载三联抗结核药硫酸钙/氨基酸聚合物人工骨体内缓释实验研究

Triple anti-tuberculosis drugs calcium sulfate/amino acid polymer artificial bone complex in vivo sustained release, an experimental study

中文关键词:  抗结核药  硫酸钙/氨基酸聚合物  人工骨  体内缓释  大鼠

英文关键词:Anti-tuberculosis drugs  Calcium sulfate/amino acid polymer  Artificial bone  Vivo sustained release  Rat

中文摘要:

  【摘要】 目的：观察载异烟肼、利福平、吡嗪酰胺三联抗结核药硫酸钙/氨基酸聚合物人工骨在大鼠体内的缓释效果。方法：取6～7周龄SD大鼠80只，随机分为实验组与对照组，实验组载三联抗结核药人工骨植入大鼠骶脊肌内，40只；对照组植入空白未载药人工骨于大鼠骶脊肌内，40只；术后1d、3d、1周、2周、4周、6周、8周、12周处死大鼠，每次处死实验组、对照组大鼠各5只，应用高效液相色谱法检测大鼠植入人工骨局部周边组织及血液中三种药物浓度，2周及6周时HE染色观察大鼠肝、肾病理组织学变化。结果：植入载三联抗痨药人工骨局部周边1cm肌肉组织中，术后1d、3d、1周、2周、4周、6周、8周、12周时，高效液相色谱法检测异烟肼为4.09±0.56μg/ml、2.45±1.33μg/ml、2.12±1.56μg/ml、1.58±4.12μg/ml、2.09±2.35μg/ml、2.31±1.44μg/ml、4.26±2.17μg/ml、3.79±0.49μg/ml；利福平为4.02±1.14μg/ml、1.90±0.11μg/ml、1.88±0.90μg/ml、0.79±1.08μg/ml、0.86±0.44μg/ml、0.89±0.98μg/ml、3.92±1.09μg/ml、3.57±0.22μg/ml；吡嗪酰胺为460.87±1.41μg/ml、440.91±1.69μg/ml、430.21±0.86μg/ml、340.73±1.45μg/ml、320.85±2.0μg/ml、270.61±1.0μg/ml、230.38±0.48μg/ml；12周时植骨块局部组织，周边1cm肌肉组织异烟肼、利福平、吡嗪酰胺能达到10倍最低抑菌浓度，静脉血三种药物平均浓度为2.79μg/ml、2.02μg/ml、4.38μg/ml低于植骨块局部周边浓度；肝、肾组织组织病理学检查未见损伤。结论：载三联抗结核药硫酸钙/氨基酸聚合物人工骨体内释放平稳，可实现体内局部用药缓释；其可直接植入体内，对肝、肾组织无明显药物损伤。

英文摘要:

  【Abstract】 Objectives: To observe the control release of complex of isoniazid, rifampicin, pyrazinamide triple anti-tuberculosis drugs calcium sulfate/amino acid polymer artificial bone in rats. Methods: 80 SD rats with the age of 6-7 weeks, were randomly divided into the experimental group and the control group, the experimental group(n=40) was implanted with triple anti-tuberculosis drugs bone in sacral spinal muscular; while the control group(n=40) was implanted with blank boneonly. 1 day, 3 days, 1 week, 2 weeks, 4 weeks, 6 weeks, 8 weeks, 12 weeks after transplantation, 5 rats in each group were killed, high performance liquid chromatography assay rats were used to test the drug concentration in sample tissue and blood, HE stainings of rat liver and kidney were used for histological tests. Results: The triple anti-tuberculosis drugs bone in soft tissue of 1cm surrounding tissue after 1 day, 3 days, 1 week, 2 weeks, 4 weeks, 6 weeks, 8 weeks, 12 weeks days meassured by High Performance Liquid Chromatography isoniazid was 4.09±0.56μg/ml, 2.45±1.33μg/ml, 2.12±1.56μg/ml, 1.58±4.12μg/ml, 2.09±2.35μg/ml, 2.31±1.44μg/ml, 4.26±2.17μg/ml, 3.79±0.49μg/ml respectively; the rifampin was 4.02±1.14μg/ml, 1.90±0.11μg/ml, 1.88±0.90μg/ml, 0.79±1.08μg/ml, 0.86±0.44μg/ml, 0.89±0.98μg/ml, 3.92±1.09μg/ml, 3.57±0.22μg/ml; the pyrazinamide was 460.87±1.41μg/ml, 440.91±1.69μg/ml, 430.21±0.86μg/ml, 340.73±1.45μg/ml, 320.85±2.0μg/ml 270.61±1.0μg/ml, 230.38±0.48μg/ml; the concentration in tissue 12 weeks later, reached 10 times the minimum inhibitory concentration. The average concentration of three drugs in venous blood were 2.79μg/ml, 2.02μg/ml, 4.38μg/ml respectively; histopathology showed no liver and kidney damage. Conclusions: The complex of triple anti-tuberculosis drugs calcium sulfate/amino acid polymer artificial bone can reach control release in vivo, meanwhile it is of no adverse reaction to liver and kidney tissue.