格列美脲凝胶骨架控释贴剂的研制及大鼠体内药效学研究  

Studies on the preparation of glimepiride gel-matrix controlled-release patch and its pharmacodynamics in rats

作　　者：张援 [1] 许实波 [2] 朱良 [2] 陈颖  陈丽琼 [2] 马争 [4] 

机构地区：[1]中山大学药学院药物药理研究室,广东,广州,510275,广东省体育科学研究所省重点实验室,广东,广州,510663 [2]中山大学药学院药物药理研究室,广东,广州,510275 [3]广东省体育科学研究所省重点实验室,广东,广州,510663 [4]山西医科大学公共卫生学院,山西,太原,030001

出　　处：《中国药学杂志》2004年第10期772-775,共4页Chinese Pharmaceutical Journal

摘　　要：目的 研制格列美脲凝胶骨架控释贴剂,并评价其经皮吸收对正常大鼠的降血糖作用。方法 浇铸法制备格列美脲控释贴剂,以正交方法优化成膜骨架材料配比,设计最佳基质控释系统;首次建立格列美脲贴剂体外透皮速率常数的HPLC测定方法,考察不同基质组成及二元复合透皮吸收促进剂对药物透皮吸收的影响;按照胰岛素类及降血糖药的新药(西药)临床前研究指导原则进行降血糖试验和糖耐量试验,评价贴剂对正常大鼠经皮给药后的降血糖作用。结果　药剂学研究表明,当成膜骨架材料配比为改性PVA-PVP-乳糖=20:2:1,透皮促进剂氮酮和油酸以3％浓度按2:1比例合用时,贴剂的体外透皮速率常数最大;对正常大鼠的药效学研究显示,该贴剂能明显减少给药次数,显著降低正常大鼠空腹血糖(P<0.01),显著增加糖耐量(P<0.001),降糖作用明显。结论　格列美脲凝胶骨架控释贴剂可以经皮肤给药达到显著的降糖药效,血药浓度平稳,给药次数减少,患者依从性提高,因此具有良好的开发应用前景。OBJECTIVE: To prepare glimepiride gel-matrix controlled-release patch and to investigate its antihyperglycemic effects in normal rats after transdermal absorption. METHODS: The controlled-release patch was prepared through cast moulding and its film-matrix formula was optimized with orthogonal experimental design. A HPLC method was developed to determine the permeation rate of glimepiride-TDDS through rabbit skin in vitro for the first time. Then the effects of different matrix composition and various combined penetration enhancer ratios on the transcutaneous permeability of glimepiride-TDDS were observed. The antihyperglycemic test and the oral glucose tolerance test (OGTT) were carried out to evaluate the antidiabetic effects according to the New Drug (Western Medicine) Preclinical Study Guide Principle. RESULTS: The pharmaceutic study showed that the transdermal system had the largest permeation rate when the film-matrix was composed of improved-PVA, PVP and lactose in the proportion of 20:2:1 and when Azone was mixed with oil acid by the ratio of 2:1 at the concentration of 3%. The in vivo pharmacodynamic study of glimepiride patch in normal rats demonstrated that the patch evidently minimized administration frequency, markedly reduced fasting serum glucose (FSG) and significantly increased the oral glucose tolerance. CONCLUSION: The glimepiride gel-matrix controlled-release patch possessed evident antidiabetic effects. It could steadily penetrate into body via skin, maintain effective serum concentration for quite a long time, minimize administration frequency and therefore improve patient compliance. Thus, the glimepiride-TDDS may have a prosperous future.

关 键 词：格列美脲 凝胶骨架控释贴剂 透皮吸收 透皮给药系统 糖耐量试验 降血糖作用 

分 类 号：R969[医药卫生—药理学]