JPH1017478A - Preventing or therapeutic agent for ulcerative colitis - Google Patents

Abstract

PROBLEM TO BE SOLVED: To prepare a medicine, excellent in therapeutic effects and hardly causing adverse effects by including a trehalose utilized as a preserving liquid for organs, an additive to pharmaceutical preparations, a cosmetic, etc., as an active ingredient. SOLUTION: This preventing or therapeutic agent for ulcerative colitis comprises a trehalose as an active ingredient. The trehalose is nonreducing disaccharides widely distributing in natural products such as yeasts, molds, marine animals or seaweeds and can be obtained by a method for thermal extraction from the natural products with ethanol or fermentation with microorganisms. The trehalose concentration can be selected within the range of 0.5-100wt./vol.% when administering the agent as a solid pharmaceutical preparation and 0.5-20wt.% when administering the agent as a transfusion pharmaceutical preparation. Furthermore, the agent can be used for preventing recrudescence or relapse in the remitting period of the ulcerative colitis. The agent is capable of manifesting excellent effects by suppressing the formation of erosion in colitic mucous membranes.

Description

DETAILED DESCRIPTION OF THE INVENTION

[0001]

The present invention relates to an excellent preventive or therapeutic agent for ulcerative colitis having trehalose as an active ingredient and having few side effects.

[0002]

2. Description of the Related Art Ulcerative colitis is a nonspecific inflammatory bowel disease that forms erosions or ulcers in the mucosal layer or submucosal layer of the colonic mucosa, and its clinical symptoms include diarrhea, bloody stool, abdominal pain and weight loss. Characteristic findings are listed. In Japan, the disease has been relatively rare in the past, but the number of patients has been increasing year by year due to the westernization of eating habits in recent years. Various causes, such as the theory of intestinal bacterial infection, the theory of food allergy, the theory of vascular disorders, the theory of autonomic nervous disorders, and the theory of immune abnormalities, are thought to be the causes, but details are still unknown and fundamental treatment has been established. It has not been done yet. At present, as drug therapy, steroid hormones, salazosulfapyridine, immunosuppressants and the like are administered alone or in combination. However, not only the therapeutic effect is insufficient, but also the occurrence of side effects is not so small, and there is a demand for a drug having a better preventive or therapeutic effect. On the other hand, trehalose is widely used in organ preservation solutions, formulation additives, cosmetics, and the like, but is not known to have any preventive or therapeutic effect on ulcerative colitis.

[0003]

SUMMARY OF THE INVENTION An object of the present invention is to provide an agent for preventing or treating ulcerative colitis which has few side effects and is excellent in therapeutic effect.

[0004]

Means for Solving the Problems The present inventors have conducted intensive studies in order to solve such problems, and as a result, have found that trehalose is extremely effective in preventing or treating ulcerative colitis. Was completed.

That is, the present invention relates to a prophylactic or therapeutic agent for ulcerative colitis comprising trehalose as an active ingredient.

Further, the agent for preventing or treating ulcerative colitis of the present invention can also be used for preventing relapse and relapse during remission.

Trehalose used in the present invention is a non-reducing disaccharide widely distributed in natural products such as yeasts, molds, marine animals and seaweeds. A fermentation method is known. In terms of chemical structure, D-glucose is formed by bonding reducing groups, and from the bonding mode, three kinds of isomers of α, α-trehalose, α, β-trehalose or β, β-trehalose are formed. Although present, any can be used in the present invention. Of these, it is preferable to use naturally occurring α, α-trehalose.

The above-mentioned agent for preventing and treating ulcerative colitis comprising trehalose as an active ingredient of the present invention may be administered alone as a preparation containing the same alone, but in combination with a pharmaceutically acceptable pharmaceutical adjuvant. It can be used in combination with an oral pharmaceutical composition or a high-calorie infusion or used as a parenteral composition by adding to an infusion preparation.

As the dosage form of the pharmaceutical composition, various forms can be selected according to the purpose of treatment, and typical examples thereof include tablets, pills, granules, capsules, powders, syrups and the like. Parenteral preparations such as oral preparations, suppositories, liquid preparations, suspensions, and emulsions are included. Such a preparation can be produced by a known method by adding a pharmacologically or pharmaceutically acceptable additive as necessary. In the manufacture of oral preparations, for example, commonly used excipients such as lactose, sucrose, starch, crystalline cellulose, corn starch, etc., disintegrants such as carboxymethylcellulose, agar, gelatin powder, binding of polyvinyl alcohol, methylcellulose, hydroxypropylcellulose, etc. Agents, lubricants such as silica, magnesium stearate and talc, and coating agents such as hydroxypropylmethylcellulose and sucrose may be used.
In the production of oral solutions such as solutions, suspensions, and syrups, and injections, they are not dissolved or suspended in distilled water for injection, physiological saline, and the like. Adjusters, isotonic agents, stabilizers, diluents and the like may be added as necessary. Furthermore, various amino acids, sugars, electrolytes and the like may be added to the agent for preventing and treating ulcerative colitis of the present invention.

The medicament for preventing or treating ulcerative colitis according to the present invention may optionally contain other medicinal ingredients in addition to trehalose.

The trehalose concentration can be appropriately selected within the range of 0.5 to 100 w / w% when administered as a solid preparation, and 0.5 to 20 w / v% when administered as an infusion preparation.

The dose of the preventive and therapeutic agent for ulcerative colitis of the present invention varies depending on the method of administration, the age, body weight, symptoms, etc. of the patient, but usually 10 to 1000 mg per day for oral administration to adults. / Kg, preferably 50-300
The dose can be appropriately adjusted and administered in the range of mg / kg.

[0013]

Next, the present invention will be described in detail with reference to examples, but the present invention is not limited to these examples.

Example 1 Seven-week-old SD male rats were used to randomly extract five normal rats, and the remaining animals were examined for colitis to determine the difference in average body weight between the groups. The animals were grouped into groups of 7 to 10 animals so that they did not occur. Thereafter, a 3% aqueous solution of dextran sulfate sodium (hereinafter abbreviated as DDS) was placed in a water-absorbing bottle and rats were allowed to freely drink water every day. In the normal group, purified water was similarly allowed to freely drink instead of the DDS aqueous solution. Trehalose 150mg / kg 3% DDS
Oral administration twice daily for 10 days from the start of drinking water. Similarly, a 0.5% aqueous solution of carboxymethylcellulose was orally administered to the normal group and the control group. The animals were dissected the day after the final administration of the test substance, and the length of the large intestine (colon and small intestine) and the erosion area of the large intestine mucosa were measured, and hematological examination (white blood cells, red blood cells, hemoglobin concentration, hematocrit value) was performed. In addition, the erosion area of the large intestine mucosa was determined by a method established by our company (Jpn Pharmacology, 102, 343-350 (199).
3)).

[0015]

[Table 1]

Table 1 shows the results of measuring the length of the large intestine and the erosion area of the large intestine mucosa. Erosion of the colonic mucosa was significantly suppressed by oral administration of trehalose. further,
The length of the large intestine, which was significantly shortened with the onset of colitis, which is an indicator of colon wall thickening, was also clearly improved.

[0017]

[Table 2]

Table 2 shows the results of hematological examination. Trehalose significantly improved the increase in white blood cell count, an indicator of colitis onset. In addition, anemia is a characteristic symptom of ulcerative colitis, and a significant improvement was also shown with respect to a decrease in hemoglobin concentration and hematocrit level, which are indicators thereof.

The preparation examples are shown below. [Formulation Example 1] Tablet A tablet having the following composition is produced by a conventional method. Composition in 1 tablet (200mg) Trehalose 100mg Corn starch 45mg Lactose 50mg Hydroxypropylcellulose 4mg Magnesium stearate 1mg

Formulation Example 2 Capsules Capsules having the following composition are produced by a conventional method. 1 capsule (1 tablet 200mg) Trehalose 100mg Lactose 25mg Corn starch 65mg Hydroxypropylcellulose 10mg

[Formulation Example 3] Injection An injection having the following composition is produced by a conventional method. 1 ampoule (1 bottle 20ml) Trehalose 8g Sodium chloride 0.2g Distilled water qs

[0022]

EFFECT OF THE INVENTION The agent for preventing or treating ulcerative colitis of the present invention exerts an excellent effect because it suppresses the formation of erosions in the colonic mucosa.

Continued on the front page (72) Inventor Mikiko Kataoka Shiga Prefecture Koga Gunko Nishimachi Oaza 59-27-513 (72) Inventor Takeda Dennai 1-1-17-14 Nakasho, Otsu City, Shiga Prefecture 822

Claims (1)

[Claims] An agent for preventing or treating ulcerative colitis comprising trehalose as an active ingredient.