JPH0368515A - Antiallergic drug - Google Patents

Abstract

(57) [Summary] This bulletin contains application data before electronic filing, so abstract data is not recorded.

Description

DETAILED DESCRIPTION OF THE INVENTION [Industrial Field of Application] The present invention relates to compounds that have 5-lipoxygenase inhibitory activity, cyclooxygenase inhibitory activity and hyaluronidase inhibitory activity, and are useful as medicines such as anti-allergic agents.

[Prior art and problems] Arachidonic acid is an unsaturated fatty acid with 20 carbon atoms,
Since mammals cannot synthesize it in their bodies, they must be obtained from outside, and are considered one of the essential fatty acids.

The metabolic pathway of arachidonic acid is called the arachidonic acid cascade, and typical examples include the cyclooxingenase system that synthesizes the prostagranone series and the thromboxane series, and the boxygenase system that synthesizes the leukotriene series.

In recent years, due to pollution problems and environmental changes in Japan, the number of patients with allergic diseases such as bronchial asthma and hay fever is increasing.

Furthermore, with the increase in the elderly population, the number of patients with cardiovascular diseases caused by blood clots is increasing, which has become a major social problem.

Abnormalities in the metabolism of arachidonic acid are thought to be one of the causes of these diseases, and as mentioned above, 5-riboquinease and cyclooxygenase are important enzymes of the arachidonic acid cascade. Inhibitors are thought to be useful as medicines to treat various pathological conditions based on abnormalities in arachidonic acid metabolism, such as inflammation, thrombosis, allergies, and asthma.

Therefore, searches and development of drugs using 5-lipoxygenase inhibition and cyclooxygenase inhibition as indicators have been conducted.

Hyaluronic acid is also a mucopolysaccharide found in mesenchymal tissue.
It is composed of D-glucuronic acid and N-acetylglucosamine, and is thought to be useful in preventing the invasion and spread of microorganisms and toxins.

Hyaluronidase is an enzyme that has the effect of hydrolyzing this hyaluronic acid, and is also related to type I allergic reactions, and is said to be an enzyme that controls the degranulation reaction from mast cells.

Therefore, this hyaluronidase action inhibition activity is considered to be one indicator for searching for drugs with antiallergic action.

[Means for Solving the Problems] The present inventors sought a compound having a 5-lipoxygenase inhibitory effect and a cyclooxygenase inhibitory effect, and a compound having a hyaluronidase inhibitory effect, which are effective in treating diseases caused by abnormal arachidonic acid metabolism. He was conducting intensive research.

As a result, the herbal medicine mulberry bark, which is also used clinically, its original plant mulberry (Morus Ihou, etc.) or other related plants, the herbal medicine licorice, its original plant licorice (Northwestern licorice, Tohoku licorice, etc.), or others. We have discovered that some flavonoids contained in plants of the same genus, Epimedium, or other plants of the same genus have excellent 5-lipoxygenase, cyclooxygenase, and/or hyaluronidase inhibitory effects, leading us to complete the present invention. Ta.

That is, the present invention is based on these findings,
As shown below.

(1) The following formula ■ ■ [However, R1 represents a hydrogen atom, a hydroxyphenyl group, or a hydroxyphenyl group, and R2 represents a 3-methyl-
2-butenyl group, methoxyphenyl group, methoxyphenyl group, or rhamnopyranosiloxol group, R3 represents a hydrogen atom or 3-methyl-2-butenyl station, R4 represents a hydrogen atom, 3-methyl- An anti-allergic agent containing as an active ingredient a compound represented by a 2-butenyl group or a group {circle around (2)} (in which Y represents either a hydrogen atom or a 3-methyl-2-butenyl group).

(2) Anti-allergic compound containing a compound represented by the following formula ■ ■ (where R6 represents a 3-methyl-2-butenyl group or a 3-hydroxy-3-methylbutyl group) as an active ingredient (3)
An anti-allergic agent containing a compound represented by the following formula (1) in which R7 represents a hydrogen atom or a 3-methyl-2-butenyl group as an active ingredient.

(4) The following formula■ (however, R6 is a group ■, Indicates either ■ or ■. An anti-allergic agent containing the compound represented by as an active ingredient.

(5) Anti-allergy containing a compound represented by the following formula IX as an active ingredient (6)
An anti-allergic agent containing a compound represented by the following formula X (wherein R6 represents either a group M or ■) as an active ingredient.

Hereinafter, the compounds of Formulas I, ■, ■, ■, IX and X are collectively referred to as compounds of the formula.

For example, the following methods can be used to obtain the compound of the formula.

After defatting the roots or whole plants of mulberry, licorice, epimedium or each of the various plants with n-hexane, if necessary,
Extract with an organic solvent such as benzene, ethyl acetate, ethanol, methanol, etc., remove the solvent from the extract, dissolve the resulting residue in a solvent such as methanol, benzene, ethyl acetate, etc., and add water, methanol, ethanol, acetic acid. , chloroform, ethyl acetate, n-hexane, acetone, and Hensen as an elution solvent. Dex L+-(-20 or other Sephadex, reversed phase silica gel, silica gel, polyamide, activated carbon, cellulose, etc., is used as a carrier at least once for column chromatography, and while confirming the target component by thin layer chromatography. It can be obtained by fractionation.

Further, in some cases, the product may be purified by recrystallization using a suitable solvent such as benzene, ether, n-hexane, acetone, methanol, or ethanol.

A specific example of the production of the compound of the formula is shown below.

Specific Example 1 Root bark of cultivated mulberry (Morus 1hou) was dried to a dry weight of 26 (9), defatted with n-hexane, and extracted sequentially with benzene and ethyl acetate. The solvent of the extracted limb was distilled off under reduced pressure to obtain 300 g of benzene extract and 1.3 kg of ethyl acetate extract.

Next, benzene extract 3009 was dissolved in methanol to obtain 200 g of methanol-soluble extract. 100 g of this methanol-soluble extract was subjected to column chromatography using silica gel and eluted with a benzene-methanol system. The benzene elution area was searched using thin layer chromatography, and the area containing spots that emitted dark blue fluorescence under ultraviolet irradiation was collected. Colorless plate-like crystals of 200 JIg were obtained by crystallization.

The physical and chemical properties of this colorless plate-like crystal are described in the literature [Hetero
cycle, 9, 1593 (197 g)].

Specific Example 2 In the column chromatography using silica gel in Specific Example 1, the 1% methanol-benzene eluate was purified by preparative thin layer chromatography, recrystallized from benzene-ethyl ether, and a pale yellow prismatic product 14 was obtained. M9
I got it.

The physical and chemical properties of this pale yellow prism nucleus crystal are described in the literature [Ch.
em, Pharm, Bull, , 26.1453 (
197g)] was consistent with that of Kwanon C described.

Specific Example 3 In the column chromatography using silica gel in Specific Example 1, the 1% methanol-benzene eluate was purified by preparative thin layer chromatography, and ethyl ether-n-
Recrystallized from hexane, colorless prismatic product 230
I got Q.

The physical and chemical properties of this colorless prism core crystal are described in the literature [PIa
The results were consistent with those of Kwanone E described in [Nta Med, 42, 79 (1981)].

Concrete Example 4 In the column chromatography using silica gel in Concrete Example 1, the 2% methanol-benzene eluate was searched for by preparative thin layer chromatography, and the part that showed green color in the ferric chloride reaction was collected and reconstituted with methanol. Perform crystallization and obtain yellow needle crystals 60311? I got it.

The physical and chemical properties of this yellow needle crystal are described in the literature [Chem, P.
harm, Bull, 26.1453 (1978)]
It corresponded to that of the described oxine dihydromorsin.

Specific Example 5 In the column chromatography using silica gel in Specific Example 1, the 0.1% methanol-benzene eluate was searched for by preparative thin layer chromatography, and the part showing green color due to the ferric chloride reaction was collected, and the methanol The soluble portion was further subjected to column chromatography using silica gel, the water-saturated benzene eluted portion was searched for by thin layer chromatography, the portion showing green color due to the ferric chloride reaction was collected, and the portion was separated from ethyl ether n-hexane. By recrystallization, 2.49 pale yellow prismatic crystals were obtained.

The physical and chemical properties of this pale yellow prism nucleus crystal are described in the literature [Ch.
em, Pharm, Bull, , 26.1394 (1
978) It was consistent with that of Mornon described in .

Specific example 6 3009 was taken from the ethyl acetate extract of specific example 1,
It was subjected to silica gel column chromatography using benzene-methanol as an eluent. The 5% benzene-methanol eluate was further mixed with benzene-acetone (3:2
) was subjected to preparative thin layer chromatography using a ferric chloride reaction with an Rf value of 4.4.
Areas that turned brown after seconds were collected.

This was again subjected to column chromatography using silica gel, and the eluate was +2 with 25% acetone-n-hexane.
I got a 9.

Furthermore, 59 was taken from this and purified by preparative thin layer chromatography to obtain 2 g of pale yellow powder.

The physical and chemical properties of this pale yellow powder are described in the literature [11eter
occycles, 14.1943 (1980)]. It matched that of 1.

Specific Example 7 The same operation as in Specific Example 6 was performed to obtain a pale yellow powder of 30 degrees 9.

The physical and chemical properties of this pale yellow powder are described in the literature [PIanta
Med., 47, 151 C1983).

Specific Example 8 In the column chromatography using benzene-methanol as the eluent in Specific Example 6, the 5% methanol-benzene eluate was further subjected to silica gel thin layer chromatography using benzene-acetone (III) as the developing solvent. Then, 20 g of a portion having an Rr value of 0.4 and exhibiting a green color due to the ferric chloride reaction and turning brown after 20-30 seconds was obtained.

From this, 300 Ng was taken and purified by preparative thin layer chromatography to obtain pale yellow powder 77119.

The physical and chemical properties of this pale yellow powder are described in the literature [Chem].

Pharm, Bull, 28, 2548 (1980)
] I myself; It matched that of Kwannon G of ldt.

Concrete Example 9 In the column chromatography using benzene-methanol as the eluent group in Concrete Example 6, the 3% methanol-benzene eluate was searched for using silica gel thin layer chromatography, and the region emitting dark blue fluorescence under ultraviolet irradiation was found. Collected.

21 was taken from this, separated by preparative 711i layer chromatography, and further purified by Sephadex LH-20 column chromatography to produce colorless powder 3.
0itg was obtained.

The physicochemical properties of this colorless powder are described in the literature [Chem.

Pharm, Bull, 33.3195 (198
5)] was consistent with that of Marbellofuran G described.

Specific Example 10 Commercially available mulberry bark 8 and 9 were sequentially extracted with n-hexane, benzene, and methanol, and the solvent of the methanol extract was distilled off under reduced pressure to obtain 300 g of methanol extract.

This methanol extracted extract was dissolved in ethyl acetate and the solvent was distilled off to obtain ethyl acetate soluble extract 709. This ethyl acetate-soluble extract was subjected to column chromatography using silica gel to obtain 8 g of a 20-25% acetone-benzene eluate. This was further purified by preparative thin layer chromatography to obtain yellow powder 29.

The physicochemical properties of this yellow powder are described in the literature [11eterocyc Ies, 16, 214
1 (1981)] was consistent with that of Sangenon C.

Specific example 1! Extract 6 kg of the above-ground parts of Tohoku licorice with ethanol, and distill off the solvent from the resulting extract to obtain an ethanol extract of 590 kg.
I got g.

Add 300g of this ethanol extract to Amberlight XAD.
-2 column chromatography and eluted with water-methanol-benzene system.

The methanol eluate was washed with n-hexane and then concentrated to obtain methanol fraction 949.

This methanol fraction 949 was subjected to silica gel column chromatography and eluted with a benzene-methanol system. Fractions 1 and 2 were obtained from the benzene eluate, and fractions were obtained from the 0.7 to 0.8% methanol-benzene eluate. I got 3.

Fraction 1 was recrystallized from benzene-acetone to obtain pale yellow needles +1 (1 g).

The physical and chemical properties of this pale yellow needle crystal are described in the literature [Tetra
hedron, 26.1977 (1970), Hete
rocycles, 291369 (1989)].

Specific Example 12 Fraction 2 obtained in Specific Example 11 was subjected to preparative thin layer chromatography and recrystallized from benzene to obtain 60 square crystals of pale yellow needles.

The physical and chemical properties of this pale yellow needle crystal are described in the literature [11eLe
rocycles, 29, +369 (198
9)] was consistent with that of Gankaonin B described in [9].

Specific Example 13 Furucnoyon 3 obtained in Specific Example 11 was subjected to preparative thin layer chromatography and recrystallized from benzene-methanol to obtain colorless needle crystals 25.

The physical and chemical properties of this colorless needle crystal are described in the literature [11eter
ocyles, 29, 1369 (lH9)].

Specific Example 14 The underground part 1.4b of Epimedium was extracted with ethanol, and the solvent was distilled off under reduced pressure to obtain 54.49 ml of ethanol extract.

Next, this extract was subjected to column chromatography using silica gel and eluted with a water-saturated benzene-methanol system. Water saturated benzene:methanol-9:l to 4:
The eluted portion was recrystallized from methanol to obtain 840 cm of yellow needle-like crystals.

The physical and chemical properties of this yellow needle crystal are described in the literature [PhyLoc
hemistry, 27.259 (1988)].

Specific example 15 4.8 kg of northwest licorice was mixed with n-hexane, benzene,
It was extracted sequentially with acetone. The solvent of the extract was distilled off under reduced pressure to obtain 110 g of benzene extract. 100 g of benzene extract was taken from this and subjected to column chromatography using silica gel.
1), benzene, and benzene acetone.

The benzene eluate was purified by preparative thin layer chromatography and purified at 500 J! Colorless needle crystals of No. 9 were obtained.

The physical and chemical properties of this colorless needle crystal are described in the literature [11eter
ocycles, 27, 2309 (198g)
] It was consistent with that of the paste Corisodin.

Next, it is explained that the compound of the formula has excellent 5-lipoxygenase inhibitory effect, ncroquinogenase inhibitory effect, and hyaluronidase inhibitory effect, and is useful as a medicine such as an antiallergic agent, an antiinflammatory agent, and a cardiovascular drug. ,
This will be explained using an experimental example.

Experimental example 1 (5-lipoxygenase inhibitory effect) RBL I
The cultured cells were divided into I
Suspended in 50d phosphate buffer (pH 7,4) containing xMEDTA and 10% ethylene glycol, and after sonication, incubated at +0,000xG for 10 min and further 10 min.
The supernatant obtained by centrifugation at 5,000×G for 60 minutes was used as a 5-lipoxygenase enzyme preparation.

As a substrate, IO secondary arachidonic acid, the enzyme preparation prepared as described above, and the dimethyl sulfoxide solution of the compound obtained in the specific example were placed in a test tube and allowed to react at 37°C for 10 minutes.

As an internal standard, 107 J of 0.25 M butyl-3,5-dinitrobenzoate was added and 1.8 J of n-hexane was added.
Extracted with d. The amount of 5-HETE in this was measured by high performance liquid chromatography [column; TSKgelODS
-80TM (manufactured by TOYO5ODA), mobile phase: acetonitrile:water:acetic acid (60:40:0°02), flow rate: ld/min, detection: ultraviolet light (235nIIL)].

From this result, the inhibition rate was calculated using the following formula.

-S Inhibition rate (%) = -x I OO C: 5-) IET when the compound obtained in the specific example is not included
Peak area of E (corrected by internal standard) S: 5-HE T when the compound obtained in the specific example was added
Peak area of E (Uramasa based on internal standard) The 5-lipoxygenase inhibition rate of the compound of formula is shown in Table 1.

(See blank below) Table 1 5-lipoxygenase inhibition rate> The above results confirmed the excellent 5-lipoxygenase inhibitory effect of the compound of the formula.

Experimental Example 2 (Cyclooxygenase inhibitory effect) Microsomes prepared from rabbit kidney medulla (IO011) were placed in a test tube.
i), potassium phosphate buffer (pH 7.5) adjusted to a final concentration of 0.1 M, tryptophan adjusted to a final concentration of 10 M, glutathione adjusted to a final concentration of 4 x H,
Hemoglobin adjusted to a final concentration of 0.25xM, the compound obtained in the specific example, and (1-''C)-arachidonic acid (5XlO'dpm), which is a reaction substrate, were taken in a total amount of 200.

After incubation for 15 min at 37°C, IN HCl 50
The reaction was stopped by adding the following: P G as a carrier to this
Et was added and extracted twice with +Infl ether.

After concentrating the extract, thin layer chromatography (developing solvent:
The reaction product was separated using chloroform:methanol:acetic acid (18:I:I).

Color was developed with iodine vapor, a portion corresponding to PGBt was scraped off, radioactivity was measured with a liquid scintillation counter, and inhibition rate was determined using the following formula.

-S Inhibition rate (%) - X I 00 C: Radioactivity when the compound obtained in the specific example is not included S: Radioactivity when adding the compound obtained in the specific column The results are shown in Table 2.

Table 2 Inhibition rate against cyclooxygenase> The above results confirmed the excellent cyclooxygenase inhibitory effect of the compound of the formula.

Experimental Example 3 (Hyaluronidase inhibitory effect) 0.5 in a test tube
M acetate buffer (pi-14,0) 100 m, compound solution obtained in the specific example 50 A and oxygen solution 100 m (0,23
1g, Sigma, Type-l-S) and 37
The reaction was carried out at ℃ for 20 minutes. Next, as an activator, 50 d of Compound 48/80 solution (0
, 2■) and reacted for 20 minutes at 37°C, the substrate hyaluronic acid solution 200% (0,66JfLi)
was added to start the enzyme reaction. After reacting at 37°C for 40 minutes, 35% of IN sodium hydroxide solution was added to stop the reaction, and Morgan-Elson
The amount of product was measured by color development using method n).

That is, 0.8M potassium borate buffer (
PH9, 1) 100- was added, heated in a boiling water bath for 3 minutes, cooled with water, Ehrlich's reagent 3I11 was added, reacted at 37°C for 20 minutes, the absorbance at 585 nm was measured, and the inhibition rate was determined by the following formula.

Inhibition rate (%) − -B × 100 A: Absorbance when the compound obtained in the specific example is not included B: Absorbance when adding the compound obtained in the specific example The results are shown in Table 3.

Table 3 <Inhibition rate against hyaluronidase> From the above results, the excellent hyaluronidase inhibitory effect of the compound of the formula was confirmed.

Next, an acute toxicity test of the compound of the formula was conducted using ICR male mice, and there was no death after oral administration of 1.09/9, indicating that it was a highly safe drug.

Thus, the compound of the formula has extremely low toxicity and high safety.

Next, the dosage and formulation of compounds of formula will be described.

The compounds of the formula can be administered to animals and humans neat or with conventional pharmaceutical carriers.

The dosage form is not particularly limited and may be selected and used as required, including tablets, capsules, granules, fine granules,
Examples include oral preparations such as powders, parenteral preparations such as injections, and Zentai.

In order to achieve the desired effect as an oral agent, adults should usually take 5Qxy to 5g of the compound of the formula in divided doses several times a day, although this will vary depending on the age, weight, and severity of the disease of the patient. I think it's 4 hits.

Oral agents include, for example, starch, lactose, sucrose, mannitol,
It is manufactured using conventional methods using carboxymethyl cellulose, corn starch, inorganic salts, etc.

In addition to the excipients mentioned above, binders, disintegrants, surfactants, lubricants, fluidity promoters, flavoring agents, coloring agents, fragrances, and the like can be used in this type of preparation as appropriate. Specific examples of each are shown below.

[Binder] Starch, dextrin, gum arabic powder, gelatin,
Hydroquinepropyl starch, methylcellulose, sodium carboxymethylcellulose, hydroxypropylcellulose, crystalline cellulose, ethylcellulose, polyvinylpyrrolidone, macrogol.

[Disintegrant co-starch, hydroxypropyl starch, carboxymethylcellulose sodium, carboxyl methylcellulose calcium, strength, ruboxin methylcellulose, low substituted hydroxypropylcellulose.

[Surfactant] Sodium lauryl sulfate, soybean lecithin, sucrose fatty acid ester, polysorbate 80° [Lubricant] Talc, waxes, hydrogenated vegetable oil, sucrose fatty acid ester, magnesium stearate, calcium stearate, aluminum stearate, Polyethylene glycol.

[Fluidity promoter] Light anhydrous silicic acid, dry aluminum hydroxide gel, synthetic aluminum silicate, magnesium silicate.

The compounds of the invention can also be administered as suspensions, emulsions, syrups, elixirs,
These various dosage forms may contain flavoring agents and coloring agents.

In order to exert the desired effect as a parenteral agent, it is usual for adults to administer the compound of formula 0.1 mg to I9 by intravenous injection per day, depending on the patient's age, weight, and severity of the disease. , intravenous drip, subcutaneous injection, and intramuscular injection are considered appropriate.

This parenteral preparation is manufactured according to a conventional method, and generally contains distilled water for injection, physiological saline, glucose aqueous diluent, vegetable oil for injection, sesame oil, peanut oil, soybean oil, corn oil, propylene glycol, polyethylene glycol, etc. as a diluent. Can be used. Furthermore, a bactericide, a preservative, and a stabilizer may be added as necessary. In addition, from the viewpoint of stability, this parenteral preparation may be filled into a vial or the like and then frozen, water removed by ordinary freeze-drying techniques, and a liquid preparation prepared from the freeze-dried product immediately before use. Furthermore, isotonizing agents, stabilizers, preservatives, neutralizing agents, etc. may be added as appropriate.

Other parenteral preparations include liquid preparations for external use, liniments such as ointments, and heavy doses for intrarectal administration, and are manufactured according to conventional methods.

Next, the present invention will be explained in more detail with reference to Examples.
The present invention is not limited to this in any way.

Example 1 ■Corn starch 449 ■Crystalline cellulose 409 ■Carboxymethyl cellulose calcium 59 ■Light silicic anhydride 0.59 ■Magnesium stearate 0.59 ■Specific example! Compound obtained with
10g Total 100g According to the above recipe, ① to ③ were mixed uniformly and compressed using a tablet machine to obtain some 200 Q tablets.

This tablet-tablet contains the compound 20M9 obtained in Example 1, and an adult should take 10 to 25 tablets in several doses per day.

Example 2 ■ Crystalline cellulose 845 g ■ Magnesium stearate 0.59 ■ Calcium carboxymethyl cellulose 5 g ■ Compound obtained in Example 2 109 Total 100 parts ■, ■, and part of ■ were uniformly mixed according to the above recipe, and compressed. After molding, crush, add the remaining amounts of ■ and ■, mix, compress and mold using a tablet machine, and make a portion of 2 Q OR9
tablets were obtained.

This tablet contains 20xg of the compound obtained in Example 2, and an adult should take 10 to 25 tablets in several doses per day.

Example 3 ■ Crystalline cellulose 49.59 ■ 10% hydroxypropyl cellulose ethanol solution 359 ■ Carboxymethyl cellulose calcium 5 ■ Magnesium stearate 0.59 ■ Compound obtained in specific example 3 109 Total 1009 - According to the prescription described in ■, Mix ■ and ■ uniformly,
After the mixture was netted in a conventional manner, granulated using an extrusion granulator, dried and crushed, ① and ③ were mixed and compression molded using a tablet machine to obtain tablets weighing 200 zg each.

These tablets contain the compound 20R9 obtained in Example 3, and are taken by adults in 10 to 25 tablets per day in several doses.

Example 4 ■Corn starch 3459 ■Magnesium stearate 50g ■Carboxine methyl cellulose calcium 59 ■Light silicic anhydride 0.59■Compound obtained in Example 4 109 Total 100g Mix ■~■ uniformly according to the above recipe and compress. After compression molding with a molding machine, it was crushed with a crusher and sieved to obtain granules.

This granule NF contains compound 10011 obtained in specific example 4.
9, and adults should take 2 to 5 g per day in several doses.

Example 5 ■ Crystalline cellulose 559 ■ 10% hydroquinepropylcellulose ethanol solution 359 ■ Compound obtained in Example 5 log Total 100 g According to the above recipe, ■ to ■ were homogeneously mixed and suspended. After going into an extrusion granulator and granulating, the mixture was dried and sieved to obtain granules.

This granule R9 contains the compound obtained in specific example 5 + oox9
It contains 2 to 5 g per day for adults, divided into several doses.

Example 6 ■Corn starch 89.59■Light silicic anhydride 0.59■Compound obtained in specific example 6
tog total 1009 Mix ■～■ uniformly according to the above recipe, 200 R
9 was filled into a No. 2 capsule.

One capsule of this capsule contains 20 ml of the compound obtained in Example 6, and an adult should take 10 to 25 capsules a day in several doses.

Example 7 ■ Soybean oil 59 ■ Distilled water for injection 895g ■ Soybean phospholipid 2.5g ■ Glycerin
2g ■ Compound obtained in Example 7 1g Total amount 100g Dissolve ■ in ■ and ■ according to the above recipe, and add ■
The solutions of (1) and (2) were added and emulsified to obtain an injection.

Claims (6)

[Claims] (1) Formula I below ▲ Numerical formulas, chemical formulas, tables, etc. are included ▼ [However, R_1 represents a hydrogen atom, hydroxyphenyl group, or dihydroxyphenyl group, and R_2 represents a 3-methyl-2-butenyl group, methoxyphenyl group, or methoxyphenyl group. Represents a hydroxyphenyl group or rhamnopyranosiloxyl group, R_3 represents a hydrogen atom or a 3-methyl-2-butenyl group, R_4 represents a hydrogen atom, a 3-methyl-2-butenyl group or a group II ▲ Numerical formula, chemical formula, An anti-allergic agent containing a compound represented by the following as an active ingredient: (2) Formula III below ▲There are mathematical formulas, chemical formulas, tables, etc.▼ (However, R_5 represents a 3-methyl-2-butenyl group or a 3-hydroxy-3-methylbutyl group) as an active ingredient. Anti-allergic agent. (3) Formula IV below ▲ There are mathematical formulas, chemical formulas, tables, etc. ▼ (However, R_6 indicates either group V, VI or VII, ▲ There are mathematical formulas, chemical formulas, tables, etc. ▼ R_7 is a hydrogen atom or 3- An anti-allergic agent containing a compound represented by (representing a methyl-2-butenyl group) as an active ingredient. (4) Formula VIII below ▲Contains mathematical formulas, chemical formulas, tables, etc.▼ An anti-allergic agent containing the compound represented by as an active ingredient. (5) The following formula IX ▲Contains mathematical formulas, chemical formulas, tables, etc.▼ An anti-allergic agent containing the compound represented by as an active ingredient. (6) The compound represented by the following formula An anti-allergic agent.