JPH11106345A - Transfusion of nutrient - Google Patents

Abstract

PROBLEM TO BE SOLVED: To obtain a transfusion of nutrient, capable of improving a nutritional state of a patient having decreased glucose tolerance, and advancing utilization factor of sugar by formulating a carbohydrate and a polyhydric alcohol in good balance. SOLUTION: This transfusion of nutrient includes a carbohydrate (especially preferably a glucose) and a polyhydric alcohol (especially preferably glycerin). The mixing amounts of the carbohydrate and the polyhydric alcohol are preferably 0.01-600 g/L and 0.01-300 g/L respectively. The using amount of the polyhydric alcohol is preferably 0.1-20 pts.wt. based on 10 pts.wt. carbohydrate. The transfusion of the nutrient is preferably regulated so as to have pH4.0-7.5. For example, the transfusion of the nutrient is obtained by formulating 0.01-600 g carbohydrate, 0.01-300 g polyhydric alcohol, 0-250 mEq Na, 0-200 mEq K, 0-50 mEq Ca, 0-50 mEq Mg, 0-250 mEq chlorine, 0-100 μmol Zn, and 0-60 mmol P per 1 L.

Description

DETAILED DESCRIPTION OF THE INVENTION

[0001]

BACKGROUND OF THE INVENTION 1. Field of the Invention The present invention relates to a nutritional infusion containing a saccharide and a polyhydric alcohol for improving the nutritional status of a patient having a reduced glucose tolerance and increasing the utilization of sugar.

[0002]

2. Description of the Related Art Conventionally, patients who are unable or difficult to perform nutritional supplementation or oral nutrition before and after surgery in the field of surgery have been used, for example, infusions of carbohydrates, amino acids, fat emulsions and electrolytes. It is administered intravenously by appropriately mixing various infusions. However, during invasive procedures such as surgery, glucose tolerance in the living body is reduced, and glucose-containing infusions are used despite the reduced glucose utilization rate (Okumura et al., JJPEN, 7 (4), 667, 1986). In fact, in a clinical setting, a carbohydrate-containing infusion for the purpose of calorie and hydration is useful as a maintenance infusion, and glucose is the first sugar to be selected. Therefore, most of the commercially available carbohydrate-containing infusions mainly use glucose as a carbohydrate and use fructose, maltose, xylitol, sorbitol, and the like. At present, no consideration has been given to the time of the decline. Therefore, a new infusion agent capable of increasing the utilization rate of sugar even when glucose tolerance is reduced has been desired.

[0003]

SUMMARY OF THE INVENTION In view of the above situation, an object of the present invention is to provide a new nutritional infusion for improving the nutritional status of a patient having a reduced glucose tolerance and increasing the utilization of sugar. Is to do.

[0004]

Means for Solving the Problems As a result of intensive studies on the above problems, the present inventors have found that the above problems can be solved by blending a carbohydrate and a polyhydric alcohol in a nutritional infusion with a good balance. The present invention has been completed.

[0005] That is, the present invention relates to an infusion for improving the nutritional status of a patient having a reduced glucose tolerance and enhancing the utilization rate of sugar, and comprising a carbohydrate and a polyhydric alcohol. Get involved.

[0006] In particular, according to the present invention, there is provided a nutritional infusion having at least the following composition and having a pH adjusted to 4.0 to 7.5. Ingredients Amount (in 1 liter) Carbohydrate 0.01-600 g Polyhydric alcohol 0.01-300 g Sodium 0-250 mEq Potassium 0-200 mEq Calcium 0-50 mEq Magnesium 0-50 mEq Chlorine 0-250 mEq Zinc 0-100 μmol Phosphorus 0-60 mmol

[0007] The nutrient infusion of the present invention has the above-mentioned constitution, and is characterized by improving the nutritional status of a patient with impaired glucose tolerance and increasing the utilization of sugar by administering intravenously. Have.

[0008]

BEST MODE FOR CARRYING OUT THE INVENTION Monosaccharides, disaccharides, sugar alcohols and the like are used as the carbohydrates constituting the nutritional infusion of the present invention. For example, glucose, fructose, maltose,
Xylitol, sorbitol, lactose, galactose and the like can be mentioned. Two or more of these may be used as a mixture, but glucose is particularly preferably used.
Glycerin is preferred as the polyhydric alcohol used in the present invention.

In the present invention, the compounding amount of the above-mentioned saccharide and polyhydric alcohol is an amount sufficient to improve the nutritional status of a patient having reduced glucose tolerance and to enhance the utilization of sugar, and In an amount that does not adversely affect the metabolism in Specifically, each is 0.01 to 600 g / l, 0.01 to
300 g / l, more preferably 0.02 to 400
g / l, 0.01 to 200 g / l.

The amount of the polyhydric alcohol used in the present invention is 0.1 to 2 parts by weight per 10 parts by weight of the saccharide.
0 parts by weight, preferably in the range of 0.5 to 10 parts by weight.

Further, as a raw material for providing the electrolyte composition of the nutrient infusion of the present invention, various water-soluble salts conventionally used in infusions can be mentioned. For example, various water-soluble salts required for maintaining the electrolyte balance of a living body can be mentioned. And water-soluble salts of inorganic components (sodium, potassium, calcium, magnesium, phosphorus, etc.). Specifically, sodium bicarbonate, sodium carbonate, sodium dihydrogen phosphate, disodium hydrogen phosphate, sodium acetate, sodium lactate, sodium citrate, sodium chloride, sodium sulfate, potassium chloride, potassium iodide, diphosphate Potassium hydrogen, dipotassium hydrogen phosphate, potassium lactate, potassium citrate, potassium acetate, potassium lactate, calcium lactate, sodium glycerophosphate, potassium glycerophosphate, calcium glycerophosphate, calcium gluconate, calcium chloride, magnesium chloride, magnesium sulfate, acetic acid Magnesium and the like.

The amount of the above-mentioned electrolyte may be the same as usual, and can be appropriately determined according to the required amount of the patient. For example, specific amounts of sodium are 20 to 150 mEq, 5 to 50 mEq for potassium, 2 to 10 mEq for calcium, 1 to 8 mEq for magnesium, 20 to 150 mEq for chlorine, 0 to 30 μmol of zinc, and 0 to 30 μmol of phosphorus per liter.
About 20 mmol is preferable.

It is also possible to add bicarbonate ion, acetate ion and lactate ion as an alkalinizing agent to the nutritional infusion of the present invention, if necessary.

The nutritional infusion of the present invention can be produced according to a known infusion method. For example, a predetermined component is weighed, mixed and dissolved in a corresponding amount of distilled water for injection, and a stabilizer such as sodium sulfite or a pH adjuster can be added as necessary. PH of the nutritional infusion of the present invention
Generally ranges from 4.0 to 7.5, preferably 4.5.
It is adjusted to about 6.5, and can be carried out using a usual pH adjuster, for example, acids such as hydrochloric acid, acetic acid, citric acid, lactic acid and malic acid, and alkalis such as sodium hydroxide and potassium hydroxide. In particular, when citric acid is used, it has a chelating ability, which helps to prevent the formation of a hardly soluble precipitate.

The infusion solution prepared above is filtered through a 0.22 μm membrane filter, and the filtrate is filled in a suitable container such as a glass container or a plastic container (eg, polyethylene, polypropylene, polyvinyl chloride, ethylene-vinyl acetate copolymer). Then, the space is replaced with nitrogen, sealed tightly, and sterilized (high-pressure steam sterilization, hot water immersion sterilization, hot water shower sterilization, etc.) is performed at about 100 to 130 ° C. for 10 to 60 minutes according to a conventional method.

The nutritional infusion of the present invention is administered parenterally alone or, if necessary, mixed with an infusion of amino acids, fat emulsions and the like, drugs and the like. The daily dose is appropriately determined according to the condition of the patient.
The volume is preferably about 2,000 to 2,000 ml.

Furthermore, in the case of the nutritional infusion of the present invention utilizing an amino acid infusion, it is important to separately store the amino acid infusion and the carbohydrate-containing infusion in a container having a plurality of chambers in order to prevent the Maillard reaction. . In a preferred embodiment of the nutritional infusion of the present invention, for example, the nutritional infusion of the present invention can be accommodated in the first chamber, and the amino acid infusion can be accommodated in the second chamber.

Examples of the amino acid include various amino acids conventionally used for nutritional supplementation, such as L-isoleucine, L-leucine, L-valine and L-valine.
-Lysine, L-methionine, L-phenylalanine, L
-Threonine, L-tryptophan, L-arginine,
L-histidine, glycine, L-alanine, L-proline, L-aspartic acid, L-serine, L-tyrosine,
L-glutamic acid, L-cysteine and the like are exemplified. The amino acids are usually used in the form of free amino acids, but pharmacologically acceptable salts, such as metal salts with sodium and potassium, acetic acid, organic acid salts with malic acid, hydrochloric acid,
It may be in the form of a mineral salt with sulfuric acid.

Furthermore, if necessary, trace elements, various vitamins, etc. can be added. As trace elements,
Elements required to maintain the balance of the body that have been used for infusions (zinc, iodine, manganese,
Copper, iron, etc.), for example, zinc chloride, zinc sulfate, iron sulfate, ferrous chloride, ferric chloride, iron gluconate, copper sulfate, manganese chloride, manganese sulfate, potassium iodide, sodium iodide, etc. Is mentioned.

Examples of the vitamins include retinol palmitate, thiamine hydrochloride, ribofuramine, pyridoxine hydrochloride, cyanocobalamin, ascorbic acid, cholecalciferol, tocopherol acetate, nicotinamide, calcium pantothenate, folic acid, biotin, phytonadione and the like.

[0021]

EXAMPLES Hereinafter, the present invention will be described in more detail with reference to Examples and Test Examples, but the present invention is not limited thereto.

Example 1 50 g of glucose, 25 g of glycerin, 1.46 g of sodium chloride, 0.82 g of sodium acetate (trihydrate), 0.1 g of calcium chloride (dihydrate).
37 g, magnesium chloride (hexahydrate) 0.51 g, dipotassium hydrogen phosphate 1.74 g and zinc sulfate (heptahydrate)
0.0014 g was sequentially dissolved in distilled water for injection, the pH was adjusted to 5.0 with citric acid, and the total amount was adjusted to 1000 ml with distilled water for injection. The mixture was filtered through a 0.22 μm membrane filter and dispensed into 500-ml plastic bags for infusion in 500-ml portions. This was sterilized by high-pressure steam at 121 ° C. for 20 minutes, and then packaged in a gas-barrier packaging material.
A nutritional infusion of the present invention was produced.

Example 2 A nutrient infusion of the present invention was produced in the same manner as in Example 1 except that glucose was 25 g and glycerin was 50 g.

Comparative Example 1 A comparative liquid 1 was prepared in the same manner as in Example 1 except that 75 g of glucose was used.

Comparative Example 2 A comparative liquid 2 was prepared in the same manner as in Example 1 except that glycerin was 75 g.

[Stability test] The infusion solutions of Examples and Comparative Examples were stored at 40 ° C. for 3 months, and then colored (transmittance: 430 n).
m), appearance (presence or absence of precipitation), glucose decomposition (absorbance at 284 nm) and pH were measured.

As a result, even after sterilization and storage for 3 months, the infusions of Example and Comparative Example 2 showed no change in coloring, appearance, decomposition of glucose and pH. On the other hand, in Comparative Example 1, after storage for 3 months, no change was observed in appearance and pH, but decomposition of glucose and accompanying coloring were observed. Table 1 shows the results.

[0028]

[Table 1]

[Action mechanism] SD with a weight of 160 to 220 g
Streptozotocin 45 mg / kg was administered to male rats to produce diabetic rats. Seven days later, a silicone rubber catheter was inserted and placed into the root of the superior vena cava from the jugular vein so that intravenous administration was possible without restraint. Then, the infusions of Example 1 and Comparative Example 1 were applied to model rats for 27 days.
The administration was carried out at a rate of 0 ml / kg / day until the next day (4 animals per group). In addition, a catheter was similarly placed in a normal rat, and Comparative Solution 1 was administered in the same manner (4 animals). next day,
Immediately after the end of the infusion administration, rats in each group were administered a ¹⁴ C-labeled glucose solution. Immediately after administration, 2
After breeding for 4 hours, ¹⁴ CO ₂ was collected and the excretion rate of ¹⁴ CO _{2 in} breath was measured. The results are shown in FIG.

In the example group, the utilization rate of glucose, which was reduced in the disease state, was significantly increased to the level of the normal group as compared with the comparative example group. From these results, it became clear that the nutritional infusion of the present invention enhances the utilization rate of glucose.

[Nutrition evaluation test] Streptozotocin 45 mg / kg was administered to SD male rats weighing 160 to 220 g.
Was administered to produce diabetic rats. Seven days later, a silicone rubber catheter was inserted and placed from the jugular vein at the origin of the superior vena cava so that intravenous administration was possible without restraint.
Then, the infusion of Example 1 and Comparative Example 1 was added at 270 ml / k.
The animals were administered at a rate of g / day for 3 days (4 animals per group). Three days later, the body weight, blood glucose concentration and blood insulin concentration of each group of rats were measured. Table 2 shows the results.

[0032]

[Table 2]

In the example group, weight loss was significantly suppressed as compared with the comparative example group. In addition, the blood insulin concentration also showed a high value in the example group. There was no difference between the two groups in blood glucose concentration. From this result, it was clarified that the nutritional infusion of the present invention was excellent also in the nutritional effect.

[0034]

As described above, the nutritional infusion of the present invention comprises:
Since the carbohydrate and the polyhydric alcohol are blended in a well-balanced manner, it is possible to improve the nutritional status of a patient whose glucose tolerance is reduced at the time of invasion such as a surgical operation, and to increase the sugar utilization rate.

[Brief description of the drawings]

FIG. 1 is a graph showing the glucose utilization rates of a group administered with a nutritional infusion solution of the present invention and a group administered with a comparative example in Test Example 2.

────────────────────────────────────────────────── ─── Continued on the front page (51) Int.Cl. ⁶ Identification code FI A61K 33/30 A61K 33/30 (72) Inventor Kazuhisa Ozeki 1658 Onoshihara, Yasu-cho, Yasu-gun, Shiga Prefecture Japan Hoechst Marion Roussel Inside the Development Laboratory Co., Ltd. (72) Inventor Taiji Nakano 1658, Oshinohara, Yasu-cho, Yasu-gun, Shiga Prefecture Japan Inside the Development Laboratory, Hoechst Marion Roussel Co., Ltd. Japan Hoechst Marion Roussel Co., Ltd.

Claims (3)

[Claims] 1. An infusion for improving the nutritional status of a patient with reduced glucose tolerance and enhancing the utilization of sugar, wherein the infusion contains saccharides and polyhydric alcohols. Agent. 2. The composition has at least the following composition and has a pH of 4.0.
The nutritional infusion according to claim 1, wherein the nutritional infusion is adjusted to 7.5. Ingredients Amount (in 1 liter) Carbohydrate 0.01-600 g Polyhydric alcohol 0.01-300 g Sodium 0-250 mEq Potassium 0-200 mEq Calcium 0-50 mEq Magnesium 0-50 mEq Chlorine 0-250 mEq Zinc 0-100 μmol Phosphorus 0-60 mmol 3. The nutritional infusion according to claim 1, wherein the carbohydrate is glucose and the polyhydric alcohol is glycerin.