JPS6230794A - Production of concentrated aqueous solution of glycyrrhizin - Google Patents

Abstract

(57) [Abstract] This bulletin contains application data before electronic filing, so abstract data is not recorded.

Description

DETAILED DESCRIPTION OF THE INVENTION The present invention relates to a method for producing a concentrated aqueous solution of sparingly water-soluble glycyrrhizin and its monosalt useful as a pharmaceutical at room temperature.

Glycyrrhizin is well known to be a useful substance that has strong anti-allergic and anti-inflammatory effects, as well as the ability to improve liver function abnormalities in chronic liver diseases. Glycyrrhizin and its monosalts are difficult to dissolve in water at room temperature, and When dissolved at high temperatures, they tend to precipitate into a gel as the temperature decreases.

Therefore, when producing these aqueous solutions, the actual situation is that they are heated to, for example, 40 to 50°C, and dissolved in the presence of an appropriate amount of alkali.

However, depending on the raw material, trace amounts of flavonoid pigments may be present as impurities, which may cause the solution to be colored pale yellow.

On the other hand, di- and tri-salts of glycyrrhizin are soluble in water but have problems with purity and coloring, so they are mainly used as food additives and cosmetics, and are used as raw materials for products that require high purity such as injections. It is not used as.

Therefore, the present inventor has made extensive research into a method for dissolving glycyrrhizin or its salts at high concentrations at room temperature, and what is more noteworthy is that an excess amount of solid creatinine is suspended in a saturated solution of creatinine. It was discovered that when a large amount of glycyrrhizin or its monosalt was added to the solution, the creatinine crystals disappeared and more glycyrrhizin than expected was still dissolved in the monosalt. It was discovered that by diluting with water if desired, the concentration currently used as a medicine, that is, 0.1 to 2%, could be achieved without any problems, and the present invention was completed based on a method for producing the main liquid.

Examples of the monosalt of glycyrrhizin used in the present invention include ammonium salt, sodium salt, and potassium salt.

To produce a concentrated aqueous solution of glycyrrhizin or its monosalt according to the present invention, first a nearly saturated solution of creatinine (creatinine content of about 7% or more) is prepared,
Add it little by little while stirring at any temperature within After addition, stirring is generally continued for 1 to 8 hours to obtain a clear, free-flowing, concentrated solution of glycyrrhizin or its monosalt.

Since the pH of the solution obtained in this way is usually within the range of 5.0 to 5.8, it may be treated with an alkali hydroxide such as sodium hydroxide or potassium hydroxide, sodium carbonate, sodium bicarbonate, etc., if necessary. PH of alkali carbonate, etc.
After setting the PR to 6.0 to 7.0 with a regulator, it may be diluted with water to a desired concentration.

For example, the raw aqueous solution of glycyrrhizin or its monosalt of the present invention may have a glycyrrhizin content of 0.
Dilute with water to a concentration of 2%, then add 0.1% and 2.0% of L-cysteine and glycine, respectively.
If added in such a manner, it is useful as a raw material for glycyrrhizin-containing liquid preparations, such as antiallergic injections and liver damage injections.

Hereinafter, the present invention will be specifically explained with reference to Examples.

Example 1 Creatinine 101 was dissolved in 100 d of water with stirring, and glycyrrhizin 202 was added little by little at room temperature (2(1)) and stirring was continued for about 2 hours, resulting in a completely clear and free-flowing 20% concentrated solution of glycyrrhizin. ('l'H
5,2) is obtained.

The pH of this solution was adjusted to 6.7 with IN sodium hydroxide, and then diluted to 10 t with water, resulting in a 0.2% glycyrrhizin aqueous solution (PH 6,8) Example 2 Substitute for glycyrrhizin in Example 1 A concentrated solution (pH 5,62) of ammonium salt of glycyrrhizinate with a concentration of 20≦ as glycyrrhizin was obtained by the same method using monoammonium salt 20.49.
After adjusting the pH to 6.7 with sodium hydroxide,
diluted to give 0.0 oz as glycyrrhizin.
An aqueous solution (PH 6,8) of 25'≦ was obtained.

Example 3 A 20% concentrated solution (pH 5,65) of potassium glycyrrhizinate was obtained as glycyrrhizin in the same manner as in Example 1, using 20.99% monopotassium salt instead of glycyrrhizin.

Example 4 Creatinine 20f was suspended in 100' of water while stirring, and glycyrrhizin 40f was added to this at room temperature (25°C).
Add 9 little by little and continue stirring for about 3 hours to obtain a clear and free-flowing concentrated solution of glycyrrhizin (PH5.20).
I got it.

After adjusting the PR of this solution to 6.7 with IN sodium hydroxide, it was diluted with water to 2t to obtain a 2% glycyrrhizin aqueous solution (pHs, s).

Example 5

Claims (1)

[Claims] 1. A method for producing a concentrated aqueous solution of glycyrrhizin or a monosalt thereof, which comprises dissolving glycyrrhizin or a monosalt thereof in the presence of creatinine at room temperature.