复方积雪草凝胶贴剂体外透皮及在体瘢痕实验

Studies on Percutaneous Absorption in vitro and Hypertrophic Scare Healing Enhancement of Compound Centella Asiatica Gel Patches

目的:研究复方积雪草凝胶贴剂的透皮特性及其对增生性瘢痕的治疗效果。方法:以12 h内累积透过量(Q12 h)为指标,比较复方积雪草凝胶贴剂与市售积雪苷霜软膏以及市售芦荟胶的透皮性。建立增生性瘢痕模型,将36只SD大鼠按完全随机法随机分为6组:正常对照组、模型组、积雪苷霜软膏阳性对照组(以积雪草总苷计12.5 mg)、复方积雪草凝胶贴剂高(以积雪草总苷计15 mg)、中(以积雪草总苷计12.5 mg)、低(以积雪草总苷计10 mg)剂量组,每组6只。以瘢痕转归时间和瘢痕面积为指标,探索药物促瘢痕愈合的作用。结果:复方积雪草凝胶贴剂与积雪苷霜软膏中的积雪草总苷Q12h分别为260.43μg·cm^-2和198.87μg·cm^-2;复方积雪草凝胶贴剂与芦荟胶中的芦荟多糖Q12h分别为33.64μg·cm^-2和23.41μg·cm^-2,且主药体外透皮动力学均符合零级模型。各给药组大鼠的创面愈合时间和上皮化时间与模型组相比差异无统计学意义(P>0.05);阳性对照组及复方积雪草凝胶贴剂各剂量组大鼠的瘢痕愈合时间与模型组相比均显著缩短(P<0.05或P<0.01),且高、中剂量组与阳性对照组相比差异有统计学意义(P<0.05)。在伤口愈合后的第3天和第6天,各组大鼠的瘢痕面积差异均无统计学意义(P>0.05);伤口愈合后的第9天,阳性对照组及复方积雪草凝胶贴剂高、中剂量组与模型组相比瘢痕面积显著减小(P<0.05或P<0.01),复方积雪草凝胶贴剂各剂量组与阳性对照组相比差异均无统计学意义(P>0.05);伤口愈合的第12天,阳性对照组及复方积雪草凝胶贴剂各剂量组与模型组比较均显著减小(P<0.05或P<0.01),高、中剂量组与阳性对照组相比差异有统计学意义(P<0.05)。结论:制备的高、中剂量复方积雪草凝胶贴剂有较好的促瘢痕愈合的作用。芦荟凝胶的加入促进了瘢痕愈合。

Objective: To study the transdermal properties and hypertrophic scar healing enhancement of compound centella asiatica gel patches.Methods: The transdermal permeability of compound centella asiatica gel patches,the commercially available centella triterpenes cream and the commercially available aloe vera gel were compared by the cumulative permeation amount in 12 h (Q12h ).The hypertrophic scar model was established.Totally 36 rats were randomly divided into 6 groups with 6 rats in each group: the normal control group,the model group,centella triterpenes cream positive control group (be equal to 12.5 mg asiaticoside),compound centella asiatica gel patch high (be equal to 15 mg asiaticoside),medium (be equal to 12.5 mg asiaticoside) and low (be equal to 10 mg asiaticoside) dosage groups.The role of drugs in promoting scar healing was explored by using scar outcome time and scar area as the indicators.Results: The Q12h of centella asiatica total glycosides from centella asiatica gel patches and centella triterpenes cream was 260.43 μg·cm^-2 and 198.87 μg·cm^-2,respectively.The Q12h of aloe polysaccharide from compound centella asiatica gel patches and aloe vera gel was 33.64 μg·cm^-2 and 23.41 μg·cm^-2,respectively.The in vitro transdermal kinetics of the main drug was in line with the zero-order model.There was no significant difference in the wound healing time and epithelization time between the administration groups and the model group (P>0.05).Compared with that in the model group,the scar healing time in the positive control group and compound asiatica gel patch group was significantly shorter (P<0.05 or P<0.01).There was significant difference between the medium dose group and the positive control group (P<0.05).On the 3rd and 6th day after the wound healing,each group showed no significant difference in the scar area (P>0.05).On the 9th day after the wound healing,the scar area in the positive con-trol group and compound asiatica gel patch group was bigger,and that in the medium dose group was significantly smaller than that in the model group (P<0.05 or P<0.01).There was no significant difference between asiatica gel patch groups and the positive control group (P>0.05).On the 12th day of the wound healing,the scar area in the positive control group and compound asiatica gel patch groups decreased significantly when compared with that in the model group(P<0.05 or P<0.01).There was significant difference between high and medium dose groups and the positive control group (P<0.05).Conclusion: The prepared high and medium dose compound centella asiatica gel patches show good effect on scar healing.The addition of aloe vera gel can promote scar healing.