Aphios Corporation

Current manufacturing methods for natural pharmaceuticals use large volumes of toxic organic solvents to extract the active ingredients that occur in trace amounts (5 to 500 parts per million). Process yields are low, and procedures are time-consuming and resource-intensive. The toxic organic solvents used are not readily recyclable, require expensive disposal and often leave toxic residuals.

For example, paclitaxel (Taxol^®) was initially isolated from the bark of the slow growing Pacific yew, Taxus brevifolia, by several toxic organic solvents in as many as 19 processing steps. The bark of 100 to 200 year old Pacific yews was used, even though it killed the tree, because it was a relatively clean matrix that made the isolation possible. The manufacturing of paclitaxel from yew bark was thus based on a species that was becoming rapidly endangered and a technology that generated a significant amount of environmental waste.

However, the isolation and purification of paclitaxel from yew needles, the renewable portion of the tree, by conventional organic solvent procedures was made extremely difficult by the presence of non-polar waxes, lipids, chlorophylls and other bioactive compounds in the yew needle.

Aphios has been able circumvent these manufacturing difficulties and resource limitations by utilizing SuperFluids™ to selectively extract and purify paclitaxel and related taxoids from yew needles (leaves), a renewable biomass resource, of the cloned ornamental yew, Taxus media “hicksii” in five steps. The ornamental yew is traditionally utilized for landscaping in the Northeast corridor of the United States, and is readily available in yew farms. Aphios’ technology can also be utilized with needles from the wild, bark, roots and other parts of yew trees. A comparison between conventional organic phase extraction and Aphios’ SuperFluids™ extraction and purification (CXP) process indicates that the CXP process results in:

Fast and selective extraction and purification of several products — paclitaxel, 10-DAB and cephalomannine with high purities (> 99.5 %) versus 1 product
Reduced number of extraction and purification steps, from 19 to 5
Decreased taxoid extraction time from several days to less than 24 hours
Significantly reduced use of organic solvents requiring safe disposal
Higher overall yields at lower manufacturing costs from yew needles, a renewable biomass resource