Heparin prodrugs and drug delivery stents formed therefrom

摘要

A prodrug comprising a heparin and a drug is provided. The prodrug can be used to form a coating on a medical device. The prodrug can also be used with a polymeric material to form a coating on a medical device. The polymeric material can be a hydrophobic polymer, a hydrophilic polymer, a non-fouling polymer, or combinations thereof. The medical device can be implanted in a human being for the treatment of a disease such as atherosclerosis, thrombosis, restenosis, hemorrhage, vascular dissection or perforation, vascular aneurysm, vulnerable plaque, chronic total occlusion, claudication, anastomotic proliferation for vein and artificial grafts, bile duct obstruction, ureter obstruction, tumor obstruction, or combinations thereof.

主权项

1. A prodrug of a drug, said prodrug comprising the drug, heparin, and a polymer,
wherein the heparin is covalently linked to the polymer, wherein the drug is covalently linked to the heparin, wherein the drug is not pharmacologically active in the presence of the covalent linkage between the drug and the heparin, wherein the covalent linkage of the drug to the heparin is either hydrolytically or enzymatically unstable, wherein the covalent linkage between the drug and the heparin is hydrolytically or enzymatically cleaved under in vivo conditions, and wherein the polymer is selected from the group consisting of poly(L-lysine-co-hyaluronic acid) (PLL-co-HA), poly(L-lysine-co-phosphoryl choline) (PLL-co-PC), poly(ethylimine-co-hyaluronic acid) (PEI-co-HA), poly(ethylimine-co-phosphoryl choline) (PEI-co-PC), poly(L-lysine-g-hyaluronic acid) (PLL-g-HA), poly(L-lysine-g-phosphoryl choline) (PLL-g-PC), poly(ethylimine-g-hyaluronic acid) (PEI-g-HA), and poly(ethylimine-g-phosphoryl choline) (PEI-g-PC).