JP2898930B2 - Gastrointestinal symptom improver - Google Patents

Description

DETAILED DESCRIPTION OF THE INVENTION

[0001]

BACKGROUND OF THE INVENTION 1. Field of the Invention The present invention relates to an agent for improving digestive symptoms.

[0002]

2. Description of the Related Art Of the pathological conditions that have been diagnosed as chronic gastritis, those that have chronic symptoms in the upper abdomen despite no organic diseases in the digestive tract have recently been reported as non-arthur dyspepsia. -ulcer dyspepsia: NU
The concept of D) has been introduced, and it is being elucidated that the manifestation of this symptom is due to abnormalities in gastrointestinal motility.

[0003] Despite no organic disorders in the digestive tract, stomach sagging, nausea, vomiting, anorexia, abdominal bloating,
Complaints of gastrointestinal symptoms such as heartburn, upper abdominal pain, and belching are called gastrointestinal complaints.In the treatment of such gastrointestinal complaints, treatments for gastritis have been used conventionally, but the therapeutic effect is sufficient. Not. In recent years, gastrointestinal motility regulators such as cisapride (a gastrointestinal motility stimulating agent) and trimebutine maleate (a gastrointestinal motility regulating agent) have come to be used for treatment, but they are not always satisfactory in terms of efficacy. Not something to do.

[0004]

The present inventors have conducted intensive studies to provide a gastrointestinal motility regulator superior to the above-mentioned existing gastrointestinal motility regulators. Aminobenzamide compounds or salts thereof known as compounds useful as antipeptic ulcer agents (JP-A-55-31027, JP-A-56-18947)
No. JP-A-61-267542) has a gastrointestinal motility regulating action and is useful as a gastrointestinal symptom improving agent or a gastrointestinal motility regulating agent, and completed the present invention.

[0005]

According to the present invention, there is provided an image processing apparatus comprising:

[0006]

Embedded image [Wherein, R ¹ and R ² each independently represent a lower alkoxyl group, and R ³ represents a hydrogen atom, a lower acyl group, a lower alkyl group, a lower alkoxycarbonyl group, or -X-
SO ₃ M (wherein, X represents a lower alkylene group, M represents an alkali metal or an alkaline earth metal), R ⁴ represents a hydrogen atom, a halogen atom or a lower alkoxyl group, and R ⁵ represents an amino group. Group, morpholino group or lower alkylamino group (the lower alkylamino group may be substituted with a hydroxyl group in the alkyl moiety), and n is 1 to 6
Means an integer. ] Or a salt thereof, as an active ingredient.

Further, the present invention provides the following gastrointestinal symptom improving agent:
That is, the present invention relates to an agent for improving gastrointestinal symptoms in gastritis without erosion or bleeding, comprising an aminobenzamide compound represented by the formula (1) or a salt thereof as an active ingredient,
Also,

The present invention relates to an agent for improving digestive symptoms in chronic gastritis without erosion or bleeding, comprising an aminobenzamide compound represented by the formula (1) or a salt thereof as an active ingredient.

[0009] The present invention also relates to a therapeutic agent for complaints of gastrointestinal dysfunction comprising an aminobenzamide compound represented by the formula (1) or a salt thereof as an active ingredient.

Furthermore, the present invention relates to a gastrointestinal motility regulator comprising an aminobenzamide compound represented by the formula (1) or a salt thereof as an active ingredient.

The present invention relates to a gastric motility regulator containing an aminobenzamide compound represented by the formula (1) or a salt thereof as an active ingredient.

The present invention relates to a gastric motility promoter containing an aminobenzamide compound represented by the formula (1) or a salt thereof as an active ingredient.

The present invention relates to a gastric emptying regulator containing an aminobenzamide compound represented by the formula (1) or a salt thereof as an active ingredient, and further comprises an aminobenzamide compound represented by the formula (1) or a salt thereof as an active ingredient. The present invention relates to a therapeutic agent for chronic insufficiency type chronic gastritis.

According to the present invention, the active ingredient is 3-[[[2-
(3,4-dimethoxyphenyl) ethyl] carbamoyl] methyl] amino-N-methylbenzamide.
The present invention relates to a gastrointestinal symptom ameliorating agent, a gastrointestinal symptom ameliorating agent for gastritis without erosion or bleeding, a gastrointestinal symptom ameliorating agent for chronic gastritis without erosion or bleeding or a therapeutic agent for indefinite complaints.

Furthermore, the present invention provides a method for preparing an active ingredient comprising 3-[[[2
-(3,4-dimethoxyphenyl) ethyl] carbamoyl] methyl] amino-N-methylbenzamide.
The present invention relates to a gastrointestinal motility regulator, a gastric motility regulator, a gastric motility promoter, a gastric emptying regulator, or a therapeutic agent for chronic insufficiency type gastritis.

The gastrointestinal symptom ameliorating agent according to the present invention refers to an agent for ameliorating a clinical symptom in humans of indefinite complaints of gastrointestinal tract.

Here, the gastrointestinal indefinite complaint means gastric leaning, nausea, vomiting, loss of appetite, abdominal bloating, heartburn, upper abdominal pain, belching, etc., even though there is no organic disease in the digestive system. Symptoms of gastrointestinal symptoms.

The gastrointestinal symptom improving agent in gastritis refers to the above gastrointestinal symptom improving agent in gastritis, and the gastrointestinal symptom improving agent in chronic gastritis refers to the above gastrointestinal symptom improving agent in chronic gastritis.

Here, gastritis generally refers to inflammatory diseases of the stomach wall as gastritis, but mainly means non-specific mucosal inflammation, and is classified into acute gastritis and chronic gastritis according to the circumstances. Chronic gastritis is classified into superficial gastritis, atrophic gastritis, and hypertrophic gastritis according to the commonly used classification of R. Schindler.

Further, the therapeutic agent for indefinite digestive complaints according to the present invention refers to a drug effective for treating the above-mentioned intestinal indefinite complaints.

Next, the gastrointestinal motility regulator of the present invention,
The gastric motility regulator, gastric motility promoter, gastric emptying regulator, and gastric emptying promoter will be described.

The regulation of gastrointestinal motility refers to the enhancement and control of motor function in the gastrointestinal tract such as the esophagus, stomach, small intestine and large intestine. It refers to the excretory function, the stirring function, etc., and a drug that regulates these functions is called a gastrointestinal motility regulator. In addition,
These functions have been confirmed by experimental animals such as mice by quantification of phenol red administered as an indicator of gastric contents.

The regulation of gastric motility refers to the enhancement and control of motility in the gastrointestinal tract, particularly in the stomach. Drugs that regulate the function are called gastric motility regulators. Particularly, a drug that promotes gastric motility is called a gastric motility promoter.

Further, the regulation of gastric emptying refers to a function of excreting gastric contents such as food in the stomach and a partial digest thereof from the pylorus, and a drug regulating the function is called a gastric emptying regulator. Drugs that promote gastric emptying, in particular, are called gastric emptying promoters.

The aminobenzamide compound or a salt thereof, which is an active ingredient of the agent for improving gastrointestinal symptoms according to the present invention, is already known to have an anti-ulcer effect. The effect is a completely different effect.

The aminobenzamide compound or its salt, which is an active ingredient of the agent for improving gastrointestinal symptoms according to the present invention, improves the gastrointestinal insufficiency complaint, which is a cause of gastrointestinal insufficiency complaints. It is brought about by things. On the other hand, the anti-ulcer effect of the aminobenzamide compound or a salt thereof, which is an active ingredient of the gastrointestinal symptom-ameliorating agent according to the present invention, is based on the blood flow improving effect of gastric mucosa (Arzneim.-Forsch./Drug Res. 40 (I), 3, 27
6-281, 1990), which is not directly related to the gastric emptying promoting action disclosed in the present invention.

Furthermore, regarding the relationship between gastric emptying and various gastrointestinal diseases such as ulcers and indeterminate complaints of the upper abdomen, only a small decrease in gastric emptying in gastric ulcers was recognized, but the gastric emptying ability in the upper abdominal complaints was not recognized. The decline has been reported to be significant (Pharma Medica Vol. 857-63, 1990).

Therefore, although the causal relationship between the ulcer and the abnormality in the gastrointestinal tract is weak, it is considered that the gastrointestinal indefinite complaint is caused by the abnormality in the gastrointestinal tract.

It is also a great difference between ulcers that have an organic disease and gastrointestinal complaints that they do not have an organic disease.

The substituents in the aminobenzamide compound represented by the formula (1) will be described below.

The lower alkoxyl group in the formula (1) includes a methoxy group, an ethoxy group, a propoxy group, a butoxy group, a pentyloxy group and a hexyloxy group.

The lower acyl group in the formula (1) includes an acetyl group, a propionyl group, a butyryl group, an isobutyryl group, a valeryl group, an isovaleryl group, a pivaloyl group and a hexanoyl group.

As the lower alkyl group in the formula (1),
Examples include a methyl group, an ethyl group, a propyl group, an isopropyl group, a butyl group, a tertiary butyl group, a pentyl group and a hexyl group.

The lower alkylene group in the formula (1) includes a methylene group, an ethylene group, a propylene group, a butylene group, an amylene group and a hexylene group.

The lower alkylamino group in the formula (1) means a mono-lower alkylamino group or a di-lower alkylamino group, and the lower alkyl groups of the di-lower alkylamino group may be the same or different.

Examples of the salt of the aminobenzamide compound represented by the formula (1) include acid addition salts with inorganic acids such as hydrochloric acid and sulfuric acid and organic acids such as picric acid.

The aminobenzamide compounds and salts thereof according to the present invention are disclosed in JP-A-55-31027 and JP-A-5-31027.
It can be produced by the methods described in JP-A-6-18947 and JP-A-61-267542.

The following are nine specific examples of the aminobenzamide compounds according to the present invention, from {A} to {I}.

{A} 3-[[[2- (3,4-dimethoxyphenyl) ethyl] carbamoyl] methyl] amino-
N-methylbenzamide

[0040]

Embedded image

{B} 3-[[[2- (3,4-dimethoxyphenyl) ethyl] carbamoyl] methyl] amino-
N-ethylbenzamide

[0042]

Embedded image

{C} 3-[[[2- (3,4-dimethoxyphenyl) ethyl] carbamoyl] methyl] amino-
N, N-dimethylbenzamide

[0044]

Embedded image

{D} 3-[[[2- (3,4-dimethoxyphenyl) ethyl] carbamoyl] methyl] amino-
N- (2-hydroxyethyl) benzamide

[0046]

Embedded image

{E} 1- [3-[[[2- (3,4-dimethoxyphenyl) ethyl] carbamoyl] methyl] amino] benzoylmorpholine

[0048]

Embedded image

{F} 2-[[[2- (3,4-dimethoxyphenyl) ethyl] carbamoyl] methyl] amino-
4-methoxy-N-methylbenzamide

[0050]

Embedded image

{G} 2-[[[2- (3,4-dimethoxyphenyl) ethyl] carbamoyl] methyl] amino-
5-methoxy-N-methylbenzamide

[0052]

Embedded image

{H} 2-[[[2- (3,4-dimethoxyphenyl) ethyl] carbamoyl] methyl] amino-
N-methylbenzamide

[0054]

Embedded image

{I} 3- [N-sulfomethyl-N-
Sodium salt of [[[2- (3,4-dimethoxyphenyl) ethyl] carbamoyl] methyl] amino] benzamide

[0056]

Embedded image

In the present invention, specific examples of the aminobenzamide compound are described in JP-A-55-3102.
7, JP-A-56-18947, JP-A-61-267
The compound is different from the compound name described in No. 542, but is the same compound.

Among the above specific examples, the most typical one is the compound {A}, and its general name is ecabapide.

The agent for improving gastrointestinal symptoms or the gastrointestinal motility regulator of the present invention is used for improving gastrointestinal symptoms in gastritis, especially chronic gastritis, or for controlling gastrointestinal motility such as esophagus, stomach, small intestine and large intestine, particularly gastric stomach. It is used as a motility regulator, a gastric motility promoter, specifically a gastric emptying regulator, and further as a gastric emptying promoter.

The agent for improving gastrointestinal symptoms or the agent for regulating gastrointestinal motility of the present invention can be administered orally or parenterally, but is usually administered orally.

The gastrointestinal symptom-ameliorating agent or gastrointestinal motility regulator of the present invention can be formulated into various dosage forms by known formulation techniques, and commonly used excipients, binders, Appropriate additives such as disintegrants and lubricants can be added.

The following are excipients that can be used as additives:
Examples of binders, disintegrants and lubricants are given.

The excipients that can be used include lactose, starch, crystalline cellulose, light anhydrous silicic acid and the like.

Examples of usable binders include crystalline cellulose, mannitol, dextrin, hydroxypropylcellulose and polyvinylpyrrolidone.

Examples of usable disintegrants include starch, carboxymethylcellulose and calcium carboxymethylcellulose.

Examples of usable lubricants include talc, magnesium stearate and the like.

The additives that can be added to the preparation must be harmless to the living body at the dosage of the preparation and do not impair the therapeutic effect of the active ingredient of the preparation.

Representative preparations of the gastrointestinal symptom improving agent or gastrointestinal motility regulator of the present invention include oral preparations.
Specific examples include capsules, granules, fine granules, pills, powders, tablets and the like, and particularly preferably fine granules and tablets.

The dosage of the gastrointestinal symptom ameliorating agent or gastrointestinal motility regulator of the present invention is usually 30 to 600 mg of an active ingredient per adult per day, preferably 75 to 75 mg.
-600 mg, particularly preferably 3 per day per adult
00 mg. In addition, the dosage can be appropriately increased or decreased depending on age, body weight, symptoms, and the like.

When the agent for improving gastrointestinal symptoms or the agent for regulating gastrointestinal motility according to the present invention is provided as an oral preparation, the administration period may be before, between or after meals, and may be one day per day.
You may take up to three times.

The aminobenzamide compound and the salt thereof according to the present invention have an LD ₅₀ value of 2 g / kg or more in oral administration as shown in an acute toxicity test using mice and are extremely low toxic compounds (JP 1955-310
No. 27, JP-A-56-18947, JP-A-61-26
No. 7542), which is a highly safe compound for administration to the human body.

Hereinafter, the present invention will be described in further detail with reference to Examples and Test Examples, but the present invention should not be limited to these.

[0073]

EXAMPLES In the following Examples and Test Examples, Compound A: 3
-[[[2- (3,4-dimethoxyphenyl) ethyl]
Carbamoyl] methyl] amino-N-methylbenzamide was used.

Example 1 A tablet was prepared according to the following formulation and in accordance with the tablet section of the Japanese Pharmacopoeia General Rules for Preparations to obtain an uncoated tablet.

Ingredient Amount Compound A 100 mg Excipient 73 mg Disintegrant 6 mg Binder 7 mg Lubricant 4 mg Dye trace 1 tablet total 190 mg

The naked tablets obtained by the above formulation were coated with 10 mg of a film film mainly composed of a water-soluble film base to prepare a test preparation.

Example 2 A tablet was prepared according to the following formulation and in accordance with the tablet section of the Japanese Pharmacopoeia General Rules for Preparations to obtain an uncoated tablet.

Ingredient Amount Compound A 100 mg Excipient 38 mg Disintegrant 5 mg Binder 5 mg Lubricant 2 mg Pigment Trace 1 tablet Total 150 mg

The naked tablet obtained by the above formulation was coated with 8 mg of a film film mainly composed of a water-soluble film base to prepare a test preparation.

Example 3 A tablet was prepared according to the following formulation in accordance with the tablet section of the Japanese Pharmacopoeia General Rules for Preparations to obtain an uncoated tablet.

Component Amount Compound A 100 mg Excipient 9 mg Disintegrant 6 mg Binder 4 mg Lubricant 1 mg Pigment trace 1 tablet total 120 mg

The naked tablet obtained by the above-mentioned formulation was coated with 7 mg of a film film mainly composed of a water-soluble film base to prepare a test preparation.

[0083]

[Test example]

Test Example 1 Effect on gastric emptying in a model of cholecystokinin-induced gastric emptying delay (phenol red method): 6- to 7-week-old male Slc: ddY mouse (body weight 20-30 g, Shizuoka experimental animal) fasted overnight An untreated cholecystokinin administration group (No. 1 shown in Table 1), a group receiving cholecystokinin after Compound A administration (No. 2 to No. 2)
4), a group in which cholecystokinin was administered after administration of a positive control drug (cisapride) (No. 5) and a group in which no drug was treated with cholecystokinin (No. 6) were used in experiments. One group of mice was used as 5 to 15 mice.

First, 90 minutes before the administration of phenol red,
In the mice of the compound A administration group (Nos. 2 to 4), 0.5
% Of carboxymethylcellulose was added to Compound A at 1 mg / kg, 3 mg / kg or 1 mg / kg.
0 mg / kg was orally administered to the positive control drug administration group (No.
In the mouse of 5), a suspension of cisapride suspended in 0.5% carboxymethylcellulose was treated with 3 mg of cisapride.
/ Kg orally, and 0.5% carboxymethylcellulose was orally administered to each of the mice in the group treated with no drug treated cholecystokinin (No. 1) and the group treated with no drug treated cholecystokinin (No. 6). . Then, 5 minutes before administration of phenol red, a cholecystokinin (CCK8s; Sigma) solution dissolved in distilled water and diluted with physiological saline was added.
Cholecystokinin 5 μg / kg was intraperitoneally administered to mice in each administration group. A phenol red solution dissolved in 1% methylcellulose was orally administered to mice of each administration group at 0.2 mg / 0.3 ml of phenol red. Thirty minutes after the administration of phenol red, the mice were sacrificed by cervical dislocation, the phenol red remaining in the stomach removed was quantified, and the gastric emptying rate (%) was calculated by the following formula.

Stomach emptying rate (%) = [1- (recovered amount of phenol red of drug-administered mouse / X)] × 100 (X is the recovery of phenol red remaining in the stomach that was sacrificed immediately after administration of phenol red and extirpated. The average value is shown.)

[0086]

[Table 1]

As is clear from Table 1, the gastric emptying rate of mice to which 5 μg / kg of cholecystokinin was administered intraperitoneally was reduced to less than one third. The administration of 1 mg / kg, 3 mg / kg, or 10 mg / kg of Compound A to such a mouse having a reduced gastric emptying rate improved the gastric emptying rate of the mouse in a dose-dependent manner.

Test Example 2 Effect on gastric emptying in dopamine-induced gastric emptying delay model (phenol red method):
A 6-7 week-old male Slc: ddY mouse (body weight: 28-32 g, Shizuoka experimental animal) fasted overnight was administered with a drug-untreated dopamine administration group (No. 1 shown in Table 2). Group (Nos. 2 to 5) and a group receiving dopamine after administration of a positive control drug (cisapride) (N
o. 6), divided into drug-untreated dopamine-untreated groups (No. 7) and used in experiments. One group of mice was used as 7 mice.

First, 90 minutes before the administration of phenol red,
In the mice of the compound A administration group (Nos. 2 to 5), 0.5
% Of carboxymethylcellulose was added to Compound A at 0.01 mg / kg and 0.03 mg / kg.
kg, 0.1 mg / kg or 0.3 mg / kg orally, and mice in the positive control drug administration group (No. 6):
A cisapride suspension suspended in 0.5% carboxymethylcellulose was orally administered with cisapride at 3 mg / kg, and each of a drug-untreated dopamine administration group (No. 1) and a drug-untreated dopamine untreated group (No. 7) 0.5% for mice
Carboxymethylcellulose was administered orally. Then
Five minutes before the administration of phenol red, a dopamine solution dissolved in distilled water and diluted with physiological saline was intraperitoneally administered to mice of each administration group at 30 mg / kg dopamine. A phenol red solution dissolved in 1% methylcellulose was orally administered to mice in each administration group at 0.2 mg / 0.3 ml. Thirty minutes after the administration of phenol red, the mice were sacrificed by cervical dislocation, the phenol red remaining in the stomach removed was quantified, and the gastric emptying rate (%) was calculated by the following formula.

Gastric emptying rate (%) = [1- (recovered amount of phenol red of drug-administered mice / X)] × 100 (X is the recovery of phenol red remaining in the stomach that was sacrificed immediately after the administration of phenol red and extirpated from the mice. The average value is shown.)

[0091]

[Table 2]

As is clear from Table 2, 30 mg / kg
The gastric emptying rate of mice given intraperitoneal dopamine was 20%.
It decreased to less than 1 /. For mice with such reduced gastric emptying rate, 0.01 mg / kg, 0.03 mg / k
Administration of g, 0.1 mg / kg or 0.3 mg / kg Compound A improved gastric emptying in mice.

Test Example 3 Effects on Patient's Subjective Symptoms and Gastric Emptying Patients diagnosed with chronic gastritis or the like despite having no organic disease in their stomachs and having chronic moderate or higher upper abdominal bloating. Eight patients who had and had other gastrointestinal symptoms (stomach sagging, nausea, vomiting, anorexia, heartburn, etc.) and also had delayed gastric emptying were used as subjects.

The test subject prepared the test preparation of Example 1 twice
Tablets 3 times a day (daily dose of compound A 600mg),
They were taken 15-30 minutes before lunch and dinner and continued for 2 weeks. Subjective symptoms were examined before and 2 weeks after administration (Table 3), and gastric emptying was performed before and 2 weeks after administration (Table 4).

The subjective symptoms were examined based on the presence or absence of symptoms before administration and two weeks after administration (Table 3).

[0096] The gastric emptying test was carried out by using Heading [B
r. J. Pharmacol. 47: 415-421,1973] et al. That is, for subjects who fasted the night before and forbid all medication, 1.5 g of acetaminophen was added to the test meal (200 ml of liquid natural food OKUNOS-A) at 9:00 am, and the mixture was thoroughly stirred to take the drug. He was prohibited from eating and drinking until the end, and was allowed to sit. Blood was collected before taking the medicine and blood was collected 45 minutes after taking the medicine by heparinization. Next, the serum was separated, and the serum acetaminophen concentration was measured by high performance liquid chromatography (HPLC) (Table 4).

[0097]

[Table 3]

[0098]

[Table 4]

As is clear from Tables 3 and 4, 1 to
When Compound A was administered to 8 patients, the subjective symptoms completely disappeared after 2 weeks of administration, and gastric emptying was improved in 7 out of 8 patients.

[0100]

The aminobenzamide compound or a salt thereof according to the present invention exhibits excellent gastrointestinal symptom ameliorating action, gastrointestinal motility regulating action and gastric emptying promoting action, It is very useful as a gastrointestinal symptom improving agent for gastritis without erosion or bleeding or a gastrointestinal symptom improving agent for chronic gastritis without erosion or bleeding.

Continued on the front page (72) Inventor Satoshi Hatanaka 1-16-13 Kita-Kasai, Edogawa-ku, Tokyo Daiichi Pharmaceutical Co., Ltd. Tokyo R & D Center-(72) Inventor Keiko Kawabayashi 1-16 Kita-Kasai, Edogawa-ku, Tokyo No. 13 Daiichi Pharmaceutical Co., Ltd. Tokyo R & D Center-Examiner Takanobu Morii (56) References JP-A-55-31027 (JP, A) JP-A-56-18947 (JP, A) JP-A-61- 267542 (JP, A) JP-A-1-228948 (JP, A) Chem. Pharm. Bull. , Vol. 40 No. 10 (1992) p. 2712-2719 Arzneim. -Forsch. , Vol. 40 No. 3 (1990) p. 276-281 Jpn. J. Pharmacol. , Vol. 48 No. 2 (1988) p. 299 -302 (58) Fields investigated (Int. Cl. ⁶ , DB name) A61K 31/165 A61K 31/185 A61K 31/535 CA (STN) MEDLINE (STN)

Claims (15)

(57) [Claims] (1) Formula (1) [Wherein, R ¹ and R ² each independently represent a lower alkoxyl group, and R ³ represents a hydrogen atom, a lower acyl group, a lower alkyl group, a lower alkoxycarbonyl group, or -X-
SO ₃ M (wherein X represents a lower alkylene group, M represents an alkali metal or an alkaline earth metal), R ⁴ represents a hydrogen atom, a halogen atom or a lower alkoxyl group, and R ⁵ Represents an amino group, a morpholino group or a lower alkylamino group (the lower alkylamino group may be substituted with a hydroxyl group in the alkyl moiety), and n represents an integer of 1 to 6. A gastrointestinal symptom ameliorating agent comprising the aminobenzamide compound represented by the formula (I) or a salt thereof as an active ingredient. 2. An agent for improving gastrointestinal symptoms in gastritis without erosion or bleeding, comprising an aminobenzamide compound represented by the formula (1) or a salt thereof as an active ingredient. 3. An agent for improving gastrointestinal symptoms in chronic gastritis without erosion or bleeding, comprising an aminobenzamide compound represented by the formula (1) or a salt thereof as an active ingredient. 4. An agent for treating gastrointestinal indeterminate complaints comprising an aminobenzamide compound represented by the formula (1) or a salt thereof as an active ingredient. 5. A gastric motility promoter comprising an aminobenzamide compound represented by the formula (1) or a salt thereof as an active ingredient. 6. A gastric emptying regulator comprising an aminobenzamide compound represented by the formula (1) or a salt thereof as an active ingredient. 7. A therapeutic agent for chronic insufficiency-type gastritis comprising an aminobenzamide compound represented by the formula (1) or a salt thereof as an active ingredient. 8. [3-[[[2- (3,4-dimethoxyphenyl) ethyl] carbamoyl] methyl] amino-N-
An agent for improving gastrointestinal symptoms comprising methylbenzamide as an active ingredient. 9. [3-[[2- (3,4-dimethoxyphenyl) ethyl] carbamoyl] methyl] amino-N-
An agent for improving gastrointestinal symptoms in gastritis without erosion or bleeding, comprising methylbenzamide as an active ingredient. 10. [3-[[2- (3,4-dimethoxyphenyl) ethyl] carbamoyl] methyl] amino-N
-An agent for improving gastrointestinal symptoms in chronic gastritis without erosion or bleeding, comprising methylbenzamide as an active ingredient. 11. [3-[[2- (3,4-dimethoxyphenyl) ethyl] carbamoyl] methyl] amino-N
-A therapeutic agent for unidentified digestive complaints comprising methylbenzamide as an active ingredient. 12. [3-[[[2- (3,4-dimethoxyphenyl) ethyl] carbamoyl] methyl] amino-N
-A gastric motility regulator comprising methylbenzamide as an active ingredient. 13. [3-[[2- (3,4-Dimethoxyphenyl) ethyl] carbamoyl] methyl] amino-N
-A gastric motility promoter containing methylbenzamide as an active ingredient. 14. [3-[[[2- (3,4-dimethoxyphenyl) ethyl] carbamoyl] methyl] amino-N
-A gastric emptying regulator containing methylbenzamide as an active ingredient. 15. [3-[[[2- (3,4-dimethoxyphenyl) ethyl] carbamoyl] methyl] amino-N
-A therapeutic agent for insufficiency chronic gastritis comprising methylbenzamide as an active ingredient.