WO2022174720A1 - 载药医疗器械及其制备方法 - Google Patents
载药医疗器械及其制备方法 Download PDFInfo
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- WO2022174720A1 WO2022174720A1 PCT/CN2022/073345 CN2022073345W WO2022174720A1 WO 2022174720 A1 WO2022174720 A1 WO 2022174720A1 CN 2022073345 W CN2022073345 W CN 2022073345W WO 2022174720 A1 WO2022174720 A1 WO 2022174720A1
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- drug
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- rapamycin
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- inhibitors
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Abstract
Description
球囊表面残余药量(%) | |
实施例1 | 6% |
实施例2 | 5% |
实施例3 | 5% |
实施例4 | 6% |
实施例5 | 8% |
实施例6 | 4% |
实施例7 | 5% |
实施例8 | 5% |
实施例9 | 7% |
实施例10 | 6% |
实施例11 | 9% |
实施例12 | 8% |
对比例1 | 12% |
对比例2 | 8% |
实施例 | 损失率 | 晶体形态 | 最大长径比范围 | 最大长度 |
实施例1 | 8% | 长柱 | 3-7 | 5μm |
实施例2 | 15% | 长柱 | 3-6 | 7μm |
实施例3 | 6% | 长柱 | 2-7 | 6μm |
实施例4 | 24% | 长柱 | 8-15 | 15μm |
实施例5 | 17% | 长柱 | 3-9 | 10μm |
实施例6 | 7% | 长柱 | 3-7 | 8μm |
实施例7 | 12% | 长柱 | 2-8 | 7μm |
实施例8 | 10% | 长柱 | 3-7 | 8μm |
实施例9 | 8% | 长柱 | 4-10 | 3μm |
实施例10 | 7% | 长柱 | 5-10 | 8μm |
实施例11 | 8% | 长柱晶簇 | 4-9 | 8μm |
实施例12 | 13% | 长柱 | 9-16 | 9μm |
对比例1 | 38% | 针状 | 60 | 28μm |
对比例2 | 30% | 圆粒状 | 1 | 10μm |
Claims (14)
- 载药医疗器械,包含一医疗器械本体以及至少一药物涂层,所述药物涂层附着于所述医疗器械本体表面的至少一侧,其中:所述药物涂层的主要成分包括大环内酯类药物,所述药物涂层包括具有三条以上的棱的长柱体晶体,和/或所述药物涂层包括具有三条以上的棱的长柱体晶体形成的晶簇,所述长柱体晶体的长径比为(1~40):1。
- 根据权利要求1所述的载药医疗器械,其中,所述长柱体晶体包含至少两个相邻夹角小于90度的侧面。
- 根据权利要求1所述的载药医疗器械,其中,所述长柱体晶体的长度为小于25μm。
- 根据权利要求1所述的载药医疗器械,其中,所述药物涂层附着于所述医疗器械本体表面一侧的损失率小于或等于24%。
- 根据权利要求1所述的载药医疗器械,其中,所述大环内酯类药物包括雷帕霉素、佐他莫司、依维莫司、坦西莫司、比欧莫司、7-O-去甲基雷帕霉素、替西罗莫司、地磷莫司、40-O-(2-羟基)乙基-雷帕霉素、32-脱氧雷帕霉素、Biolimus A9、ABT-578、SDZ RAD、SAR943的一种或多种。
- 根据权利要求1所述的载药医疗器械,其中,所述药物涂层还具有以下a)~d)的至少一种:a)所述长柱体晶体的上下底面之一具有药物转运载体层,所述药物转运载体层的主要成分包括氯化钙、聚乙烯吡咯烷酮、聚乙烯醇、胶原、明胶、多糖、硬脂酸、碘普罗胺、碘帕醇、碘海醇、碘佛醇、尿素、枸橼酸、葡聚糖、聚山梨酯、山梨糖醇、壳聚糖、泊洛沙姆、羧甲基纤维素钠、羟丙基甲基纤维、透明质酸钠、藻酸钠、紫胶铵盐、丁酰柠檬酸三正己酯、虫胶以及PEG中的至少一种;b)所述药物涂层包含抗氧化剂,选自二丁基羟基甲苯、丁基羟基苯甲醚、抗坏血酸、棕榈酸酯、生育酚、普罗布考、维生素E以及聚乙二醇琥珀酸酯中的至少一种;c)所述药物涂层包含有机结晶成核剂,选自有机酸盐类、二苄叉山梨醇类、二酰胺类化合物、酰肼类化合物中的至少一种;d)所述药物涂层包含除大环内酯类药物以外的至少一种其他活性药物,选自紫杉醇、紫杉醇衍生物、西洛他唑、噻氯匹定、磷酸二酯酶抑制剂、萘呋胺酯、己酮可可碱、利伐沙班、阿哌沙班、达比加群酯、替罗非班、凝血酶抑制剂、Xa因子抑制剂、维生素K抑制剂、环氧化酶抑制剂、ADP受体拮抗抑制剂、血小板糖蛋白Ⅱb/Ⅲa受体拮抗剂、地塞米松、泼尼松龙、皮质酮、布地奈德、利钠肽、雌激素、柳氮磺吡啶和氨水杨酸、阿西美辛、七叶皂苷、氨基蝶呤、抗霉菌素、三氧化二砷、马兜铃酸、阿司匹林、小糪碱、银杏酚、内皮他汀、血管他汀、血管肽素、能够阻断平滑肌细胞增殖的单克隆抗体、左氧氟沙星、羟基喜树碱、长春花碱、长春新碱、阿霉素、5-氟尿嘧啶、顺铂、双膦酸盐、选择性雌激素受体调节剂、雷尼酸锶、放线菌素D、环孢霉素A、环孢霉素C、布雷菲德菌素A、松弛素、鸟苷酸活化酶调节剂、硝酰基前体药物CXL-1020、硝酸酯类药物、硝普钠、硝酸甘油、胸苷激酶抑制剂抗生素、奈西立肽、钙通道阻滞剂如地尔硫卓、维拉帕米、尼卡地平、血小板血管扩张剂刺激磷蛋白、血管扩张剂刺激磷蛋白、罂粟碱、腺苷、硫酸镁、烟酸占替诺以及尼可地尔中的至少一种;所述紫杉醇衍生物包括多烯紫杉醇、白蛋白结合型紫杉醇、nap-紫杉醇中的一种或多种。
- 载药医疗器械的制备方法,包括:1)将大环内酯类药物晶体粉末分散于溶剂中,加入刚性微球进行震荡,过滤除去所述刚性微球得到悬液;2)取一医疗器械本体,将所述悬液涂置于所述的医疗器械本体表面,干燥得到医疗 器械中间体;3)将所述大环内酯类药物的过饱和溶液涂置于所述的医疗器械中间体表面,干燥。
- 根据权利要求7所述的载药医疗器械的制备方法,其特征在于,所述悬液包含粒径为100nm~1000nm的大环内酯类药物的结晶微颗粒。
- 根据权利要求8所述的载药医疗器械的制备方法,其中,所述过饱和溶液的浓度为1mg/mL~100mg/mL。
- 根据权利要求7~9任一项所述的载药医疗器械的制备方法,其中,所述溶剂包括正庚烷、正己烷、戊烷、环己烷中的至少一种。
- 根据权利要求8或9任一项所述的载药医疗器械的制备方法,其中,所述刚性微球的材质包括氧化锆、氮化硅、硬质不锈钢、硬质碳化钨、烧结刚玉、玛瑙中的至少一种,且所述刚性微球的粒径为所述结晶微颗粒粒径的800~1200倍。
- 根据权利要求7所述的载药医疗器械的制备方法,其中,在步骤2)中,所述医疗器械本体的表面设置有药物转运载体层,所述药物转运载体层的主要成分包括氯化钙、聚乙烯吡咯烷酮、聚乙烯醇、胶原、明胶、多糖、硬脂酸、碘普罗胺、碘帕醇、碘海醇、碘佛醇、尿素、枸橼酸、葡聚糖、聚山梨酯、山梨糖醇、壳聚糖、泊洛沙姆、羧甲基纤维素钠、羟丙基甲基纤维、透明质酸钠、藻酸钠、紫胶铵盐、丁酰柠檬酸三正己酯、虫胶以及PEG中的至少一种。
- 根据权利要求7所述的载药医疗器械的制备方法,还包括取有机结晶成核剂溶液喷涂于所述中间体表面并干燥,所述有机结晶成核剂选自有机酸盐类、二苄叉山梨醇类、二酰胺类化合物、酰肼类化合物中的至少一种。
- 根据权利要求7所述的载药医疗器械的制备方法,其中,所述大环内酯类药物的过饱和溶液中还含有抗氧化剂和/或除大环内酯类药物以外的至少一种其他活性药物;所述抗氧化剂选自二丁基羟基甲苯、丁基羟基苯甲醚、抗坏血酸、棕榈酸酯、生育酚、普罗布考、维生素E以及聚乙二醇琥珀酸酯中的至少一种;所述除大环内酯类药物以外的至少一种其他活性药物选自紫杉醇、紫杉醇衍生物、西洛他唑、噻氯匹定、磷酸二酯酶抑制剂、萘呋胺酯、己酮可可碱、利伐沙班、阿哌沙班、达比加群酯、替罗非班、凝血酶抑制剂、Xa因子抑制剂、维生素K抑制剂、环氧化酶抑制剂、ADP受体拮抗抑制剂、血小板糖蛋白Ⅱb/Ⅲa受体拮抗剂、地塞米松、泼尼松龙、皮质酮、布地奈德、利钠肽、雌激素、柳氮磺吡啶和氨水杨酸、阿西美辛、七叶皂苷、氨基蝶呤、抗霉菌素、三氧化二砷、马兜铃酸、阿司匹林、小糪碱、银杏酚、内皮他汀、血管他汀、血管肽素、能够阻断平滑肌细胞增殖的单克隆抗体、左氧氟沙星、羟基喜树碱、长春花碱、长春新碱、阿霉素、5-氟尿嘧啶、顺铂、双膦酸盐、选择性雌激素受体调节剂、雷尼酸锶、放线菌素D、环孢霉素A、环孢霉素C、布雷菲德菌素A、松弛素、鸟苷酸活化酶调节剂、硝酰基前体药物CXL-1020、硝酸酯类药物、硝普钠、硝酸甘油、胸苷激酶抑制剂、抗生素、奈西立肽、钙通道阻滞剂如地尔硫卓、维拉帕米、尼卡地平、血小板血管扩张剂刺激磷蛋白、血管扩张剂刺激磷蛋白、罂粟碱、腺苷、硫酸镁、烟酸占替诺以及尼可地尔中的至少一种;所述紫杉醇衍生物包括多烯紫杉醇、白蛋白结合型紫杉醇、nap-紫杉醇中的一种或多种。
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CN115300675A (zh) * | 2022-03-21 | 2022-11-08 | 上海以心医疗器械有限公司 | 一种药物涂层医疗器械及其制备方法与应用、药物涂层及其应用 |
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