JPS63216824A - anti-peptic ulcer agent - 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 provides an anti-peptic ulcer agent, more specifically a novel anti-peptic fjk containing an active ingredient extracted from a plant belonging to the Iridaceae family.
Regarding S agent.

[Conventional technology and its problems]

Many natural products, especially plants, are known to exhibit various medicinal effects, and some of these plants have been used as folk medicines since ancient times. For example, among plants of the genus Iris of the Iridaceae family, Ir1s florent
tna L, ), purple squirrel (I.

germanica L, ), Shigoriiiris (1,
The rhizome of Pallida LAMARK) is called iris root, and is often used in powder form as a flavoring agent for spraying, toothpaste, washing powder, etc. Ichihaha again (1, tecto
rumMAXIM) is a rhizome called Enpicon.
It is used as an emetic, laxative, and for throat cancer.

On the other hand, although many substances having anti-peptic ulcer effects have been discovered from natural products, they have not always been satisfactory from the viewpoint of effectiveness, safety and usefulness as pharmaceuticals.

[Means for solving problems]

The present inventors have conducted extensive research to extract anti-peptic ulcer agents from plants, and have found that there is a component in the alcoholic extract of plants of the genus Iris, family Iridaceae, that has an excellent anti-peptic 15N ulcer effect. Heading, the invention was completed.

That is, the present invention contains as an active ingredient an alcohol-soluble fraction having the following properties, which is obtained by partitioning and extracting an ether-insoluble fraction of an alcohol-extracted fraction of a rhizome of a plant belonging to the genus Iris in the Iridaceae family with alcohol/water. The present invention provides an anti-peptic ulcer agent characterized by:

■Solubility Easily soluble in methanol and n-butanol, almost insoluble in ethyl ether, chloroform, benzene, and ethyl acetate.

■Total nitrogen amount 5.0 weight t% or less.

Examples of plants of the genus Iris of the Iridaceae family containing the active ingredient of the present invention include iris iris, iris iris, iris iris, and iris iris, but iris iris is particularly preferred.

In order to extract the active ingredient of the present invention from these plants of the genus Iris of the family Iridaceae, the rhizomes of the plants of the genus Iris of the family Iridaceae are first subjected to dialcohol extraction, then an ether-insoluble fraction is obtained from the obtained alcoholic extract, and this is extracted with alcohol. This is carried out by performing partition extraction with /water and separating the alcohol-soluble fraction.

Alcohol extraction is carried out, for example, by cutting and drying the rhizome of a plant of the genus Iris in the Iridaceae family, adding alcohol to it, stirring or leaving it to stand, and then treating it with P. Examples of the alcohol used include methanol, ethanol, and isopronoQ alcohol, with methanol being preferred. The extraction operation is preferably carried out at 10 to 80°C with stirring for 1 to 6 hours. The obtained alcoholic extract is preferably converted into an alcoholic extract by concentrating it under reduced pressure.

The ether-insoluble fraction can be obtained, for example, by suspending the alcohol extract in water, adding ether thereto, and removing the ether layer. The ether used is
Ethyl ether is preferred.

The extraction operation is carried out by adding 1 to 10, preferably 2 to 3 parts by volume of ether to the aqueous suspension and removing the ether layer.

The alcohol-sensitive fraction, which is the active ingredient of the present invention, can be extracted from the ether-insoluble fraction by, for example, adding alcohol to the aqueous layer and partitioning and extracting the alcohol layer. The alcohol is preferably a water-soluble alcohol, such as n-butanol. The extraction operation is carried out by adding 1 to 10, preferably 2 to 3 volumes of butanol to the volume of water and separating the butanol.

By concentrating the obtained butanol layer, the active ingredient of the anti-peptic ulcer agent of the present invention can be obtained.

The thus obtained active ingredient of the present invention has the following physicochemical properties.

■Solubility Easily soluble in methanol and n-butanol, almost insoluble in ethyl ether, chloroform, benzene, and ethyl acetate.

■Total nitrogen content 5.0% by weight or less ■Color reaction Anthrone sulfuric acid reaction, Liberman reaction, diazo reaction,
7-engineering reaction, concentrated sulfuric acid reaction, sodium hydroxide reaction,
Positive for aluminum chloride reaction.

■Infrared absorption spectrum (KBr tablet method) Figure 1 ■Ultraviolet absorption spectrum (methanol solution) Figure 2 Next, the pharmacological action and toxicity of the active ingredient of the present invention will be shown.

<Pharmacological action> The active ingredient of the present invention is combined with Tween 80.
) was suspended in a 10% 0% sodium carboxymethylcellulose MC-Na) aqueous solution containing 0.1% of the sample solution. The vehicle alone was used as a control. The animals used were Crj: CD (SD) rats (body weight 1l50
-19(') was used as 1 #10 animals.

After draining the contents of the removed stomach, 2% formalin solution 1
0- was injected, both ends of the esophagus and duodenum were ligated with arterial Flemen, and fixed in 2-thiformin solution. After fixation, the helmet was incised along the large bone, and the presence or absence of ulcer formation was observed and the ulcer index (total of ulcer length M) was measured under a stereoscopic microscope (XIO).

Statistical treatment Ulcer incidence (%) is expressed as a percentage of the number of animals with ulcers relative to the number of animals used in one group, and is expressed as the ulcer index (UlcerInde).
x, U, 1. (abbreviated as ) is shown as the average value of the total ulcer length of each individual. The inhibition rate (%) was calculated using the following formula.

A 5student's t-test method was used to test the significance of the ulcer coefficient between the test group and the control group, and the significance level was set at a critical level of less than 5 (P<0.05).

(1) Orally administer indomethacin ulcer sample solution or vehicle from 1041// to 10
Minutes later, indomethacin (30η/floor) @ turbid solution 5 d/
Kg was injected subcutaneously in the back. After indomethacin treatment 7
After being fasted for an hour and kept under water, the animal was killed in layers by cervical dislocation and the helmet was removed. The extracted helmet was treated as described above, and the ti# armpit was observed and its strength was determined. The results are shown in Figure 1.

Table 1 ◆ Diaper: P < 0.05 (2) Aspirin ulcer specimen solution or vehicle was administered orally at 10 me/K99, and 30 minutes later, aspirin (300■/Kf) suspension 10 was administered.
s//~ was administered orally. After administering aspirin, the animal was left without food for 5 hours and kept under water, and the vertebrae were killed by dislocation and the helmet was removed. The excised stomachs were treated as described above, and the ulcers were observed and their strength determined.

The results are shown in Table 2.

Table 2! Nina: P(0,05 (3) Stress I*9 Orally administered to bird sample fluid or vehicle t-10s+j/,
After 30 minutes, the rat was placed in a fixation device and kept in a water bath (23±
After immersing the helmet in water (1°C), the helmet was removed in layers by vertebral dislocation. The removed scalpel was treated as described above, and the ulcer was observed and its strength determined. The results are shown in Table 3.

Below is Table 3 in the margin: p < o, o s ku toxicity> The acute toxicity test for oral administration of the active ingredient of the present invention was carried out by d.
When conducted using dY male mice, zooooη/
There were no cases of death during oral administration of Kg.

In addition to the active ingredient, the anti-peptic ulcer agent containing the active ingredient of the present invention having the above-mentioned effects may contain ingredients used in ordinary pharmaceutical preparations, such as binders, lubricants, and excipients. ,
Disintegrants, wetting agents, additives, emulsifiers, preservatives, etc. can be added. As for the dosage form, dosage forms for oral administration such as powders, regular granules, tablets, capsules, and liquids are preferred. Binders include syrup, gum arabic, gelatin, Solpit, tragacanth, polyvinylpyrrolidone, etc., and astringents include magnesium stearate, talc,
Examples of excipients include lactose, sugar, corn starch, calcium phosphate, sorbitol, glycine, etc. Disintegrants include potato starch, carboquine methyl cellulose calcium, etc. Wetting agents include Examples of additives include sodium lauryl, methyl cellulose, gelatin, hydroxyethyl cellulose, carboxymethyl cellulose, stearic aluminum glue, hydrogenated edible fat, etc., and emulsifiers include lecithin and monooleic acid. Examples of the preservative include sorbitan and gum arabic, and examples of the preservative include propyl p-hydroxybenzoate and sorbic acid.

The administration sensitivity of the anti-peptic ulcer agent of the present invention is determined by the patient's age, weight,
Although it varies depending on the severity of the disease, in the case of oral administration, it is usually preferable for adults to use the active ingredient at a dose of 1 to L000 .mu./Kf per day, and this is preferably administered in divided doses of about 3 times a day.

〔Effect of the invention〕

The anti-peptic ulcer agent of the present invention has an excellent peptic ulcer treatment effect, is highly safe, and is useful as a medicine.

〔Example〕

EXAMPLES Next, the present invention will be described in detail with reference to Examples, but the present invention is not limited thereto.

Example 1 Production of the active ingredient of the present invention: Irisite, a plant of the genus Iris, family Iridaceae
ctorum MAxiM) Cut and dry the rhizome, part 1
Add methanol 40001111 to 000t and heat to 80℃
After heating and stirring for 3 hours, the mixture is filtered while still warm to obtain a first extract.

Add 4,000 ml of methanol to the residue and repeat the above operation to obtain a second extract. The first and second extracts were combined and concentrated to dryness under reduced pressure at 50° C. or lower to obtain a methanol extract of 280 f'fr.

After adding 560 ml of water to methanol extract 2802 to make a suspension, partition extraction was performed with 1000 tRt of ethyl ether to remove ethyl ether. Furthermore, 1000 mg of ethyl ether was added to the remaining aqueous layer, and the above operation was repeated 2 times.
The ethyl ether layer was removed several times. 500 ad of n-butanol was added to the remaining aqueous layer, and partition extraction was performed to obtain n-
Obtain the butanol layer. Furthermore, 500 m of n-butanol was added to the remaining aqueous layer, and the above operation was repeated twice to obtain the n-butanol.
- The butanol layers were combined and concentrated to dryness under reduced pressure at 50°C or lower to obtain n-butanol fraction C) 123
I got t. The obtained active ingredient of the present invention had the above-mentioned physicochemical properties.

Example 2 Capsules: The active ingredient of the present invention (Example 1) is 350 cm, and lactose is 501 cm.
Capsule contents of 1F, 46 mg of crystalline cellulose, 10 wqs of &IJ vinylpyrrolidone, 2 qs of talc, and 2 ml of magnesium stearate were prepared and filled into gelatin capsules.

Example 3 Tablet: 350 μ of the active ingredient of the present invention (Example 1) and 50 w of lactose
Ig, corn starch 37■, gum arabic 1O■,
Talc IWli and magnesium stearate 2'Ni were added, and 450 square tablets per 91 tablets were obtained in a conventional manner.

Example 4 Sugar-coated tablet: 250 ml of the active ingredient of the present invention (Example 1) and milk a! t
55 w9%) Corn starch 37.5 ~, gum arabic & 6■, magnesium stearate 2.5■, Merck 24η, titanium oxide 0.4 Cape, calcium carbonate 44
Using F% gelatin 6T #9, sucrose 12211Ig and a dye, tablets were compressed and coated according to a conventional method to obtain sugar-coated tablets with a weight of 550 η per tablet.

Example 5 Oral solution: 250v of the active ingredient of the present invention (Example 1) and 50cm of sodium carboxymethylcellulose, ? 60 x 250 ml of hydrogenated castor oil and 52 kg of refined sucrose were added, and purified water was added to give a total volume of 100 ml.

[Brief explanation of the drawing]

FIG. 1 shows the infrared absorption spectrum of the active ingredient of the anti-peptic ulcer agent of the present invention, and FIG. 2 shows the ultraviolet absorption spectrum thereof. Applicant: Zeria Pharmaceutical Co., Ltd. (=-'-' -1

Claims (1)

[Scope of Claims] 1. An alcohol-soluble fraction having the following properties obtained by partitioning and extracting an ether-insoluble fraction of an alcohol-extracted fraction of a rhizome of a plant belonging to the Iridaceae family and the genus Iris with alcohol/water as an active ingredient. An anti-peptic ulcer agent characterized by comprising: (1) Solubility Easily soluble in methanol and n-butanol, almost insoluble in ethyl ether, chloroform, benzene, and ethyl acetate. (2) Total nitrogen content 5.0% by weight or less.