三氯生水凝胶乳化抗菌剂在兔膝损伤关节腔内药代动力学的实验研究

Triclosan pharmacokinetic in the knee injecting antibacterial emulsions with triclosan and hydrogel in the injured knee of rabbits

目的:通过对4种三氯生水凝胶乳剂进行对比分析,比较不同乳剂给药后,兔关节腔的三氯生水平和作用时间。方法:实验分为三氯生乳剂组(对照组)、三氯生透明质酸乳剂组、三氯生几丁糖乳剂组、三氯生透明质酸几丁糖聚合水凝胶乳剂组,选取同窝雄兔32只(64膝)随机分为4组(A、B、C、D),每组8只(16膝),双膝手术,术后第7 d同时给药,分别于给药后6 h、12 h、24 h、48 h抽取关节液0.5 mL,采用高效液相色谱分析比较4种乳剂在兔损伤膝关节腔关节液内三氯生浓度及作用时间。结果:各组关节液三氯生维持时间无明显差异。各组关节液三氯生峰浓度比较:①对照组[三氯生乳剂组,(8.601±0.067)mg.mL-1]显著高于其他各组(P<0.05);②透明质酸组[(5.751±0.018)mg.mL-1]低于几丁糖组[(6.003±0.155)mg.mL-1]及聚合水凝胶组[(7.026±0.137)mg.mL-1],但仅对聚合水凝胶组有显著性意义(P<0.05)。各组关节液三氯生平均浓度比较:①对照组[(5.141±0.056)mg.mL-1]显著高于其他各组(P<0.05);②几丁糖组[(3.687±0.018)mg.mL-1]低于透明质酸组[(3.652±0.155)mg.mL-1]及聚合水凝胶组[(4.341±0.127)mg.mL-1],尤其对聚合水凝胶组有显著性意义(P<0.05)。结论:实验表明,与三氯生乳剂和三氯生聚合水凝胶乳剂相比,三氯生透明质酸乳剂和三氯生几丁糖乳剂可显著降低关节腔三氯生水平,进而增加膝关节腔药物维持时间。但维持时间较短,需不断重复给药。

Objective：Through Experimental analysis of Dispense four species of antibacterial emulsions,to compare the concentration and time course of triclosan joint cavity after the injection.Methods：The test were divided into four groups：triclosan group（control group）,triclosan-hydrogel acid,triclosan-chitosan and triclosan-hydrogel acid /chitosan,32（64 knees）rabbits of the same brood were divided into 4 groups（A、B、C、D） randomly,with 8（16 knees）rabbits in each group.6 days after both knees surgery injecting antibacterial emulsions at the same time.In each group choosing 4 knees each time at 6,12,24,48 hours after instillation,the 0.5 mL joint fluid was analyzed with HPLC,to compare the concentration and time course of triclosan in in joint cavity after the injection.Results：To compare the time course of triclosan in joint cavity,the time course resulted in a lower level in controlled group and combined hydrogel group compared to group Tri-HA and group Tri-CH（P0.05）;To compare the peak concentration of triclosan in joint cavity：①The peak concentration of controlled group [（8.601±0.067） mg·mL-1] resulted in a higher level than other groups（P0.05）.②The peak concentration of group Tri-HA [（0.751±0.018） mg·mL-1] resulted in a higher level than group Tri-CH [（6.003±0.155） mg·mL-1]and combined hydrogel group [（7.026±0.137） mg·mL-1],especially for controlled group（P0.05）.To compare the average concentration of triclosan in joint cavity：①The average concentration of controlled group [（5.141±0.056） mg·mL-1] resulted in a higher level than other groups（P0.05）.②The average concentration of group Tri-CH [（3.687±0.018） mg·mL-1] resulted in a higher level than group Tri-HA [（3.652±0.155） mg·mL-1] and combined hydrogel group [（4.341±0.127） mg·mL-1],especially for controlled group（P0.05）.Conclusion：Our experiment in joint cavity shows that triclosan-hydrogel acid and triclosan-chitosan emulsions achieve lower triclosan level in joint cavity and longer time course compared to triclosan emulsions as well as combined hydrogel emulsions.But just maintain short time,repeated injection was indispensable.