JPH11217331A - Therapeutic agent for diabetes mellitus and hyperlipemia - Google Patents

Abstract

PROBLEM TO BE SOLVED: To obtain a therapeutic agent for diabetes mellitus and hyperlipemia having excellent blood glucose- and blood lipid-lowering action by making the agent include a specific urea derivative. SOLUTION: This therapeutic agent contains a compound represented by the formula (R1 is H, chlorine, bromine or methoxy; R2 is a lower alkyl, a cycloalkyl, phenyl, a halogen, methyl or a nitro-substituted phenyl) as an active ingredient. The amount effective in treating diabetes mellitus and/or hyperlipemia is usually 0.1-500 mg as a compound represented by the above formula and the compound is administered in dosages, usually one or more times, generally 1-4 times and is administered at daily total dosage of 0.1-2,000 mg, generally 1-1,000 mg based on adult having 70 kg weight.

Description

DETAILED DESCRIPTION OF THE INVENTION

[0001]

The present invention relates to a therapeutic agent for diabetes and a therapeutic agent for hyperlipidemia, which has a blood glucose and blood lipid lowering action.

[0002]

BACKGROUND OF THE INVENTION Diabetes is the most common of the serious metabolic diseases affecting humans and occurs as a relative or absolute lack of insulin action. Conventionally, various biguanide compounds or sulfonylurea compounds have been used as therapeutic agents for diabetes. However, biguanide compounds cause lactic acidosis, and sulfonylurea compounds have a potent hypoglycemic effect, but they often cause severe hypoglycemia, so that precautions for use are necessary.

[0003] JP-A-63-79864, JP-A-63-79864
JP-A-270655, JP-A-64-52749, and JP-A-2-85247 disclose chemical formula 2 (wherein R1 represents a hydrogen atom, a halogen atom, a methyl group or a methoxy group,
2 represents a lower alkyl group, a cyclohexyl group, a phenyl group or a substituted phenyl group, and X represents an oxygen atom or a sulfur atom. ) And thiourea derivatives represented by the formula (1) are reported, which have an anti-ulcer effect and a histamine release inhibitory effect.

[0004]

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[0005]

SUMMARY OF THE INVENTION An object of the present invention is to provide a therapeutic agent for diabetes and / or hyperlipidemia having an excellent blood glucose and blood lipid lowering action.

[0006]

Means for Solving the Problems The inventors of the present invention have conducted intensive studies to solve the above-mentioned problems. As a result, the present inventors have found that urea derivatives have excellent blood glucose and blood lipid lowering effects, and that urea derivatives improve insulin resistance. It was found to be effective, and the present invention was completed. That is, the present invention relates to a compound represented by the formula (3) wherein R 1 is substituted with a hydrogen atom, a chlorine atom, a bromine atom or a methoxy group, and R 2 is substituted with a lower alkyl group, a cyclohexyl group, a phenyl group or a halogen atom, a methyl group or a nitro group. A phenyl group) is provided as an active ingredient, a therapeutic agent for diabetes and / or a therapeutic agent for hyperlipidemia. The term "lower alkyl group" used in the present invention means a methyl group, an ethyl group, a propyl group, an isopropyl group, or a butyl group.

[0007]

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[0008] The effective amount to treat diabetes and / or hyperlipidemia depends on normal factors such as the nature of the problem, its severity and weight. However, the unit dose is
Usually, the compound represented by the formula is 0.1 to 500 mg. Typically, a unit dose is administered at least once a day, more usually 1 dose.
Administered 1 to 4 times a day for a total daily dose of e.g.
Dosage is to be in the range of 0.1 to 2000 mg, more usually 1 to 1000 mg per kg adult.

The compound represented by the above formula (3) is orally administered as it is or together with a conventional pharmaceutical carrier, but may be a composition administered by another route such as injection. Particularly suitable oral dosage forms are unit dosage forms such as tablets and capsules.

As the carrier, besides excipients, binders, disintegrants, surfactants, lubricants, fluidity promoters, flavoring agents, coloring agents, fragrances and the like can be used. Suitable carriers include, for example, lactose, dextrose, sucrose, sorbitol,
Examples include mannitol, starch, gum acacia, calcium phosphate, alginate, calcium silicate, microcrystalline cellulose, cellulose, polyvinylpyrrolidone, carboxymethylcellulose, magnesium stearate, sodium laurate and the like.

[0011]

The present invention will be described in detail with reference to the following examples. Production Example To 15 ml of acetonitrile, 0.03 mol of an α-aminomethylbenzenemethanol derivative was added, and 0.03 mol of isocyanates were gradually added dropwise with stirring. After completion of the dropwise addition, the mixture was stirred at room temperature for 1 hour. After completion of the reaction, the resultant was left overnight in a refrigerator, and the precipitated crystals were collected by filtration to obtain a urea derivative. (Recrystallized from EtOH-water)

Example 1 A compound represented by Chemical Formula 4 was mixed with powdered feed (CE-2, manufactured by CLEA Japan) at a ratio of 0.032% to obtain KK-Ay.
/ Ta mice (male, 8-10 weeks old, 1 group: 6-10 mice)
For 4 days. During this time, water was given ad libitum. Approximately 12 hours later, blood was collected and collected in plasma (3000 rpm,
Glucose and triglyceride values were measured by an enzyme method using an Iatrochrome GLU-LQ kit (manufactured by Yatron) and a Clintech TG-S kit (manufactured by Yatron), respectively. Table 1 and Table 2 show the results.
Shows the reduction rate (%) with respect to the group not administered with the drug. In addition,
In the above test, no toxicological adverse effects were observed. The physical condition of the test animals did not show any adverse reactions to the treatment.

[0013]

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[0014]

[Table 1]

[0015]

[Table 2]

Example 2 Formulation Example Microcrystalline cellulose 84.5 g Magnesium stearate 0.5 g Carboxymethylcellulose calcium 5 g Active ingredient 10 g According to the above-mentioned formulation, and a part of them was mixed uniformly, compression-molded, and then crushed. The remaining amounts of and were added and mixed, followed by compression molding with a tableting machine to obtain a tablet of 200 mg per tablet (containing 20 mg of the active ingredient).

[0017]

As described in detail above, according to the therapeutic agent of the present invention, diabetes or hyperlipidemia can be effectively treated,
It has an excellent effect that it can be prevented.

Claims (1)

[Claims] (1) wherein R1 is substituted with a hydrogen atom, a chlorine atom, a bromine atom or a methoxy group, and R2 is substituted with a lower alkyl group, a cyclohexyl group, a phenyl group or a halogen atom, a methyl group or a nitro group; A therapeutic agent for diabetes and / or a therapeutic agent for hyperlipidemia, comprising a compound represented by the formula: Embedded image