JPS6342607B2 - - Google Patents

Description

DETAILED DESCRIPTION OF THE INVENTION The present invention relates to a high-calorie infusion preparation, and more particularly to a high-calorie infusion preparation containing a sugar fatty acid ester as a nutrient.

People get the nutrients they need from food, but nutritional infusion therapy has long been used for people who are unable to eat food due to illness or other reasons. Nutrient infusion therapy is a therapy in which nutrient infusions, such as the widely used glucose solution, are intravenously injected into a patient's peripheral veins. In this case, the glucose solution used has a concentration of approximately 5% by weight, so the amount of fluid that can be supplied to the human body per day is approximately 2 to 3, so the number of calories that can be replenished per day using this method. The amount is at most
It was only 400-600 Cal. It has been difficult to supply more than 400 to 600 Cal per day by this method because increasing the glucose concentration increases osmotic pressure, which stimulates peripheral blood vessel walls and makes it easier to cause phlebitis.

In recent years, sugar, amino acids, and fat have been used to
High calorie infusion therapy is being developed that allows administration of 3000 Cal. This is a high-calorie solution made by adding amino acids and fat to the conventional nutritional infusion containing only sugar, and a major contribution was made in particular by making it possible to use fat, which has more than twice the calories of sugar and amino acids. ing. However, since fat does not mix with water, it is currently used as an emulsion by adding an emulsifier such as egg yolk lecithin. However, when this emulsion is mixed with infusion preparations or drugs (for example, electrolyte infusion preparations, gelatin, dextran, etc.), the fat particles aggregate or become coarse, making intravenous administration impossible.

In view of the current situation, the present inventors have arrived at the present invention as a result of intensive research aimed at providing an infusion preparation that is high in calories and free from the problem of aggregation of fat and the like.

That is, the present invention is a high-calorie infusion preparation containing a nutrient, which is characterized by containing a sugar fatty acid ester as the nutrient.

When the sugar fatty acid ester contained in the infusion preparation of the present invention enters the body, it is hydrolyzed into sugar and fatty acid by the action of enzymes, etc. Therefore, when the infusion preparation of the present invention is used, both sugar and fatty acid of calories can be ingested. Furthermore, since the sugar fatty acid ester used in the present invention also acts as a surfactant, it easily dissolves in water, so there is no need to worry about problems such as water insolubility, and addition of other fats is also possible. This has the great advantage of being possible. Furthermore, it is useful that the types of sugar and fatty acid can be selected arbitrarily, and that depending on the type of fatty acid, antibacterial effects can be expected.

The infusion preparation of the present invention can be produced by dissolving the sugar fatty acid ester in water. The concentration of sugar fatty acid esters in the infusion preparation is preferably
It is 0.001 to 80% by weight.

The sugar fatty acid ester used in the present invention refers to one in which a sugar and a fatty acid are ester bonded.

Natural products and synthetic products are known as such sugar fatty acid esters, and natural products can be obtained by isolating and purifying them by conventional methods such as chromatography, while synthetic products can be obtained by, for example, combining sugar and fatty acids. It can be synthesized by conventional methods such as transesterification with alcohol ester or reaction between sugar and fatty acid halide. In addition, in the case of synthetic products, the number of fatty acids bonded to the sugar can be arbitrarily changed depending on the reaction conditions (as many as the number of hydroxyl groups that can be esterified in the sugar), and several different types of fatty acids can be combined with one sugar. They can also be combined.

Examples of sugars include glycerose, dihydroxyacetone, erythrose, threose, erythrulose, arabinose, ribose, lyxose, xylose, ribulose, xylulose, glucose, mannose, allose, altrose, talose, galactose, idose, gulose, fructose, psicose, tagatose. , sorbose, xylitol, arabitol, sorbitol, mantol, aldoheptose, ketoheptose, ketooctose, ketononose, deoxypentose, deoxyhexose, dideoxyhexose, aldidole, uronic acid, ketoaldonic acid, ascorbic acid, amino acids, monosaccharides such as sialic acid, xylobiose , xylo-oligosaccharides such as xylotriose, galactooligosaccharides such as agarobiose, glyco-oligosaccharides such as maltose, isomaltose, maltotriose, maltotetraose, maltopentaose, cellobiose, mannooligosaccharides, fructo-oligosaccharides such as inulobiose, glucosamines Oligosaccharides such as hetero-oligosaccharides such as oligosaccharides, uronic acid oligosaccharides, sucrose, and epicellobiose, homopolysaccharides such as pentosans such as arabinan and xylan, glucan, hexosane such as amylopectin, mucopolysaccharides, and glycosaminoglycans Among them, monosaccharides and oligosaccharides are particularly preferred. In addition, examples of fatty acids include formic acid, acetic acid, propionic acid, butyric acid, valeric acid, caproic acid,
Saturated fatty acids such as enanthic acid, caprylic acid, pelargonic acid, capric acid, lauric acid, myristic acid, palmitic acid, stearic acid, arachidic acid, behenic acid, lignoceric acid, cerotic acid, tuccinic acid, Linderic acid, tuzunic acid, Fisetolenic acid,
Myristoleic acid, palmitoleic acid, petroselic acid, oleic acid, ricinoleic acid, petroselic acid, vaccenic acid, linoleic acid, linolenic acid, linoleaidic acid, elaidic acid, eleostearic acid, punicic acid, parinaric acid, gadolenic acid, arachidone acid, eicosadienoic acid, eicosatrienoic acid, eicosenoic acid, erucic acid, unsaturated fatty acids such as mycomycin, futhienoic acid, mycocerosinic acid,
Mycolic acid, isoacid, tuberculostearic acid,
Examples include branched chain fatty acids such as stericlic acid,
Particularly preferred are long chain fatty acids.

The high-calorie infusion preparation of the present invention can be mixed with a large amount of sugar solution, electrolyte infusion preparation, amino acid solution, fat emulsion, etc., as necessary, and may also be mixed with other drugs such as antibiotics and anticancer drugs. It is also possible to do so.

The high-calorie infusion preparation of the present invention is useful not only as a calorie source, but also in supplying essential fatty acids essential for long-term infusion therapy.

Hereinafter, the present invention will be explained in more detail with reference to Examples.

Example 1 Glucose linoleic acid ester was synthesized from glucose and methyl linoleate by a conventional transesterification reaction, and glucose linoleic acid monoester was isolated and purified by chromatography. 100 g of this glucose linoleic acid monoester
When dissolved in ml of distilled water for injection, a homogeneous solution was obtained. This product was administered to rabbits weighing 2.5 kg through the ear vein at a rate of 1 ml/min. This is 100
When administered at a dose of ml/day for 20 days, there was almost no decrease in the weight of the rabbits.

For comparison, commercially available 8% was applied to rabbits weighing 2.4 kg.
When the glucose solution was administered at the same amount of 100 ml/day for 20 days, the weight decreased to 1.5 kg.

From the above results, it was confirmed that glucose linoleic acid monoester is useful as a calorie source.

Example 2 Fructose oleate was synthesized from fructose and ethyl oleate by a conventional transesterification reaction, and fructose oleate diester was isolated and purified by chromatography. When administered to rabbits in the same manner as in Example 1, almost no decrease in body weight was observed.

Example 3 Sorbitol oleate was synthesized by a conventional transesterification reaction of sorbitol and methyl oleate. When this product was administered to rabbits in the same manner as in Example 1, almost no decrease in body weight was observed.

Example 4 10 g of glucose linoleic acid monoester synthesized in Example 1 was added to 30 ml of a commercially available 50% glucose solution,
When mixed with a solution consisting of 75 ml of a commercially available 7% L-amino acid infusion, 20 ml of a commercially available electrolyte infusion, and 25 ml of distilled water for injection, it was uniformly dissolved.

The obtained solution was administered to a rabbit weighing 2.6 kg through the ear vein at a rate of 1 ml/min. When the blood pressure, respiratory rate, and heart rate of the rabbits were measured after administration, blood pressure,
Almost no changes were observed in either respiratory rate or heart rate. When the same amount of this solution was administered for one month, the weight of the rabbit increased by 0.2 kg.

For comparison, the solution without glucose linoleic acid ester was similarly administered to rabbits (weight 2.7 kg).
After administering the drug for a month, body weight decreased by 0.6 kg.

Example 5 Maltose and linoleic acid chloride at 60℃ for 24 hours
Maltose linoleic acid ester was synthesized by reacting for hours, and maltose linoleic acid monoester was isolated and purified by chromatography.

10g of this maltose linoleic acid monoester
A homogeneous solution was obtained by dissolving in 100 ml of distilled water for injection.
This solution was administered to a rabbit weighing 2.7 kg by 0.5 kg via the ear vein.
Administered at a rate of ml/min. 25ml/day of this
When administered for 20 days, there was almost no decrease in the weight of the rabbits.

For comparison, when a rabbit weighing 2.8 kg was given the same amount of 25 ml/day of 10% maltose solution for 20 days, the rabbit's weight decreased to 1.9 kg.

Example 6 Maltotriose and linoleic acid chloride were reacted in the same manner as in Example 5 to synthesize maltotriose linoleic acid ester, and maltotriose linoleic acid monoester was isolated and purified by chromatography.

When this product was administered to rabbits in the same manner as in Example 5, almost no decrease in the weight of the rabbits was observed.

Claims (1)

[Scope of Claims] 1. A high-calorie infusion preparation containing a nutrient, which is characterized by containing a sugar fatty acid ester as the nutrient. 2. The high-calorie infusion preparation according to claim 1, wherein the sugar fatty acid ester is a sugar fatty acid ester consisting of sugar and long-chain fatty acid. 3. The high-calorie infusion preparation according to claim 1, wherein the sugar fatty acid ester is a sugar fatty acid ester consisting of a monosaccharide and a fatty acid.