WO2002074303A1

WO2002074303A1 - Amino acid compositions for ameliorating kidney failure

Info

Publication number: WO2002074303A1
Application number: PCT/JP2002/002501
Authority: WO
Inventors: Takashi Abe; Hiroshi Tsuchita
Original assignee: Riken; Meiji Dairies Corporation
Priority date: 2001-03-15
Filing date: 2002-03-15
Publication date: 2002-09-26
Also published as: JP2002275059A

Abstract

Amino acid compositions or amino acid solutions for ameliorating kidney failure characterized by containing threonine, proline, glycine, valine, isoleucine, leucine, tyrosine, phenylalanine, lysine, aspartic acid, serine, glutamic acid, alanine, methionine, tryptophan, histidine and arginine; and amino acid compositions or amino acid solutions deleting tryptophan from the above-described ones. These amino acid compositions show a low urea nitrogen level, which is an indication of the effect of ameliorating kidney failure, and a low acute toxication mortality and a low knockdown ratio. In case of using these amino acid compositions, kidney failure scarcely outbreaks or, if any, can be relatively easily ameliorated.

Description

Amino acid composition for knowledge of renal impairment

TECHNICAL FIELD 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 a patient with renal dysfunction contained in saliva secreted by a hornet (Vespa) larva. The present invention relates to an amino acid composition and an amino acid composition solution that can be effectively administered to an animal. Background of the Invention

The present inventors have heretofore clarified the composition of the amino acid composition contained in the saliva secreted by the larvae of the larva of Poa annua, and have been studying its use.

As a result, it was found that among the many amino acid compositions contained in the saliva, the amino acid composition designated as VAAM exhibited a motor function redaction (Patent No. 2518692). Includes sustained muscle strength, nourishment, nourishment, and recovery from fatigue.

On the other hand, the kidney, a type of H storage device, has the function of filtering out urine components in blood and excreting it outside the body. The kidney, which plays such a role, may overload and suffer from renal insufficiency, including renal cancer, when drinking, smoking, staying up late, etc.

Conventionally, these diseases have been treated by administering synthetic drugs to patients, but these synthetic drugs are usually toxic even if they have excellent medicinal properties, and even if their kidney functions are improved 碰! It has the disadvantage that it does not lead to a radical cure. Disclosure of the invention Accordingly, 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 activity and having substantially no side effects.

The present invention is characterized in that it comprises threonine, proline, glycine, norin, isoleucine, leucine, thioxacin, phenylalanine, lysine, aspartic acid, serine, glutamic acid, alanine, methionine, tributofan, histidine and arginine. It is an amino acid composition for relieving renal dysfunction, and an amino acid composition obtained by removing tributophan from such a composition also has an effect of improving renal dysfunction. Further, the present invention includes an amino acid composition solution, preferably a solution, having substantially the same composition as these compositions in the liquid phase. Each amino acid has a specific preferred ratio of H bonds.

As mentioned above, it has been clarified that VAAM has a motility-enhancing effect as an apparent mechanism of action and enhances lipid metabolism. The present inventors have elucidated in detail whether or not such a motility male action by VA AM effectively acts on improvement of other diseases that are not directly linked to a motility male action. investigated.

The kidneys have the same functions as described above, especially when performing intense exercise for a long time, and have a close relationship with the regulation of blood pressure and other circulatory functions and the discharge of waste products produced by exercise. Enhancement is integral to the function of total rise: ¾t. In addition, when alcohol is consumed excessively, there is a tendency for the accumulation of aging in the kidneys, and renal dysfunction may occur if the function is not properly enhanced. Furthermore, if renal dysfunction is not properly dealt with after renal dysfunction, renal dysfunction may be incomplete and unrecoverable.

The present inventors have proposed to administer a VAAM having a specific composition (having a composition different from that of a known VAAM) to such a patient having renal dysfunction or to a healthy subject before renal dysfunction appears. However, they have found that the renal dysfunction is improved or that the occurrence of renal dysfunction can be suppressed, and the present invention has been achieved. ,

The first depleted amino acid according to the present invention (hereinafter referred to as the first invention) contains 17 kinds of amino acids as essential components, and each amino acid is particularly contained in a specific set. desirable. So threonine 2-15 moles, proline 4-30 moles, glycine? -20 mol, valine 4-8 mol, isoleucine 3-9 mol, leucine 2-12 mol, tyrosine 1-9 mol, phenylealanine 0.5-5 mol, lysine 5-11 mol, aspartic acid 0.1 ~ 5 moles, serine 0.1 ~ 5mol, glutamic acid 0.1 ~ 4mol, alanine 0.1 ~ 12mol, methionine 0.1 ~ 5mol, tryptophan 0.1 ~ 5mol, histidine 0,1 ~ 5 Mol and arginine in a ratio of 0.1 to 5 mol, and may contain amino acids other than the above, water-soluble vitamins, acids such as citric acid, or other small amounts of additives. good.

The second amino acid composition according to the present invention (hereinafter referred to as the second invention) contains 16 kinds of amino acids as an essential component in a specific composition ratio, and a thread obtained by removing tributophan from the amino acid composition of the first invention. This tributophan-free amino acid composition also has the same or slightly inferior renal dysfunction as the first invention. Each amino acid is L-amino acid.

The amino acid composition and the solution thereof according to the first and second inventions have a lower urea nitrogen concentration, which is an index for renal dysfunction, as compared to other amino acid exfoliated substances, and further have acute poisoning. Both mortality and knockdown rates are low, and the use of this amino acid composition makes it difficult to observe renal function and even relatively easily improves the disorder if it appears.

If one or more amino acids are removed from the amino acid composition of the first invention, the above-mentioned renal dysfunction is less likely to be improved, but the amino acid composition or the amino acid solution from which only tryptophan has been removed (second invention) Is an exception, and although not as good as the amino acid composition or solution of the first invention, it has a renal dysfunction, and can be used sufficiently depending on the degree of renal dysfunction. It is desirable that this amino acid compound also contains each amino acid in the same ratio as in the first invention except for tributophan.

The amino acid composition of the present invention can be used for improving renal dysfunction in general, but can be used for / for especially aryleic renal dysfunction.

The amino acid compositions of the first and second inventions dissolve in water even when ingested as a powder, It may be taken as a solution or the like. The ingestion method can also be administered via a suitable administration route such as oral administration, rectal administration, intravenous injection, and infusion.

In the case of oral administration, in addition to administration of the composition itself, it may be mixed with pharmaceutically acceptable carriers, excipients, and diluents, and used as a powder, granule, m-pouch (troche, etc.) However, solid powders and tablets may take some time to absorb, so the oral administration of the composition itself may be difficult, in which case suitable excipients, for example salts such as sodium chloride, pH modifiers When used as an injection, it may be dissolved in sterile distilled water after adding an appropriate slow-release or isotonic agent.

The timing of ingestion is not particularly limited, and it can be taken at any time before and after renal dysfunction appears. It is preferable to ingest as a drink as a drug for the purpose of). Since the amino acid composition of the present invention has low toxicity, its dosage can be set widely, and it is usually 0.5 to 5 g at a time, preferably 1 to 5 at a time, depending on the administration method and purpose of use. 2 g, 1 to 20 g, preferably 4 to 10 g per day. When administered or ingested as a solution, the solution 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 1 to 4% by weight at a time, 100 to 400 ml.

As is clear from the examples of the present invention, the amino acid compositions of the first and second inventions have a remarkable inhibitory and healing effect on renal dysfunction, and the amino acid compositions are naturally occurring amino acids. Since it is derived from acid, it has low toxicity and has an extremely effective renal dysfunction improving effect.

As described above, the amino acid composition of the present invention may be used as a solution, particularly as an aqueous solution. In this case, the solution of the first or second invention may be dissolved in water to prepare a solution. Alternatively, the above-mentioned composition may be realized in a solution by separately dissolving the individual amino acids in water. BRIEF DESCRIPTION OF THE FIGURES FIG. 1 is a graph showing the concentration of urea nitrogen when each amino acid composition was administered to a group of mice in which alcoholic renal dysfunction had occurred.

FIG. 2 is a graph showing the 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 was administered to a group of mice in which alcoholic renal dysfunction occurred. BEST MODE FOR CARRYING OUT THE INVENTION

Next, Examples and Comparative Examples relating to the test for improving renal dysfunction of the amino acid composition according to the present invention are described, but these are not intended to 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.

[Measurement of urea nitrogen]

In this example, the occurrence of renal dysfunction and healing were determined using urea nitrogen. Urea, along with creatinine and uric acid, is the most important product of nitrogen-containing substances and is excreted mainly through the kidneys. Therefore, measurement of urea is an important index for diagnosing renal dysfunction and observing the course of initial therapy.

In addition, a clinical diagnostic kit of Wako Pure Chemical Industries, Ltd. was used for measurement of urea nitrogen.

Measurement of urea nitrogen ·

Measurement of urea nitrogen The following reagents were used.

Chromogenic solution A

Phosphoric acid 6 mol / liter

Thiosemicarbazide 0.66 mmol liter

Iron alum Chromogenic stock solution B

Diacetyl monooxime 59 millimoles Z lit

Decolorizing liquid

Potassium permanganate 0.2 mol Z liter

50 mg / dl Next, the principle of measuring urea nitrogen using such a reagent will be described.

When a color reagent containing diacetyl monoxime and thiosemicarbazide, which is strongly acidic, is added to the sample and heated in a boiling water bath, the urea in the sample turns red. By measuring the red PJ¾¾ concentration, the urea nitrogen J¾ in the sample is calculated. Measurement of urea nitrogen

The measurement of urea nitrogen was performed as follows.

To the sample 0.001 was added 1 ml of a color developing solution (color developing solution A: color developing solution B = 5: 1). Shake well and heat in a vigorously boiling water bath for 25 minutes. Cooled immediately in running water for 2-3 minutes. Using the blinded reagent as a control, the measured values of the measured sample and the standard sample at 530 were measured with a photometer.

The urea nitrogen key of the measurement sample was measured using a line created using a standard sample.

Next, using the above-mentioned measurement method, the quality of the renal dysfunction of each amino acid composition was confirmed. Examples 1 and 2 and Comparative Examples;

6 to 8 week old ddy male mice (SPF) are given in groups of 5 and fed with unlimited feed ^ !? They were raised in a clean room. In Example 2 and Comparative Examples 1 to 10, the same ^^ night was administered to 10 to 12 mice, respectively.

A sickle night containing a composition (VAAM) of 17 kinds of amino acids having a predetermined composition shown in the column of Example 1 in Table 1 was prepared by mixing commercially available amino acids and dissolving in water. . This test was orally administered to a disgusting mouse every 12 hours at a dose of 37.5 1 / g body weight. The administration was carried out under these conditions from the first to the fifth administration, and the sixth administration was forcibly induced alcoholic renal dysfunction by administering the same amount of 25% ethanol instead of the nutrient solution. The administration was stopped, and 12 hours after the ethanol administration, the abdominal vena cava was removed. The blood was allowed to stand at room temperature for 30 minutes afterwards, the supernatant was centrifuged, and the urea nitrogen concentration was measured as described above.

Instead of VAAM of Example 1, 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 administered to a mouse under the same conditions as in Example 1 and the strength was 25%. The urea nitrogen boat was measured 12 hours after throwing ethanol. Although not shown in the table, DW (Comparative Example 6, distilled water), 2% Trp (Comparative Example 7, 2% tributophan aqueous solution), 0.25% Tyr (Comparative Example 8, 0.25% tyrosine aqueous solution) )., 2% Lys (Comparative Example 9, 2% lysine in water and control (Comparative Example 10, amino acids, eel, water and alcohol, etc.) And the concentration was measured).

The results are shown in the graph of FIG.

Furthermore, the acute poisoning mortality of mice treated with each amino acid composition is shown in Fig. 2 \ Z

Are shown in the graph of FIG.

All measurements were expressed as mean standard deviation. Test for significance

went. A risk rate of 5% or less was determined to be significant.

For example, the symbols a to h attached to the amount of urea tt element in each amino acid composition in the graph of Fig. 1 indicate that there is no significant difference in the amount of urea nitrogen between two or more amino acid compositions having the same sign. ing. For example, there is no significant difference between VAAM and V— Since there is no common sign between M and DW, there is a significant difference in the amount of urea nitrogen between the two;

table 1

Discussion on Examples 1-2 and Comparative Examples 1-10

Among the amino acid compositions of Examples and Comparative Examples, VAAM of Example 1 had significantly lower urea nitrogen than any of the remaining amino acid compositions except for the control and V-Trp. It has been clarified that the amino acid composition containing no tryptophan has a high effect of improving renal function. The acute poisoning mortality shown in Figure 2 was zero for V-Tyr and slightly more than 5% for VAAM and CAAM. 2% Tru and V-Lys exceeded 15%, V-Trp reached 20%, and V-9 exceeded 20%. D. W. reached 25%, and V-1 reached around 30%. Thus, VAAM was less toxic than other amino acid compositions.

In the knockdown rate shown in FIG. 3, VAAM was the lowest, and the knockdown rate of other amino acid compositions reached 2.5 to 7 times that of VAAM. Especially in V-Tyr where mortality was 0 The highest downtime rate was reached, reaching nearly 70%. These results indicate that VAAM is the best at controlling acute alcohol poisoning. It became clear that renal dysfunction was good.

Thus, the acute poisoning mortality and knockdown rate of the mice shown in Figures 2 and 3, respectively, were the lowest in VAAM (excluding the acute poisoning mortality in V-Tyr), with about 6% and about 11%, respectively. there were. Acute poisoning mortality rate and knockdown rate are as low as 20% and 30%, respectively, for V-Trp as described above. The effect of improving renal dysfunction is excellent, but the level of toxicity is satisfactory. However, it was also superior to many other amino acid compositions in this toxicity.

Taken together, it is clear that VAAM suppresses alcohol-induced renal dysfunction more markedly than other amino acid compositions, and at the same time restores the function of the entire individual. V—Trp, which is a composition obtained by removing tributane from VAAM, is

Although not as effective as VAAM, it has an effect of improving renal dysfunction. However, it was found that when amino acids were further removed, the renal dysfunction was reduced and the use was not sufficiently improved.

Claims

I '0 Claims

1. A renal dysfunction characterized by comprising threonine, proline, glycine, paline, isoleucine, leucine, tyrosine, phenylalanine, lysine, aspartic acid, serine, glutamic acid, alanine, methionine, tributofan, histidine and arginine. Amino acid composition or amino acid solution for use. '

2. For each amino acid, 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, Hue Dilualanine 0.5-5 mol, lysine 5-11 mol, aspartic acid 0.1-5 mol, serine 0.1-1-5 mol, glutamic acid 0.1-4 mol, alanine 0.1-12 mol, methionine 0 The renal dysfunction improving amino acid composition according to claim 1, comprising 1 to 5 mol, tryptophan 0.1 to 5 mol, histidine 0.1 to 5 mol, and arginine 0.1 to 5 mol. Amino acid solution.

3. No tryptophan, characterized by comprising threonine, proline, glycine, valine, isoleucine, leucine, tyrosine, fenilalanine, lysine, aspartic acid, serine, glutamic acid, alanine, methionine, histidine and arginine. Kidney dysfunction Amino acid composition or amino acid solution for female benefit.

4. For each amino acid, threonine 2-15 moles, proline 4-30 moles, glycine 7-20 moles, palin 4-8 moles, isoleucine 3-9 moles, leucine 2-12 moles, tyrosine 1-9 moles, Hue Dilualanine 0.5-5 mol, lysine 5-11 mol, aspartic acid 0.1-5 mol, serine 0.1-1 mol, glutamic acid 0.1-4 mol, alanine 0.1-12 mol, methionine 0 1 to 5 mol, 0.1 to 5 mol of histidine and 0.1 to 5 mol of arginine 4. The amino acid composition or amino acid solution for improving renal dysfunction without tributophan according to claim 3.

5. The amino acid composition or amino acid solution according to any one of claims 1 to 4, which is for improving alcoholic renal function.