地佐辛聚乳酸-羟基乙酸嵌段共聚物微球的制备及鉴定  

Preparation and verification of dezocine polylactic acid-glycolic acid block copolymer microspheres

作　　者：孙熠[1] 王海云[1] 赵茗姝 王心怡 华伟 Sun Yi;Wang Haiyun;Zhao Mingshu;Wang Xinyi;Hua Wei(The Third Central Clinical College of Tianjin Medical University Department of Anesthesiology,Nankai University Affiliated the Third Central Hospital Tianjin Key Laboratory of Extracorporeal Life Support for Critical Diseases Tianjin Artificial Cell Engineering Technology Research Center Tianjin Institute of Hepatobiliary Disease,Tianjin 300170,China)

机构地区：[1]天津医科大学三中心临床学院、南开大学附属第三中心医院麻醉科、天津市重症疾病体外生命支持重点实验室、天津市人工细胞工程技术研究中心、天津市肝胆疾病研究所,天津300170

出　　处：《中华麻醉学杂志》2023年第11期1378-1381,共4页Chinese Journal of Anesthesiology

基　　金：天津市卫生健康委员会科技基金面上项目(MS20013);天津市医学重点学科(专科)建设项目资助(TJYXZDXK-072C)。

摘　　要：目的制备地佐辛聚乳酸-羟基乙酸嵌段共聚物(PLGA)微球并进行鉴定。方法地佐辛PLGA微球制备:地佐辛120 mg、PLGA 0.1 g与其助溶添加剂泊洛沙姆0.1 g分散于四氢呋喃溶剂中, 配置成有机相溶液;氯化钠、聚乙二醇溶解于注射用水中, 形成内水相溶液和外水相溶液;机相溶液20 ml与内水相溶液20 ml混合, 形成水相/油相初乳后, 加入外水相溶液中, 形成水相/油相/水相复乳, 与冻干粉保护剂充分混合冷冻干燥, 制成地佐辛PLGA微球。鉴定:清洁级健康雄性SD大鼠18只, 10~12周龄, 体质量220~260 g, 采用随机数字表法分为3组(n=6):对照组(C组)、地佐辛普通制剂组(D1组)和地佐辛PLGA微球组(D2组), 分别肌肉注射生理盐水、地佐辛注射液(药物剂量1 mg)及地佐辛PLGA微球注射液(药物剂量0.2 μg)0.2 ml。于给药后30 min(T_(1))、1 h(T_(2))、2 h(T_(3))、3 h(T_(4))、4 h(T_(5))、5 h(T_(6))、6 h(T_(7))、7 h(T_(8))和8 h(T_(9))时测定血浆地佐辛浓度, 于T_(1)~T_(3)、T_(5)和T_(9)时测定热缩足潜伏期;肌肉注射后第7天, 取注射部位组织, HE染色后观察炎症反应情况。结果与C组比较, D1组T_(1)~T_(3)时及D2组T_(1)~T_(3)、T_(5)和T_(9)时热缩足潜伏期延长(P<0.05);与D1组比较, D2组T_(5)、T_(9)时热缩足潜伏期延长, T_(6)~T_(9)时血浆地佐辛浓度升高(P<0.05)。与T_(2)时比较, D1组T_(4)~T_(9)时血浆地佐辛浓度降低(P<0.05), D2组T_(3)~T_(9)时血浆地佐辛浓度差异无统计学意义(P>0.05)。肌肉注射后第7天, 各组局部组织均未见炎症产生, 病理学结果未见明显差异。结论本研究成功制备了地佐辛PLGA微球缓释剂型, 对大鼠可维持平稳的血药浓度, 有效延长药物作用时间, 具有显著缓释作用。Objective To prepare and preliminary verify dezocine polylactic acid-glycolic acid block copolymer(PLGA)microspheres.Methods Preparation of dezocine PLGA microspheres Dezocine 120 mg,PLGA 0.1 g and the solubilizing additive poloxamer 0.1 g were dispersed in tetrahydrofuran solvent to form an organic phase solution.Sodium chloride and polyethylene glycol were dissolved in water for injection to form an inner aqueous phase solution and an outer aqueous phase solution.After the organic phase solution 20 ml was mixed with the inner aqueous phase solution 20 ml to form a water/oil colostrum,the water/oil colostrum was added to the outer aqueous phase solution to form a water/oil/water multiple emulsion,which was fully mixed with lyophilized powder protective agent and freeze-dried to prepare dezocine PLGA microspheres.Verification Eighteen clean-grade healthy male Sprague-Dawley rats,aged 10-12 weeks,weighing 220-260 g,were divided into 3 groups(n=6 each)by a random number table method:control group(group C),dezocine ordinary preparation group(group D1)and dezocine PLGA microspheres group(group D2).Normal saline,dezocine injectio(dose 1 mg)and dezocine PLGA microsphere injectio(dose 0.2μg)0.2 ml were intramuscularly injected in C,D1 and D2 groups,respectively.The concentrations of dezocine in plasma were measured at 30 min and 1,2,3,4,5,6,7 and 8 h after administration,and thermal paw withdrawal latency was measured at T_(1)-T_(3),T_(5) and T_(9).Tissues from the injection site were obtained on day 7 after intramuscular injection,and the inflammatory response was observed after HE staining.Results Compared with group C,the thermal paw withdrawal latency was significantly prolonged at T_(1)-T_(3) in group D1 and at T_(1)-T_(3),T_(5) and T_(9) in group D2(P<0.05).Compared with group D1,the thermal paw withdrawal latency was significantly prolonged at T_(5) and T_(9),and the plasma concentrations of dezocine were increased at T_(6)-T_(9) in group D2(P<0.05).Compared with the values at T_(2),the plasma concentrations of

关 键 词：缓释制剂 聚乳酸-聚乙醇酸共聚物 地佐辛 

分 类 号：R943[医药卫生—药剂学]