JPH0414646B2 - - Google Patents

Description

〔Technical field〕

The present invention relates to an infusion solution containing reducing sugars, branched chain amino acids, and electrolytes. More specifically, the present invention relates to a novel infusion solution that uses branched chain amino acids as amino acids. [Prior Art] Since muscle protein is used as a calorie source during surgery, after surgery, and during catabolic periods such as starvation, there is a problem in that muscle protein collapses. It is known that administration of branched chain amino acids is effective in suppressing the breakdown of muscle proteins ("Surgery and Metabolism/Nutrition" Vol. 16, No. 4, 1982, 12).
(Refer to pages 524-531, published in May). In addition, reducing sugars such as glycose, maltose, and fructose are excellent sugars that suppress muscle protein breakdown by effectively utilizing amino acids and serve as a calorie source. Additionally, electrolytes need to be replenished to maintain electrolyte balance. When these preparations are mixed and sterilized in advance and manufactured, it is possible to save the effort of mixing them at the time of use and to prevent the intrusion of bacteria during mixing. However, when each of the above preparations is blended in advance and heat sterilized, Maillard
There is a problem in that a reaction occurs and coloring occurs. Conventionally, infusion preparations containing amino acids have generally contained essential amino acids such as L-methionine, L-phenylalanine, and L-tryptophan in addition to branched-chain amino acids, and are effective during the catabolic phase. There are no known infusion preparations that use only branched chain amino acids or branched chain amino acids as the main ingredient for the purpose of this effect. Moreover, it was predicted that it would be difficult to produce the product without coloring, as there is a concern that heat sterilization after blending a large amount of branched chain amino acids with reducing sugars may cause the aforementioned Maillard reaction. . Purpose of the Invention Under such circumstances, the present inventors have conducted extensive research to develop a new infusion solution useful during the catabolic phase, and have surprisingly found that only branched chain amino acids or branched chain amino acids can be used as amino acids. It was discovered that by using it as a main component, it is useful during the catabolic phase and, contrary to expectations, it is possible to suppress the Maillard reaction after heat sterilization, leading to the completion of the present invention. Therefore, the purpose of the present invention is to use reducing sugars that are excellent as a calorie source, branched chain amino acids that are effective in suppressing the breakdown of muscle proteins during the catabolic period such as during and after surgery, and furthermore to help maintain electrolyte balance. It is an object of the present invention to provide a novel infusion solution which is formulated so as to simultaneously contain an electrolyte that needs to be replenished in a preferable composition and which does not become substantially colored after heat sterilization. Detailed Description of the Invention The present invention, which meets the above objectives, is characterized by having the composition and blending amount shown in Table 1, and contains reducing sugars, branched chain amino acids, and electrolytes that are substantially uncolored after heat sterilization. It is an infusion agent.

【table】

[Table] In the present invention, heat sterilization means sterilization by heating such as high pressure steam sterilization (autoclave sterilization). Substantially no coloring after heat sterilization means that the transmittance is at least 98% when measured with a spectrophotometer (420 nm) after at least 14 days at room temperature after sterilization, or when observed with the naked eye. It is defined as having a substantially colorless and clear appearance when Glucose and/or maltose are preferably used as reducing sugars used in the infusion solution of the present invention. Fructose can also be used. The branched chain amino acids used in the present invention are L-
These are leucine, L-isoleucine, and L-valine, and the infusion preparation of the present invention always contains each of the three, and the total amount thereof is 10 to 33
g/ range. Furthermore, the amount of branched chain amino acids to be blended is preferably within the range shown in Table 2 below.

[Table] As the electrolyte, inorganic salts and/or organic salts are preferably used. Further, zinc, copper, iron, manganese, chromium, selenium, iodine, etc. can be included in the infusion solution of the present invention in advance. Examples of the sodium source of the electrolyte used in the infusion preparation of the present invention include inorganic salts such as sodium hydroxide, sodium chloride, sodium hydrogen phosphate, and sodium dihydrogen phosphate, and organic salts such as sodium lactate and sodium acetate. Yes, sources of potassium include potassium hydroxide, potassium chloride,
Potassium hydrogen phosphate, potassium dihydrogen phosphate,
Sodium chloride, potassium chloride, calcium chloride, magnesium chloride, etc. can be used as a source of chlor, calcium chloride etc. can be used as a source of calcium, and phosphoric acid-hydrogen can be used as a source of phosphorus. Sodium, sodium dihydrogen phosphate, potassium hydrogen phosphate, potassium dihydrogen phosphate, etc. can be used. Furthermore, as sources of zinc, copper, iron, manganese, chromium, selenium, iodine, etc. used in the infusion solution of the present invention, any compounds used in the production of general infusion solutions and injections can be suitably used. can be used. Surprisingly, the infusion preparation containing reducing sugars, branched chain amino acids and electrolytes of the present invention
Even after heat sterilization for 1 minute and at least 14 days at room temperature, the Maillard reaction is suppressed and the product remains clear and colorless. The pH of the infusion solution of the present invention is preferably 3.5 to 7.0. It may also contain substances necessary for the preparation of infusions, such as stabilizers and PH regulators. The infusion preparation of the present invention is administered by intravenous injection from peripheral veins or central veins. Dosage is generally for adults 1
The daily amount is 500-1000ml. EXAMPLES Hereinafter, the present invention will be explained in detail with reference to Examples, but the present invention is not limited to these in any way. Example 1 Maltose 500.0g Sodium chloride 60.0g Potassium chloride 3.0g Calcium chloride (dihydrate) 2.0g Sodium lactate 31.0g L-valine 59.0g L-isoleucine 63.0g L-leucine 77.0g Sodium bisulfite 2.0g or more were injected Dissolve in distilled water 7 and adjust the pH to 4.9 by adding lactic acid. Next, add distilled water to bring the total volume to 10, filter with a filter (manufactured by Millipore), dispense into 250ml soft plastic bags, seal, and sterilize with high pressure steam at 110℃ for 30 minutes (autoclave sterilization) ) to obtain an infusion solution containing reducing sugars, branched chain amino acids, and electrolytes. The transmittance of the infusion solution after sterilization was measured using a spectrophotometer (420 nm), and the result was 99.8%, and the appearance was clear and colorless. Example 2 Maltose 500.0g Sodium chloride 60.0g Potassium chloride 3.0g Calcium chloride (dihydrate) 2.0g Sodium lactate 31.0g L-valine 28.5g L-isoleucine 24.6g L-leucine 46.9g Sodium bisulfite 2.0g or more were injected Dissolve in distilled water 7 and adjust the pH to 4.9 by adding lactic acid. Next, add distilled water to bring the total volume to 10, filter with a filter (manufactured by Millipore), dispense into soft plastic bags with a capacity of 500 ml and 1, and seal, then heat at 110°C for 30 minutes.
Perform high pressure steam sterilization (autoclave sterilization),
An infusion solution containing reducing sugar, branched chain amino acids and electrolytes is obtained. The transmittance of the infusion solution after sterilization was measured using a spectrophotometer (420 nm), and the result was 100.0%, and the appearance was clear and colorless. Example 3 Maltose 500.0g Sodium chloride 60.0g Potassium chloride 3.0g Calcium chloride (dihydrate) 2.0g Sodium lactate 31.0g L-valine 59.0g L-isoleucine 63.0g L-leucine 77.0g Sodium bisulfite 2.0g or more were injected Dissolve in distilled water 7, add 1N sodium hydroxide, and adjust the pH to 6.5. Next, add distilled water to bring the total volume to 10%, filter with a filter (manufactured by Millipore), dispense into soft plastic bags with a capacity of 250ml, seal, and store at 110℃ for 30 minutes.
High-pressure steam sterilization (autoclave sterilization) is performed for 1 minute to obtain an infusion solution containing reducing sugars, branched chain amino acids, and electrolytes. The transmittance of the infusion solution after sterilization was measured using a spectrophotometer (420 nm), and the result was 99.3%, and the appearance was clear and colorless. Example 4 Glucose 500.0g Sodium lactate 30.3g Potassium chloride 20.1g Magnesium chloride (hexahydrate) 3.0g Potassium hydrogen phosphate 2.6g L-valine 92.6g L-isoleucine 84.0g L-leucine 123.5g Sodium hydrogen sulfite 3.0g Dissolve the above in distilled water for injection 7, add 10% malic acid, and adjust the pH to 4.9. Next, add distilled water to bring the total volume to 10, filter with a filter (manufactured by Millipore), dispense into 500ml vials, seal, and sterilize with high pressure steam (autoclave) at 110℃ for 30 minutes. An infusion solution containing reducing sugars, branched chain amino acids and electrolytes is obtained. The transmittance of the infusion solution after sterilization was measured using a spectrophotometer (420 nm), and the result was 99.7%, and the appearance was clear and colorless. Example 5 Glucose 750.0g Sodium lactate 30.3g Potassium chloride 20.1g Magnesium chloride (hexahydrate) 3.0g Potassium hydrogen phosphate 2.6g L-valine 83.3g L-isoleucine 75.6g L-leucine 111.2g Sodium hydrogen sulfite 3.0g Dissolve the above in distilled water for injection 7, add lactic acid, and adjust the pH to 4.6. Next, add distilled water to bring the total volume to 10, filter with a filter (manufactured by Millipore), dispense into 500ml vials, seal, and sterilize with high pressure steam (autoclave) at 110℃ for 30 minutes. An infusion solution containing reducing sugars, amino acids and electrolytes is obtained. The transmittance of the infusion solution after sterilization was measured using a spectrophotometer (420 nm), and the result was 99.8%, and the appearance was clear and colorless. Example 6 Glucose 2000.0g Sodium chloride 41.8g Magnesium chloride (hexahydrate) 14.5g Calcium lactate (pentahydrate) 13.2g Potassium dihydrogen phosphate 15.7g Potassium citrate (monohydrate) 33.9g Sodium lactate 16.0g Sulfuric acid Zinc (heptahydrate) 0.043g L-valine 77.0g L-isoleucine 66.4g L-leucine 126.6g Sodium bisulfite 5.0g Dissolve the above in distilled water for injection 7, add 10% malic acid, and adjust the pH to 4.3. Adjust to. Next, add distilled water to bring the total volume to 10,000 ml, filter with a filter (manufactured by Millipore), dispense into soft plastic bags with a capacity of 1, and after sealing, autoclave sterilize at 110°C for 30 minutes ( autoclave sterilization).
An infusion solution containing reducing sugar, branched chain amino acids and electrolytes is obtained. The transmittance of the infusion solution after sterilization was measured using a spectrophotometer (420 nm), and the result was 98.3%, and the appearance was clear and colorless. Example 7 Glucose 2800.0g Sodium chloride 41.8g Magnesium chloride (hexahydrate) 14.5g Calcium lactate 13.2g Potassium dihydrogen phosphate 15.7g Potassium citrate 33.9g Sodium lactate 16.0g Zinc sulfate 0.043g L-valine 28.5g L- Isoleucine 24.6g L-leucine 46.9g Sodium hydrogen sulfite 3.0g Dissolve the above in distilled water for injection 7, add lactic acid, and adjust the pH to 4.6. Next, add distilled water to bring the total volume to 10,000 ml, filter with a filter (manufactured by Millipore), dispense into soft plastic bags with a capacity of 1, and after sealing, autoclave sterilize at 110°C for 30 minutes ( Autoclave sterilization) to remove reducing sugars,
An infusion solution containing branched chain amino acids and electrolytes is obtained. The transmittance of the infusion solution after sterilization was measured using a spectrophotometer (420 nm), and the result was 99.4%, and the appearance was clear and colorless. Effects of the Invention As described above, the present invention provides a novel infusion solution containing a reducing sugar, a branched chain amino acid, and an electrolyte. Since the infusion preparation according to the present invention uses only branched chain amino acids or branched chain amino acids as the main ingredient, it is possible to suppress the breakdown of muscle protein during the catabolic period such as during and after surgery. In addition, since there is virtually no coloration even after time passes after heat sterilization, it is possible to prevent a decrease in amino acids and a decrease in nutritional value due to coloration. Furthermore, according to the present invention, reducing sugars, amino acids, and electrolytes are mixed in advance and provided in a sterilized state, which saves the trouble of mixing each preparation at the time of use and eliminates the problem of contamination by bacteria.

Claims (1)

[Scope of Claims] 1. An infusion solution containing reducing sugars, branched-chain amino acids, and electrolytes that are substantially uncolored after heat sterilization, and having the composition and amount shown in the table below. 【table】