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Preparation of protoaescigenin from escin.

Mariusz M. Gruza 1Oliwia Zegrocka-Stendel 2Tomasz Giller 1Marta Łaszcz 1Kamil Jatczak 1Bogdan Zagrodzki 1Grzegorz Grynkiewicz 1

1. Instytut Farmaceutyczny (PRI), Rydygiera 8, Warszawa 01-793, Poland
2. Medical Univeristy of Warsaw (WUM), Żwirki i Wigury 61, Warszawa 02-097, Poland

β-Escin (β-Aescin) is an active ingredient of popular OTC drugs (Escin, Reparil, Venitan) with anti-inflammatory, vasoprotective and vasoconstrictor effects. It is used in treatment of chronic venous insufficiency (CVI) and also in cosmetics. The substance obtained from the seed of the horse chestnut (Aesculus hippocastanum) is a mixture of over a dozen saponins, which comprise polyhydroxylated triterpene aglycone of olean-12-ene type, acidic oligosaccharide, and some short chain fatty acid residues. Preparative separation of native mixture of escins would be a daunting task since even analytical HPLC is difficult and inconclusive until supported by a suitable collection of  standard compounds for positive identification.

In connection with a project aimed at new, semisynthetic, vasoactive compounds, it has been decided to obtain escin sapogenins by partial degradation of native saponins. Preparation of escin aglycons was achieved in two-step hydrolysis, in which glycosidic and ester substituents were removed sequentially. It has been confirmed that the main terpenoid constituent of escin mixture is protoaescigenin (approximately 50% of the saponin hydrolyzate), but its isolation in state of reasonable purity by scalable process posed considerable difficulty.  

A method of preparation of protoaescigenin of purity >98% from β-escin without using chromatography was developed. The method consists of three steps (Scheme 1): i) successive acidic and alkaline hydrolyses, ii) isolation of the protoaescigenin concentrate, iii) purification of the concentrate by crystallization and obtaining pure protoaescigenin. The method was successfully scaled up to a kilogram scale, allowing to obtain certified protoaescigenin as a prospective fine chemical and/or pharmaceutical intermediate.

Scheme 1

Preliminary polymorphism studies indicated that obtained crystals of protoaescigenin represent a sapogenin monohydrate which has not been reported in patent or published scientific literature.

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Related papers

Presentation: Poster at VIII Multidyscyplinarna Konferencja Nauki o Leku, by Mariusz M. Gruza
See On-line Journal of VIII Multidyscyplinarna Konferencja Nauki o Leku

Submitted: 2012-03-06 08:42
Revised:   2012-03-30 08:10