CS214902B1 - Method of making the thebain - Google Patents

Description

The invention relates to a process for producing thebaine from Papaver bracteatum Lindl., In particular from roots and / or de-capped capsules.

Thebaine, one of the minor opium alkaloids, is an important raw material for the production of pharmaceutically valuable codeine and partially synthetic analgesics of the morphinan series with a very potent effect without addictive addiction.

So far, thebaine has been obtained from a mixture of side alkaloids which are lost in the production of morphine and codeine from opium or poppy. Recently, Papaver bracteatum Lindl. Has become the new source of thebaine, in which thebaine is the main alkaloid, practically the only one in P. bracteatum Halle III. The prior art method of producing thebaine of this kind consists in extracting the ground dry drug (roots or capsule capsules) after previous alkalization in the extractor with various solvents, for example methanol or methylene chloride, for 2 to hours. After concentrating in vacuo, the extract is stirred with a 1-3% sulfuric acid solution and the acidic aqueous phase is basified with ammonia or an alkali metal hydroxide solution after filtration. The precipitated crude thebaine is filtered off with suction and the filtrate is extracted with an organic solvent, for example ether. The aspirated crude thebaine and thebaine obtained by evaporating the extracts were then purified by crystallization from anhydrous or diluted ethanol, optionally by conversion to a salt, for example acid tartrate. Another known method of isolating thebaine is based on extracting the drug with dilute aqueous solutions of inorganic or organic acids, for example 0.1% hydrochloric acid, 0.2% sulfuric acid, 0.2% tartaric acid, 1% acetic acid and the like. The aqueous acid extracts are then concentrated in vacuo, alkaline to liberate thebaine, which is further purified by conventional means.

A significant improvement of the prior art is the process for producing thebaine from Papaver bracteatum Lindl., Of 214902, the name of the roots and / or of the desiccated capsules according to the invention, characterized in that the starting comminuted dry drug after alkalization with aqueous ammonia, hydroxide or alkaline carbonate metal or an aqueous suspension of an alkaline earth metal oxide or hydroxide, is extracted, preferably by percolation, at a temperature of 15 to 40 ° C, with an aromatic hydrocarbon of 6 to 8 carbon atoms, preferably toluene, in a weight ratio of 6: 1 to 12 to 1 The extract was evaporated and the residue isolated in the form of hydrogen tartrate.

The extract obtained after completion of the percolation is evaporated, preferably under vacuum, to dryness, the residue is dissolved in the required amount of ethanol in the hot state, filtered and thebaine is precipitated from the filtrate in the form of hydrogen tartrate by adding a hot solution of tartaric acid in ethanol. The required amount of tartaric acid is determined by the semi-quantitative determination of thebaine and the acid is used in an excess of 10% by weight. The precipitated thebaine hydrogen tartrate can be further purified by crystallization, for example from 80% ethanol.

The process for producing thebaine according to the invention has a number of advantages over prior art processes. Percolation occurs at lower temperatures, is quantitative, the extract is clear, poorly colored and very pure.

The solvent can be regenerated almost without loss and can be used for further percolation without further purification. The crude residue contains very few ballast substances and it is not necessary to purify it by precipitation from aqueous salt solutions prior to precipitation of the hydrogen tartrate, so that no additional auxiliary chemicals are required. The whole process is quick and economical. Unlike acidic aqueous extractions, it is not necessary to concentrate large volumes of acidic aqueous extracts in vacuo. This operation is very demanding in terms of energy and time and can cause losses. Thebaine is well soluble and virtually indefinitely stable in aromatic hydrocarbons and does not react with them, which cannot be said to be chlorinated paraffinic hydrocarbons, in particular dichloromethane and chloroform (S. Pfeifer et al., Pharmazie 27, 639, 648, 734, 1972; R). (Besselievre et al., Bull. Soc. Chim. France 1972, 1477). Methanol, which is very toxic, extracts a large amount of non-basic ballasts from the drug, which can cause considerable difficulties (emulsion formation, product coloring, etc.).

From the above, the advantages of the process according to the invention are obvious, the nature and details of which are apparent from the examples. Example 1

In the homogenizer, 100 g of dry ground poppy or roots of Papaver bracteatum are moistened with 20 ml of a 5% aqueous ammonia solution to give a free-flowing homogeneous mass which is percolated with toluene in a percolator at room temperature (20-25 ° C) at 100 ml / /throw. The first 1000 ml of toluene percolate contained 98.99% of the thebaine by analytical determination. The toluene percolate is evaporated to dryness in vacuo, the residue is dissolved in ethanol at elevated temperature, filtered and ethanolic tartaric acid solution, also prepared while hot, is added to the filtrate. The cooled thebaine hydrogen tartrate is filtered off with suction after cooling and recrystallized from 80% ethanol.

Example 2

Dry ground roots or poppies or their mixture of 100 g Papaver bracteatum are well mixed with 20 ml of a 3,3% calcium hydroxide suspension (0,5 g of calcium oxide in 20 ml of water) and percolated with toluene in a percolator at 35 ° C at a rate of 80 ml / hr and 1000 ml percolate collected. The toluene solution, which contained 99.12% of total thebaine by analytical determination, was evaporated to dryness in vacuo and the residue was treated with thebaine hydrogen tartrate as in Example 1.

Claims (1)

SUBJECT Process for producing thebaine from Papaver bracteatum Lindl., In particular from roots and / or de-capped capsules, characterized in that the starting crumb dry drug after alkalization with an aqueous solution of ammonia, alkali metal hydroxide or carbonate or an aqueous suspension of alkaline earth metal oxide or hydroxide, extracts, preferably by percolation, at a temperature of 15 to 40 ° C, with an aromatic hydrocarbon of 6 to 8 carbon atoms, preferably toluene, in a weight ratio of 6: 1 to 12: 1 based on the weight of the starting drug, then extracts and evaporates Thebaine is isolated as the hydrogen tartrate.