CN115444818A - 一种基于丝素蛋白纳米纤维的滴眼药物增溶辅料及含该辅料药物的制备方法 - Google Patents
一种基于丝素蛋白纳米纤维的滴眼药物增溶辅料及含该辅料药物的制备方法 Download PDFInfo
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Abstract
本发明提供了一种基于丝素蛋白纳米纤维的滴眼药物增溶辅料及含该辅料药物的制备方法，具体为：将丝素蛋白纳米纤维的水相分散液在50‑400W功率下超声1‑15min将纤维打断，形成长度<50nm的丝素蛋白纳米纤维，冷冻干燥获得丝素蛋白纳米纤维的粉末。将粉末再分散在叔丁醇中，加入抗炎症药物，超声并搅拌辅助至药物完全溶解，冷冻干燥后得到丝素蛋白纳米纤维‑药物复合物的干粉制剂。将干粉制剂再分散溶解于无菌缓冲液中，控制抗炎药物的最终质量百分浓度为0.1‑1.0％，并加入防腐剂、pH调节剂、等渗调节剂之后无菌过滤分装，即为丝素蛋白纳米纤维增溶的滴眼药物。其中，丝素蛋白纳米纤维通过已有技术获得，防腐剂、pH调节剂、等渗调节剂按照已有技术添加。该方法适用性广，可广泛用于不同种类眼科药物的增溶和分散，形成的丝素蛋白纳米纤维‑药物复合物安全性好、稳定性高、溶解度大，有很好的社会价值和应用前景。
Description
技术领域
本发明涉及一种用于滴眼剂的增溶性辅料，属于眼部载体药的技术领域。
背景技术
眼内疾病的传统给药方式大多基于有创伤性的眼内注射或者眼内植入药物。发展新型非侵入性的眼表给药(以滴眼为主)制剂是近年研究的热点。然而，由于眼部结构复杂和存在许多屏障，许多滴眼剂型药物的治疗效果欠佳。例如，受药物在眼表快速流失、房水屏障等影响，常规滴眼液中的药物很难在视网膜组织达到有效药物浓度，只有约10％的药物能够进入眼内组织，导致药物的生物利用度较低，需要反复给药维持药物浓度，病人耐受性差。而且，大多数药物的水溶性差，直接制备得到的油剂滴眼液对眼部刺激性大，不利于患者的顺应性。
为了改善上述缺陷，凝胶、微粒、胶粒等药物辅料形式被开发，以增加药物的水相分散性并延长药物滞留时间，从而改善滴眼剂的有效性、顺应性和生物利用度。此类辅料多为黏性亲水胶体(或胶束)物质，常见的有高分子聚合物(聚乙烯醇、聚维酮、聚乙二醇、卡波姆、嵌段聚合物等)和纤维素衍生物(甲基纤维素、羟丙基纤维素等)等。例如，中国专利(CN110664752 A)将聚乙二醇-聚甲基丙烯酸甘油酯嵌段共聚物置于乙醇中自我组装成交联胶束，包载那他霉素后得到的那他霉素聚合物胶束滴眼液，能够延长那他霉素的释放时间，减少用药次数。文献(Journal of Controlled Release,2000,69,379-388)以卡波姆和泊洛沙姆为辅料，制备出凝胶型滴眼剂，药物水相分散性良好，保药能力强，明显提高了药物的眼部生物利用度。但是，上述辅料的制备过程通常较为复杂，制备过程中使用了有毒试剂等。制备基于天然高分子材料的滴眼液具有重要应用价值。
丝素蛋白是开发新型药物载体、可植入机体的生物材料、高性能复合材料的重要研究对象。作为药物载体，丝素蛋白分子及其纳米颗粒被广泛报道，即利用丝素蛋白与药物分子间的疏水力、静电力等将药物负载或包埋，为药物增溶、控释等创造条件。与其他材料相比，丝素蛋白具有生物相容性高、绿色可降解、来源广泛、提取过程简单等优点。例如，文献(Advanced Materials Research,2013,796,117-120)对比了丝素蛋白微球负载药物及其在不同pH条件下的释放速率；中国专利(CN107157952 A)报道了一种载药丝素蛋白纳米颗粒，提高了药物在细胞内的摄取量，延长了药物的滞留时间；中国专利(CN106362223 A)制备了一种多孔丝素蛋白微针给药装置，将丝素蛋白分子与溶胀剂、药物等混合后浇筑于模具中得到丝素蛋白复合微针。中国专利(CN107260742 A)报道了一种抗肿瘤纳米纤维药膜的制备方法，将药物负载在静电纺丝得到的丝素蛋白纤维(纤维直径>50nm)上，形成药物控制释放体系，实现药物的持续释放。但是，将丝素蛋白纳米纤维(纤维直径<20nm)作为非侵入性的滴眼剂药物增溶辅料未见报道。
发明内容
本发明针对现有技术存在的上述不足，提出一种基于丝素蛋白纳米纤维的滴眼药物增溶辅料及含该辅料药物的制备方法。
为实现上述目的，本发明采用的技术方案为：将丝素蛋白纳米纤维的水相分散液在50-400W功率下超声1-15min将纤维打断，形成长度<50nm的丝素蛋白纳米纤维，冷冻干燥获得丝素蛋白纳米纤维的粉末。将粉末再分散在叔丁醇中，加入抗炎症药物，超声并搅拌辅助至药物完全溶解，冷冻干燥后得到丝素蛋白纳米纤维-药物复合物的干粉制剂。将此干粉制剂再分散溶解于无菌缓冲液中，控制抗炎药物的最终质量百分浓度为0.1-1.0％，并加入防腐剂、pH调节剂、等渗调节剂之后无菌过滤分装，即为丝素蛋白纳米纤维增溶的滴眼药物。
所述滴眼药物，包括抗炎症药物为主药，以及防腐剂、pH调节剂、等渗调节剂，其特征在于还包括丝素蛋白纳米纤维为药物增溶辅料。
所述丝素蛋白纳米纤维通过已有技术获得，其在水中分散的质量分数为0.01-2.0％，主药和丝素蛋白纳米纤维的质量比在1：5-1：30之间。
所述抗炎症药物一般为疏水性药物，包括但不限于姜黄素、杨梅素、氧氟沙星等眼科抗炎药物中的一种或几种。
所述无菌缓冲液为常用磷酸盐缓冲液或硼酸盐缓冲液，pH值为7.4，丝素蛋白纳米纤维-药物复合物在无菌缓冲液中的分散性好、分散稳定性高。
所述防腐剂、pH调节剂、等渗调节剂按照已有技术添加。
本发明的有益效果
本发明创新性地研究了蚕丝纳米纤维作为滴眼剂药物辅料的性能，操作步骤简单，对设备的要求低，制备过程绿色环保，生产成本低，不使用有毒、有害试剂；蚕丝纳米纤维对多种疏水性抗炎症类药物的载药量大、增溶效果明显，提高了药物的稳定性和溶解度，能够实现大规模工业化制备。具体为：
1.本发明所用到的蚕丝纳米纤维广泛易得、价格低廉、无细胞毒性，制备过程不涉及有毒、有害试剂，且纤维的尺寸分布均匀(纤维形貌如图1所示)。
2.蚕丝纳米纤维对多种疏水性药物的负载量高(例如，对姜黄素的负载量可达～78mg/g)，负载后的药物水相分散性好(如图2)、稳定性高(例如，图3中，室温放置两个月仍稳定，无沉淀析出)，满足主药对溶解度和稳定性的要求。
3.本发明制备过程中对实验设备的要求低，制备过程只需要磁力搅拌器、超声破碎仪和冷冻干燥仪。
4.该方法利用丝素蛋白纳米纤维的高生物相容性、多官能团及结合位点、高透明性、及其在多种溶剂中的高分散稳定性等优点，通过丝素蛋白纳米纤维与药物的结合实现药物的增溶，更好地发挥药物疗效。
5.该方法适用性广，可广泛用于不同种类药物的增溶，形成的丝素蛋白纳米纤维-药物复合物安全性好、稳定性高、溶解度大。
综上所述，本发明制备过程操作简单，生产成本低，绿色环保，生产周期短，不涉及大型仪器设备；蚕丝纳米纤维作为辅料可明显提高药物的溶解度和稳定性，满足滴眼剂要求，有很好的社会价值和应用前景。
附图说明
图1：蚕丝纳米纤维的SEM形貌图
图2：蚕丝蛋白纳米纤维负载姜黄素(左)和杨梅素(右)的磷酸盐缓冲溶液照片
图3：蚕丝蛋白纳米纤维负载姜黄素的磷酸盐缓冲溶液在室温下放置两个月后的照片
具体实施方式
下面结合附图和具体实施例对本发明进行详细说明：本实施例在以本发明技术方案为前提下进行实施，给出了详细的实施方式和具体的操作过程，但本发明的保护范围不限于下述的实施例。
实施例1
以抗炎药物姜黄素为例，实施蚕丝纳米纤维增溶的滴眼药物制备：
将10mL质量分数为0.5wt.％的丝素蛋白纳米纤维水相分散液在100W功率下超声分散1.5min，获得直径分布2-28nm，长度分布1000-3000nm的丝素蛋白纳米纤维，冷冻干燥得到粉末(如图1)。将粉末再分散在10mL叔丁醇中，加入20mg姜黄素，20W功率超声1min，冷冻干燥得到丝素蛋白纳米纤维-姜黄素的干粉制剂(姜黄素负载量为78mg/g)。用10mL磷酸盐缓冲液分散溶解干粉制剂，加入防腐剂苯扎氯铵、等渗调节剂氯化钠，pH调节至7.4，无菌过滤分装即可。激光粒度仪测得姜黄素胶束平均粒径为93nm，分散均一性良好。将该姜黄素胶束滴眼剂在室温条件下保存2个月，姜黄素的渗漏量小于10％。
实施例2
以抗炎药物姜黄素为例，实施蚕丝纳米纤维增溶的滴眼药物制备：
将10mL质量分数为0.5wt.％的丝素蛋白纳米纤维水相分散液在300W功率下超声分散1.5min，获得直径分布2-28nm，长度分布100-600nm的丝素蛋白纳米纤维，冷冻干燥得到粉末。将粉末再分散在10mL叔丁醇中，加入30mg姜黄素，20W功率超声1min，冷冻干燥得到丝素蛋白纳米纤维-姜黄素的干粉制剂(姜黄素负载量为72mg/g)。用10mL磷酸盐缓冲液分散溶解干粉制剂，加入防腐剂苯扎氯铵、等渗调节剂氯化钠，pH调节至7.4，无菌过滤分装即可。激光粒度仪测得姜黄素胶束平均粒径为73nm，分散均一性良好。将该姜黄素胶束滴眼剂在室温条件下保存2个月，姜黄素的渗漏量小于5％。
实施例3
以抗炎药物杨梅素为例，实施蚕丝纳米纤维增溶的滴眼药物制备：
将10mL质量分数为0.5wt.％的丝素蛋白纳米纤维水相分散液在100W功率下超声分散1.5min，获得直径分布2-28nm，长度分布1000-3000nm的丝素蛋白纳米纤维，冷冻干燥得到粉末。将粉末再分散在10mL叔丁醇中，加入20mg杨梅素，20W功率超声1min，冷冻干燥得到丝素蛋白纳米纤维-杨梅素的干粉制剂(杨梅素负载量为54mg/g)。用10mL磷酸盐缓冲液分散溶解干粉制剂，加入防腐剂苯扎氯铵、等渗调节剂氯化钠，pH调节至7.4，无菌过滤分装即可。激光粒度仪测得杨梅素胶束平均粒径为106nm，分散均一性良好。将该姜黄素胶束滴眼剂在室温条件下保存2个月，杨梅素的渗漏量小于6％。
Claims (6)
1.一种基于丝素蛋白纳米纤维的滴眼药物增溶辅料及含该辅料药物的制备方法，其特征在于：将丝素蛋白纳米纤维的水相分散液在50-400W功率下超声1-15min将纤维打断，形成长度<50nm的丝素蛋白纳米纤维，冷冻干燥获得丝素蛋白纳米纤维的粉末。将粉末再分散在叔丁醇中，加入抗炎症药物，超声并搅拌辅助至药物完全溶解，冷冻干燥后得到丝素蛋白纳米纤维-药物复合物的干粉制剂。将此干粉制剂再分散溶解于无菌缓冲液中，控制抗炎药物的最终质量百分浓度为0.1-1.0％，并加入防腐剂、pH调节剂、等渗调节剂之后无菌过滤分装，即为丝素蛋白纳米纤维增溶的滴眼药物。
2.按权利要求1方法得到的滴眼药物，包括抗炎症药物为主药，以及防腐剂、pH调节剂、等渗调节剂，其特征在于还包括丝素蛋白纳米纤维为药物增溶辅料。
3.按权利要求1和2所述的基于丝素蛋白纳米纤维的滴眼药物增溶辅料及含该辅料药物的制备方法，其特征在于：所述丝素蛋白纳米纤维通过已有技术获得，其在水中分散的质量分数为0.01-2.0％，主药和丝素蛋白纳米纤维的质量比在1：5-1：30之间。
4.按权利要求1和2所述的基于丝素蛋白纳米纤维的滴眼药物增溶辅料及含该辅料药物的制备方法，其特征在于：所述抗炎症药物一般为疏水性药物，包括但不限于姜黄素、杨梅素、氧氟沙星等眼科抗炎药物中的一种或几种。
5.按权利要求1和2所述的基于丝素蛋白纳米纤维的滴眼药物增溶辅料及含该辅料药物的制备方法，其特征在于：所述无菌缓冲液为常用磷酸盐缓冲液或硼酸盐缓冲液，pH值为7.4，丝素蛋白纳米纤维-药物复合物在无菌缓冲液中的分散性好、分散稳定性高。
6.按权利要求1和2所述的基于丝素蛋白纳米纤维的滴眼药物增溶辅料及含该辅料药物的制备方法，其特征在于：防腐剂、pH调节剂、等渗调节剂按照已有技术添加。
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Citations (6)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| KR20160036523A (ko) * | 2014-09-25 | 2016-04-04 | 서울대학교산학협력단 | 피브로인 미립구를 포함하는 약물 전달체 및 그 제조방법 |
| CN105862144A (zh) * | 2016-04-05 | 2016-08-17 | 西南大学 | 一种丝素纳米纤维高效制备方法及其应用 |
| CN106474482A (zh) * | 2016-09-28 | 2017-03-08 | 武汉纺织大学 | 一种丝素蛋白纳米颗粒及其制备方法和应用 |
| US20170107264A1 (en) * | 2014-03-27 | 2017-04-20 | Simatech Incorporation | Freeze-dried powder of high molecular weight silk fibroin, preparation method therefor and use thereof |
| CN107157952A (zh) * | 2017-06-30 | 2017-09-15 | 广东工业大学 | 一种丝素蛋白纳米粒和载药丝素蛋白纳米粒 |
| CN114712311A (zh) * | 2022-04-15 | 2022-07-08 | 青岛科技大学 | 一种丝素蛋白肽自组装载药纳米粒的制备及其肾保护作用 |
-
2022
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Patent Citations (6)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US20170107264A1 (en) * | 2014-03-27 | 2017-04-20 | Simatech Incorporation | Freeze-dried powder of high molecular weight silk fibroin, preparation method therefor and use thereof |
| KR20160036523A (ko) * | 2014-09-25 | 2016-04-04 | 서울대학교산학협력단 | 피브로인 미립구를 포함하는 약물 전달체 및 그 제조방법 |
| CN105862144A (zh) * | 2016-04-05 | 2016-08-17 | 西南大学 | 一种丝素纳米纤维高效制备方法及其应用 |
| CN106474482A (zh) * | 2016-09-28 | 2017-03-08 | 武汉纺织大学 | 一种丝素蛋白纳米颗粒及其制备方法和应用 |
| CN107157952A (zh) * | 2017-06-30 | 2017-09-15 | 广东工业大学 | 一种丝素蛋白纳米粒和载药丝素蛋白纳米粒 |
| CN114712311A (zh) * | 2022-04-15 | 2022-07-08 | 青岛科技大学 | 一种丝素蛋白肽自组装载药纳米粒的制备及其肾保护作用 |
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