中国组织工程研究
中國組織工程研究
중국조직공정연구
Journal of Clinical Rehabilitative Tissue Engineering Research
2013年
29期
5345-5350
,共6页
鲍玉成%张文龙%王勇%张洁%王咏梅
鮑玉成%張文龍%王勇%張潔%王詠梅
포옥성%장문룡%왕용%장길%왕영매
生物材料%生物材料与药物控释%异烟肼%利福平%聚乳酸-羟基乙酸共聚物%缓释%体外%体内%骨结核%省级基金
生物材料%生物材料與藥物控釋%異煙肼%利福平%聚乳痠-羥基乙痠共聚物%緩釋%體外%體內%骨結覈%省級基金
생물재료%생물재료여약물공석%이연정%리복평%취유산-간기을산공취물%완석%체외%체내%골결핵%성급기금
biomaterials%biomaterials and controlled drug release%isoniazid%rifampicin%polylactic acid-glycolic acid copolymer%slow release%in vitro%in vivo%bone tuberculosis%provincial grants-supported paper
背景：骨结核患者常规用药，病灶处结核药物的有效浓度低，治疗效果差。目的：制备一种可直接植入骨结核病灶内的，且具有在骨结核周围组织能够长期保持一定的抗结核药物浓度，起到提高骨结核的治愈率有效治疗的新型生物材料。方法：采用乳剂-溶剂挥发法制备利福平-聚乳酸-羟基乙酸共聚物微球和异烟肼-聚乳酸-羟基乙酸共聚物微球，利用生物黏合剂α-氰基丙烯酸烷基酯将2种微球加工成长效缓释双组分药物载体，观察缓释双药物载体体外释药特性；然后将缓释双药物载体置入兔股骨转子间骨缺损部位，观察载药缓释载体植入后不同时间点药物释放浓度、组织相容性及骨缺损的愈合情况。结果与结论：利福平-聚乳酸-羟基乙酸微球平均粒径(240±13)μm，载药率为(26±1.5)%。异烟肼-聚乳酸-羟基乙酸微球平均粒径(250±10)μm，载药率为(28±1.8)%。利福平、异烟肼，90 d体外累积释放率可达到80%和90%。90 d体内释放利福平和异烟肼的浓度可达(0.5±0.4)和(0.6±0.3)μg/g。缓释双药物载体置入兔股骨转子间骨缺损部位可见筋膜、肌纤维之间出现少量中性粒细胞浸润，59 d 后肌肉组织中性粒细胞明显减少，X射线平片显示骨缺损明显缩小。提示该载体能够长时间保持骨结核周围组织中一定的药物浓度，弥补血中药物浓度不足，有望在骨结核手术治疗中提供一种新型的双药物缓释载体。
揹景：骨結覈患者常規用藥，病竈處結覈藥物的有效濃度低，治療效果差。目的：製備一種可直接植入骨結覈病竈內的，且具有在骨結覈週圍組織能夠長期保持一定的抗結覈藥物濃度，起到提高骨結覈的治愈率有效治療的新型生物材料。方法：採用乳劑-溶劑揮髮法製備利福平-聚乳痠-羥基乙痠共聚物微毬和異煙肼-聚乳痠-羥基乙痠共聚物微毬，利用生物黏閤劑α-氰基丙烯痠烷基酯將2種微毬加工成長效緩釋雙組分藥物載體，觀察緩釋雙藥物載體體外釋藥特性；然後將緩釋雙藥物載體置入兔股骨轉子間骨缺損部位，觀察載藥緩釋載體植入後不同時間點藥物釋放濃度、組織相容性及骨缺損的愈閤情況。結果與結論：利福平-聚乳痠-羥基乙痠微毬平均粒徑(240±13)μm，載藥率為(26±1.5)%。異煙肼-聚乳痠-羥基乙痠微毬平均粒徑(250±10)μm，載藥率為(28±1.8)%。利福平、異煙肼，90 d體外纍積釋放率可達到80%和90%。90 d體內釋放利福平和異煙肼的濃度可達(0.5±0.4)和(0.6±0.3)μg/g。緩釋雙藥物載體置入兔股骨轉子間骨缺損部位可見觔膜、肌纖維之間齣現少量中性粒細胞浸潤，59 d 後肌肉組織中性粒細胞明顯減少，X射線平片顯示骨缺損明顯縮小。提示該載體能夠長時間保持骨結覈週圍組織中一定的藥物濃度，瀰補血中藥物濃度不足，有望在骨結覈手術治療中提供一種新型的雙藥物緩釋載體。
배경：골결핵환자상규용약，병조처결핵약물적유효농도저，치료효과차。목적：제비일충가직접식입골결핵병조내적，차구유재골결핵주위조직능구장기보지일정적항결핵약물농도，기도제고골결핵적치유솔유효치료적신형생물재료。방법：채용유제-용제휘발법제비리복평-취유산-간기을산공취물미구화이연정-취유산-간기을산공취물미구，이용생물점합제α-청기병희산완기지장2충미구가공성장효완석쌍조분약물재체，관찰완석쌍약물재체체외석약특성；연후장완석쌍약물재체치입토고골전자간골결손부위，관찰재약완석재체식입후불동시간점약물석방농도、조직상용성급골결손적유합정황。결과여결론：리복평-취유산-간기을산미구평균립경(240±13)μm，재약솔위(26±1.5)%。이연정-취유산-간기을산미구평균립경(250±10)μm，재약솔위(28±1.8)%。리복평、이연정，90 d체외루적석방솔가체도80%화90%。90 d체내석방리복평화이연정적농도가체(0.5±0.4)화(0.6±0.3)μg/g。완석쌍약물재체치입토고골전자간골결손부위가견근막、기섬유지간출현소량중성립세포침윤，59 d 후기육조직중성립세포명현감소，X사선평편현시골결손명현축소。제시해재체능구장시간보지골결핵주위조직중일정적약물농도，미보혈중약물농도불족，유망재골결핵수술치료중제공일충신형적쌍약물완석재체。
BACKGROUND: During conventional treatment for bone tuberculosis, there is a low effective concentration of anti-tuberculosis drugs, and the therapeutic effect is poor. OBJECTIVE:To develop a new biomaterial as a slow-release artificial carrier that can be directly implanted into the surrounding tissue of bone tuberculosis, maintain a certain anti-tuberculosis drug concentration for a long time, thereby playing an effective therapeutic action. METHODS:Rifampicin/polylactic acid/glycolic acid microspheres and isoniazid/polylactic acid/glycolic acid microspheres were prepared using the emulsion-solvent evaporation method. Usingα-cyanoacrylate, a biological adhesive, two kinds of microspheres were processed into a long-term slow-release bicomponent drug carrier. Then, in vitro release characteristics of the dual-drug sustained-release carrier were observed. After that, the dual-drug sustained-release carrier was implanted into rabbit intertrochanteric femur bone defects for observing drug release concentrations, histocompatibility and bone defect healing at different time points after drug delivery carrier implantation. RESULTS AND CONCLUSION:For rifampicin/polylactic acid/glycolic acid microspheres, the mean particle size was (240±13)μm, and the drug loading load rate was (26±1.5)%. For isoniazid/polylactic acid/glycolic acid microspheres, the mean particle size was (250±10)μm, and drug loading rate was (28±1.8)%. The in vitro cumulative release rate could reach 80%for rifampicin and 90%for isoniazid at day 90. The in vivo released concentration of rifampicin and isoniazid within 90 days was (0.5±0.4) and (0.6±0.3)μg/g, respectively. There were a smal amount of infiltrated neutrophils between the fascia and muscle fibers after the drug delivery carrier was implanted, and the amount of neutrophils in the muscle were reduced significantly at day 59. X-ray plain film showed that bone defects decreased obviously in size. These findings indicate that this dual-drug sustained-release carrier can maintain a certain anti-tuberculosis drug concentration in the surrounding tissues of bone tuberculosis, which is expected to provide a new type of dual-drug delivery carrier in the surgical treatment of bone tuberculosis.
