JP4845384B2 - Antiallergic composition and use thereof - Google Patents

Description

  The present invention relates to an extract of Citrurus plants and uses thereof, and more specifically, an antiallergic composition containing an extract or extract from Citrurus plants as an active ingredient, and a novel compound contained in the extract About.

  Citrullus Colocynthis is an annual herbaceous cucurbitaceae (Cucurbitaceae) native to North Africa and native to the desert region from northern Africa to northwestern India. The fruit is about 10 cm in diameter, and is known to have a strong armpit action and gastric mucosa protective action. Further, white sponge-like Colocynth pulp or this decoction or extract obtained by drying the pulp part excluding the peel and seeds from the fruit is used for chronic constipation. The main component that exhibits this armpit action is a bitter glucoside called “Colocynthin”, which is reported to be contained in about 0.6% in the fruit (Non-patent Document 1).

It has been reported that colosin fruit contains flavonoid glycosides, cucurbin-type triterpene glycosides, fatty acids and the like in addition to the above-mentioned bitter glycosides (Non-patent Document 2).
Yoshiaki Honda, edited by the Japanese Pharmaceutical Society, Health and Medicine Series, Herbs, Spices, and Herbal Medicines-Silk Road Medicine,-Maruzen, published in November 2001 NAR Hatam, DA Whiting, NJ Yousif, Phytochemistry, 28, 1268-1271 (1989)

  This time, the present inventors conducted extensive research on the functional components contained in the methanol extract of the dried pulp of Citrullus colosinsis, and as a result, found a new compound that had never been reported so far and determined its chemical structure. As a result of the determination, the above extract was newly found to have antiallergic activity, and the present invention was completed.

Therefore, the present invention is an antiallergic composition characterized by containing, as an active ingredient, an extract or extract obtained by extraction from a Citrurus plant with a lower aliphatic alcohol or a hydrated product thereof.
In addition, the extract or extract used in the antiallergic composition of the present invention contains at least the formula (1):

で表される化合物、および式(2)：

And a compound represented by formula (2):

The compound represented by these is included.
The present invention is also a health food containing the antiallergic composition described above.

  According to the present invention, a plant-derived natural extract can be used as an antiallergic composition having antiallergic activity. Novel compounds are also provided.

The antiallergic composition of the present invention contains, as an active ingredient, an extract or extract extracted from a Citrurus plant using a lower aliphatic alcohol or a hydrated product thereof. Examples of Citrullus plants include Citrullus colocynthis, Citrullus lanatus, Citrullus Vulgaris, and similar plants, and one or more of these can be used. .
Citrullus plant is an annual plant and its production area is not particularly limited, but it is generally distributed in desert areas from Central Asia to northern Africa. In particular, those from Egypt are preferred. These plants usually use fruits. For the fruit, only the flesh may be used except for the skin and seeds. Further, a part of the fruit or pulp may be used after drying, or may be used as it is.

In order to obtain an extract from a Citrullus plant, for example, the skin and seeds are removed from the fruit, and the obtained pulp is directly or dried or pulverized, about 1 to 50 times (weight), preferably 1 to It is appropriate to extract using about 30 times lower aliphatic alcohol or its hydrate. Examples of lower aliphatic alcohols include aliphatic alcohols having 1 to 4 carbon atoms, such as methanol, ethanol, propanol, n-butanol, and t-butanol. Further, it may be a lower aliphatic alcohol hydrate containing about 1 to 30% by weight of water.
Extraction can be performed by digestion or thermal immersion. For example, it is appropriate to carry out by immersing the pulp in the solvent at a temperature of about 50 to 85 ° C. with or without shaking. In the case of immersion under shaking, it is appropriate to carry out for about 30 minutes to 10 hours, and in the case of immersion under non-shaking, it is appropriate to carry out for about 1 day to 20 days. Although it is possible to immerse at a temperature lower than the above temperature, in that case, it is appropriate to immerse for a longer time than the above time. The extraction process may be performed only once for the same raw material, but is preferably performed a plurality of times, for example, about 2 to 5 times.

The obtained extract may be concentrated to obtain an extract. Concentration is preferably performed under low temperature and low pressure. This concentration may be carried out until dry. In addition, you may filter before concentrating and may concentrate a filtrate. The extract may be in a concentrated state, or may be in the form of powder or lyophilized product. As a method of concentrating, a method of obtaining a powder or lyophilized product, a method known in the art can be used.
The obtained extract may be subjected to purification treatment before and after concentration. As the purification treatment, a chromatographic method, an elution method using an ion exchange resin, partition extraction with a solvent, or the like can be employed alone or in combination. For example, examples of the chromatographic method include normal phase chromatography, reverse phase chromatography, high performance liquid chromatography, centrifugal liquid chromatography, column chromatography, thin layer chromatography and the like, or a method of combining them. . In this case, purification conditions such as a carrier and an elution solvent can be appropriately selected according to various chromatographies.

  In particular, it is preferable to concentrate the extract to obtain an extract, which is distributed using ethyl acetate and water, and the resulting aqueous phase is further partitioned and extracted using butanol. Partition extraction can be performed according to a method commonly used in the art, such as room temperature, shaking or non-shaking, and each obtained soluble fraction may be subjected to the purification treatment described above. .

  The extract or extract of the present invention usually preferably contains any one of the compounds represented by the above formulas (1) and (2) and the following formulas (3) to (15). More preferably, it contains any one of the compounds 1) and (2).

  Here, the compounds of the formulas (3) to (15) are known compounds, but the compounds represented by the formulas (1) and (2) have been found as novel compounds. The compounds of formula (1) and formula (2) have been found to inhibit passive skin anaphylaxis (PCA) responses using mice.

The above extract or extract and compound are used as they are or diluted with an appropriate medium and used in the form of pharmaceuticals such as solid preparations or liquid preparations by methods known in the field of manufacturing pharmaceuticals. be able to.
These forms can be produced by adding pharmaceutically acceptable pharmaceutical additives to the active ingredient.

When producing solid preparations such as tablets, powders, granules, pharmaceutically acceptable excipients include excipients (e.g., sugars such as lactose, sucrose, starches such as corn starch, Celluloses such as crystalline cellulose, gum arabic, magnesium aluminate metasilicate, calcium phosphate, etc., lubricants (eg, magnesium stearate, talc, polyethylene glycol, etc.), binders (eg, sugars such as mannitol, sucrose, Crystalline cellulose, polyvinylpyrrolidone, hydroxypropylmethylcellulose, etc.), disintegrating agents (eg starches such as potato starch, celluloses such as carboxymethylcellulose, cross-linked polyvinylpyrrolidone, etc.), colorants, flavoring agents, etc. can be used. .
Tablets can be coated with conventional techniques, such as film coating, so that the active ingredient can be immediate, delayed or sustained release.

  Capsules can be obtained by mixing the active ingredient with an appropriate excipient and filling the resulting mixture into gelatin soft or hard capsules.

  Liquid formulations may be in the form of, for example, aqueous or oily suspensions, solutions, emulsions, syrups or elixirs, and may be provided as a dry product that is regenerated with water or other suitable excipients prior to use. Good.

  In the case of producing such a liquid preparation, as a pharmaceutically acceptable pharmaceutical additive, a solvent (for example, an oily solvent such as olive oil or soybean oil, a hydrophilic solvent such as water, alcohol, or propylene glycol), Solubilizers (eg, polyethylene glycol, cholesterol, etc.), emulsifiers (eg, surfactants), suspending agents (polyvinyl compounds, hydrophilic polymers such as cellulose, surfactants, etc.), preservatives (eg, Parabens, sorbic acid, etc.), coloring agents, flavoring agents and the like can be used.

  Moreover, the said extract or extract and each compound contained in them can be utilized for health food. Health food means a food that is more active than normal food, and is intended for health, health maintenance and promotion, for example, liquid or semi-solid, solid products, specifically powders, In addition to granules, tablets, capsules or liquids, confectionery such as cookies, rice crackers, jelly, yokan, yogurt and manju, soft drinks, teas, nutritional drinks, soups and the like can be mentioned.

In the production process of these foods or to the final product, the above-mentioned extract or the like can be added by mixing, coating, spraying or the like to obtain a health food.
The amount of the extract or extract and compound used can be appropriately adjusted depending on the degree of concentration, purification, severity of the disease, body weight of the user, age, etc., for example, the extract or extract per adult The extract includes about 100 to 20,000 mg depending on the degree of purification, water content, etc., and about 1 to 200 mg in the state of the compound, and is preferably taken about 30 minutes before meals about 3 times a day.
In addition, when used as a health food, an amount that does not adversely affect the taste and appearance of the food, for example, 1 kg of the target food, the above extract or extract or compound is in the range of about 10 to 100,000 mg. It is suitable to use in.

Examples of the extract of the present invention, novel compounds and their actions will be specifically described below.
Production Example 1 Citrullus colosinsis extract
Extraction of citrullus colossinus with methanol 2.5 kg of dried citrullus colossinus pulp (produced in Egypt) was pulverized, methanol (Nacalai Tesque, special grade) (10 L) was added, and the mixture was extracted with heating under reflux for 3 hours. After extraction, the mixture was filtered with a fold-fold filter paper (manufactured by Advantech, No. 2 filter paper). Methanol (10 L) was further added to the extraction residue, and the mixture was heated to reflux for 3 hours, and similarly filtered. Extraction was carried out three times in total, and the extracts were combined, and the solvent was distilled off under reduced pressure using a rotary evaporator to obtain 347.2 g of citrulus colosinsis methanol extract (yield from crude drug: 13.89%).

Solvent fractionation of citrullus colosinis methanol extract
Citrulus colosinsis methanol extract (288.3 g) was partitioned and extracted into an ethyl acetate-water (1: 1, v / v) mixture.
Further, butanol was added to the aqueous layer for solvent extraction, and the solvent was distilled off under vacuum from the ethyl acetate transfer part, the butanol transfer part and the water transfer part, and 131.0 g (6.31%) and 57.8 g ( 2.78%) and 99.5 g (4.79%) of extract were obtained.

Separation of ethyl acetate migration part extract Normal acetate silica gel column chromatography [Fuji Silysia, BW-200, 150-350 mesh, 540 g, mobile phase: n-hexane: ethyl acetate = 20: 1 → 15: 1 → 10: 1 → 5: 1 → 2: 1 → 1: 1 → 1: 2 → ethyl acetate 100% → methanol 100%] to elute and separate, cucurbitacin E 2-O-β- Glucopyranoside (Formula (7), 41.89 g) was obtained.

Separation and purification of butanol transition part extract
Normal phase silica gel column chromatography of butanol transition part extract [Fuji Silysia, BW-200, 150-350 mesh, 540 g, mobile phase: chloroform (manufactured by Nacalai Tesque, special grade): methanol: n-hexane (Nacalai Tesque) Manufactured, special grade) = 20: 3: 1 → 15: 3: 1 → 10: 3: 1 → 7: 3: 1 → 6: 4: 1 → 0: 1: 0] Eleven fractions were obtained.

  The obtained fraction 2 was subjected to column chromatography using ODS (octadecylsilyl) column chromatography (manufactured by Fuji Silysia Co., Ltd., Chromatorex ODS DM1020T, 150 to 350 mesh), and methanol-water (methanol 30% → 50 as a mobile phase). % → 75% → 100%), and cucurbitacin L 2-O-β-glucopyranoside (formula (11), 0.3464 g) and cucurbitacin E 2-O-β-glucopyranoside (formula (7), 0.0831 g) )

  Fraction 8 was separated by ODS column chromatography using methanol-water (methanol 30% → 40% → 60% → 100%) as the mobile phase to obtain isovitexin (formula (4), 0.735 g). It was. The fraction 8-2 obtained by this ODS column chromatography is further subjected to high performance liquid chromatography (hereinafter referred to as HPLC) using 10% acetonitrile as a mobile phase [detector: Shimadzu differential refraction type detector RID-6A, pump: Shimadzu LC -10A, HPLC column: YMC, YMC-Pack ODS-A (250 × 20 mm, id)] to give 4-hydroxybenzyl β-D-glucopyranoside (formula (15), 0.0179 g) It was. Further, fraction 8-6 was subjected to HPLC using 55% methanol as a mobile phase to obtain a compound of the formula (2) (0.0782 g).

  Fractions 4 and 5 obtained by the above butanol extraction were combined and separated by ODS column chromatography using methanol-water (methanol 15% → 30% → 50% → 100%) as a mobile phase. Fraction 4,5-2 was further subjected to HPLC using 25% methanol as a mobile phase to obtain 4- (β-D-galactopyranosyloxy) -benzaldehyde (formula (14), 0.0105 g). Fractions 4,5-4 were subjected to HPLC using 55% methanol as a mobile phase to obtain a compound of the formula (1) from fraction 4,5-4-2 (0.0712 g). Further, the fraction 4,5-4-6 was subjected to HPLC using a polyamine column [YMC-Pack Polyamine II (250 × 20 mm, id)] manufactured by YMC, and cucurbitacin J 2-O-β-glucopyranoside ( Formula (9), 0.0297 g) and cucurbitacin K 2-O-β-glucopyranoside (formula (10), 0.0146 g) were obtained.

  Fractions 6 and 7 obtained by the above butanol extraction were combined and separated by ODS column chromatography using methanol-water (methanol 15% → 30% → 50% → 100%) as a mobile phase. Fraction 6,7-3 was further subjected to HPLC using 50% methanol as a mobile phase to obtain isoorentin 3′-methyl ether (formula (3), 0.0691 g). Also, fractions 6,7-4 were subjected to HPLC using 35% acetonitrile as a mobile phase to give (22,27) -hexanocucurbitacin I 2-O-β-glucopyranoside (formula (6), 0.0245 g). Obtained.

  Fraction 3 obtained by the above butanol extraction was separated by ODS column chromatography using methanol-water (methanol 30% → 50% → 100%) as a mobile phase, and the obtained fraction 3-1 was further obtained. Benzyl β-D-glucopyranoside (formula (12), 0.0141 g) was obtained by HPLC using 40% methanol as a mobile phase. Fraction 3-2 was further subjected to HPLC using 50% methanol as a mobile phase to obtain (22,27) -hexanocucurbitacin I 2-O-β-glucopyranoside (formula (6), 0.0569 g). It was. Fraction 3-3 was further subjected to HPLC using 55% methanol as a mobile phase to obtain cucurbitacin I 2-O-β-glucopyranoside (formula (8), 0.3638 g).

  Fraction 9 obtained by the above butanol extraction was separated by ODS column chromatography using methanol-water (methanol 15% → 30% → 50% → 100%) as a mobile phase, and gastrozin (formula (13) 0.070 g) was obtained.

  Fraction 10 obtained by the above butanol extraction was separated using methanol-water (methanol 15% → 30% → 50% → 100%) as a mobile phase by ODS column chromatography, and isosaponaline (formula (5) 0.0088 g) was obtained.

Among the obtained compounds, the physical properties of the compounds of formulas (1) and (2), which are novel compounds, are shown below. The structural formula of the compound was determined by NMR method.
Compound of formula (1):
Yellow powder;
[α] _D ²⁷ -26.18 ° (c = 0.58, CH ₃ OH);
High resolution positive FAB-MS
Calculated value C ₃₈ H ₅₄ O ₁₄ (M + Na) ⁺ : 757.3411
Found: 757.3418;
UV (MeOH, nm, log ε): 236.0 (4.041);
CD (MeOH, nm, Δε): 229 (-1.116), 279 (+0.631), 330 (-0.638);
IR (KBr, cm ^-1 ): 3440,1718,1686,1680,1650,1637,1078;
FAB-MS: (M + Na) ⁺ : 757 Negative FAB-MS: (MH) ^- : 733

¹ H-NMR (500MHz, CD ₃ OD, δ)
¹³ C-NMR (125 MHz, CD ₃ OD, δ c )

Physical properties of the compound of formula (2):
Yellow powder;
[α] _D ²⁷ -26.18 ° (c = 0.58, CH ₃ OH);
High resolution positive FAB-MS
Calculated value C ₄₂ H ₆₂ O ₁₅ (M + Na) ⁺ : 829.3986
Actual measurement value: 829.3978;
UV (MeOH, nm, log ε): 255 (3.82);
CD (MeOH, nm, Δε): 236 (−0.343), 271 (+0.409), 338 (−0.364);
IR (KBr, cm ^-1 ): 3569, 1686, 1655, 1637, 1037;
FAB-MS: (M + Na) ⁺ : 829, negative FAB-MS: (MH) ⁻ : 805

¹ H-NMR (500 MHz, CD ₃ OD, δ)
¹³ C-NMR (125 MHz, CD ₃ OD, δ c )

Reaction of compound of formula (1) with β-glucosidase The compound of formula (1) above (10 mg) is dissolved in 2 ml of 0.2 M acetate buffer (pH 5.0), and 20 mg of β-glucosidase (derived from almonds) , Manufactured by Oriental Yeast Co., Ltd.) and stirred at 37 ° C. for 1 week. Quench with ethanol, evaporate the solvent under vacuum, silica gel column (1.0 g) with 100% methanol as mobile phase and ODS column (1.0 g with methanol: water = 1: 1 to 100% methanol as mobile phase) ) To separate the following formula (1a):

As a result, 3.0 mg (yield: 38.5%) of the compound represented by the formula:

Reaction of Compound of Formula (1) with Hesperidinase The compound of formula (1) above (6.5 mg) was dissolved in 2 ml of 0.2 M acetate buffer (pH 3.8), and 20 mg of hesperidinase (Aspergillus niger) ), Manufactured by Sigma, Inc.) was added and stirred at 40 ° C. for 48 hours. Quench with ethanol, evaporate the solvent under vacuum, silica gel column (1.0 g) with 100% methanol as mobile phase and ODS column (1.0 g with methanol: water = 1: 1 to 100% methanol as mobile phase) ) To obtain 4.2 mg (yield 83%) of the compound represented by the above formula (1a).

The physical properties of the compound of the above formula (1a) were as follows.
White powder;
[α] _D ²⁷ + 12.67 ° (c = 0.05, CH ₃ OH);
High resolution positive FAB-MS
Calculated value C ₃₂ H ₄₄ O ₉ (M + Na) ⁺ : 595.2883
Actual value: 595.2891;
UV (MeOH, nm, log ε): 256.6 (3.580);
CD (MeOH, nm, Δε): 227 (−0.797), 290 (+1.373), 328 (-1.320);
IR (KBr, cm ^-1 ): 2432, 1736, 1701, 1664, 1648, 1086;
FAB-MS: (M + Na) ⁺ : 595 Negative FAB-MS: (MH) ^- : 571

¹ H-NMR (500 MHz, CD ₃ OD, δ)
¹³ C-NMR (125 MHz, CD ₃ OD, δ c )

Reaction of Compound of Formula (2) with β-Glucosidase The compound of Formula (2) above was reacted with β-glucosidase in the same manner as described above, but the compound of Formula (2) was almost 100%. It was recovered in recovery rate and no reaction occurred.

Reaction of compound of formula (2) with cellulase The compound of formula (2) (10 mg) above was dissolved in 2 ml of 0.2 M acetate buffer (pH 5.0), and 20 mg of cellulase (derived from Aspergillus niger, Sigma And stirred at 37 ° C. for 15 hours. Quench with ethanol, evaporate the solvent under vacuum, separate with silica gel column (1.5 g) using chloroform: methanol = 4: 1 (volume ratio) mixture as mobile phase, and formula (2a):

Thus, 6.2 mg (yield: 76.0%) of the compound represented by the formula:
The physical properties of the compound of the above formula (2a) were as follows.
White powder;
[α] _D ²⁷ + 1.4 ° (c = 0.36, CH ₃ OH);
High resolution positive FAB-MS
Calculated value C ₃₆ H ₅₄ O ₁₁ (M + Na) ⁺ : 683.3407
Actual measurement value: 683.3398;
UV (MeOH, nm, log ε): 257.4 (1.94);
CD (MeOH, nm, Δε): 240 (−0.229), 274 (+0.308), 332 (−0.171);
IR (KBr, cm ^-1 ): 3569, 1686, 1655, 1560, 1541, 1508;
FAB-MS: (M + Na) ⁺ : 683, negative FAB-MS: (MH) ^- : 659

¹ H-NMR (500 MHz, CD ₃ OD, δ)
¹³ C-NMR (125 MHz, CD ₃ OD, δ c )

  Further, the compound of the above formula (2a) was reacted with β-glucosidase in the same manner as described above, but no reaction occurred.

  When the compound of the above formula (2a) (6 mg) was reacted with hesperidinase in the same manner as described above, the following formula (2b):

As a result, 4.0 mg (yield: 88.4%) of the compound represented by the formula:
The physical properties of the compound of the above formula (2b) were as follows.
White powder;
[α] _D ²⁷ + 45.15 ° (c = 0.20, CH ₃ OH)
High resolution EI-MS
Calculated value C ₃₀ H ₄₂ O ₆ (M ⁺ ): 498.281
Actual measurement value: 498.2986;
UV (MeOH, nm, log ε): 268.2 (3.67);
CD (MeOH, nm, Δε): 245 (-0.945), 285 (+2.279), 330 (-1.778);
IR (KBr, cm ^-1 ): 3440, 1718, 1686, 1655, 1637, 1039;
EI-MS (70ev,%): 498 (M ⁺ , 9), 164 (100)

¹ H-NMR (500 MHz, CD ₃ OD, δ)
¹³ C-NMR (125 MHz, CD ₃ OD, δ c )

The ¹³ C-NMR data for the compounds of the above formulas (1), (1a), (2), (2a) and (2b) are shown in Table 1 below. ¹³ C-NMR was measured at 125 MHz in CD ₃ OD.

Example 1
Citrullus colosinsis methanol extract obtained as described above, ethyl acetate transfer part, butanol transfer part and water transfer part from water transfer part in ethyl acetate extraction, and compound of formula (1) and formula ( In order to examine the antiallergic activity of the compound of 2), a PCA reaction test was conducted using mice according to the following method.

PCA reaction test using mouse pinna
The test described in Matsuda H. et al., Bioorg. Med. Chem. Lett., 13, 3197-3202 (2003) was partially modified. That is, 10 μl of diluted anti-DNP IgE (20 μg / ml-PBS) was injected intradermally into both ears of ddY male mice (body weight 25-30 g), and 47 hours later, the test substance was added with gum arabic powder. The suspension was orally administered at a dose of 10 ml / kg. However, they were fasted for 16 to 20 hours before administration of the test substance. One hour later, a mixture of 2% Evans blue and DNP-BSA (1 mg / ml) as an antigen was intravenously administered at a dose of 0.25 ml / mouse. After 30 minutes, the mice were euthanized, the auricles were cut out and dissolved in 1 M KOH solution. To this, 4.5 ml of acetone / 0.2 M phosphoric acid mixture (13: 5 v / v) was added and mixed. After centrifugation, the absorbance of the supernatant was measured at a measurement wavelength of 620 nm. Note that. Tranilast, known as an antiallergic agent, was used as a comparative control substance.

  The results are shown in Table 2. Absorbance values are expressed as mean ± standard error.

  From Table 2, it can be seen that the compounds of formula (1) and formula (2) have PCA reaction inhibitory activity.

Example 2
In order to examine the gastric mucosa protective action of the methanol extract of citrullus colosinsis obtained as described above, the inhibitory action against ethanol and indomethacin-induced gastric mucosal damage was examined according to the following method.

Measurement of inhibitory effect on ethanol-induced gastric mucosal damage Test substance suspended in gum arabic powder was orally administered to Sprague-Dawley male rats (body weight approximately 250 g, fasted for approximately 24 hours before administration) (5 ml / kg) 19.5 hours later, 99.5% ethanol (1.5 mL / rat) was orally administered. After 1 hour, the stomach was removed from the rat, fixed with 1.5% formalin, the stomach was opened, and the length of damage (mm, damage factor) occurring in the gastric mucosa was measured. As a comparative control substance, cetraxate hydrochloride known as a gastritis / ulcer treatment drug was used.
The results obtained are shown in Table 3 below. The value of the damage coefficient is expressed as an average value ± standard error. The ED50 was 8.0 mg / kg for the methanol extract and 15.3 mg / kg for cetraxate hydrochloride.

Measurement of inhibitory action against indomethacin-induced gastric mucosal damage Suspension of test substance in gum arabic powder was orally administered to Sprague-Dawley male rats (body weight approximately 250 g, fasted for approximately 24 hours before administration) (5 ml / kg) 1 hour later, indomethacin (20 mg / kg) was orally administered. After 4 hours, the stomach was excised from the rat and fixed with 1.5% formalin, then the stomach was cut open and the length of damage (mm, damage factor) occurring in the gastric mucosa was measured. Cetraxate hydrochloride was used as a comparative control substance.
The results obtained are shown in Table 4 below. The value of the damage coefficient is expressed as an average value ± standard error.

  From the results in Tables 3 and 4 above, it can be seen that the methanol extract of Citrulus colossinsis has an excellent gastric mucosa protective action.

Example 3
The above-mentioned methanol extract was freeze-dried, and the obtained powder was kneaded into the dough in the process of producing rice crackers to produce rice crackers.

  According to the present invention, an antiallergic composition containing a plant-derived natural extract can be provided. Moreover, the health food containing a natural extract can be obtained using this composition.

Claims (3)

The following formula (1):

And a compound represented by formula (2):

Compound represented by. The compound according to claim 1, wherein the compounds of the formulas (1) and (2) are contained in the fruit of Citrulus colossinsis, which is a Citrurus genus plant. The active ingredient is at least the following formula (1):

A compound represented by, and the formula (2):

The antiallergic composition which is a compound represented by these.