比较环糊精包合滴眼液与典必殊~?兔离体角膜和巩膜的透过性研究  

Comparison of the Corneal and Scleral Penetration Between Cyclodextrin-containing Eye Drops and TobraDex~? in Rabbits Ex Vivo

作　　者：赵欣 卢红 王小桐 王旭玲 杨强[1] ZHAO Xin;LU Hong;WANG Xiao-tong;WANG Xv-ling;YANG Qiang(Shenyang Xingqi Pharmaceutical Co.,Ltd.,Liaoning Shenyang 110164,China)

机构地区：[1]沈阳兴齐眼药股份有限公司,辽宁沈阳110164

出　　处：《辽宁化工》2018年第7期636-638,共3页Liaoning Chemical Industry

摘　　要：目的为了提高水不溶性地塞米松点眼的生物利用度,配置了水溶性的环糊精包合滴眼液。本文比较环糊精包合滴眼液与普通混悬剂典必殊兔离体角膜和巩膜的透过性,为开发新型的眼用制剂提供依据。方法采用Franz扩散池和健康成年新西兰雄性兔的角膜、巩膜进行渗透实验,用已验证的LC-MS/MS法测定渗透液中地塞米松和妥布霉素的浓度,考察累积渗透量(Qn)。结果环糊精包合滴眼液和典必殊中地塞米松在兔离体角膜的Qn分别为7.63,19.15μg/cm^2(p<0.05),妥布霉素在兔离体角膜的Qn分别为45.27,322.28μg/cm^2(p<0.05)。而两制剂地塞米松在兔离体巩膜的Qn分别为132.44,30.45μg/cm^2(p<0.05),妥布霉素在兔离体巩膜的Qn分别为964.38,1 107.07μg/cm^2(p>0.05)。对于环糊精包合滴眼液无论是地塞米松还是妥布霉素体外角膜的Qn都显著低于典必殊;环糊精包合滴眼液中妥布霉素体外巩膜的Qn与典必殊相比没有显著水平差异,而地塞米松Qn显著增高。结论开发含环糊精包合滴眼液可能具有透巩膜给药的潜在优势,如结膜下注射,Tenon囊下注射和球后注射等。Due to limited aqueous solubility of dexamethasone,a water-soluble cyclodextrin-containing dexamethasone complex was prepared to increase the topical bioavailability. In this paper, the difference in corneal and scleral penetration between cyclodextrin-containing eye drop and TobraDex ex vivo in NZ white rabbit was compared. At first,6 healthy rabbits were sacrificed by overdosing with anesthetics to collect their corneas and scleras. And then, Franz diffusion pool was used to evaluate the permeability of the two formulations by calculating the cumulative permeation amounts（Qn）. At last, concentrations of dexamethasone and tobramycin were determined using a validated LC-MS/MS method. The results showed that： for cornea, Qn of dexamethasone in cyclodextrin-containing eye drops and TobraDex were 7.63, 19.15 μg/cm2（p〈0.05）, and Qn of tobramycin were 45.27, 322.28 μg/cm2（p〈0.05）, respectively. For sclera, Qn of dexamethasone of these two formulations were 132.44, 30.45μg/cm2（p〈0.05） and Qn of tobramycin were 964.38, 1107.07μg/cm2（p〉0.05）, respectively. Qn of both dexamethasone and tobramycin in cyclodextrin-containing eye drop were significantly lower than those in TobraDex. However, Qn of dexamethasone in cyclodextrin-containing eye drop was significantly higher in sclera, while tobramycin level was the same. So it＇s suggested that development of the cyclodextrin-containing eye drop should have a potential advantage via trans-scleral administration such as sub-conjunctiva, sub-tenon and retrobulbar injection.

关 键 词：环糊精包合滴眼液 典必殊 累积渗透量 离体 

分 类 号：R969.1[医药卫生—药理学]