Study On Design Of Peripherial Artery Drugeluting Stent With Sirolimus And Heparin And Its Inhibition Of In-stent Restenosis

The intravascular stenting has been the main therapeutic tool of vascular obstructive disease.However,the in-stent restenosis rate of traditional intravascular stenting was as high as 15-60% and had been the restrictive factor to the development of intravascular stenting.The success of drug-eluting stent provided a new way to reducing in-stent restenosis rate to 0-3.0%.At present,the studies about coronary drug-eluting stent home and abroad were the main stream,while those of peripheral artery were rarely reported.The drug-eluting stent has gained satisfactory clinical result,but the appearance of "drug burst release" and "delayed endothelialization" impacted its clinical application.Our study designed the drug membrane with sirolimus-heparin-polylactide coglycotide complex on the platform of native peripheral shape memory metal stent,and carried out systemic a series of studies on its surface nature,blood compatibility,degrading process,drug release in vitro and animal imaging evaluation in order to eliminating the "drug burst release" and "delayed endothelialization". Our study might provid some foundation experience to native sirolimus-heparin eluting stent of peripheral artery.The study included three parts:Partâ… one: the preparation of native sirolimus-PLGA membrane and its pharmacokinetics study.Purpose:to evaluate the "burst release" controlling of native sirolimus-PLGA membrane.Method:coated 12 niccolum-titanium alloy peripheral stents with self-made sirolimus-PLGA membrane and evaluated its surface nature,blood compatibility,degrading process and pharmacokinetics in vitro.Result:the whole 12 stents had smooth surface and uniform membrane thickness,without membrane rhagades and falling off.The platelets were fewer then the control ones and stayed in a stable state.PLGA degraded 20% within 2 weeks and speeded up in 2-6 weeks to complete degradation.The drug release lasted for 50 days.The releasing dose within 1,9,30 days was 11.02%,41.23%,79.44% separately.Conclusion:the native sirolimus-PLGA membrane kept smooth and even and controlled "burst release" effectively.Partâ…¡:the study on making native sirolimus-heparin eluting stent of peripheral artery and its efficiency.Purpose:to evaluate the stent's physical efficiency biocompatibility and pharmacokinetics in vitro.Method:coated PLGA-heparin complex to the Sirolimus-coated stents with selfmade printing equipment to gain the multiple membrane.Ecaluated the physical and degrading efficiency,blood compatibility,drug releasing mode of the stents coated with multiple membrane.Result:the stents had good surface and passed assemblage and dilation test successfully.The degrading test showed that our membrane degraded slower and longer and that the microcrystalline form of the drug in the carrier influenced the following release.The drug releasing test showed that the membrane with different ratio of PLGA had different degrading speed. Exactly,the PLGA of ratio 50/50 had a higher diffusion rate then that of ratio 75/25 or 80/20.The stents carrying different dose of drug showed different releasing speed and the stents coated with 50% drug released faster then the 30% ones though no obvious difference.The drug released faster in dynamic circumstance then in static circumstance.The drug release test of stents with multiple membrane showed that the releasing curve of the stents group with sirolimus in the first and second layer was linear one though the slope rate had a slight change.The heparin layer showed a "burst release" of 60% and slowed down later with a release dose of 70% within 1 month.The blood compatibility test indicated that platelet adhesion on, PLGA membrane was reduced,no generous aggregation.The PLGA membrane with drugs had even less platelet adhesion.The clotting time of drug coating was prolonged and blood coagulation factors were activated in a low level. Blood coagulation factors were least activated by stents carring 50% sirolimus.Conclusion:the stent with multiple membrane had satisfactory biocompatibility,eliminated the "burst release" and drug release lasted for 50 days.Partâ…¢:the imaging evaluation of native sirolimus-heparin eluting stent of peripheral artery.Purpose:to evaluate the compliance,visibility,radial force and restenosis inhibition efficiency.Method:8 sirolimus-heparin eluting stents,8 sirolimus eluting stents and 8 bare stents were implanted into peripheral arteries of 12 dogs.The dogs accepted strictly anticoagulation.1/2 of them were killed 30 days later and the others were killed after 2 months.The condition of implanted nature including plasticity,tenacity,adaptability for curvature,visibility of trace were investigated.The in-stent thrombosis,in-stent diameter,late loss of lumina and in-stent restenosis rate were evaluated mainly.Result:the whole 24 stents were successfully implanted into dogs' peripheral arteries without complication.The stents had satisfactory plasticity and visibility.No recovery and skip was found during in the process of implantation.The imaging following up indicated no thrombosis and intimal hyperplasy.60 days later,one sirolimus stent and one bare stent occurred obstruction due to obvious thrombosis;one opposite sirolimus-heparin stent occurred intimal hyperplasy.One sirolimus-heparin stent and one sirolimus stent had intimal hyperplasy. One case was found stenosis in the segment proximate to sirolimus-heparin stent.Conclusion:the native peripheral sirolimus-heparin eluting stent had good plasticity and visibility to X-ray.There's no recovery and skip during implantation. The native sirolimus-heparin eluting stent of peripheral artery could provid a strong radial force and efficiency of anticoagulation.The in-stent restenosis and thrombosis was reduced to the least degree.