JPH06256186A - Amino acid preparation for cancer - Google Patents

Abstract

PURPOSE:To obtain a preparation for improving low-nutrition state of cancer and exhibiting excellent effect on growth control of tumor, comprising D-valine and seven kinds of essential amino acids except L-valine. CONSTITUTION:The preparation comprises D-valine, L-leucine, L-isoleucine, L-lysine, L-methionine, L-phenylalanine, L-threonine and L-tryptophan. The amounts of the amino acids are preferably 1-21g D-valine, 5.2-12g isoleucine, 8.5-17.5g L-leucine, 3.5-21g L-lysine, 0.5-16.5g L-methionine, 0.4-16g L- phenylalanine, 2-9g L-threonine and 0.8-3.6g L-tryptophan based on 100g of the whole amino acids of the preparation. The preparation is usually useful as transfusion solution or enteral solution. The dose of the preparation is preferably 10-70g calculated as the weight of the whole amino acids as a standard daily.

Description

Detailed Description of the Invention

[0001]

TECHNICAL FIELD The present invention relates to an amino acid preparation useful for cancer patients.

[0002]

2. Description of the Related Art Amino acid preparations for cancer patients have been studied for a long time and various formulations have been proposed. For example, those not containing L-methionine (JP-A-55-35)
No. 049), those containing no L-valine (Japanese Patent Laid-Open No. Sho 6-66).
2-135420), those not containing L-isoleucine (JP-A-62-135421) or L
-Excessive arginine (new drug and clinical, 26 (1
0), 1877 (1977)) and the like. These preparations are intended to suppress tumor growth and improve therapeutic effects by administering a nutritionally unbalanced amino acid composition, but it also causes inconvenience to the living body. Therefore, it has the disadvantage that it contributes to the malnutrition of cancer patients, which in turn aggravates the medical condition.

[0003]

DISCLOSURE OF THE INVENTION The present invention is intended to provide an amino acid preparation which exerts an excellent effect on improving the malnutrition of cancer patients and suppressing tumor growth.

[0004]

The present inventors have prepared an amino acid preparation of essential amino acid type or total amino acid type by using D-valine instead of L-valine, and have its nutritional effect and tumor growth inhibition. I researched the effect. As a result, they have found that the above problems can be solved with a composition containing at least D-valine and seven essential amino acids other than L-valine, and have completed the present invention.

That is, the present invention is at least D-valine, L-leucine, L-isoleucine, L-lysine, L
-An amino acid preparation for cancer characterized by containing methionine, L-phenylalanine, L-threonine and L-tryptophan.

As a preferred embodiment of the present invention, there can be mentioned, for example, an amino acid preparation containing the following amino acids within the following composition range.

[0007]

[Table 2]

The amino acid used in the present invention is not only in a free form but also in a pharmacologically acceptable salt, for example, a metal salt such as sodium salt, a mineral salt such as hydrochloride, an organic acid salt such as acetate, or L-. 2 such as the salt of arginine and L-glutamic acid
It can be used in the form of a salt consisting of certain amino acids.
In addition, the above-mentioned amino acids are, for example, N-acetyl-L-tryptophan, N-acetyl-L-cysteine and the like N-.
An acyl derivative, or glycyl-D-valine,
It may be used as an oligopeptide such as L-leucyl-D-valine, L-isoleucyl-D-valine, L-alanyl-L-tryptophan. In addition, L-cysteine is
Part or all of it can be replaced with L-cystine.

In addition to the above-mentioned amino acids, the amino acid preparation for cancer of the present invention may contain, if necessary, sugars, lipids, electrolytes, vitamins, trace elements and the like. As the sugar, glucose, maltose, fructose, xylitol, sorbitol, trehalose, etc., as the lipid, soybean oil, safflower oil, perilla oil, linseed oil, fish oil, etc., as the electrolyte, sodium chloride, sodium acetate , Sodium citrate, potassium chloride, calcium chloride, calcium gluconate, magnesium chloride, magnesium sulfate, sodium dihydrogen phosphate, dipotassium hydrogen phosphate, and the like, as vitamins, vitamin A, vitamin Bs, vitamin C, Examples include vitamin Ds, vitamin E, nicotinic acid, biotin, folic acid, and the like, and examples of trace elements include zinc, iron, manganese, copper, iodine, selenium, and cobalt.

The amino acid preparation for cancer of the present invention is generally used for cancer patients who cannot or cannot obtain a nutritional source orally due to surgery or other causes, or who tend to have insufficient nutritional intake. It is used as an infusion solution or an enteral solution, but may be applied as a preparation such as a syrup, granules, fine granules or the like to an orally administrable cancer patient. These preparations can be produced according to known methods by using, if necessary, pH adjusting agents, stabilizers or pharmaceutical additives such as excipients, binders, corrigents and the like.

The dose of the amino acid preparation for cancer of the present invention is 10 to 70 g of total amino acid weight per day for an adult, and may be appropriately increased or decreased depending on the patient's disease state, nutritional condition, age, body weight and the like. Good.

The cancer amino acid preparation of the present invention shows the same growth inhibitory effect on tumor cells as the L-valine deficient amino acid preparation, and shows an excellent nutrition improving effect on the living body.

[0013]

【Example】

Example 1 The following amino acids were dissolved in distilled water for injection at the following concentrations and sterilized by filtration. Then, this solution was filled in a 500 ml glass bottle or a synthetic resin bag, and the space was replaced with nitrogen and then sealed and heat-sterilized by a conventional method to obtain the target amino acid preparation for cancer.

[0014]

[Table 3]

Example 2 An amino acid preparation for cancer containing the following amino acids at the following concentrations was produced in the same manner as in Example 1.

[0016]

[Table 4]

Example 3 620 g of powder obtained by mixing the following amino acids in the following ratios:
After 200 g of microcrystalline cellulose and 78 g of potato starch were uniformly mixed, a wetting liquid was added and kneaded, and columnar granules were obtained by an extrusion granulation method.

[0018]

[Table 5]

Next, as an infusion agent (test solution) for testing, I
Solution, Solution II and Solution III were prepared as follows. Solution I: Equivalent mixture of 365 ml of the infusion agent of Example 1 and a commercially available sugar / electrolyte infusion agent, Palemental A and Palemental B (trade name, manufactured by Morishita Roussel KK) (Table 6) 63.
Prepared by mixing with 5 ml. Solution II: The formulation did not contain only D-valine in Solution I. Solution III: A formulation (conventional integrated infusion) in which only D-valine in solution I was replaced with L-valine.

[0020]

[Table 6]

Test Example 1 [Method] 1.6 × 10 ⁷ cells of ascites hepatoma AH109A were transplanted subcutaneously on the back of Donryu rats (7 rats per group) weighing 160 to 180 g, and 7 days after transplantation. The test solution was continuously administered for 7 days through a silicone catheter placed in the central vein of the eye. The daily dose is 25
It was set to 2 ml / kg. After the administration, body weight was measured, and immediately after ether anesthesia, blood was collected from the abdominal aorta (heparin and ED).
Then, the amount of albumin, the amount of total protein, the amount of hematocrit, the amount of hemoglobin, and the number of red blood cells were measured. Furthermore, the tumor tissue was excised, its weight was measured, and the tumor growth inhibition rate was calculated by the following formula.

[0022]

[Equation 1]

[Results] (1) Nutritional effect Regarding body weight, albumin amount, and total protein amount, no significant difference was observed between the I-solution administration group and the III-solution administration group, but only for the II-solution administration group. Also showed a significantly lower value. That is, it was revealed that the infusion solution of the present invention exhibits a nutritional effect equivalent to that of the conventional integrated type infusion solution.

(2) Tumor growth inhibitory effect Regarding the tumor weight (mean ± standard deviation), the liquid administration groups I and II showed a significantly lower value than the liquid administration group at a risk rate of 1% or less. The data and the tumor growth inhibition rate are shown in Table 7. From this table, it can be seen that the tumor growth inhibition rates of solution I and solution II are almost the same. That is, it was revealed that the infusion solution of the present invention exhibits a tumor growth inhibitory effect equivalent to that of the L-valine-deficient infusion solution.

[0025]

[Table 7]

(3) Anemia improving effect Hematocrit (mean ± standard deviation), hemoglobin amount (mean ± standard deviation) and red blood cell count (mean ± standard deviation) are shown in Table 8. In all of them, the liquid I administration group showed a significant increase at a risk rate of 5% or less compared to the other groups. That is, it was revealed that the infusion solution of the present invention exhibits an excellent effect in improving anemia symptoms in a cancer-bearing state.

[0027]

[Table 8]

[0028]

EFFECTS OF THE INVENTION By applying the amino acid preparation for cancer of the present invention to cancer patients, excellent effects can be expected in suppressing tumor growth and improving malnutrition.

Claims (2)

[Claims] 1. At least D-valine, L-leucine, L
-An amino acid preparation for cancer characterized by containing isoleucine, L-lysine, L-methionine, L-phenylalanine, L-threonine and L-tryptophan. 2. The amino acid preparation for cancer according to claim 1, which contains the following amino acids within the following composition range. [Table 1]