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目的:探讨载三联抗结核药物硫酸钙/聚氨基酸人工材料在模拟体液中的药物缓释性能。方法:避光环境下以100:3:3:12的比例称取硫酸钙/氨基酸复合材料500mg、异烟肼(isoniazid,INH)15mg、利福平(rifampicin,RFP)15mg、吡嗪酰胺(pyrazinamide,PZA)60mg制备载药人工缓释材料,将其置于模拟体液中,分别于浸泡3h、12h、24h、36h、48h、60h、72h、1~14周时取材料浸提液,应用高效液相色谱法(HPLC)检测其中INH、RFP、PZA三种药物的浓度,并据其计算单位时间段内药物释出质量。结果:载三联抗结核药的硫酸钙/聚氨基酸人工材料在模拟体液中浸泡3h时浸提液中释出INH、RFP、PZA的浓度分别达到152.96±1.32μg/ml、92.90±2.17μg/ml和334.90±12.3μg/ml,在8周前各时间点的浸提液中,3种药物浓度均较高;至8周时PZA的释出浓度、10周时RFP释出浓度、11周时INH的释出浓度仍高于其10倍的最小抑菌浓度,之后逐渐降低;未载药硫酸钙/聚氨基酸人工材料在有效检测时间内药物出峰时间处未见有意义杂质峰出现。结论:载三联抗结核药硫酸钙/聚氨基酸人工材料具有较为平稳、持续时间较长的有效缓释性能,三种药物在模拟体液中释出药物的浓度均可达到体内杀死结核分枝杆菌的浓度。
Objective: To investigate the sustained-release properties of drug-loaded three-drug-resistant calcium sulfate / polyamino acid artificial materials in simulated body fluids. Methods: 500 mg of calcium sulfate / amino acid composite, 15 mg of isoniazid (INH), 15 mg of rifampicin (RFP) and 15 mg of pyrazinamide pyrazinamide, PZA) 60mg were used to prepare the drug-loaded artificial sustained-release material and placed in simulated body fluid. The material extracts were taken at 3h, 12h, 24h, 36h, 48h, 60h, 72h and 1 ~ The concentrations of INH, RFP and PZA were measured by HPLC, and the drug release quality was calculated according to the concentration of INH, RFP and PZA. Results: The concentrations of INH, RFP and PZA released from the extracts of the calcium sulfate / polyamino acid artificial material containing triple anti-TB drugs in the simulated body fluid for 3h were 152.96 ± 1.32μg / ml and 92.90 ± 2.17μg / ml, respectively And 334.90 ± 12.3 μg / ml, respectively. The concentration of three drugs in the extracts at each time point 8 weeks before were higher; the release concentration of PZA at 8 weeks, the release concentration of RFP at 10 weeks, INH release concentration is still higher than its 10-fold minimum inhibitory concentration, and then gradually decreased; undeveloped calcium sulfate / polyamino acid artificial material in the effective detection time of drug peak time no significant impurity peaks appear. CONCLUSION: The calcium sulfate / polyamino acid artificial material with triple anti-TB drug has a relatively stable and sustained sustained release performance. The concentrations of the three drugs released in the simulated body fluid can reach the level of in vivo killing of Mycobacterium tuberculosis concentration.