JPS62126185A - Production of isoflavone derivative - Google Patents

Abstract

PURPOSE:To industrially and advantageously obtain the titled compound useful for a medicament, by bringing an extract solution of pueraria root as it is or after distilling a solvent off, into contact with a synthetic adsorbent resin to adsorb an isoflavone derivative, followed by elution thereof by using such as an organic solvent. CONSTITUTION:An extract solution of pueraria root (root of Pueraria Iobata Ohwi, etc. are preferred), as it is or after distilling a solvent off, preferably after adjusting its pH at 5.5-7.0, is brought into contact with a synthetic adsorbent resin (example; styrene-divinylbenzene polymeric resin, etc.) to adsorb an isoblavone derivative expressed by the formula. The the compound is eluted with an organic solvent (preferably methanol) or a mixed solvent of the organic solvent with water to obtain the aimed compound. By utilizing the extract solution of the pueraria root produced in production of pueraria starch, it can be produced at a lower cost.

Description

DETAILED DESCRIPTION OF THE INVENTION [Field of Industrial Application] The present invention relates to a simple and inexpensive method for producing isoflavone derivatives.

[Prior Art and Problems] Kudzu root, which belongs to the leguminosae family, is called kudzu root and has been used in Chinese medicine as a Japanese and Chinese medicine since ancient times.

This arrowroot contains isoflavone derivatives such as puerarin, daidzein, and daidzein expressed by the following formula, and daidzein has a papaverine-like antispasmodic effect in the isolated small intestine of mice [Pharmaceutical Journal, 9
7, 103 (1977)], many pharmacological actions are known. Therefore, if these isoflavone derivatives are to be provided as pharmaceuticals in the future, how to obtain them cheaply and in large quantities will be an important factor.

Conventionally, isoflavone derivatives have been obtained by purifying an extract of arrowroot with an organic solvent or a water-containing organic solvent by column chromatography using alumina, silica gel, or the like as an adsorbent.

In addition, lead acetate is added to the polar solvent extract of arrowroot or the waste liquid from M starch production to remove the precipitate, and ammonia is added to the Shito liquid to make it neutral or weakly basic. A known method is to obtain the active ingredient by treating with hydrogen sulfide.

However, when these methods are applied to industrial large-scale purification, there are disadvantages such as a significant increase in the amount of loading on the adsorbent and complicated operations due to scale expansion. Derivatives are available in small quantities and are expensive. Furthermore, industrial purification of isoflavone derivatives has hardly been carried out.

[Means for Solving the Problems] As a result of intensive study on a method for obtaining isoflavone derivatives at low cost and in large quantities, the present inventors have synthesized the extract by distilling off the solvent from the extract of arrowroot. Isoflavone derivatives can be obtained inexpensively and in large amounts by contacting with an adsorption resin to adsorb the isoflavone derivatives, and then eluting them from the synthetic resin using an organic solvent or a mixed solvent of an organic solvent and water. They discovered this and completed the present invention.

The present invention will be explained in detail below.

When obtaining an extract of arrowroot, the arrowroot used for extraction is a root of the genus Puerariae, more preferably a root of the genus Puerariae.
uelaria Iobata Ohwi (Puer
aria pseudo-hirsuta Tang
et fang) or Pueraria Iobat
aOhwi var, chinensis (Ben
th) The root of Ohwi (Leguminosae) can be used. Examples of the extraction solvent include water, an aqueous solvent such as methanol, and ethanol, or a mixed solvent of water and an aqueous solvent, and extraction is performed within a temperature range from room temperature to the boiling point of the extraction solvent.

Currently, arrowroot starch is produced by extracting arrowroot with water and removing the water-insoluble starch precipitated in the extract.At this time, the arrowroot extract is discarded as waste liquid.
The extract of arrowroot as referred to in the present invention also includes such waste liquid. Therefore, isoflavone derivatives can be obtained at lower cost by using the extract of arrowroot root used in the production of arrowroot starch, which has not been used at all in the past.

Next, the extract is brought into contact with a synthetic adsorption resin, either as it is or after the solvent is distilled off, to adsorb isoflavone derivatives. If the extract has a difference in acidity or basicity, add an appropriate acid or alkali as needed to improve the adsorption rate of isoflavone derivatives to the synthetic adsorption resin.
It is desirable to maintain the condition at about 15.5 to pl+7.0, and examples of the acid in this case include acetic acid, hydrochloric acid, etc., and examples of the alkali include sodium hydrogen carbonate, sodium hydroxide, etc.

In addition, if an aqueous solvent is used as the extraction solvent during the extraction, it is desirable to distill off the used aqueous solvent from the extract in order to improve the adsorption rate of isoflavone derivatives to the synthetic adsorption resin. .

Specific examples of synthetic adsorption resins include “Diaion HP Resin” (manufactured by Mitsubishi Chemical Corporation) and “Amberlite
Examples include "AD Resin" (manufactured by Rohm and Haas Co., Ltd.) and "Duolite S Resin" (manufactured by Diamond Shamrotsuta Co., Ltd.).

The extract and the synthetic adsorption resin may be contacted by either a batch method or a column method. In the case of a batch method, the synthetic adsorption resin can be placed in a suitable container and stirred as appropriate, or by other common methods. In the case of a column method, this can be achieved by a commonly used method, and the elution rate can be appropriately selected by considering various conditions such as the size of the column and the elution solvent used. Since both the batch method and the column method described above involve physical adsorption, the temperature is preferably about room temperature.

Next, the isoflavone derivative adsorbed on the synthetic adsorption resin is eluted using an organic solvent or a mixed solvent of an organic solvent and water. In this case, either a batch method or a column method may be used, and the solvent used for elution may be an organic solvent or a mixed solvent of an organic solvent and water. The type, concentration, and amount of the elution solvent are appropriately selected in consideration of various conditions such as whether the elution is performed by a column method or a batch method, and the type and m of the synthetic adsorption resin used.

Specific examples of organic solvents include methanol, ethanol,
Examples include isopropanol and acetone, preferably alcohols or a mixed solvent of alcohols and water, and more preferably methanol or a mixed solvent of methanol and water.

If the eluate obtained by the batch method or the eluate obtained by the column method contains multiple components,
Purified by commonly used separation and purification techniques (e.g. countercurrent distribution, recrystallization, column chromatography, etc.),
Can be isolated.

The synthetic adsorption resin used in the method for producing isoflavone derivatives of the present invention can be used in a suitable organic solvent (e.g., alcohol-based,
acetone-based organic solvents, etc.) or alkaline agents (e.g.
By washing and regenerating with sodium hydroxide, potassium hydroxide, etc., it can be used repeatedly and is very economical.

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

Example 1 Add 7 drops of water to 2.2 kg of finely chopped arrowroot, pulverize the arrowroot in water, filter the obtained solution with a cloth, leave it overnight, and then add 2QOJ of the supernatant to 5N water. pl with sodium oxide solution
Adjusted to +6.0. Next, 200Δ methanol and 2
The above solution was added to a resin tower filled with 80 d of styrene-divinylbenzene polymer resin (Diaion HP-20, manufactured by Mitsubishi Chemical Industries, Ltd.) which had been washed and activated with 00- water, and the inside of the resin tower was It was passed through at 11jJ/min, and then washed by adding 600-ml water and then 10% methanol aqueous solution. After washing, first add 70% to the resin tower.
% methanol aqueous solution 200Δ at elution rate 10 mfJ/m
A brown solution containing buerarin and daidzein was passed through the solution, and then 80° of methanol was passed through the solution to obtain a brown solution containing daidzein.

Example 2 Supernatant 500, -d of arrowroot extract obtained in Example 1 above
Passed through gauze and diluted with 5N sodium hydroxide solution to pH 6.
, adjusted to 0. Next, 400mf! of methanol and 4
Styrene-vinylbenzene polymer resin activated with 00-water (manufactured by Mitsubishi Chemical Corporation, Diaion HP)
-20) 200- was added to the above solution and left at room temperature for 4 hours with occasional stirring. This mixture was passed through a patterned funnel, the residue was transferred to a column, and washed by adding 400 ml of water. Two portions of a 70% aqueous methanol solution were passed through the column at an elution rate of 50111/min. A brown solution containing puerarin and daidzein was obtained, and then 245 methanol was passed through the solution at an elution rate of 50 mfJ/min to obtain a brown solution containing daidzein.

Claims (1)

[Claims] The extract of kudzu root is brought into contact with a synthetic adsorption resin, either as it is or after the solvent is distilled off, to adsorb isoflavone derivatives.Then, the isoflavone derivatives are eluted from the synthetic resin using an organic solvent or a mixed solvent of an organic solvent and water. A method for producing an isoflavone derivative, the method comprising obtaining a derivative.