本文選題：伏立康唑 + 緩釋系統(tǒng)��； 參考：《青島大學》2010年碩士論文

【摘要】： 目的評價玻璃體腔內(nèi)植入伏立康唑緩釋系統(tǒng)(VCZ-DDS)對兔煙曲霉菌性眼內(nèi)炎的影響,探索最佳給藥劑量,探討VCZ-DDS的體內(nèi)釋放規(guī)律。 方法伏立康唑以PLGA為載體制成VCZ-DDS。新西蘭大白兔42只,玻璃體腔內(nèi)注入濃度為103CFU/mL煙曲霉菌孢子懸液,48小時后進行治療并觀察。實驗兔隨機分為6組：A組為空白對照組(6只眼),B組為空白PLGA植入(6只眼),C組為100μg/0.1mL伏立康唑眼內(nèi)注射(6只眼),D組為0.5mgVCZ-DDS植入(8只眼),E組為0.9mgVCZ-DDS植入(8只眼),F組為1.2mgVCZ-DDS植入(8只眼),B-F組均聯(lián)合玻璃體切除術(shù)。術(shù)后不同時間點檢測前房閃輝、房水細胞及玻璃體混濁度,抽取玻璃體腔液涂片查菌絲及真菌培養(yǎng),并組織病理學檢查,觀察真菌及藥物對眼組織的影響。另取健康新西蘭大白兔6只,玻璃體切割術(shù)后植入1.2mgVCZ-DDS1枚,術(shù)后不同時間點抽取玻璃體腔液,應(yīng)用高效液相色譜-質(zhì)譜分析法(HPLC-MS-MS)檢測伏立康唑藥物濃度。 結(jié)果A、B組所有眼均發(fā)生眼內(nèi)炎,并迅速發(fā)展為全眼球炎,至眼球萎縮,接種后第1周內(nèi)兩組差異無統(tǒng)計學意義(P≥0.212)。C、D、E、F組炎癥反應(yīng)均較A、B組輕(P≤0.046)。C組玻璃體混濁度較E、F組重(P≤0.044),前3周前房反應(yīng)較E、F組重(P≤0.031)。第10、14天時,D組玻璃體渾濁度較F組輕(P=0.023),但與E組相似(P≥0.144)。術(shù)后兩個月,所有炎癥控制眼,眼底清晰,無復發(fā)。玻璃體腔液涂片,A、B、C組查見菌絲,真菌培養(yǎng)均有陽性標本,其余各組涂片及培養(yǎng)全部為陰性。組織病理學,治愈眼結(jié)構(gòu)正常；炎癥未控制眼多萎縮,球壁結(jié)構(gòu)破壞。 結(jié)論玻璃體腔植入緩釋系統(tǒng)明顯優(yōu)于玻璃體腔注射給藥,VCZ-DDS玻璃體腔植入治療煙曲霉菌性眼內(nèi)炎安全有效,含伏立康唑1.2mg的緩釋系統(tǒng)療效最佳。
[Abstract]:Objective to evaluate the effect of VCZ-DDS implanted into vitreous cavity on rabbit endophthalmitis of tobacillus fumigatus, and to explore the optimal dosage and release rule of VCZ-DDS in vivo. Methods VCZ-DDS was prepared by VCZ-DDS using PLGA as carrier. Forty-two New Zealand white rabbits were injected with 103 CFU / mL aspergillus fumigatus spore suspension for 48 hours. The experimental rabbits were randomly divided into 6 groups: group A as blank control group (6 eyes), group B as blank PLGA implantation (6 eyes), group C: 100 渭 g / 0.1 mL intraocular injection of voleconazole (6 eyes), group D: 0.5 mg VCZ-DDS implantation (8 eyes), group E 0.9 mg VCZ-DDS implantation (8 eyes) and group F 1.2mgVCZ-DDS implantation. Vitrectomy combined with B-F group (8 eyes). The turbidity of anterior chamber flashes, aqueous humor cells and vitreous bodies were detected at different time points after operation. The mycelium and fungal culture were examined by vitreous cavity smears, and the effects of fungi and drugs on the ocular tissue were observed by histopathological examination. Another 6 healthy New Zealand white rabbits were implanted with 1.2 mg VCZ-DDS1 after vitrectomy. Vitreous cavity fluid was extracted at different time points after vitrectomy. The concentration of voriconazole was determined by high performance liquid chromatography-mass spectrometry (HPLC-MS-MS). Results in group A, endophthalmitis occurred in all eyes and developed rapidly into total ophthalmitis and atrophy. In the first week after inoculation, there was no significant difference between the two groups (P 鈮，

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