Compositions and devices incorporating water-insoluble therapeutic agents and methods of the use thereof
Various aspects of the present invention provide compositions and implantable devices including a water-insoluble therapeutic agent solubilized in a matrix of a gallate-containing compound. Other aspects provide methods of manufacturing and using such compositions and devices.
1. A medical device comprising:
a base structure having a surface, and
a first coating on the surface comprising a first water-insoluble therapeutic agent and a gallate-containing compound, and
a second coating on the first coating comprising a second water-insoluble therapeutic agent and the gallate-containing compound,
wherein the first coating and the second coating are free of a polymeric material and wherein the second coating adheres directly to the first coating and forms an outermost surface of the medical device; wherein the gallate containing compound is selected from the group consisting of epi gallo catechin gallate, tannic acid and epi catechin gallate.
2. The medical device of claim 1 , wherein the gallate containing compound is selected from a group consisting of epi gallo catechin gallate and tannic acid.
3. The medical device of claim 2 , wherein the gallate containing compound is tannic acid.
4. The medical device of claim 2 , wherein the gallate containing compound is epi gallo catechin gallate.
5. The medical device of claim 1 , wherein the first and second water-insoluble therapeutic agents are taxane compounds.
6. The medical device of claim 5 , wherein at least one of the taxane compounds is paclitaxel.
7. The medical device of claim 5 , wherein the first and second water-insoluble therapeutic agents are paclitaxel.
8. The medical device of claim 1 , wherein the first coating comprises between 0.5 micrograms per mm 2 and 3 micrograms per mm 2 of the first water-insoluble therapeutic agent and wherein the second coating comprises between 0.5 micrograms per mm 2 and 2 micrograms per mm 2 of the second water-insoluble therapeutic agent.
9. The medical device of claim 1 , wherein the medical device is selected from the group consisting of a stent, a vascular stent, a ureteral stent, a catheter, a balloon, a balloon catheter, a stent graft, a wire guide, and a cannula.
10. The medical device of claim 1 , wherein the medical device comprises a balloon or a stent.
11. The medical device of claim 10 , wherein the medical device comprises a stent.
12. The medical device of claim 10 , wherein the medical device comprises a balloon.
13. The medical device of claim 1 , wherein the first coating comprises the first water-insoluble therapeutic agent solubilized within a matrix of the gallate-containing compound, and wherein the second coating comprises the second water-insoluble therapeutic agent solubilized within a matrix of the gallate-containing compound.
14. The medical device of claim 1 , wherein the first coating and the second coating are free of a non-polymer carrier modifying a rate of release of the first and second therapeutic agents.
15. The medical device of claim 1 , wherein the at least one of the first and the second water-insoluble therapeutic agents is selected from the group consisting of an immunosuppressive agent, a macrolide immunosuppressive agent, an antiproliferative agent, a microtubule stabilizing agent, a restenosis-inhibiting agent, and an inhibitor of the mammalian target of rapamycin.
16. A medical device comprising:
a balloon having a surface, and
a first coating on the surface comprising a first taxane agent and tannic acid or epi gallo catechin gallate, and
a second coating on the first coating comprising a second taxane agent and tannic acid or epi gallo catechin gallate,
wherein the first coating and the second coating are free of a polymeric material and wherein the second coating adheres directly to the first coating and forms an outermost surface of the medical device.
17. The medical device of claim 16 , wherein the first coating comprises paclitaxel and tannic acid.
18. The medical device of claim 16 , wherein the first coating comprises paclitaxel and epi gallo catechin gallate.