【摘要】：背景： 慢性骨髓炎由于其病情復(fù)雜、病程長、局部骨質(zhì)缺損、容易復(fù)發(fā)等特點，一直是困擾骨科醫(yī)生的醫(yī)學(xué)難題。根據(jù)慢性骨髓炎的病理變化及治療原則，以病灶局部清創(chuàng)、敏感抗生素的選擇應(yīng)用、修復(fù)病變區(qū)域的骨缺損為指導(dǎo)思想，臨床醫(yī)生進行了諸多嘗試。局部使用聚甲基丙烯酸甲酯（PMMA）水泥為載體釋放高劑量抗生素連同應(yīng)用全身性抗生素，是現(xiàn)階段臨床治療慢性骨髓炎的標(biāo)準(zhǔn)方案。然而，PMMA具有水泥聚合反應(yīng)過程中加熱、需二次手術(shù)取出等缺點。最近，磷酸鈣骨水泥（CPC）已被用作骨替代和擴增，，并在聚合過程中不發(fā)熱、對加載藥物活性無影響。對磷酸鈣骨水泥(CPC)加載萬古霉素（VCM）與聚甲基丙烯酸甲酯骨水泥(PMMA)加載萬古霉素(VCM)釋放藥物濃度、時間的差異,國內(nèi)仍未有明確研究。 目的: 對比磷酸鈣骨水泥(CPC)加載VCM與聚甲基丙烯酸甲酯骨水泥(PMMA)加載VCM釋放藥物濃度、時間的差異，為臨床應(yīng)用提供實驗基礎(chǔ)。 方法： 測試樣本包括磷酸鈣骨水泥或聚甲基丙烯酸甲酯骨水泥粉末、萬古霉素和配比液（5:0.25:1.6克）。各樣品浸漬于磷酸鹽緩沖鹽水(PBS)中，每天更換浸泡液，每周留取第一天、第三天洗脫液，持續(xù)8周。8周后解凍樣品，通過高效液相色譜法（評價性HPLC）測定浸泡液中萬古霉素濃度。 結(jié)果： 萬古霉素從磷酸鈣骨水泥/萬古霉素復(fù)合體中洗脫濃度在第1天最大，然后急劇下降但可以繼續(xù)有效洗脫至少53天。萬古霉素對于MRSA的最小抑制濃度（MIC）的是0.78-3.13微克/毫升,磷酸鈣骨水泥萬古霉素復(fù)合體第53天浸泡液中的的萬古霉素仍遠大于MIC。 萬古霉素從聚甲基丙烯酸甲酯骨水泥/萬古霉素復(fù)合體中洗脫濃度在第1天最大，然后急劇下降但可以繼續(xù)洗脫39天。然而，洗脫液中萬古霉素濃度在第36天基本低于MRSA的MIC，無法達到有效殺菌效果。 第1天萬古霉素在磷酸鈣骨水泥/萬古霉素復(fù)合體中的洗脫濃度是聚甲基丙烯酸甲酯骨水泥/萬古霉素復(fù)合體的1.30倍，第1周為1.37倍，第2周為1.96倍，第3周為3.12倍,第4周為3.93倍，第5周為6.30倍。萬古霉素從磷酸鈣骨水泥/萬古霉素復(fù)合體和聚甲基丙烯酸甲酯骨水泥/萬古霉素復(fù)合體可以檢測到的釋放周期分別為53天，39天。 結(jié)論： 與聚甲基丙烯酸甲酯骨水泥相比，磷酸鈣骨水泥釋放萬古霉素的時間更長、劑量更大，是治療慢性骨髓炎的理想的藥物緩釋載體。
[Abstract]:Background: chronic osteomyelitis is a difficult medical problem for orthopedic doctors because of its complex condition, long course of disease, local bone defect and easy recurrence. According to the pathological changes and treatment principles of chronic osteomyelitis, the clinicians made many attempts with the guiding ideology of local debridement, the selection of sensitive antibiotics and the repair of bone defects in the diseased areas. Local use of polymethyl methacrylate (PMMA) cement as a carrier to release high dose antibiotics together with systemic antibiotics is the current standard for the treatment of chronic osteomyelitis. However, PMMA has the disadvantages of heating during cement polymerization and requiring secondary surgical removal. Recently, calcium phosphate cement (CPC) has been used as bone substitute and amplification, and it has no effect on drug activity during polymerization. The time difference of vancomycin (VCM) loaded with calcium phosphate cement (CPC) and (PMMA) loading vancomycin (VCM) (PMMA) has not been clearly studied in China. Objective: to compare the concentration and time of calcium phosphate cement (CPC) loaded VCM and polymethyl methacrylate cement (PMMA) loaded VCM in order to provide experimental basis for clinical application. Methods: the test samples included calcium phosphate cement or polymethyl methacrylate cement powder, vancomycin and mixture solution (5: 0.25: 1.6 g). Each sample was impregnated with phosphate buffer saline (PBS). The solution was changed daily, the first day and the third day of each week were retained. The samples were thawed after 8 weeks. The concentration of vancomycin in soaking solution was determined by high performance liquid chromatography (HPLC). Results: the elution concentration of vancomycin from calcium phosphate cement / vancomycin complex was the highest on the first day and then decreased sharply but could continue to be eluted effectively for at least 53 days. The minimum inhibitory concentration of vancomycin on MRSA was 0.78-3.13 渭 g / ml, and the vancomycin in the solution of calcium phosphate cement vancomycin complex on the 53rd day was still much larger than MIC.. The elution concentration of vancomycin from polymethyl methacrylate bone cement / vancomycin complex was the highest on day 1, then decreased sharply but could be eluted for 39 days. However, the concentration of vancomycin in eluent was lower than that of MIC, with MRSA on the 36th day. On day 1, the elution concentration of vancomycin in calcium phosphate cement / vancomycin complex was 1.30 times as much as that of polymethyl methacrylate bone cement / vancomycin complex, 1.37 times in the first week, 1.96 times in the second week and 3.12 times in the third week. It was 3.93 times in the fourth week and 6.30 times in the fifth week. The release periods of vancomycin from calcium phosphate cement / vancomycin complex and polymethyl methacrylate cement / vancomycin complex were 53 days / 39 days respectively. Conclusion: compared with polymethyl methacrylate cement, calcium phosphate cement can release vancomycin for longer time and larger dosage. It is an ideal drug delivery carrier for the treatment of chronic osteomyelitis.
【學(xué)位授予單位】：吉林大學(xué)
【學(xué)位級別】：碩士
【學(xué)位授予年份】：2015
【分類號】：R681.2

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