JP4253856B2 - Gastrointestinal motor function improver - Google Patents

Description

【００２１】
表１の結果より、Ｌ−グルタミンはドーパミンＤ２受容体に対する作用がないことが確認された。
【００２２】
試験例３ 急性毒性試験
一夜絶食した５週齢のＣｒｊ：ＣＤ系雄性ラットを用い（１群８匹）、Ｌ−グルタミン１０００mg／kgを経口投与し、１週間にわたって観察を行ったが、死亡例はなくＬ−グルタミンの副作用は認められなかった。
【００２３】
【発明の効果】
本発明の消化管運動機能改善剤は、胃または腸管内に存在する内容物を速やかに排出させることにより腹部不定愁訴および腹部膨満感を改善し、しかも、安全で優れた消化管運動機能改善効果を有する。
【図面の簡単な説明】
【図１】試験例１におけるコントロール群の消化管中のビーズの推移を表すグラフである。
【図２】試験例１におけるＬ−グルタミン投与群ラットの消化管中のビーズの推移を表すグラフである。
【図３】試験例１におけるシサプリド投与群ラットの消化管中のビーズの推移を表すグラフである。
【図４】試験例１におけるアトロピン投与群の消化管中のビーズの推移を表すグラフである。[0001]
BACKGROUND OF THE INVENTION
The present invention is a gastrointestinal function improving agent characterized by containing glutamine as an active ingredient, particularly an action to improve abdominal indefinite complaints and abdominal fullness by quickly draining the contents present in the stomach or intestinal tract. The present invention relates to a preparation containing glutamine.
[0002]
[Prior art]
Conventionally, cisapride and metoclopramide having 5-HT4 receptor agonist activity have a gastrointestinal motility enhancing action, such as chronic gastritis, abdominal distension, reflux esophagitis, abdominal indefinite complaints and pseudo-intestinal obstruction Used for treatment. However, metoclopramide has been shown to have side effects of extrapyramidal symptoms due to its action on central dopamine D2 receptors, and Parkinson's symptoms have also been shown in cisapride. Therefore, it is extremely difficult to obtain the expected efficacy without causing side effects on these drugs.
[0003]
On the other hand, there are various reports on glutamine, which is a biological component. For example, Digestive Disease, 20, 626 (1975) describes the protective action of glutamine on gastric mucosal cells.
[0004]
On the other hand, glutamine is well known as an amino acid having a high physiological activity among amino acids, and it has been reported that glutamine serves as an energy source for the small intestinal mucosa and further prevents atrophy of the small intestine after withdrawal of TPN. For example, Wilmore et al discloses in JP-T 63-501214 that glutamine is added to an amino acid infusion to treat catabolic dysfunction.
However, it is not known at all that glutamine has a gastrointestinal motility function improving action.
[0005]
[Problems to be solved by the invention]
Accordingly, an object of the present invention is to provide a drug that improves abdominal indefinite complaints and a feeling of fullness of the abdomen in patients with various types of gastrointestinal motility functions and is safe and has a strong effect of improving gastrointestinal motility functions. is there.
[0006]
[Means for Solving the Problems]
As a result of diligent research to solve the above-mentioned problems, the present inventors have improved the abdominal indefinite complaints and abdominal fullness in patients with various gastrointestinal motility functions without causing side effects of glutamine. As a result, the present invention has been completed.
[0007]
That is, the present invention relates to a gastrointestinal motility function improving agent characterized by containing glutamine as an active ingredient.
[0008]
The agent for improving gastrointestinal motility function of the present invention can be effectively applied as a glutamine preparation to various patients with reduced gastrointestinal motility function, and exhibits an excellent effect in improving abdominal indefinite complaints and abdominal distension by its application, such as side effects Don't worry.
[0009]
Glutamine used in the present invention is usually used in the form of a free amino acid, but it is not particularly necessary to be in a free form, and it is not necessary to be in a free form, and is hydrolyzed in vivo to a free amino acid in the form of a pharmacologically acceptable salt. It can also be used in the form of ester or peptide to be converted. As the salt form of glutamine, its metal salt or acid addition salt is used. The metal salt is preferably an alkali metal salt such as sodium or potassium. As the form of the acid addition salt, mineral acid salts such as hydrochloride and sulfate, and organic acid salts such as acetate and malate are used. In addition, any of D-isomer, L-isomer and DL-isomer, which are optical isomers, can be used.
[0010]
In the present invention, when glutamine is used as a gastrointestinal motility improving agent, glutamine may be administered orally as it is, but enteral administration or intravenous administration is also possible. The glutamine used in the present invention can be used alone as a preparation containing only this, but a better effect can be obtained by using it together with other amino acids (for example, arginine, branched chain amino acids, taurine, etc.).
[0011]
The dosage form can be prepared in the form of powder, powder, granule, tablet, capsule, liquid, emulsion, suspension and the like. In that case, pharmaceutically acceptable solid or liquid suitable excipients, lubricants, flavor correctors, fragrances, fillers, solvents, emulsifiers and other pharmaceutical additives, stabilizers and pH adjustment It can be prepared by adding an adjuvant such as an agent.
[0012]
The agent for improving gastrointestinal motility function of the present invention is used for patients with various abdominal complaints and abdominal bloating at the time of various gastrointestinal motility function declines, and the dosage is used for the sex, body type, constitution, age and symptoms of the patient. Although it varies depending on the dosage form, when administered orally, it is appropriate that glutamine is 0.02 to 0.5 g / kg / day, preferably 0.05 to 0.3 g / kg / day. The administration of glutamine is preferably carried out once to several times a day so that the daily dose falls within the above range.
[0013]
【Example】
Hereinafter, although this invention is demonstrated in detail based on a formulation example and a test example, this invention is not limited to these.
[0014]
Example 1
By a conventional method, a tablet having the following composition is produced.
Composition L-glutamine 100mg in one tablet (200mg)
Corn starch 40mg
Lactose 54mg
Hydroxypropylcellulose 5mg
Magnesium stearate 1mg
[0015]
Example 2
A capsule having the following composition is produced by a conventional method.
Composition L-glutamine 100 mg in one capsule (200 mg)
Cornstarch 65mg
Lactose 25mg
Hydroxypropylcellulose 10mg
[0016]
Example 3
A granule having the following composition is produced by a conventional method.
Composition L-Glutamine 50mg in 200mg of granules
Corn starch 40mg
Lactose 59mg
Microcrystalline cellulose 39mg
Hydroxypropylcellulose 2mg
Carboxymethylcellulose 10mg
[0017]
Test Example 1 Gastrointestinal motor function test Seven-week-old Crj: CD male rats fasted overnight (7 rats per group), the control group was distilled water, the glutamine administration group was L-glutamine 100 mg / kg, cisapride In the administration group, cisapride 10 mg / kg was orally administered, and in the atropine administration group, atropine 5 mg / kg was subcutaneously administered. One hour after drug administration, 100 beads having a diameter of 1 mm were orally administered. 30 minutes after administration of the beads, the abdomen was opened under ether anesthesia, the blood was lethal from the abdominal aorta, and the stomach, duodenum and small intestine were immediately removed. The stomach was divided into G, and the duodenum to small intestine was divided into four equal parts, and represented by B1 to B4 from the duodenum side. The number of beads present at each site is shown in FIGS.
[0018]
FIG. 1 is a control group (distilled water administration), FIG. 2 is an L-glutamine administration group, FIG. 3 is a cisapride administration group (having a gastrointestinal motility improvement effect), and FIG. The transition of beads in the gastrointestinal tract in the case of (suppressing movement) is shown. In the control group and the atropine administration group, many beads are observed in the stomach (G), but in the L-glutamine administration group, many beads are observed in the small intestine site (B3) as in the cisapride administration group, and gastrointestinal motility is promoted. It became clear.
[0019]
Test Example 2 Anti-Dopamine Test Using 5-week-old male males of the week of Crj: CD that were fasted overnight (4 rats per group), the glutamine administration group was L-glutamine 100, 1000 mg / kg, and the cisapride administration group was cisapride 100 and 1000 mg. In the metoclopramide administration group, metoclopramide 100 and 1000 mg / kg were orally administered, and general symptoms including catalepsy 1 hour after administration and drooping of eyelids 1 hour after administration were observed. Catalepsy puts one rat's forelimb on a 5cm diameter and 4cm height column and scores the rest time (0 seconds: 0 points, 1-10 seconds: 1 point, 11-20 seconds: 2 points) 21 to 30 seconds: 3 points, 31 seconds or more: 4 points) and expressed as an average of 3 times. The results are shown in Table 1.
[0020]
[Table 1]

[0021]
From the results in Table 1, it was confirmed that L-glutamine had no action on the dopamine D2 receptor.
[0022]
Test Example 3 Acute Toxicity Test Using 5-week-old Crj: CD male rats fasted overnight (8 rats per group), L-glutamine 1000 mg / kg was orally administered and observed for 1 week. There was no side effect of L-glutamine.
[0023]
【The invention's effect】
The agent for improving gastrointestinal motility function of the present invention improves abdominal indefinite complaints and a feeling of fullness of the abdomen by quickly discharging the contents present in the stomach or intestinal tract, and has a safe and excellent gastrointestinal motility function improving effect Have
[Brief description of the drawings]
1 is a graph showing the transition of beads in the digestive tract of a control group in Test Example 1. FIG.
2 is a graph showing the transition of beads in the gastrointestinal tract of L-glutamine administration group rats in Test Example 1. FIG.
3 is a graph showing the transition of beads in the gastrointestinal tract of rats treated with cisapride in Test Example 1. FIG.
4 is a graph showing the transition of beads in the digestive tract of the atropine administration group in Test Example 1. FIG.

Claims (1)

  A gastric motor function improving agent characterized by containing glutamine as an active ingredient.

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