JPS5924966B2 - Anti-inflammatory agent containing an aminobenzoic acid derivative or a pharmaceutically acceptable salt thereof as an active ingredient - Google Patents

Description

DETAILED DESCRIPTION OF THE INVENTION The present invention relates to an anti-inflammatory agent containing an aminobenzoic acid derivative represented by the following general formula 1 or a pharmaceutically acceptable salt thereof as an active ingredient.

R, -NH (H゜゜゜゜゜゜゜゜'
Indicates galactose, rhamnose or mannose residues.

] Conventionally, synthetic compounds and antibiotics have been used as anticancer agents, but although these have lacked a cancer-killing effect, they have the disadvantage of being highly toxic and causing side effects because they also act on normal cells.

Therefore, recently, polysaccharides of various origins have attracted attention because they exhibit anticancer effects by enhancing the immune capacity of the host. The present inventors have already developed and provided to society an anticancer agent made from a basidiomycete-derived polysaccharide, and while researching the structure and activity of this anticancer agent, they discovered a remarkable anti-inflammatory effect in the compound represented by general formula 1 above. , has completed the present invention. Although the compound represented by the general formula (1) above (hereinafter referred to as "this substance") has a simple structure, it has extremely low toxicity and has no antibacterial activity, so there is no need to worry about disturbing the intestinal flora. , long-term administration is possible.

Furthermore, it is an extremely safe drug that does not have mutagenicity or affect cell-mediated or humoral immunity,6 and therefore poses no risk of teratogenicity or allergic reactions in healthy people. In addition, both of these substances have carrageenan edema inhibitory effects and granuloma inhibitory effects. It has anti-exudation action and adjuvant arthritis suppressing action, and is useful as an anti-inflammatory agent. There are three types of carboxyl group positions in this substance, p-6m- and 0-, and there may be some differences in the activity of each.
Essentially all are useful.

Pharmaceutically acceptable salts of aminobenzoic acid refer to salts of alkali metals, and the alkali metals usually include Na, K, M
g, Ca, Al, etc. are preferred, and Na is particularly preferred.
Furthermore, the sugar part is. It has a 6-membered ring (pyranose) structure. The method for producing this substance is exemplified below.

Aminobenzoic acid 1,5-59, sugar (L-arabinose,
D-xylose. D-glucose. D-galactose,
L-rhamnose or D-mannose) 2.0-6.4
g. Ammonium chloride 0.05-0.5f! 95~1
The mixture is heated and condensed under reflux of 10 to 90 mt of 00% ethanol or pure methanol.

If crystals precipitate after being left at room temperature or in a cold place for a while, filter the reaction solution and discard the crystals in water. After thorough washing with alcohol, ether, etc., recrystallize from methanol water or ethanol water. A well-known method may be used to substitute the hydrogen of the carboxyl group with a base.

That is, this substance is dissolved in an alcoholic aqueous solvent and an inorganic salt is added for substitution. The physicochemical properties of this substance obtained by the above production method are shown in Table 1 below.

Further, infrared absorption spectra are shown in FIGS. 1 to 24. The analysis method in Table 1 is as follows. (1) Fusion
Point Measured using a Yanagimoto micro melting point measuring device.

(2) Elemental analysis Measured using Yanagimoto CHN coater MT2 type.

(3) Using a UV Hitachi EPS-3T self-recording spectrophotometer, -H was measured using an alcohol monoaqueous system, and -Na was measured using water as a solvent.

(4) Measured by the KBr method using IR Japan Spectroscopy DS-701G model.

The book number matches the sample Na in Table 1.

Next, the toxicological properties of this substance are shown.

1) Acute toxicity Acute toxicity was investigated by intraperitoneal and forced oral administration using ICR-JCL mice.

This substance was dissolved in physiological saline for intraperitoneal administration, and in distilled water for oral administration,6 and the solution was adjusted to a predetermined amount using a syringe or stomach tube. Post-administration observation of toxicity was continued, and LD and O values were determined from the mortality rate over time up to 67 days.

The findings were obtained through autopsy in both surviving and dead cases. L1) 50 value is Litchfield-Wilcoxon (Litchfi
It was determined by the graphical calculation method. The results are shown in Table 2. Both are LD5 regardless of intraperitoneal or oral administration.
With an O value of 69/IC9 or higher, it is a low toxicity substance that is well within the range of so-called "ordinary medicines" 6 In addition, 6 out of 10 types of compounds 6, or more than half, have an LD5O value of 109/Kg
Based on the above, it can be said that this drug is extremely safe.

2) Antibacterial activity The substance was dissolved in distilled water to prepare a 2-fold dilution series. 2 This dilution was mixed with 9-fold volume of heated and dissolved agar medium, poured into a Petri dish, and plated.

Heart infusion agar (bacteria) and Sabouraud agar (fungi) were used as the culture medium, and after smearing and inoculating a test medium that had been precultured for 6 days, the bacteria were incubated at 37°C for 20 to 24 hours. Fungi at 25℃. 3-7
The cells were cultured for several days and the presence or absence of growth was examined. The following bacterial species were used as test bacteria. Pseudomonas aeruginosa (PseudOmO
nasaeruginOsaIAMl5l4) Escherichia coli (
Staphylococcus aureus (EscherichiacOliIFOl2734)
eus2O9P) Bacillus subtilis
lisIAMlO69) Baker's Yeast (SaccharOm
Candida albicans ATCC75
2) TrichOphytOnmentagr
OphytesIFO6l24) Black mold (Asperg
As a result, this substance did not inhibit the growth of any bacteria at a concentration of 1 mg/'ml.

3) Mutagenicity First, we destroyed it using Rec-Assay.

That is, a recombinant Bacillus subt.
B. ilis M45) and the recombinant repair carrier strain (B. suOtil
isHl7) on B-agar medium (Nikuko scratch 109,
Polypeptone 10f! , NaCl 59, agar 159, distilled water 1000 ml, pH 7.0) were streaked so that the starting points did not touch each other.

Dissolve this substance in sterilized water, absorb 0.05ml of it into a circular door paper with a diameter of 8 squares, and immediately leave it standing so as to cover the starting point of the streak, and culture it overnight at 37°C to grow. The length of the inhibition zone was measured. Kanamycin was used as a negative control, and mitomycin C was used as a positive control. Next, a reverse mutation test was performed on SalmOnellatyphimur-IumTA9.
8 and TAlOO (both require histidine).

0.5mM biothione-0.5mM histidine solution 1/1
0 volume of soft agar solution (NaCl69, agar 69, distilled water 1000ml) 2TIL1, bacterial solution 0.1ml, drug solution 0
．． 1a was added, mixed well, and layered on a minimal agar medium.

The cells were cultured at 37°C for 2 days and the number of revertant colonies was counted.

Furilfuramide (AF2) was used as a positive control.

The results of Rec-Assay are shown in Table 3. The results of the reverse mutation test are shown in Table 4.

In the Rec-Assay, this substance did not show mutagenicity even at high concentrations, but the sodium P-aminobenzoate derivative was particularly excellent. In addition, in the reverse mutation test, no change was observed in the mutation incidence rate due to this substance compared to the non-additive control even when a high concentration was applied, proving that it is a highly safe drug. 4) Delayed intradermal reaction ICR-JC to understand the effect of this substance on cell-mediated immunity
Knee reaction using sheep red blood cells as an antigen using L mice (
FOOtpadreactiOn) was performed.

1070 volumes of sheep red blood cells were suspended in physiological saline, and 0.2 TI11 of this solution was injected through the tail vein for primary sensitization. After 7 days, 0.05 ml of a suspension of 4070 volumes of sheep red blood cells was added to the foot. Secondary sensitization was performed by injecting the mice into the skin, and the foot thickness was measured the next day. This substance is 250W mainly on the day of primary sensitization! 9/Kg was administered intraperitoneally 5 times daily. As a result, no significant difference was observed in the increase in foot thickness in the group administered with this substance compared to the control (non-administered) group.

5) Antibody production ability In order to understand the effect of this substance on humoral immunity, CR-JC
For L mice, a 1070 volume suspension of sheep red blood cells was administered at 0.
2 ml was injected into the tail vein for sensitization, and on the 7th day after sensitization, blood was collected and antibody production ability was measured by red blood cell agglutination reaction.

The substance was intraperitoneally administered at 250 mg/Kg five times on consecutive days, mainly on the day of sensitization. Result is. No significant difference was observed in the agglutination titer between the group administered with this substance and the control group.

Next, we will discuss the pharmacological properties of this substance.

1) Carrageenin edema suppression effect VanArmanet. al. (1963), 1000 samples/K9 were orally administered by force to 6-week-old female Doryu rats (purchased from Tokyo Experimental Animals Co., Ltd.), each group consisting of 10 rats. 170 Carr in right hind foot 1 hour after administration
0.1 ml of ageee[]In saline suspension was injected, the paw volume was measured over time, and the inhibition rate was determined using the following formula.

(1-T/C)XlOO=1. R. (70) T: Administration group average foot kneeling volume C: Control group I The results are shown in Table 5.

All of the compounds tested were found to have an edema-suppressing effect, but sodium p-aminobenzoate-N-D-xyloside and sodium p-aminobenzoate-N-L-arabinoside had an inhibitory rate (1. R.70) and 50 each
．． 6% and 38.3%, indicating an excellent effect. 2) Granuloma suppressive effect Winteret. al. (1963),
Six-week-old female rats (Tokyo Experimental Animals), 6 weeks old per group.
(Purchased from Co., Ltd.) under the dorsal skin, with the midline symmetrical, 30
Two ±1 mg COttOnwOOl pellets were implanted and the sample was orally administered at 1000 W/Kg for 7 consecutive days. 8
On the second day, the granulation was removed, the dry weight was measured, and the inhibition rate was determined in the same manner as in 1) above.

The results are shown in Table 5.

Granulation weights were smaller in all compound administration groups than in the control group, and the inhibitory effect of the six substances was observed, but sodium p-aminobenzoate-N-D-mannoside. The effects of p-aminobenzoic acid sodium-N-L-rhamnoside and p-aminobenzoic acid-N-D-glucoside were relatively excellent. Similarly, cotton pellet granulomas were obtained for p-Rham, p-Xyl, and p-Man, and 18
．． 5, 11.9, 27.0 were obtained.

3) Anti-exudation effect Bariset. al. (1965) et al.
Six-week-old female rats (Tokyo Experimental Animals), 6 weeks old per group.
A pouch was made to inject air into the subcutaneous region of the back of a human (purchased from Co., Ltd.), and 1% CrOtOnOll (in sesame oil) was placed in the pouch.
Inject 5ml. Sample 10mg/K9 or 1000mg
/Kg was orally administered for 5 consecutive days, and on the 6th day, the amount of exudate in the pouch was measured and the inhibition rate was determined in the same manner as in 1) above.

The results are shown in Table 5.

All the compounds tested had an anti-exudation effect, especially sodium p-aminobenzoate-N-D-xyloside and sodium p-aminobenzoate-N-L-arabinoside at oral administration of 1000~/Kg. are 39 each
．． It is noteworthy that it shows a suppression rate of 770, 25.270. 1) Adjuvant arthritis suppressive effect According to the method of Fujiwara et al.
eriumtuberculOsis). 14
Select rats with similar hindlimb volume to the rice field and prepare 10 rats per group. From the 15th day, sample 10mf/K9 or 10001V/
K9 was orally administered for 7 days continuously, and the hindlimb volume was measured.
), the suppression rate was determined in the same manner as in

The results are shown in Table 5.

All the compounds tested exhibited inhibitory effects, especially sodium p-aminobenzoate-N-D-xyloside, which had an inhibition rate (1.R.) of 41,370, sodium p-aminobenzoate-N-D-xyloside. NL-rhamnoside 35.9%, p-
Aminobenzoic acid-N-L-arabinoside is 35.2? It showed remarkable medicinal efficacy. Next, we will discuss the formulation of this substance.

When used as an anti-inflammatory agent, this substance can be used in any convenient form to obtain its medicinal effect depending on the type and symptoms of the disease, and can be used alone or in a mixture with a pharmaceutically acceptable diluent and other drugs. Can be used as

The substance is applied orally or parenterally.

Therefore, it may take any form for oral or parenteral administration. The substances can be provided in dosage unit form.

It contains an effective amount of the active ingredient and is in the form of a powder. 6 tablets of granules, 6 sugar-coated tablets, 6 capsules, 6 suppositories, and 6 suspensions. It can take the form of a liquid, emulsion, ampoule, injection, etc. The diluent may be a solid 6 liquid, a semi-solid 6 or an ingestible capsule, such as the following: i.e. excipients, fillers. Binding agent. Wetting agent, disintegrating agent, surface active agent, lubricant, dispersing agent, buffering agent, fragrance 6 preservative, solubilizing agent. Such as solvents. Furthermore, one type or a mixture of one or more types of these may be used. The anti-inflammatory agent of the present invention can be produced by any known method.

The active ingredients in the compositions used in the present invention generally range from 0.01% to 100% by weight. %included. The anti-inflammatory agent of the present invention can be administered orally or parenterally to humans and animals, but oral administration is preferred.

It includes oral administration and sublingual administration. Parenteral administration includes injections such as subcutaneous, intramuscular, and intravenous infusions. The dosage of the anti-inflammatory agent of the present invention depends on whether it is an animal or a human being, and is influenced by age, individual differences, medical conditions, etc. For subjects, the oral dosage of this substance is 1k9.
The parenteral dosage is 0.1 to 1000 W1f per day, preferably 1 to 500 W1f per day, and 0.01 to 200 W1f, preferably 0.1 to 100 W1f per day, administered in 1 to 4 divided doses.

Hereinafter, the present invention will be explained in more detail by showing formulation examples and manufacturing examples of the substances of the present invention. Formulation Example 1 is uniformly mixed to form a powder or fine granules.

Further, this powder was put into a capsule container to form a capsule. Formulation example 2
After uniformly mixing and blending VV, the mixture is crushed, granulated, dried, and sieved to form granules.

Formulation Example 3 Sodium O-aminobenzoate in Example 2
Sodium O-aminobenzoate instead of xyloside
Granules are prepared in the same manner using N-D-glucoside, 4 parts of calcium stearate are added to 96 parts of the granules, and the mixture is compressed to form tablets with a diameter of 10 mm.

Formulation example 4 Granules are prepared in the same manner as in Example 2 using

10 parts of crystalline cellulose is added to 90 parts of the obtained granules and compressed to form tablets with a diameter of 8 mm, and white gelatin and precipitated calcium carbonate are added to form sugar-coated tablets.
Formulation Example 5 is heated and mixed and then sterilized to prepare an injection.

Production Example 1 Production method of P-aminobenzoic acid-N-L-arabinoside monosodium salt: p-aminobenzoic acid 4.69, V-arabinose 51. Ammonium chloride 0.59 40m 19470
Heat condensation in ethyl alcohol under reflux.

If you leave the reaction solution in the refrigerator, you will see the precipitation of crystals. The reaction solution was passed through the mouth, the crystals were washed with ether, and re-crystallized several times from 650% methyl alcohol to obtain colorless crystals. The yield was 45.870.

It was obtained in this way. P-Aminobenzoic acid-N-L
- Gradually dissolve arabinoside in a 170 aqueous solution containing a calculated amount of NaOH, filter out insoluble matter, and concentrate the 6-mouth solution under reduced pressure.
Add a large excess of acetone and dehydrate. Drying gave colorless crystals.

Yield 10070. The total yield was 45.870.

Production example 20-Aminobenzoic acid-NL-arapinoside monosodium salt production method: 30 m of anthranilic acid 2,39, L-arabinose 2,59, and ammonium chloride 0.29
1. Heat condensation in methyl alcohol under reflux.

After the reaction, if left at room temperature, crystals will precipitate.

The crystals obtained by passing the reaction solution through the mouth were washed with water, 6 methyl alcohol, and 6 ether to obtain colorless needle-shaped or disc-shaped crystals. The yield was 61.270.

The anthranilic acid-N-L-arabinoside thus obtained was gradually dissolved in a 1% aqueous solution containing the calculated amount of NaOH, and the insoluble matter was filtered out. The oral fluid was concentrated under reduced pressure, a large excess of acetone was added, dehydrated, and then dried to obtain colorless crystals.

Yield 100%. The overall yield was 61.3%.

Production example 3Production method of P-aminobenzoic acid-N-D-xyloside monosodium salt: P-aminobenzoic acid 2.39, D-xylose 2.5! ! ．． Ammonium chloride 0.059 2
Heat condensation in 5 ml of ethyl alcohol under reflux.

Although crystals precipitate during the reaction, add more solvent and continue heating to complete the reaction.

After leaving it in a cold place, the reaction solution was sipped, and the crystals were dissolved in water and
Wash with dilute methyl alcohol and a small amount of ether. 9
Recrystallization from 4% ethyl alcohol gave colorless needle-like crystals. The yield was 73.7%.

6P-aminobenzoic acid monoN-D thus obtained
- Xyloside was gradually dissolved in a 170 aqueous solution containing the calculated amount of NaOH, the insoluble matter was filtered out, the oral solution was concentrated under reduced pressure, and 6 large excess of acetone was added. After dehydration, colorless crystals were obtained by drying. .

Yield 10070. The T0ta1 yield was 73.770.

Production example 40-aminobenzoic acid-N-D-xyloside N
Production method of a salt: anthranilic acid 2.39, D-xylose 2.59. 0.29 ammonium chloride is heated and condensed in 35 m2 of ethyl alcohol under reflux.

After the reaction, the mixture was concentrated to about 1/2 under reduced pressure, and when left at room temperature, crystals were observed to precipitate.

After passing the reaction solution through the mouth, the crystals were mixed with 6 parts of water and 6 parts of methyl alcohol.
If washed with ether and recrystallized from ethyl alcohol,
Colorless needle crystals were obtained. The yield was 74.6%.

Anthranilic acid-N-D- obtained in this way
Xyloside was gradually dissolved in a 1% aqueous solution containing the calculated amount of NaOH, the insoluble matter was filtered out, the solution was concentrated under reduced pressure, a large excess of acetone was added, and the solution was dehydrated and dried to obtain colorless crystals. .

The yield was 10,070, and the T0ta1 yield was 74.670.

Production example 5P-aminobenzoic acid-N-D-glucoside-
Production method of Na salt: 50ml of P-aminobenzoic acid 59, D-glucose 6.49, ammonium chloride 0.59
470 ethyl alcohol under reflux for 6 hours.

After the reaction, the mixture was concentrated to about 1/3 under reduced pressure and left in a cool place, whereupon the entire liquid became gelatinous.

Add a small amount of water, warm again to dissolve, and then leave it in the refrigerator to see crystals precipitate. Pass the reaction solution and remove the crystals.
Wash with water, dilute ethyl alcohol and a small amount of ether,
Recrystallization from 5070 methyl alcohol gave colorless needle-like crystals.

The yield was 33.770.

Thus obtained, P-aminobenzoic acid monoN-D
- Glucoside was gradually dissolved in a 170 aqueous solution containing a calculated amount of NaOH, insoluble matter was filtered through the mouth, the oral fluid was concentrated under reduced pressure, a large excess of acetone was added, and the solution was dehydrated and dried to obtain colorless crystals.

Yield 100%. The TOtal yield was 33.7%.

Production example 60-aminobenzoic acid-N-D-glucoside-
Method for producing Na salt: 4.61 g of anthranilic acid, 6.0 g of D-glucose. Ammonium chloride 0.59 40m19
570 ethyl alcohol under reflux.

After the reaction, concentrate to about 1/3 under reduced pressure and leave in the refrigerator overnight to observe crystal precipitation.

The reaction solution was passed through the mouth, the crystals were washed with water, methyl alcohol, and ether, and recrystallized twice from methyl alcohol to obtain colorless needle crystals.

The yield was 4.670.

The anthranilic acid-N-D-glucoside thus obtained was gradually dissolved in a 170 aqueous solution containing the calculated amount of NaOH, the insoluble material was filtered through the mouth, the oral fluid was concentrated under reduced pressure, and a large excess of acetone was added. After dehydration and drying, colorless crystals were obtained.

The yield was 10,070, and the T0ta1 yield was 4.670.

Production Example 7 Process for producing P-aminobenzoic acid-N-D-galactoside-Na salt: P-aminobenzoic acid 1.5f! ,I
) - galactose 29v ammonium chloride 0.19 3
Heat condensation in 0 mj 94% ethyl alcohol under reflux.

After the reaction, concentrate under reduced pressure for 6 minutes and leave in a cool place to observe the precipitation of crystals. The reaction solution was passed through the mouth, six crystals were washed with water, dilute methyl alcohol, and a small amount of ether, and recrystallized from methyl alcohol to obtain colorless needle-like crystals.

The yield was 18.170. Obtained in this way,
P-aminobenzoic acid-N-D-galactoside was gradually dissolved in a 170 aqueous solution containing a calculated amount of NaOH, the insoluble material was filtered through the mouth, the oral fluid was stirred under reduced pressure, a large excess of acetone was added, and after dehydration, Drying gave colorless crystals.

The yield was 100701T0ta1, 18.1%.

Production example 80-Aminobenzoic acid-ND-galactoside-Na salt production method: anthranilic acid 2,49, D-galactose 3,09. 30m of ammonium chloride 0.29
Heat condensation in 19570 ethyl alcohol under reflux.

After the reaction, the mixture was concentrated to about 1/2 under reduced pressure and left at room temperature for 6 minutes, and crystals were observed to precipitate.

After the reaction, pass through the mouth and wash the crystals with water, methyl alcohol, and ether. Recrystallization from 9570 ethyl alcohol gave colorless needle-like crystals.

The yield was 16.4%.

The thus obtained anthranilic acid-N-D-galactoside was gradually dissolved in a 1% aqueous solution containing a calculated amount of NaOH, the insoluble material was filtered off, the oral liquid was concentrated under reduced pressure, and a large excess of acetone was added. was added, dehydrated and dried to obtain colorless crystals.

Yield 100%, TOta! The yield was 16.470.

Production Example 9 Process for producing P-aminobenzoic acid-N-L-rhamnoside monosodium salt: P-aminobenzoic acid 39, L-rhamnose 41. 0.1 g of ammonium chloride is heated and condensed in 94% ethyl alcohol under reflux cooling.

After the reaction, if left at room temperature, crystals will precipitate.

The reaction solution is passed through the mouth, the crystals are washed with water and diluted methyl alcohol, and then recrystallized from 50% methyl alcohol to obtain colorless needle-shaped crystals.

The yield was 30.9%.

It was obtained in this way. P-Aminobenzoic acid-N-L
- Rhamnoside was gradually dissolved in a 170 aqueous solution containing a calculated amount of NaOH, the insoluble matter was filtered out, and the oral liquid was concentrated under reduced pressure,
A large excess of acetone was added and the mixture was dehydrated and dried to obtain colorless crystals.

The yield was 10σ%, and the TOtal yield was 30.9%.

Production Example 3 Production Methods of 100-Aminobenzoic Acid-N-L-Rhamnoside Mono-Na Salt: Anthranilic Acid 2,39, L-Rhamnose 2.89. 25d of ammonium chloride 0.29
Heat condensation in methyl alcohol under reflux.

After the reaction, if left at room temperature, crystals will precipitate.

The reaction solution is passed through the mouth, the crystals are washed with water and methyl alcohol, and then recrystallized from 50% methyl alcohol to obtain colorless needle-shaped crystals. The yield was 9.8%.

The thus obtained anthranilic acid-N-L-rhamnoside was gradually dissolved in a 1% aqueous solution containing a calculated amount of NaOH, the insoluble matter was filtered off, and the oral liquid was concentrated under reduced pressure to obtain a 6-large excess. Acetone was added, dehydrated, and then dried to obtain colorless crystals.

The yield was 100%, and the Talal yield was 9.8%. Production Example 11 Method for producing P-aminobenzoic acid-N-D-mannoside mono-Na salt: P-aminobenzoic acid 2f! , D-mannose 31
and 0.29 ammonium chloride to 1 methyl alcohol
The condensation reaction is carried out by heating for about 1 hour under reflux in 0 ml of water.

After the reaction, the product is left at room temperature to precipitate crystals. The crystals were then separated, washed with water, dilute ethyl alcohol, and a small amount of ether, and then recrystallized using 5070 methyl alcohol. P-Aminobenzoic acid-N-
Colorless needle crystals of D-mannoside were obtained. Yield 56.1
It was 70. The hydrate of P-aminobenzoic acid monoN-D-mannoside obtained as described above was mixed with a total amount of NaO
The mixture is gradually added to a 170 aqueous solution containing H, dissolved, concentrated under reduced pressure, and an excess of ethyl alcohol is added to form a precipitate.

When this precipitate is collected, dehydrated, and dried, colorless crystals are obtained. These crystals were further recrystallized using an aqueous solution consisting of 5 parts of water, 6 parts of acetone, and colorless crystals of sodium P-aminobenzoate mono-N-D-mannoside were obtained. Yield: 95%, TOtal yield 53.3%. Production example 12m-aminobenzoic acid-N-D-mannoside-N
Production method of a salt; m-aminobenzoic acid 29, P-mannose 396 ammonium chloride 0.2f! ．． was heated and condensed in 10 ml of ethyl alcohol under reflux in a water bath at 95-96°C.

After a while of heating the reaction product, a thick crystal mass is precipitated. The crystals obtained by passing the reaction solution through the mouth were thoroughly washed with water and methyl alcohol, and then recrystallized from methyl alcohol to obtain colorless needle-like crystals.

The yield was 33.070.

6m-Aminobenzoic acid-N-P thus obtained
- Gradually dissolve the mannoside in a 170 aqueous solution containing the calculated amount of NaOH, and if there is any insoluble matter, sift through the mouth, concentrate the oral fluid under reduced pressure, add a large excess of ethanol, dehydrate for 6 minutes, and then dry to obtain colorless crystals. Ta.

The yield was 100%, and the TOtal yield was 33%.

[Brief explanation of drawings]

Figures 1 to 24 of the attached drawings are shown in Table 1/F6.
The infrared absorption spectra of each of compounds 1 to 24 are shown below.

Claims (1)

[Claims] 1 General formula ▲ Numerical formula, chemical formula, table, etc. ▼ [In the formula, R_1 represents arabinose, xylose, glucose, galactose, rhamnose, or mannose residue. ] An anti-inflammatory agent containing at least one aminobenzoic acid derivative or a pharmaceutically acceptable salt thereof as an active ingredient. 2. Aminobenzoic acid derivatives have a general formula ▲ mathematical formula, chemical formula, table, etc. ▼ [In the formula, R represents arabinose, xylose, glucose, galactose, rhamnose, or mannose residue. ] The anti-inflammatory agent according to claim 1. 3. The anti-inflammatory agent according to claim 1 or 2, which is in oral administration form. 4. The anti-inflammatory agent according to claim 1 or 2, which is in parenteral administration form.