Elastin stabilization of connective tissue
A method and product are provided for the treatment of connective tissue weakened due to destruction of tissue architecture, and in particular due to elastin degradation. The treatment agents employ certain unique properties of phenolic compounds to develop a protocol for reducing elastin degradation, such as that occurring during aneurysm formation in vasculature. According to the invention, elastin can be stabilized in vivo and destruction of connective tissue, such as that leading to life-threatening aneurysms in vasculature, can be tempered or halted all together. The treatment agents can be delivered or administered acutely or chronically according to various delivery methods, including sustained release methods incorporating perivascular or endovascular patches, use of microsphere carriers, hydrogels, or osmotic pumps.
1. An implantable element for stabilization of blood vessel in a living subject, comprising a structural element selected from a group consisting of a vascular graft, a stent graft, and a stent and a therapeutic composition associated with the structural element,
wherein the therapeutic composition comprises a phenolic compound having a plurality of phenolic groups at an effective concentration that crosslinks elastin in the blood vessel in vivo to stabilize the blood vessel, and
wherein the therapeutic composition is substantially free of unbound gallic acid and has a pH between about 4 and about 9.
2. The implantable element of claim 1 wherein the structural element is a stent graft that is configured to reinforce a section of blood vessel that has aneurysm without removal of the section of the blood vessel.
3. The implantable element of claim 1 wherein the structural element is a vascular graft comprising a tubular element that forms a suitable replacement for a section of blood vessel that has aneurysm.
4. The implantable element of claim 1 wherein the structural element comprises a bio-absorbable material.
5. The implantable element of claim 1 wherein the therapeutic composition is associated with the structural element in the form of a coating.
6. The implantable element of claim 1 wherein the therapeutic composition is embedded in the structural element.
7. The implantable element of claim 1 wherein the phenolic compound is tannic acid or an analog of tannic acid, pentagalloylglucose or an analog of pentagalloylglucose, a combination thereof, or a pharmaceutically acceptable salt thereof.
8. The implantable element of claim 1 wherein the therapeutic composition comprises from about 0.0001 w/v % to about 10 w/v % of the phenolic compound.
9. The implantable element of claim 1 wherein the therapeutic composition further comprises glutaraldehyde.
10. The implantable element of claim 1 wherein the therapeutic composition further comprises a drug delivery vehicle comprising a sustained release drug delivery vehicle.
11. The implantable element of claim 1 wherein the therapeutic composition further comprises a drug delivery vehicle comprising a hydrogel.
12. The implantable element of claim 10 wherein the therapeutic composition is encapsulated in the drug delivery vehicle.
13. A method for stabilization of blood vessel of a living subject using an implantable element that comprises a structural element selected from a group consisting of a vascular graft, a stent graft, and a stent and a therapeutic composition associated with the structural element, wherein the therapeutic composition comprises a phenolic compound having a plurality of phenolic groups at an effective concentration that crosslinks elastin in the blood vessel in vivo to stabilize the blood vessel, the method comprising,
implanting the implantable element in the blood vessel, and
allowing the therapeutic composition to elute from the implantable element to stabilize the blood vessel.
14. The method of claim 13 wherein the phenolic compound is tannic acid or an analog of tannic acid, pentagalloylglucose or an analog of pentagalloylglucose, a combination thereof, or a pharmaceutically acceptable salt thereof.
15. The method of claim 13 wherein the implanting step comprises replacing a section of blood vessel that has aneurysm with the vascular graft.
16. The method of claim 13 wherein the implanting step comprises deployment of the stent at an aneurysm.
17. The method of claim 16 wherein the stent stabilizes the blood vessel that has the aneurysm.
18. The method of claim 13 wherein the implanting step comprises reinforcing a section of blood vessel that has aneurysm with the stent graft without removal of the section of the blood vessel.
19. The method of claim 13 wherein the therapeutic composition further comprises a drug delivery vehicle comprising a sustained release drug delivery vehicle to allow sustained elution of the therapeutic composition from the structural element.
20. The method of claim 13 further comprising treating the blood vessel with glutaraldehyde before, during, or after the implantation of the implantable element.