中国组织工程研究

中国组织工程研究 ›› 2018, Vol. 22 ›› Issue (14): 2133-2139.doi: 10.3969/j.issn.2095-4344.0843

• 组织工程骨及软骨材料 tissue-engineered bone and cartilage materials •    下一篇

载抗结核药物聚甲基丙烯酸甲酯骨水泥的体外缓释性能观察

袁虎成1，石仕元2，马文鑫3，杨小英4，王嘉铭5，王自立3   

  1. 1宁夏医科大学，宁夏回族自治区银川市 750004；2浙江中医药大学附属浙江省中西医结合医院骨伤科，浙江省杭州市 310003；宁夏医科大学总医院，3脊柱骨科，4药理研究室，宁夏回族自治区银川市 750004；5浙江农林大学中药学院，浙江省杭州市 311300
  • 收稿日期:2018-03-26 出版日期:2018-05-18 发布日期:2018-05-18
  • 通讯作者: 王自立，主任医师，教授，博士生导师，宁夏医科大学总医院脊柱骨科，宁夏回族自治区银川市 750004
  • 作者简介:袁虎成，男，1985年生，回族，宁夏回族自治区银川市人，宁夏医科大学在读硕士，主要从事骨科临床及基础研究工作。
  • 基金资助:

    国家自然科学基金项目(81060149)；宁夏自然科学基金项目(NZ17145)

Sustained-releasing performance of polymethyl methacrylate bone cement carrying antituberculosis drugs in vitro

Yuan Hu-cheng1, Shi Shi-yuan2, Ma Wen-xin3, Yang Xiao-ying4, Wang Jia-ming5, Wang Zi-li3   

  1. 1Ningxia Medical University, Yinchuan 750004, Ningxia Hui Autonomous Region, China; 2Department of Orthopedics, Red Cross Hospital of Hangzhou, Zhejiang Chinese Medical University, Hangzhou 310003, Zhejiang Province, China; 3Department of Orthopedics, 4Department of Pharmacology, General Hospital of Ningxia Medical University, Yinchuan 750004, Ningxia Hui Autonomous Region, China; 5School of Traditional Chinese Medicine, Zhejiang A&F University, Hangzhou 311300, Zhejiang Province, China
  • Received:2018-03-26 Online:2018-05-18 Published:2018-05-18
  • Contact: Wang Zi-li, Chief physician, Professor, Doctoral supervisor, Department of Orthopedics, General Hospital of Ningxia Medical University, Yinchuan 750004, Ningxia Hui Autonomous Region, China
  • About author:Yuan Hu-cheng, Master candidate, Ningxia Medical University, Yinchuan 750004, Ningxia Hui Autonomous Region, China
  • Supported by:

     the National Natural Science Foundation of China, No. 81060149; Ningxia Natural Science Foundation, No. NZ17145

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摘要：

文章快速阅读：

 

文题释义：
药物缓释系统：又称药物控释体系，是将高分子聚合物材料作为载体，再将药物包埋在聚合物载体中，制成平面、球型、圆柱体等形式，包埋在其中的药物随时间变化呈一定速度的释放，达到对疾病更有效治疗目的的给药方法。
聚甲基丙烯酸甲酯：以丙烯酸及其酯类聚合所得到的聚合物统称丙烯酸类树酯，相应的塑料统称聚丙烯酸类塑料，其中以聚甲基丙烯酸甲酯应用最广泛。
 
背景：载抗生素骨水泥在预防、治疗人工关节置换后感染的研究及临床应用较多，然而有关载抗结核药物骨水泥的研究较少。
目的：探讨载抗结核药物聚甲基丙烯酸甲酯骨水泥在PBS模拟体液中的药物缓释性能。

方法：采用等量递增法将骨水泥SimpLex P与8种抗结核药(吡嗪酰胺、异烟肼、利福喷丁、丙硫异烟胺、卷曲霉素、利福平、莫西沙星、阿米卡星)分别按40 g∶1.5 g、40 g∶2.5 g的比例混合，制备载抗结核药骨水泥标准试件16组，每组5个样本，共80个样本；对照组将40 g骨水泥粉剂与其液相单体同法混匀，制备非载药骨水泥标准试件1组，共5个样本。将所有试件浸泡于PBS模拟体液中，在不同的时间点取浸提液，采用高效液相色谱法测定其中药物浓度。

结果与结论：吡嗪酰胺1.5 g组、吡嗪酰胺2.5 g组、异烟肼1.5 g组、异烟肼2.5 g组、利福喷丁1.5 g组、利福喷丁2.5 g组、丙硫异烟胺1.5 g组、丙硫异烟胺2.5 g组、卷曲霉素1.5 g组、卷曲霉素2.5 g组、利福平1.5 g组、利福平2.5 g组、莫西沙星1.5 g组、莫西沙星2.5 g组、阿米卡星1.5 g组、阿米卡星2.5 g组在PBS中的有效释药时间分别可达到45，60，60，45，60，45，150，150，150，150，45，60，90，90，60，90 d，均具有良好的释药特性，尤其丙硫异烟胺1.5 g组、丙硫异烟胺2.5 g组、卷曲霉素1.5 g组、卷曲霉素2.5 g组、莫西沙星1.5 g组、莫西沙星2.5 g组、阿米卡星2.5 g组具有较长的释药周期，符合临床用药的要求；但结合前期研究，异烟肼、利福平、利福喷丁、丙硫异烟胺可明显降低骨水泥的机械强度，故不适于制备载抗结核药物骨水泥；吡嗪酰胺、阿米卡星、莫西沙星、卷曲霉素不影响骨水泥的机械强度，适于制备载抗结核药物骨水泥。

关键词: 抗结核药, 聚甲基丙烯酸甲酯, 骨水泥, 缓释性能, 高效液相, 生物材料

Abstract:

  BACKGROUND: Antibiotic loaded bone cement has been well studied in clinical prevention and treatment of postoperative infection after artificial joint replacement. However, little is reported on antituberculotic-loaded bone cement.

OBJECTIVE: To investigate the drug release properties of polymethyl methacrylate bone cement carrying antituberculosis drugs in a simulated body fluid (phosphate buffer solution, PBS).
METHODS: The bone cement SimpLex P and antituberculosis drugs, including pyrazinamide, isoniazid, rifapentine, prothionamide, capreomycin, rifampicin, moxifloxacin, and amikacin, were mixed at 40 g:1.5 g and 40 g: 2.5 g ratios to prepare 16 groups of experimental specimens (n=5 per group). In addition, 40 g of bone cement powder was mixed with the liquid monomer to prepare a group of non-loaded bone cement specimens (control group, n=5). Either experimental or control specimens were soaked in PBS simulated body fluid, and then the extractions were taken at different time points to measure concentrations of antituberculosis drugs by high performance liquid chromatography.

RESULTS AND CONCLUSION: The effective sustained-releasing time in the PBS simulated body fluid was 45 and 60 days for 1.5 g and  2.5 g groups of pyrazinamide, was 60 and 45 days for 1.5 g and 2.5 g groups of isoniazid, was 60 and 45 days for 1.5 g and 2.5 g groups of rifapentine, was 150 and 150 days for 1.5 g and 2.5 g groups of protionamide, was 150 and 150 days for 1.5 g and 2.5 g groups of capreomycin, was 45 and 60 days for 1.5 g and 2.5g groups of rifampicin, was 90 and 90 days for 1.5 g and 2.5 g groups of moxifloxacin, and was 60 and 90 days for 1.5 g and 2.5 g groups of amikacin, respectively. All the drug carriers had good drug release characteristics. Especially the 1.5 g and 2.5 g groups of protionamide, 1.5 g and 2.5 g groups of capreomycin, 1.5 g and 2.5 g groups of moxifloxacin and 2.5 g group of amikacin showed a longer period of drug release in accordance with the clinical need. However, our preliminary findings showed that the mechanical strength of the composite bone cement was considerably reduced by isoniazid, rifampicin, rifapentine, or protionamide, while the SimpLex P bone cement carrying pyrazinamide, amikacin, moxifloxacin, or capreomycin showed no changes in the mechanical strength. Therefore, pyrazinamide, amikacin, moxifloxacin, and capreomycin are suitable for the preparation of bone cements carrying antituberculosis drugs.

中国组织工程研究杂志出版内容重点：生物材料；骨生物材料; 口腔生物材料; 纳米材料; 缓释材料; 材料相容性；组织工程

Key words: Antitubercular Agents, Tuberculosis, Osteoarticular, Chromatography, High Pressure Liquid, Delayed-Action Preparations, Tissue Engineering

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