JPS5965018A - Treating and preventing agent for peptic ulcer - Google Patents

Abstract

PURPOSE:A treating and preventing agent for peptic ulcer, obtained by distributing and fractionating an extract of a cinnamon with hot water with ethyl ether, and recovering a water-soluble fraction to give a water-soluble constituent, and using the resultant water-soluble constituent derived from the cinnamon as an active constituent. CONSTITUTION:A treating and preventing agent for peptic ulcer obtained by distributing and fractionating an extract of a cinnamon with hot water with ethyl ether, recovering the resultant water-soluble fraction, and using the resultant water-soluble constituent derived from the cinnamon [hereinafter abbreviated to component (A)] as an active constituent. The extraction with the hot water is preferably carried out at 100 deg.C for about 2hr, and the extract is preferably concentrated to 0.2% in a warm bath before the distribution and fractionation with the ethyl ether. The component (A) has powerful increasing action on the blood stream in the stomach membrane and promoting action on the repair of the stomach membrane, particularly the inhibitory action on the secretion of the gastric acid, and further effective against the stress ulcer and serotonin ulcer. The component (A) is administrable in any form of an injection or oral agent.

Description

DETAILED DESCRIPTION OF THE INVENTION [Kibatsu 9] relates to a preventive agent for the treatment of gastrointestinal ulcers, which contains a water-soluble component of cinnamon white rice (hereinafter referred to as component A) as an active ingredient. Cinnamon bark is a Chinese herbal medicine derived from a plant in the Lauraceae family, and has traditionally been treated as something similar to mulberry. However, the present inventors have been screening the pharmacological effects of component A contained in cinnamon, and have found that it has a strong gastric acid secretion suppressing effect, gastric mucosal blood flow increasing effect, gastric acid secretion suppressing effect, and gastric mucosal repair effect. In terms of its promoting effect and suppressing effect on gastric acid secretion, it is comparable to cimetidine, which is currently considered to be a powerful anti-ulcer agent.
It also prevents stress ulcers and serotonin ulcers.
They discovered that it has a therapeutic effect and completed the present invention.

Component A can be obtained by adding ethyl ether to a hot water extract of cinnamon, performing distribution fractionation, and collecting the aqueous fraction.

The temperature of the hot water extract is preferably about 100°C, and the extraction time is preferably about the same from 1 to 4 o'clock, especially about 2 hours. Before the extract was subjected to partition fractionation with ethyl ether,
It is preferable to concentrate in a warm bath to about 0.1 to 0.4%, especially about 0.2%. The extract thus obtained (
The extract is subjected to circulation distribution fractionation using concentrated &[ti minityl ether, and in this case, it is preferable to use an equal amount of ethyl ethyl to the extract.

A specific example of the method for obtaining the above component A is as follows: 3° wide open cinnamon (111) is crushed, extracted with 100°C hot water lO2 for 1 hour, and further extracted with KlfiJ amount of hot water. After extraction for 1 hour, both solutions were combined and turned dark green to 21 fC using a rotary evaporator in a 40°C bath. This concentrate has an isoelectric (21
) was added to ethyl ether and fractionated (
After 8 transfers, remove the ethyl ether fraction (essential oil, cinnamic aldehyde, etc.) and collect the water-soluble fraction.

Component A is obtained by reducing this water-soluble fraction to about 200° C. in a hot bath at 40'C and then freeze-drying it. This product is stable when stored under refrigeration at 2 to 8°C, and is used after being dissolved in physiological saline solution before use.

This component can be subjected to other desired known treatments such as filtration, heat treatment, etc. that can be used as a pharmaceutical product.

Next, I would like to show you the results of the experiments I conducted to confirm the effects, acute toxicity tests, administration methods, etc. of the ingredients.

The effect of ingredient A was investigated by causing (1) pylorus ligation ulcer, (2) serotonin ulcer, and (3) cold stress ulcer in Chugakuri Effect Fruit 111JJ.〇(1) Pylorus ligation ulcer Shay The method of Gastroente et al.
ro-1ogy, 5.43. (1945))/(
A pylorus ligation ulcer was created according to the procedure. In other words, male Wistar rats (body weight 160-18(1)) were fasted for 24 hours and the pylorus was ligated under ether anesthesia. After being left in a fasted and water-fast state for 18 hours, the rat was excised under ether anesthesia. The total sum of the long axis of the hemorrhagic erodion and ulcers that occurred in Maekuto was evaluated as an ulcer index.

The specimens (component A, physiological saline in the amounts shown in Table 1, and raw J!I! saline as a control) were intraperitoneally administered 8 hours after the ligation.

(2) Serotonin A tumor Wistar male rats 160-1 fasted for 48 hours
8 (U Omf/T!, g noserotonin, creatinine, and sulfate are administered subcutaneously on the back of the patient, and the abdomen is opened and examined after 24 hours. In addition, the sample (A to 100mfz)
Physiological saline containing components and physiological saline as a control) were administered intraperitoneally before the start of the test (>8 o'rr before seroton administration).

(3) Cold stress ulcer (SL) fasted for 24 hours) 160-180F
was confined in a wire mesh trap and restrained at 4° ±l 'C.
After being left in a cold room for 5 hours, the abdomen was opened and assayed. The ulcer index was expressed as the sum of the major axes of hemorrhagic erodions. In addition, the specimen (100my/Kg (raw mu salt water containing DA component and physiological saline as a control) Fio test start (restraint start) 3
0 minutes ago, the trap was administered into the pus cavity.

All of the experimental results of (1), (2), and (3) above are shown in Table 11, Table 2, and Table 3, respectively.

Table 1 Table 2 (1 person, lower, b) Table 3 Based on the results shown in Table 1] It is clear that 10% of the 1A component
In the 0M+2/nori administration group, the incidence of antral ligation ulcer was suppressed by 94% compared to the control physiological saline administration group.

As is clear from the results shown in Table 2, A component 1oom
In the yAy administration group, the incidence of serotonin ulcers was suppressed by 98%.

As is clear from the results shown in Table 3, component A 100
The incidence of cold stomosis ulcers was suppressed by 100% in the m 97Kg administration group.

(1) Conditional action We conducted an investigation regarding the anti-ulcer action mechanism of component A.

(υ The inhibitory effect on gastric juice secretion was investigated. Administration was performed by intraperitoneal administration.

The prefluid secretion suppressing activity was determined by the method of Shayl et al.
astroenterology 26, 906
.

(1954)). That is, male Wistar rats (body weight 160-180) were fasted for 24 hours.
The fluid volume, total acidity, and total pepsin activity of the stored gastric fluid 18 hours after the pylorus was ligated in f) were measured. Take the total acidity or phenolphthalein as an indicator and set it to 115ON.
Determined by titration with NaOH, total pepsin activity tri
, Anson method using casein as the base nail (Brlt, J. Pharmacol, 1
B.

54, (1958)). Sample (A component 1
00 mr/y4 saline containing saline and physiological saline as a control) were administered intraperitoneally 3 hours after ligation.

The results are shown in Table 4. When 100 mWlKf of component A was intraperitoneally administered to the control group, the intraperitoneal fluid volume was suppressed by 46.3%. In addition, similar suppression was observed in total acidity and total pepsin activity, and the risk rate was 0.1% or less, which was statistically determined to be appropriate.

(1) Toxicity Component A exhibits acute toxicity in ddY male mice, exhibiting an LD5° of 4740 mWlKf when administered intraperitoneally, ensuring high safety.

Low Dosage and administration method A component level, 1 to 800 m/day from the results of the above test
W/ni? , a = good case L.

Component A can be administered in both injection and oral forms. Poetry used as an injection is administered intravenously or intramuscularly as distilled water for injection, for example, at the time of use. When used as an oral drug, it is administered as a capsule, tablet, powder, or oral liquid preparation.
The kari is prepared according to methods well known to those skilled in the art as described in the Japanese Pharmacopoeia.

The gastrointestinal ulcer treatment and prevention agent consisting of component A has extremely low toxicity and exhibits remarkable efficacy against mulberry leaves, making it extremely reliable as a drug for the treatment and prevention of ulcers.

Example 1 (oral preparation) (1) Ingredient A 100mf (2) Naikutada Fine Granules Boiled 209 (manufactured by Fuji Chemical) 46.6m? (3) Crystalline cellulose 24.0tl (4)
Carboxyl methyl cellulose
4. 0
m9(5) Magnesium stearate 0.
4m'y(1), (3) and O2(4) all in advance] 0 (17. Soche's sieve, 111n pieces. This <1), X3), (4) and (2) After drying each to reduce the moisture content to a certain level, mix the kumquats in a blender at the above weight ratio. 1. All wages equally. (5) was added to the mixed rice, mixed for a window time (30 seconds), and the mixed rice was tableted (punch:
6.31Jφ, 6.0 ax R), 1 tablet 80
It was made into my tablet.

This cutting may be coated with a commonly used gastric soluble film coating agent (eg, polyvinyl acecool diethylamino acetate) or an edible coloring agent, depending on the size of the grain.

Ten Example 2 (capsules) kl) AI Shobun 50g (
2) Milk m 9a5r (3) Magnesium stearate 152 Weigh each of the above ingredients, mix them uniformly to a total of 1000f, and fill 200n of the mixed powder into hard gelatin capsules.

Claims (1)

[Claims] (υ Treatment for gastrointestinal ulcers using a water-soluble component derived from cinnamon as an active ingredient, which can be obtained by adding ethyl ether to a hot water extract of cinnamon, partitioning it, and collecting the water-soluble fraction. Prophylactic agent. (2) The agent for treating and preventing gastrointestinal ulcers according to claim (1), which is in the form of a powder, tablet, or capsule for oral administration. (3) The agent is in the form of an intravenous, intramuscular or oral administration. The gastrointestinal ulcer according to claim (1), which is in liquid form for administration.
+8 comrades preventive agent.