JPS6130522A - Preparation of transfusion solution containing saccharide, amino acid and electrolyte - Google Patents

Abstract

PURPOSE:A transfusion solution, containing maltose, an amino acid and electrolyte, adjusted to a specific pH with a specific organic acid salt as the electrolyte, and having improved stability. CONSTITUTION:A transfusion solution containing maltose, an amino acid and electrolyte. A mixture of an organic acid salt with an inorganic acid salt is used as the electrolyte, e.g. having the composition shown in the table, and a lactate is used as the organic acid salt. The pH is adjusted to 5-7 with lactic acid and/ or a mineral acid to give the aimed stable transfusion solution without discoloration. Since a nutrient transfusion solution is used in a large amount for a long time, an undesirable disorder, e.g. vascular pain, is caused by administration to peripheral veins with increasing acidity of the transfusion solution. Therefore, the pH must be approached to a neutral value. If the pH is >=5, the solution tends to be colored. The coloration of the lactate is minimum at >=5pH in the organic acid salt.

Description

DETAILED DESCRIPTION OF THE INVENTION Field of Industrial Application The present invention relates to a method for producing an infusion solution containing maltose, an amino acid and an electrolyte in one drug and having excellent stability.

Prior art and its problems Among sugars, amino acids, and electrolytes, which are the main components of infusions administered as complete parenteral nutrition, the amino acids include inleucine, leucine, methionine, phenylalanine, threonine, valine, tryptophan, lysine, arginine, and histidine. In addition to essential amino acids such as aspartic acid, glutamic acid, alanine, cystine, amino (3p?, F, proline, serine, tyrosine, etc.) are appropriately blended, and electrolytes include potassium, sodium, magnesium, calcium, phosphorus, and chloro. Ion-supplying salts are used, generally in the form of chlorides, sulfates, phosphates and organic acid salts. Together with these, infusion preparations containing maltose as sugar have not yet been produced. Currently, the above-mentioned formulations of each component are manufactured separately and are mixed at the time of use and administered to patients.Combining these formulations into a single formulation is a Although it is expected to be useful in reducing the number of steps required and the possibility of bacterial contamination, the biggest problem with combined preparations is the browning reaction (Maillard reaction) between sugar and amino acids in an aqueous solution. This causes the preparation to become easily colored, resulting in poor sterilization resistance and storage stability.Furthermore, as such nutritional infusions are often used for long periods of time, the pH of the infusion may become acidic. Indeed, when administered into peripheral veins, undesirable disorders such as vascular pain occur.

Therefore, in formulating a formulation, it is required to bring the pH as close to neutral as possible. Glucose is commonly used as a sugar, but using maltose instead makes it possible to use maltose at twice the concentration of glucose without changing the osmotic pressure, since one molecule of maltose is made up of two molecules of glucose. It has the advantage of being able to supply more calories from the peripheral blood vessels, making it useful.

Against this background, the present inventor conducted various studies in order to combine maltose, amino acids, and IT electrolyte into a single preparation, and as a result, as will be described later, coloring is pH dependent, and M is 5 or more. The present invention was completed based on the discovery that coloration is more likely to occur at pH 5 or higher, and that among organic acid salts, lactate reduces coloration the least at pH 5 or higher.

OBJECTS OF THE INVENTION The object of the present invention is to provide an infusion solution that simultaneously contains maltose, amino acids, and amino acids and does not change color.

XenoC composition of the invention The present invention is an infusion containing maltose, an amino acid, and an electrolyte, and uses lactate as an organic salt in the infusion that uses an organic acid salt or a mixture of #4 acid salt and a salt-resistant salt as the electrolyte. , pH 5-7 with lactic acid and/or mineral
A method of manufacturing an infusion solution, which consists of adjusting the

Description of examples The present invention will be explained in detail below.

Table 1 Maltose 20
v/v%Amino acid group heptaacid 74 thorium 0.0
3 #Phosphate-potassium
0.08 #Magnesium sulfate
0.1 calcium chloride
0.06 #yumin #fun”
0.074 moz/1 Hydrochloric acid or sodium hydroxide Appropriate amount Rice amino acid group content (W/V%) Inleucine 0.28
i Leucine 0.39i Lysine hydrochloride 0.34i Methionine 0.18i Phenylmalanine 0.43i) Rheoene 0.
2; tryptophan 0.072 i valine 0.29i arginine salt salt 0.4; histidine salt #mO, 2; asparagine @ 0.2i glutamic acid 0.06; alania o, i 6; cystine 0.008; ymi/ Vinegar reO, 61i Proline 0.08; Serine O, OS; Tyrosine 0.02゜ US addition] Organic acid salts compared: Sodium hetate; Sodium succinate; Sodium lactate; Sodium malate; Sodium tartrate; Citric acid acid sodium.

The pH of the aqueous solution containing maltose, amino acids, and electrolyte shown in Table 1 above was adjusted to pH 4, 5, or 6 using salt or sodium hydroxide, and the mixture was filled into an ampoule, and the ampoule space was replaced with nitrogen and melted closed. Heated at ℃ for 60 minutes. Some of the sample solutions were colored yellow to yellow, so
In order to change the intensity of coloring, the absorption yC at 420 nm was turned off.
1 liter was determined.

Large absorbance indicates strong gravel coloration. The results are shown in Table 2 below.
Shown below.

Table 2 Sodium acetate 4 0.0255
0.052 6 0.481 Sodium lactate 4 0.0275
0.041 6 0.097 Sodium citrate 4 0. ()
285 0.035 6 0.323 Sodium succinate 4 0.02
25 0.033 6 0.314 Sodium malate 4 '0.
0215 0.028 6 0.295 From the data in Table 2 above, the coloration after heating is almost unrelated to the type of organic acid salt added at pH 4 and 5.
At pH 5, the coloring becomes significantly stronger, and it can be seen that the strength of the coloring varies considerably depending on the type of organic acid salt. Among them, sodium lactate has the least effect, and sodium acetate has the most effect.

Figure 1 shows the following composition: maltose 20 w/v% amino acid t! %' Sodium tetrachloride
0.03 #Phosphate intoxication-potassium 0
．． 08 〃Magnesium sulfate 0.1〃 Calcium chloride 0.06 M acidic Iia
Sodium sulfate 0, 0.02, 0.04 #Sodium lactate 0.83 v (0,07
4 mol/l) Hydrochloric acid (appropriate) Adjust the pH of a water bath solution with the same rice content as in Table 1 with hydrochloric acid, and boil at 100°C.
This is a graph showing the relationship between color tone and pI (pH in the range of 4 to 7) and the effect of addition of acidic sodium sulfite when heated for 60 minutes at It can be seen that the coloring becomes stronger as the pH increases.For comparison, the results when 0.074 mol/sodium citrate was added instead of sodium lactate (pH 6 only) are shown. However, even in the presence of acidic sodium sulfate, the coloring was stronger than when sodium lactate was added.

From the above study results, it is clear that selecting lactate as the organic acid salt in an infusion containing maltose, amino acids, and electrolytes is extremely useful in suppressing coloration when formulated at a pH of 5 or higher. . However, as the pH increases to 7, the coloring increases, so - Practically desirable pH
The range is 5-7, preferably 5.5-6.5. For this reason, lactic acid is used when AII+9'2 is used for pH adjustment.

As is clear from the detailed description above, the present invention provides an infusion solution containing maltose, amino acids, and an electrolyte that supplies all or selected ions of potassium, sodium, magnesium, calcium, phosphorus, and chlorine. When the electrolyte is in the form of an organic acid, lactate is used, and lactic acid and/or mineral acid are used to adjust the pH to 5 to 7, and if necessary, water-soluble 1h sulfate or Add acid sulfite or pyrosilisulfate.

Examples are given below, but they are not intended to limit the scope of the present invention in any way.

*Oval example 1 Maltose 2001 Arginine
2.61 Inleucine 2.2P Histidine 1.370 Icine 3.1
1 Amino #%1-acid 4.81 Lysine hydrochloride 2.71 Proline 0.6
fI methionine 1.41 gelin
0.61 Phenylalanine 3.31 Tyrosine 0.2P threonine: / 1
．． 6fiL Sodium Chloride 0.53P Tryptophan 0.65 Potassium Li 1.0
5Ff Barin 2.2F? Dipotassium phosphate 0.52fI alanine 1.2
P m City Magnesium 0.37F Asparagine #1.6p Calcium chloride 0.61 Glutamine 4.7fI Sodium lactate 5.
81 Cysteine hydrochloride 0.06p Sodium acid sulfite 0.41 or more are dissolved in 700 g of distilled water for injection, and 10% lactic acid is added to adjust the pH to 6.4. Add distilled water to make a total H1t, and filter with a Millipore filter to 1t.
500m7! After filling it into an infusion vial, it was sterilized according to the Japanese Pharmacopoeia General Tests Sterilization Method.

A clear and colorless infusion solution was obtained.

Example 2 Example 1-i In Example 1, the pH was adjusted to 6 using N/10 hydrochloric acid instead of 10% lactic acid, and the following procedure was carried out in the same manner as in Example 1. Itf! ! An infusion of J Seimei was obtained.

Example 3 In Example 1, calcium lactate (1.21) was used instead of calcium chloride, and N/10*# was added to adjust the pH (3
Adjust to. The procedure was then carried out in the same manner as in Example 1 to obtain a colorless and clear infusion solution.

Effects of the Invention According to the present invention, a stable infusion solution that simultaneously contains maltose, amino acids, and electrolytes and does not change color is provided.

4. 1+'Q il- Explanation of the Drawings Figure 1 is a graph showing the relationship between 7)H and color tone (based on absorbance) 1 of an infusion solution containing maltose, amino acids, and electrolytes.

Patent applicant: Daigo Nutritional Chemical Co., Ltd. Figure 1 Hi

Claims (1)

[Claims] 1. An infusion containing maltose, an amino acid, and an electrolyte that uses an organic acid salt or a mixture of an organic acid salt and an inorganic acid salt as the electrolyte, using lactate as the organic acid salt, and lactic acid and/or A method for producing an infusion solution, which comprises adjusting the pH to 5 to 7 with a mineral acid.