硫酸钙链霉素的颗粒体外缓释性能的研究
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摘要
目的了解载结核药链霉素的硫酸钙缓释颗粒在体外的药物缓释性能。方法实验组,将链霉素与医用硫酸钙混合制备成载药颗粒,将其置于模拟体液中,取1 d、2 d、3 d、1周、2周、4周、6周、8周、10周时缓冲液为样本,高效液相色谱法(HPLC)检测其中链霉素药物的浓度,绘制药物缓释曲线。空白组,医用硫酸钙制备成未载药颗粒。结果医用硫酸钙5 cc与链霉素1 g为最佳配比。载链霉素硫酸钙颗粒在模拟体液中浸泡,缓释颗粒3 d时累计释放量15.33%。在8周前的样本液中,药物浓度均较高;至8周时链霉素的释出浓度、仍达到的最小抑菌浓度,之后逐渐降低。未载链霉素的硫酸钙颗粒在有效检测时间内药物出峰时间处未见波峰出现。结论硫酸钙链霉素颗粒具有效缓释性能。8周内模拟体液中释出药物的浓度均可达到抑制结核分枝杆菌的浓度。
Objective To understand the drug release properties of calcium sulfate sustained-release granules carrying the tuberculosis drug streptomycin in vitro. Methods In the experimental group, streptomycin was mixed with medical calcium sulfate to prepare drug-loaded granules, which were placed in simulated body fluids. The buffer at 1 day, 2 days, 3 days, 1 week, 2, 4, 6, 8 and 10 weeks was used as a sample. The concentration of streptomycin was detected by high performance liquid chromatography(HPLC), and the drug sustained-release curve was drawn. In the blank group, medical calcium sulfate was prepared as unloaded particles. Results The medical calcium sulfate 5 cc and streptomycin 1 g were the best ratio. The streptomycin calcium sulfate particles were soaked in the simulated body fluid,and the cumulative release of the sustained-release particles was 15.33%. In the sample solution before 8 weeks, the drug concentration was higher. Release concentration of streptomycin and still reached minimum inhibitory concentration at 8 weeks, and then gradually decreased. Calcium sulfate particles without streptomycin showed no peaks at the peak time of the drug during the effective detection time. Conclusion Calcium sulfate streptomycin granules have a slow release property. The concentration of the drug released in the simulated body fluid can reach the concentration of inhibiting tuberculosis within 8 weeks.
Objective To understand the drug release properties of calcium sulfate sustained-release granules carrying the tuberculosis drug streptomycin in vitro. Methods In the experimental group, streptomycin was mixed with medical calcium sulfate to prepare drug-loaded granules, which were placed in simulated body fluids. The buffer at 1 day, 2 days, 3 days, 1 week, 2, 4, 6, 8 and 10 weeks was used as a sample. The concentration of streptomycin was detected by high performance liquid chromatography(HPLC), and the drug sustained-release curve was drawn. In the blank group, medical calcium sulfate was prepared as unloaded particles. Results The medical calcium sulfate 5 cc and streptomycin 1 g were the best ratio. The streptomycin calcium sulfate particles were soaked in the simulated body fluid,and the cumulative release of the sustained-release particles was 15.33%. In the sample solution before 8 weeks, the drug concentration was higher. Release concentration of streptomycin and still reached minimum inhibitory concentration at 8 weeks, and then gradually decreased. Calcium sulfate particles without streptomycin showed no peaks at the peak time of the drug during the effective detection time. Conclusion Calcium sulfate streptomycin granules have a slow release property. The concentration of the drug released in the simulated body fluid can reach the concentration of inhibiting tuberculosis within 8 weeks.
引文
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[12]普有登,汤逊。硫酸钙骨移植替代材料的研究及应用进展[J].中国矫形外科杂志,2011,19(11):931-933.
[13]Yashavantha Kumar C,Nalini KB,Menon J,et al.Calcium sulfate as bone graft substitute in the treatment of osseous bone defects,a prospective study[J].Journal of Clinical&Diagnostic Research Jcdr,2013,7(12):2926-2928.
[14]张俊山,王自力,施建党,等.复合三联抗抗结核药人工缓释材料体外抗结核性能[J].脊柱外科杂志,2014,12(6):380-384.
[15]龙娜,吕竹芬.微球缓释系统的突释现象及其影响因素[J].中国药师,2010,13(3):421-423.
[16]周林.抗结核药物研究进展[J].中国临床医生,2013,41(3):14-17.
[17]刘海涛,施建党,王骞,等.载三联抗痨药硫酸钙/聚氨基酸缓释人工材料体外缓释性能的观察[J].中国脊柱脊髓杂志,2015,25(3):239-244.
[2]李大伟,马远征.骨关节结核局部药物缓释材料研究进展[J].中国防痨杂志,2013,35:(5):376-378.
[3]Diacon AH,Donald PR.The early bactericidal activity of antituberculosis drugs[J].Expert Rev Anti Infect Ther,2014,12(2):223-237.
[4]王骞,耿广起,丛晓明,等.载三联抗痨药硫酸钙/聚氨基酸缓释材料在兔脊柱结核模型体内的缓释性能[J].中国组织工程研究,2017,21(10):1520-1526.
[5]Mistry S,Roy S,Maitra NJ,et al.A novel,multi-barrier,drug eluting calcium sulfate/biphasic calcium phosphate biodegradable composite bone cement for treatment of experimental MRSA osteomyelitis in rabbit model[J].JControl Release,2016,239:169-181.
[6]Liu P,Jiang H,Li S,et al.Determination of anti-tuberculosis drug concentration and distribution from sustained release microspheres in the vertebrae of a spinal tuberculosis rabbit model[J].J Orthop Res,2017,35(1):200-208.
[7]德向研,施建党,王自立,等.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[J].中国脊柱脊髓杂志,2013,23(6):531-536.
[8]Wang P,Liu P,Peng H,et al.Biocompatibility evaluation of dicalcium phosphate/calcium sulfate/poly(amino acid)composite for orthopedic tissue engineering in vitro and in vivo[J].J Biomater Sci Polym Ed,2016,27(11):1170-1186.
[9]Wu CC,Hsu LH,Tsai YF,et al.Enhancement of biodegradation and osseointegration of poly(ε-caprolactone)/calcium phosphate ceramic composite screws for osteofixation using calcium sulfate[J].Biomed Mater,2016,11(2):125-132.
[10]陈勇忠,王剑火,张朋,等.含链霉素医用硫酸钙人工骨修复胸腰椎结核骨缺损[J].中国组织工程研究,2014,18(5):802-805.
[11]陈勇忠,王剑火,张朋,等.一期后路病灶清除混合植骨内固定术治疗胸腰椎结核[J].临床骨科杂志,2014,17(6):626-632.
[12]普有登,汤逊。硫酸钙骨移植替代材料的研究及应用进展[J].中国矫形外科杂志,2011,19(11):931-933.
[13]Yashavantha Kumar C,Nalini KB,Menon J,et al.Calcium sulfate as bone graft substitute in the treatment of osseous bone defects,a prospective study[J].Journal of Clinical&Diagnostic Research Jcdr,2013,7(12):2926-2928.
[14]张俊山,王自力,施建党,等.复合三联抗抗结核药人工缓释材料体外抗结核性能[J].脊柱外科杂志,2014,12(6):380-384.
[15]龙娜,吕竹芬.微球缓释系统的突释现象及其影响因素[J].中国药师,2010,13(3):421-423.
[16]周林.抗结核药物研究进展[J].中国临床医生,2013,41(3):14-17.
[17]刘海涛,施建党,王骞,等.载三联抗痨药硫酸钙/聚氨基酸缓释人工材料体外缓释性能的观察[J].中国脊柱脊髓杂志,2015,25(3):239-244.