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目的考察低相对分子质量肝素凝胶经皮给药后大鼠皮肤和血液中低分子量肝素含量,评价其透皮药动学特征。方法SD大鼠腹部脱毛后经皮给予低分子量肝素凝胶,应用微透析采样技术结合比色法测定大鼠皮肤中低分子量肝素浓度随时间变化的影响,通过剪尾取血和Coatest Heparin试剂盒测定大鼠血液中低分子量肝素浓度随时间变化的影响。结果低分子量肝素凝胶经皮给药后,大鼠皮肤药物浓度达峰时间(tmax)为270 min、皮下最大药物浓度(cmax)是(4.40±0.54)IU·m L-1、t1/2为(137.04±87.98)min、AUC0-t为(911.76±330.69)IU·m L-1·min-1、MRT0-t为(322.67±40.94)min;大鼠血液内药物浓度达峰时间(tmax)为540 min、血液内最大药物浓度(cmax)是(2.23±0.40)IU·m L-1、t1/2为(294.99±183.74)min、AUC0-t为(110.59±212.41)IU·m L-1·min、MRT0-t为(422.48±52.96)min。结论在体微透析技术结合比色法可用于低分子量肝素凝胶透皮吸收药动学特征,方法操作简便、灵敏度高、专属性强。低分子量肝素凝胶经皮给药后具有缓慢透皮、浓度稳定的特点。
Objective To investigate the low molecular weight heparin content of rat skin and blood after transdermal administration of low molecular weight heparin gel to evaluate its transdermal pharmacokinetic characteristics. Methods Low-molecular-weight heparin gel was administered transdermally in the abdomen of SD rats. The effect of low molecular weight heparin concentration on the skin of rats was observed by microdialysis sampling combined with colorimetric method. The tail bleeding and Coatest Heparin kit The effect of low molecular weight heparin concentration in blood on the change of time was determined. Results After transdermal administration of low molecular weight heparin gel, the peak skin time (tmax) of rat skin was 270 min and the maximum subcutaneous cmax was (4.40 ± 0.54) IU · m L-1, t1 / 2 Was (137.04 ± 87.98) min, the AUC0-t was (911.76 ± 330.69) IU · m L-1 · min-1, and the MRT0-t was (322.67 ± 40.94) min. ) Was 540 min, the maximum blood concentration (cmax) was (2.23 ± 0.40) IU · m L-1, t1 / 2 was (294.99 ± 183.74) min and AUC0-t was (110.59 ± 212.41) IU · m L -1 · min, MRT0-t was (422.48 ± 52.96) min. Conclusion Body microdialysis combined with colorimetric method can be used for low molecular weight heparin gel transdermal absorption pharmacokinetic characteristics, the method is simple, high sensitivity and specificity. Low molecular weight heparin gel after transdermal delivery with slow transdermal, stable concentration characteristics.