Quaternary chelidonine and alkaloid derivatives, process for their preparation and their use in manufacture of medicaments

摘要

Disclosed is a process for the manufacture of an alkaloid reaction product comprising at least one alkaloid derivative other than sanguinarine and N-methylprotopine chloride, the derivative having a quaternary nitrogen, the process comprising: a) providing a reaction mixture comprising an organic solvent, al least one alkaloid present in the herb Chelidonium majus L. and being selected from the group consisting of chelidonine, protopione, stylopine, allocryptopine, homochelidonine, chelamidine, chelamine, L-sparteine and oxychelidonine, and an alkylating agent, and carrying out an alkylation reaction by reacting the at least one alkaloid with the alkylating agent in the presence of the organic solvent, to allow for the formation of at least one alkaloid derivative having a quaternary nitrogen; b) after termination of the reaction subjecting the resulting reaction mixture to at least one washing step with an aqueous solvent or water, to remove water-soluble compounds present in the reaction mixture; and c) subjecting the washed reaction mixture to a treatment with a strong acid in gaseous or liquid form, thereby converting at least one quaternary alkaloid derivative into a water soluble form.