JPS59184124A - Agent for improving energy metabolism - Google Patents

Abstract

PURPOSE:To provide an agent for improving the energy metabolism, capable of remarkably mitigating the adynamia caused by renal insufficiency, diabetes, etc., by using one or more compounds selected from glycocyamine which is a metabolic precursor of creatine phosphate, its derivative and its acid addition salt. CONSTITUTION:The titled improving agent is prepared by using one or more compounds selected from glycocyamine, a glycocyamine derivative which can be converted to glycocyamine in the living body (e.g. glycocyamine ethyl ester) and its acid addition salt (e.g. glycocyamine hydrochloride). It has been found newly that the glycocyamine administered externally to the body exhibits remarkable effect to improve the energy metabolism. That is, the energy metabolism of the skeletal muscle lowered by renal diseases, diabetes, etc. can be improved and the nutrition state can be restored. It is preferably administered in the form of tablet, capsule, injection, etc. Dose: preferably 500-1,500mg daily for oral administration.

Description

Detailed Description of the Invention The present invention uses glycocyamine, which is a metabolic precursor of creatine phosphate, which is an energy storage substance in skeletal muscles, a derivative of glycocyamine that is converted to glycocyamine in the body, or a salt thereof as an active ingredient. Contains an energy metabolism improving agent.

Previously, it has been reported that renal disease patients and diabetic patients often have muscle weakness and wasting, as well as electromyographic and morphological abnormalities, but there are no drugs that can improve these symptoms. It has not been discovered yet.

As a result of intensive research in view of the above situation, the present inventors have found that glyphcyamine has a remarkable effect on improving energy metabolism, that is,
The present inventors have discovered that the present invention has the effect of significantly alleviating symptoms such as muscle weakness during renal failure, and have completed the present invention.

Glycocyamine is a known compound (Organic Synthesis, Collective Volume III, 440 (1955)
)) It is known as a precursor of creatine phosphate, which is a high-energy substance, but the fact that externally given glycocyamine has pharmacological effects such as improving energy metabolism has not been disclosed until now. .

Hereinafter, the pharmacological action of glycocyamine according to the present invention will be explained in detail.

EXAMPLE Behavioral Pharmacological Test in Renal Failure Model Using male Wistar rats (Nippon Talea) weighing 170 to 180 kg, the cortex of one kidney was surgically excised and removed under bentoparbital sodium anesthesia. Two weeks later, the other kidney was removed.

Blood urea nitrogen (BUN) 2 weeks after the aforementioned nephrectomy
and plasma creatinine (Cr) were measured, and the concentrations were 60 to 120 ■/# and 0.8 to 2.1 m, respectively.
y/di range was used as a renal failure pathology model.

These renal failure rats were divided into 6 groups, and group (A) was given tap water;
Group (E) included tap water containing 0.01% glycocyamine;
Group C) was given free access to tap water containing 0.1% glycocyamine along with commercially available solid feed for 4 weeks. Two and four weeks after the start of intake, the sliding angle of the rats was examined using the inclined plate method, and a swimming fatigue test was conducted at the fourth week. As a control, healthy rats of the same age as the model animals) (Group D)
A similar test was also carried out.

The results are shown in Table 1, and the glycocyamine administration group (
In Group B, Group 0), an increase in the sliding angle and an extension of the swimming time were observed.

Table 1 Effect of glyphcyamine on muscle strength and recovery from muscle fatigue*, #: Significant difference with a risk rate of 5% or 1% or less.

Effects similar to those described above were also observed in acid addition salts of glycocyamine and those that are metabolized in vivo and converted to glycocyamine, such as glycodiamine hydrochloride and ethyl ester of glycocyamine.

Example: Nutritional test in a renal failure model The weight gain of each group shown in Experiment 1 was 24.1 ± 3.1/4 weeks for the tap water intake group (A), while (B) 8η. 0
．． 01% glycocyamine water intake group: 32.6±a, 2
y/; r71, (e) details of 0.1% glycocyamine water intake was 30.6 ± 5.2y/4 weeks (B), (C)
The addition of glycocyamine was proven to improve nutrition in rats with renal insufficiency, as the group showed weight gain.

Therefore, in order to further clarify the nutritional effects of glycocyamine, we administered 0.7 mmole/day of glycocyamine to the same renal failure model rats under total parenteral nutrition (CTPN method), and compared nitrogen balance with a TPN group that does not contain glycocyamine. did. The results are shown in Figure 1, and the control TP
Compared to the N group, the nitrogen balance in the glycocyamine-containing TPN group was significantly positive after the 38th day, and the cumulative nitrogen balance during the experimental period was -68,6■N1 in the glycocyamine-containing TPN group.
Control group -220°5N. Considering the above-mentioned improvement in weight gain and experiments on nitrogen balance, the addition of glycocyamine improved the protein metabolism of the living body, and it was thought that this was based on the improvement of energy metabolism by the administration of glycocyamine.

As is clear from the results of the above pharmacological tests, glycocyamine is clinically useful because it improves energy metabolism in skeletal muscles and restores nutritional status by administering it when production is decreased due to kidney disease, diabetes, etc. it is conceivable that.

Next, the administration method and dosage of glycocyamine, glycocyamine derivatives, or salts thereof according to the present invention will be described.

The pharmacologically effective glycocyamine, derivatives thereof, or salts thereof of the present invention can be administered by direct administration of the compound, but preferably in a pharmaceutically acceptable excipient. Administering the agent as a dosage composition in a processed form yields good results.

More specifically, the composition for administration will be as shown in the formulation examples below. Preferably, the formulation is in the form of tablets, granules, fine granules, powders, hard capsules, soft capsules, injections, suppositories, buccal preparations, or buccal preparations. however,
There is no particular need to limit the dosage form to these, and as long as it is an administrable dosage form, it will not prevent the expression of pharmacological effects after administration.

Formulation example 1 Capsule A pharmaceutical composition is manufactured according to the following recipe.

Component Amount Glycocyamine 150 ■Lactic acid
75■ Starch 25rng Talc 5rnI/Magnesium Stearate 2■ Pass these ingredients through a sieve, mix and place in a hard capsule.

Formulation example 2 Tablets A pharmaceutical composition is manufactured according to the following recipe.

Constituent Quantity Glycocyamine 150■! % acid
40 ■ Starch 1
5 ■ Carboxymethyl cellulose 10 ■ Methyl cellulose 8 q talc
1WuI Magnesium Stearate lmi Pass these ingredients through a sieve,
Mix and tablet.

Formulation example 6 Suppositories A pharmaceutical composition is manufactured according to the following recipe.

Component Amount Glycocyamine 150 rng Witepsol H-158501 ng These ingredients are separated, mixed, and poured into a suppository mold.

Formulation example 4 Injection A pharmaceutical composition is manufactured according to the following recipe.

Component Amount Glycocyamine 150 ■ Sodium chloride 40 ■ Distilled water for injection
5rnI! These ingredients are mixed and dissolved, filtered, poured into an ampoule, sealed and sterilized.

The daily dose of glycocyamine, derivatives thereof, or acid addition salts thereof according to the present invention for adult males is 200 mg orally.
01ng or 4. OOOrng, preferably 500
fng or +, soomi+.

[Brief explanation of the drawing]

Figure 1 shows the effect of glycocyamine on nitrogen balance. Patent applicant Morishita Pharmaceutical Co., Ltd. Figure 1

Claims (1)

[Claims] An energy metabolism improving agent comprising at least one of glycocyamine, a glycocyamine derivative that is converted into glycocyamine in vivo, and an acid addition salt thereof.