JP3280726B2 - Anti-ulcer agent - Google Patents

Description

DETAILED DESCRIPTION OF THE INVENTION

[0001]

The present invention relates to a novel anti-ulcer agent. More specifically, the present invention relates to an anti-ulcer agent containing dehydroepiandrosterone sulfate or a pharmaceutically acceptable salt thereof as an active ingredient.

[0002]

2. Description of the Related Art Dehydroepiandrosterone sulfate (hereinafter abbreviated as DHAS) or a pharmacologically acceptable salt thereof improves dysfunction of the cervix at the end of pregnancy and furthermore, susceptibility of uterine muscle to oxytocin. The sodium salt is widely used as a cervical ripening agent to improve the preparatory state of pregnancy by improving the pregnancy (see Japanese Patent Publication No. 55-27884). Also, DHAS
For treatment of dementia (see JP-A-62-99328), treatment and prevention of hyperlipidemia (see JP-A-64-40428), treatment of osteoporosis (see JP-A-3-209328), etc. The application of is known. However, there is no report that DHAS or a pharmacologically acceptable salt thereof has an anti-ulcer effect.

[0003]

An object of the present invention is to provide a novel anti-ulcer agent.

[0004]

Means for Solving the Problems The present inventors have found that DHAS or a pharmacologically acceptable salt thereof exhibits excellent antiulcer activity, and completed the present invention.

[0005] Examples of the pharmacologically acceptable salts of DHAS used in the present invention include salts of alkali metals such as sodium and potassium, and salts of organic amines such as arginine and ethanolamine.

DHA as an active ingredient of the antiulcer agent of the present invention
S or a pharmacologically acceptable salt thereof exhibits excellent antiulcer activity as described below.

The anti-ulcer agent of the present invention is usually administered orally or parenterally to humans.

[0008] Dosage forms for oral administration include tablets, granules, fine granules, powders and the like.
It is produced by a conventional method by appropriately adding ordinary pharmaceutical additives such as lactose, corn starch, crystalline cellulose, magnesium stearate, hydroxypropylcellulose and talc to S or a pharmacologically acceptable salt thereof.

Injections for parenteral administration include lyophilized preparations dissolved at the time of use, for example, DHAS or a pharmacologically acceptable salt thereof as a stabilizer, such as glycine, alanine, leucine, arginine, histidine. Neutral or basic amino acids, macrogol 1,500, macrogol 4,000, macrogol such as macrogol 6000 and / or dextran with an average molecular weight of 30,000 to 100,000 etc. are appropriately added, dissolved in purified water and frozen by a conventional method. Obtained by drying.

The dose of the antiulcer agent of the present invention varies depending on the condition, administration route, age, body weight, etc. of the patient.
It is usually in the range of 5 to 100 mg / kg as DHAS per day, and it is administered once or in two or three times.

[0011]

EFFECT OF THE INVENTION DHAS which is an active ingredient of the drug of the present invention
Or a pharmacologically acceptable salt thereof exhibits excellent anti-ulcer activity as shown in the following Test Examples (Test Example 1 described later)
4). Further, the toxicity is low (see Test Example 5 described later).

Accordingly, the medicament of the present invention is useful for treating and preventing peptic ulcers such as gastric ulcer and duodenal ulcer.

Hereinafter, the effects of the present invention will be described in more detail with reference to test examples.

Test Example 1 Anti-ethanol ulcer test (oral administration) (1) Sodium salt of test compound DHAS (2) Test method SD rats male rats (weight: 190 to 240 g, 6 to 12 rats per group) after fasting for 24 hours The test compound administration group was orally administered the test compound dissolved in distilled water, and the control group was administered only the distilled water alone. Two hours after oral administration, 99.5% ethanol was orally administered (dose volume: 5 ml / kg). One hour after the administration of ethanol, the rat was sacrificed, the stomach was removed, and 10 ml of a 1% formalin solution was injected into the stomach and fixed. The stomach was incised along the greater curvature, the major diameter (mm) of the ulcer generated in the glandular stomach was measured, and the total per animal was defined as the ulcer index. The inhibition rate was calculated from the average value of the ulcer index of the test compound administration group and the average value of the ulcer index of the control group. (3) Test results Table 1 shows the test results.

[0015]

[Table 1]

Test Example 2 Anti-indomethacin ulcer test (subcutaneous administration) (1) Test compound Same as Test Example 1. (2) Test method 24 male SD rats (body weight: 200-250 g, 10 rats per group)
After a period of fasting, a test compound dissolved in distilled water was administered subcutaneously to the test compound administration group, and only distilled water was administered subcutaneously to the control group (dose volume: 2 ml / rat). Two hours after subcutaneous administration, indomethacin (dose 30 mg / rat) was orally administered. Four hours after the administration of indomethacin, the rats were sacrificed and the stomach was removed. Thereafter, the excised stomach was treated with formalin in the same manner as in Test Example 1, and the ulcer index and the inhibition rate were calculated. (3) Test results Table 2 shows the test results.

[0017]

[Table 2]

Test Example 3 Anti-ethanol ulcer test (subcutaneous administration) (1) Test compound Same as Test Example 1. (2) Test method 24 male SD rats (body weight: 200-250 g, 10 rats per group)
After a period of fasting, a test compound dissolved in distilled water was administered subcutaneously to the test compound administration group, and only distilled water was administered subcutaneously to the control group (dose volume: 2 ml / rat). Two hours after subcutaneous administration, 100% ethanol (dose volume: 1 ml / rat) was orally administered. One hour after the administration of ethanol, the rat was sacrificed and the stomach was removed. Thereafter, the excised stomach was treated with formalin in the same manner as in Test Example 1, and the ulcer index and the inhibition rate were calculated. (3) Test results Table 3 shows the test results.

[0019]

[Table 3]

Test Example 4 Anti-Water Immersion Restraint Stress Ulcer Test (Subcutaneous Administration) (1) Test Compound Same as Test Example 1. (2) Test method Male SD rats (body weight: 200 to 250 g, 10 rats per group) were subcutaneously administered with a test compound dissolved in distilled water once a day for 2 days to the test compound administration group (dose 100 mg / day). 2 ml / rat). Then, the rats were placed in a stress cage and immersed in a water tank 2 hours after the third administration after a 24-hour fast. Six hours later, the rats were sacrificed and the stomach was removed. Thereafter, the excised stomach was treated with formalin in the same manner as in Test Example 1, and the ulcer index and the inhibition rate were calculated. (3) Test results Table 4 shows the test results.

[0021]

[Table 4]

Test Example 5 Acute toxicity test (1) Test compound Same as Test Example 1. (2) Test method ICR mouse (body weight 23 to 25 g, female 19 to 21 g, 10 per group)
) Were orally or subcutaneously administered a test compound dissolved in distilled water. 7 days after the administration, observing the presence or absence of mouse deaths were calculated LD ₅₀ values by Weil from mortality (Weil) method. (3) Test results Table 5 shows the test results.

[0023]

[Table 5]

[0024]

The present invention will be specifically described below with reference to examples.

[0025] Example 1 (Tablet) [Formulation] Ingredient amount (g) 2 hydrate of the sodium salt of DHAS 500 Lactose 100 Corn starch 300 Crystalline cellulose 80 Hydroxypropylcellulose 10 Magnesium stearate 10 Actions of the Mix each component uniformly, and mix 1 tablet 25
Compress to make 0 mg tablet.

[0026] Example 2 (Injection) [Formulation] and dihydrate 40 Glycine 40 [Operation] glycine was added with purified water solubility of Ingredient weight (g) of sodium salt of DHAS, while warming DHAS After dissolving by adding sodium salt dihydrate, the total volume is adjusted to 2 l. Then, after sterile filtration, 5 ml each is filled into an injection container and freeze-dried to obtain an injection for dissolution at the time of use.

The Example 3 (Injection) [Formulation] was mixed with Macrogol to Ingredient weight (g) sodium salt 100 Macrogol 4000 200 [Operation] sodium salt of DHAS of DHAS, dissolved in purified water Then, the total amount is 2 l. Then, after aseptic filtration, filling 10 ml each in a container for injection,
Lyophilize to obtain an injection for dissolution before use.

Continuation of front page (58) Fields investigated (Int. Cl. ⁷ , DB name) A61K 31/565 C07J 1/00 CA (STN) REGISTRY (STN)

Claims (2)

(57) [Claims] 1. An anti-ulcer agent comprising dehydroepiandrosterone sulfate or a pharmaceutically acceptable salt thereof as an active ingredient. 2. An anti-ulcer agent comprising a sodium salt of dehydroepiandrosterone sulfate as an active ingredient.