JPH0381219A - Remedy for gastric mucosal disorder - Google Patents

Abstract

PURPOSE:To obtain the subject remedy, containing taurine as an active ingredient and capable of not only administering in a large amount but also exhibiting remarkable effects on inhibition of gastric mucosal disorder caused by ischemia, ammonia, etc., with hardly any side effects. CONSTITUTION:A remedy containing taurine (2-aminoethanesulfonic acid) which has been used as a cardiac function improver for congestive cardiac insufficiency or a hepatic function improver in hyperbilirubinemia (except obstructive jaundice) as an active ingredient. The effective does of the taurine is within the dose range of 5-1500mg per patient and normally in several divided portions and in the total daily dose within the range of 20-2000mg per day.

Description

DETAILED DESCRIPTION OF THE INVENTION The present invention relates to a therapeutic agent for gastric mucosal disorders containing taurine as an active ingredient.

In recent years, it has been shown that when the intestinal tract becomes ischemic, the production of superoxide anion (0) and hydrogen peroxide (202) and the activity of myeloperoxidase (MPO) increase, which can have a cytotoxic effect. It has been reported. For example, 0'', Granger et al.
l 5cand 198B, 5upp1.548:4
7-63> ischemia reperfusion (1 schei
It has been reported that xanthine oxidase is activated under (ia-reperfusion), and the increased oxygen impairs the mucosal microcirculatory system.

On the other hand, N^DP derived from neutrophils is another source of O;
The pathway from H oxidase is emphasized. 05 is transformed into 202 by dismutation or superoxide dismutase (SOD) catalysis, but then H2
In the presence of neutrophil myeloperoxidase (MPO), O2 causes the oxidation of (L) and hypochlorous acid (MPO).
(C, S, Foote et al., Nature 301.715 (1983)
). The lamina propria of the gastrointestinal tract, including the stomach, contains many phagocytes including neutrophils, and the presence of the MPO has been reported. OCf is highly reactive and contains chloramine (NH), which reacts with ammonia and exhibits strong cytotoxicity in living organisms.
2O〉 and exhibits tissue-damaging properties.

In recent years, Campylobacter pylori
It is presumed that there is a causal relationship between chronic active gastritis, gastric ulcer, and duodenal ulcer, and Campylobacter pylori has been proven to be the cause of gastritis (J, R , Naren and B, J, v-
Sial, Lancet i, 1273 (1983
)).

The presence of ammonia at 0 to 50 mH is recognized in the human stomach. This ammonia is produced from urea in the body by urease derived from infected Campylobacter pylori, which means that ammonia is high in the stomach where Campylobacter pylori is present.
This has been proven by the fact that when urea is administered to the stomach where pylori is present, it rapidly changes to ammonia (B, J., Marcial et al., Lancet I, 965 (1986
)).

Thus, the relationship with ammonia is considered important as one of the pathophysiology of gastric mucosal disorders caused by Campylobacter pylori, and therefore, drugs that suppress ammonia disorders are clinically considered therapeutic agents for gastric mucosal disorders. It is considered to be useful as a.

The present invention was completed by discovering that taurine has a strong inhibitory effect on gastric mucosal disorders caused by stress such as ammonia and ischemia, and provides treatment for gastric mucosal disorders using taurine as an active ingredient. The aim is to provide a drug.

Taurine is a sulfur-containing amino acid (2-aminoethanesulfone M) said to have been discovered in the bile of calves, and is present in the bodies of various animals, including humans, and is produced in vivo by decarboxylation of cystic acid.

In particular, it is said to be most abundant in the myocardium, and in bile it is present in the form of taurocholic acid condensed with various cholic acids. Taurine's D5o value is approximately 7000■/
It is a substance that is more than suitable for use (orally administered to mice) and has extremely low toxicity.

Taurine has conventionally been used as an agent for improving cardiac function in oral heart failure and as an agent for improving liver function in hyperbilirubinemia (excluding obstructive yellow scarring), but taurine has been used as an agent for improving cardiac function in cases of oral heart failure and as an agent for improving liver function in hyperbilirubinemia (excluding obstructive yellow scarring). Nothing was known about its effects.

The present invention provides a therapeutic agent for gastric mucosal disorders containing taurine as an active ingredient.

In the present invention, "gastric mucosal disorder" refers to gastritis and gastric ulcer, and more specifically, gastritis includes active chronic gastritis with strong neutrophil infiltration infected with Campylobacter pylori, chronic stress gastritis, and acute gastritis. show. Furthermore, the therapeutic agent for gastric mucosal disorders of the present invention can also be used as a prophylactic agent against the above-mentioned gastric mucosal disorders.

The effective amount of taurine, which is the active ingredient of the therapeutic agent for gastric mucosal disorders of the present invention, is 1 to 5000 μl, preferably 5 to 1500 μl.
This is the range of Rg.

The active ingredient can be used, for example, in the form of tablets, capsules, elixirs, microcapsules or suspensions.

The taurine used as the active ingredient of the present invention is generally administered in doses ranging from 5 to 150,011 g per patient in several doses for patients who require treatment or prevention of gastric mucosal disorders.
It can be administered orally at a total daily dose of 20-2000011 g per day. The dosage of taurine can vary depending on the severity of the disease, the weight of the patient, and other factors recognized by those skilled in the art.

Taurine, a pharmaceutically acceptable salt of taurine, or a mixture of 5 to 1,500 Rg thereof used as an active ingredient in the therapeutic agent for gastric mucosal disorders of the present invention may be present in a pharmaceutically acceptable vehicle, carrier, excipient, or binder. , preservatives, stabilizers, flavoring agents, etc., in unit dosage form as required by generally accepted pharmaceutical practice.

The amount of active substance in these compositions or preparations is determined to provide a suitable dosage within the indicated range.

Specific auxiliary agents that can be mixed into tablets, capsules, etc. are shown below. Binders such as tragacanth, gum arabic, corn starch or gelatin; Excipients such as microcellulose; Leavening agents such as corn starch, pre-gelatinized starch, alginic acid etc.; Lubricants such as magnesium stearate: Sweetening agents such as sugar, lactose or saccharin; Flavoring agents such as peppermint, red pepper oil or cherry. When the dosage unit form is a capsule, materials of the above type can further include a liquid carrier such as an oil or fat. Various other materials can also be present as coatings or to otherwise modify the physical form of the dosage unit. For example, tablets may be coated with shellac, sugar or both. A syrup or elixir may contain the active compound, sucrose as a sweetening agent, methyl and propylparabens as preservatives, a dye and flavoring, such as cherry or orange flavor.

Since the therapeutic agent for gastric mucosal disorders of the present invention contains taurine as an active ingredient, it not only has almost no side effects and can be administered in large quantities, but also has remarkable effects on suppressing gastric mucosal disorders caused by ischemia, ammonia, etc. have.

The present invention will be explained in more detail with reference to the following examples.

Example 2 A 4-hour dose of SD male rats (250 g) was used under urethane anesthesia.
roentero+ooy 64.1130-1135
(1973)) in VitrO chambers (C'halbeir) were prepared. That is, after making a midline incision in the rat's abdomen, the stomach was pulled out, the vascular nerves were preserved, the stomach was injected from the anterior dorsal region to the body of the stomach, and the stomach was fixed in an acrylic chamber.

The gastric mucosa in the chamber was filled with 2 m of physiological saline, and the gastric mucosal potential difference (potential diNerence)
) and gastric mucosal blood flow were continuously measured. The gastric mucosal potential difference was measured using an agar bridge, with the interested electrode placed in the chamber and the indifferent electrode subcutaneously, and continuous measurement was made with a millivoltmeter. Gastric mucosal blood flow was measured using a laser blood flow meter (Periflux) by placing a probe perpendicular to the mucosal surface from above the chamber with a stereotaxic device (Narisige). The average value of the obtained results is 5student's-t test
A comparative study was conducted.

After the gastric mucosal potential difference and gastric mucosal blood flow were stabilized, the following experiment was conducted based on a general test method for the drug effect of a therapeutic agent for gastric mucosal disorders.

(B) In the ammonia-ischemia model, blood was removed from the Talat femoral vein to reduce gastric mucosal blood flow;
0 mH ammonia (in physiological saline) was administered into the chamber, and the gastric mucosal potential difference and gastric mucosal blood flow were measured up to 1 hour after administration.1 hour after ammonia administration, gastric mucosa that had turned red was observed using a stereoscopic microscope. The area of the part was measured and defined as an ulcer coefficient (unit interval 2).

On the other hand, add 30 iM taurine 2d to the chamber.
Similar blood removal and ammonia administration were performed for the group that had been administered minutes before, and the effects were observed.

As a result, when 30a+H ammonia was administered into the chamber of a rat that had undergone blood removal treatment, the gastric mucosal potential difference immediately decreased markedly, and after 1 hour, the value of the potential difference changed to the value before ammonia administration (100 %), and clear macroscopic gastric mucosal lesions were observed. At this time, the ulcer index was 12.6±9.21 m1+2.

In contrast, in the taurine pretreatment group, when blood was removed and 30mM ammonia was administered, the rate of decrease in potential difference after 1 hour was 108% of the value (100%) before ammonia administration.
%, and the ulcer index decreased to 2.5±3.0 layer 2, and macroscopic lesions were almost completely suppressed. That is, the above results indicate that gastric mucosal damage caused by ischemia plus low concentration ammonia is completely inhibited by taurine pretreatment.

In addition, another group was treated with blood removal and two
00jly/dl urea 1d and urease activity 200
IU/- of Campylobacter pylori 1d was administered, and subsequent changes in the gastric mucosa were examined.

As a result, in the group in which Campylobacter pylori was administered into the chamber, the ulcer index after 1 hour was 32 ± 9.
It became jI112. Meanwhile, 250 mM taurine 2d
In the group pre-administered 30 minutes before, the ulcer index after 1 hour was 5±3a#+2, indicating a significant suppressive effect on macroscopic gastric mucosal damage.

Claims (1)

[Claims] (1) A therapeutic agent for gastric mucosal disorders containing taurine as an active ingredient.