JP2007023018A - Allergic rhinitis-improving agent - Google Patents

Abstract

<P>PROBLEM TO BE SOLVED: To provide a highly safe composition for internal use excellent in improving effect for allergic rhinitis. <P>SOLUTION: The allergic rhinitis-improving agent for internal use contains a xylooligosaccharide composition comprising acidic xylooligosaccharide having ≥1 uronic acid residue per 1 molecule and 2-15 average degree of polymerization as an effective component. The acidic xylooligosaccharide is preferably obtained by preparing a complex by enzymatically and/or physicochemically treating lignocellulose material, subsequently hydrolyzing the complex and separating from the hydrolyzed product. <P>COPYRIGHT: (C)2007,JPO&INPIT

Description

  The present invention relates to an allergic rhinitis improving agent that is highly safe for the human body and has an improving effect on allergic rhinitis such as hay fever.

In recent years, so-called hay fever using pollen such as cedar and hinoki as an antigen has been increasing, which has become a major social problem. Hay fever is an allergic disease with pollen as an antigen, and symptoms include runny nose and headache due to rhinitis, itching of the mucous membrane of the eyes, and the like. Among them, runny nose and headache due to rhinitis are particularly serious problems.
When pollen adheres to the mucous membrane of the nose, an antibody against pollen (IgE) is produced in the mucosa, and this antibody binds to mast cells present in the mucosa. Next, when pollen invades, when pollen binds to the antibody part bound to mast cells, chemical mediators such as histamine and prostaglandins are released, and these chemical mediators act on the nervous system, causing runny nose, sneezing, etc. Causes hay fever symptoms (see Non-Patent Document 1).
As a prevention / treatment method for hay fever, drugs that suppress these chemical mediators (antihistamines, histamine antagonists, etc.) are generally used. However, the use of these chemical mediator inhibitors may cause side effects such as fatigue, drowsiness, dry mouth, headache, and digestive disorders, and there are concerns about safety to the human body when used for a long time. (See Non-Patent Document 2).
The present applicants have reported a method for producing acidic xylo-oligosaccharides (see Patent Document 1), and have reported on hay fever ameliorating action of acidic xylo-oligosaccharides for external use (see Patent Document 2). However, there is no literature reporting on the hay fever ameliorating effect of internal use of acidic xylo-oligosaccharides.
RM Naclerio N. Engl. J. Med., 313, 65 (1985) Toshiji Oda Therapeutic Drug Manual (Medical School) 1993 p180 JP 2003-183303 A JP-A-2005-112826

  The subject of this invention makes it a subject to provide the highly safe composition excellent in the improvement effect of allergic rhinitis.

As a result of intensive studies to solve the above problems, the present inventors have found that an acidic xylo-oligosaccharide composition to which a uronic acid residue is added has an excellent allergic rhinitis improving effect for internal use.
The present invention adopts the following configuration in order to solve the above problems. That is, the first of the present invention is “an allergic rhinitis remedy for internal use characterized by containing an acidic xylo-oligosaccharide having a uronic acid residue in the xylo-oligosaccharide molecule as an active ingredient”.
According to a second aspect of the present invention, in the first aspect, the acidic xylo-oligosaccharide is a mixed composition of oligosaccharides having different degrees of xylose polymerization, and the average degree of polymerization is 2.0 to 15.0. Is an allergic rhinitis improving agent for internal use.
A third aspect of the present invention is the composite of the xylooligosaccharide component and the lignin component obtained by subjecting the lignocellulose material to enzymatic and / or physicochemical treatment in the first or second invention. Then, the complex is subjected to an acid hydrolysis treatment to obtain a xylo-oligosaccharide mixture, and from the resulting xylo-oligosaccharide mixture, xylo-oligosaccharide having at least one uronic acid residue as a side chain in one molecule is decomposed. It is an allergic rhinitis remedy for internal use, which is obtained by
A fourth aspect of the present invention is the internal allergic rhinitis improving agent characterized in that the uronic acid is glucuronic acid or 4-O-methyl-glucuronic acid in the first to third inventions.

  According to the present invention, a highly safe allergic rhinitis improving agent excellent in allergic rhinitis improving effect is provided.

Hereinafter, although the structure of this invention is explained in full detail, this invention is not limited by this. The xylooligosaccharide refers to a xylose polymer that is a dimer of xylose, a xylotriose that is a trimer, or a tetramer to a 20-mer polymer of xylose. The acidic xylo-oligosaccharide used in the present invention means one having at least one uronic acid residue in one molecule of xylo-oligosaccharide.
Moreover, the mixed composition of the oligosaccharide from which the polymerization degree of xylose differs may be sufficient. Generally, it is often obtained as such a composition in order to produce it from a natural product. Hereinafter, an acidic xylo-oligosaccharide composition will be mainly described.

  The average degree of polymerization of the composition is preferably 2.0 to 15.0, more preferably 2.0 to 11.0. The difference between the upper limit and the lower limit of the xylose chain length is preferably 20 or less, and more preferably 10 or less. Uronic acid is known in nature as a component of a polysaccharide having various physiological activities such as pectin, pectinic acid, alginic acid, hyaluronic acid, heparin, chondroitin sulfate, and deltaman sulfate. Although it does not specifically limit as uronic acid in this invention, Glucuronic acid or 4-0-methyl-glucuronic acid is preferable.

If the acidic xylo-oligosaccharide composition as described above can be obtained, its production method is not particularly limited. (1) A method of extracting xylan from wood and enzymatically decomposing it (cellulase research group published, Cellulase Research) Newsletter Volume 16, issued on June 14, 2001, p17-26), (2) Lignocellulose material is treated enzymatically and / or physicochemically to obtain a complex of xylooligosaccharide component and lignin component, Then, the complex is subjected to an acid hydrolysis treatment to obtain a xylooligosaccharide mixture, and a method for separating xylooligosaccharide having at least one uronic acid residue as a side chain in one molecule from the obtained xylooligosaccharide mixture is mentioned. It is done.
In particular, the method (2) is preferable because it can produce a large amount of a polymer having a relatively high degree of polymerization, such as a 5-10 mer, at a low cost.

  The acidic oligosaccharide composition can be obtained through a hydrolysis process, a concentration process, a dilute acid treatment process, and a purification process using a lignocellulosic material derived from chemical pulp as a raw material. In the hydrolysis process, xylan in lignocellulose is selectively hydrolyzed with dilute acid treatment, high-temperature and high-pressure steam (cooking / explosion) treatment, or hemicellulase, and a high molecular weight complex composed of xylooligosaccharide and lignin is intermediated. Get as a body. In the concentration step, the xylooligosaccharide-lignin-like substance complex is concentrated by a reverse osmosis membrane or the like, and oligosaccharides having a low polymerization degree, low-molecular impurities, and the like can be removed. In the concentration step, a reverse osmosis membrane is preferably used, but ultrafiltration membrane, salting out, dialysis and the like are also possible. A lignin-like substance is released from the complex by the diluted acid treatment step of the obtained concentrated liquid, and a diluted acid-treated liquid containing acidic xylo-oligosaccharides and neutral xylo-oligosaccharides can be obtained. At this time, the lignin-like substance separated from the complex condenses and precipitates under acidic conditions and can be removed by filtration using a ceramic filter or filter paper. In the dilute acid treatment step, acid hydrolysis is preferably used, but enzymatic degradation using lignin degrading enzyme or the like is also possible.

  The purification process includes an ultrafiltration process, a decolorization process, and an adsorption process. Some lignin-like substances remain in the solution as soluble polymers, but are removed by an ultrafiltration process, and most of impurities such as coloring substances are removed by a decolorization process using activated carbon. In the ultrafiltration step, an ultrafiltration membrane is preferably used, but reverse osmosis membrane, salting out, dialysis and the like are also possible. Acid xylo-oligosaccharides and neutral xylo-oligosaccharides are dissolved in the sugar solution thus obtained. Only an acidic xylo-oligosaccharide can be extracted from this sugar solution by an adsorption process using an ion exchange resin. First, the sugar solution is treated with a strong cation exchange resin to remove metal ions in the sugar solution. Next, sulfate ions and the like in the sugar solution are removed using a strong anion exchange resin. In this step, simultaneously with the removal of sulfate ions, a part of the organic acid, which is a weak acid, and the colored component are simultaneously removed. The sugar solution treated with the strong anion exchange resin is treated again with the strong cation exchange resin to further remove metal ions. Finally, it is treated with a weak anion exchange resin to adsorb acidic xylo-oligosaccharides to the resin.

By eluting the acidic oligosaccharide adsorbed on the resin with a low-concentration salt (NaCl, CaCl ₂ , KCl, MgCl _2, etc.), an acidic xylooligosaccharide solution free from impurities can be obtained. From this solution, for example, a powder of a white acidic xylo-oligosaccharide composition can be obtained by spray drying or freeze-drying treatment.

  The merit of the above-mentioned production method of acidic xylooligosaccharide composition using chemical pulp-derived lignocellulose as a raw material and high molecular weight complex consisting of xylooligosaccharide and lignin as an intermediate is economical and acidic with high average polymerization degree of xylose. The xylo-oligosaccharide composition is easily obtained. The average degree of polymerization can be changed, for example, by adjusting dilute acid treatment conditions or treating with hemicellulase again. In addition, by changing the salt concentration of the eluate used for elution of the weak anion exchange resin, acidic xylo-oligosaccharide compositions having different numbers of uronic acid residues bound per molecule can be obtained. Furthermore, it is also possible to obtain an acidic xylo-oligosaccharide composition in which the uronic acid binding site is limited to the terminal by acting an appropriate xylanase or hemicellulase.

Although the ingestion form of the allergic rhinitis improving agent containing the acidic xylo-oligosaccharide of the present invention may be ingested directly, it can be added to beverages or foods. When ingested directly, it may be pulverized or tableted by tableting.
The allergic rhinitis improving agent containing acidic xylooligosaccharides in the present invention can be used as a medical food by mixing with other foods, enteral nutrients, other nutritional components, or pharmaceuticals. It can also be provided as a quasi-drug or pharmaceutical by mixing with ingredients generally used in quasi-drugs or pharmaceuticals. It should be noted that the above-mentioned foods, medical foods and pharmaceuticals can be used not only as humans but also as foods for dogs and cats and functional foods.

EXAMPLES Hereinafter, although an Example demonstrates this invention in detail, this invention is not limited by this. First, an outline of each measurement method and Preparation Examples 1 to 3 of acidic xylo-oligosaccharides (UX10, UX5, UX2) contained as active ingredients in the present invention are shown.
<Outline of measurement method>
(1) Quantification of total sugar amount The total sugar amount is prepared using D-xylose (manufactured by Wako Pure Chemical Industries, Ltd.) with a calibration curve, and the phenol-sulfuric acid method (quantitative method for reducing sugar, published by Academic Publishing Center). And quantified.
(2) Quantification of reducing sugar amount The reducing sugar amount was prepared by using D-xylose (manufactured by Wako Pure Chemical Industries, Ltd.) as a calibration curve, and the Sommoji-Nelson method (quantitative method for reducing sugar, published by Academic Publishing Center). And quantified.
(3) Determination of the amount of uronic acid The uronic acid was prepared using a calibration curve using D-glucuronic acid (manufactured by Wako Pure Chemical Industries, Ltd.), with the carbazole sulfate method (quantitative method for reducing sugar, published by the Academic Publishing Center) Quantified.
(4) Determination of average degree of polymerization Keep the sample sugar solution at 50 ° C, centrifuge at 15,000 rpm for 15 minutes to remove insoluble matter, and divide the total sugar amount in the supernatant by the amount of reducing sugar (both converted to xylose). The average degree of polymerization was determined.
(5) Method for analysis of acidic xylooligosaccharides:
The oligosaccharide chain distribution was analyzed using an ion chromatograph (Dionex, analytical column: Carbo Pac PA-10). A 100 mM NaOH solution is used as a separation solvent, and sodium acetate is added to the above-mentioned separation solvent so as to have a concentration of 500 mM as an elution solvent, so that the separation solvent: elution solvent = 10: 0 to 4: 6 in a solution ratio. A simple linear gradient was combined and separated. From the obtained chromatogram, the difference between the upper limit and the lower limit of the xylose chain length was determined.
(6) Determination of the number of uronic acid residues per molecule of oligosaccharide The sample sugar solution was kept at 50 ° C. and centrifuged at 15,000 rpm for 15 minutes to remove insoluble matters, and the amount of uronic acid in the supernatant (D- The number of uronic acid residues per oligosaccharide molecule was determined by dividing the glucuronic acid equivalent) by the amount of reducing sugar (xylose equivalent).
(7) Definition of enzyme titer Kaxylan (manufactured by Sigma) was used for measuring the activity of xylanase used as an enzyme. The enzyme titer is defined by measuring the reducing power of reducing sugar obtained by xylanase degrading xylan using the DNS method (quantitative method for reducing sugar, published by the Society Press), and 1 micromole of xylose per minute. The amount of enzyme that generates a reducing power corresponding to 1 was defined as 1 unit.

<Preparation Example: Preparation Example of Acidic Xylooligosaccharide>
<Preparation Example 1>
Oxygen delignified pulp slurry (kappa number 9.6, pulp viscosity 25.1 cps) was obtained from mixed hardwood chips (domestic hardwood 70%, eucalyptus 30%) as a raw material through kraft cooking and oxygen delignification processes. After the pulp was filtered and washed from the slurry, the following enzyme treatment with xylanase was performed using a pulp slurry adjusted to a pulp concentration of 10% and pH 8.
After adding xylanase produced by Bacillus sp. S-2113 strain (National Institute of Advanced Industrial Science and Technology, Patent Microorganism Deposit Center, Deposited Strain FERM BP-5264) to 1 unit / g of pulp, 120 at 60 ° C. Treated for minutes. Thereafter, the pulp residue was removed by filtration to obtain 1050 L of an enzyme treatment liquid.
Next, the obtained enzyme treatment solution was subjected to a concentration step, a dilute acid treatment step, and a purification step in this order.
In the concentration step, a concentrated solution (40-fold concentration) was prepared using a reverse osmosis membrane (Nonto Denko Corporation, RONTR-7410). In the dilute acid treatment step, the pH of the obtained concentrated solution was adjusted to 3.5 and then heat-treated at 121 ° C. for 60 minutes to form precipitates of polymer contaminants such as lignin. Further, the precipitate was removed by ceramic filter filtration to obtain a diluted acid treatment solution.
In the purification process, the ultrafiltration / decolorization process and the adsorption process were performed in this order. In the ultrafiltration / decolorization step, after passing the dilute acid treatment solution through an ultrafiltration membrane (Osmonics, molecular weight cut off 8000), addition of 770 g of activated carbon (Wako Pure Chemical Industries, Ltd.) and ceramic filter filtration To obtain a decolorization treatment solution. In the adsorption process, the decolorization treatment liquid is a strong cation exchange resin (PK218 manufactured by Mitsubishi Chemical Corporation), a strong anion exchange resin (PA408 manufactured by Mitsubishi Chemical Corporation), and a strong cation exchange resin (manufactured by Mitsubishi Chemical Corporation). PK218) Each was sequentially passed through a column packed with 100 kg, and then applied to a column packed with 100 kg of a weak anion exchange resin (WA30 manufactured by Mitsubishi Chemical Corporation). The solution eluted from the weak anion exchange resin packed column with a 75 mM NaCl solution was spray-dried to obtain acidic xylo-oligosaccharide powder (total sugar amount 353 g, recovery rate 13.1%). Hereinafter, this acidic xylo-oligosaccharide is referred to as UX10. According to the measurement method described above, UX10 was a sugar composition compound having an average degree of polymerization of 10.3, a difference between the upper limit and the lower limit of the xylose chain length of 10, and one uronic acid residue per molecule of acidic xylooligosaccharide.

<Preparation Example 2>
To 1160 ml of the diluted acid treatment solution obtained in the same manner as in Preparation Example 1, 28 mg of Sumiteam X (Xylanase manufactured by Shin Nippon Chemical Industry Co., Ltd.) was added and reacted at 40 ° C. for 20 hours. After inactivating the enzyme by heat treatment (70 ° C., 1 hour), the Sumiteam X treatment solution was subjected to the same purification step as in Preparation Example 1 to produce acid xylo-oligosaccharide powder (total sugar amount 21.3 g, recovery rate 22. 2%). Hereinafter, this acidic xylo-oligosaccharide is referred to as UX5. According to the measurement method described above, UX5 was a sugar composition compound having an average degree of polymerization of 4.8, a difference between the upper limit and the lower limit of the xylose chain length of 9, and one uronic acid residue per molecule of acidic xylooligosaccharide.

<Preparation Example 3>
To 100 ml of 10% aqueous solution of UX10 obtained from Preparation Example 1, 50 mg of Sumiteam X (Xylanase manufactured by Shin Nippon Chemical Industry Co., Ltd.) was added, reacted at 60 ° C. for 20 hours, and then 10 g of weak anion exchange resin (WA30). To a column packed with After the column was washed with water, the solution eluted with 75 mM NaCl solution was lyophilized to obtain acidic xylooligosaccharide powder (total sugar amount 2.1 g, recovery rate 21%). Hereinafter, this acidic xylo-oligosaccharide is referred to as UX2. According to the measurement method described above, UX2 was a saccharide composition compound having an average degree of polymerization of 2.3, a difference between the upper limit and the lower limit of the xylose chain length of 2, and one uronic acid residue per molecule of acidic xylooligosaccharide.

<Examples 1-3 and Comparative Example 1>
An aqueous solution containing three types of acidic xylo-oligosaccharides (UX2, UX5, UX10) having different average polymerization degrees obtained by the above-described adjustment examples was prepared. This acidic xylooligosaccharide aqueous solution was orally administered to guinea pigs, and after sensitization and induction with TDI (Toluene-2,4-disisocynate), the number of sneezing and the amount of nasal secretions were measured.

<Example 1>
Example 5 was prepared by dissolving 5 g of acidic xylo-oligosaccharide (UX2) in 100 ml of distilled water to prepare a 5.0% aqueous solution of acidic xylo-oligosaccharide.

<Example 2>
Example 5 was prepared by dissolving 5 g of acidic xylo-oligosaccharide (UX5) in 100 ml of distilled water to prepare an aqueous solution of acidic xylo-oligosaccharide having a concentration of 5.0%.

<Example 3>
Example 5 was prepared by dissolving 5 g of acidic xylo-oligosaccharide (UX10) in 100 ml of distilled water to prepare a 5.0% aqueous solution of acidic xylo-oligosaccharide.

<Comparative Example 1>
Distilled water containing no acidic xylo-oligosaccharide was used as Comparative Example 1.

<Guinea pig oral administration test>
Hartley guinea pigs (4 weeks old: male, 5 animals in each test group) were preliminarily raised for 1 week, and 10% TDI (dissolved in ethyl acetate) was added dropwise to the guinea pig nose (left and right) at 10 μl / day (first day) Eyes to 5th day, 8th day, 15th day, 22nd day). The aqueous solutions of Examples 1 to 3 were orally administered using a stomach tube so that the dose of acidic xylo-oligosaccharide per kg of guinea pig body weight was 0.1 g from the TDI application start date (Day 1) (5 times / week) For 3 weeks). On the other hand, as a blank experiment, 2 ml of the distilled water of Comparative Example 1 was administered per guinea pig (5 times / week, continued for 3 weeks). On the 27th day, 10 μl each of 5% TDI was dropped on the nose (left and right) of the guinea pig, and the number of sneezing and nasal secretion were measured for 15 minutes. The results are shown in Table 1.

  In the test section (Examples 1 to 3) in which acidic xylo-oligosaccharides (UX2, UX5, UX10) were orally administered, the number of sneezing and the amount of nasal discharge were low compared to the blank (Comparative Example 1).

<Examples 4 to 6 and Comparative Example 2>
Capsules containing three types of acidic xylo-oligosaccharides (UX2, UX5, UX10) with different average degrees of polymerization obtained by the above-described adjustment examples were prepared, and a pollen allergy improvement test (monitor test) was conducted by volunteers.

<Example 4>
A capsule containing 250 mg (powder) of acidic xylo-oligosaccharide (UX2) was prepared and used as Example 4.

<Example 5>
A capsule containing 250 mg (powder) of acidic xylo-oligosaccharide (UX5) was prepared and used as Example 5.

<Example 6>
A capsule containing 250 mg (powder) of acidic xylo-oligosaccharide (UX10) was prepared as Example 6.

<Comparative example 2>
A capsule containing no acidic xylo-oligosaccharide was prepared and used as Comparative Example 2.

<Pollenosis improvement test>
The 40 patients with hay fever were divided into 4 groups (1 group: 10 persons), and the following monitor test was conducted in the middle of March when the symptoms of hay fever were severe. Each patient was orally ingested with capsules of Examples 4 to 6 and Comparative Example 2 for 2 weeks (4 capsules per day), and after use, a questionnaire about symptoms was performed. The symptom was evaluated in the following 4 stages, and the average value and standard deviation (SD) of the scores of 10 people were calculated. The results are shown in Table 2.

<Symptoms>
Deteriorated: 0
No change: 1
Pollen alleviated slightly: 2
Pollen alleviation: 3

  In the test section in which the capsules (Examples 4 to 6) containing acidic xylo-oligosaccharides (UX2, UX5, UX10) were taken, an effect of improving hay fever was observed.

<Examples 7 to 9 and Comparative Example 3>
An aqueous solution (dissolved in distilled water) containing 1.5% concentration (w / w) of three types of acidic xylo-oligosaccharides (UX2, UX5, UX10) having different average degrees of polymerization obtained by the above-described adjustment examples was prepared. Example 7 (UX2), Example 8 (UX5), and Example 9 (UX10). Moreover, it was set as the comparative example 3 using distilled water as control.

<Mouse oral administration test>
Balb / c mice (6 weeks old male, 8 animals in each test group) were preliminarily raised for 1 week, and then 100 μl of cedar pollen extract (containing aluminum hydroxide) was intraperitoneally administered to the mice (once / week for a total of 3). Times). In the fourth week, blood was collected from the tail vein, and the IgE concentration in the serum was measured by ELISA. Mice were grouped so that the IgE concentration was uniform in each test group, and from the fourth week onward, the acid xylo-oligosaccharides of Examples 7 to 9 and the distilled water of Comparative Example 3 were orally administered once a day ( Dose: 100 mg / kg body weight of mouse). During the acidic xylo-oligosaccharide administration period, 10 μl of Japanese cedar pollen extract was administered intranasally once a day. In the eighth week, after the cedar pollen extract was administered into the nasal cavity, the number of sneezing and the number of scratches around the nose were measured for 5 minutes. Moreover, the IgE density | concentration in serum was measured in the 8th week. The results are shown in Table 3.

  In the test groups (Examples 7 to 9) in which acidic xylo-oligosaccharides (UX2, UX5, UX10) were orally administered, the number of sneezing and the number of nasal scratches were reduced as compared with the control (Comparative Example 3). Moreover, in the test sections (Examples 7 to 9) in which acidic xylo-oligosaccharides (UX2, UX5, UX10) were orally administered, the IgE concentration in serum, which is an index of allergy, decreased.

<Example 10>
<Safety test>
As a safety test for acidic xylooligosaccharides, a skin irritation test and an acute oral toxicity test were conducted.
<Skin irritation test>
100 μl of 2% by weight acidic xylo-oligosaccharide (UX2, UX5, UX10) aqueous solution was applied to the back skin of C3H mice (male, 6 weeks old, manufactured by Charles River Japan) after hair removal for about 1 month. , Was applied continuously (once / day, 10 animals per group). Abnormalities such as erythema, edema, and inflammation were not particularly observed in the mouse back skin during the application period and 2 weeks after the application was completed. In addition, compared with the blank (water application group), no significant difference (P <0.05) was observed in the body weight transition.
<Acute oral toxicity test>
A 60% by mass acidic xylo-oligosaccharide (UX2, UX5, UX10) aqueous solution was orally administered to each ICR mouse (male, 6 weeks old, manufactured by Charles River Japan Co., Ltd.) using a stomach tube (dosage amount). : 5 g / mouse body weight 1 kg, 10 in each group). There were no deaths until 2 weeks after administration. In addition, there was no significant difference (P <0.05) in weight transition compared to the blank (water administration group).

<Example 11>
<Stability test>
A 60% by mass aqueous acid xylo-oligosaccharide (UX2, UX5, UX10) aqueous solution was prepared and stored at room temperature. The acid xylooligosaccharide aqueous solution immediately after preparation and after storage for 1 month was analyzed by ion chromatogram. The chromatogram pattern of the sample after 1 month storage did not change compared to the sample immediately after preparation. Further, the difference in the area of each peak in the chromatogram was less than 5% between the sample stored for 1 month and the sample immediately after preparation.

According to the present invention, a highly safe composition for the human body excellent in the allergic rhinitis improving effect is provided.

Claims (4)

  An allergic rhinitis improving agent for internal use, which comprises an acidic xylo-oligosaccharide having a uronic acid residue in the xylo-oligosaccharide molecule as an active ingredient.   The allergic rhinitis for internal use according to claim 1, wherein the acidic xylooligosaccharide is a mixed composition of oligosaccharides having different degrees of polymerization of xylose and having an average degree of polymerization of 2.0 to 15.0. Improver.   The acidic xylo-oligosaccharide is “a lignocellulosic material is enzymatically and / or physicochemically treated to obtain a complex of xylo-oligosaccharide component and lignin component, and then the complex is subjected to an acid hydrolysis treatment to form a xylooligosaccharide mixture. The obtained xylo-oligosaccharide mixture is obtained by decomposing xylo-oligosaccharide having at least one uronic acid residue as a side chain in one molecule ". 2. Allergic rhinitis improving agent for internal use according to 2. The internal allergic rhinitis improving agent according to any one of claims 1 to 3, wherein the uronic acid is glucuronic acid or 4-O-methyl-glucuronic acid.