盐酸四环素胃内漂浮微球的研制

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摘要目的采用离子胶凝法制备盐酸四环素胃内漂浮微球，改善其胃内释药及抗幽门螺旋杆菌治疗时的疗效。方法选用壳聚糖及海藻酸钠为载体，以NaHCO3为起泡剂；通过正交试验考察海藻酸钠与药物用量比、壳聚糖浓度、CaCl2浓度、海藻酸钠与NaHCO3用量比等对其体外漂浮性能、体外释放、包封率、成球性的影响，筛选出最佳工艺。结果最优工艺条件：壳聚糖浓度为8 mg/mL，海藻酸钠与药物比例为4∶1，CaCl2浓度为20 mg/mL，海藻酸钠与NaHCO3比例为2∶1，所制备的盐酸四环素胃内漂浮12 h微球漂浮率为95%，包封率为79.90%，形态良好，体外试验具备缓释性。结论该盐酸四环素胃内漂浮微球达到了胃内滞留要求，可提高吸收及抗幽门螺旋杆菌疗效，减少口服给药次数，可解决现有上市剂型的不足。

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	钟磊1 卞芳1 赵朝阳2 张洪1

关键词 ：盐酸四环素, 胃内漂浮微球, 壳聚糖, 海藻酸钠, 正交试验

Abstract：Objective To prepare Tetracycline Hydrochloride gastric floating microspheres using ionic gelation method, and to improve drug release percentage and therapeutic effect of anti-Helicobacter pylori. Methods Chitosan and alginate were chosen as the carriers, and NaHCO3 was utilized as the foaming agent. The orthogonal experiment was adopted to investigate the weight ration of tetracycline/alginate and alginate/NaHCO3, as well as the concentration of CaCl2 and chitosan. Therefore, the optimum preparation was determined by evaluating floating performances, drug release, encapsulation efficiency and balling index. Results The optimal conditions were as followed: the concentration of chitosan was 8 mg/mL, the weight ration of alginate/tetracycline was 4∶1, the concentration of CaCl2 was 20 mg/mL, and the weight ration of alginate/NaHCO3 was 2∶1. The microcapsules could float in stomach for 24 h with a floating rate of 95%, and the encapsulation efficiency was 79.90%. The in vitro experiments suggested that these floating microspheres had good sustain-release properties. Conclusion According to the results above, tetracycline gastric floating microspheres meet the requirements of gastric retention, which can increase drug absorption and therapeutic effect of anti-Helicobacter pylori, reduce dosing frequency, and have more selection of dosage forms.

Key words： Tetracycline Hydrochloride Gastric floating microspheres Chitosan Alginate Orthogonal experiment

基金资助:国家自然科学基金青年项目（81503072）。

通讯作者: 张洪（1962-），男，药理学硕士，硕士生导师，主要从事消化系统疾病治疗药物的药剂学与药理学研究。

作者简介: 钟磊（1984-），男，武汉大学第一临床学院2012级生物工程专业在读硕士研究生，主要从事消化系统疾病治疗药物的药剂学研究。

引用本文:

钟磊1 卞芳1 赵朝阳2 张洪1. 盐酸四环素胃内漂浮微球的研制[J]. 中国医药导报, 2018, 15(7): 23-26.
ZHONG Lei1 BIAN Fang1 ZHAO Chaoyang2 ZHANG Hong1. Study on Tetracycline Hydrochloride gastric floating microspheres. 中国医药导报, 2018, 15(7): 23-26.

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http://www.yiyaodaobao.com.cn/CN/ 或 http://www.yiyaodaobao.com.cn/CN/Y2018/V15/I7/23

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