蛋白类药物口服药剂的设计与稳定性研究  

Design and Stability of Oral Protein Drugs

作　　者：张涵 原续波[1] ZHANG Han;YUAN Xu-bo(School of Materials Science and Engineering,Tianjin University,Tianjin 300350,China)

机构地区：[1]天津大学材料科学与工程学院,天津300350

出　　处：《高分子通报》2022年第5期67-76,共10页Polymer Bulletin

摘　　要：口服给药具有方便、安全、患者依存性强等优势,是理想的给药途径,但蛋白类药物在口服过程中易被胃酸及蛋白酶分解而失活,导致生物利用度较低。本实验设计了一种药物载体,用于蛋白类药物口服给药,解决了蛋白类药物在胃肠道中易失活的问题。以葡萄糖氧化酶为蛋白药物模型,通过在蛋白质表面原位自由基聚合反应制备葡萄糖氧化酶纳米微囊,低温干燥后研磨成粉末封装在胶囊中。以羟丙甲纤维素为原料,通过酯化反应制备醋酸羟丙甲纤维素琥珀酸酯,将其作为肠溶包衣材料对以上胶囊进行包衣,得到肠溶胶囊。通过模拟胃肠道内的环境,对肠溶胶囊进行体外释放实验及蛋白活性测试。结果显示,在胃液环境下,该肠溶胶囊2h内不溶解,且胶囊内的葡萄糖氧化酶保持较高活性;在肠液环境下,肠溶胶囊溶解,被纳米微囊包载的葡萄糖氧化酶活性明显高于游离态葡萄糖氧化酶。以上实验结果证明了该载药体系可以解决口服蛋白类药物在胃肠道中易被胃酸及蛋白酶分解而失活的问题。Oral administration has the advantages of convenience,safety,and strong patient dependence which is an ideal route of administration.However,protein drugs are easily degraded by gastric acid and protease during oral administration resulting in low bioavailability.In this paper,a drug carrier was designed for oral administration of protein drugs,which solved the problem that protein drugs were easily inactivated in the gastrointestinal tract.Glucose oxidase nanocapsules were prepared by in-situ free radical polymerization on the surface of the protein using glucose oxidase as a protein drug model,and the nanocapsules were grounded into powder and encapsulated in the capsul after dried at low temperature.Hypromellose was used as a raw material to prepare hypromellose acetate succinate,which was used as an enteric coating material to coat the above-mentioned capsules to obtain enteric capsules.By simulating the environment in the gastrointestinal tract,in vitro release experiments and activity tests were performed.The results showed that the enteric-coated capsule did not dissolve within 2h under the environment of gastric juice,and the glucose oxidase in the capsule maintained high activity.Under the environment of intestinal juice,the enteric-coated capsule was dissolved and the activity of the glucose oxidase encapsulated by the nanocapsules was significantly higher than that of free glucose oxidase.The above experimental results proved that the drug-carrying system could solve the problem that oral protein drugs were easily decomposed by gastric acid and protease in the gastrointestinal tract and became inactivated.

关 键 词：蛋白类药物 口服给药 纳米微囊 醋酸羟丙甲纤维素琥珀酸酯 蛋白活性 

分 类 号：TQ460.1[化学工程—制药化工]