苦参碱类生物碱传递体凝胶剂对奶牛乳房炎主要病原菌的药效学研究

Pharmacodynamics of the transfersome gel of Sophora flavescens Ait.Alkaloids on the main bacterial pathogens of cow mastitis

苦参碱类生物碱(SFAA)传递体凝胶剂是以逆相蒸发法将SFAA按比例混合制成传递体,并以卡波姆为凝胶基质制备成SFAA传递体凝胶剂。为评价SFAA传递体凝胶剂的药效,本研究通过体外药物累积释放度、累积透过量、皮肤内残留量以及稳态渗透速率检测,评价其释放性质和透皮吸收效果;通过最低抑菌/杀菌浓度试验,评价其对引起奶牛乳房炎常见病原菌的抑杀效果。结果显示,传递体凝胶剂组在24 h累积透过量是普通凝胶剂组的2.22倍(p<0.05),传递体凝胶剂组在皮肤层中的滞留量是普通凝胶剂组的5.27倍(p<0.05),而传递体凝胶剂组稳态渗透速率也明显高于普通凝胶剂组(p<0.05)。该制剂对大肠杆菌、金黄色葡萄球菌、无乳链球菌和停乳链球菌的最低抑菌剂量(MIC)分别为3.13 mg/mL、6.25 mg/mL、0.78 mg/mL和0.78 mg/mL,其最低杀菌剂量(MBC)分别为6.25 mg/mL、6.25 mg/mL、1.56 mg/mL和0.78 mg/mL。上述结果表明,SFAA传递体凝胶剂具有良好的透皮吸收效果,对上述4种病原菌均有较强的抑菌/杀菌作用。本研究为奶牛乳房炎防治新药研制提供了借鉴,也为临床用药提供了数据支持。

The pharmacodynamics of the transfersome gel of Sophora flavescens Ait. Alkaloids （SFAA） were evaluated through the release of nature, absorption effect and antibacterial/bactericidal effect test. By measuring the cumulative release of SFAA in vitro, the cumulative penetration, the residual amount in the skin and the steady state permeation rate, release properties and transdermal absorption effect on the gel of SFAA were evaluated. The killing effects on common pathogenic bacteria inducing cow mastitis were also evaluated by the minimum inhibitory concentration （MIC） and minimum bactericidal concentration （MBC） tests. Compared with the common gel group, the transfersome gel group was 2.22 times in cumulative transmission at 24 hrs （p〈0.05）, it was 5.27 times for retention in the skin layer （p〈0.05）, and it was higher in the steady state permeation rate （p〈0.05）. The MICs of SFAA to Escherichia coli, Staphylococcus aureus, S.agalactiae and S.dysgalactiae, were 3.13 mg/mL, 6.25 mg/mL, 0.78 mg/mL, 0.78 mg/mL respectively, and the MBCs were 6.25 mg/mL, 6.25 mg/mL, 1.56 mg/mL, 0.78 mg/mL, respectively.The transfersome gel of SFAA had effective transdermal absorption and antibacterial effects on the 4 kinds of bacterial pathogens of cow mastitis. This study provides a reference for the development of new drugs in prevention and treatment of cow mastitis, also provides data support for clinical medication of it.