几丁糖庆大霉素局部药物释放系统的临床应用研究

CLINICAL STUDY OF GENTAMYCIN LOADED CHITOSAN DRUG DELIVERY SYSTEM

对几丁糖庆大霉素局部药物释放系统治疗慢性骨髓炎的疗效及体内动力学行为进行研究，为其临床推广应用提供理论依据。采用外科病灶清除术后残腔内置入几丁糖庆大霉素缓释药治疗慢性骨髓炎１８例。监测术后不同时间庆大霉素血药浓度，血尿素氮（ＢＵＮ）和肌酐（Ｃｒ）值，局部引流液中庆大霉素浓度。以术后切口愈合情况、临床表现和Ｘ线片评定疗效。结果，血药浓度峰值（０．８３μｇ／ｍｌ）在２４小时出现，维持时间为４天；术后ＢＵＮ和Ｃｒ值无增加；术后局部引流液中庆大霉素浓度为金黄色葡萄球菌最低抑菌浓度数百倍。１８例患者均获随访，随访时间６个月～３４个月，平均２４．８个月。初期愈合１６例，无一例复发。认为，几丁糖庆大霉素缓释药是临床治疗慢性骨髓炎的有效方法，具有简便安全，且无需二期取出载体的优点，为临床推广应用提供了理论依据。

An clinical and pharmacokinetic study for a drug delivery system (DDS) of gentamycin loaded chitosan bar were carried out with the purpose to evaluate its efficacy and giving further data for its clinical applications. Eighteen cases of chronic osteomyelitis were treated by surgical necrectomy with implantation of gentamycin load chitosan bar in the prepared bone cavity. After operation, the concentration of gentamycin in serum and wound drainage fluid were examined at different times and blood urea nitrogen (BUN) and serum creatinine (Cr) as well. The clinical results were evaluated by the conditions of wound healing and clinical and roentgenographic manifestations. The results showed that the serum gentamycin concentration reached its peak level (0.86 μg/ml) at 24 hours after operation and lasted for 4 days. No increase in the concentrations of BUN and Cr were observed after implantation. The gentamycin concentration in wound drainage fluid was several hundred times higher than the minimum inhibitory concentration (MIC) for staphylococcus aureus. All of the 18 cases were followed up for 24.8 months (in an range of 6～34 months) 16 patients received initial cure and without any recurrence. So, it could be concluded that the gentamycin loaded chitosan DDS was a simple and effective method for the treatment of chronic osteomylitis without the necessity to carry out a second operation to remove the drug carrier, and it was sound to popularize its clincal application.