Triterpenes from natural sources for parenteral and topical application

Triterpenes are secondary plant metabolites widespread in fruit peels, leaves and stem barks. Especially the lupan-, oleanan-, and ursantriterpenes display various anti-tumor, anti-inflammatory, anti-bacterial, anti-viral and hepatoprotective effects in the absence of prominent toxicity [1,2]. Therefore, triterpenes are a promising group of lead compounds for the development of new active agents. A screening of 80 plant materials identified triterpene rich (>1g/100g dm) plant parts. These were used to obtain dry extracts by accelerated solvent extraction resulting in a triterpene content of 50–90g/100g [3]. Depending on the plant material, betulin, betulinic acid, oleanolic acid, ursolic acid or an equal mixture of these substances are the main components of the dry extracts. These extracts can be used as starting materials for further pharmaceutical development. However, the poor solubility in aqueous solvents and oil has prevented the large scale use of these compounds and delayed the development process for years.

One approach for the solubilisation of triterpene acids is the complexation with cyclodextrins which allows the application of triterpenes in aqueous systems. For example, cyclodextrin solubilised oleanolic acid derived from Viscum album L. showed prominent anti-tumor activity in murine and human skin cancer cell lines. The betulin extract from Betulae cortex is able to form an emulsifier-free pickering emulsion (W/O) [4]. It was effective in the treatment of actinic keratoses [5]. In conclusion, triterpene extracts are a promising source of new parenteral or topical formulations useful for the treatment of a variety of diseases, including cancer.

References: 1. Liu, J. (2005)J Ethnopharmacol 100:92–4 2. Eiznhamer, DA., Xu, ZQ. (2004) IDrugs 7:359–73 3. Laszczyk, M. et al. (2006) Planta Med 72:1389–95 4. Daniels, R., Laszczyk, MN. (2008) Pharm. Ztg. 153:34–35. 5. Huyke, C. et. al. (2006)J Dtsch Dermatol Ges 4:132–136.