JPH0390021A - Medicine preparation containing zingerol derivative - Google Patents

Abstract

PURPOSE:To obtain an agent for suppressing production of active oxygen in a living thing and antiphlogistic containing a zingerol derivative and useful as preventive or remedy for chronic rheumatism, hepatitis, carcinogenesis, ulcer of digestive organs, disorder of various organs by re-circulation of ischemia. CONSTITUTION:The aimed active oxygen suppressing agent in a living thing and antiphlogistic containing a zingerol derivative expressed by formula I (R is CH2CH2 or CH=CH; Y is CH=CH or CH2Z; Z is CO, formula II or CH2), e.g. a compound expressed by formula III as an active ingredient, having strong production suppressing action against active oxygen produced in a living thing influenced on crisis of the above-mentioned disease and being extremely low in toxicity and capable of extremely readily treating and therefore useful as preventive or remedy for the above-mentioned diseases. Furthermore, dose of the above-mentioned compound is normally 100-3000mg, preferably 200-500mg/ adult day and preferably divided once to three times and the above-mentioned compound is especially preferably orally administered.

Description

DETAILED DESCRIPTION OF THE INVENTION [Industrial Field of Application] The present invention relates to an in vivo active oxygen production inhibitor and an anti-inflammatory agent containing a gingerol derivative.

[Prior Art and Problems to be Solved by the Invention] Active oxygen produced in living organisms has various harmful biological effects. Matsucord showed in vitro that hyaluronic acid in the joint cavity was broken down into small molecules by active oxygen, and was the first to show that active oxygen is involved in inflammation (Mc
Cord 5science, Volume 185, 529-5
31, 1974). It has also been shown that active oxygen has the effect of increasing vascular permeability, promoting the synthesis of prostaglandin, and attracting cells, and it is clear that it is closely related to inflammation. Burk heart
) indicates that cartilage is destroyed by active oxygen.
Thritis and Rheumatism 19
88.29, pp. 379-387) showed that active oxygen is involved in joint destruction in rheumatoid arthritis.

Active oxygen species are also considered important in the pathogenesis of ischemic organ damage (Granger, D, N, et al.
terology 1981, vol. 81, p. 22).

Active oxygen species have also been shown to be associated with carcinogenesis. The causative agent for 60 to 70% of the effects of radiation on living organisms is active oxygen, and one of its most extreme effects is DNA strand scission. Aromatic hydrocarbons such as benzpyrene, which are carcinogens, become radicals and combine with DNA and proteins, causing sudden displacement and carcinogenesis.

Active oxygen is said to be involved in the pathogenesis of liver damage caused by microsomal metabolism of foreign substances such as carbon tetrachloride, and liver damage caused by radiation.

As described above, it is clear that active oxygen is involved in the onset of various Npa organ damage and irritating pathological conditions due to rheumatoid arthritis, hepatitis, carcinogenesis, gastrointestinal ulcers, and ischemia reperfusion.

Therefore, it has been a challenge to find substances that suppress the production of active oxygen and are effective in treating these diseases.

The present inventors have combined various gingerol derivatives, and as a result of intensive research on their active oxygen production inhibiting effects, have discovered that the gingerol derivatives related to the present invention have a strong active oxygen production inhibiting effect, and have completed the present invention. reached.

The gingerol derivatives of the present invention, which have an active oxygen production suppressing effect, suppress the production of active oxygen and are useful for various organ disorders caused by rheumatoid arthritis, hepatitis, carcinogenesis, gastrointestinal ulcers, and ischemia reperfusion.

[Means to solve the problem]

The present invention relates to the general formula (1) [wherein R represents a hydrogen atom or a lower alkyl group, and X represents -
This is an in vivo active oxygen production inhibitor containing a gingerol derivative represented by CH2-CH2- or -CH-CH-.

Furthermore, the present invention is an anti-inflammatory agent containing the gingerol derivative described above.

In the definition of R in the above formula (1), the lower alkyl group refers to a linear or branched alkyl group having 1 to 4 carbon atoms, and preferred examples include methyl, ethyl, n-propyl, and n-butyl. etc. can be mentioned.

The gingerol derivative represented by the above formula (1) of the present invention is produced by a Claisen reaction between a benzylidene acetone derivative having the formula (n) [wherein R1 represents a methoxymethyl group or a hydrogen atom] and capric acid imidazole amide, or by a Claisen reaction between a benzylidene acetone derivative having the formula (n) [wherein R1 represents a methoxymethyl group or a hydrogen atom] and capric acid imidazole amide, It can be obtained by carrying out an aldol reaction with a compound, followed by a deprotecting group reaction, an alkylation reaction, a catalytic reduction, and a dehydration reaction.

The gingerol derivative (1) of the present invention is used as an active oxygen production inhibitor and an anti-inflammatory agent, and the dosage varies depending on the symptoms, but is generally an adult artificial daily dose of t00 to 3000 μ, preferably 200 to 500 μ, depending on the symptoms. It is advisable to administer the drug in 1 to 3 divided doses as necessary. The administration method can take any form suitable for administration, and oral administration is particularly preferred, but intravenous injection is also possible.

The compound of the present invention can be used as an active ingredient or one of the active ingredients alone or mixed with a pharmaceutical carrier or excipient in a conventional manner, and can be used as a tablet, sugar-coated tablet, powder, capsule, granule, suspension, emulsion, or injection. It can be applied in various forms such as liquid formulations. Examples of carriers or excipients include calcium carbonate, calcium phosphate, starch, glucose, lactose, dextrin, alginic acid, mannitol, talc, magnesium stearate, and the like.

Next, the present invention will be explained in more detail by showing production examples, working examples, and test examples, but the present invention is not limited thereto.

Production Example 1 Diisopropylamine under argon atmosphere 8. Dissolve Llg in 200 ml of dry tetrahydrofuran and heat at -15°C.
After cooling to , 40.2 ml of a 1.8 M n-butyllithium hexane solution was added dropwise. dry tetrahydrofuran 5
After dropping 14.0 g of 4-(3,4-dimethoxymethyloxyphenyl)-3-buten-2-one dissolved in 0 ml at -15°C, the mixture was stirred at the same temperature for 20 minutes. After cooling to -78°C, 11.7 g of capric acid imidazolamide dissolved in 50 ml of dry tetrahydrofuran was added dropwise, and the mixture was stirred at the same temperature for 3 hours and at room temperature for 12 hours. After adding saturated brine to the reaction solution and separating the organic layer, the aqueous layer is extracted with ethyl acetate. The organic layer is washed with 2N hydrochloric acid, a saturated aqueous sodium bicarbonate solution, and saturated brine, dried over anhydrous magnesium sulfate, and then the solvent is distilled off under reduced pressure. The residue was subjected to silica gel column chromatography, and 1-(3,4-dimethoxymethyloxyphenyl)-1-tetradecene-3,5-dione 14. f3. get.

7.44 g of this Claisen reaction adduct was dissolved in 150 ml of methanol-tetrahydrofuran (1: lv/v), 15 ml of 6N hydrochloric acid was added, and the mixture was stirred at 60°C for 15 minutes. The solvent was distilled off under reduced pressure, and the precipitated crystals were collected by filtration and washed with water to give 1-(3,4-dihydroxyphenyl).
-1-tetradecene-3,5-dione (m) 5.71.
get. The spectroscopic data of this product is expressed by the following formula (II[)
support the configuration of

'HNMR (DMSO-dB): 0.83 (3H, t, J-4, 5H2), 1.00-
1.80 (14H, +a), 2.87 (2H, t, J-
6.5Hz), 5.78 (IH, S), 8.43<L
H, d, J=15.5Hz), 6.87-7.17(
3H, m), 7.44 (LH, d, J-15, 5H2)
Production Example 2 0.50 g of 1-(3,4-dihydroxyphenyl)-1-tetradecene-3,5-dione was added to 10 m of methanol.
After adding 5% palladium on carbon and tor and reacting in a hydrogen gas atmosphere for 5 hours, the reaction mixture was filtered and the solvent was distilled off under reduced pressure. The residue was subjected to silica gel column chromatography, and 046 g of 1-(3,4-dihydroxyphenyl)-3,5-tetradecanedione (IV) was obtained from the fraction eluted with methylene chloride. Spectroscopic data of this product support the structure of formula (IV) below.

IHNMR (DCR3) δ: 0.87 (3H, t, J-5,0Hz), L, 0O-1
, 83 (L4H, m), 2.07-2.93 (6H, i
), 5.39 (LH,s), 6.27-6.73 (3
H, layer) Production Example 3 Under an argon atmosphere, 8.74 g of diisopropylamine was dissolved in 200 ml of dry tetrahydrofuran, and the mixture was heated to -15°C.
After cooling to , 55.7 ml of a 1.6 M n-butyllithium hexane solution was added dropwise. dry tetrafuran 200
19.2 g of 4-(3,4-dimethoxymethyloxyphenyl)-3-buten-2-one dissolved in ml
After the dropwise addition at 5°C, the mixture was stirred at the same temperature for 0.5 hour.

After cooling to −78° C., 23.81 i of caprinaldehyde dissolved in 80 ml of dry tetrahydrofuran was added dropwise, and the mixture was stirred at the same temperature for 2.5 hours. After adding 30 ml of methanol, the mixture was returned to room temperature, saturated brine was added, the organic layer was separated, and the aqueous layer was extracted with diethyl ether.

The organic layer was treated with 2N hydrochloric acid, a saturated aqueous sodium bicarbonate solution,
After washing with saturated saline and drying with anhydrous magnesium sulfate,
The solvent is removed under reduced pressure. The residue was subjected to silica gel column chromatography using methylene chloride-hexane (1:1
v/v) From the elution fraction, 27.8 g of 1-(3,4-dimethoxymethyloxyphenyl)-5-hydroxy-1-tetradecen-3-one was obtained.

After dissolving 194 g of titanium tetrachloride in 50 ml of methylene chloride and cooling to -78° C., 19.3 g of this aldol reaction adduct dissolved in 250 ml of methylene chloride was added dropwise and stirred at the same temperature for 0.5 hour.

After raising the temperature to room temperature, add 1500 ml of ethyl acetate and 50 ml of water.
0 ml is added, the organic layer is separated and the aqueous layer is extracted with ethyl acetate. The organic layer was treated with a saturated aqueous sodium bicarbonate solution,
After washing with saturated brine and drying over anhydrous magnesium sulfate, the solvent was distilled off under reduced pressure. The obtained crude crystals are washed with ethanol-methylene chloride (3:97 v/v) to obtain 843 g of 1-(3,4-dihydroxyphenyl)-5-hydroxy-1-tetradecen-3-one (V). Spectroscopic data of this product support the structure of formula (V) below.

'HNMR (DMSO-dB): 0.85 (3H, t, J-5Hz), 1.03-1.
67 (16H, m), 2.88 (2H, d, J-GHz
), 3.87-4.10 (lH, m), 6.38 (L
) [, d, J-16Hz), 8.87-7.10 (3
H, +g), 7.33 (IH, d, J = 1BHz) Production example 4 7.22 g of 1-(3,4-dihydroxyphenyl)-5-hydroxy-1-tetradecen-3-one was dissolved in 200 ml of ethyl acetate. Dissolved in 5% palladium on carbon 1.0
0. After reacting for 15 hours under a hydrogen gas atmosphere, the reaction solution was filtered and the solvent was distilled off under reduced pressure.

The residue was subjected to silica gel column chromatography, and 1-(3,4-dihydroxyphenyl)5-hydroxytetradecan-3-one (Vl) 5.94. get. Spectroscopic data of this product support the structure of formula (VI) below.

'1 (NMR (CD (1! 3) δ: 0.87 (3H, t, J = 4.5Hz), 1.07-1
．． 82 (46H, 11), 2.47 (2H, d, J=6
．． 0Hz), 2.58-2.75 (4H, +g), 3.
80-4.23 (IH, m), 8.20-8.80 (
3H, i) Production Example 5 3.30 g of 1-(3,4-dihydroxyphenyl)-5-hydroxytetradecan-3-one and 0.30 g of p-toluenesulfonic acid hydrate. was dissolved in 88 ml of methanol-benzene (1:1Qv/v) and heated under reflux for 4 hours. A saturated aqueous sodium hydrogen carbonate solution was added to the reaction solution, the organic layer was separated, the aqueous layer was extracted with ethyl acetate, the organic layer was washed with a saturated aqueous sodium hydrogen carbonate solution and saturated brine, dried over anhydrous magnesium sulfate, and the solvent is distilled off under reduced pressure. The residue was subjected to silica gel column chromatography, and 1-(3,4-dihydroxyphenyl)-4- was extracted from the methanol-methylene chloride (1:9 v/v) elution fraction.
3.00 g of tetradecen-3-one (■) are obtained. Spectroscopic data of this product support the structure of the following formula (■).

5H NMR (CDCff 3 ) δ: o, 88 (
3H, t, J-5Hz), 1.01-2.38 (16H
v), 2.80-2.90 (4H, m), 8.08 (
LH, d, J-18Hz), 6.28-7.23 (4H
Production Example 6 7 g of 1-(3,4-dihydroxyphenyl)-4-tetradecen-3-one OJ was dissolved in 5 ml of methanol, 5% palladium carbon OJO was added, and the mixture was reacted for 25 hours under a hydrogen gas atmosphere. , the reaction mixture is filtered and the solvent is removed under reduced pressure. The residue was subjected to silica gel column chromatography using methanol-methylene chloride (5:95
v/v) 042 g of 1-(3,4-dihydroxyphenyl)-3-tetradecanone (■) was obtained from the elution fraction.

Spectroscopic data of this product support the structure of the following formula (■).

'HNMR (CDC, l? 3') δ: 0.87 (3H
, t, J-8H2), 1.05-1.73 (18H, m
), 2.20-2.87 (6H, 11), 8J7-8
．． 84 (3H, shoes) Production example 7 Under argon atmosphere, 12.50 g of diisopropylamine
was dissolved in 100 ml of dry tetrahydrofuran, -15
After cooling to °C, 8247 ml of a 1.8 M n-butyllithium hexane solution was added dropwise, and the mixture was stirred at the same temperature for 10 minutes.

After cooling to -78℃, dry tetrahydrofuran 100ml
22.58 g of 4-(4-benzyloxy-3-methoxyphenyl)-3-buten-2-one dissolved in the solution was added dropwise, and the mixture was stirred at the same temperature for 40 minutes. To this was added 19.0 ml of capricaldehyde dissolved in 30 ml of dry tetrahydrofuran.
31. was added dropwise and stirred at the same temperature for 4 hours.

The reaction mixture is diluted with ether, saturated brine is added, the aqueous layer is separated, and the aqueous layer is extracted with ether. The organic layers are combined and washed with 2N hydrochloric acid, a saturated aqueous sodium bicarbonate solution, and saturated brine, dried over anhydrous magnesium sulfate, and then the solvent is distilled off under reduced pressure. The residue was subjected to silica gel column chromatography, and 1-(
18.87 g of 4-benzyloxy-3-methoxyphenyl)-5-hydroxy-1-tetradecen-3-one
obtain. The obtained 1-(4-benzyloxy-3-
11.09 g of methoxyphenyl)-5-hydroxy, -1-tetradecen-3-one was dissolved in 200 ml of methanol, 1.00 g of 10% palladium on carbon was added, and the reaction mixture was reacted for 15 hours under a hydrogen gas atmosphere. was filtered and the solvent was removed under reduced pressure.

The residue was subjected to silica gel column chromatography, and 1-(4-hydroxy-3-
8.10 g of methoxyphenyl)-5-hydroxy-3-tetradecanone ((10)-gingerol) are obtained.

Spectroscopic data of this product support the structure of formula (IX) below.

'HNMR (CDCII3) δ: 0.88 (3H, t, J=5Hz), 1.05-1.
58 (16H, n), 2.50 (2H, d, J-6Hz
), 2.65-2.95 (4H, 11), 3.79 (3
H,s), 6.41-8.85 (3H,m) Production Example 8 Under an argon atmosphere, 5.57g of diisopropylamine was dissolved in 50ml of dry tetrahydrofuran, and after cooling to -15°C, 1.6M n-butyl 34.4 ml of a hexane solution of lithium was added dropwise, and the mixture was stirred at the same temperature for 10 minutes.

4-(3) dissolved in 50 ml of dry tetrahydrofuran
-methoxy-4-methoxymethyloxyphenyl)-3
- After dropping 10.00 [of buten-2-one] at -15°C,
Stir for 20 minutes. Add 1 part dry tetrahydrofuran to this
Add 5.81 g of trimethylchlorosilane dissolved in 0 ml and stir at the same temperature for 1 hour. Saturated brine was added to the reaction mixture, the aqueous layer was separated, ether was extracted from the aqueous layer, the organic layers were combined, washed with a saturated aqueous sodium bicarbonate solution and saturated brine, dried over anhydrous magnesium sulfate, and the solvent was removed. Distillation under reduced pressure yields a dinolic silyl ether, which is used in the next reaction without purification.

100 of titanium tetrachloride s, t'yr cooled to -78°C
m1 methylene chloride solution, n-capric aldehyde 6.
73 g of a 10 ml methylene chloride solution are added dropwise. At the same temperature, 50 ml of the previously obtained enol silyl ether solution in methylene chloride was added dropwise over 15 minutes, and the mixture was stirred at -78°C for 1 hour. After adding 3 ml of methanol to the reaction mixture and further adding saturated brine to separate the aqueous layer, the aqueous layer is extracted with methylene chloride.

The organic layer is washed with a saturated aqueous sodium bicarbonate solution and saturated brine, dried over anhydrous magnesium sulfate, and then the solvent is distilled off under reduced pressure. The residue was subjected to silica gel column chromatography, and 1-(4-hydroxy-3-methoxyphenyl)-5-hydroxy-1-tetradecen-3-one was extracted from the fraction eluted with methylene chloride-hexane (3: lv/v). ((10)-dehydrozingerol) 8.02g
get.

Spectroscopic data of this product support the structure of formula (X) below.

IH NMR (CD (J! 3') 0.87 (3H, t, J-51 (z), 2.75 (2H
, d, J-8H2), 8.50 (IH, d, J=16Hz), 7.44 (IH
, d, J=18Hz) δ: 1.07-1.71 (16H, I), 3.85 (3H, s), 6.50-7.17 (3H, +g), Production Example 9 Under argon atmosphere , 6.93 g of diisopropylamine was dissolved in 100 ml of dry tetrahydrofuran and heated to -15°C.
After cooling to , 44.2 ml of a 1.8 M n-butyllithium hexane solution was added dropwise, and the mixture was stirred at the same temperature for 20 minutes.

After cooling to -78°C, 15.15 g of 4-(3-methoxy-4-methoxymethyloxyphenyl)-3-buten-2-one dissolved in 80 ml of dry tetrahydrofuran is added dropwise and stirred at the same temperature for 20 minutes. . 14.50 g of capric acid imidazolamide dissolved in 30 ml of dry tetrahydrofuran was added dropwise at the same temperature for 2 hours, then at room temperature for 2 hours.
Stir for 0 hours. After adding saturated sodium chloride to the reaction mixture and separating the organic layer, the aqueous layer is extracted with ethyl acetate. The organic layer is washed with 2N hydrochloric acid, a saturated aqueous sodium bicarbonate solution, and saturated brine, dried over anhydrous magnesium sulfate, and then the solvent is distilled off under reduced pressure. The residue was subjected to silica gel column chromatography, and 1-(3
-methoxy-4-methoxymethyloxyphenyl)-1
-tetradecene-3,5-dione 17.00. get.

2.11 g of 1-(3-methoxy-4-methoxymethyloxyphenyl)-1-tetradecene-3,5-dione
and tetrahydrofuran-methanol (1:1 v/v
), and add 4.0 ml of 6N hydrochloric acid to make 6
Stir for 10 minutes at 0°C.

The reaction solution was concentrated under reduced pressure, saturated brine was added, and the mixture was extracted with methylene chloride. The organic layer was washed with saturated brine, dried over anhydrous magnesium sulfate, and the solvent was distilled off under reduced pressure.
1-(4-hydroxy-3-methoxyphenyl)-1-
1.88 g of tetradecene-3,5-dione are obtained.

1-(4-hydroxy-3-methoxyphenyl)-1-
Tetradecene-3,5-dione 1. Hi to methanol 4
After adding 10% palladium on carbon o, aor and reacting in a hydrogen gas atmosphere for 18 hours, the reaction mixture was filtered and the solvent was distilled off under reduced pressure. The residue was subjected to silica gel column chromatography, and 1.45 g of 1-(4-hydroxy-3-methoxyphenyl)3,5-tetradecanedione ((10)-gingerdione) was obtained from the fraction eluted with methylene chloride.

Spectroscopic data of this product support the structure of the following formula (XI,).

5) I NMR (CDCI! 3) δ:
0.88 (3H, t, J=5Hz), 1.06-1.8
9 (14H, m), 2.07-3.07 (6H, ■)
, 3.82 (3H, s), 5.40 (IH, s),
6.50-6.90(3H,i) Production example 10 1-(4-hydroxy-3-methoxyphenyl)-5
-Hydroxy-3-tetradecanone 0.90g and p-)
Luenesulfonic acid hydrate 0.1Of benzene 30m
1 and heated under reflux for 3 hours. A saturated aqueous sodium hydrogen carbonate solution was added to the reaction solution, the organic layer was separated, the aqueous layer was extracted with ethyl acetate, the organic layer was washed with a saturated aqueous sodium hydrogen carbonate solution and saturated brine, dried over anhydrous magnesium sulfate, and the solvent is distilled off under reduced pressure.

The residue was subjected to preparative TLC, developed with methylene chloride, and extracted with methylene chloride from the band of RfO, 2 to 0.4, yielding 1-(4-hydroxy-3-methoxyphenyl)-4-tetradecen-3-one ( , (10)
-Shogaol) Obtain 0.50f. Spectroscopic data of this product support the following structural formula (XI).

IHNMR (CDCR3) δ: 0.87 (3H, t, J-5Hz), 1.02-1.8
0 (14H, m), 1.9O-247 (2H, m),
2.82 (4H, br, s), 3.83 (3H, s),
8.02 (IH, d, J-1 [1Hz), 6.5
0-7.00 (4H, ■) [Test Example] Active Oxygen Production Inhibitory Effect The compound of the present invention was investigated for its inhibitory effect on the production of active oxygen (superoxide anion radical) from human peripheral blood-derived neutrophils.

Human peripheral blood was collected in the presence of heparin, red blood cells were separated using the dextran method, and then Lymphoprep (specific gravity 1.
Neutrophils are collected by specific gravity method using 077). Superoxide anion radicals were measured by the cytochrome C reduction method.

That is, neutrophils (106 cells) received ferricytochrome C (2
4μM), catalase (40u/ml) sample was added, and then stimulated with N-formyl-L-methionyl-L-leucyl-L-phenylalanine (2,5X 10-7M) and cytochalasin B (5μ/ml). 0D550-540 before and after stimulation using a three-wavelength spectrophotometer.
The absorbance difference of (OD - OD) was measured 55
0 540 (ΔOD). Sample dissolved in DMSO55
0-540. The inhibition rate (%) was determined by the following formula, and IC5o was calculated based on this.

80 D 5s. -540,: Difference in absorbance Δ0D550-540s' before and after addition of DM SO The results of the difference in absorbance before and after addition of the sample are shown in Table 1.

From the results in Table 1, it is clear that the compounds of the present invention exhibit an active oxygen production inhibiting effect.

Although not shown in the above table, similar inhibitory effects were also observed for other compounds related to the present invention.

Suppressive effect on adjuvant arthritis The compound of the present invention (■) was investigated for its effect on adjuvant arthritis (chronic rheumatoid arthritis pathology model) in Lewis rats.

6 week old male Lewis rat (weight 130-180 g)
A group of 5 animals was used for the test. 0.2■ Mycobacterium butyricum (Mycobacterium butyricum)
A suspension of dried bacterial cells (C. utilicum) in liquid paraffin was injected subcutaneously into the right hind foot pad of each group of rats.

The compound was suspended in 5% Tween 80 and given 1% from the day after sensitization.
It was orally administered once a day (100 mg/kg). The hindlimb volume of the rats in the drug administration group and the control group (no drug administration group) was measured over time, and the inhibitory effect of the adjuvant on arthritis was investigated. Calculate the rate of increase in footrest volume (edema) based on the hindlimb volume before sensitization, calculate the inhibition rate from the ratio with the control group, and calculate the results on day 15 and day 21 after sensitization. Shown in Table 2.

From the results in Table 2, it is clear that Compound A of the present invention exhibits an inhibitory effect on adjuvant arthritis.

Although not shown in the above table, similar inhibitory effects were also observed for other compounds related to the present invention.

[Acute toxicity]

Compound A was found to have anti-rheumatic activity, but no toxicity such as weight loss was observed when these compounds were administered intraperitoneally to male ICR mice at a dose of 500 μ/kg.

Example 1 Capsule [Prescription] Main drug: Compound rv ioo Excipient: Corn starch 98 mg Compound IV (1-(3,4-dihydroxyphenyl)-L), a crude drug
Add excipients to 5-tetradecanedione), make it into powder or granules, add a lubricant and mix evenly, fill in hard capsules, and mix with active oxygen production inhibitor or anti-inflammatory agent. do.

Example 2 Tablet [Formulation] Main drug: Compound IV 50■ Excipient: Crystalline cellulose 671g: Corn starch 89wg Dilactose 44■ Disintegrant: Calcium carboxymethyl cellulose 25mg Binder: Hydroxyprobil cell, loin 82.5 (2) Excipients, disintegrants and binders are added to Compound (2), which is a crude drug, and the mixture is evenly mixed, then made into granules, and then a lubricant is added to form compressed tablets. Further, if necessary, the resulting tablets may be coated with a suitable coating (eg, hydroxypropylmethylcellulose, shellac, etc.).

〔Effect of the invention〕

As described above, the present invention is a preparation containing a gingerol derivative represented by the general formula I as an active ingredient, which has an effect of suppressing active oxygen production from neutrophils, and which is a typical agent for rheumatoid arthritis. It has an inhibitory effect on adjuvant arthritis, which is a model. Furthermore, the compounds of the present invention have extremely low toxicity and are therefore very easy to handle.

Therefore, the gingerol derivatives represented by the general formula I of the present invention are extremely effective as anti-inflammatory agents, therapeutic agents for hepatitis, anti-carcinogenic agents, and preventive agents for various organ disorders caused by ischemia reperfusion.

Claims (2)

[Claims] (1) General formula (I) ▲Mathematical formulas, chemical formulas, tables, etc.▼(I) [In the formula, R represents a hydrogen atom or a lower alkyl group, and X represents -
CH_2-CH_2- or -CH=CH-, Y is -CH=CH- or -CH_2-Z- (in the formula, Z is C=O
, ▲ There are mathematical formulas, chemical formulas, tables, etc. ▼ or ▲ Mathematical formulas,
An inhibitor of active oxygen production in living organisms containing a gingerol derivative represented by the chemical formula, table, etc. (2) General formula (I) ▲Mathematical formulas, chemical formulas, tables, etc.▼(I) [In the formula, R represents a hydrogen atom or a lower alkyl group, and X represents -
CH_2-CH_2- or -CH=CH-, Y is -CH=CH- or -CH_2-Z-, where Z is C=O,
An anti-inflammatory agent containing a gingerol derivative represented by ▲There are mathematical formulas, chemical formulas, tables, etc.▼ or ▲There are mathematical formulas, chemical formulas, tables, etc.▼).