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

English Keywords:Anti-tuberculosis drugs  Calcium sulfate/amino acid polymer  Artificial bone  Vivo sustained release  Rat

English Abstract:

  【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.