Warszawski Uniwersytet Medyczny

Instytut Farmaceutyczny

Zaklady Farmaceutyczne Polpharma S.a.

Marta Laszcz

Oliwia Zegrocka-Stendel

Grzegorz Grynkiewicz

Kamil Jatczak

Mariusz Marek Gruza

Katarzyna Koziak

Piotr Cmoch

Malgorzata Dutkiewicz

Dorota Maciejko

Krzysztof Bojakowski

Katarzyna Filip

Iwona Grabowska

Tomasz Giller

Magdalena Kowalewska

Joanna Zagrodzka

Described herein is compound including a protoescigenin derivative having pharmacological properties. Also described are a process of its preparation, and the use of such a compound as a medicament, especially for treating vascular disorders. A pharmaceutical composition comprising such compound is further described.

Protoescigenin derivative, process of its preparation, use of said compound and pharmaceutical composition comprising that compound

A process for the preparation of protoescigenin by hydrolysis of escin isolated from. The process includes the following steps: a two-step hydrolysis first under acidic and then basic conditions, enrichment of the crude mixture of sapogenins with protoescigenin, an isolation of the mixture of sapogenins in a solid form, and a purification of the obtained solid and isolation of high purity protoescigenin. The invention also relates to protoescigenin monohydrate in a crystalline form and the preparation thereof. Protoescigenin is a polyhydroxy aglycone, which can be used as a synthon in the chemical modifications of naturally occurring saponins.

Process for the preparation of protoescigenin

A process for the preparation of solifenacin and/or the pharmaceutically acceptable salts thereof of high pharmaceutical purity is characterized in that 3-(R)-quinuclidinoloxy anion generated in situ from 3-(R)-quinuclidinol in a presence of strong base in polar organic solvent is subject to acylation with (S)-1-phenyl-1,2,3,4-tetrahydroisoquinolinecarbonyl chloride of chemical purity at least 98%, while maintaining constant anion excess in a reaction mixture, and after reaction completion solifenacin base is optionally transformed into solifenacin salt according to standard procedures. (S)-1-Phenyl-1,2,3,4-tetrahydroisoquinolinecarbonyl chloride of chemical purity at least 98% is obtained in a reaction of (S)-1-phenyl-1,2,3,4-tetrahydroisoquinoline and molar excess of phosgene in a presence of tertiary aromatic amine in aromatic hydrocarbon, and isolated in a crystalline form.

Process for preparation of solifenacin and/or the pharmaceutically acceptable salts thereof of high pharmaceutical purity

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Warsaw, Poland

Marta Laszcz