RU2329048C1 - Method of ursolic acid production - Google Patents

Abstract

FIELD: medicine.

SUBSTANCE: berry waste - pressed skins of black chokeberry Aronia Melanocarpa - are extracted with isopropyl alcohol at room temperature followed with release of end product by concentration to 1/8-1/10 volumes and cooling of isopropanol extract, separation of deposited paste, processed by caustic potash solution in isopropyl alcohol, with following acidation of filtered solution with diluted hydrochloric acid to pH 6-7.

EFFECT: method is producible, fire-safe and cost-effective.

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Description

The invention relates to methods for producing ursolic acid of the formula I

from plant materials, specifically to a method for the isolation of ursolic acid from air-dried waste berries after processing them for juices and extracts.

The known method [Ryabinin A.A. URSOLIC ACID IN FRUIT FRUITS Lingonberries, Journal of General Chemistry, 1946, Volume 16, issue 4-5, pp. 771-774] of obtaining ursolic acid in an individual state from waste from the production of lingonberry juice - air-dried waste berries. The method consists in extracting the waste with acetone or sulfuric ether, concentrating the extract extracts by distillation of the extractant, sequentially washing the concentrate with benzene and extraction with boiling ethyl alcohol, concentrating the alcohol extracts and crystallization, after which the precipitated crystalline mass is treated with a boiling alcohol solution of alkali (ursolic acid is converted into a solution in in the form of potassium salt), the solution is filtered, crystallized upon cooling and precipitated potassium ursolate is separated, the treatment of which is diluted Brine acid isolated ursolic acid, which, after washing with water and drying, was crystallized from ethanol to obtain ursolic acid in the individual state.

The disadvantages of the analogue method is the use of complex multi-stage technology, including the manipulation of large volumes of toxic and fire hazardous extractants-flammable liquids (acetone, sulfur ether, benzene), as well as the use of relatively scarce raw materials - waste of wild lingonberry.

The prototype method of the claimed is obtaining ursolic acid from waste berries of wild cranberries Oxycoccus quadripetalus G. [SU 1816346 Shevtsov SA, Raldugin VA, Schukin G.I. METHOD FOR PRODUCING URSOLIC ACID, 1995.09.27], which consists in extracting dried cranberry berries extracts with isopropyl alcohol (after processing it into juice), evaporating the extract, washing the concentrate with petroleum ether, dissolving the residue in a 5% methanol solution of alkali, and filtering, acidification of the resulting solution with hydrochloric acid and drying of the precipitate - ursolic acid.

The disadvantage of the prototype method is the lack of raw materials, due to the limited raw material base of wild cranberries in Russia and the fact that the cranberry pressing is a secondary raw material of the food industry, effectively utilized in the production of food products - jams.

The technological disadvantages of the prototype method are the need for thorough drying of the extracts due to the use of water-immiscible deficient petroleum ether during washing of the extract concentrate, the complexity and fire hazard of washing the concentrate with petroleum ether and subsequent drying from petroleum ether, and the use of toxic methanol in the treatment of the extract concentrate with alkali solution.

The problem to which the invention is directed, is to obtain ursolic acid from available raw materials in a technologically advanced, fireproof and cost-effective manner.

The task of ensuring the availability of raw materials is solved by the fact that waste from the production of Aronia Melanocarpa aronia juice, a widely cultivated and high-yielding crop, is used for the production of ursolic acid.

The task of creating a cost-effective and safe technology is solved by the fact that the air-dry waste of berries is extracted with isopropanol at room temperature, the extract is concentrated to 1 / 8-1 / 10 volume, cools and the precipitated paste is separated, which is dissolved in isopropanol solution potassium hydroxide, filtered, the solution was acidified with dilute hydrochloric acid and crystalline ursolic acid was separated, which was further crystallized from ethanol.

The examples below indicate that by concentrating the extract to a volume greater than 1/5 of the total volume of the used extractant (with a total extractor hydraulic module of 12 l / kg), the technical ursolic acid is not completely isolated in the form of a paste. Concentration of the extract to a volume of less than 1 / 10-1 / 12 of the total volume of extractant used leads to the production of a paste contaminated with a large amount of impurities, which reduces the yield of ursolic acid at the stage of purification. It was shown that the optimal volume of the extract concentrate is 1 / 8-1 / 10 of the total extractant volume (with a total hydraulic module of 12 l / kg).

The extraction is carried out in laboratory conditions (examples 1-4) using standard glass equipment and in pilot conditions using a stainless steel apparatus with a capacity of 700 l (example 5).

Example 1. Air-dry extracts of chokeberry berries (1 kg) are extracted with isopropyl alcohol 3 times 4 l, the total extract is concentrated by evaporation to 2.4 l (1/5 of the volume of the used extractant) and chilled to + 5 ° С, the precipitated paste is filtered off, upon drying in air, a yellow-gray powder-1 (22 g) is obtained. The latter is treated with a 5% isopropanol solution of KOH (0.2 L), filtered, then the solution is acidified with 5% hydrochloric acid to pH 6-7 and the precipitated pale yellow powder-2 is separated, which is crystallized from ethanol and 4.2 g of ursolic acid are obtained.

Examples 2-4. Air-dry pressed (1 kg) is extracted under the conditions of example 1, the extract is concentrated to 1/8, 1/10, 1/12 of the total volume of the used extractant and chilled. The precipitated paste is separated by filtration and dried. The processing of powder-1 and the allocation of ursolic acid is carried out similarly to that described in example 1. Data on the yields of powder-1 and ursolic acid are presented in the table.

Example 1 Example 2 Example 3 Example 4 Example 5 Squeeze weight, kg one one one one one hundred Extragent volume and extraction ratio 3 × 4 L 3 × 4 L 3 × 4 L 3 × 4 L 3 × 400 l The volume of concentrated extract, l 2.4 (1/5) * 1.5 (1/8) * 1 (1/10) * 1 (1/12) * 150 (1/8) * The amount of dried powder-1, g 22 28 38 43 ** The output of ursolic acid after crystallization, g 4.2 5,0 4.6 4,5 480 g * The ratio of the volume of extract concentrate to the volume of extractant used. ** The paste without drying is treated with a solution of potassium hydroxide in isopropyl alcohol.

Example 5. Air-dry extracts (100 kg) are extracted with isopropyl alcohol 3 times 400 L each, the combined extract is concentrated to a volume of ~ 150 L and chilled to + 5 ° C. The precipitated paste is filtered on a suction filter and, without drying, it is treated with a boiling 5% solution of potassium hydroxide in iso-propanol (20 L). The mixture is filtered, the solution is acidified with 5% hydrochloric acid to a pH of 6-7. The precipitated powder-2 is separated on a suction filter, washed with water, dried in air and crystallized from ethanol to obtain 480 g of ursolic acid with mp 278-280 ° C [lit. data: so pl. 280-282 ° C (from ethanol)].

Thus, the proposed method allows you to get ursolic acid from affordable and cheap raw materials - squeeze-waste berries of aronia; exclude the use of toxic and flammable solvents - methanol and petroleum ether.

Claims (1)

A method of producing ursolic acid from wastes of berries by extraction with isopropyl alcohol at room temperature followed by isolation of the target product, characterized in that the extracts of Aronia Melanocarpa aronia berries are used as berries wastes, and the extraction of the target product is carried out by concentrating the extract to 1 / 8-1 / 10 of the volume of extractant used, cooling with isopropanol concentrate, separating the precipitated paste, treating it with potassium hydroxide solution in isopropyl alcohol, acidifying to pH 6-7 filters nnogo solution with dilute hydrochloric acid.