JPH07223944A - Therapeutic agent for inflammatory intestinal disease - Google Patents

Abstract

PURPOSE:To obtain a therapeutic agent for inflammatory intestinal diseases, containing bucillamine or its salt as the active component and having an excellent inhibitory effect on mucosal disorder. CONSTITUTION:The compound represented by the formula or its salt is contained as the active component and subjected to preparation into a dosage form of tablet, granule, powder, capsule, injection, etc. This medicine is administrated in an amount of 10 to 1000mg/day in one to several times. The inflammatory intestinal diseases are intractable intestinal diseases caused by a cryptogenic damage to the mucosal membrane of the digestive tube and taking a chronic course. Typical examples of these diseases are ulcerative colitis and Crohn's disease and bucillamine of the formula has an excellent inhibitory effect on a mucosal disorder caused by carrageenin.

Description

Detailed Description of the Invention

[0001]

BACKGROUND OF THE INVENTION 1. Field of the Invention The present invention relates to a therapeutic agent for inflammatory bowel disease containing bucillamine or a salt thereof as an active ingredient.

[0002]

2. Description of the Related Art Inflammatory bowel disease is a refractory bowel disease that has a chronic course of unknown cause represented by ulcerative colitis and Crohn's disease.

Ulcerative colitis is a diffuse non-specific inflammatory disease of unknown cause that mainly affects the mucous membrane of the large intestine, especially the rectum, and often forms erosions and ulcers. On the other hand, Crohn's disease is a granulomatous inflammatory disease with fibrosis and ulcer which can occur in any part of the mucous membrane of the digestive tract.

[0004] Treatment of inflammatory bowel disease is carried out by medical therapy and surgical therapy, but the medical therapy is the main because of frequent recurrence after surgery. Medical treatment is roughly divided into nutrition therapy and drug therapy. Nutritional therapy is performed by parenteral nutrition or enteral nutrition, and is aimed at preventing recurrence by not stimulating the intestinal tract. In drug therapy, steroids, salazosulfapyridine, immunosuppressants, etc. are used, but all have strong side effects. Although much research has been conducted so far on the development of drugs suitable as therapeutic agents for inflammatory bowel disease, the development of new therapeutic agents for inflammatory bowel disease is still desired.

On the other hand, it has already been reported that bucillamine is useful as an anti-rheumatic drug, an antiseptic drug, a hepatopathy inhibitor, a cataract drug, a diabetes drug, an anti-osteoporosis drug, a renal disease drug, and a cystinuria drug. It is done (Japanese public Sho 60-
11888, JP 56-5388, JP 62-13922, JP 63-13964, JP 4-154721, JP 4-15
4722, JP-A-4-342524, and JP-A-5-186341), it is known that they are excellent drugs with high safety.

[0006]

It was a very interesting subject to find out a new pharmacological action of bucillamine which is useful as a medicine.

[0007]

[Means for Solving the Problems] In order to find out a new pharmacological action of bucillamine, the present inventor examined the action on mucosal disorders. As a result, they have found that bucillamine has an excellent inhibitory effect on mucosal disorders and is useful as a therapeutic agent for inflammatory bowel disease.

[0008]

DISCLOSURE OF THE INVENTION The present invention relates to a therapeutic agent for inflammatory bowel disease containing bucillamine represented by the following formula [I] or a salt thereof (hereinafter referred to as the present compound) as an active ingredient.

[0009]

[Chemical 2] The salt in the present compound is not particularly limited as long as it is a pharmaceutically acceptable salt, and examples thereof include sodium salt and potassium salt.

[0010] Inflammatory bowel disease is a refractory bowel disease in which the mucosa of the gastrointestinal tract, represented by ulcerative colitis and Crohn's disease, suffers from a disorder of unknown cause and which follows a chronic course. Steroids, salazosulfapyridine, immunosuppressants and the like are used in drug therapy for inflammatory bowel disease, but all have strong side effects.

Therefore, the present inventor examined the effect on carrageenin-induced mucosal damage in order to examine the usefulness of bucillamine for inflammatory bowel disease. As a result, detailed data will be described in the section of the effect of the invention, but it is recognized that bucillamine has an excellent inhibitory action against mucosal disorders and is useful as a therapeutic agent for inflammatory bowel disease. It was

The compound may be administered orally or parenterally, and the dosage form may be a commercially available tablet or JP-B-56-538.
Examples thereof include tablets, granules, powders, capsules, injections and the like described in JP-B No. 8 and JP-B-60-11888.

The dose of the present compound in the therapeutic agent of the present invention can be appropriately selected depending on the symptoms, age, dosage form and the like, but 10 to 1000 mg per day may be administered once or in several divided doses.

[0014]

EXAMPLES Next, the composition of the following formulation examples will be illustrated as examples.

(1) Oral drug

The tablet may be coated with a film which is usually used, and may be further coated with sugar.

[0017]

[0018]

[0019]

(2) Injectable solution An aqueous solution of the present compound (pH 6.5 to 7.0) containing 250 mg of the present compound in 5 ml of the aqueous solution.

[0021]

【The invention's effect】

[Pharmacological test] As one of animal models of ulcerative colitis,
It is known that an immunological operation using carrageenin produces an ulcerative lesion similar to human ulcerative colitis in the rabbit colon (Cancer Res., 46, 1374-1376 (198).
6)). Furthermore, as a histopathological evaluation method, it has been reported that a method in which mucosal disorder items are listed, each item is quantified by the degree of the disorder, and the total score is scored as a histopathological score value ( Journal of the Japanese Society of Gastroenterology, 90, 24-32 (1993)). Therefore, the action of bucillamine was examined according to the methods described in these documents.

(Experimental method) Male New Zealand white rabbits (body weight: about 2.2 kg) were sensitized with a 1% carrageenin-Freund's complete adjuvant mixture solution, and one week after the sensitization treatment, 0.3% carrageenin 400 ml / kg / day. 8
Continuous administration for a week caused mucosal damage in the large intestine. Bucillamine was 0 (control), 100 or 300 mg / kg / day, and 0.3% carrageenin was continuously administered for 8 weeks from 1 week after the sensitization treatment. After 9 weeks from the sensitization treatment, the rabbit was sacrificed, the large intestine was removed, and the histopathological search was performed.

Table 1 shows the items of the findings of mucosal disorders based on the evaluated inflammatory changes and the criteria for scoring.

[0024]

[Table 1] (Results) Table 2 shows the pathological tissue score value, which is the total score of the evaluation of each item of findings of mucosal disorders based on inflammatory changes.
The numerical values shown in Table 2 are average values of the pathological tissue score values for each rabbit used in each group. The n value in Table 2 is the number of rabbits that make up each rabbit group.

[0025]

[Table 2] As shown in Table 2, the bucillamine administration group had a significantly lower pathological specimen tissue score value than the control group, and mucosal damage was suppressed. The action was concentration-dependent.

From the above, bucillamine has an excellent inhibitory effect on carrageenin-induced mucosal damage,
It has been found to be useful as a therapeutic agent for inflammatory bowel disease.

Claims (1)

[Claims] 1. A therapeutic agent for inflammatory bowel disease, which comprises bucillamine represented by the following formula [I] or a salt thereof as an active ingredient. [Chemical 1]