Multi-layered structure for drug reservoir and drug eluting stent including the same
Disclosed is a multi-layered structure for drug reservoir, comprising a first micelle layer for crosslinking and adhesion, comprising a drug, a multi-arm polymer, a phenol derivative, and a dopa derivative and having a one or two-layered structure; a second micelle layer for crosslinking, being stacked on the first micelle layer, comprising a drug, a multi-arm polymer, and a phenol derivative, and having a one or two-layered structure; and a physiologically active material layer, being stacked on the second micelle layer, comprising a physiologically active material, a water-soluble polymer, and a phenol derivative, and having a one or two-layered structure.
1. A drug eluting stent comprising: a stent body having a surface; and a coating layer having at least three layers disposed over at least a portion of the stent body; wherein the at least three layers of the coating layer comprising:
a first layer disposed over the surface of the stent body, wherein the first layer comprising paclitaxel embedded within at least one layer of crosslinked 4 arm-polypropylene oxide-polyethylene oxide-tyraminedopamine (4 arm-PPO-PEO-TA/DA) conjugates, wherein the crosslinking of the at least one layer of the first layer being formed by reacting the 4 arm-PPO-PEO-TA/DA conjugates with at least one oxidizing agent;
a second layer disposed over the first layer, wherein the second layer comprising paclitaxel embedded within at least one layer of crosslinked 4 arm-polypropylene oxide-polyethylene oxide-tyramine (4 arm-PPO-PEO-TA) conjugates, wherein the crosslinking of the at least one layer of the second layer being formed by reacting the 4 arm-PPO-PEO-TA conjugates with at least one oxidizing agent;
wherein the first layer and the second layer being joined together with crosslinkings formed by reacting at least one oxidizing agent with the tyramine/dopamine attached to the 4 arm-PPO-PEO-TA/DA conjugates of the first layer and the tyramine attached to the 4 arm-PPO-PEO-TA conjugates of the second layer; and
a third layer disposed over the second layer, wherein the said third layer comprising a crosslinked heparin-polyethylene glycol-tyramine (heparin-PEG-TA) conjugates, wherein the crosslinking of the third layer being formed by reacting the heparin-PEG-TA conjugates with at least one oxidizing agent;
wherein the second layer and the third layer being joined together with crosslinkings formed by reacting at least one oxidizing agent with the tyramine attached to the 4arm-PPO-PEO-TA conjugates of the second layer and the tyramine attached to the heparin-PEG-TA conjugates of the third layer.
2. The drug eluting stent according to claim 1 , wherein the first layer comprising 10, 20, or 30 repeating layers of the crosslinked 4 arm-PPO-PEO-TA/DA conjugates, wherein the repeating layers within the first layer being joined together with crosslinkings formed by reacting at least one oxidizing agent with the tyramine/dopamine attached to the each individual layer of the 4 arm-PPO-PEO-TA/DA conjugates of the first layer.
3. The drug eluting stent according to claim 1 , wherein the second layer comprising 10, 20, or 30 repeating layers of the crosslinked 4 arm-PPO-PEO-TA conjugates, wherein the repeating layers within the second layer being joined together with crosslinkings formed by reacting at least one oxidizing agent with the tyramine attached to the each individual layer of the 4 arm-PPO-PEO-TA conjugates of the second layer.