Consistent and enhanced production of anti-cancer drugs from the Madagascar periwinkle plant

INV-19070

Background

The Madagascar periwinkle plant has been used for vinblastine (VBL) and vincristine (VCR) since the 1960s. These chemical compounds have been listed on “World Health Organization’s Model List of Essential Medicines”. However, due to high cost, low concentration in extracts, and unpredictable supply, the applications of VBL and VCR as essential medicines are limited. Due to the low concentrations in the leaves, VBL and VCR are currently obtained through a semi-synthetic process involving the condensation of their more abundant precursors, catharanthine (C) and vindoline (V) using hazardous chemicals.

There a strong market need for these compounds and a strong need for a process that can achieve a much higher yield of these compounds, making them more available to patients, and at a more affordable cost. A better method of extraction is needed.

Technology Overview

Researchers have put forward in-situ technology where VBL and VCR are produced in the leaves directly. The periwinkle plants were culminated under special growth and treatment conditions. These conditions help in increasing the concentration of catharanthine and vindoline, the precursors of desired drugs (content is 5-9 times higher). Our technology produces these drugs directly from leaves by in situ enzymatic-synthesis: 1) first, we cultivate periwinkle plants under “special growth conditions” investigated in our laboratory to enhance the precursor concentration and enzyme levels in the leaves; 2) next, the enzymes in the leaves, which are responsible for VBL and VCR biosynthesis, convert the leaf-associated precursors to the desired products in a single vessel, without the initial isolation of the precursors and the hazardous reagents used in semi-synthesis. Our technology is simpler with fewer steps, greener by eliminating the hazardous reagents used in semi-synthesis, reducing the production cost and the drug cost to the patient.