 6 hours) at the same position as the IgE antibody band in lane 5. No such bands were observed in the control in lane 1 or the sample not treated with IgE antibody in lane 4.

When the relative intensity of this band (control is taken as 1) was calculated, the relative intensity of lane 2 (treated for 24 hours) was about 3.9, and the relative intensity of lane 2 (treated for 6 hours) was about 1.6, and it was confirmed that the amount of IgE antibody contained in the medium increased by adding fig tea. In other words, it was confirmed that fig tea has an IgE antibody dissociation effect. It was also confirmed that the longer the treatment time of sensitized cells with fig tea, the stronger the antibody dissociation effect became. Therefore, it was confirmed that the possibility of suppressing type I allergy increases if the treatment time of sensitized cells with fig tea is extended.
In this example, the fig tea "Rinshizuku" was used, but similar effects and mechanisms of action were observed with other fig teas (data not shown).

The above results confirmed that fig tea has an antibody dissociating effect. Other plants besides figs, such as loquat, senna, and rooibos, were also used to investigate whether extracts from these plants had an antibody dissociating effect.

As mentioned above, the results of immunoblotting for loquat tea, senna tea, and rooibos tea were obtained using the same method as for fig tea (results not shown), and the resulting relative intensities (control is set at 1) are shown in Figure 4.

As a result, the relative IgE antibody dissociation level for fig tea was approximately 3.9, the relative IgE antibody dissociation level for loquat tea was approximately 3.2, the relative IgE antibody dissociation level for senna tea was approximately 2.5, and the relative IgE antibody dissociation level for rooibos tea was approximately 2.6. From the above results, it was confirmed that fig tea, loquat tea, senna tea, and rooibos tea also have an antibody dissociation effect.

The amount of β-hexosaminidase (β-Hex), which is released simultaneously with the inflammatory substance histamine during cell degranulation, was measured for fig tea, loquat tea, senna tea and rooibos tea, and used as an index of degranulation.

The antigen DNP-BSA was added to the sensitized cells to a final concentration of 10 μg/mL, and the antigen-antibody reaction was carried out for 30 minutes at 37° C. to induce degranulation. The plate was left on ice for 10 minutes to stop the reaction, and 50 μL of the buffer supernatant was collected in a 96-well plate, and an equal amount of β-Hex substrate solution (1 mM p-nitrophenyl-N-acetyl-β-D-glucosaminide dissolved in 0.1 M citrate buffer, pH 4.5) was added, and the reaction was carried out at 37° C. for 1 hour.
The enzyme reaction was stopped by adding 0.1 M carbonate-bicarbonate buffer (pH 10.4) and a color reaction was carried out, and the absorbance at 405 nm was measured.

The evaluation results of β-Hex release (anti-allergic effect) of fig tea, loquat tea, senna tea and rooibos tea are shown in Figure 5.
When the amount of β-Hex released in the cell line added with PBS (-) as control is taken as 100%, the amount of β-Hex released when fig tea is added at the time of sensitization is about 12%, the amount of β-Hex released when loquat tea is added at the time of sensitization is about 29%, the amount of β-Hex released when senna tea is added at the time of sensitization is about 41%, and the amount of β-Hex released when rooibos tea is added at the time of sensitization is about 45%.In this way, in the cell line added with fig tea, loquat tea, senna tea and rooibos tea, the amount of β-Hex released is suppressed to about 40%, and it is recognized that the amount of released inflammatory substance histamine released during degranulation is also suppressed to the same extent.Therefore, it is found that loquat tea, senna tea and rooibos tea have the same anti-I type allergy effect as fig tea.

In other words, fig tea, loquat tea, senna tea and rooibos tea were found to have an anti-type I allergy suppressing component that contains as an active ingredient an antibody dissociating composition that has the effect of dissociating IgE antibodies against sensitized mast cells or basophil cells.

Example 2
We investigated how the allergy suppression effect of the anti-type I allergy suppressing component changes when an allergy suppression enhancing component extracted from a plant different from the plant from which the antibody dissociating composition was extracted is added to the above-mentioned fig tea, loquat tea, senna tea, and rooibos tea.

As the allergy-suppressing enhancing component, a hot water solution of onion peel powder (hereinafter referred to as onion peel powder) was used.
The antibody dissociation effect (anti-allergic effect) when onion peel powder was used alone was examined in the same manner as in Example 1. When the amount of β-Hex released in the cell line to which control PBS(-) was added was taken as 100%, the amount of β-Hex released when onion peel powder was added immediately before the addition of the antigen was about 23% ( FIG. 6 ).
The above-mentioned fig tea, loquat tea, senna tea and rooibos tea were added to the cell line at the time of sensitization, but onion peel powder was added just before the antigen addition. Since inflammatory cells exist at various stages in the body, it is believed that the more points of action, such as components acting at the time of sensitization and components acting at the time of antigen-antibody reaction, the more effectively allergies can be suppressed, so the timing of addition is varied.

The anti-type I allergy suppression enhancing agent of the present invention has an anti-type I allergy suppression component containing an antibody dissociation composition as an active ingredient, and an allergy suppression enhancing component extracted from a plant different from the plant from which the antibody dissociation composition was extracted. Therefore, as the anti-type I allergy suppression enhancing agent of the present invention, an agent was prepared by adding fig tea, loquat tea, senna tea and rooibos tea, each of which is an anti-type I allergy suppression component, to onion peel powder, which is an allergy suppression enhancing component.

In these anti-type I allergy suppression enhancers, the addition ratio of the anti-type I allergy suppression component and the allergy suppression enhancer was 50% (1:1). The antibody dissociation effect (anti-allergy effect) of these anti-type I allergy suppression enhancers was performed in accordance with Example 1.

As shown in FIG. 6, when the amount of β-Hex released in the cell line to which the control PBS(-) was added was taken as 100%, the amount of β-Hex released when fig tea was added at the time of sensitization and onion peel powder was added immediately before the addition of the antigen (Example 1 of the present invention) was about 7%. When loquat tea was added at the time of sensitization and onion peel powder was added immediately before the addition of the antigen (Example 2 of the present invention) the amount of β-Hex released was about 19%. When senna tea was added at the time of sensitization and onion peel powder was added immediately before the addition of the antigen (Example 3 of the present invention) the amount of β-Hex released was about 21%. When rooibos tea was added at the time of sensitization and onion peel powder was added immediately before the addition of the antigen (Example 4 of the present invention) the amount of β-Hex released was about 10%.

In this way, it was found that the inhibitory effect on type I allergy was enhanced by about 3.3 times (23/7) when fig tea was added at the time of sensitization and onion peel powder was added immediately before the addition of the antigen (Invention Example 1).

In addition, when loquat tea was added at the time of sensitization and onion peel powder was added immediately before the addition of the antigen (Invention Example 2), the inhibitory effect on type I allergy was found to be enhanced by approximately 1.2 times (23/19).

In addition, when senna tea was added at the time of sensitization and onion peel powder was added immediately before the addition of the antigen (Invention Example 3), the inhibitory effect on type I allergy was found to be enhanced by approximately 1.1 times (23/21).

In addition, when rooibos tea was added at the time of sensitization and onion peel powder was added immediately before the addition of the antigen (Invention Example 4), the inhibitory effect on type I allergy was found to be enhanced by approximately 2.3 times (23/10).

Although no data is shown, the results of the type I allergy suppression effect when green tea or Baozhong tea extract containing the anti-allergic component methylated catechin was added to fig tea, loquat tea, senna tea and rooibos tea respectively were different from the results of the type I allergy suppression effect of this example. Therefore, it was recognized that the mechanism of action of the allergy suppression enhancing component contained in the anti-type I allergy suppression enhancing agent of the present invention is different from the mechanism of action of green tea or Baozhong tea extract containing methylated catechin.

Example 3
In Example 2, onion peel powder was used as the allergy suppression enhancing ingredient, and it was investigated whether a hot water solution of ginger powder (hereinafter referred to as ginger powder) contains an allergy suppression enhancing ingredient.

The antibody dissociation effect (anti-allergic effect) of ginger powder alone was examined in the same manner as in Example 1. When the amount of β-Hex released in the cell line to which the control PBS(-) was added was taken as 100%, the amount of β-Hex released when ginger powder was added immediately before the addition of the antigen was approximately 66% (Figure 7).

On the other hand, an anti-type I allergy suppression enhancer was prepared by adding 50% of fig tea, an anti-type I allergy suppression component, to ginger powder, an allergy suppression enhancer. The antibody dissociation effect (anti-allergy effect) of this anti-type I allergy suppression enhancer was examined in accordance with Example 1.

As shown in Figure 7, when the amount of β-Hex released in the cell line to which the control PBS(-) was added was taken as 100%, the amount of β-Hex released when fig tea was added at the time of sensitization and ginger powder was added immediately before the addition of the antigen (Invention Example 5) was approximately 27%. Thus, it was found that the inhibitory effect on type I allergy was enhanced by approximately 2.4 times (66/27) when fig tea was added at the time of sensitization and ginger powder was added immediately before the addition of the antigen (Invention Example 5).

For comparison, Figure 8 shows the results of investigating whether 28 other ingredients contain allergy suppression enhancing ingredients. For comparison, Figure 8 also shows data on fig tea alone and in combination with onion peel and ginger (a total of 31 types of data are shown).

The other 28 ingredients used for comparison include buckwheat tea (Itoen Co., Ltd.), Arame (Uwabe Foods Co., Ltd.), Pu'er tea (Kokudairou Co., Ltd.), Benifuuki green tea (Yamamotoyama Co., Ltd.), corn tea (Daizo Japan Co., Ltd.), black bean tea (Uji Moritoku Co., Ltd.), strawberry fruit (Sagahonoka: produced in Kagoshima Prefecture), green onion (green part: produced in Kochi Prefecture), red shiso tea (Zenyakuno Co., Ltd.), hijiki tea (Bandai Co., Ltd.), peppermint (House Foods Corporation), and strawberry stems (Sagahonoka: produced in Kagoshima Prefecture). , kelp tea (Uji Moritoku Co., Ltd.), black tea (Mitsui Norin Co., Ltd.), burdock tea (Unimat Riken Co., Ltd.), young barley leaves (Ito Kampo Pharmaceutical Co., Ltd.), persimmon leaf tea (Mikuniya Zengoro), cocoa (Morinaga & Co., Ltd.), green onions (white parts: from Kochi Prefecture), celery, turmeric (Amami Medicinal Herb Farm), parsley (curly leaf variety), Chinese chives (from Nagasaki Prefecture), kale (Yakult Health Foods Co., Ltd.), oolong tea (Uji Moritoku Co., Ltd.), dried shrimp (Ogura Foods Co., Ltd.), broccoli, and myoga were used.

Extracts of these ingredients were prepared using known methods, and an investigation was carried out to see how the allergy-suppressing effects of the anti-type I allergy-suppressing ingredients changed when each extract was added to fig tea.

As shown in Figure 8 and Table 1, when the amount of β-Hex released in the cell line to which the control PBS(-) was added was taken as 100%, the amount of β-Hex released when fig tea was added at the time of sensitization was approximately 30%. In addition, when onion peel and ginger were used in combination, the amounts of β-Hex released were approximately 13% and 27%, respectively. On the other hand, when the above 28 comparative materials were added, the amount of β-Hex released was approximately 45-211%.

Therefore, it was determined that the above 28 comparative materials do not contain the allergy suppression enhancing component contained in the anti-type I allergy suppression enhancing agent of the present invention.

Example 4
In the above-mentioned examples, the addition ratio of the anti-type I allergy suppressing component and the allergy suppression enhancing component was 50% (1:1). In this example, we investigated how the allergy suppressing effect changes when the mixing ratio of fig tea (containing the anti-type I allergy suppressing component) and onion peel powder (containing the allergy suppression enhancing component) is changed. The experiment was performed in the same manner as the above-mentioned examples, except that the addition ratio of the anti-type I allergy suppressing component and the allergy suppression enhancing component was changed.

As a result, as shown in Figure 9, an enhancing effect was confirmed even with a mixture ratio of fig tea:onion peel powder of 3:1. In other words, when the amount of β-Hex released in the cell line to which the control PBS(-) was added was taken as 100%, the amount of β-Hex released when fig tea was added at the time of sensitization was approximately 17%. On the other hand, when the mixture ratio of fig tea:onion peel powder was 3:1, the amount of β-Hex released was approximately 10%.

In this way, when the mixture of fig tea and onion peel powder was 3:1, the inhibitory effect on type I allergy was found to be approximately 1.7 times (17/10) stronger.

The anti-type I allergy suppression enhancer of the present invention and the method of using the anti-type I allergy suppression enhancer can be used to alleviate, suppress, or prevent type I allergy symptoms.

Claims (2)

An anti-type I allergy suppressing component containing as an active ingredient an antibody dissociating composition having an effect of dissociating IgE antibodies against sensitized mast cells or basophil cells, and
The antibody dissociating composition contains an allergy suppression enhancing component extracted from a plant different from the plant from which the antibody dissociating composition is extracted,
The antibody dissociation composition is an extract obtained by extracting leaves of any one of fig, loquat, rooibos, and senna with hot water, and the allergy suppression enhancing component includes a composition extracted from onion with hot water, or
The antibody dissociation composition is an extract obtained by extracting fig leaves with hot water, and the allergy suppression enhancing component includes a composition extracted from ginger with hot water;
The anti-type I allergy suppression enhancer, wherein the hot water has a temperature of 80 to 100°C . An anti-type I allergy suppressing component containing as an active ingredient an antibody dissociating composition having an effect of dissociating IgE antibodies against sensitized mast cells or basophil cells, and
The antibody dissociating composition contains an allergy suppression enhancing component extracted from a plant different from the plant from which the antibody dissociating composition is extracted,
The antibody dissociation composition is an extract obtained by extracting leaves of any one of fig, loquat, rooibos, and senna with hot water, and the allergy suppression enhancing component includes a composition extracted from onion with hot water, or
The antibody dissociation composition is an extract obtained by extracting fig leaves with hot water, and the allergy suppression enhancing component includes a composition extracted from ginger with hot water;
The food for enhancing suppression of anti-type I allergy , wherein the hot water has a temperature of 80 to 100°C .