JP2004043490A - Nutrient infusion - Google Patents

Abstract

<P>PROBLEM TO BE SOLVED: To provide a nutrient infusion excellent in both stability in an aqueous state and availability in an organism and containing a glucide with high safety as well. <P>SOLUTION: This nutrient infusion contains trehalose as a glucide calorie source and is subjected to high-pressure steam sterilization. Accordingly, the glucide is highly concentrated when necessary, and is so controlled as to have a pH of 5.5 or higher. Therefore, the extremely useful nutrient infusion which is used as a basic solution for hyperalimentary liquid administered through a central vein or as a medium calorie infusion administered through a peripheral vein is provided. <P>COPYRIGHT: (C)2004,JPO

Description

The present invention relates to a nutritional infusion containing trehalose and sterilized by autoclaving.

グ ル コ ー ス Conventionally, glucose, fructose, maltose, sorbitol, xylitol and the like have been used as a source of carbohydrate calories in nutritional infusions.

However, these saccharides are not always satisfactory in terms of stability in an aqueous solution state, availability in a living body, or safety.

For example, glucose has a problem that it is easily decomposed when the pH of an aqueous solution is 5.5 or more. Therefore, the pH of a glucose-containing infusion is usually adjusted to 5.5 or less, but administration of such a non-physiological acidic solution from a peripheral vein may cause phlebitis (Fonkalsrud EW). et al., J. Surg. Res., 8 , 539 (1968)). Fructose may induce acidosis by inducing an increase in blood lactic acid (edited by Munemoto Ito et al., “Side Effects of Drugs”, Chugai Medical, Tokyo, 1991, p. 83). Maltose, sorbitol and xylitol have a problem in that when administered intravenously at a normal rate, a significant part of the maltose, sorbitol and xylitol are excreted in the urine without much use (Shunji Matsuzaki, Pharmaceutical Therapy, 6 , 295 (1973)). In addition, in the case of monosaccharides such as glucose, when it is desired to increase the amount of calories by administering a certain amount of an infusion solution, the range of the concentration that can be increased is about one-half the concentration possible with the disaccharide due to the problem of osmotic pressure. There is a restriction of up to.
Fonkalsrud EW et al., J. Surg. Res., 8, 539 (1968) Edited by M. Ito et al., "Side Effects of Pharmaceuticals," Chugai Medical Company, Tokyo, 1991, p. 83 Matsuzaki Shunji, Pharmacotherapy, 6,295 (1973)

課題 An object of the present invention is to provide a nutrient infusion containing a carbohydrate which is excellent in both stability in an aqueous solution state and utilization rate in a living body and is highly safe.

The present inventors have examined various problems of the background art using various carbohydrates that have not been used as a calorie source of a nutritional infusion. As a result, they have found that the above problem can be solved by using trehalose, which is a disaccharide, and have completed the present invention.

That is, the present invention provides a nutrient infusion containing trehalose as a carbohydrate source and being subjected to high-pressure steam sterilization.

ト レ The trehalose according to the present invention includes three kinds of α, α-trehalose, α, β-trehalose, and β, β-trehalose, and is more preferably naturally occurring α, α-trehalose.

The nutrient infusion of the present invention can contain necessary nutrients such as electrolytes and vitamins in addition to trehalose. For example, as a preferred preparation, one or more of the elements contained in the electrolytes shown in Table 1 in the concentration range shown in Table 1 can be used together with 10 to 500 g of trehalose in 1000 ml.

Examples of the electrolyte containing the element include sodium hydroxide, sodium chloride, sodium acetate, sodium lactate, sodium citrate, potassium chloride, potassium lactate, potassium citrate, calcium acetate, calcium lactate, calcium gluconate, calcium pantothenate, and sulfuric acid. Magnesium, sodium monohydrogen phosphate, potassium monohydrogen phosphate, sodium dihydrogen phosphate, potassium dihydrogen phosphate, hydrochloric acid, zinc sulfate, zinc chloride, iron sulfate, ferrous chloride, ferric chloride, copper sulfate, Examples thereof include sodium iodide, potassium iodide, and manganese sulfate.

The nutritional infusion of the present invention can be easily produced by autoclaving.

100 g of α, α-trehalose was dissolved in distilled water to make the total volume 1000 ml. This solution was filtered through a membrane filter having a pore size of 0.22 μm, filled in a 200-ml glass bottle, and the space was replaced with nitrogen gas and sealed. This was subjected to high-pressure steam sterilization according to a conventional method to obtain a nutritional infusion.

500 g of αα, α-trehalose was dissolved in distilled water to make 950 ml, the pH was adjusted to 7.0 with a 1N aqueous sodium hydroxide solution, and the total amount was made 1000 ml. Thereafter, a nutritional infusion was obtained in the same manner as in Example 1.

(4) The compositions shown in Table 2 below were dissolved in distilled water to make 950 ml, the pH was adjusted to 5.0 with 1N hydrochloric acid, and the total amount was made to 1000 ml. Thereafter, a nutritional infusion was obtained in the same manner as in Example 1.

栄 養 A nutrient infusion was obtained in the same manner as in Example 3, except that the pH was adjusted to 6.0 with a 1N aqueous sodium hydroxide solution in the process of Example 3.

栄 養 A nutrient infusion was obtained in the same manner as in Example 3 except that the pH was adjusted to 7.0 with a 1N aqueous sodium hydroxide solution in the process of Example 3.

(4) The compositions shown in Table 3 below were dissolved in distilled water to make 950 ml, the pH was adjusted to 7.0 with a 1N aqueous sodium hydroxide solution, and the total amount was made to 1000 ml. Thereafter, a nutritional infusion was obtained in the same manner as in Example 1.

(4) The compositions shown in Table 4 below were dissolved in distilled water to make 950 ml, the pH was adjusted to 7.0 with a 1N aqueous sodium hydroxide solution, and the total amount was made to 1000 ml. Thereafter, a nutritional infusion was obtained in the same manner as in Example 1.

対 照 Control solutions 1 to 10 (Table 5 below) used together with the nutritional infusions of Examples 1 to 7 in the test examples described below were prepared according to the method of Example 1.

Test example 1

A Japanese white male rabbit (4 birds per group) weighing 2.0 to 2.5 kg was placed in a fixing device, and the nutrient infusion of Example 1 and each of the test solutions of Control Solutions 1 and 2 were injected through the auricular vein at 5 ml / vol. The administration was continued for 4 hours at a rate of kg / hr. After the administration, the rabbits were transferred to individual metabolic cages, and urine was collected for 24 hours. During the experimental period, the animals were fasted and watered. The sugar in the collected urine was measured, and the excretion rate was calculated. As a result (Table 6 below), α, α-trehalose was found to be a carbohydrate having a good utilization rate in a living body, similarly to glucose.

Test example 2

に つ き The osmotic pressure ratio of the nutritional infusion solution of Example 2 and the control solution 3 was measured using physiological saline as a standard.

Next, after high-pressure steam sterilization at 105 ° C. for 90 minutes, the transmittance of light having a wavelength of 430 nm was measured as an index of the degree of coloring. Further, each liquid after the sterilization was diluted 10 times with distilled water, and the absorbance at a wavelength of 284 nm was measured as an index of carbohydrate decomposition.

か ら From the results of these measurements (Table 7 below), it can be seen that α, α-trehalose is more advantageous for increasing the concentration of carbohydrates than glucose and is extremely stable at pH 7.0.

Test example 3

栄 養 Each of the nutritional infusions of Examples 3 to 7 and the control solutions 4 to 10 was subjected to high-pressure steam sterilization at 105 ° C. for 90 minutes, and then the absorbance at a wavelength of 284 nm and the transmittance of light at a wavelength of 430 nm were measured. In addition, each absorbance of the nutrient infusion solution of Example 6 and the control solution 10 was diluted 6 times with distilled water and measured. As a result (Table 8 below), it was found that α, α-trehalose was most excellent in stability at pH 5.0 to 7.0.

ＳＤ 10 ml / kg (5 g / kg) of the nutritional infusion of Example 2 was rapidly administered to the SD rats (5 rats) weighing 230 to 260 g from the tail vein. As a result, no deaths were observed and no notable general symptoms were observed.

@ Trehalose is a disaccharide that is sufficiently stable even when the pH of the aqueous solution is around 7, has a high availability in living organisms, and has high safety. Therefore, according to the present invention, the concentration of carbohydrates can be increased as necessary, and the pH can be adjusted to 5.5 or more. An extremely useful nutritional infusion can be provided as a medium-calorie infusion.

Claims (3)

(4) A nutritional infusion containing trehalose as a carbohydrate calorie source and being autoclaved. (4) The nutritional infusion according to (1), wherein the transmittance of 430 nm light after the high-pressure steam sterilization is 99.7% or more. (3) The nutritional infusion according to (1) or (2), wherein the trehalose is α, α-trehalose or β, β-trehalose.