Aphios
Granted United States Patent for the Crystallization of Complex
Molecules such as Taxol™
May
07, 2001
— Aphios
Corporation today announced that it was granted United States
Patent No. 6,221,153, entitled “Method for Producing Large
Crystals of Complex Molecules,” on April 24, 2001.
This
invention relates to methods for making highly ordered,
large-sized crystals of complex molecules such as paclitaxel
(Taxol™) and bryostatin 1, both
potent anti-cancer drugs. The methods, by virtue of the
nature of the crystal product, have utility in purification
processes, quality control, material handling and as tools
for qualitative analysis and rational drug design. The
invention features the use of critical, supercritical or
near-critical fluids, compressed gases, and/or liquefied
gases that are utilized as anti-solvents. Such anti-solvents
are added to a solution containing a solute such as paclitaxel.
The addition of critical, supercritical or near-critical
fluids, compressed gases, and/or liquefied gases changes
the nature of the solution, forcing the solute to leave
the solution as large-sized, highly ordered crystals.
Crystallization
is an important step in the purification of organic materials,
in particular, natural therapeutics. Improved crystallization
processes can provide routes to higher purity final products.
Such high quality, pure crystals are of great value for
a variety of industrial and research applications. They
can be utilized to resolve a frequent problem in pharmaceutical
research - the difficulty of obtaining large single crystals
for X-ray structural analysis to determine molecular conformations.
Crystallization
is also frequently used as a method of purification in the
biotechnology and pharmaceutical industries. Higher ordered
crystals will typically result in a more highly purified
product. Larger crystals can also impart advantages in
packaging and handling operations, and in the manufacturing
of controlled release materials.
Through the use of supercritical and near-critical carbon dioxide with small
molar quantities of a cosolvent (SuperFluids™),
Aphios has crystallized the anticancer drug paclitaxel (molecular
weight 854) in considerably larger crystal size, improved
morphology, higher purity and improved yields than can be
achieved by conventional organic phase techniques. The worldwide
marketplace for Taxol™ was in excess
of $1.6 billion in 2000. Dr. Trevor Castor, President &
CEO, Aphios Corporation states: “To our knowledge, these
are the largest and most well ordered paclitaxel crystals
grown to date.” The SuperFluids™
CRY (crystallization) process was also successfully
utilized to crystallize bryostatin 1 (molecular weight 905),
a marine natural product and an anti-cancer compound now
in Phase II clinical trials sponsored by the National Cancer
Institute.
Additionally, Aphios isolates and manufactures an all-natural Taxol™ from the needles (leaves) of the yew tree by utilizing a SuperFluids™
process that is cost-effective and environmental-friendly
[U.S. Pat. No. 5,440,055, Aug. 08, 1995]. The Company
is developing an enhanced liposomal formulation of paclitaxel
called Taxosomes .
Research has demonstrated that Taxosomes
are more effective and less toxic than Taxol
[U.S. Pat. No. 5,554,382, Sept. 10, 1996, and U.S. Pat. No. 5,776, 486, July
07, 1998].
____________________________________________________________
Taxol™ - Registered
Trademark of the Bristol-Meyers Squibb Company
SuperFluids™
- Trademark of Aphios Corporation
###
