Methods for making comb-type antithrombotic conjugate wherein
substantially all side chains of water soluble poly(vinyl alcohol) (PVA)
are extended by ring-opening polymerization to form a copolymer wherein
substantially all terminals are conjugated to an antithrombotic molecule.
In addition, a method is provided for applying a coating comprising a
comb-type anti-thrombotic conjugate to at least a portion of an
implantable device to prevent or reduce the formation of thrombosis on
the surface of the device. A first or sub-layer of the coating is
prepared by mixing a polymeric material and a biologically active agent
with a solvent, thereby forming a homogeneous solution. A second or outer
layer comprising a comb-type anti-thrombotic conjugate may be applied
over the inner drug-containing layers using, for example, a dip coating
or spray coating process. Alternatively the comb-type antithrombotic
conjugate may be used as a matrix material to encapsulate a
pharmaceutical agent to form microspheres or nanospheres before
depositing the microspheres or nanospheres onto a medical device.