JP3773210B2 - Trehalose-containing fat emulsion - Google Patents

Description

【００１８】
試験例２
１２１℃で２０分間高圧蒸気滅菌した後の実施例１の輸液剤及び比較液１について、６０℃で１週間保存した。冷却後、各溶液の外観観察及び粒度分布、ｐＨ並びに遊離脂肪酸（ＦＦＡ）の測定を行った。外観及び粒度分布は２つの溶液間に差はなく良好な乳化状態を保ったが、ｐＨ及びＦＦＡに大きな差を生じた（表２）。つまり、グルコースを含有する比較液におけるＦＦＡは実施例１の輸液剤に比べ約６倍の濃度に上昇した。これらの結果より本発明に係わるα、α−トレハロース含有脂肪乳剤は、製剤学的安定性に優れ、全く問題ないことが判った。以上のことより、α、α−トレハロースは安定な糖質素材であり、グルコースと異なり、脂肪乳剤に配合してもｐＨの低下や、有害な遊離脂肪酸の生成を促進しないことが明かとなった。
【００１９】
【表２】

【００２０】
【発明の効果】
本発明によれば、糖質カロリー源と脂肪とを一剤に配合し、製剤学的な安定性と安全性に問題のない栄養組成物を提供することができる。[0001]
[Industrial application fields]
The present invention relates to a nutritional composition, and more particularly to a preparation containing trehalose as a sugar source in a fat emulsion.
[0002]
[Prior art]
It is known that carbohydrates play an important role in the energy metabolism of fat, and that the use of carbohydrates increases when fat is administered (Kazuhiro Yoshida et al., Journal of Postoperative Metabolism Research Group, 13 89 (1978)). Therefore, a preparation in which a carbohydrate is mixed with fat is sufficiently significant clinically. However, glucose generally used as a nutrient infusion material is easily decomposed in a neutral aqueous solution in which a fat emulsion is stable, and generates an organic acid such as formic acid or levulinic acid, thereby lowering the pH of the solution (Hiroko Saito et al. Analytical Chemistry, 33, T15 (1984)), and this decrease in pH is concerned with an increase in free fatty acid production from fat emulsions (I. Hakansson, Acta Chemica Scandinavica, 20 , 2267 (1966)). ). Since these free fatty acids are harmful to the living body, long-term stability and safety cannot be maintained with a fat emulsion formulated with glucose.
[0003]
[Problems to be solved by the invention]
An object of the present invention is to provide a nutritional composition that contains a saccharide calorie source and a fat that are easily used by a living body and contains no problems in pharmaceutical stability and safety.
[0004]
[Means for Solving the Problems]
As a result of intensive studies in view of the above circumstances, the present inventors have found that the above problems can be solved by using trehalose as a saccharide calorie source, and have completed the present invention.
[0005]
That is, the present invention provides a nutritional composition containing trehalose and simple lipids as active ingredients for imparting nutrition .
[0006]
In the present invention, the preferred concentrations of trehalose and simple lipid are 2 to 40% (w / v) trehalose and 2 to 30% (w / v) fat.
[0007]
There are three types of trehalose used in the present invention, α, α-trehalose, α, β-trehalose or β, β-trehalose, and naturally occurring α, α-trehalose.
Examples of the fat include preferably simple lipids such as refined soybean oil, safflower oil, linseed oil, sesame oil, coconut oil, and the like, or animal oils such as whale oil and fish oil.
[0008]
The nutritional composition of the present invention includes electrolytes such as sodium chloride, potassium citrate, and potassium dihydrogen phosphate, organic acids such as acetic acid, citric acid, and lactic acid, or zinc, as long as they do not affect the stability of the fat emulsion. Trace elements such as copper, iron, and manganese can be included.
Water can be used when formulating in liquid form, and emulsifiers such as lecithin and glycerin, emulsifying aids, solubilizing aids and other formulation additives can be added as appropriate regardless of the dosage form. Needless to say.
[0009]
The nutritional composition of the present invention is usually used as an infusion for intravenous administration. These preparations can be produced according to known methods.
[0010]
[Action]
Trehalose is a pharmacologically stable disaccharide, and even when incorporated in a fat emulsion, it does not decompose to lower the pH or promote the production of free fatty acids. Therefore, it is possible to provide a stable and safe nutritional composition by mixing both in one agent without any special pharmacological measures.
[0011]
【Example】
Example 1
To 100 g of purified soybean oil, 12 g of purified soybean lecithin and 25 g of glycerin were added, heated on an oil bath, and stirred with a Polytron homogenizer. After cooling the solution, an appropriate amount of distilled water was added, and rough emulsification was performed with a polytron homogenizer. The liquid after rough emulsification was subjected to high-pressure emulsification using a microfluidizer. 250 ml of an aqueous solution in which 80 g of trehalose was dissolved in advance was added to the obtained emulsion, and the total liquid volume was adjusted to 1000 ml with distilled water. Next, the pH was adjusted to about 7 with an aqueous sodium hydrogen carbonate solution and filtered through a membrane filter. The filtrate was filled into a 200 ml vial and autoclaved at 121 ° C. for 20 minutes to obtain the intended trehalose-containing fat emulsion.
[0012]
Example 2
To 100 g of purified soybean oil, 12 g of purified egg yolk lecithin and 25 g of glycerin were added, heated on an oil bath, and stirred with a Polytron homogenizer. After cooling the solution, 400 ml of an aqueous solution containing 150 g of α, α-trehalose was added, and rough emulsification was performed with a polytron homogenizer. The liquid after rough emulsification was subjected to high-pressure emulsification using a microfluidizer. Distilled water was added to the obtained emulsion to adjust the total liquid volume to 1000 ml. After filtration through a membrane filter, the filtrate was filled into a 200 ml vial and autoclaved at 121 ° C. for 20 minutes to obtain the intended trehalose-containing fat emulsion.
[0013]
Example 3
To 200 g of purified sesame oil, 12 g of purified egg yolk lecithin and 400 ml of an aqueous solution containing 50 g of α, α-trehalose were added, and rough emulsification was performed with a polytron homogenizer. The liquid after rough emulsification was subjected to high-pressure emulsification using a microfluidizer. Distilled water was added to the obtained emulsion to adjust the total liquid volume to 1000 ml. After filtration through a membrane filter, the filtrate was filled into a 200 ml vial and autoclaved at 121 ° C. for 20 minutes to obtain the intended trehalose-containing fat emulsion.
[0014]
Next, a comparative solution 1 for test was prepared.
[0015]
Comparative solution 1
A glucose-containing fat emulsion before high-pressure steam sterilization was obtained in the same manner as in Example 1 except that glucose (the same amount) was used instead of α, α-trehalose in Example 1, and used as Comparative Solution 1.
[0016]
Test example 1
About the infusion agent before the high pressure steam sterilization of Example 1, and the comparison liquid 1, high pressure steam sterilization was performed for 20 minutes at 121 degreeC. After cooling, the appearance of each solution was observed and the particle size distribution, pH, and free fatty acid (FFA) were measured. Appearance and particle size distribution did not differ between the two solutions and maintained a good emulsified state, but produced a large difference in pH. That is, the pH of Comparative Solution 1 containing glucose was greatly reduced before and after sterilization (Table 1). From these results, it was found that the α, α-trehalose-containing fat emulsion according to the present invention was excellent in pharmaceutical stability and had no problem at all.
[0017]
[Table 1]

[0018]
Test example 2
The infusion preparation of Example 1 and Comparative Solution 1 after autoclaving at 121 ° C. for 20 minutes were stored at 60 ° C. for 1 week. After cooling, the appearance of each solution was observed and the particle size distribution, pH, and free fatty acid (FFA) were measured. Appearance and particle size distribution did not differ between the two solutions and maintained a good emulsified state, but produced significant differences in pH and FFA (Table 2). That is, the FFA in the comparative solution containing glucose increased to a concentration about 6 times that of the infusion preparation of Example 1. From these results, it was found that the α, α-trehalose-containing fat emulsion according to the present invention was excellent in pharmaceutical stability and had no problem at all. From the above, it became clear that α, α-trehalose is a stable saccharide material and unlike glucose, it does not promote pH reduction or generation of harmful free fatty acids even when blended into a fat emulsion. .
[0019]
[Table 2]

[0020]
【The invention's effect】
ADVANTAGE OF THE INVENTION According to this invention, a saccharide calorie source and fat can be mix | blended in 1 agent, and the nutritional composition which does not have a problem in pharmacological stability and safety can be provided.

Claims (3)

A nutritional composition containing a saccharide and fat as the active ingredient as a source of calories, carbohydrate source of calories is alpha, an α- trehalose, and the fat source is simple lipid, in addition to these trace elemental nutritional composition, wherein the active ingredient der Rukoto. Further nutritional composition of claim 1 wherein the at least one element selected electrolyte and organic acids or colleagues and wherein the active ingredient der Rukoto. The nutritional composition according to claim 1 or 2, wherein the concentrations of α, α- trehalose and simple lipid are 2 to 40% (w / v) and 2 to 30% (w / v), respectively.