JPS6287597A - Maltopentaose fatty acid ester and transfusion solution containing same - Google Patents

Abstract

NEW MATERIAL:A compound which is obtained by esterifying maltopentaose with linoleic acid or alpha-linolenic acid in the 1-position. EXAMPLE:Maltopentaose 1-0-linolenate. USE:A component is intravenous nutrient transfusion containing saccharides and essential fatty acids. Since linoleic or alpha-linolenic acid, a hydrophobic and essential fatty acid, is converted into a water-soluble derivative, the fatty acid can be included in the transfusion solution containing saccharides in no need of emulsification. Thus, a homogeneous transfusion solution with high qualityl, safety and rich nutirents is obtained. PREPARATION:The condensation reaction between a reactive derivative of linoleic acid or alpha-linolenic acid such as thiazolidinethione-linoleic acid amide and maltopentaose is effected in a solvent such as pyridine in the presence of sodium hydride.

Description

Detailed Description of the Invention 10 Background of the Invention (Technical Field) The present invention relates to maltopentaose fatty acid esters in which the 1st position of maltopentaose is esterified with linoleic acid or α-linolenic acid, and the maltopentaose fatty acid esters. and regarding infusion preparations containing all carbohydrates.

(Prior Art) Various infusion preparations containing carbohydrates are commercially available, but some of them contain the essential fatty acids linoleic acid and α-linolenic acid in water-soluble form, and contain carbohydrates. There are no intravenous fluids. This is because these fatty acids are originally hydrophobic.

Further, there is no known substance in which linoleic acid or α-linolenic acid is subjected to a regioselective esterification reaction to the 1-position hydroxyl group of maltopentaose. Furthermore, conventional methods for producing only mixtures of mono-, di-, and triesters, or mixtures of monoesters have not been disclosed, and methods for selectively producing single monoesters have not been disclosed. There was no known infusion solution that uses the compound alone and is stable in terms of quality and pharmacology.

■Purpose of the Invention The present inventors have conducted extensive research to simultaneously incorporate essential fatty acids, which are hydrophobic in nature, into an infusion containing carbohydrates without emulsifying them.
The novel maltopentamase fatty acid ester esterified with linoleic acid or α-linolenic acid at the position of The inventors succeeded in preparing an infusion solution containing carbohydrates and discovered that the infusion solution is a highly stable nutritional infusion solution, leading to the completion of the present invention.

That is, an object of the present invention is to provide a novel water-soluble malto-intaose fatty acid ester. A further object of the present invention is to provide an infusion solution containing linoleic acid and α-linolenic acid in water-soluble form.

The present invention, which achieves the above object, is a novel malto-intaose fatty acid ester in which the first position of maltopentaose is esterified with linoleic acid or α-linolenic acid. The present invention also provides an infusion solution comprising an aqueous solution containing the maltointaose fatty acid ester and carbohydrates.

The aqueous solution further contains an electrolyte, and the concentration range of the elements in the 1L maltopentaose fatty acid ester and the electrolyte is 50-MoU/l malto-intaose-1-0-1,1, Q4Q. Esther 5~100 S! /1 maltopentaose-1
-0-α-Ril 4'2 esthetics) L/2~30. Li/l Sodium 0-100 mmol/l Potassium
Um 10-60 mmol/l salt
Element O~100 mmol/l phosphorus
3-10 mmol/! magnesium
1 to 6 mmol/1 calcium 1
~ J mmol/l zinc
0 to 40 micromo missing/lr ROM
It is preferably 0 to 1 micromol/l.

Detailed Description of the Invention The maltopentaose fatty acid ester of the present invention can be obtained by condensing a reactive derivative of a fatty acid with malto-intaose in a hot medium in the presence of an alkali hydride. The maltopentaose fatty acid varnish f, It/ contains linoleic acid or α-linolenic acid, which are essential fatty acids, and can be administered into the body as a nutrient, but is particularly preferably in the form of an infusion solution as detailed below.

The infusion preparation of the present invention can be obtained by adding carbohydrates, maltopentaose fatty acid esters, and, if necessary, electrolytes to distilled water for injection and stirring. Its preferable composition and blending amount are shown in Table 1.

Table 1 The electrolyte containing sodium in Table 1 is NPL.
Cl! Sodium lactate, sodium acetate 9 Sodium citrate, KCl, K2HP for potassium
O4, KH2PO4, potassium glucuronate, potassium acetate, potassium citrate, and M for magnesium.
gCl2. MgSO4, calcium lactate, CaCl2 *calcium glucuronate, zinc Zn8041Zn C42, chromium, Cr(OAC), CrCl3, all of which can be selected and used as appropriate. .

The infusion of the present invention is filled into a vial or a soft plastic container that is inert to the infusion, the filling opening is then sealed, and the container is sterilized by high-pressure steam sterilization (autoclave sterilization). .

The container is preferably a plastic container that is inert to the infusion, and should be used to prevent contamination due to contact with the outside air.
In view of preventing deterioration of the infusion solution such as gelatinization due to oxygen in the outside air, it is desirable to use a soft plastic bag that is inert to the infusion solution and does not require introducing outside air into the container through a ventilation needle.

As the material for this bag, soft vinyl chloride resin, ethylene-vinyl acetate copolymer, etc. are used.

The soft vinyl chloride resin may be, for example, one obtained by graft polymerization or block polymerization of a plastic monomer to vinyl chloride, or one obtained by blending a plastic polymer with polyvinyl chloride.

During sterilization, by removing all gas from the container before VC bacteria, even if the reactivity of the infusion solution increases due to heat, it is possible to minimize the deterioration of the infusion solution.

Intravenous fluids packed in plastic containers? When performing high-pressure steam sterilization, remove gases that are active against infusions from around the container. For example, by sterilizing in a gas atmosphere that is inert to infusions, plastics whose gas permeability increases at high temperatures can be used. It can overcome the drawbacks of containers.

(9) Specific effects of the invention As described above, the present invention provides a novel maltopentaose fatty acid ester.

The malto(ntaose) fatty acid ester according to the present invention can impart water solubility to linoleic acid or α-linolenic acid, which are originally hydrophobic, so that it can be used without emulsifying linoleic acid or α-linolenic acid. It can be included in an infusion solution containing.

It was confirmed that the maltopentaose fatty acid ester used in agent 14ii of the present invention has excellent water bathability and is excellent as a water bath conductor for fatty acids.

Furthermore, the hemolytic toxicity of the infusion preparation of the present invention was investigated, and no hemolytic toxicity was observed when administered intravenously, confirming its excellent safety.

In addition, the ester contained in the infusion of the present invention is a monoester in which the 1st position of maltopentaose is esterified, and is different from conventional mixtures of mono-, di-, and triesters, and can be obtained by purification. Unlike a mixture of monoesters, it is a monoester that is selectively esterified at the 1st position, so it is possible to prepare a uniform infusion solution, and the quality and quality
It is also superior in terms of safety and reputation.

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

Production Example-1 Under an atmosphere of argon, 24 μm of oily hydrogenated IJ (containing 60%) was added to a dry pyridine solution containing 7.4581 g of maltopentaose at room temperature.

After 3 minutes, thiazolicinthione-linoleic acid amide 1.1
A layer of 46.9 dissolved in 3 rnl of dry piricin was added. Subsequently, after reacting at room temperature for 3.5 hours, the reaction mixture was cooled on ice, and a saturated ammonium chloride aqueous solution f1.0.5
Added rnl. From this, pyridine was completely distilled off under reduced pressure at room temperature to obtain a residue of 8.802F. The residue was diluted with acetone 100%
The suspension was suspended in m1 at room temperature, and an acetone-insoluble portion of 8.712.9 was obtained by suction treatment. The acetone insoluble matter was suspended in 160 mJ of a mixed hot medium of chloroform and methanol (2:1) at room temperature, and the insoluble matter was filtered off by suction filtration. The heating medium was distilled off under reduced pressure from this mother liquor, and maltopentaose-1-
1.191.9 of 0-linoleic acid ester was obtained. The spectral data of this ester are as follows.

1150, 1080, 1030 Production Example-2 - Maltopentaose and thiazolidinethione-α-linolenic acid amide, maltopentaose-1-0-α-linolenic acid ester Kinzensho by the same operation as in Branching Example-1 . The spectral data of this ester are as follows.

1150, 1080, 1030 Example 1 Maltopentaose-1-0-IJ nolic acid ester 2
All of the components listed in V//V and Table 2 were dissolved in sterilized distilled water in the proportions listed under stirring. The resulting aqueous solution was adjusted to pH 5.5.

The aqueous solution (all sterile-filtered) was dispensed into soft plastic bags of 500 ml and sealed, and then heated at 121°C at 20°C.
It is sterilized using pressure steam for 1 minute to make a mucous agent.

Table 2 Example 2 Maltopentaose-1-0-linoleic acid ester 2.
5 w/v % and maltopentaose-1-0-α
- An infusion solution was obtained in the same manner as in Example 1 except that 0.5 vr/v% of linolenic acid ester was contained.

Trial Example A catheter was placed in the jugular vein of 30 male Wistar rats (around 1).They were divided into 3 groups, and the 1st group served as a control with glucose 10 vy/v% having the composition shown in Table 2 of Example 1. The solution containing @ was administered continuously for 4 hours at a flow rate of 5 doses/hour for 5 days.The second group received the infusion prepared in Example 1, and the third group received the infusion prepared in Example 2. The drug was administered in the same manner.As a result of examining the change in the number of red blood cells due to the infusion drug, there was no significant difference between the three groups as shown in Table 3.No abnormalities were observed in each organ, and the average increase in body weight was The first group is 10.3g, the second group is 12.4g.
At 11.8 fi in Group 3, the number increased steadily, no abnormal findings were observed due to infusion, and no signs of sex were observed.

(Ba1 secret) Table 3 Rate of change in red blood cell count (correspondence)

Claims (3)

[Claims] (1) Maltopentaose fatty acid ester in which the 1st position of maltopentaose is esterified with linoleic acid or α-linolenic acid. (2) An infusion solution comprising an aqueous solution containing a maltopentaose fatty acid ester in which the first position of maltopentaose is esterified with linoleic acid or α-linolenic acid and a carbohydrate. (3) The aqueous solution contains an electrolyte, and the concentration range of carbohydrates, maltopentaose fatty acid esters, and elements in the electrolyte is carbohydrate
50-350g/l maltopentaose-1-O-linoleic acid ester
5-100g/l Maltopentaose-1-O-α-linolenic acid ester 2-30g/l Sodium
0-100 mmol/l potassium
10-60 mmol/l chlorine
0-100 mmol/l phosphorus
3-10 mmol/l magnesium
1-6 mmol/l calcium
1-6 mmol/l zinc
0-40 micromol/l chromium
The infusion preparation according to claim 2, which has a concentration of 0 to 1 micromol/l.