JP2002275059A - Amino acid composition for improving renal dysfunction - Google Patents

Abstract

(57) [Problem] To administer a conventional synthetic drug for improving renal dysfunction, the risk of side effects is large, and satisfactory results have not been obtained. An object of the present invention is to provide a naturally occurring amino acid composition having a remarkable renal dysfunction-improving activity and having substantially no side effects. SOLUTION: The amino acid composition for improving renal dysfunction comprising threonine, proline, glycine, valine, isoleucine, leucine, tyrosine, phenylalanine, lysine, aspartic acid, serine, glutamic acid, alanine, methionine, tryptophan, histidine and arginine. Or an amino acid solution. This amino acid composition has a low urea nitrogen concentration which is an index of the renal dysfunction improving action,
Furthermore, both acute poisoning mortality and knockdown rate are low, and when this amino acid composition is used, renal dysfunction is less likely to appear,
In addition, even if it appears, the obstacle is relatively easily improved.

Description

DETAILED DESCRIPTION OF THE INVENTION

[0001]

The present invention relates to an amino acid composition and an amino acid composition solution having a remarkable ameliorating effect on renal dysfunction, and more particularly to wasp (Vespa).
The present invention relates to an amino acid composition and an amino acid composition solution which are contained in saliva secreted by the larva of the genus) and can be effectively administered to patients with renal dysfunction.

[0002]

2. Description of the Related Art The present inventors have studied the saliva secreted by wasp larvae, clarified the composition of the amino acid composition contained therein, and studied the use thereof. As a result, it has been found that, out of the numerous amino acid compositions contained in the saliva, an amino acid composition designated as VAAM exhibits a motor function-enhancing effect (Japanese Patent No. 2518692). This hyperactivity effect includes
Includes sustained muscle strength, nourishment, nutrition, and recovery from fatigue.

[0003]

On the other hand, the kidney, which is a kind of organ, has a function of filtering urine in blood and excreting it outside the body. If the kidneys having such functions continue to be inexorable, such as drinking, smoking, or staying up late, an excessive burden is imposed, and the kidneys may suffer from renal failure including renal cancer.

Conventionally, these diseases have been dealt with by administering synthetic drugs to patients. However, such synthetic drugs are usually toxic even if they have excellent efficacy, and their renal function is improved. However, it also has the disadvantage that side effects are easily exerted on other organs and do not lead to a fundamental healing. Therefore, an object of the present invention is to provide an amino acid composition and an amino acid composition solution having a remarkable renal dysfunction-improving action and having substantially no side effects.

[0005]

SUMMARY OF THE INVENTION The present invention provides threonine,
Proline, glycine, valine, isoleucine, leucine, tyrosine, phenylalanine, lysine, aspartic acid, serine, glutamic acid, alanine, methionine,
An amino acid composition for improving renal dysfunction, comprising tryptophan, histidine and arginine. An amino acid composition obtained by removing tryptophan from such a composition also has a renal dysfunction improving effect. Furthermore, the present invention includes an amino acid composition solution, preferably an aqueous solution, having substantially the same composition as these compositions in the liquid phase.
Each amino acid has a specific preferred proportion.

Hereinafter, the present invention will be described in detail. As described above, it has been clarified that VAAM has a motility-enhancing action with a complicated mechanism of action and enhances lipid metabolism. The present inventors have studied in detail whether such a motor function-enhancing action of VAAM effectively affects the improvement of other diseases that are not directly linked to the motor function-enhancing action. The kidney has the function as described above, especially when performing intense exercise for a long time, regulating circulatory functions such as blood pressure,
Closely related to the excretion of waste products produced by exercise, renal hyperfunction is indispensable for hyperactivity of all organs. If alcohol is consumed excessively, waste products tend to accumulate in the kidneys, and renal dysfunction may appear if function is not properly enhanced. Furthermore, renal dysfunction may worsen and become incurable if not properly addressed after renal dysfunction has appeared.

The inventors of the present invention administer a VAAM having a specific composition (having a composition different from known VAAMs) to a patient having such renal dysfunction or to a healthy person before renal dysfunction appears. As a result, the present inventors have found that renal dysfunction can be improved or the appearance of renal dysfunction can be suppressed, and the present invention has been achieved. The first amino acid composition (hereinafter referred to as the first invention) according to the present invention contains 17 kinds of amino acids as essential components, and it is particularly preferable that each amino acid is contained at a specific composition ratio. That is, 2-15 mol of threonine, 4-30 mol of proline, 7-20 mol of glycine, 4-8 mol of valine, 3-9 mol of isoleucine.
Mol, leucine 2-12 mol, tyrosine 1-9 mol, phenylalanine 0.5-5 mol, lysine 5-11 mol, aspartic acid 0.1-5 mol, serine 0.1-5 mol, glutamic acid 0.1-4 mol, alanine 0.1-12 mol , Methionine 0.1
-5 mol, tryptophan 0.1-5 mol, histidine 0.1
It is preferable to contain the compound in an amount of about 5 to 5 mol and 0.1 to 5 mol of arginine. In addition, it may contain amino acids other than those described above, water-soluble vitamins, acids such as citric acid, or other small amounts of additives.

The second amino acid composition according to the present invention (hereinafter referred to as the second invention) contains 16 kinds of amino acids as essential components at a specific composition ratio, and excludes tryptophan from the amino acid composition of the first invention. This tryptophan-free amino acid composition also has a renal dysfunction-improving activity equivalent to or slightly inferior to that of the first invention. Preferably, each amino acid is an L-amino acid. The amino acid compositions of the first and second inventions may be taken in powder form or may be dissolved in water and taken as an aqueous solution or the like. The ingestion method can also be administered via general administration routes such as oral administration, rectal administration, intravenous injection, and infusion.

In the case of oral administration, in addition to administering the composition itself, it is mixed with pharmaceutically acceptable carriers, excipients, and diluents and used as powders, granules, tablets, capsules, troches and the like. May be. However, solid powders and tablets may take time to be absorbed, so oral administration of the composition itself is desirable. In this case, it may be administered as the above-mentioned solution together with a suitable additive, for example, a salt such as sodium chloride, a pH adjusting agent, and a chelating agent. When used as an injection, a solution prepared by adding an appropriate buffer or isotonic agent and dissolving it in sterilized distilled water may be used.

The timing of ingestion is not particularly limited, and it can be taken at any time before and after the onset of renal dysfunction.
It is preferably taken as a powdered beverage, a beverage as a medicinal product for nutritional tonicity or nutritional supplementation). Since the amino acid composition of the present invention has low toxicity, its dosage can be set widely, and it is usually taken once depending on the administration method and purpose of use.
0.5-5 g, preferably 1-2 g at a time, 1-20 g / day
g, preferably 4 to 10 g. When administered or ingested as a solution, it is administered or ingested as a solution of about 0.5 to 10% by weight at a time, 10 to 1000 ml at a time, preferably 100 to 400 ml at a time as a 1 to 4% by weight.

As will be apparent from the examples described below, the amino acid compositions of the first and second inventions have remarkable inhibitory and curative effects on renal dysfunction, and the amino acid compositions are naturally occurring. Since it is derived from amino acids, it has low toxicity and has an extremely effective renal dysfunction improving effect. The amino acid composition of the present invention may be used as a solution as described above, particularly as an aqueous solution. In this case, the composition of the first or second invention may be directly dissolved in water to prepare a solution, or Individual amino acids may be separately dissolved in water to achieve the above composition in solution.

[0012]

Next, Examples and Comparative Examples relating to the test for improving renal dysfunction of the amino acid composition according to the present invention will be described, but these do not limit the present invention. Before describing individual examples and the like relating to the amino acid composition, measurement of the concentration of each substance of urea nitrogen used in each Example and Comparative Example will be described.

[0013] In the measurement embodiment urea nitrogen were determined the expression and healing of renal dysfunction with urea nitrogen. Urea is the final metabolite of nitrogen-containing substances, along with creatinine and uric acid, and is excreted mainly through the kidneys. Therefore, measurement of urea is an important index for diagnosing renal dysfunction and observing the course of treatment. Note that a clinical diagnostic kit manufactured by Wako Pure Chemical Industries, Ltd. was used for the measurement of urea nitrogen.

Measurement of urea nitrogen The following reagents were used for measurement of urea nitrogen. Color concentrate A phosphoric acid 6 mol / liter thiosemicarbazide 0.66 mmol / l iron alum color concentrate B diacetyl oxime 59 mmol / l destaining solution of potassium permanganate 0.2 mol / l standard solution of urea nitrogen 50 mg / dl

Next, the principle of measuring urea nitrogen using such a reagent will be described. When a coloring reagent containing diacetyl monooxime and thiosemicarbazide which is strongly acidic and is added to the sample to be measured and heated in a boiling water bath, urea in the sample turns red. By measuring the red absorbance, the concentration of urea nitrogen in the sample is calculated.

Urea nitrogen measurement method Urea nitrogen was measured as follows. 0.004m sample
1m of the color reagent solution (color solution A: color solution B = 5: 1)
l added. Shake well and in a boiling water bath 2
Heat for 5 minutes. Cooled immediately in running water for 2-3 minutes.
As a control, 530n of the sample to be measured and the standard sample
The absorbance at m was measured with a spectrophotometer. Urea nitrogen concentration of a sample to be measured was measured using a calibration curve created using a standard sample.

Next, using the above-described measurement method, the effect of various amino acid compositions on the improvement of renal dysfunction was confirmed.

Examples 1 and 2 and Comparative Examples 1 to 10 A group of 5 male to 6-week-old ddy mice (SPF) was bred in a clean room while being fed a normal diet with unlimited feeding. In Examples 1 and 2 and Comparative Examples 1 to 10, the same nutrient solution was administered to 10 to 12 mice, respectively. A nutrient solution containing a composition (VAAM) having 17 kinds of amino acids in a predetermined composition shown in the column of Example 1 of Table 1 was prepared by mixing commercially available amino acids and dissolving in water. This nutrient solution was orally administered to the mouse every 12 hours at a concentration of 37.5 μl / g body weight. The administration was carried out under these conditions from the first to the fifth administration, and at the sixth administration, the same amount of 25% ethanol was administered in place of the nutrient solution to forcibly cause alcoholic renal dysfunction. The administration was stopped, and blood was collected from the abdominal vena cava 12 hours after ethanol administration. The blood was allowed to stand at room temperature for 30 minutes after blood collection, and then the serum was centrifuged, and the urea nitrogen concentration was measured by the method described above.

Instead of the VAAM of the first embodiment, V-Trp
(Example 2), CAAM (Comparative Example 1), V-1 (Comparative Example 2), V-9 (Comparative Example 3), V-Tyr (Comparative Example 4), and V-Lys (Comparative Example 5) were implemented. The mice were administered under the same conditions as in Example 1 and the urea nitrogen concentration was measured 12 hours after administration of 25% ethanol. Although not shown in the table,
D. W. (Comparative Example 6, distilled water) 2% Trp (Comparative Example 7,
2% tryptophan aqueous solution), 0.25% Tyr (Comparative Example 8,
0.25% tyrosine aqueous solution), 2% Lys (Comparative Example 9, 2% lysine aqueous solution) and control (Comparative Example 10, amino acid,
Blood was collected from mice bred under the same conditions except that no nutrient solution, water, alcohol, and the like were administered, and the concentration was measured.). The results are shown in the graph of FIG. Further, the acute poisoning mortality of the mice to which each amino acid composition was administered is shown in FIG. 2, and the knockdown rate is shown in the graph of FIG. All measurements were expressed as mean ± standard deviation. The significance test was performed by the Student's t test. A risk rate of 5% or less was determined to have a significant difference. For example, the symbols a to h attached to the urea nitrogen content of each amino acid composition in the graph of FIG. 1 indicate that there is no significant difference in the urea nitrogen content between two or more amino acid compositions having the same code. ing. For example, there is no significant difference between VAAM and V-Trp because they both have the sign a. W.
Since there is no common sign between and, it indicates that there is a significant difference in the amount of urea nitrogen between the two.

[0020]

[Table 1]

Considerations for Examples 1-2 and Comparative Examples 1-10
The amino acid composition of observation Examples and Comparative Examples, VAAM of Example 1 urea nitrogen is lower than the rest of which amino acid composition. V-Trp was lower than VAAM after the control except for the control, and it was revealed that the amino acid composition containing no tryptophan has a high effect of improving renal dysfunction. In the acute poisoning mortality shown in FIG. 2, V-Ty
r was 0, VAAM and CAAM were just over 5%. 2% T
rp and V-Lys exceed 15%, V-Trp reaches 20%, and V
-9 was over 20%. Further, D. W. Reaches 25% and V-
1 reached around 30%. Thus, VAAM was less toxic than other amino acid compositions.

In the knockdown rate shown in FIG.
M was the lowest, and the knockdown rate of other amino acid compositions reached 2.5 to 7 times that of VAAM. In particular, in the case of V-Tyr having a mortality of 0, the knockdown rate reached almost 70%, which was the highest. These results indicate that VAAM is the best inhibitor of acute alcoholism. It was revealed that the effect of improving renal dysfunction was high. Thus, the acute toxicity poisoning mortality and the knockdown rate of the mice shown in FIGS. 2 and 3, respectively, were lowest for VAAM (V-Tyr).
Mortality rate of acute poisoning), about 6% and about 11%, respectively
Met. Regarding the above-mentioned V-Trp, the acute poisoning mortality and the knockdown rate were not so low at 20% and 30%, respectively, and the renal dysfunction improving effect was excellent, but the toxicity was not at a satisfactory level. However, this toxicity was also superior to many other amino acid compositions.

From the above results, it is clear that VAAM suppresses renal dysfunction caused by alcohol more remarkably than other amino acid compositions, and at the same time, restores the function of the whole individual. V-Trp, which is a composition obtained by removing tryptophan from VAAM, has an effect of improving renal dysfunction, though not as much as VAAM. However, it was found that when the amino acid was further removed, the renal dysfunction improving effect was weakened and did not have a sufficient improving effect.

[0024]

The present invention provides threonine, proline, glycine, valine, isoleucine, leucine, tyrosine, phenylalanine, lysine, aspartic acid, serine, glutamic acid, alanine, methionine, tryptophan,
An amino acid composition or an amino acid solution for improving renal dysfunction, comprising histidine and arginine (claim 1), wherein each amino acid is threonine 2-15.
Mol, proline 4-30 mol, glycine 7-20 mol, valine 4-8 mol, isoleucine 3-9 mol, leucine 2
12 mol, tyrosine 1-9 mol, phenylalanine 0.5-
5 mol, lysine 5-11 mol, aspartic acid 0.1-5 mol, serine 0.1-5 mol, glutamic acid 0.1-4 mol, alanine 0.1-12 mol, methionine 0.1-5 mol, tryptophan 0.1-5 mol, histidine 0.1-5 mol Molar and arginine are particularly preferably contained in a proportion of 0.1 to 5 mol (claim 2). Compared with other amino acid compositions, this amino acid composition and its solution have a lower urea nitrogen concentration, which is an index of the renal dysfunction improving effect, and further have lower acute poisoning mortality and knockdown rate. When an object is used, renal dysfunction is less likely to occur, and even if it does, the disorder is relatively easily improved.

When one or more amino acids are removed from the amino acid composition, the above-mentioned effect of improving renal dysfunction is less likely to be exhibited, except for an amino acid composition or an amino acid solution from which only tryptophan has been removed (Claim 3). Although not as effective as the amino acid composition or solution according to claim 1, it has a renal dysfunction improving effect and can be used sufficiently depending on the degree of renal dysfunction. It is desirable that this amino acid composition also contains each amino acid in the same ratio as in claim 2 except for tryptophan (claim 4). Although the amino acid composition of the present invention is effective for improving renal dysfunction in general, it can be used particularly effectively for alcoholic renal dysfunction (claim 5).

[Brief description of the drawings]

FIG. 1 is a graph showing the concentration of urea nitrogen when each amino acid composition is administered to a group of mice in which alcoholic renal dysfunction has occurred.

FIG. 2 is a graph showing acute poisoning mortality when each amino acid composition was administered to a group of mice in which alcoholic renal dysfunction occurred.

FIG. 3 is a graph showing the knockdown rate when each amino acid composition is administered to a group of mice in which alcoholic renal dysfunction has occurred.

 ────────────────────────────────────────────────── ─── Continuing on the front page (72) Inventor Hiroshi Tsuchida 1-6-6 Hoyacho, Nishi-Tokyo, Tokyo F-term (reference) 4C076 AA11 CC17 4C206 AA01 AA02 FA53 MA03 MA04 MA10 MA37 NA06 ZA81

Claims (5)

[Claims] 1. A renal function comprising threonine, proline, glycine, valine, isoleucine, leucine, tyrosine, phenylalanine, lysine, aspartic acid, serine, glutamic acid, alanine, methionine, tryptophan, histidine and arginine. Amino acid composition or amino acid solution for improving disorder. 2. The method of claim 1, wherein each amino acid is 2 to 15 moles of threonine,
Proline 4 to 30 mol, glycine 7 to 20 mol, valine 4 to
8 mol, isoleucine 3-9 mol, leucine 2-12 mol, tyrosine 1-9 mol, phenylalanine 0.5-5 mol, lysine 5-11 mol, aspartic acid 0.1-5 mol,
Serine 0.1-5 mol, glutamic acid 0.1-4 mol, alanine 0.1-12 mol, methionine 0.1-5 mol, tryptophan 0.1-5 mol, histidine 0.1-5 mol and arginine
2. The amino acid composition or amino acid solution for improving renal dysfunction according to claim 1, comprising 0.1 to 5 mol. 3. A tryptophan-free kidney comprising threonine, proline, glycine, valine, isoleucine, leucine, tyrosine, phenylalanine, lysine, aspartic acid, serine, glutamic acid, alanine, methionine, histidine and arginine. Amino acid composition or amino acid solution for improving dysfunction. 4. The method of claim 1, wherein each amino acid is 2 to 15 moles of threonine,
Proline 4 to 30 mol, glycine 7 to 20 mol, valine 4 to
8 mol, isoleucine 3-9 mol, leucine 2-12 mol, tyrosine 1-9 mol, phenylalanine 0.5-5 mol, lysine 5-11 mol, aspartic acid 0.1-5 mol,
Serine 0.1-5 mol, glutamic acid 0.1-4 mol, alanine 0.1-12 mol, methionine 0.1-5 mol, histidine 0.
The tryptophan-free amino acid composition or amino acid solution for improving renal dysfunction according to claim 3, comprising 1 to 5 mol of arginine and 0.1 to 5 mol of arginine. 5. The amino acid composition or amino acid solution according to claim 1, which is used for improving alcoholic renal dysfunction.