JPH03153625A - Antiallergic agent - Google Patents

Abstract

PURPOSE:To obtain an antiallergic agent useful for remedy of allergic disease such as bronchial asthma or pollinosis having 5-lipoxygenase-inhibiting action and Schultz-Dale reaction-suppressing action containing specific lignans as active ingredients. CONSTITUTION:Lignans expressed by formula I or formula II (A is OH or acetoxyl) are contained in the aimed agent as active ingredients. An extracted solution of said compound is obtained by extraction of Cannabis Semen using a solvent selected from water, methanol, ethanol, acetone, ethyl acetate and methyl ethyl ketone in heating at from 0 deg.C to a temperature below boiling point of used solvent or extraction with ultrasonic wave at from 0 deg.C to room temperature. Said extracted solution is suspended in water and fractionation- extracted using a low polar solvent, then a water-soluble part is fractionation- extracted with ethyl acetate, n-butanol or methyl ethyl ketone, thus a resultant extracted solution is subjected to column chromatography or high-performance liquid chromatography in several times and an eluate is taken out, then fraction of the eluate is recrystallized or pulverized to afford the aimed agent.

Description

Detailed Description of the Invention [Industrial Application Field] The present invention relates to lignans which have a 5-lipoxingenase inhibitory effect and a Schuljz-dale reaction inhibitory effect and which can be used as medicines such as anti-allergic agents. It is related to.

[Prior Art and Problems] In recent years, with the pollution problems and environmental changes in our country, the number of people suffering from allergic diseases such as bronchial asthma and hay fever has increased, and this has become a major social problem.

5-Riboquingenase is an enzyme that oxidizes the 5-position of arachidonic acid, and its inhibitor is said to be involved in anti-allergic and anti-inflammatory effects.

On the other hand, the Schulzdale reaction involves chemical mediators released during the antigen-antibody reaction in the body, causing bronchoconstriction, and drugs that suppress this reaction have anti-allergic effects. You can expect it.

[Means for Solving the Problems] The present invention has a 5-lipoxygenase inhibitory effect and 5chultz-dal which are effective in treating allergic diseases.
As a result of extensive research in search of compounds that have an e-reaction inhibitory effect, lignans represented by the following formula
-dale reaction inhibiting effect, and the present invention was completed.

The present invention is as shown below.

An anti-allergic agent containing as an active ingredient a lignan represented by the following formula I (where A represents a hydroxyl group or an acetoxyl group) or a lignan represented by the following formula I (where A is the same as above).

Hereinafter, the compounds represented by formula 1 and formula (2) will be collectively referred to as compounds of the formula.

A compound of the formula can be obtained, for example, as follows.

Seed seeds [dried seeds of Cannabis 5tiva L] are heated to a temperature from 0°C to 14 points or less of the solvent used using one or more mixed solvents selected from water, methanol, ethanol, acetone, ethyl acetate, and methyl ethyl ketone. Extraction is performed by heating or ultrasonic extraction at 0°C to room temperature to obtain an extract.

This extract is suspended in water, partitioned extraction is performed using a puddling solvent, and the remaining water-soluble portion after removing low polar contaminants is extracted with one selected from ethyl acetate, n-butanol, methyl ethyl ketone or Extract is obtained by performing partition extraction using a mixed solvent of more than that amount.

The extract is subjected to column chromatography or high performance liquid chromatography once or several times as it is or after drying, and the eluate is fractionated to obtain both fractions. At this time, water, methanol, ethanol, acetone,
Tetrahydrofuran, ethyl acetate, acetonitrile, chloroform, benzene, ether, petroleum ether, n-
Single or mixed solvents such as hexane can be used.

The compound of the formula can be obtained by recrystallizing or powdering both components thus obtained.

Also, some of the compounds of the formula can be obtained by acetylating the compound obtained as described above.

Examples of low polar solvents include benzene, chloroform, ether, n-hexane, and cyclohexane.

Examples of adsorbents for column chromatography or high performance liquid chromatography include Noriyoku Gel, 0DS-NOυ
Examples include gel, porous polymer gel, and the like.

For recrystallization or powdering, a single or mixed solvent of water, methanol, ethanol, acetone, ethyl acetate, tetrahydrofuran, benzene, chloroform, ether, petroleum ether, n-hexane, cyclohexane, etc. is used.

For the acetylation, a general acetylating agent can be used, for example, the reaction may be carried out with acetic anhydride in pyridine.

Next, a specific example of the production of the compound of the formula will be shown.

Specific example 1 Asako 10 to 9 water-ethanol (III) EH! So 3
Extraction with heating under reflux was performed three times. The obtained extracts were combined and the solvent was distilled off under reduced pressure to obtain a dry extract of 3.44 to 9. This extract was suspended in 20 g of water, and 21 g of chloroform was added.
It was extracted three times. The remaining aqueous layer was diluted with 2M n-butanol.
The mixture was partitioned and extracted four times to obtain an n-butanol extract. For the n-butanol extract, the solvent was distilled off under reduced pressure, and the dry extract 2
39.19 was obtained. This dried extract is 3f water! ni@muddy,
Porous polymer gel (Diaion HP-20, 2f
! .

Mitsubishi Kasei Co., Ltd.) column chromatography, water 4
011. It was sequentially eluted with methanol at 50C. The solvent in the methanol eluted portion was distilled off under reduced pressure to obtain a dry extract of 171.
7g was obtained.

Apply this extract to Noriyoku Gel (Kieselgel 60.7)
The residue was subjected to column chromatography (locMφ×460) using a 0-230 mesh (manufactured by Merck & Co.), and eluted with a mixed solvent of chloroform-methanol.

The fraction eluted with chloroform-methanol (5:I) was subjected to medium pressure licage gel column chromatography-cc.
rc column, 22xxφ×30α, manufactured by Kusano Kagaku Co., Ltd.), and the fraction eluted with a mixed solvent of benzene-acetone (III) was eluted with chloroporum-methanol (1:I).
Recrystallized with a mixed solvent of 4601t9, a colorless fine needle-like substance
I got it.

The physical and chemical properties of this colorless fine acicular substance are as follows.
.

Biol, Chem, 45(11), 2593(19
g+) Grossamide of Kokisen
It was consistent with the physical and chemical properties of

Melting point: 133-135°C FAB-MS m/z: 625 (M+H)' Infrared absorption spectrum ν = P: = α-I: 3296, +65
6.1614.1600°514 Ultraviolet absorption spectrum λ wa number” nypt (Io
gε) = 289 (4, 28), 305 (4, 31).

322(4,35) Proton nuclear magnetic resonance spectrum (δ ppm+ in Acetone-da): 2.
74 (IH, ddd, J=6.7.l4Hz) 2.79
(2H,t, J = 7H2).

2.87 (IH, dt, J = 6.14Hz) 3.40 (
IH, dat, J = 6.7.14Hz).

3. 5 5 (2H, dt, J = 6.7
Hz) 3.71 (I H, rr+), 3.81 (3
H,s).

3.84 (3H, s) 4.19 (I H, d, J=8.5Hz) 6.03 (
I H,d j = 8.5 Hz).

6.44 (I H, br s) 6.4.8 (I H, d, J=16Hz) 6.77 (2
H, d, J = 8.5Hz).

6.81 (2H,d, J = 8.5 Hz)6.
84 (2H, br), 6.99 (I H, br s
) 7.0 (I H, br).

7.07 (2H, d, J = 8.5 Hz).

7.0 8 (2H, dj = 8.5 Hz).

7.4 0 (l H, br) 7.4 1 (LH, d, J = 161 (z).

7.4 7(I Hlbr) 'c-Fji magnetic resonance spectrum (δ ppm in Acetone-de): g4
．． 7(t), 35.5(t), 41.5(t)42.1
(t), 56.3 (q), 56.4 (q).

57.8(d), 89.0(d), I I O, 6(d
) 111.3(d), 115.9(d).

116.1(d)X2. I 16.9(d)X2118
．． 9(d)l I 9.2(d).

119.9(d), 129.2(s).

129.6 (s), 130.5 (d) x 2130.6 (
d) x2, 130.6 (s) 130.9 (s), 132
．． 6(s).

141.4(d), 148.5(s) 150.6 (s), +56.7 (s).

156.8 (s), l 67.5 (s).

170.4(s) Specific Example 2 Compound 10011y obtained in Specific Example 1 was dissolved in dry pyridine 10
After adding 5 d of acetic anhydride and stirring at room temperature for 12 hours, the reaction solution was left in ice water, and 100% of ethyl acetate was added.
It was distributed and extracted. After drying the ethyl acetate layer over sodium sulfate, the solvent was distilled off under reduced pressure and recrystallized with a mixed solvent of chloroform, moon, and chlorohexane (Ill) to obtain a colorless needle-like substance 1.
1519 was obtained.

The physical and chemical properties of this colorless acicular substance are as shown below, and it is a compound in which A is an acetoxyl group, that is, a compound in which A in the formula
ic, Biol, CheL, 45(If), 2593
(1981)] described triacedergrosamide (Tr
iacetyl grossamide).

Melting point・204~205℃ P A B -M S ta/z near 51 (M
+ H)' Infrared absorption spectrum ν2:=α゛1゜1762.1650,1618.15341512.1
222 Ultraviolet absorption spectrum λ 甚'; 13n! ! 1(l
og ε) = 305 (4, 30), 321 (4, 34)
Proton nuclear magnetic resonance spectrum (δ ppm in CDCl5): 2.26 (3H, s), 2.29 (3H, s).

2.30 (3H, s).

2.81 (2H, dtj=7.14Hz).

2.85 (21(, t, J=7Hz).

3.49 (2f(, dL, J=7.14Hz).

3.57C214,d(,J=7,1414z)3.7
7 (31i, s), 3. 8 9 (3H,
s).

4.04 (l H, d, J = 6.7 Hz).

5.97 (I H, br) 6.03 (I H, d, J = 6.7 Hz) 6
．． 13 (IH, d, J=15.5Hz).

6.17 (IH, br), 6.80 (IH, s).

6.89 (IH, brd, J = 8 Hz).

8.94 (I H, s), 6.98 (I H, m)6.
98 (lH,d, J = 8 Hz).

6.98 (2H, d, J = 8 Hz).

7.0 1 (2H, d, J = 8H2).

7, I 2 (2H, d, J = 8 Hz).

7.20(2H,d, J = 8 Hz>7.47(
IH, d, J = I5.5Hz) 3C-nuclear magnetic resonance spectrum (δ ppm in CDCl5): 20.5 (q), 2 1.0 (q) x 2.34.6 (shi ) 35.0 (t ), 40.7(t), 40.8(t)
55.9(q), 56.1(q), 57.8(d).

87.9(d), l 09.7(d), l I 2.3
(d).

116.7(d), I+7.6(d).

118.7(d), 121.7(d) x 2121.7(
d)×2. l 22.9 (d) 129.4 (s),!
29.6(d)x2゜129.7(d)x2,136.
0(s) 136.5(s), 139.1(s) 139.6(s), 140.4(d).

144.7 (s), I 49.2 (s).

49.2(s),! 49.8 (s) 151.2 (s) x 2.166.0 (s) 1 69.0
(s), 1 69.6 (s).

1 70.1 (s)
-354 (ODS), 50xxφ×50α, manufactured by Yamamura Chemical Co., Ltd.], and the fraction eluted with a mixed solvent of water-methanol (1.1) was powdered with methanol to obtain 740 yg of a white powdery substance.

Due to the physical and chemical properties shown below, this white powdery substance is a compound represented by A of 2H or a hydroxyl group, that is, 6.7
-cyhydroxy-4-(3,4-nohydroquinphenyl)-N',N'-bis-[2-(4-hydroquinphenyl)ethyl]-2,3-naphthalene dicarboxamide (
6,7-Dihydroxy-4-(3,4-dihy
droxyphenyl)-N', N'-bis-[
2-(4hydroxyphenyI)ethyIcor2.3-napNhsIenedrcarboxamr
It was determined that de).

F D −M S m/z: 595 (M + F(
)' Infrared absorption spectrum ν knee tα-I: 336
8.1616.1580. ! 5+6 ultraviolet absorption spectrum λ 2aE” nm (Iogε): 257 (4,7
9) Proton nuclear magnetic resonance spectrum (δ ppm in DMSO-do): 2.29 (2
H, t, J=7Hz) 2.72 (2H, t, J=7Hz).

3.06 (2H, br t, J = 7 +-(z
).

3.4.0 (2H, br t, J = 7 Hz)
.

6.58 (l H, dd, J = 2.8 Hz)6
．． 65 (2H, d, J=8Hz).

6.69 (2H, d j = 8 Hz) 6.72
(lH,d, J = 2 Hz).

6.80 (IH, d, J=8Hz) 6.86 (IH,s).

6.87 (2H, d, J = 8 Hz) 7.03
(2H, d, J = 8 Hz) 7.17 (l H
, s), 7.29 (I H, br).

7.68 (I H, br), 7.73 (l H, br
s) +30-nuclear magnetic resonance spectrum (δ ppm in DMSO-da): 33.4 (t
), 33.9 (t), 40.4 (shi) 10.7 (t),
108.7(d), 109.8(d) 114.6(d)
, I l 4.8(d) x 4117.7(d), 121
．． 1 (d).

124.4 (d), 127.4 (s) 128.3 (s), I 28.6 (s) 12
8.6(d)x2. I 28.8(d)x2I 28.
9 (s), 129.3 (s) 129.4 (s) 130.
6 (s) 134.8 (s), 144.1 (s) x 2147.1 (
s), I 47.5 (s) 155.1 (s) 155.2
(s) 167.5 (s), 168.3 (s) Specific example 4 Compound 920 xq obtained in specific example 3 was mixed with dry birinone 10
After adding 5- acetic anhydride and stirring at room temperature for 12 hours, the reaction solution was left in ice water, and ethyl acetate 100-
It was distributed and extracted. After drying the ethyl acetate layer over sodium sulfate, the solvent was distilled off under reduced pressure and recrystallized from ethyl acetate-chloroform (1:l) to obtain 1.18 g of colorless needles.

The physicochemical properties of this colorless acicular substance are as shown below, and it is a compound in which A in formula (1) is an acetoxyl group, that is, 6,7-diacetoxy-4(3,4-diacetoquinphenyl)-N' , N''-bis-[2(4-acetoquinphenyl)ethyl]-2,3-naphthalene rupoxamide (6,7-Diacetoxy-4-(34-d
iacetoxyphenyl)-N', N''-b
is-[2-(4acetoxyphenyl)eth
yl]-2,3-naphthalene dicarb
The structure was determined to be that of oxamide).

Melting point: 204-207°C FD-MS m/z: 847 (M+H)' Infrared absorption spectrum ν '4P* C71-''+768.16
40.1548.1198 Ultraviolet absorption spectrum λ
=:υy+m(logε)244(4,60),295
(3,80) Proton nuclear magnetic resonance spectrum (δ ppm in CDC1z): 2.24 (3H, s), 2.26 (3H, s) 2.27
(3[(,s), 2.29(3)1.s)2.31(3
H, s), 2.33 (3H, s) 2.42 (2H, dt
, J=7.14Hz) 2.90(2+(,t, J=8H
z).

3.26 (2H, ddL, J=7.7.14Hz).

3.62 (2H, dd, J = 7.71-1z)6
．． 20 (I) (, br s).

6.94 (2H, d, J = 8 Hz) 7, OO (2H, d, J = 8 t-1z) 7.
10(2)1. d, J=81-(z).

7.12 (I H, dd, J = 2.8 + (z)
7.14 (I H, d,, 1 = 2Hz) 7.18 (I
H, br).

7.25 (3H, d, J=8Hz) 7.34 (IH, s), 7.64 (IH, s) 7.86
(I H, s) 13c-Nuclear magnetic resonance spectrum (δ ppm in CDCl5): 20.6 (q) x 2.20.7 (q) x 2° 21.1 (
q)x2.34.1(t).

34.9(t), 41.2(t), 41.4(t).

120.2(d), l 21.5(d) x 2121.
7(d)x2,122. o(d).

123.6(d), 125.5(d).

128.4(d), 12g, 5(d) 129.8(d
)X2,129.8(d)x2130.8(s),I
30. '9 (s) 132.1 (s), 133.2 (s) 135.1 (s), 135.4 (s) 136.5 (s) x 2, 142.0 (s) 142.3 (
s), l 42.4 (s).

143.0(s), 149.1(s) 149.3(s), 167.7(s).

168.0 (s), 68.1 (s).

168.3(s), 168.8(s).

169.5(s), 169.6(s) Next, an experimental example will be given showing that the compound of the formula has excellent 5-ribokinogenase action and 5chultz-dale reaction inhibitory action and is useful as an antiallergic agent. I will explain.

Experimental example 1 (5-riboxinogenase inhibitory effect) RBL-1
Cultured cells were added with lxME to 5x108 cells/-.
After sonication, the cod was suspended in 50% cod phosphate buffer (pH 7,4) containing DTA and 10% ethylene glycol.
0,0OOxG'tl - 10 minutes, plus +05,00
The supernatant obtained by centrifugation at 0°×G for 60 minutes was used as a 5-lipoxygenase enzyme preparation.

A dimethyl sulfoxide (DMSO) solution of 1 (l arachidonic acid as a substrate), the enzyme preparation prepared as described above, and the compound obtained in the specific example was placed in a test tube and allowed to react at 37°C for 10 minutes. 10 d of 0.25M butyl-3,5-dinitrobenzoate was added as an internal standard, and extracted with 1.8-hexane.

The amount of 5-HETE in this was determined by high performance liquid chromatography [column: TSK gel, ODS-
80M T (TOYO5ODA), mobile phase niacetonitrile; water; acetic acid (60·40:0.02), flow rate: I-
/min, detection: ultraviolet light (254 m)]. From this result, the inhibition rate was calculated using the following formula, and the results are shown in Table 1.

Inhibition rate = ' Peak Area (Corrected by Internal Mark) The results shown in Table 1 and above confirm that the compound of the formula has the ability to inhibit 5-]novoxygenase.

Experimental example 2 (Schultz-dale reaction inhibition test)
Ovalbumin (hereinafter referred to as OA) 119 was administered as an antigen to male Hartley guinea pigs after a body weight of 200 gH, and pertussis vaccine (2 x bacterial cells) was administered as an adjuvant.
Active sensitization was performed by intraperitoneally administering Id). Booster sensitization with OAl 19 was then performed every 1 to 2 weeks, and animals were weaned 1.5 months after the initial sensitization. The animal was sacrificed by blood and its trachea was removed and used for experiments.

The trachea specimen was prepared by connecting six rings with a width of 1 to 2 xx, and 95% 0. It was suspended in a 20 d Magnus tube filled with Tyrode's solution at 32° C. through which -5% COt was bubbled. A load of o, sg was applied to the tracheal specimen, and isotropic contraction was measured.

10. After the contraction induced by M carbachol stabilized, the antigen OAIm/- was added to induce the Nurzudale reaction, and its inhibition rate (1 (calculated with the contraction induced by IA/A carbachol as 100%) was determined. It is shown in Table 2.

The compound obtained in the specific example was dissolved in 0.5% ethanol and added to 10 portions of antigen stimulation.

From the results shown in Table 2 and above, it was confirmed that the compound of the formula has an inhibitory effect on the Schulsorsol reaction.

Next, the dosage and formulation of the compound of the formula (1) will be explained.

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

The dosage form is not particularly limited and can be selected and used as appropriate, including oral preparations such as tablets, capsules) L/M1, granules, fine granules, and powders, injections, and suppositories. Examples include parenteral agents such as.

In order to achieve the desired effect as an oral agent, the usual adult dosage is 50M9 to 5g of the compound of the formula several times a day, depending on the age, weight, and degree of illness. It seems appropriate to take 1 ton per minute.

Oral agents include, for example, starch, lactose, sucrose, mannitol,
It is manufactured using carboquinomethylcellulose, cornstarch, inorganic salts, etc. according to conventional methods.

In addition to excipients, binders, disintegrants, surfactants, lubricants, fluidity promoters, flavoring agents, coloring agents, six ingredients, etc. may be used in this type of preparation. can. Specific examples of each are shown below.

[Binder] Starch, dextrin, gum arabic powder, gelatin,
Hydroxopropyl starch, methylcellulose, sodium carboxylmethylcellulose, hydroquinepropylcellulose, crystalline cellulose, ethylcellulose, polyvinylpyrrolidone, macrogol.

[Disintegrant] Starch, hydroquinepropyl starch, sodium carboxymethylcellulose, carpoquinemethylcellulose carunium, carboxymethylcellulose, low substituted hydroquinepropylcellulose.

[Surfactant sodium colauryl sulfate, soybean lentin, sugar fat 1!
Jj acid ester, polysorbate 80° [lubric acid ester, waxes, hydrogenated vegetable oil, sugar fatty acid ester, magnesium stearate, carunium stearate, aluminum stearate, polyethylene glycol.

Oral direct movement promoter] Light anhydrous silicic acid, dry aluminum hydroxide gel, synthetic aluminum silicate, magnesium silicate.

The compound of the formula can also be administered as a liquid solution, an emulsion, a nolopub, or an elixir, and these six dosage forms may contain a flavoring agent and a coloring agent.

In order for a parenteral drug to have the desired effect, it will vary depending on the patient's age, weight, and severity of the disease, but the usual adult dosage for the compound of the formula is 0.1 per day! ! Intravenous injections of up to 9 to 1 g, intravenous drip infusions, subcutaneous injections, and intramuscular injections are considered appropriate.

This parenteral preparation is manufactured according to a conventional method, and generally contains distilled water for injection, physiological saline, aqueous glucose solution, 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 can be frozen after being filled into a vial, water is removed by ordinary freeze-drying techniques, and a liquid preparation can be re-prepared from the freeze-dried product immediately before use. Furthermore, isotonizing agents, stabilizers, preservatives, soothing agents, etc. may be added as appropriate.

Other parenteral preparations include external solutions, liniments such as ointments, and suppositories for direct administration, which 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 in any way by this.

Example 1 ■Corn starch 44g ■Crystalline cellulose 409 ■Calcium carboxymethyl cellulose 59 ■Light anhydrous silicic acid 0.590 Magnenium stearate 0.59 ■Compound obtained in 1
toy total 1009 According to the above recipe, ■ to ■ were mixed uniformly and compression molded using a tablet machine to obtain some tablets of 20019.

These tablets contain H-containing compound 20M9, which was iC in Example 1, and are taken by adults in 10 to 25 tablets divided into several doses per day.

Example 2 ■ Crystalline cellulose 84.59 ■ Magnenium stearate 0.59 ■ Calcium carboxymethyl cellulose 5 g ■ Compound obtained in Example 2 10 g Total 100 g According to the above recipe, parts of ■, ■, and ■ were uniformly mixed, After compression molding, the mixture was pulverized, the remaining amounts of (1) and (2) were added and mixed, and the mixture was compressed with one trowel of a tablet machine to obtain 200 tablets.

These tablets contain 20 compounds of the compound obtained in Example 2, and are taken by adults in 10 to 25 tablets divided into several doses per day.

Example 3 ■ Crystalline cellulose 49.59 ■ 10% hydroxypropyl cellulose ethanol solution 359 ■ Carboxymethyl cellulose calcium 59 ■ Magnesium stearate 059 0 Compound obtained in Example 3 +09 Total 1009 ■, ■, and ■ were uniformly mixed according to the above recipe After mixing the mixture with the following ingredients, sagging using a conventional method, granulating with an extrusion granulator, drying and crushing, mix ① and ②, and compress and mold with a tablet machine to obtain a portion of 20019 tablets. Ta.

These tablets contain the compound 2019 obtained in Specific Example 3, and are taken by adults in 10 to 25 tablets a day in several doses.

Implementation PI 4 ■ Corn starch 34.59 ■ Magnenium stearate 509 ■ Calcium carboxymethyl cellulose 5 g ■ Light anhydrous silicic acid 059 ■ Compound obtained in Example 4 tog Total 100 g Mix ■ to ■ uniformly according to the above recipe and compression mold. After compression molding in a machine, it was crushed in a crusher and sieved to obtain granules.

This granule Ig contains the compound 100Q obtained in Specific Example 4, and is taken by adults at 2 to 5 g per day in several doses.

Example 5 ■Crystalline cellulose 559 0IO% hydroquinopropylcellulose ethanol solution 35g ■Compound obtained in specific example 1! 09 Total 100g According to the above recipe, ■ to ■ were mixed uniformly and made into a paste. After going into an extrusion granulator and granulating, the mixture was dried and sieved to obtain granules.

This granule I2 contains the compound 1001 obtained in ρ11.
9 contains H, 2 to 5 per day for adults. Take in several doses.

Example 6 ■Corn starch 89.59■Light silicic anhydride o, sg■I cotton compound in specific example 2
109 total 1009 Mix ■～■ uniformly according to the above recipe, 200 z
9 was filled into a No. 2 capsule.

This capsule contains 6 capsules of the compound 20I2 obtained in Example 2, and is taken by adults in 25 capsules of IEJIO in several doses.

Example 7 ■Soybean oil 5g ■Distilled water for injection 8959 ■Soybean phospholipid 2.5g ■Glycerin 2゜■Compound obtained in Example 3 ■2 Total amount 100! ? Dissolve ■ in ■ and ■ according to the above recipe, and add ■ to this
The solutions of (1) and (2) were added and emulsified to obtain an injection.

Claims (2)

[Claims] (1) An anti-allergic agent containing lignans represented by the following formula I (where A represents a hydroxyl group or an acetoxyl group) as an active ingredient. (2) An anti-allergic agent containing lignans as an active ingredient represented by the following formula II ▲Mathical formula, chemical formula, table, etc.▼ (However, A is the same as above.)