1、大連垠藝生物材料研制開發(fā)有限公司 DALIAN YINYI BIOMATERIALS DEVELOPMENT CO., LTD.,新一代載藥技術(shù)，更安全的選擇 New Generation Technology，Your Safer Choice,垠藝TM紫杉醇微孔載藥冠狀動脈支架系統(tǒng),大連垠藝生物材料研制開發(fā)有限公司 DALIAN YINYI BIOMATERIALS DEVELOPMENT CO., LTD.,藥物涂層支架的發(fā)展趨勢,聚合物涂層支架,可降解涂層支架,無涂層藥物支架,可降解藥物支架,第一代DES Cypher Taxus Endeavor Firebird Partner ,

2、第二代DES 垠藝TM,第三代DES ？,改良的第一代DES Excel 愛克賽爾,大連垠藝生物材料研制開發(fā)有限公司 DALIAN YINYI BIOMATERIALS DEVELOPMENT CO., LTD.,第一代藥物涂層支架的作用,金屬支架,多聚體涂層,藥物,抑制平滑肌細(xì)胞增生 促進(jìn)內(nèi)皮細(xì)胞生長 抑制炎性反應(yīng),藥物載體、控制釋放,機械性壓迫斑塊 機械性支撐血管,大連垠藝生物材料研制開發(fā)有限公司 DALIAN YINYI BIOMATERIALS DEVELOPMENT CO., LTD.,第一代藥物涂層支架的長期狀況,金屬支架,多聚體涂層,藥物,100%代謝，無殘留,無作用 永久存在,

3、機械性支撐 永久存在,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 the use of its product the CY

4、PHER 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 angioplasty procedures to open clo

5、gged 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 implantation. The Food and Drug

6、 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 thrombosis risk and what factor

7、s 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 differs from the rate seen in

8、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 the diameter of the vessel

9、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 of an adequate antiplalelet

10、 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 increase the thrombosis ris

11、k. 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 /MedWatch). Cordis, in cooperation with FDA, will continue to monitor the issue.,大連垠藝生物材料研制開發(fā)有限

12、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 intervention (PCI). Although these stents

13、 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 samples taken after implantation of

14、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 The American Heart Association,多聚體載藥

15、（Polymer-based）支架已被廣泛應(yīng)用于心臟介入治療中，較裸金屬支架的再狹窄率明顯降低，但晚期血栓 - 這一威脅生命的嚴(yán)重并發(fā)癥的發(fā)生正逐步顯現(xiàn) 從動物和人體尸檢標(biāo)本的病理生理學(xué)數(shù)據(jù)可以看出，對照裸金屬支架，多聚體載藥（ Polymer-based）支架導(dǎo)致動脈內(nèi)膜修復(fù)的明顯延遲，出現(xiàn)明顯的纖維化和不完全的動脈血管內(nèi)皮化,大連垠藝生物材料研制開發(fā)有限公司 DALIAN YINYI BIOMATERIALS DEVELOPMENT CO., LTD.,第一代藥物支架多聚體涂層存在的問題,Pictures from TCT presentation,多聚體材料（選材差、粘度高等）導(dǎo)致嚴(yán)重的

16、涂層剝脫或粘連 生產(chǎn)工藝不佳導(dǎo)致涂層鼓起或有碎屑，加大了遠(yuǎn)端血管栓塞風(fēng)險,大連垠藝生物材料研制開發(fā)有限公司 DALIAN YINYI BIOMATERIALS DEVELOPMENT CO., LTD.,改良的第一代藥物支架,“可降解涂層” 新穎的概念，一點點疑問： 藥物釋放的同時涂層不斷降解，兩者能否達(dá)到動態(tài)平衡 載藥層降解過程對血管內(nèi)皮修復(fù)有無影響 載藥層能夠及時地全部降解 載藥層降解后是否影響支架與血管壁的緊密貼合,大連垠藝生物材料研制開發(fā)有限公司 DALIAN YINYI BIOMATERIALS DEVELOPMENT CO., LTD.,第二代藥物涂層支架,大連垠藝生物材料研制開發(fā)

17、有限公司 DALIAN YINYI BIOMATERIALS DEVELOPMENT CO., LTD.,藥物支架,新一代藥物控釋系統(tǒng),藥物,金屬支架平臺,垠藝TM藥物涂層支架的組成結(jié)構(gòu),大連垠藝生物材料研制開發(fā)有限公司 DALIAN YINYI BIOMATERIALS DEVELOPMENT CO., LTD.,放棄傳統(tǒng)多聚體載藥方式 采用首創(chuàng)的微孔控釋載藥技術(shù),國產(chǎn)首個無聚合物涂層的藥物支架,大連垠藝生物材料研制開發(fā)有限公司 DALIAN YINYI BIOMATERIALS DEVELOPMENT CO., LTD.,垠藝TM支架微孔載藥理論依據(jù),參考文獻(xiàn) Zentralbl Chir

18、. 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-dependent leukocyte migration. J Anat. 2006 Oct;209(4):495-502. Cell-matrix bio

19、logy 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 Genet Dev. 2005 Feb;15(1):102-11. Cellular abnormalities of blood vessels as targ

20、ets 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 mechanisms involved in the regulation of the endothelial nitric oxide synthase. Mol

21、 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.,材料學(xué)文獻(xiàn)中明確指出直徑5m以下的微孔利于內(nèi)皮細(xì)胞的生長 國際材料領(lǐng)域文獻(xiàn)支持上述觀點,大連垠藝生物材料研制開發(fā)有限公司 DALIAN YINYI BIOMATERIALS DEVELOPMENT CO., LTD

22、.,確切的動物實驗依據(jù),微孔支架植入兔子體內(nèi)10天，可見內(nèi)皮細(xì)胞完全包被支架表面,大連垠藝生物材料研制開發(fā)有限公司 DALIAN YINYI BIOMATERIALS DEVELOPMENT CO., LTD.,科學(xué)的微孔控釋技術(shù)參數(shù),10天釋放 72% 30天釋放 95% 60天內(nèi)釋放100%,60天以后 = 100%裸支架,大連垠藝生物材料研制開發(fā)有限公司 DALIAN YINYI BIOMATERIALS DEVELOPMENT CO., LTD.,藥物支架,藥物控釋系統(tǒng),藥物,金屬支架平臺,藥物涂層支架的組成結(jié)構(gòu),大連垠藝生物材料研制開發(fā)有限公司 DALIAN YINYI BIOMAT

23、ERIALS DEVELOPMENT CO., LTD.,完美的金屬支架平臺,支撐段呈主次波交錯，使徑向支撐力增強的同時具有良好的柔順性 次波幅短，有效避免了支架輸送過程中翹起現(xiàn)象 形波峰增強支架徑向支撐力 支架兩端波幅相等，便于支架的準(zhǔn)確定位,主次波,形波峰,大連垠藝生物材料研制開發(fā)有限公司 DALIAN YINYI BIOMATERIALS DEVELOPMENT CO., LTD.,完美的金屬支架平臺,主波間以“S”型柔順段連接 柔順段無銳角，增強徑向抗壓性，減少軸向回縮,S形柔順段,大連垠藝生物材料研制開發(fā)有限公司 DALIAN YINYI BIOMATERIALS DEVELOPME

24、NT CO., LTD.,優(yōu)化的幾何構(gòu)型確保支架最佳的物理性能 支架外表面和血管壁真正緊密的貼合 較大的側(cè)孔保證側(cè)支血管通暢 良好的透視性能以精確定位,完美的金屬支架平臺,大連垠藝生物材料研制開發(fā)有限公司 DALIAN YINYI BIOMATERIALS DEVELOPMENT CO., LTD.,徑向支撐力和拉伸強度試驗證明： 垠藝TM微孔支架力學(xué)性能與非微孔支架無差異,優(yōu)秀的力學(xué)性能,大連垠藝生物材料研制開發(fā)有限公司 DALIAN YINYI BIOMATERIALS DEVELOPMENT CO., LTD.,歐洲權(quán)威實驗室檢測結(jié)果： 垠藝TM微孔支架金屬耐疲勞性能合格,以國際標(biāo)準(zhǔn)把握

25、產(chǎn)品質(zhì)量,大連垠藝生物材料研制開發(fā)有限公司 DALIAN YINYI BIOMATERIALS DEVELOPMENT CO., LTD.,優(yōu)異的球囊輸送系統(tǒng),球囊材料：聚酰胺 遠(yuǎn)端輸送桿外徑：2.7F 近端輸送桿外徑：1.9F 命名壓（NP）：6atm 標(biāo)定爆裂壓（RBP）：16atm 折疊方式：三折順時針,大連垠藝生物材料研制開發(fā)有限公司 DALIAN YINYI BIOMATERIALS DEVELOPMENT CO., LTD.,球囊順應(yīng)性表,1bar0.98692atm 球囊命名壓（NP） 球囊標(biāo)定爆破壓（RBP）,大連垠藝生物材料研制開發(fā)有限公司 DALIAN YINYI BIOM

26、ATERIALS DEVELOPMENT CO., LTD.,藥物支架,藥物控釋系統(tǒng),藥物,金屬支架平臺,藥物涂層支架的組成結(jié)構(gòu),大連垠藝生物材料研制開發(fā)有限公司 DALIAN YINYI BIOMATERIALS DEVELOPMENT CO., LTD.,垠藝TM微孔載藥支架的藥物,1967年美國化學(xué)家Wall和Wani等首先發(fā)現(xiàn) 一種從太平洋紫杉樹皮中提取二萜抗腫瘤成分 1992年底，獲得美國FDA批準(zhǔn)上市，現(xiàn)已被廣泛應(yīng)用于醫(yī)療領(lǐng)域,紫杉醇（Pacilitaxel，商品名TAXOL）,大連垠藝生物材料研制開發(fā)有限公司 DALIAN YINYI BIOMATERIALS DEVELOPME

27、NT CO., LTD.,作用靶點為微管 作用于細(xì)胞分裂的G2和M期 促進(jìn)微管蛋白聚合,保持微管蛋白穩(wěn)定,抑制平滑肌細(xì)胞有絲分裂 對DNA、RNA及蛋白質(zhì)合成沒有明顯作用，對DNA模板亦無損傷作用,紫杉醇的作用機制,大連垠藝生物材料研制開發(fā)有限公司 DALIAN YINYI BIOMATERIALS DEVELOPMENT CO., LTD.,垠藝TM支架載藥量：1.0g/mm2 理論最大血藥濃度：0.025g/ml 遠(yuǎn)遠(yuǎn)小于紫杉醇安全血藥濃度,支架藥物的安全保證,大連垠藝生物材料研制開發(fā)有限公司 DALIAN YINYI BIOMATERIALS DEVELOPMENT CO., LTD.,

28、支架藥物的比較,雷帕霉素和紫杉醇均能有效地抑制平滑肌細(xì)胞的增生 全球大量的臨床使用及試驗均已證明兩種藥物的安全性 截至目前，沒有任何試驗、理論及文獻(xiàn)能夠證明兩者間的優(yōu)劣 截至目前，同樣沒有證據(jù)證明雷帕霉素衍生物與紫杉醇的優(yōu)劣 雷帕霉素療效優(yōu)于紫杉醇的觀點是不正確的 雷帕霉素衍生物療效優(yōu)于紫杉醇的觀點更沒有依據(jù),大連垠藝生物材料研制開發(fā)有限公司 DALIAN YINYI BIOMATERIALS DEVELOPMENT CO., LTD.,垠藝TM紫杉醇微孔載藥支架臨床驗證結(jié)果,大連垠藝生物材料研制開發(fā)有限公司 DALIAN YINYI BIOMATERIALS DEVELOPMENT CO.,

29、 LTD.,垠藝TM紫杉醇微孔載藥支架臨床驗證,大連醫(yī)科大學(xué)第一附屬醫(yī)院和首都醫(yī)科大學(xué)附屬同仁醫(yī)院心內(nèi)科共同參與,大連垠藝生物材料研制開發(fā)有限公司 DALIAN YINYI BIOMATERIALS DEVELOPMENT CO., LTD.,垠藝TM紫杉醇微孔載藥支架臨床驗證,大連垠藝生物材料研制開發(fā)有限公司 DALIAN YINYI BIOMATERIALS DEVELOPMENT CO., LTD.,垠藝TM紫杉醇微孔載藥冠脈支架臨床驗證,大連垠藝生物材料研制開發(fā)有限公司 DALIAN YINYI BIOMATERIALS DEVELOPMENT CO., LTD.,臨床驗證病例一 患者

30、男性 臨床診斷：冠心病，不穩(wěn)定心絞痛 LCX植入一枚垠藝TM支架（3.5X28mm） 一年后病情穩(wěn)定，造影隨訪無再狹窄,PRE-PCI,POST-PCI,1 year FU,臨床驗證病例二 患者女性 臨床診斷：冠心病，不穩(wěn)定心絞痛 RCA植入一枚垠藝TM支架（3.5X23mm） 一年后病情穩(wěn)定，造影隨訪無再狹窄,PRE-PCI,POST-PCI,1 year FU,大連垠藝生物材料研制開發(fā)有限公司 DALIAN YINYI BIOMATERIALS DEVELOPMENT CO., LTD.,臨床驗證病例三 患者男性 臨床診斷：冠心病，急性心梗 LAD植入兩枚垠藝TM支架（3.0X18mm、3.0X1