Patent ID: 6303148
Filing Date: 2001-10-16
Classification: A61K,Y10S

Abstract:
A method to produce degradable microspheres which effect controlled release of a desired releasable therapeutic substance when in contact with an animal body which method comprises(a) providing a ternary two phase system of(1) a first water-soluble polymer which is crosslinkable and which, when crosslinked, can be degraded when in contact with an animal body;(2) a second water-soluble polymer, and(3) water,wherein said ternary system is characterized by a phase diagram and wherein said ternary system forms one phase when composition of the ternary system is below the binodal in said phase diagram and forms two phases when the composition of the ternary system is above the binodal in said phase diagram, and wherein the composition of said ternary two phase system provided is above said binodal and is capable of forming a continuous phase and a discontinuous phase;(b) forming a continuous and discontinuous phase, wherein said first, crosslinkable, polymer which, when crosslinked, can be degraded when in contact with an animal body is the discontinuous phase in said two-phase system and the second polymer is the continuous phase in said two-phase system, said two phase system having been obtained by adjusting the amounts of water, first polymer and second polymer so as to place the system above the binodal, andwherein a releasable therapeutic substance is present in said two-phase system,(c) crosslinking said first polymer to form solid degradable microspheres, wherein the degree of crosslinking and water content are adjusted so as to result in pore sizes in said microspheres which are equal to or less than the hydrodynamic diameter of the releasable therapeutic substance, said pores thus entrapping said releasable therapeutic substance, and(d) separating the continuous phase from the discontinuous phase to recover the microspheres,thus obtaining microspheres which exhibit controlled release of the releasable therapeutic substance when in contact with animal body by effecting expansion of the pores through degradation of said crosslinked first polymer in the animal body.