JPH04159295A - Flavonoid glycoside and 5-lipoxygenase inhibitor containing the flavonoid glycoside as an active ingredient - 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 Application Field] The present invention relates to a flavonoid glycoside that has a 5-lipoxygenase inhibitory effect and is useful as a medicine such as an antiallergic agent and an antiinflammatory agent.

[Prior Art and Problems] In recent years, with the pollution problems and environmental changes in our country, the number of people living with allergic diseases such as 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.

Therefore, searches and development efforts have been made for drugs that exhibit anti-inflammatory and anti-allergic effects using 5-lipoxygenase inhibitory effects as an indicator.

[Means for Solving the Problems] The present inventors have discovered 5-5 effective treatments for allergic diseases, etc.
As a result of extensive research in search of compounds with riboquinogenase inhibitory effects, we discovered that Epimedium (Epimedium), a member of the Berberaceae family, was found.
The present inventors have discovered that flavonoid glycosides contained in P. diun koreanum NAKAI) and other plants of the same genus have a 5-riboquine genease inhibitory effect, leading to the completion of the present invention.

That is, the present invention provides the following formula I (wherein R8 is rhamnose 3-1 xylose or rhamnose 7-1 fucose in which the 4-position is acetylated,
R2 represents a hydrogen atom or glucose, and R3 represents a hydrogen atom or a methyl group. ) and a 5-riboxingenase inhibitor containing the flavonoid glycoside as an active ingredient.

Hereinafter, the compound represented by formula I will be referred to as the compound of the present invention.

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

The stems and leaves of Epimedium are extracted or distributed extracted once or more with at least one solvent selected from acetone, methanol, ethanol, butanol, chloroform, hexane, and water, and the solvent is removed from the resulting extract, and the resulting residue is extracted with hexane. , benzene, noethyl ether, petroleum ether,
Using at least one solvent selected from ethyl acetate, chloroform, acetone, tetrahydrofuran, acetonitrile, methanol, ethanol, and water as the elution solvent, porous polymers such as Diaion HP-20 and MCI Gel CHP2UP, Sephadex LH-20, etc. The compound of the present invention can be obtained by subjecting the compound to column chromatography using Sephadex, reversed-phase silica gel, silica gel, polyamide, cellulose, etc. as a carrier, or high performance liquid chromatography once or several times.

Next, the fact that the compound of the present invention has an excellent 5-lipoxygenase inhibitory effect and is useful as an antiallergic agent and an antiinflammatory agent will be explained with reference to experimental examples.

Experimental example RBL 1 cultured cells were treated with I x M ethylenediaminetetraacetic acid (EDTA) so that the concentration was 5XIO@cell/d.
and 50 fins suspended in phosphate buffer (pH 7,4) containing 10% ethylene glycol and after sonication, 10.0
The supernatant was centrifuged at 00xG for 10 minutes and at 105,000xG for 60 minutes, and the supernatant was used as a 5-ribokinogenase enzyme preparation.

Acetone solutions of various concentrations of IOAM Araki, tonic acid as a substrate, the enzyme preparation prepared as described above, and the compounds obtained in Examples were placed in test tubes and reacted at 37° C. for 10 minutes. Butyl 3,5 at 0.25M as internal standard
- Add 107 J of dinitrobenzoate, add 1 J of hexane
．． Extracted with 87.

The amount of 5-HETE in this was measured by high performance liquid chromatography [column, TSKgel ODS-80TM (T
Mobile phase, tetrahydrofuran: acetonitrile: 1% acetic acid (5:5:9): flow rate, l-
/min: detection, measured by ultraviolet light (235 hawk)].

From this result, the inhibition rate was calculated using the following formula, and the 50% inhibitory concentration (IC5O) was determined.

C Peak area of 5-HETE when the compound obtained in Example is not included (corrected by internal standard) S. 5-HETE when the compound obtained in Example is added
TE peak area (corrected by internal standard) Table 1 shows the inhibition rate (%) at 10o- and r C5o (M ) of the compounds obtained in the examples.

Inhibition rate against 5-lipoxygenase in Table 1 From the above results, it was confirmed that the compound of the present invention had an inhibitory effect on 5-ribokinogenase.

Next, the dosage and formulation of the compound of the present invention will be explained.

The compounds of the present invention can be administered to animals and humans either neat or with conventional pharmaceutical carriers. The dosage form is not particularly limited and may be selected and used as appropriate, and may include oral dosage forms such as tablets, capsules, granules, fine granules, and powders, and parenteral dosage forms such as injections and halved tablets. It will be done.

In order to exert the desired effect as an oral agent, it is necessary to administer the compound of the present invention in an amount of 30 to 45,019 times per day, depending on the age, body weight, and severity of the disease. It seems appropriate to take it.

In the present invention, oral preparations such as tablets, capsules, and granules are manufactured according to conventional methods using, for example, starch, lactose, sucrose, mannitol, carboxymethyl cellulose, cornstarch, inorganic salts, and the like.

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

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

[Disintegrant] Starch, hydroxypropyl starch, sodium carboxymethyl cellulose, calcium carboxymethyl cellulose, carboxymethyl cellulose, low substituted hydroxypropyl cellulose. - [Surfactant] Sodium lauryl sulfate, soybean lecithin, sucrose fatty acid ester, polysorbate 80° [Lubricant] Talc, waxes, hydrogenated vegetable oil, noyose fatty acid ester, magnesium stearate, calcium stearate, aluminum stearate , polyethylene glycol.

[Fluidity promoters: light silicic anhydride, dry aluminum hydroxide gel, synthetic aluminum silicate, magnenoum silicate.

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

In order to exert the desired effect as a parenteral agent, although it varies depending on the patient's age, weight, and degree of disease, the compound of the present invention is usually administered intravenously at a dose of 011 to 50!9 per day for adults. , intravenous drip, subcutaneous injection, and intramuscular injection are considered appropriate.

This parenteral preparation is manufactured according to a conventional method, and generally uses 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. be able to. 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, 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, soothing agents, etc. may be added as appropriate.

Other parenteral preparations include external solutions, ointments such as ointments, and rectal administration of halved dogfish, etc., 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 in any way by this.

Example 1 20 kg of finely chopped epimedium stems and leaves were mixed with 400 ρ of methanol.
The solvent was removed from the resulting extract to obtain methanol extract 28009. Water was added to this methanol extract, and partition extraction was performed in the order of hexane, chloroform, and butanol to obtain 146 g of hexano extract, 213 g of chloroform extract, and 6269 g of butanol extract.

Next, add 380g of this butanol extract to Diaion HP.
Column chromatography using -20 was carried out, and elution was performed with increasing amounts of water first and methanol sequentially. ), water-methanol (1:9) and methanol eluting fractions A, B, C, DSE and F
were obtained respectively.

The fractions were subjected to silica gel column chromatography,
Elute with chloroform-methanol (85:15),
D-1 fraction and D-2 fraction were obtained as eluates.

The D-1 fraction was further subjected to silica gel column chromatography using chloroform-methanol-water (7:1.8
:0.2) was eluted with YMCpack.
D-ODS-105-10120A 0DS (manufactured by Yamamura Kagaku Kenkyushin, the same applies hereinafter) was subjected to high performance liquid chromatography, and acetonitrile-methanol-water (5:2
:1 (1) and fractionated, yellow amorphous product 170
I got R9.

This yellow amorphous product is 4'-methoxy-5-hydroquine-8-(3,3-dimethylallyl)flavone 3-0-β-D-quinropyranonol (l→3)-4 from the physical and chemical properties shown below. It was determined to be -0-acetyl-α-L-rhamnopyranone-7-0-β-D-glucopyranoside.

Specific optical rotation [α] o: 110.4' Mass spectrum FAB-MS m/z: 851.3 [M+H de HR-
FAB-MS m/z: C40H610to ([M + Hdo) calculated value: 851
．． 2930 Actual value: 851.2974 Infrared absorption spectrum ν 7"we'1l-1:34
24.1650.1598.1512 Ultraviolet absorption spectrum λ:'a2I''77111 (10gε): 35
0.8 (4,03), 315.0 (4,13).

271.4(4,39) Proton nuclear magnetic resonance spectrum (δ +) P+a in D M S O-d glo
, 72 (3H,d, J = 6.3 Hz).

1.61 (3H, s), 1.68 (3H, s).

1.9.7 (3H, s).

2.99 (IH, dd, J=7.7, 8.9Hz).

3.12 (IH, t, J=8.9Hz).

3.25 (IH, dd, J=6.3, 9.9Hz).

3.58 (lH, dd, J=7.4, 14.0Hz)
.

3.78 (IH, dd, J=5.2, 11.3Hz).

3.78 (I H, dd, J = 3.0.9.9
Hz).

3. 88 (3H, s).

4.14 (l H, dd, J = 1.8.3.0
Hz).

4.22 (I Hld, J = 7.6 Hz).

4.84 (IH, t, J=9.9Hz).

5.01 (IH, bd, J = 7.8 Hz).

5.17 (IH, bt, J=7.2Hz).

5.31 (IH, d, J=1.7Hz).

6.64 (IH, s).

7.16 (2H, d, J=8.8Hz).

7.9 1 (2H, d, J = 8.8 Hz
).

1 2.5 8(l H, 5) 13c-Nuclear magnetic resonance spectrum (δ ppm in DMS O-da): l 6.
9(q), 17.7(q), 20.7(q).

21.3(t), 25.4(q), 55.4(q).

60.5(t), 65.6(d), 68.3(d).

69.2(d), 69.5(d), 69.5(d).

71.2(d), 72.7t:d), 73.2(d).

76.3(d), 76.4(d), 76.4(d).

77.0(d), 98.1(d), 100.5(d).

101.3(d), 105.5(d).

105.5(s), 108.4(s).

114.0(d), 114.0(d).

122.0(s), 122.0(d).

130.5(d), 130.5(d).

131.1 (s), 134.1 (s).

1 153.0(゛)・157.3(゛)・
158.9 (s), 160.5 (s).

161.4(s), 169.6(s).

178.0 (s) Example 2 The D-2 fraction obtained in Example 1 was subjected to MCI gel CHP20.
A fraction was obtained by column chromatography using P and eluting with water-methanol (55:45). The fraction was divided into several times, and YilCpack D-ODS-105-
The product was subjected to high performance liquid chromatography using 1012080DS and eluted with acetonitrile-methanol-water (5:2213) to obtain 751 g of yellow amorphous skeleton crystals.

This yellow amorphous skeleton crystal has 4
°-Methoxy-5-hydroquine-8-(3,3-dimethylallyl)flavone 3-0-β-D-fucopyranosyl (l→2)-α-L-rhamnopyranosyto 7-〇-β
-D-glucopyranondo.

Specific optical rotation [α]D-97.0°Mass spectrum FAB-MS m/z:823.3[M+H]”HR
-FAB-MS m/z CzsHs+ O+e ([M + H]”) Calculated value: 8
23.2972 Actual value: 823.3025 Infrared absorption spectrum ν 2Iσ-13404,16
56,1600 Ultraviolet absorption spectrum λ 'm'a2'' (lOgε
)・271.6 (4,39), 316.0 (4,13)
.

351.6 (4,03) Proton nuclear magnetic resonance spectrum (δ ppm in DMS O-d,): 0.
88 (3H,d, J = 6.2 Hz).

0.98 (3H, d, J=6.4Hz).

1.61 (3H, s), 1.70 (3H, s).

3.86 (3H, s).

4.04 (I H, dd, J = 1.5.3.7
Hz).

4.39 (l H, d, J = 5.0 Hz).

4.53 (IH, d, J=9.8Hz).

4.62 (IH, t, J = 5.6 Hz).

4.86 (IH, d, J=5.0Hz).

5.00 (IH, d, J=7.6Hz).

5.19 (IH, t, J=7.1Hz).

5.33 (IH, d, J=5.3Hz).

5.5 0(I H, bdj = l, 5
Hz).

6.6 4 (l H, s).

7.1 6 (2H, d, J=9.0Hz).

7.93 (2H, d, J=9.0Hz).

1 2.64 (I H, 5) 13C-nuclear magnetic resonance spectrum (δ ppm in DMSO-dll) 16.2 (q
), 17.3(q), 17.7(q).

21.3(t), 25.3(Q), 55.5(Q).

60.5(t), 69.6(d), 7 o, I(d).

70.1(d), 70.4(d), 70.6(d).

70.8(d), 71.7(d), 73.1(d).

73.2(d), 76.5(d), 77.1(d).

s l, 3(d), 9 s, x(d), 100.5(d
).

101.1(d), 105.4(s).

106.5(d), 108.3(s).

114.1(d), 114.1(d).

122.0(s), 122.1(d).

130.4(d), 130.4(d).

1 3 1. 0(s), 1 3 4. 8(s).

1 5 2.9 (s), 1 5 6.9 (s).

1 59.0 (s), I 6 0.4 (s).

161.4 (s), 178.2 (s) Example 3 The f2D-2 fraction obtained in Example 1 was subjected to MCI gel CHP.
Column chromatography using 20P, water-
Both fractions were obtained, eluting with methanol (55:45). Divide both parts into several times, and use YMCpack D-ODS-1O5
-10120A ODS was subjected to high performance liquid chromatography, and acetonitrile-methanol-water (5:
2:14) to obtain 351 g of yellow amorphous skeleton crystals.

Due to the physical and chemical properties shown below, this yellow amorphous skeleton crystal is
．． 4°-Nohydroquine-8-(3,3-dimethylallyl)flavone 3-0-β~D-xylopyranosyl (1→
3) -4-0-acetyl-α-L-rhamnopyranonodo7-0-β-D-glucopyranoside.

Specific optical rotation [α Q: 125.5° mass spectrum FAB-MS m/z:837.3j:M+H:.

HR-FAB-MS m/z: C311H490to (5M "H:'): Calculated value
837.2816 Actual value: 837.2817 Infrared absorption spectrum ν ;-ken α-13420,1
650, 1602, 1512 ultraviolet absorption spectrum λ
";'a":I"ym(logε)・350.4(4
,07), 320.0(4,10).

270.4 (4,38) Proton nuclear magnetic resonance spectrum (δ ppm in DMS O-d a) 0.73
(3H,d, J = 6.2 Hz).

1.61 (3H, s), 1.69 (3H, s).

1.98 (3H, s).

2.99 (I H, dd, J = 7.6.8.8
Hz).

3.11 (IH, t, J=8.8Hz).

3.34 (IH, dd, J=6.2.IO, 0Hz).

3.57 (IH, dd, J=7.4.14.2Hz)
.

3.77 (lH, dd, J=5.2,1 1.3Hz)
.

3.8 1(l H, dd, J = 3.0, I
O, 0Hz).

4. 1 5 (l H, m).

4. 2 3 (l H, d, J = 7.
6 Hz).

4.86 (IH, t, J=IO, 0Hz).

5. 0 0 (l H, bd, J = 7.
7 Hz).

5.17 (IH, bt, J=7.IHz).

5.3 2 (l H,d, J = 1.6
Hz).

6.6 4 (l H, s).

6.9 6 (2H, d, J = 8.8 Hz
).

7.7 8 (2Hld, J = 8.8 Hz
).

1 2.5 4 (I H, 5) 13C-nuclear magnetic resonance spectrum (δ ppm in DMS O-d s): 16.9
(Q), 17.7(Q), 20.7(Q).

21.3(t), 25.4(Q), 60.5(t).

e s, 7(d), 6 s, a(d), 69.4(d)
.

69.6(d), 69.6(d), 71.2(d).

72.8(d), 73.3(d), 76.4(d).

761(d) 176.5(d), 771(d).

9 8.0 (d), 1 0 0.5 (d), 1 0 1
．． 3(d).

1　0　5.4(s), 1　0　5.5(d).

1 0 8.2 (s), 1 1 5.4 (d).

1 1 5.4 (d), 1 20.0 (s).

1 2 2.1 (d), 1 3 0.6 (d).

1 3 0.6 (d), 1 3 1. 0(s).

1 3 3.7 (s), 1 5 2.9 (s).

1.5 7.7 (s), 1.5 9.0 (s).

1　6　0.4(s), 1　6　0.7(s).

1 7 0.0 (s), 1 7 8.0 (s) Example 4 The Di fraction obtained in Example 1 was applied to MCI gel CHP20P.
A fraction was obtained by column chromatography using water-methanol (55:45). The fraction was divided into several times, and YMCpack D-ODS-1O5-10
The product was subjected to high performance liquid chromatography using 120A ODS and eluted with acetonitrile-water (22Nia 8) to obtain yellow amorphous skeleton crystals 181119.

Due to the physical and chemical properties shown below, this yellow amorphous skeleton crystal is
．． 4°-nohydroquine-8-(3,3-dimethylallyl)flavone 3-0-β-D-fucopyranonol (l→2
)-α-L-rhamnopyranonedo 7-0 to β-D-glucopyranoside.

Specific optical rotation [α: 114.7° Mass spectrum FAB-MS m/z: 809.4 [M+H]'HR
-FAB-MS m/z: C3@H4eO+s ([M + Hi'): Calculated value: 8
09.2894 Actual value: 809.2868 Infrared absorption spectrum ν; Iα-1=3400.1
650.1598.1512 Ultraviolet absorption spectrum λ
Z”a2)I7rIL(log E): 352.
2 (4,09), 323.0 (4,10).

270.4(4,36) Proton nuclear magnetic resonance spectrum (δ ppm in DMS O-d s):
0.87 (3H, d, J=6.
4H2).

0.99 (3H, d, J = 6.4 Hz).

1.61 (3H, s), 1.70 (3H, s).

4. 0 4 (l H, dd, J = 1.
5. 3. 7 1(z).

4.3 9 (I H, d, J = 5.0 Hz).

4.53 (l H, dj=9.8Hz).

4.62 (IH, t, J=5.6Hz).

4.8 6 (I H-, d, J = 5.0
Hz).

5.0 0(l H, d, J = 7.3 H
z).

5.1 8 (L H,t, J = 6.8
Hz).

5.5 2 (I H, bd, J = l, 5
Hz).

6.6 3 (L H, s).

6.95 (2H, d, J=8.8Hz).

7.8 3 (2Hld, J = 8.8 Hz)
.

1 2.6 0(l H, 5) 13c-nuclear magnetic resonance spectrum (δ ppg+ in DMSO-d s): 1
6.2(q), 17.3(Q), 17.8(Q).

21.3(t), 25.4(q), 60.6(t).

69.6(d), 70.1(d), 70.1(d).

70.4(d), 70.7(d), 70.8(d).

71.7(d), 73.1(d), 73.3(d).

76.5(d), 77.1(d), 81.3(d).

98.0(d), 100.5(d).

1　0　1.0(d), 1　05.4(s).

1.06.6 (cl), 1.08.2 (s).

1 1 5.4 (d), 1 1 5.4 (cl).

l　　　20.4(s), 1　22.2(d).

1 30.5 (d), 1 30.5 (d).

130.9 (s), 1 34.5 (s).

1 52.8 (s), 1 57.4 (s).

1 59.0 (s), 1 60.2 (s).

160.4 (s), 1 78.1 (s) Example 5 The E fraction obtained in Example 1 was subjected to silica gel column chromatography, and chloroform-methanol-water (1
4:3, 2:0.3) were obtained. The fraction was divided into several times, and YMCpack D-ODS-1+l5-
High performance liquid chromatography using 10120A ODS was performed using acetonitrile-methanol-water (5:2).
:6) to obtain yellow amorphous skeleton crystals 24119.

This yellow amorphous skeleton crystal has 4
'~methoxy-5,7-cyhydroxy-8-(3.

3-dimethylallyl) flavone was determined to be 3-0-β-D-fucopyranonor(1→2)-α-L-rhamnopyranosodo.

Specific optical rotation [α]o: 99.3° Mass spectrum FAB-MS m/z: 661.3cM+H]'HR
-FAB-MS m/z C33Halo 14 ([M + H Co).

Calculated value: 661.2467 Actual value: 661.2496 Infrared absorption spectrum ν -2'xCM-': 343
2.1658.1614゜1594.1508 Ultraviolet absorption spectrum λ: a2” rIM (log
ε): 351.0 (3,97), 305.6 (4,11
).

271.6 (4,38) Proton nuclear magnetic resonance spectrum (δ ppm in DMS O-d s): 0.
87 (3H,d, J = 5.9 Hz).

0.97 (3Hl, d, J = 6.4 Hz).

1.62(3)1. s), 1.69 (3H, s).

3.8 5 (3H, s), 4.0 1 (I H, bd
d).

5.1 6 (IH, t, J=6.8Hz).

5.4 8 (l H, bd, J = 1.5
Hz).

6.3　0　(I　　　H,s　).

7.1 5 (2H, d, J = 9.0 Hz).

7.9 0 (2H, d, J = 9.0 Hz).

1 2.5 9(l H, 5) 13c-Nuclear magnetic resonance spectrum (δ ppm in DMS O-d s): 16
．． 2(Q), 17.3(Q), 17.7(Q).

21.1 (t), 25.3 (Q), 55, . 4
(q).

70.1(d), 70.1(d), 7 Q, 3(d).

70.6(d), 70.8(d), 71.7(d).

73.0(d), 81.3(d), 98.4(d).

101.0(d), 103.8(s).

105.9(s), 106.5(d).

114.0(d), 114.0(d).

122.2(s), l22.3(d).

130.2(d), 130.2(d).

1 3 0.8 (s), 1 3 4. 6(s).

1 5 3.7 (s), 1 5 6.2 (s).

158.8 (s), 161.2 (s).

1 6 2.0 (s), 1 7 7.8 (s) Example 6 ■Corn starch 449 ■Crystalline cellulose 409 ■Carpoquine methylcellulose carnoum 59 ■Light silicic anhydride 0.5g■Magnenium stearate 0.5g■ Compound obtained in Example 1
10g Total 100g According to the above recipe, ① to ② were mixed uniformly and compressed using a tablet machine to obtain a portion of 200119 tablets.

This tablet contains compound 20II+9 obtained in Example 1.
It contains 5 to 15 tablets per day for adults, divided into several doses.

Example 7 ■Crystalline cellulose 8459 ■Magnesium stearate 059 ■Calfoquin methylcellulose carnoum 59 ■Compound obtained in Example 2 +o9 Total 100 g According to the above recipe, parts of ■, ■, and ■ were uniformly mixed, After compression molding, it was pulverized, the remaining amounts of (1) and (2) were added and mixed, and the mixture was compressed and molded using a tablet machine to obtain a portion of 20019 tablets.

This tablet contains 20xg of the compound obtained in Example 2, and adults should take 5 to 15 tablets a day in several doses.

Example 8 ■Crystalline cellulose 49.59■10% hydroxypropylcellulose ethanol solution 35g ■Carboxymethylcellulose carunium 5g ■Magnesium stearate 059 ■Compound obtained in Example 3 1O9 Total 100g Prepare ■, ■, and ■ according to the above recipe. After uniformly mixing, netting by a conventional method, granulating with an extrusion granulator, drying and crushing, ① and ② were mixed, and compression molded with a tablet machine to make a portion of 200 N9. Got the tablets.

These tablets contain 20~ of the compound obtained in Example 3, and are taken by adults in 5 to 15 tablets a day in several doses.

Example 9 ■Corn starch 3459 ■Magnenoum stearate 509 ■Carboxymethylcellulose carnoum 5g ■Light silicic anhydride 059 ■Compound obtained in Example 4 +09 Total 1009 According to the above recipe, ■~■ were mixed uniformly and molded using a compression molding machine. After compression molding, the mixture was crushed using a crusher, sieved, and ground into granules.

This granule 19 contains compound 10019 obtained in Example 4.
It contains 1 to 39 doses per day for adults, divided into several doses.

Example 10 ■ Crystalline cellulose 559 ■ 10% hydroquinopropyl cellulose ethanol solution 359 ■ Compound obtained in Example 5 Log total 1009 According to the above recipe, ■ to ■ were homogeneously mixed and suspended. After granulation using an extrusion granulator, the mixture was dried and sieved to obtain granules.

This granule 19 contains compound 10019 obtained in Example 5.
It contains 1 to 3 g per day for adults, divided into several doses.

Example 11 ■Corn starch 89.59■Light silicic anhydride 059 ■Compound obtained in Example 1 10 Total 1009 Mix ■~■ uniformly according to the above recipe, and mix 200 m
9 was filled into a No. 2 capsule.

This capsule contains the compound 20R9 obtained in Example 1, and adults take 5 to 15 capsules a day in several doses.

Example 12 ■ Distilled water for injection Appropriate amount ■ Glucose 200 yg ■ Example 2
Compound obtained in 200119 total amount 10
〇- After dissolving ① and ② in distilled water for injection, they were injected into the ampoule of 5- and autoclaved at 121'C for 15 minutes to obtain an injection.

Claims (2)

[Claims] (1) The following formula I ▲There are mathematical formulas, chemical formulas, tables, etc.▼ I (In the formula, R_1 is rhamnose^3-^1 xylose or rhamnose^2-^1 fucose, which is acetylated at the 4-position, and R_2 is rhamnose^2-^1 fucose. Hydrogen atom or glucose, R_
3 represents a hydrogen atom or a methyl group. ) is a flavonoid glycoside. (2) The following formula I ▲ There are mathematical formulas, chemical formulas, tables, etc. ▼ I (In the formula, R_1 is rhamnose^3-^1 xylose or rhamnose^2-^1 fucose, which is acetylated at the 4-position, and R_2 is rhamnose^2-^1 fucose. Hydrogen atom or glucose, R_
3 represents a hydrogen atom or a methyl group. ) A 5-lipoxygenase inhibitor containing a flavonoid glycoside represented by the following as an active ingredient.