肺靶向制剂——硫酸链霉素明胶微球的药理学研究

Pharmacological study on the streptomycin sulfate gelatin microsphere lung targeting delivery system

以１２５Ｉ标记硫酸链霉素明胶微球，小鼠静脉注射后测定其体内分布，结果表明硫酸链霉素明胶微球在小鼠肺部浓度最高，由靶向性参数判定硫酸链霉素明胶微球靶向作用明显，靶向效率较高。用微生物分析法测定并比较了肺组织中硫酸链霉素及其明胶微球的浓度，结果显示，在硫酸链霉素明胶微球给药量约为硫酸链霉素一半的情况下，肺部的药物浓度仍可达到或超过非微球剂。用苏通氏培养基二倍稀释法测得硫酸链霉素及其明胶微球ＭＩＣ值均为０．２ｍｇ／Ｌ。小鼠实验性肺结核治疗结果表明，以实际硫酸链霉素量计，微球剂约为非微球剂的１／３时，即可达到相同的治疗作用，当用药量约为非微球剂的２／３时。

A pharmacological study had been conducted on streptomycin sulfate gelatin microsphere (SM GMS). The difference were compared and analyzed between SM GMS and streptomycin sulfate (SM) in distribution, pharmacokinetics and antituberculosis activity. Following the iv 125 I SM GMS to mice, the result showed that lung exhibited the highest SM GMS concentration. According to the targeting parameters, the SM GMS was regarded as notable targeting efficiency. The pharmacokinetics in lung for SM GMS could be described as two compartment model. The cup plate assay was also employed to determine the SM concentration in lung and serum. The result showed that concentration of SM GMS in lung reached or exceded that of SM even the dose of SM GMS was as about half as that of SM. The pharmacokinetics in serum for SM GMS could be described as two compartment model. MICs of SM and SM GMS for Mycobacterium tuberculosis H 37 RV on Sauton′s medium were both 0.2 mg/L, showing SM GMS exhibited a slower release of drug in vitro. SM GMS was also found to be more effective in the treatment of experimental tuberculosis of the lung in mice. When SM GMS was administrated at about a third dose of SM, it showed the same activity as that of SM. At two thirds dose of SM, SM GMS demonstrated markedly higher antituberculosis activity.