JPS6251616A - Glucide transfusion agent - Google Patents

Abstract

PURPOSE:A glucide transfusion agent, obtained by incorporating palatinose with a specific saccharide or sugaralcohol and suitable for treating hypoglycemia, etc. CONSTITUTION:A glucide transfusion agent obtained by incorporating palatinose with at least one saccharide or sugaralcohol selected from monosaccharides, e.g. glucose or fructose, disaccharides, e.g. maltose, and monosugaralcohol, e.g. sorbitol or xylitol at 7:3-9:1 weight ratio of the saccharide to the sugaralcohol and dissolving the resultant mixture in distilled water for injection to a given concentration, filtering the formed solution through a membranefilter to remove undissolved materials, filling the filtrate in a specified container and sterilizing the filled solution while heating. EFFECT:The osmotic pressure of the palatinose is 1/2 of that of the monosaccharide and the palatinose can be used in a concentration of twice that of the monosaccharide. The palatinose is hydrolyzed into glucose and fructose in the tissue, absorbed and utilized when parenterally administered and both can be simultaneously supplied.

Description

DETAILED DESCRIPTION OF THE INVENTION 10. Background of the Invention [Technical Field] The present invention relates to a novel carbohydrate infusion. More specifically, the present invention relates to a carbohydrate infusion prepared by blending palatinose with a specific substance or sugar alcohol.

The carbohydrate infusion preparation of the present invention has a low rate of urinary excretion of 9-glycosides when administered to the human body, and is therefore suitably used for the treatment of hypoglycemia and the like.

[Prior art and its problems]

Carbohydrate infusions have conventionally been prepared using glucose, fructose, maltose, sorbitol, xylitol, etc. as carbohydrates. These carbohydrates are non-toxic and can be used effectively within the body, so they are excellent as hydration, calorie replenishment, and therapeutic agents for hypoglycemia and the like.

However, monomers such as glucose, fructose, norbitol, and x'J)-l raise the osmotic pressure by about twice as much as two types such as maltose, which limits the administration rate and concentration. Glucose is widely used in current doses, but caution is required when administering it to diabetic patients as it may induce hyperglycemia. Maltose has the advantage that it can be administered at twice the concentration or at twice the rate of monosaccharides, but its urinary excretion rate is higher than that of glucose, so even if it is administered at a normal rate, the urinary excretion rate is considerably higher, or 9. Osmotic diuresis causes polyuria, which puts a heavy burden on the kidneys.

In order to improve these drawbacks, carbohydrate infusion preparations using palatinose as bran have recently been proposed (Japanese Patent Application Laid-Open Nos. 59-219232 and 60-1121).

Since palatinose is a nonadaccharide consisting of lucose and fructose, the increase in osmotic pressure is smaller than that of monosaccharides. Furthermore, it is broken down in the body to produce glucose and fructose, so it is nutritionally balanced, and its decomposition rate is slower than maltose, so it retains calories for a long time. Although palatinose has many advantages as a carbohydrate infusion, it has the disadvantage of being excreted into the urine at a rate as high as that of maltose.

■0 Purpose of the Invention The present inventors conducted intensive research to improve the above-mentioned drawbacks and found that when a specific sugar alcohol is added to palatinose, the amount of palatinose in the urine is unexpectedly lower than when administered alone. It was found that the excretion of The present invention was completed based on this new knowledge.

Therefore, an object of the present invention is to provide a carbohydrate infusion in which the excretion of palatinose into the urine is suppressed.

10 Detailed Description of the Invention The carbohydrate infusion preparation of the present invention is made by blending palatinose with at least one sugar or sugar alcohol selected from monosaccharides, two types, and monosaccharide alcohols.

Palatinose used in the present invention is naturally contained in honey and cane, and glucose and fructose are α-1,
There are two types with 6 bonds. Industrially, for example, immobilized α
- Produced from shake cloth using glucosyltransferase (Japanese Patent Publication No. 5B-56959).

There are no particular restrictions on the monosaccharides, two types of monosaccharides, and monosaccharide alcohols to be added to palatinose, but glucose or fructose is preferably used as the monosaccharide, maltose is the two types of monosaccharides, and nrubitol or xylitol is preferably used as the monosaccharide alcohol. In addition, the blending ratio of palatinose and sugar or sugar alcohol is not critical, but is between 7:3 and 9:1.
The range of (weight ratio) is preferable. Carbohydrate infusions are usually prepared to be isotonic with blood. The isotonic sugar concentration for monosaccharides is approximately 5 w/w/
Since 10≠T for the two types of v % s, the concentration is appropriately determined depending on the type of sugar to be blended and the blending ratio.

Preparation of the carbohydrate infusion of the present invention does not require any special equipment or techniques, and can be easily prepared according to conventional methods. For example, purified Palatinose, which does not contain pyrogens, and the above sugar or sugar alcohol are mixed at a ratio of 7:3 to 9:1 (weight ratio), and dissolved in distilled water for injection to a predetermined concentration. Prepare. Next, this solution is passed through a menglan filter to remove insoluble matter, and after being filled into a designated container, it is heat sterilized.

The carbohydrate infusion of the present invention is administered intravenously using a commercially available drip device. The dosage in this case is appropriately determined depending on the patient's condition and the purpose of use.

The osmolality of palatinose is about 2% of that of monosaccharides.
Can be used at twice the concentration. Furthermore, when palatinose is administered parenterally, it is hydrolyzed into glucose and fructose in tissues and absorbed and utilized, so that glucose and fructose can be supplied simultaneously. Palatinose increases blood sugar levels more slowly and sustainably than maltose, and is not as dependent on insulin as glucose, making it an excellent raw material for infusions for patients with impaired glucose tolerance.・As a result of a mutagenicity test using bacteria, solatinose has mutagenicity.As a result of an acute toxicity test using rats, LD5Q is 32,000 W when administered orally.
/Kf or more. For chronic toxicity, 1500.
As a result of forcibly administering doses of 3,000 and 4,500 k/4 to rats, no toxic symptoms or significant changes in body weight, food intake, water intake, or urine output, which could be attributed to sample administration, were observed.

In the present invention, many studies have already been carried out regarding the safety of the above-mentioned sugars and sugar alcohols that are incorporated into palatinose, and there are no problems with their use.

Next, the present invention will be explained in more detail with reference to Examples and Test Examples.

Example 1 Pyrogenic substances were removed and nine crystalline Palatinose (purity 99.9
- Above) Dissolve 5.49 Kl and crystalline fructose λ31 noodles uniformly in 100 tons of distilled water for injection while stirring.

Next, this solution is filtered through a membrane filter to remove insoluble substances, and then dispensed into 20-capacity containers. This solution was sterilized at 110℃ for 30 minutes, and the concentration of 7.8%
CM/V) carbohydrate infusion preparation is obtained. The blending ratio of palatinose and fructose in this infusion is 7:3 (weight ratio).

Example 2 Palatinose 6.64Ky and fructose 1.66Kf
When prepared in the same manner as in Example 1 above using
w/v) carbohydrate infusion preparation is obtained. The blending ratio of palatinose and fructose in this infusion is 8:2 (weight ratio).

Example 3 Palatinose 8.56 Kfe and fructose 0.95 Kfe
When prepared in the same manner as in Example 1 above, 95 inches (W/
The carbohydrate infusion preparation V) is obtained. The mixing ratio of palatinose and fructose in this infusion solution is 9:1 (weight ratio).

A 9.5 t (V/v) carbohydrate infusion preparation is obtained in the same manner as described above except that xylitol is used instead of fructose in the above example.

Example 4 When V4 is produced in the same manner as in Example 1 using 7 palatinose noodles and 3 maltose noodles, a 10% (η~) carbohydrate infusion solution is obtained. The blending ratio of latinose and maltose in this infusion is 7:3 (weight ratio).

Example 5 When prepared in the same manner as in Example-1 above using 8 pieces of Palatinose and 2Kt1 of maltose, a 10-t (W/V) carbohydrate infusion solution is obtained. The blending ratio of /zo2tinose and maltose in this infusion solution is 8:2 (weight ratio).

Example 2 Example 6 A 10% (W/V) carbohydrate infusion solution is obtained by using 9~ of palatinose and 1~ of maltose and carrying out the same procedure as in Example 1 above. The mixing ratio of palatinose and maltose in this infusion is 9:1 (weight ratio).

Test Example The carbohydrate infusion of the present invention and the control infusion were administered to dogs,
Determine the rate of sugar excretion into the urine9.

That is, the carbohydrate infusion of the present invention and the control infusion were injected into normal male mongrel dogs (body weight 15 to 20, 5 to 7 dogs/group) that had been fasted overnight at a predetermined rate for 90 minutes through the lower leg veins. A plastic catheter was inserted into the bladder for 120 minutes at 30-minute intervals from the start of the infusion to collect urine.
The total amount of sugar in the urine was measured. Measurement is by glucose oxidase method for glucose, acetonitrile for other sugars:
The HPLC method was carried out using water (82:18) as the solvent. Total carbohydrate weight % in urine relative to total carbohydrate weight injected
was calculated. The results are shown graphically in Figures 1-3.

In each graph, it can be seen that the urinary excretion rate of the infusion solution of the present invention (infusion solution containing palatinose and sugar or sugar alcohol) is considerably lower than that of the control infusion solution (infusion solution containing only palatinose). it is obvious.

Figures 1 to 3 show the results of infusions in which glucose, sorbitol, or maltose were blended with latinose, respectively, but similar results were obtained for infusions in which fructose or xylitol were blended. Obtained next.

(1) Specific effects of the invention According to the present invention, a palatinose infusion having many advantages as a carbohydrate infusion is provided.

Like maltose, palatinose is a disaccharide, so it has the advantage of little increase in osmotic pressure. In addition, maltose decomposes to produce only glucose, whereas nozolatinose produces glucose and fructose, so it is nutritionally balanced and does not cause a sudden rise in blood glucose concentration. Additionally, it has a slower decomposition rate than maltose, so it retains calories for a long time.

The present invention further provides a carbohydrate infusion in which the rate of urinary excretion of palatinose is significantly suppressed.

/zo Latenose has the disadvantage of having a high excretion rate in urine and large losses compared to other sugars, but in the infusion preparation of the present invention, palatinose is combined with a specific sugar or sugar alcohol. Urinary excretion rate is suppressed, improving the drawbacks of palatinose infusions.

[Brief explanation of the drawing]

Figures 1, 2 and 3 show the urinary excretion rates of the carbohydrate infusion of the present invention and the control carbohydrate infusion, respectively.

Claims (1)

[Scope of Claims] 1) A carbohydrate infusion preparation comprising Palatinose and at least one sugar or sugar alcohol selected from monosaccharides, disaccharides, and monosaccharide alcohols. 2) The carbohydrate infusion preparation according to claim 1, wherein the monosaccharide is glucose or fructose. 3) The carbohydrate infusion preparation according to claim 1, wherein the disaccharide is maltose. 4) The carbohydrate infusion preparation according to claim 1, wherein the monosaccharide alcohol is sorbitol or xylitol. 5) The ratio of palatinose to sugar or sugar alcohol is 7:
The carbohydrate infusion preparation according to any one of claims 1 to 4, wherein the ratio is 3 to 9:1 (weight ratio).