复方中药透皮软膏剂的药理与毒理作用研究

目的：研究复方中药透皮软膏剂的药理学与毒理学作用.方法：将蒲公英、金银花、连翘、赤芍、黄芩等9味中药组成复方,以水提醇沉法制得干浸膏,再与油相、水相与促渗剂制成O/W型透皮软膏剂,采用局部全封闭斑贴法进行皮肤刺激试验与皮肤致敏试验.将干浸膏加纯水稀释含生药量分别为5g/ml和1g/ml两种浓度的提取液,前者供急性毒性试验用,选用昆明系小白鼠,经口染毒后,观察7 d,用K（a）rber法计算LD50;后者用G3垂熔玻璃漏斗过滤,流通蒸气灭菌20 min,供抗菌试验用,采用试管二倍稀释法,测定提取液体外对6种病原菌的抗菌活性.结果：皮肤刺激平均分值小于0.5,为无刺激物;致敏率为0,属于弱致敏物;对金黄色葡萄球菌、大肠杆菌、无乳链球菌、停乳链球菌、牛棒状杆菌、革兰氏阴性小杆菌的MIC分别为31.3、62.5、62.5、62.5、125、125 g/l,MBC分别为62.5、125、62.5、62.5、125、125g/l;小鼠口服LD50为l0 140 g/kg,LD50 95%可信限为8 610～11 940 g/kg,属于实际无毒物质.结论：该方剂提取液具有较强的体外抗菌活性,可作为替代抗生素防治奶牛乳房炎的主药,研制开发的透皮软膏剂用于乳房炎局部治疗安全无毒.

Study on Pharmacological and toxicological action of the compound TCM percutaneous ointment

Objective:To study the pharmacodynamics and toxicology of the compound traditional Chinese medicine percutaneous ointment. Methods:The desiccant extracts were made by ethanol precipitation from nine kinds of Chinese herb medicine, flos lonicerae, herba taraxaci, fructus forsythiae, radix paeoniae rubra, radix scutellariae and so on. Then they were made into O/W percutaneous ointment to carry out skin stimulation test and skin sensitization test by adding oil, water and osmosis-active substance. The desiccant extract was diluted to 5 g/ml and 1 g/ml to perform acute toxicity test by LD_ 50 method and antibacterial test by tube dilution method respectively. Results: The extract belongs to nonstimulating substance and faint sensitizer because its mean value of skin stimulation was lower than 0.5 and sensitization rate was 0 . Its minimal inhibitory concentration (MIC) to Staphylococcus aureus, E.coli, Streptococcus agalactiae, Streptococcus dysgalactiae, Corynebacterium bovis and G~- little bacillary was 31.3 g/l, 62.5 g/l, 62.5 g/l, 62.5 g/l, 125 g/l and 125 g/l, respectively, and minimal bactericidal concentration (MBC) was 62.5 g/l, 125 g/l, 62.5 g/l, 62.5 g/l, 125 g/l and 125 g/l, respectively. LD_ 50 in mice was 10 140 g/kg by oral. 95 percent confidence limit was from 8 610 g/kg to 11 940 g/kg. Conclusion:The extraction fluid had strong extracorporeal antimicrobial competence. It can be used as the chief substitute for antibiotics in preventing and treating for cow mastitis. The compound TCM percutaneous ointment made from the extraction is nontoxic and safe in treating for cow mastitis.