5-氟尿嘧啶食道支架的制备和体外研究
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摘要
临床上广泛用于介入治疗食道恶性狭窄的金属支架常伴有短期内再狭窄的发生。肿瘤的内生长(ingrowth)和过度生长(overgrowth)是导致食道支架再狭窄发生的主要原因。本文以一定的工艺手段制备了5-氟尿嘧啶食道支架给药系统。5-氟尿嘧啶食道支架不仅具备普通金属支架的优点,同时将抗癌药物定位、定向、持续、长期释放作用于肿瘤组织,以期达到对食道恶性狭窄进行治疗、防止支架再狭窄或延长支架食管内使用寿命的目的。
本文首先对5-氟尿嘧啶食道支架进行了处方前研究。建立了UV和HPLC两种体外分析方法,并对5-氟尿嘧啶(5-Fu)的理化性质进行了考察。选择了以弹性体材料中的乙烯-醋酸乙烯酯共聚物(EVA)作为药物载体,并对其成膜方法(溶剂法和机械法)进行了比较,确定了以二次机械混合压膜法进行支架药膜的制备。
支架药膜的制备过程:以哈克机和双辊机为混合装置制备了不同药物含量的药膜混合基质,以高温平板硫化仪和室温平板硫化仪为制膜装置制备了支架药膜(20,30,40,50,60wt%)。考察了混合前后药物粒子的大小(光学显微镜和AFM),药物的分散(AFM),药物和膜材的相互作用(DSC),和药膜的力学性能。药膜的AFM照片显示:药物粒子大小均匀,平均大小2～3μm左右,与混合前的粒子大小(约5μm)相比稍小,这可能是由于制膜过程中药物粒子得
Palliative relief from malignant esophageal stricture has been comprehensively obtained by using metallic stents in clinic. However, the failure of this endoluminal stent frequently occurred resulting from ingrowth and overgrowth of the device by tumor cells. A new type of esophageal stent was fabricated, which is the combination of an anticancer drug-containing stent coating and an esophageal stent. The drug-coated esophageal stent reserves the functions of traditional stents. Furthermore, this local drug delivery/medical device combination has the advantages: the drug is targeted to the esophageal cancer and its neighboring tissue, and there is no need to use high or toxic systemic doses to achieve sufficient local concentrations; and a sustained, controlled dosing level can be maintained around the device over the necessary duration. Therefore, suppression of tumor growth and improved effective lifespan of the device could be expected simultaneously.
Firstly, we conducted the preformulation studies on 5-Fu-loaded esophageal stent coatings. Two quantitive determination methods of 5-Fu, HPLC method and UV method, were established. The related physical
本文首先对5-氟尿嘧啶食道支架进行了处方前研究。建立了UV和HPLC两种体外分析方法,并对5-氟尿嘧啶(5-Fu)的理化性质进行了考察。选择了以弹性体材料中的乙烯-醋酸乙烯酯共聚物(EVA)作为药物载体,并对其成膜方法(溶剂法和机械法)进行了比较,确定了以二次机械混合压膜法进行支架药膜的制备。
支架药膜的制备过程:以哈克机和双辊机为混合装置制备了不同药物含量的药膜混合基质,以高温平板硫化仪和室温平板硫化仪为制膜装置制备了支架药膜(20,30,40,50,60wt%)。考察了混合前后药物粒子的大小(光学显微镜和AFM),药物的分散(AFM),药物和膜材的相互作用(DSC),和药膜的力学性能。药膜的AFM照片显示:药物粒子大小均匀,平均大小2～3μm左右,与混合前的粒子大小(约5μm)相比稍小,这可能是由于制膜过程中药物粒子得
Palliative relief from malignant esophageal stricture has been comprehensively obtained by using metallic stents in clinic. However, the failure of this endoluminal stent frequently occurred resulting from ingrowth and overgrowth of the device by tumor cells. A new type of esophageal stent was fabricated, which is the combination of an anticancer drug-containing stent coating and an esophageal stent. The drug-coated esophageal stent reserves the functions of traditional stents. Furthermore, this local drug delivery/medical device combination has the advantages: the drug is targeted to the esophageal cancer and its neighboring tissue, and there is no need to use high or toxic systemic doses to achieve sufficient local concentrations; and a sustained, controlled dosing level can be maintained around the device over the necessary duration. Therefore, suppression of tumor growth and improved effective lifespan of the device could be expected simultaneously.
Firstly, we conducted the preformulation studies on 5-Fu-loaded esophageal stent coatings. Two quantitive determination methods of 5-Fu, HPLC method and UV method, were established. The related physical
引文
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