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1、大连垠艺生物材料研制开发有限公司 DALIAN YINYI BIOMATERIALS DEVELOPMENT CO., LTD.,新一代载药技术，更安全的选择 New Generation Technology，Your Safer Choice,垠艺TM紫杉醇微孔载药冠状动脉支架系统,1,骄阳教育,大连垠艺生物材料研制开发有限公司 DALIAN YINYI BIOMATERIALS DEVELOPMENT CO., LTD.,药物涂层支架的发展趋势,聚合物涂层支架,可降解涂层支架,无涂层药物支架,可降解药物支架,第一代DES Cypher Taxus Endeavor Firebird Pa
2、rtner ,第二代DES 垠艺TM,第三代DES ？,改良的第一代DES Excel 爱克赛尔,2,骄阳教育,大连垠艺生物材料研制开发有限公司 DALIAN YINYI BIOMATERIALS DEVELOPMENT CO., LTD.,第一代药物涂层支架的作用,金属支架,多聚体涂层,药物,抑制平滑肌细胞增生 促进内皮细胞生长 抑制炎性反应,药物载体、控制释放,机械性压迫斑块 机械性支撑血管,3,骄阳教育,大连垠艺生物材料研制开发有限公司 DALIAN YINYI BIOMATERIALS DEVELOPMENT CO., LTD.,第一代药物涂层支架的长期状况,金属支架,多聚体涂层,药物
3、,100%代谢，无残留,无作用 永久存在,机械性支撑 永久存在,4,骄阳教育,FDA News,Cordis Corporation Issues a Health Care Professional Letter Regarding the CYPHER Stent Cordis Corporation (Cordis) has issued the attached letter to health care professionals to inform them of the rare but potential risk of thrombosis associated with t
4、he use of its product the CYPHER Sirolimus-Eluting Coronary Stent (CYPHER stent). This letter also provides clarification on the safe use of the product in accordance with the scientific evidence that led to product approval. The CYPHER stent was approved in April 2003 for patients undergoing angiop
5、lasty procedures to open clogged coronary arteries. Since the products introduction it is estimated that over 50,000 patients have received a CYPHER stent. To date, FDA has received 47 Medical Device Reports (MDRs) of stent thrombosis occurring at the time of implantation or within a few days of imp
6、lantation. The Food and Drug Administration (FDA) is carefully reviewing the reports of adverse events and is working closely with the company to determine the exact causes and reduce the incidence of thrombosis. From the reports received so far, it is unclear what effect the CYPHER stent has on thr
7、ombosis risk and what factors may contribute to the risk. As part of the approval for this product, FDA required Cordis to undertake post-approval studies which will help FDA track adverse events more accurately, as well as help determine whether the thrombosis rate in current clinical experience di
8、ffers from the rate seen in pre-approval studies. Until more is known about the situation, FDA fully supports Cordis recommendations to health care professionals which may help reduce the incidence of adverse events. These include: Selection of the appropriate stent size. The stent size should match
9、 the diameter of the vessel as closely as possible. Selection of appropriate patients for implantation. The stent is indicated for improving coronary luminal diameter in previously untreated vessels and is not indicated for the treatment of restenosis (reclogging of a previously stented vessel). Use
10、 of an adequate antiplalelet regimen. Doctors are reminded to give adequate doses of medication that reduce the risk of clot formation. Use of the proper technique for stent deployment. The stent should be fully deployed and in contact with the vessel wall. Poor stent deployment is a factor that can
11、 increase the thrombosis risk. In addition, all health care professionals are reminded and encouraged to report their experiences to FDAs Medical Device Reporting (MDR) System through MedWatch (telephone 1-800-FDA-1088 or www.fda.gov/MedWatch). Cordis, in cooperation with FDA, will continue to monit
12、or the issue.,5,骄阳教育,大连垠艺生物材料研制开发有限公司 DALIAN YINYI BIOMATERIALS DEVELOPMENT CO., LTD.,Polymer-based sirolimus- (Cypher) and paclitaxel-eluting (Taxus) drug eluting stents have become the treatment of choice for patients with symptomatic coronary artery disease undergoing percutaneous coronary interv
13、ention (PCI). Although these stents reduce rates of restenosis compared with bare metal stents (BMS), late thrombosis, a life threatening complication, has emerged as a major safety concern. Our understanding of the pathophysiology of late DES thrombosis is derived from animal and human pathologic s
14、amples taken after implantation of these devices. These data indicate that both DES cause substantial impairment in arterial healing characterized by lack of complete reendothelialization and persistence of fibrin when compared with BMS. Arterioscler Thromb Vasc Biol. 2007;27:1500-1510. Journal of T
15、he American Heart Association,多聚体载药（Polymer-based）支架已被广泛应用于心脏介入治疗中，较裸金属支架的再狭窄率明显降低，但晚期血栓 - 这一威胁生命的严重并发症的发生正逐步显现 从动物和人体尸检标本的病理生理学数据可以看出，对照裸金属支架，多聚体载药（ Polymer-based）支架导致动脉内膜修复的明显延迟，出现明显的纤维化和不完全的动脉血管内皮化,6,骄阳教育,大连垠艺生物材料研制开发有限公司 DALIAN YINYI BIOMATERIALS DEVELOPMENT CO., LTD.,第一代药物支架多聚体涂层存在的问题,Pictures
16、from TCT presentation,多聚体材料（选材差、粘度高等）导致严重的涂层剥脱或粘连 生产工艺不佳导致涂层鼓起或有碎屑，加大了远端血管栓塞风险,7,骄阳教育,大连垠艺生物材料研制开发有限公司 DALIAN YINYI BIOMATERIALS DEVELOPMENT CO., LTD.,改良的第一代药物支架,“可降解涂层” 新颖的概念，一点点疑问： 药物释放的同时涂层不断降解，两者能否达到动态平衡 载药层降解过程对血管内皮修复有无影响 载药层能够及时地全部降解 载药层降解后是否影响支架与血管壁的紧密贴合,8,骄阳教育,大连垠艺生物材料研制开发有限公司 DALIAN YINYI B
17、IOMATERIALS DEVELOPMENT CO., LTD.,第二代药物涂层支架,9,骄阳教育,大连垠艺生物材料研制开发有限公司 DALIAN YINYI BIOMATERIALS DEVELOPMENT CO., LTD.,药物支架,新一代药物控释系统,药物,金属支架平台,垠艺TM药物涂层支架的组成结构,10,骄阳教育,大连垠艺生物材料研制开发有限公司 DALIAN YINYI BIOMATERIALS DEVELOPMENT CO., LTD.,放弃传统多聚体载药方式 采用首创的微孔控释载药技术,国产首个无聚合物涂层的药物支架,11,骄阳教育,大连垠艺生物材料研制开发有限公司 DAL
18、IAN YINYI BIOMATERIALS DEVELOPMENT CO., LTD.,垠艺TM支架微孔载药理论依据,参考文献 Zentralbl Chir. 2007 Jun;132(3):236-46. Tissue engineering: in vitro creation of tissue substitutes Cell Mol Biol (Noisy-le-grand). 2006 Dec 31;52(4):8-16. Hydrogen peroxide activation of endothelial cell-associated MMPs during VCAM-1-
19、dependent leukocyte migration. J Anat. 2006 Oct;209(4):495-502. Cell-matrix biology in vascular tissue engineering. Circ Res. 2005 Nov 25;97(11):1093-107. Endothelial extracellular matrix: biosynthesis, remodeling, and functions during vascular morphogenesis and neovessel stabilization. Curr Opin Ge
20、net Dev. 2005 Feb;15(1):102-11. Cellular abnormalities of blood vessels as targets in cancer. Microsc Res Tech. 2003 Jan 1;60(1):107-14. Angiogenesis in wound repair: angiogenic growth factors and the extracellular matrix. Am J Physiol Regul Integr Comp Physiol. 2003 Jan;284(1):R1-12. Molecular mech
21、anisms involved in the regulation of the endothelial nitric oxide synthase. Mol Immunol. 2002 Dec;39(9):499-508. VCAM-1 signals during lymphocyte migration: role of reactive oxygen species. Int Rev Immunol. 2002 Jan-Feb;21(1):33-49. The molecular control of angiogenesis.,材料学文献中明确指出直径5m以下的微孔利于内皮细胞的生长
22、 国际材料领域文献支持上述观点,12,骄阳教育,大连垠艺生物材料研制开发有限公司 DALIAN YINYI BIOMATERIALS DEVELOPMENT CO., LTD.,确切的动物实验依据,微孔支架植入兔子体内10天，可见内皮细胞完全包被支架表面,13,骄阳教育,大连垠艺生物材料研制开发有限公司 DALIAN YINYI BIOMATERIALS DEVELOPMENT CO., LTD.,科学的微孔控释技术参数,10天释放 72% 30天释放 95% 60天内释放100%,60天以后 = 100%裸支架,14,骄阳教育,大连垠艺生物材料研制开发有限公司 DALIAN YINYI BI
23、OMATERIALS DEVELOPMENT CO., LTD.,药物支架,药物控释系统,药物,金属支架平台,药物涂层支架的组成结构,15,骄阳教育,大连垠艺生物材料研制开发有限公司 DALIAN YINYI BIOMATERIALS DEVELOPMENT CO., LTD.,完美的金属支架平台,支撑段呈主次波交错，使径向支撑力增强的同时具有良好的柔顺性 次波幅短，有效避免了支架输送过程中翘起现象 形波峰增强支架径向支撑力 支架两端波幅相等，便于支架的准确定位,主次波,形波峰,16,骄阳教育,大连垠艺生物材料研制开发有限公司 DALIAN YINYI BIOMATERIALS DEVELOP
24、MENT CO., LTD.,完美的金属支架平台,主波间以“S”型柔顺段连接 柔顺段无锐角，增强径向抗压性，减少轴向回缩,S形柔顺段,17,骄阳教育,大连垠艺生物材料研制开发有限公司 DALIAN YINYI BIOMATERIALS DEVELOPMENT CO., LTD.,优化的几何构型确保支架最佳的物理性能 支架外表面和血管壁真正紧密的贴合 较大的侧孔保证侧支血管通畅 良好的透视性能以精确定位,完美的金属支架平台,18,骄阳教育,大连垠艺生物材料研制开发有限公司 DALIAN YINYI BIOMATERIALS DEVELOPMENT CO., LTD.,径向支撑力和拉伸强度试验证明
25、： 垠艺TM微孔支架力学性能与非微孔支架无差异,优秀的力学性能,19,骄阳教育,大连垠艺生物材料研制开发有限公司 DALIAN YINYI BIOMATERIALS DEVELOPMENT CO., LTD.,欧洲权威实验室检测结果： 垠艺TM微孔支架金属耐疲劳性能合格,以国际标准把握产品质量,20,骄阳教育,大连垠艺生物材料研制开发有限公司 DALIAN YINYI BIOMATERIALS DEVELOPMENT CO., LTD.,优异的球囊输送系统,球囊材料：聚酰胺 远端输送杆外径：2.7F 近端输送杆外径：1.9F 命名压（NP）：6atm 标定爆裂压（RBP）：16atm 折叠方式
26、：三折顺时针,21,骄阳教育,大连垠艺生物材料研制开发有限公司 DALIAN YINYI BIOMATERIALS DEVELOPMENT CO., LTD.,球囊顺应性表,1bar0.98692atm 球囊命名压（NP） 球囊标定爆破压（RBP）,22,骄阳教育,大连垠艺生物材料研制开发有限公司 DALIAN YINYI BIOMATERIALS DEVELOPMENT CO., LTD.,药物支架,药物控释系统,药物,金属支架平台,药物涂层支架的组成结构,23,骄阳教育,大连垠艺生物材料研制开发有限公司 DALIAN YINYI BIOMATERIALS DEVELOPMENT CO.,
27、LTD.,垠艺TM微孔载药支架的药物,1967年美国化学家Wall和Wani等首先发现 一种从太平洋紫杉树皮中提取二萜抗肿瘤成分 1992年底，获得美国FDA批准上市，现已被广泛应用于医疗领域,紫杉醇（Pacilitaxel，商品名TAXOL）,24,骄阳教育,大连垠艺生物材料研制开发有限公司 DALIAN YINYI BIOMATERIALS DEVELOPMENT CO., LTD.,作用靶点为微管 作用于细胞分裂的G2和M期 促进微管蛋白聚合,保持微管蛋白稳定,抑制平滑肌细胞有丝分裂 对DNA、RNA及蛋白质合成没有明显作用，对DNA模板亦无损伤作用,紫杉醇的作用机制,25,骄阳教育,大
28、连垠艺生物材料研制开发有限公司 DALIAN YINYI BIOMATERIALS DEVELOPMENT CO., LTD.,垠艺TM支架载药量：1.0g/mm2 理论最大血药浓度：0.025g/ml 远远小于紫杉醇安全血药浓度,支架药物的安全保证,26,骄阳教育,大连垠艺生物材料研制开发有限公司 DALIAN YINYI BIOMATERIALS DEVELOPMENT CO., LTD.,支架药物的比较,雷帕霉素和紫杉醇均能有效地抑制平滑肌细胞的增生 全球大量的临床使用及试验均已证明两种药物的安全性 截至目前，没有任何试验、理论及文献能够证明两者间的优劣 截至目前，同样没有证据证明雷帕霉
29、素衍生物与紫杉醇的优劣 雷帕霉素疗效优于紫杉醇的观点是不正确的 雷帕霉素衍生物疗效优于紫杉醇的观点更没有依据,27,骄阳教育,大连垠艺生物材料研制开发有限公司 DALIAN YINYI BIOMATERIALS DEVELOPMENT CO., LTD.,垠艺TM紫杉醇微孔载药支架临床验证结果,28,骄阳教育,大连垠艺生物材料研制开发有限公司 DALIAN YINYI BIOMATERIALS DEVELOPMENT CO., LTD.,垠艺TM紫杉醇微孔载药支架临床验证,大连医科大学第一附属医院和首都医科大学附属同仁医院心内科共同参与,29,骄阳教育,大连垠艺生物材料研制开发有限公司 DAL
30、IAN YINYI BIOMATERIALS DEVELOPMENT CO., LTD.,垠艺TM紫杉醇微孔载药支架临床验证,30,骄阳教育,大连垠艺生物材料研制开发有限公司 DALIAN YINYI BIOMATERIALS DEVELOPMENT CO., LTD.,垠艺TM紫杉醇微孔载药冠脉支架临床验证,31,骄阳教育,大连垠艺生物材料研制开发有限公司 DALIAN YINYI BIOMATERIALS DEVELOPMENT CO., LTD.,临床验证病例一 患者男性 临床诊断：冠心病，不稳定心绞痛 LCX植入一枚垠艺TM支架（3.5X28mm） 一年后病情稳定，造影随访无再狭窄,P
31、RE-PCI,POST-PCI,1 year FU,32,骄阳教育,临床验证病例二 患者女性 临床诊断：冠心病，不稳定心绞痛 RCA植入一枚垠艺TM支架（3.5X23mm） 一年后病情稳定，造影随访无再狭窄,PRE-PCI,POST-PCI,1 year FU,33,骄阳教育,大连垠艺生物材料研制开发有限公司 DALIAN YINYI BIOMATERIALS DEVELOPMENT CO., LTD.,临床验证病例三 患者男性 临床诊断：冠心病，急性心梗 LAD植入两枚垠艺TM支架（3.0X18mm、3.0X12mm) 术后一年病情稳定，造影随访无再狭窄,PRE-PCI,1 year FU,
32、34,骄阳教育,大连垠艺生物材料研制开发有限公司 DALIAN YINYI BIOMATERIALS DEVELOPMENT CO., LTD.,临床病例验证四 患者女性 临床诊断：冠心病，不稳定心绞痛 RCA植入一枚垠艺TM支架（3.0X12mm) 术后14个月病情稳定，造影随访无再狭窄,PRE-PCI,POST-PCI,14 months FU,35,骄阳教育,大连垠艺生物材料研制开发有限公司 DALIAN YINYI BIOMATERIALS DEVELOPMENT CO., LTD.,垠艺TM紫杉醇微孔载药支架,通过SFDA最严格的技术审评 通过SFDA最严格的真实性核查 通过上市前最
33、长期的临床验证,36,骄阳教育,大连垠艺生物材料研制开发有限公司 DALIAN YINYI BIOMATERIALS DEVELOPMENT CO., LTD.,垠艺TM紫杉醇微孔载药支架的未来,全新的设计思路 可靠的临床效果,37,骄阳教育,大连垠艺生物材料研制开发有限公司 DALIAN YINYI BIOMATERIALS DEVELOPMENT CO., LTD.,垠艺TM紫杉醇微孔载药支架的未来,逐步上市后启动临床研究以证明使用垠艺TM支架： 有效降低第一代药物支架涂层引起的晚期血栓风险 患者术后服用“波力维”的时间减至6个月甚至更短 节约单一患者术后药物花费：20元X180天= 36
34、00元 节约国家医疗支出：3600元X100000人= 3.6亿元 ,38,骄阳教育,大连垠艺生物材料研制开发有限公司 DALIAN YINYI BIOMATERIALS DEVELOPMENT CO., LTD.,垠艺TM紫杉醇微孔载药支架,国家十五攻关项目产业化 国内第一个无高分子聚合物涂层的药物支架 全球第二个自主研发无聚合物涂层药物支架的国家 最大限度地减小晚期血栓风险 最大限度地提高患者的生存质量 最大限度地节约国家医疗资源 ,39,骄阳教育,YUKON DES System,40,骄阳教育,大连垠艺生物材料研制开发有限公司 DALIAN YINYI BIOMATERIALS DEVELOPMENT CO., LTD.,垠艺TM紫杉醇微孔载药支架规格型号,41,骄阳教育,大连垠艺生物材料研制开发有限公司 DALIAN YINYI BIOMATERIALS DEVELOPMENT CO., LTD.,谢 谢！,期待全新的开始,42,骄阳教育,