JP7208735B2 - Anti-type I allergy agent - Google Patents

Description

The present invention relates to an anti-type I allergy agent.

Allergy is defined as "systemic or local damage to the body based on an immune response". Allergic reactions are classified into types I to IV. Among them, type I, II, and III allergies are humoral immunity involving serum replacement, and type IV allergy is cellular immunity by sensitized lymphocytes.

Type I allergy is also called immediate-type allergy or anaphylactic-type allergy. Symptoms of type I allergy include hay fever, urticaria, and the like, and since a relatively large number of people have these symptoms, there is a demand for an effective anti-type I allergy agent. For example, Patent Literature 1 discloses a cosmetic or topical skin preparation having an antiallergic effect by using a carnitine derivative and/or the carnitine derivative in combination with an effect enhancer.

JP 2014-114289 A

An object of the present invention is to provide a novel anti-type I allergy agent.

One aspect of the present invention provides an anti-type I allergy agent containing a bagasse decomposition extract as an active ingredient.

The present inventors found that the bagasse decomposition extract has an anti-type I allergy effect by in vitro tests. That is, according to the anti-type I allergy agent of the present invention, symptoms of type I allergy can be suppressed (treated, alleviated or prevented).

The anti-type I allergy agent of the present invention may be based on the degranulation inhibitory action of mast cells or basophils.

The mechanism of type I allergic reaction is as follows.
(1) When antigens (allergens) such as pollen and mites invade the body, helper T cells (Th2 cells) issue commands to differentiate B cells into immunoglobulin E (IgE) antibody-producing cells.
(2) IgE antibodies specific to the antigen are produced from IgE antibody-producing cells.
(3) The IgE antibody binds to mast cells or basophils, and when the antigen binds there again, chemical mediators such as histamine and leukotrienes are secreted (degranulated), and allergic symptoms develop.

The anti-type I allergy of the present invention has at least the action of suppressing degranulation of mast cells or basophils. Therefore, the anti-type I allergy agent of the present invention can effectively suppress symptoms of type I allergy.

The decomposition extract of bagasse may be a decomposition-treated liquid obtained by at least one decomposition treatment selected from the group consisting of alkali treatment, hydrothermal treatment, acid treatment, subcritical water treatment, pulverization treatment and explosion treatment.

The bagasse decomposition extract may be a fraction obtained by passing a decomposition-treated liquid through a column filled with a solid carrier. The fixed carrier is preferably a synthetic adsorbent or an ion exchange resin.

When the immobilizing carrier is a synthetic adsorbent, the bagasse decomposition extract extracts the components adsorbed by the synthetic adsorbent with at least one solvent selected from the group consisting of water, methanol, ethanol, and mixtures thereof. It may be a fraction obtained by allowing

The synthetic adsorbent is preferably an aromatic resin, an acrylic methacrylic resin, or an acrylonitrile aliphatic resin.

The decomposition extract of bagasse is obtained by passing the decomposition treated liquid through a column filled with a synthetic adsorbent as a fixed carrier, and eluting the components adsorbed by the synthetic adsorbent with a mixed solvent of ethanol and water. In this case, the synthetic adsorbent is an unsubstituted aromatic resin, the column temperature is 20 to 60 ° C., and the volume ratio of ethanol and water in the mixed solvent (ethanol /water) may be from 50/50 to 60/40.

In another aspect, the present invention provides a mast cell or basophil degranulation inhibitor containing a bagasse decomposed extract as an active ingredient.

According to the present invention, a novel anti-type I allergy agent can be provided.

1 is a graph showing degranulation rates of Examples 1 to 3, Comparative Example 1 and a positive control. 4 is a graph showing the degranulation rates of Examples 4 to 6 and Comparative Example 1. FIG.

Embodiments of the present invention will be described below. However, the present invention is not limited to the following embodiments.

The anti-type I allergy agent in the present specification is a composition having an effect of suppressing type I allergy symptoms. The action of suppressing type I allergy symptoms may be, for example, the action of alleviating, treating, or preventing symptoms caused by type I allergy such as hay fever, hives, allergic rhinitis, and bronchial asthma. The action of suppressing type I allergy symptoms may be an action of suppressing degranulation of mast cells or basophils in the mechanism of type I allergic reaction. That is, the anti-type I allergy agent in the present specification may be an agent for suppressing degranulation of mast cells or basophils.

An anti-type I allergy agent according to one embodiment contains a bagasse decomposition extract as an active ingredient. The bagasse decomposition extract preferably contains at least one selected from the group consisting of p-coumaric acid, ferulic acid, caffeic acid, phenylpropanoids such as vanillin, and lignin and its decomposition products.

"Bagasse" typically refers to bagasse discharged during the sugar manufacturing process in the raw material sugar manufacturing process. The bagasse discharged in the sugar manufacturing process at the raw sugar factory includes not only the final bagasse that has left the final press, but also the shredded sugar cane that has been bitten into the subsequent presses including the first press. A suitable bagasse is the bagasse that is discharged after pressing the juice by the pressing process in the raw sugar mill. The bagasse varies in water content, sugar content, and composition ratio thereof depending on the type of sugar cane, harvest time, etc., but any of these bagasse can be used in the present invention. Furthermore, in the present embodiment, the bagasse used as the raw material is, for example, the bagasse remaining after pressing the cane discharged at the brown sugar manufacturing plant, similarly to the raw material sugar factory, or the sugar liquid is squeezed from the sugar cane by small-scale laboratory-level implementation. Later bagasse can also be used.

The bagasse decomposition extract may, in one embodiment, be a decomposition treated liquid of bagasse (and/or its processed product). The decomposition-treated liquid can be obtained by at least one decomposition treatment selected from the group consisting of alkali treatment, hydrothermal treatment, acid treatment, subcritical water treatment, pulverization treatment and explosion treatment. The decomposition treatment is preferably an alkali treatment or a hydrothermal treatment from the viewpoint of easily obtaining a decomposition extract of bagasse.

The alkali treatment may be a treatment of contacting the bagasse with an alkaline solution. Examples of the method of bringing the alkaline solution into contact include a method of sprinkling the bagasse with the alkaline solution, a method of immersing the bagasse in the alkaline solution, and the like. In the method of immersing the bagasse in the alkaline solution, the mixture of the bagasse and the alkaline solution may be immersed while stirring.

Alkaline solutions include sodium hydroxide aqueous solution, potassium hydroxide aqueous solution, ammonia aqueous solution and the like. Alkaline solutions may be used alone or in combination of two or more of these solutions. The alkaline solution is preferably an aqueous sodium hydroxide solution because it is inexpensive and can be easily used in the food manufacturing process.

The temperature (liquid temperature) of the alkaline solution is preferably 40° C. or higher, more preferably 100° C. or higher, and still more preferably 130° C. or higher, from the viewpoint of shortening the treatment time of the decomposition treatment. The temperature of the alkaline solution is preferably 250° C. or lower, more preferably 200° C. or lower, and still more preferably 150° C. or lower from the viewpoint of preventing the polysaccharide from remaining in the decomposition treatment liquid.

The alkali treatment may be performed under normal pressure or under pressure. When pressurized, the pressure may be 0.1 MPa or more, or 0.2 MPa or more, and may be 4.0 MPa or less, 1.6 MPa or less, or 0.5 MPa or less.

The hydrothermal treatment may be a process of contacting bagasse with hot water or steam under high pressure. More specifically, the hydrothermal treatment may be, for example, a method in which water is added so that the bagasse has a solid concentration of 0.1 to 50%, and decomposition treatment is performed under high temperature and high pressure conditions. The temperature of water or steam is preferably 130 to 250° C., and the applied pressure is preferably 0.1 to 0.5 MPa higher than the saturated steam pressure of water at each temperature.

The acid treatment may be a treatment of contacting the bagasse with an acidic solution. Dilute sulfuric acid etc. are mentioned as an acidic solution. The method of bringing the acid solution into contact with the bagasse, the temperature of the acid solution in the acid treatment, and the pressure conditions in the acid treatment may be the same as those in the alkali treatment described above.

The subcritical water treatment may be a treatment of contacting bagasse with subcritical water. The method of contacting bagasse with subcritical water may be the same as the method in the alkali treatment described above. The conditions for the subcritical water treatment are not particularly limited, but it is preferable to set the temperature of the subcritical water to 160 to 240° C. and the treatment time to 1 to 90 minutes.

The pulverization process may be a process of pulverizing the bagasse to several micrometers to several hundred micrometers by compression, impact, shear, friction, or the like. In the blasting treatment, the insoluble xylan contained in the bagasse is decomposed to some extent by hydrothermal treatment, and then the bagasse is pulverized by instantly releasing it to atmospheric pressure by opening a valve provided in the pressure-resistant reaction vessel at once. It may be processing.

After the decomposition treatment described above, the decomposition treatment liquid may be subjected to a treatment for separating the solid content and the liquid content. In this case, the liquid component obtained after the separation can be used as the decomposition treatment liquid. The method of separating solids and liquids may be separation by strainer, filtration, centrifugation, decantation, and the like.

In the decomposition treatment liquid, high-molecular components such as polysaccharides may be removed by membrane separation. In this case, the liquid component after membrane separation can be used as the decomposition treatment liquid. The separation membrane is not particularly limited as long as it is an ultrafiltration membrane (UF membrane). The molecular weight cut off of the ultrafiltration membrane is preferably 2,500 to 50,000, more preferably 2,500 to 5,000.

Ultrafiltration membrane materials include polyimide, polyethersulfone (PES), polysulfone (PS), polyacrylonitrile (PAN), polyvinylidene fluoride (PVDF), regenerated cellulose, cellulose, cellulose ester, sulfonated polysulfone, sulfonated Polyethersulfone, polyolefin, polyvinyl alcohol, polymethyl methacrylate, polytetrafluoroethylene, and the like can be used.

The filtration method of the ultrafiltration membrane may be dead-end filtration or cross-flow filtration, but cross-flow filtration is preferable from the viewpoint of suppressing membrane fouling.

As the form of the ultrafiltration membrane, an appropriate form such as a flat membrane type, a spiral type, a tubular type, or a hollow fiber type can be used. More specifically, GE Power & Water's GE series, GH series, GK series, DESAL's G-5 type, G-10 type, G-20 type, G-50 type, PW type, HWSUF type, KOCH's HFM-180, HFM-183, HFM-251, HFM-300, HFK-131, HFK-328, MPT-U20, MPS-U20P, MPS-U20S, Synder SPE1, SPE3, SPE5, SPE10, SPE30, SPV5 , SPV50, SOW30, Microza (registered trademark) UF series manufactured by Asahi Kasei Corporation having a molecular weight cut off of 3,000 to 10,000, and NTR7410 and NTR7450 manufactured by Nitto Denko Corporation.

In another embodiment, the bagasse decomposition extract may be a fraction obtained by passing the decomposition-treated liquid described above through a column filled with a solid carrier. By passing the decomposition treatment solution through the column, the component having anti-type I allergy action (active ingredient) in the decomposition treatment solution is adsorbed to the immobilizing carrier, and most of the sugars and inorganic salts flow out as they are.

The decomposition treatment liquid described above can be passed through the column directly or after being adjusted to an arbitrary concentration with water. The pH of the decomposition treatment solution may be adjusted before passing through the column. From the viewpoint of improving the adsorption rate, the decomposition treatment liquid is preferably adjusted to pH 6 or less. The pH of the decomposition treatment liquid may be more than 4.5 and 6 or less.

The fixed carrier is preferably either a synthetic adsorbent or an ion exchange resin.

The synthetic adsorbent is preferably a synthetic porous adsorbent. As the synthetic adsorbent (synthetic porous adsorbent), an organic resin is preferably used. The organic resin is preferably an aromatic resin, an acrylic methacrylic resin, or an acrylonitrile aliphatic resin.

Examples of aromatic resins include styrene-divinylbenzene resins. Examples of aromatic resins include porous resins such as aromatic resins having hydrophobic substituents, non-substituted aromatic resins, and non-substituted aromatic resins specially treated. Of these, unsubstituted aromatic resins or unsubstituted aromatic resins specially treated are preferred.

Commercially available synthetic adsorbents include Diaion (trademark) HP-10, HP-20, HP-21, HP-30, HP-40, and HP-50 (these are non-substituted aromatic resins , All are trade names, Mitsubishi Chemical Co., Ltd.); system resin, both trade names, Mitsubishi Chemical Co., Ltd.); SP-900 (aromatic resin, trade name, Mitsubishi Chemical Co., Ltd.); Amberlite (trademark) XAD-2, XAD-4, XAD-16, XAD -2000 (above, aromatic resins, all trade names, Organo Co., Ltd.); Diaion (trademark) SP-205, SP-206, SP-207 (above, aromatic resins having hydrophobic substituents, Both are trade names, Mitsubishi Chemical Co., Ltd.); HP-2MG, EX-0021 (Aromatic resins having hydrophobic substituents, both trade names, Mitsubishi Chemical Co., Ltd.); Amberlite (trademark) XAD- 7, XAD-8 (above, acrylic acid ester resin, both trade names, manufactured by Organo Co., Ltd.); Diaion (trademark) HP1MG, HP2MG (above, acrylic acid methacrylic resin, both trade names, Mitsubishi Chemical Corporation) ; Sephadex (trademark) LH20, LH60 (derivatives of cross-linked dextran, both trade names, Pharmacia Biotech Co., Ltd.), and the like. Among them, an unsubstituted aromatic resin (eg, HP-20) or an unsubstituted aromatic resin (eg, SP-850) which has undergone a special treatment is preferable.

The amount of the synthetic adsorbent to be packed in the column can be appropriately determined depending on the size of the column, the type of the synthetic adsorbent, and the like.

When a synthetic adsorbent is used as the immobilizing carrier, the flow rate of the decomposition treatment solution can be appropriately changed depending on the size of the column, the type of elution solvent, the type of synthetic adsorbent, etc., but is preferable. is SV=1 to 30 h− ¹ . Note that SV (Space Velocity) is a unit indicating how many times the resin volume of liquid is passed per hour.

The adsorbed component (active component) adsorbed by the synthetic adsorbent can be eluted with a solvent (elution solvent). From the viewpoint of recovering the adsorbed components more efficiently, it is preferable to wash away the saccharides and inorganic salts remaining in the column with water before eluting the adsorbed components. In this case, the eluted component can be a bagasse decomposition extract.

When a synthetic adsorbent is used as the immobilizing carrier, the elution solvent may be at least one selected from the group consisting of water, methanol, ethanol and mixtures thereof. The elution solvent is preferably a mixed solvent of alcohol and water, more preferably a mixed solvent of ethanol and water, and from the viewpoint that the adsorbed component can be more efficiently eluted at room temperature, the volume ratio is 50/50 to 60/40 /water), a mixed solvent of ethanol and water is more preferred.

When a synthetic adsorbent is used as the immobilizing carrier, the temperature of the column (column temperature) during elution may be room temperature. The mixing ratio can be reduced, and the adsorbed components can be eluted more efficiently. The temperature is preferably 20-60°C, more preferably 40-60°C. The inside of the column may be under normal pressure conditions or under pressurized conditions.

When a synthetic adsorbent is used as the immobilizing carrier, the elution rate can be appropriately set depending on the size of the column, the type of elution solvent, the type of synthetic adsorbent, etc., but SV = 0.1 to 10 ^{hours- 1} .

Ion exchange resins are classified into gel-type resins and porous resins such as porous, microporous, and highly porous resins based on the form of the resin, but there is no particular limitation. The ion exchange resin is preferably an anion exchange resin. As the anion exchange resin, a strongly basic anion exchange resin or a weakly basic anion exchange resin may be used. When an alkaline treatment liquid is used as a raw material, a strongly basic anion exchange resin is preferably used.

Commercially available strongly basic anion exchange resins include Diaion (trademark) PA306, PA308, PA312, PA316, PA318L, HPA25, SA10A, SA12A, SA11A, SA20A, UBA120 (above, Mitsubishi Chemical Corporation), Amberlite ( Trademarks) IRA400J, IRA402Bl, IRA404J, IRA900J, IRA904, IRA458RF, IRA958, IRA410J, IRA411, IRA910CT (manufactured by Organo Corporation), Dowex (trademark) Marathon A, Marathon MSA, MONOSPHERE550A, Marathon A2 (above, Dow Chemical Japan Co., Ltd.).

Commercially available weakly basic anion exchange resins include Diaion (trademark) WA10, WA20, WA21J, WA30 (all above, Mitsubishi Chemical Corporation), Amberlite (trademark) IRA478RF, IRA67, IRA96SB, IRA98, and XE583 (all above, Organo Co., Ltd.), Dowex (trademark) Marathon WBA, MONOSPHERE66, MONOSPHERE77 (all of which are Dow Chemical Japan Co., Ltd.), and the like.

The amount of ion-exchange resin packed in the column can be appropriately determined depending on the size of the column, the type of ion-exchange resin, and the like. ~500 times wet volume is more preferred.

The conditions for passing the liquid can be appropriately set according to the type of the pretreatment liquid, the type of the ion exchange resin, and the like. Preferably, the flow rate is SV=0.3 to 30 hours ^-1 , the flow rate is 100 to 300% of the ion exchange resin, and the column temperature is 40 to 90.degree. The inside of the column may be in a normal pressure or a pressurized state.

When an ion-exchange resin is used as the immobilizing carrier, the bagasse decomposition extract is passed through a column filled with the ion-exchange resin and eluted with an eluent such as a salt, an acid, an alcohol, or a mixed aqueous solution thereof. It may be a fraction. The eluent may be degassed.

The decomposition extract of bagasse, in one embodiment, may be a concentrate obtained by concentrating the above-described decomposition treated liquid or fraction. The concentration method may be a known method, for example, solvent distillation under reduced pressure, lyophilization, or the like. When concentrating, the decomposition-treated liquid or fraction can be concentrated 15 to 30 times, and the concentrated component can be used as a decomposition extract of bagasse.

A decomposition extract of bagasse can be obtained, for example, as follows. A 1% by mass sodium hydroxide aqueous solution is added to the bagasse so that the solid concentration is 0.1 to 50%, and the mixture is boiled at 100° C. to obtain a decomposition treatment liquid (alkaline treatment liquid). The decomposition-treated liquid is subjected to ultrafiltration with a UF membrane having a molecular weight cutoff of 2500 to 5000, and the obtained filtrate is adjusted to acidity, and then a column filled with an unsubstituted aromatic resin is added to the column. Pass the liquid at a temperature of 20 to 60°C. Thereafter, the components adsorbed on the column are eluted with a mixed solvent (elution solvent) of ethanol and water having a volume ratio of 50/50 to 60/40 (ethanol/water) at a column temperature of 20 to 60° C., and ethanol A fraction eluted within 45 times the wet volume of the aromatic resin from the start of elution with a mixed solvent of water and water is collected. The collected fractions (fractions containing components having anti-type I allergy activity) are collected and concentrated by conventional means (solvent distillation under reduced pressure, freeze-drying, etc.) to obtain a bagasse decomposition extract. be able to. The bagasse decomposition extract thus obtained can be stored as a concentrated liquid or powder extract having a solid content of 30% by mass or more. Preservation of the extract is preferably carried out by refrigeration when the extract is liquid.

As another example, the decomposition extract of bagasse can also be obtained as follows. That is, water is added to bagasse so that the solid concentration is 0.1 to 50%, hydrothermal treatment is performed with water at 130 to 250 ° C. under a pressure of 0.2 to 4.0 MPa, and solid-liquid separation is performed by filtration. to obtain a decomposition treatment liquid (hydrothermal treatment liquid). The resulting hydrothermal treatment solution was passed through a column filled with an aromatic resin that had been specially treated to be unsubstituted, at a temperature of 20 to 60 ° C., and then the components adsorbed in the column were measured at the column temperature. At 20 to 60 ° C., eluted with a mixed solvent (elution solvent) of ethanol and water at a volume ratio of 50/50 to 60/40 (ethanol/water), and collected from the start of elution with a mixed solvent of ethanol and water. Collect the fraction in which the amount of eluate obtained is within 5 times the wet volume of the aromatic resin. The collected fractions (fractions containing components having anti-type I allergy activity) are collected and concentrated by conventional means (solvent distillation under reduced pressure, freeze-drying, etc.) to obtain a bagasse decomposition extract. be able to. The bagasse decomposition extract thus obtained can be stored as a concentrated liquid or powder extract having a solid content of 30% by mass or more. Preservation of the extract is preferably carried out by refrigeration when the extract is liquid.

The bagasse decomposition extract in each of the above-described embodiments may be liquid or powder. The powdery bagasse decomposition extract is produced, for example, using a liquid bagasse decomposition extract by a spray drying method, a freeze-drying method, a fluid bed granulation method, or a pulverization method using an excipient. be able to.

The anti-type I allergy agent according to the present embodiment may consist only of the decomposition extract of bagasse, which is an active ingredient, or may further contain materials that can be used for foods, quasi-drugs, or pharmaceuticals. Materials that can be used for foods, quasi-drugs, or pharmaceuticals are not particularly limited, but examples include amino acids, proteins, carbohydrates, fats and oils, sweeteners, minerals, vitamins, flavors, excipients, and binders. , lubricants, disintegrants, emulsifiers, surfactants, bases, solubilizers, suspending agents and the like.

Proteins include, for example, milk casein, whey, soybean protein, wheat protein, egg white and the like. Carbohydrates include, for example, corn starch, cellulose, pregelatinized starch, wheat starch, rice starch, potato starch and the like. Fats and oils include, for example, salad oil, corn oil, soybean oil, safflower oil, olive oil, palm oil and the like. Sweeteners include, for example, sugars such as glucose, sucrose, fructose, high-fructose corn syrup, high-fructose corn syrup, sugar alcohols such as xylitol, erythritol, and maltitol, and artificial sweeteners such as sucralose, aspartame, saccharin, and acesulfame K. sweeteners, stevia sweeteners, and the like. Minerals include, for example, calcium, potassium, phosphorus, sodium, manganese, iron, zinc, magnesium, and salts thereof. Examples of vitamins include vitamin E, vitamin C, vitamin A, vitamin D, B vitamins, biotin, niacin and the like. Excipients include, for example, dextrin, starch, lactose, crystalline cellulose and the like. Examples of binders include polyvinyl alcohol, gelatin, hydroxypropylmethylcellulose, hydroxypropylcellulose, sodium carboxymethylcellulose, polyvinylpyrrolidone and the like. Lubricants include, for example, magnesium stearate, calcium stearate, talc and the like. Examples of disintegrants include crystalline cellulose, agar, gelatin, calcium carbonate, sodium hydrogencarbonate, dextrin and the like. Examples of emulsifiers or surfactants include sucrose fatty acid esters, citric acid, lactic acid, glycerin fatty acid esters, polyglycerin fatty acid esters, sorbitan fatty acid esters, propylene glycol fatty acid esters, and lecithin. Bases include, for example, cetostearyl alcohol, lanolin, polyethylene glycol and the like. Examples of solubilizing agents include polyethylene glycol, propylene glycol, sodium carbonate, sodium citrate and the like. Suspending agents include, for example, glyceryl monostearate, polyvinyl alcohol, polyvinylpyrrolidone, methylcellulose, hydroxymethylcellulose, sodium alginate and the like. You may use these individually by 1 type or in combination of 2 or more types.

When the anti-type I allergy agent contains other materials, the content of the bagasse decomposition extract, which is an active ingredient, may be appropriately set according to the form and purpose of use of the anti-type I allergy agent described later. , From the viewpoint of more easily suppressing degranulation of adipocytes or basophils, based on the total amount of anti-type I allergy agent, preferably 100 μg / g or more, more preferably 25 μg / g or more, still more preferably 400 μg / g or more, preferably 10 mg/g or less, more preferably 7.5 mg/g or less, still more preferably 5 mg/g or less.

The anti-type I allergy agent may be in any form such as solid (powder, granules, etc.), liquid (solution, suspension, etc.), paste, etc., and may be powders, pills, granules, tablets, capsules, It may be in any dosage form such as troches, solutions, suspensions, and the like.

In the anti-type I allergy agent of the present embodiment, in the type I allergic reaction, granules containing chemical mediators such as histamine and leukotrienes are extracellularly released from mast cells or basophils (degranulation). has an inhibitory action (degranulation inhibitory action). Therefore, according to the anti-type I allergy agent of the present embodiment, symptoms caused by type I allergic reaction can be effectively suppressed, treated or prevented.

Whether or not an anti-type I allergy agent has an inhibitory effect on degranulation is determined by the cross-linking of IgE bound to the surface of cells such as rat basophilic leukemia cells (RBL-2H3 cells) by antigens. Then, using cells that release granulocytes containing histamine, etc. to the outside of the cells, when these cells are stimulated with an antigen, the anti-type I allergy agent is added compared to the sample without the addition of the anti-type I allergy agent. It can be confirmed by calculating how much the degranulation of the sample obtained by the treatment is suppressed.

Anti-type I allergy agents can be used as foods, quasi-drugs, or pharmaceuticals. Foods may be provided in the form of, for example, health foods, foods for specified health uses, functional foods, functional foods, and supplements.

The anti-type I allergy agent may be administered parenterally such as intravenously, or may be administered orally. The anti-type I allergy agent is preferably administered orally.

When the anti-type I allergy agent is administered parenterally, the dosage is, for example, preferably 50 μg/kg (body weight) or more of the bagasse decomposition extract per administration, such as 150 μg/kg. (body weight) or more, more preferably 250 μg/kg (body weight) or more. In addition, the bagasse decomposition extract is preferably administered at a daily dose of 100 µg/kg (body weight) or more, more preferably 300 µg/kg (body weight) or more, and more preferably 500 µg/kg. (body weight) or more is more preferably administered. In addition, the bagasse decomposition extract is preferably administered at a dose of 2000 mg/kg (body weight) or less, more preferably 1500 mg/kg (body weight) or less, and 1000 mg. /kg (body weight) or less is more preferable. In addition, the content of the bagasse decomposition extract is preferably 4000 mg/kg (body weight) or less per day, more preferably 3000 mg/kg (body weight) or less, and more preferably 2000 mg/kg. It is more preferable to administer so that (body weight) is as follows. Within this range, a sufficient blood concentration can be achieved, and the anti-type I allergy effect can be exhibited better.

When the anti-type I allergy agent is orally administered, the dose of the bagasse decomposition extract is preferably 50 μg/kg (body weight) or more, preferably 100 μg/kg (body weight) per administration. It is more preferable to administer the drug so that it reaches 150 μg/kg (body weight) or more, and it is even more preferable to administer it so that it reaches 150 μg/kg (body weight) or more. In addition, the bagasse decomposition extract is preferably administered at a daily dose of 150 µg/kg (body weight) or more, more preferably 300 µg/kg (body weight) or more, and more preferably 450 µg/kg. (body weight) or more is more preferably administered. In addition, the bagasse decomposition extract is preferably administered at a dose of 1000 mg/kg (body weight) or less, more preferably 800 mg/kg (body weight) or less, and 600 mg/kg (body weight) or less. It is more preferable to administer so as to give kg (body weight) or less. In addition, the content of the bagasse decomposition extract is preferably 3000 mg/kg (body weight) or less per day, more preferably 2000 mg/kg (body weight) or less, and more preferably 1000 mg/kg. It is more preferable to administer so that (body weight) is as follows. Within this range, a sufficient blood concentration can be achieved, and the anti-type I allergy effect can be exhibited better.

Since the anti-type I allergy agent of the present embodiment has the above-described action, it can be used for patients with symptoms of type I allergy, and for allergy-naive persons who desire to prevent type I allergy. .

EXAMPLES The present invention will be described below with reference to Examples, but the present invention is not limited to these Examples. The decomposition extract of bagasse may be hereinafter simply referred to as "extract".

<Production of bagasse decomposition extract>
[Production Example 1]
15 kg of sugarcane pomace bagasse (water content: 50% by mass) and 100 L of 0.5% (w/w) sodium hydroxide aqueous solution were mixed and subjected to alkali treatment at 150°C. The mixed liquid after the alkali treatment was separated into a solid content and a liquid content to obtain about 100 L of the liquid content. Ultrafiltration was performed using a UF membrane (GE Water & Process Technology, GH8040F30) with a molecular weight cutoff of 2500 to obtain 80 L of filtrate. Synthetic adsorbent (Mitsubishi Chemical Co., Ltd., HP-20) 1L is filled in a resin tower (inner diameter 80mm, height 400mm), and the above filtrate is added to it after adjusting the pH to 6, and the flow rate is 10L / hour. (SV=10.0 (time ^-1 )).

Subsequently, 5 L of purified water was passed through the resin tower at a flow rate of 10 L/hour (SV=10.0 (time ⁻¹ )) for washing. Next, 2 L of 60% ethanol aqueous solution (ethanol/water=60/40 (volume/volume)) as an elution solvent was passed through the resin column at a flow rate of 2 L/hour (SV=2.0 (time ⁻¹ )). . Subsequently, 2 L of purified water was passed through the resin column at a flow rate of 2 L/hour (SV = 2.0 (time ^-1 )) to elute the components adsorbed by the synthetic adsorbent. The fraction eluted from the resin column was concentrated under reduced pressure to about 10 times the concentration using a rotary evaporator, and freeze-dried overnight to obtain 20 g of brown powder as a bagasse decomposition extract. This was designated as extract A.

[Production Example 2]
30 kg of bagasse (water content: 50% by mass), which is sugarcane pomace, was hydrothermally treated with 100 L of hot water at 200° C. and 1.8 MPa. The mixed liquid after the pretreatment was separated into a solid content and a liquid content to obtain about 88 L of the liquid content. Ultrafiltration was performed using a UF membrane (GE Water & Process Technology, GH8040F30) with a molecular weight cutoff of 2500 to obtain 70 L of filtrate. 1 L of synthetic adsorbent (Mitsubishi Chemical Co., Ltd., SP-850) was packed in a resin column (inner diameter 80 mm, height 400 mm), and 25 L of the above filtrate was added thereto at a flow rate of 20 L/hour (SV = 20. 0 (time ^-1 )).

Subsequently, 3.3 L of purified water was passed through the resin tower at a flow rate of 20 L/hour (SV=20.0 (time ⁻¹ )) to wash the resin. Next, 2 L of 60% ethanol aqueous solution (ethanol/water=60/40 (volume/volume)) as an elution solvent was passed through the resin column at a flow rate of 2 L/hour (SV=2.0 (time ⁻¹ )). . Subsequently, 2 L of purified water was passed through the resin column at a flow rate of 2 L/hour (SV = 2.0 (time ^-1 )) to elute the components adsorbed by the synthetic adsorbent. The fraction eluted from the resin column was concentrated under reduced pressure to about 10 times the concentration using a rotary evaporator, and freeze-dried overnight to obtain 40 g of brown powder as a bagasse decomposition extract. This was designated as Extract W.

<Test 1: RBL-2H3 cell degranulation inhibition test by extract A>
[Preparation of test solution]
Extract A was dissolved in water to prepare a 50 mg/mL test liquid stock solution. This undiluted test solution was diluted with the buffer solution shown in Table 1 below to prepare test solutions with analyte concentrations of 2000, 1000 and 500 μg/mL.

[Test operation]
RBL-2H3 cells, which are rat basophilic leukemia cells (National Institute of Biomedical Innovation, Health and Nutrition), were seeded in a 96-well plate and cultured overnight. A medium having the composition shown in Table 1 and containing an anti-DNP-IgE antibody was added, reacted at 37° C. for 2 hours, and then washed with a buffer solution. Furthermore, the prepared test solutions of 2000, 1000 and 500 µg/mL were prepared so that the final concentrations were 1000 µg/mL (Example 1), 500 µg/mL (Example 2) and 250 µg/mL (Example 3). added. Then, after reacting at 37°C for 10 minutes, DNP-labeled human serum albumin was added and reacted at 37°C for additional 3 hours. In addition, an untreated control (Comparative Example 1) was added with only the buffer solution without adding the test solution, and wortmannin (Wako Pure Chemical Industries, Ltd.) was added to a final concentration of 25 nmol / L. was similarly tested as a positive control. In addition, after addition of a medium containing no anti-DNP-IgE antibody, a buffer solution and DNP-labeled human serum albumin were sequentially added and reacted in the same manner as an antigen-unstimulated control.

After all the cell supernatant was dispensed into empty wells, a lysis buffer was added to the cells and allowed to stand at room temperature for 10 minutes to obtain a cell lysate. A p-nitrophenyl-2-acetamido-2-deoxy-β-D-glucopranoside solution (hereinafter referred to as substrate solution) was added to each of the cell supernatant and cell lysate, and reacted at 37°C for 25 minutes. After that, glycine buffer was added to stop the reaction. A glycine buffer was added to each of the cell supernatant and the cell lysate, reacted at 37° C. for 25 minutes, and then the substrate solution was added to prepare a sample blank.

[Calculation of degranulation rate]
For each sample of Examples 1 to 3, Comparative Example 1, positive control, antigen-unstimulated control, and sample blank, a microplate reader (SpectraMax M2e, Molecular Devices) was used to measure β-hexosamini present in granules. The absorbance of p-nitrophenol produced by the reaction between the dase and the substrate was measured (measurement wavelength: 405 nm, control wavelength: 650 nm).

From the absorbance of each sample with respect to the absorbance of Comparative Example 1, the release rate was determined by the following formula, and the degranulation rate was calculated from the release rate. In the formula, the "absorbance on the cell supernatant side" and the "absorbance on the cell solution side" are values obtained by subtracting the sample blank.
Release rate (%) = absorbance on cell supernatant side / (absorbance on cell supernatant side + absorbance on cell solution side)
Degranulation rate (%) = {(release rate of test solution - release rate of antigen-unstimulated control) / (release rate of untreated control - release rate of antigen-unstimulated control)} x 100

FIG. 1 shows the results of calculating the degranulation rate. The degranulation rate was 100±11.5 in Comparative Example 1, while the positive control was 39±8.4, Example 1 was 49±12.5, and Example 2 was 61±11.2. , Example 3 was 77±11.1.

<Test 2: RBL-2H3 cell degranulation inhibition test by extract W>
[Preparation of test solution]
Extract W was dissolved in ethanol to prepare a stock solution of 50 mg/mL test solution. This test liquid stock solution was diluted with the buffer solution shown in Table 1 above to prepare test liquids with specimen concentrations of 1000, 500 and 250 μg/mL.

[RBL-2H3 cell degranulation inhibition test]
Using the test solution containing the prepared extract W, the final concentration of the test solution was 500 μg/mL (Example 4), 250 μg/mL (Example 5) and 125 μg/mL (Example 5) during the test operation in Test Example 1 described above. The degranulation rate was calculated in the same manner as in Test Example 1, except that the test solution was added so as to obtain Example 6). Comparative Example 1 is an untreated control similar to Test Example 1.

FIG. 2 shows the results of calculating the degranulation rate. The degranulation rate was 100±2.9 in Comparative Example 1, 12±1.6 in Example 4, 47±4.9 in Example 5, and 80±6.0 in Example 3. was 1.

Claims (9)

An anti-type I allergy agent containing a bagasse decomposition extract as an active ingredient. The bagasse decomposition extract is a decomposition-treated liquid obtained by at least one decomposition treatment selected from the group consisting of alkali treatment, hydrothermal treatment, acid treatment, subcritical water treatment, pulverization treatment, and explosion treatment. Item 2. The anti-type I allergy agent according to item 1. 3. The anti-type I allergy agent according to claim 2, wherein the decomposition extract of bagasse is a fraction obtained by passing the decomposition-treated liquid through a column packed with an immobilizing carrier. 4. The anti-type I allergy agent according to claim 3, wherein the fixed carrier is a synthetic adsorbent or an ion exchange resin. The immobilizing carrier is a synthetic adsorbent, and the bagasse decomposition extract removes components adsorbed by the synthetic adsorbent with at least one solvent selected from the group consisting of water, methanol, ethanol, and mixtures thereof. 4. The anti-type I allergy agent according to claim 3, which is a fraction obtained by elution. The anti-type I allergy agent according to claim 4 or 5, wherein the synthetic adsorbent is an aromatic resin, an acrylic methacrylic resin, or an acrylonitrile aliphatic resin. The bagasse decomposition extract is obtained by passing the decomposition treated liquid through a column filled with a synthetic adsorbent as a fixed carrier, and eluting the components adsorbed by the synthetic adsorbent with a mixed solvent of ethanol and water. is the fraction obtained by
The synthetic adsorbent is an unsubstituted aromatic resin,
The temperature of the column is 20-60° C.,
The type I allergy agent according to claim 2, wherein the mixed solvent has a volume ratio of ethanol and water (ethanol/water) of 50/50 to 60/40. The anti-type I allergy agent according to any one of claims 1 to 7, which is based on mast cell or basophil degranulation inhibitory action. An agent for suppressing degranulation of mast cells or basophils, comprising a bagasse decomposition extract as an active ingredient.

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