中国组织工程研究 ›› 2023, Vol. 27 ›› Issue (7): 1017-1022.doi: 10.12307/2023.080

• 组织工程骨材料 tissue-engineered bone • 上一篇    下一篇

载抗结核药吡嗪酰胺、卷曲霉素、莫西沙星及阿米卡星骨水泥的体外缓释性能

袁虎成1,丁永国1,马雪花2,马文鑫3,孙建民1,王自立4,5,金卫东3,5   

  1. 1宁夏中西医结合医院疼痛科,宁夏回族自治区银川市  750021;2银川市第三人民医院大新社区卫生服务中心,宁夏回族自治区银川市  750004;3宁夏医科大学总医院,宁夏回族自治区银川市  750004;4西安国际医学中心医院,陕西省西安市  710000;5宁夏医科大学,宁夏回族自治区银川市  750004
  • 收稿日期:2021-12-06 接受日期:2022-02-22 出版日期:2023-03-08 发布日期:2022-07-18
  • 通讯作者: 金卫东,主任医师,硕士生导师,宁夏医科大学总医院,宁夏回族自治区银川市 750004;宁夏医科大学,宁夏回族自治区银川市 750004 王自立,主任医师,博士生导师,西安国际医学中心医院,陕西省西安市 710000;宁夏医科大学,宁夏回族自治区银川市 750004
  • 作者简介:袁虎成,男,1985年生,宁夏回族自治区银川市人,回族,医学硕士,主治医师,主要从事脊柱微创与疼痛相关临床与基础研究。
  • 基金资助:
    宁夏医科大学校级科研项目资助(XY201828,XY201722),项目负责人:金卫东、王自立;宁夏自然科学基金项目(NZ17145),项目负责人:马文鑫

Sustained releasing of pyrazinamide, capreomycin, moxifloxacin and amikacin loaded bone cement in vitro

Yuan Hucheng1, Ding Yongguo1, Ma Xuehua2, Ma Wenxin3, Sun Jianmin1, Wang Zili4, 5, Jin Weidong3, 5   

  1. 1Pain Department of Ningxia Integrated Traditional Chinese and Western Medicine Hospital, Yinchuan 750021; 2Daxin Community Health Service Center of Yinchuan Third People’s Hospital, Yinchuan 750004; 3General Hospital of Ningxia Medical University, Yinchuan 750004; 4Xi’an International Medical Center Hospital, Xi’an 710000, Shaanxi Province, China; 5Ningxia Medical University, Yinchuan 750004, Ningxia Hui Autonomous Region, China
  • Received:2021-12-06 Accepted:2022-02-22 Online:2023-03-08 Published:2022-07-18
  • Contact: Jin Weidong, Chief physician, Master’s supervisor, General Hospital of Ningxia Medical University, Yinchuan 750004, Ningxia Hui Autonomous Region, China; Ningxia Medical University, Yinchuan 750004, Ningxia Hui Autonomous Region, China Wang Zili, Chief physician, Doctoral supervisor, Xi’an International Medical Center Hospital, Xi’an 710000, Shaanxi Province, China; Ningxia Medical University, Yinchuan 750004, Ningxia Hui Autonomous Region, China
  • About author:Yuan Hucheng, Master, Attending physician, Pain Department of Ningxia Integrated Traditional Chinese and Western Medicine Hospital, Yinchuan 750021, Ningxia Hui Autonomous Region, China
  • Supported by:
    Scientific Research Project of Ningxia Medical University, No. XY201828, XY201722 (to JWD, WZL); the National Science Foundation of Ningxia Hui Autonomous Region, No. NZ17145 (to MWX)

摘要:

文题释义:
药物缓释体系:又称药物控释体系,是指以一种材料作为载体,将药物负载于该载体上,使药物按照预先设计的剂量,在要求的时间范围内以一定的速度在体内缓慢释放的一种新型给药系统,其优势在于节约药量、提高病灶局部药物浓度、减少全身药物毒副作用。
高效液相色谱法:又称“高压液相色谱”“高速液相色谱”“高分离度液相色谱”“近代柱色谱”等。高效液相色谱是色谱法的一个重要分支,以液体为流动相,采用高压输液系统,将具有不同极性的单一溶剂或不同比例的混合溶剂、缓冲液等流动相泵入装有固定相的色谱柱,在柱内各成分被分离后,进入检测器进行检测,从而实现对试样的分析。

背景:骨关节结核病灶清除术后口服抗结核药全身毒副作用大,寻求一种既能节约药物用量又能提高病灶局部药物浓度、降低全身血药浓度的药物缓释系统势在必行。
目的:观察载抗结核药吡嗪酰胺、卷曲霉素、莫西沙星、阿米卡星的聚甲基丙烯酸甲酯骨水泥,在PBS人工模拟体液中的缓释性能。
方法:将聚甲基丙烯酸甲酯骨水泥Palacos R粉剂分别与抗结核药吡嗪酰胺、卷曲霉素、莫西沙星、阿米卡星混合,每种药物与骨水泥粉剂有1.5 g∶40 g、2.5 g∶40 g两种比例,均加入20 mL液相单体,制备载抗结核药骨水泥标准试件8组,每组5个样本;对照组将40 g骨水泥粉剂与其20 mL液相单体混合,制备不含药骨水泥标准试件1组,共5个样本。将上述所有样本浸泡于PBS中,并置于37 ℃恒温水浴振荡器内,于设定的时间点取浸提液,采用高效液相色谱法检测药物浓度。
结果与结论:①吡嗪酰胺1.5 g组、 吡嗪酰胺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 1.5 g组、阿米卡星2.5 g组在PBS中可测到最低释药浓度的时间分别为45,60,150,150,120,120,60,90 d,其中卷曲霉素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组具有更长的释药周期,对照组无药物释出;②结果显示,载卷曲霉素(1.5,2.5 g)、莫西沙星(1.5,2.5 g)、阿米卡星(2.5 g)的聚甲基丙烯酸甲酯骨水泥释药周期长、缓释性能好。

https://orcid.org/0000-0001-7229-240X(袁虎成)

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

关键词: 聚甲基丙烯酸甲酯, 骨水泥, 抗结核药, 缓释性能, 骨关节结核, 病灶清除术, 高效液相, 缓释材料

Abstract: BACKGROUND: Oral anti-tuberculosis drugs have serious systemic side effects after removal of bone and joint tuberculosis lesions. It is imperative to seek a sustained-release drug system that can not only save drug dosage, but also increase local drug concentration in lesions and reduce systemic blood drug concentration. 
OBJECTIVE: To observe the sustained-release properties of polymethyl methacrylate bone cement loaded with antituberculosis drugs pyrazinamide, capreomycin, moxifloxacin, and amikacin in PBS artificial simulated body fluid. 
METHODS: Polymethyl methacrylate bone cement Palacos R powder was mixed with antituberculosis drugs pyrazinamide, capreomycin, moxifloxacin, and amikacin in the proportion of 40 g:1.5 g and 40 g:2.5 g, respectively. The 20 mL of liquid monomer were added to prepare 8 groups of anti-tuberculosis drug-loaded bone cement standard specimens, with 5 samples in each group. In the control group, 40 g bone cement powder and 20 mL liquid monomer were mixed in the same way to prepare 5 standard bone cement samples without drugs. The drug was soaked in PBS and placed in 37 ℃ constant temperature water bath oscillator. The extract was taken at set time points. The drug concentration of each group was determined by high performance liquid chromatography. 
RESULTS AND CONCLUSION: (1) The time of the lowest drug release concentration in PBS artificial simulated body fluid of pyrazinamide 1.5 g group, pyrazinamide 2.5 g group, capreomycin 1.5 g group, capreomycin 2.5 g group, moxifloxacin 1.5 g group, moxifloxacin 2.5 g group, amikacin 1.5 g group and amikacin 2.5 g group was 45, 60, 150, 150, 120, 120, 60 and 90 days, respectively. Among these groups, the capreomycin 1.5 g group, capreomycin 2.5 g group, moxifloxacin 1.5 g group, moxifloxacin 2.5 g group, and amikacin 2.5 g group had a longer drug release period, while the control group had no drug release. (2) It is concluded that polymethyl methacrylate bone cement loaded with capreomycin (1.5 g and 2.5 g), moxifloxacin (1.5 g and 2.5 g), and amikacin (2.5 g) has a long release cycle and good release performance.

Key words: polymethylmethacrylate, bone cement, antituberculosis drug, sustained release property, tuberculosis of bone and joint, focal debridement, high performance liquid chromatography, sustained-release material

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