JPS59186917A - Remedy for peptic ulcer - Google Patents

Abstract

PURPOSE:A remedy for peptic ulcer having both a reducing action on an attacking factor and an enhancing action on a protective factor, having low toxicity and side effect, containing a 2,3-dimethylquinoxaline-5,8-dione compound as an active ingredient. CONSTITUTION:A remedy for peptic ulcer containing a compound shown by the formula as an active ingredient. The compound shown by the formula removes defects of conventional remedy, has action to reduce attacking factor of acid, pepsin, etc., and to enhance protecting factors of the mucosa of the digestive tubes. It has no inhibitory action on secretion of gastric juice as an anticholinergic agent has. Namely the remedy promotes rebirth of tissue, without side effect on central nervous system, etc., has low toxicity, and usable continuously for a long period. A dose is 25-400mg per adult three times a day. The compound shown by the formula is obtained by reacting 2,3-dimethylamino-1,4- naphthoquinone with diacetyl in an organic solvent under heating.

Description

DETAILED DESCRIPTION OF THE INVENTION The present invention relates to a therapeutic agent for peptic ulcer, and more specifically to a therapeutic agent for peptic ulcer.
The present invention relates to a peptic ulcer therapeutic agent containing a -dimethylquinoxaline-5,8-dione compound as an active ingredient.

Peptic ulcers occur due to various causes, but generally include hyperacidity, stress, and obstruction of gastric blood circulation.

It is thought to occur due to an imbalance between aggressive factors such as acids, pepsin, and gastric juice brought about by drugs and other causes, and protective factors such as the protective power of the gastrointestinal mucosa. Conventionally, the aggressive factor is clinically isolated. As antacid, anticholinergic,
Mucosal tissue repair,
Drugs that have the effects of activating mucosal tissue, increasing mucus, and forming granulation are used, but there are almost no single drugs that can dispatch attacking factors and enhance protective factors. Moreover, many drugs that direct attack factors have side effects; for example, anticholinergic drugs have a parasympathetic nerve blocking effect, which excessively suppresses gastric juice secretion, slowing down gastric activity and reducing digestive power. Also, since antacids temporarily neutralize gastric acid, they may reverse gastric acid secretion.

The purpose of the present invention is to eliminate the shortcomings of these conventional peptic ulcer treatment agents, to have the effect of dispatching attacking factors and enhancing protective factors, have little toxicity and side effects, and have digestive properties that can withstand long-term use. The purpose of the present invention is to provide a therapeutic agent for ulcers.

The present invention provides 2,3-dimethylquinoxaline-5,8-
This is a peptic ulcer therapeutic agent containing a dione compound (hereinafter referred to as NCU-62) as an active ingredient.

NOU-62 is 2,6-dimethylamino-1,4-
It can be obtained as yellow needle-like crystals by heating and reacting naphthoquinone and diacetyl in an organic solvent. This compound has a remarkable therapeutic effect on peptic ulcers, and has extremely low side effects such as acute toxicity. Test examples to clarify these effects are shown below.

6- Test Example 1 Regarding NCiU-62, H5hay, S, A, e
tal,.

Gastroenterology, Volume 54, No. 4
A pyloric ligation ulcer test was performed according to the method described on page 6 (1945).

Specifically, male Wistar rats with a body weight of 180 to 2,002 kg were fasted for 48 hours, and the abdomen was opened under total ether anesthesia. The region just below the gastric pylorus was ligated and closed, and the test drug was administered into the duodenum or intraperitoneally. After 18 hours, the test drug was administered into the duodenum or intraperitoneally. The abdomen was opened again, the ulcer area was measured, and the ulcer inhibition rate was determined. The results are shown in Table 1.

4-1 Table 5- Test Example 2 Regarding NOU-62, K, Takagi et a
l,, JapanJ, Pharmacnl,, 1st
A stress ulcer test was conducted according to the method described in Vol. 8, p. 9 (1968).

Specifically, the test drug was administered to male Wistar rats weighing 160 to 1802 kg, which had been fasted for 24 hours, placed in a wire mesh cage for stress loading, immersed up to the substernum in a thermostatic bath at 23°C, and 6 hours later, the abdomen was opened and the main stomach was removed. The area of erosion that occurred in the area was measured, and the suppression rate of erosion was determined. The results are shown in Table 2.

Table 2-6 = Test Example 3 A male Wistar rat weighing 180-200 that had been fasted for 48 hours was subjected to laparotomy under anesthesia with ether, the region just below the pylorus of the stomach was ligated and sutured, and the test drug was injected into the duodenum, and 4 hours later. The abdomen was opened again, and the amount of gastric juice secretion (m/10100rB) and the acidity of gastric juice (
m Eq HVt) and total acid secretion (μBq H/
100 f BW) was investigated. The results are shown in Table 6.

Table 6 Note) Chi ml/100 f BW Chi+: mEqH+/1 11, μEqH+/100 f BW Test Example 4 A side effect test was conducted on NCU-62 using various test animals. The results are shown in Table 4.

Table 4 Test Example 5 NCU-62 was subjected to an acute toxicity test using various test animals according to the Lynchfield and Wilcoxon methods, and the LD5o value was measured.

The results are shown in Table 5.

As is clear from the test examples in Table 5 and above, NCU-62 significantly promotes tissue regeneration, but does not significantly inhibit gastric juice secretion. In addition, almost no other side effects, including those on the central nervous system, are observed, and acute toxicity is extremely low.

Therefore, the therapeutic agent of the present invention, which contains NCU-62 as one of its active ingredients, has the effect of dispatching attacking factors and enhancing protective factors, and is an excellent drug that can withstand long-term use with little toxicity and side effects. It is a peptic ulcer treatment.

The therapeutic agent of the present invention contains adult 1
It can be administered orally 25 to 400 times a day, three times a day.

The therapeutic agent of the present invention can be used in the form of a solid preparation for oral administration such as a powder, a granule, a single tablet, or a capsule by a conventional method using any necessary pharmaceutical carriers or excipients.

In addition to excipients such as lactose, starch, and calcium carbonate, and binders such as CMO, gum arabic, and avicel, the therapeutic agent of the present invention may also contain a lubricant, two pigments, and a flavoring agent.

EXAMPLES Hereinafter, the present invention will be specifically explained with reference to Examples, using a manufacturing example of NCU-62 as a reference example.

Reference Example 2.6-Diamitsu 1,4-naphthoquinone 1.88 r
-10= and freshly distilled diacetyl 1291 to ethanol 1
00 ml, and the mixture was heated under reflux and stirred for 1 hour. After cooling, the precipitated crystals are harvested and recrystallized from ethanol to form NCU.
-62 was obtained as yellow needle crystals, 2.216ii' (yield 960%). m, p, 255-255℃ elemental analysis value (as Cl4HION202) CHN calculated value (%) 70,58 4.23 11.
76 Actual value (%) 7065 3.97 11
．． 90 Example 1 NOU-6252, Avicel 7f, RPC-L/Engineering PA
0, 5 f, and cornstarch JP7.59 were uniformly mixed, and 0.22 of each was filled into No. 2 capsules to obtain capsules.

Example 2 NCU-6259, lactose 8.5! i', starch 5
．． 6Sl, HPc-L/Engineering PA0.45', Magnesium Stearate O, IR, Polysorbate 80
0.5F and hydrogenated oil 021 are mixed uniformly, and this is mixed with 022
Each was filled into No. 2 capsules to obtain capsules.

Example 6 NCU-6210? , NPC-L/1. PA5f and lactose 872 were uniformly kneaded and passed through a 60 Mesosie sieve.

Example 4 NOU-6210fi', lactose 502. mannitol 3
5 f, RPC! -L/IPA 4 F and 801 g of polynorbate were uniformly kneaded, passed through a 60 mesh sieve, and dried to obtain granules, which were divided into 12 portions.

Example 5 NCU-625F, lactose 61. Denzo 74f.

HPC-L/IPA O, 4f/, Polysorbate) 80 0.22, Magnesium Stearate 022.
Hydrogenated oil 0.21 mm was mixed uniformly and this was compressed into tablets of 0.162 mm to obtain tablets with 8 different diameters.

Example 6 NCU-621Of, lactose 90? were mixed uniformly to obtain a powder, which was divided into 1.22 portions.

Patent applicant: Taisho Pharmaceutical Co., Ltd. Agent Patent Attorney Tomizo Kitagawa 13-

Claims (1)

[Claims] 2,3-dimethylquinoxaline-5,8-
A peptic ulcer treatment containing a dione compound as an active ingredient.