载三联抗结核药物硫酸钙/聚氨基酸人工材料体外缓释性能的观察

The experimental study of sustained drug release of calcium sulfate/amino acid polymer artificial bone carrying 3 anti-TB drugs: an in vitro study

中文关键词:  抗结核药  硫酸钙/聚氨基酸  缓释  体外

英文关键词:Anti-TB drugs  Calcium sulfate/amino acid polymer artificial  Sustained-release  In vitro

中文摘要:

  【摘要】 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。

英文摘要:

  【Abstract】 Objectives: To explore the properties of sustained drug release of the calcium sulfate/amino acid polymer artificial bone carrying 3 anti-TB in vitro. Methods: The calcium sulfate/amino acid polymer artificial bone carrying 3 anti-TB drugs was produced in dark environment[proportion: 100∶3∶3∶12 calcium sulfate/amino acid composite 500mg, isoniazid(INH) 15mg, rifampicin(RFP) 15mg, pyrazinamide(PZA) 60mg)]. The concentration of each drug(INH, RFP, PZA) was detected by high performance liquid chromatography(HPLC) and the unit period of drug release quality at 3h, 12h, 24h, 36h, 48h, 60h, 72h, 1-14w was measured, respectively in simulated body fluid in vitro. Results: The concentration of INH, RFP and PZA release in simulated body fluid of triple anti-tuberculosis drugs calcium sulfate/poly(amino acids) bone at 3h reached 152.96±1.32μg/ml，92.90±2.17μg/ml and 334.90±12.3μg/ml, respectively, and the three kinds of drug concentrations were higher at each time point before eight weeks. The concentration of PZA at the eighth week, the concentration of RFP at the 10th week and INH at the 11th week were still 10 times higher than the minimum inhibitory concentration(MIC), then decreased gradually. There was no contamination peak in drug release of effective measurement time in control group. Conclusions: Triple anti-tuberculosis drugs calcium sulfate/poly(amino acids) bone can reach reliable and longer duration of effective drug release. Concentrations of three drugs are high enough to kill mycobacterium tuberculosis otheoretically.