JP3096052B2 - Lipid metabolism regulator - Google Patents

Description

Description: TECHNICAL FIELD The present invention relates to a lipid metabolism regulator containing proline and / or threonine as an active ingredient.

(Prior Art and Problems to be Solved by the Invention) Heretofore, there have been almost no reports on wasp larvae, particularly on saliva secreted by the larvae, and their composition has not been elucidated at all. It was also completely unclear what nutrition contributed to the muscular sustainability of the hornet.

The present inventors studied the saliva secreted by various hornet larvae, clarified its composition,
They have found that the composition acts as a very effective muscle sustaining agent, and have elucidated the active ingredient. The composition is an amino acid composition containing almost no aspartic acid or glutamic acid contained in a relatively large amount in a normal protein or its hydrolyzate, and is mainly composed of proline and glycine, and has an effect of regulating lipid metabolism. Was found to have.

The present inventors have found that, among the components of the amino acid composition described above, proline and threonine in particular have a lipid metabolism regulating action even without containing methionine, and have completed the present invention.

(Means for Solving the Problems) That is, an object of the present invention is to provide a lipid metabolism regulator characterized by containing proline and / or threonine as an active ingredient and not containing methionine.

The proline and threonine contained in the lipid metabolism regulator of the present invention are preferably L-proline and L-threonine, respectively.

In producing the lipid metabolism regulator of the present invention, commercially available proline and threonine may be used, and both may be used in a mixture at an arbitrary ratio. Usually, it may be manufactured in powder form, but when a mixture is used, both are mixed in a powder state, or proline and threonine are dissolved in distilled water, or after mixing both solutions, water is distilled off. It may be manufactured. The lipid metabolism regulator of the present invention is preferably produced at room temperature or lower.

Lipid metabolism modulators of the present invention do not express no toxicity even 20 g / kg when orally administered to mice, LD ₅₀ is around the top far the 20 g / kg.

The lipid metabolism regulator of the present invention is a blood free fatty acid regulator,
It is useful as a medicine such as a liver fat metabolism regulator and a fat body fat metabolism regulator, and as a food such as a beverage. The dosage form when used as a medicament is not particularly limited, but oral administration,
It can be via a common route of administration, such as rectal administration, injection, or administration by infusion. For oral administration, mix with a pharmaceutically acceptable carrier, excipient, diluent, etc.
It may be used as powders, granules, tablets, capsules, troches, syrups and the like. Solid powders and tablets may take time to be absorbed, so that it is preferable to add appropriate additives such as salts such as sodium chloride, a pH adjuster, a chelating agent and the like, and administer the solution as an aqueous solution. Other amino acids, water-soluble vitamins, acids such as citric acid may be added to the lipid metabolism regulator of the present invention, and drinks such as soft drinks, powdered drinks, and tonics are added with an appropriate flavor. Alternatively, it may be a beverage as a pharmaceutical for nutritional supplementation. Injections may be prepared by adding an appropriate buffer, isotonic agent and the like and dissolving in sterile distilled water, for example, by intravenous drip infusion.

Since the lipid metabolism regulator of the present invention has extremely low toxicity, its dosage can be set in a very wide range. Further, although it varies depending on the administration method and purpose of use, it is usually 0.5 to 5 g at a time, preferably 1 to 5 at a time. The daily dose is preferably 1 to 20 g, and more preferably 4 to 10 g. When these solutions are used, a single dose may be 10 to 1000 ml as a 0.5 to 10 wt% solution, preferably 100 to 400 ml as a 1 to 4 wt% solution. 0.5 to 2 wt% solution for injection
It is sufficient to administer 10 to 500 ml, preferably 100 to 300 ml per administration.

Example Proline and threonine were tested for their lipid metabolism regulating action.

Experimental method (1) Quantification of blood free fatty acids 2% proline, glycine, threonine, leucine, serine, and 20% glucose were used as samples.
Mice (6 weeks old) administered 37.5 μm per body weight were immediately anesthetized with ether after 60 minutes of forced load swimming (0.3 g load), and laparotomy and blood collection from the abdominal vena cava were performed.

The collected blood was centrifuged to remove blood cell components.

The supernatant after centrifugation was subjected to fatty acid determination using a clinical reagent manufactured by Wako Pure Chemical Industries, Ltd. based on a conventional method. Fatty acids were quantified by reacting hydrogen peroxide generated by the action of acyl-CoA synthase and acyl-CoA oxidase with peroxidase, and then coloring ethyl-N-aniline and 4-aminoampirin to absorb light at 550 nm. Was measured.

(2) Determination of Free Fatty Acid from Fat Body ・ Fat body of rat 200mg ・ Buffer solution (0.5M NaPB pH7.56: Ringer solution = 9: 1) 200μ ・ Albumin (BSA) solution (100mg / ml) 200 μm 1 mM CaCl ₂ (final concentration) 50 μl Proline and adrenaline were added thereto and reacted at 37 ° C., and the free fatty acids after 15, 30, 60 and 120 minutes were measured. The fat pad used was Wistar rat (6 weeks old) 180
Removed from ~ 200g.

(3) Measurement of Free Fatty Acid from Liver Fully phlebotomized rat liver (Wistar strain, 180-200
g), and add 40% rat serum or 40 mg / ml BSA to Kreps-Ringer solution, add proline to 2 mg / ml, react at 37 ° C, and change the free fatty acid The amount was measured.

Results (1) Changes in Blood Fatty Acid Level In order to clarify the effects of proline and threonine on the regulation of lipid metabolism, the fatty acid level was measured after standing and forced swimming after administration.

The control of the water administration group was 0.87 mEq /
It became 1.55mEq / after swimming for 60 minutes. Fatty acid value of the proline administration group was 0.87 mEq / for 60 minutes standing, and 1.76 mE for 60 minutes swimming
q /, in the glycine administration group, 0.90 mEq / in 60 minutes of standing, 1.39 mEq / in 60 minutes of swimming, and in 60 minutes of standing in the threonine administration group
0.72 mEq /, 1.70 mEq / for 60 min swimming, 0.84 mEq / for 60 min standing in leucine administration group, 1.46 mEq / for 60 min swimming,
0.83 mEq / for 60 minutes standing in the serine administration group, 60 minutes swimming
It was 1.43 mEq /. In the 20% glucose-administered group, the concentration was 0.64 mEq / for 60 minutes of standing and 1.05 mEq / for 60 minutes of swimming. In the proline and threonine administration groups, fatty acids were released more significantly than the control (FIG. 1).

(2) Release of Fatty Acid from Fat Body Conventionally, it is known that adrenaline activates adrenaline-sensitive lipase in fat body to decompose fat and release fatty acid, but similar results are obtained in this experiment. (FIG. 2). When proline was reacted in place of adrenaline under the same conditions, release of fatty acids higher than that of the control but lower than that of adrenaline was observed (FIG. 2). These results indicate that proline has the effect of releasing fatty acids from fat bodies.

(3) Release of Fatty Acid from Liver Since proline showed an action of increasing the free fatty acid level in blood, the release of fatty acid was also measured for the liver. When the liver slices were examined for the release of fatty acids by the addition of proline with a medium containing BSA as a main component, the values were slightly higher than those of the control with the lapse of time (FIG. 3).
When the main component of the medium was changed from BSA to rat serum, the action of proline was greatly increased, and significant release of fatty acids was detected. This suggests that liver tissue maintains a stable activity with respect to serum and that serum has an effect of promoting fatty acid release by proline. The above results indicate that proline releases fatty acids from liver tissue. And it is clear that blood free fatty acids, which are increased by proline, are mobilized from the fat body and liver.

[Brief description of the drawings]

FIG. 1 shows the effects of proline and threonine on blood free fatty acid levels during swimming. FIG. 2 shows the effect of proline on the release of fatty acids from fat bodies. FIG. 3 shows the effect on the release of fatty acids from the liver.

────────────────────────────────────────────────── ─── Continuing on the front page (72) Inventor Yoshizo Takiguchi 2-6-3 Otemachi, Chiyoda-ku, Tokyo Nippon Steel Corporation (56) References JP-A-4-112825 (JP, A) (58) Field surveyed (Int. Cl. ⁷ , DB name) A61K 31/198, 31/401 A23L 1/305

Claims (5)

(57) [Claims] 1. A lipid metabolism regulator comprising proline and / or threonine but not methionine. 2. A blood free fatty acid regulator comprising the lipid metabolism regulator according to claim 1 as an active ingredient. 3. A fat body fat metabolism regulator comprising the lipid metabolism regulator according to claim 1 as an active ingredient. 4. A hepatic fat metabolism regulator comprising the lipid metabolism regulator according to claim 1 as an active ingredient. 5. A food comprising the lipid metabolism regulator according to claim 1 as an active ingredient.