中华眼科杂志
中華眼科雜誌
중화안과잡지
Chinese Journal of Ophthalmology
2014年
7期
529-535
,共7页
兰碧菲%侯江平%赵春晖%孙树茂%李杰%程凌云
蘭碧菲%侯江平%趙春暉%孫樹茂%李傑%程凌雲
란벽비%후강평%조춘휘%손수무%리걸%정릉운
曲安奈德%毒理学%玻璃体内注射
麯安奈德%毒理學%玻璃體內註射
곡안내덕%독이학%파리체내주사
Triamcinolone acetonide%Toxicology%Intravitreal injection
目的 评价国产曲安奈德及醋酸曲安奈德混悬液眼部应用的安全性.方法 实验研究.通过体外将曲安奈德和醋酸曲安奈德混悬液的上清液稀释成不同比例后,用MTT比色法评价其上清液中的防腐剂和赋形剂对3种人眼细胞株的细胞毒性;选取28只健康豚鼠,根据计算机(SAS软件)生成的随机数字均分为4组,分别在豚鼠右眼的玻璃体腔注射曲安奈德或醋酸曲安奈德的上清液18μl和混悬液6μl.给药前后通过裂隙灯、间接检眼镜、眼压计、眼电生理检查及组织学石蜡切片来评价其玻璃体腔应用的安全性.体外细胞毒性研究采用Dunnett-t检验,眼电生理数据采用配对t检验,眼压数据比较采用重复测量统计方法广义估计方程.结果 未经稀释的曲安奈德和醋酸曲安奈德上清液对人眼后巩膜成纤维细胞的MTT值分别为0.046±0.036和0.044±0.05,与其各自的标准品上清液对照组(0.367±0.106和0.413±0.128)和BSS空白对照组(0.368±0.106和0.441±0.137)相比,差异均有统计学意义(P值均＜0.01).醋酸曲安奈德的上清液经1∶15或更高倍数的稀释后对人RPE细胞无细胞毒性(P＞0.05),但1∶15稀释的上清液对人Müller细胞有细胞毒性(MTT值为0.366±0.062,BSS对照组和上清液对照组的MTT值分别为0.417±0.042和0.399±0.045)(P=0.03);曲安奈德的上清液经1∶15或更高倍数的稀释对RPE及Müller细胞均未显示细胞毒性.豚鼠玻璃体腔注射这两种制剂的混悬液6μl(含药物0.25 mg,相当于人眼玻璃体腔注射0.1 ml含4 mg曲安奈德的混悬液)或上清液18μl(相当于兔眼玻璃体腔注射0.1 ml含4 mg曲安奈德混悬液中含有的防腐剂浓度)均未见眼内毒性.结论 豚鼠玻璃体腔注射6μl曲安奈德和醋酸曲安奈德混悬液均是安全的,该剂量相当于人眼玻璃体腔注射0.1 ml(含4 mg)曲安奈德混悬液.
目的 評價國產麯安奈德及醋痠麯安奈德混懸液眼部應用的安全性.方法 實驗研究.通過體外將麯安奈德和醋痠麯安奈德混懸液的上清液稀釋成不同比例後,用MTT比色法評價其上清液中的防腐劑和賦形劑對3種人眼細胞株的細胞毒性;選取28隻健康豚鼠,根據計算機(SAS軟件)生成的隨機數字均分為4組,分彆在豚鼠右眼的玻璃體腔註射麯安奈德或醋痠麯安奈德的上清液18μl和混懸液6μl.給藥前後通過裂隙燈、間接檢眼鏡、眼壓計、眼電生理檢查及組織學石蠟切片來評價其玻璃體腔應用的安全性.體外細胞毒性研究採用Dunnett-t檢驗,眼電生理數據採用配對t檢驗,眼壓數據比較採用重複測量統計方法廣義估計方程.結果 未經稀釋的麯安奈德和醋痠麯安奈德上清液對人眼後鞏膜成纖維細胞的MTT值分彆為0.046±0.036和0.044±0.05,與其各自的標準品上清液對照組(0.367±0.106和0.413±0.128)和BSS空白對照組(0.368±0.106和0.441±0.137)相比,差異均有統計學意義(P值均＜0.01).醋痠麯安奈德的上清液經1∶15或更高倍數的稀釋後對人RPE細胞無細胞毒性(P＞0.05),但1∶15稀釋的上清液對人Müller細胞有細胞毒性(MTT值為0.366±0.062,BSS對照組和上清液對照組的MTT值分彆為0.417±0.042和0.399±0.045)(P=0.03);麯安奈德的上清液經1∶15或更高倍數的稀釋對RPE及Müller細胞均未顯示細胞毒性.豚鼠玻璃體腔註射這兩種製劑的混懸液6μl(含藥物0.25 mg,相噹于人眼玻璃體腔註射0.1 ml含4 mg麯安奈德的混懸液)或上清液18μl(相噹于兔眼玻璃體腔註射0.1 ml含4 mg麯安奈德混懸液中含有的防腐劑濃度)均未見眼內毒性.結論 豚鼠玻璃體腔註射6μl麯安奈德和醋痠麯安奈德混懸液均是安全的,該劑量相噹于人眼玻璃體腔註射0.1 ml(含4 mg)麯安奈德混懸液.
목적 평개국산곡안내덕급작산곡안내덕혼현액안부응용적안전성.방법 실험연구.통과체외장곡안내덕화작산곡안내덕혼현액적상청액희석성불동비례후,용MTT비색법평개기상청액중적방부제화부형제대3충인안세포주적세포독성;선취28지건강돈서,근거계산궤(SAS연건)생성적수궤수자균분위4조,분별재돈서우안적파리체강주사곡안내덕혹작산곡안내덕적상청액18μl화혼현액6μl.급약전후통과렬극등、간접검안경、안압계、안전생리검사급조직학석사절편래평개기파리체강응용적안전성.체외세포독성연구채용Dunnett-t검험,안전생리수거채용배대t검험,안압수거비교채용중복측량통계방법엄의고계방정.결과 미경희석적곡안내덕화작산곡안내덕상청액대인안후공막성섬유세포적MTT치분별위0.046±0.036화0.044±0.05,여기각자적표준품상청액대조조(0.367±0.106화0.413±0.128)화BSS공백대조조(0.368±0.106화0.441±0.137)상비,차이균유통계학의의(P치균＜0.01).작산곡안내덕적상청액경1∶15혹경고배수적희석후대인RPE세포무세포독성(P＞0.05),단1∶15희석적상청액대인Müller세포유세포독성(MTT치위0.366±0.062,BSS대조조화상청액대조조적MTT치분별위0.417±0.042화0.399±0.045)(P=0.03);곡안내덕적상청액경1∶15혹경고배수적희석대RPE급Müller세포균미현시세포독성.돈서파리체강주사저량충제제적혼현액6μl(함약물0.25 mg,상당우인안파리체강주사0.1 ml함4 mg곡안내덕적혼현액)혹상청액18μl(상당우토안파리체강주사0.1 ml함4 mg곡안내덕혼현액중함유적방부제농도)균미견안내독성.결론 돈서파리체강주사6μl곡안내덕화작산곡안내덕혼현액균시안전적,해제량상당우인안파리체강주사0.1 ml(함4 mg)곡안내덕혼현액.
Objective To characterize the safety profile of triamcinolone acetonide made in China (Transton) and triamcinolone acetonide acetate (Tongyong) for their ocular application.Methods Experimental study.In vitro cell viability assay was performed on 3 types of human ocular cells to evaluate the cytotoxicity of the simulated vitreal concentrations (from a 1 ∶ 15 dilution as if injected into 1.5 ml of rabbit vitreous to 1∶50 dilution as if injected into 5 ml of human vitreous) of Transton and Tongyong using MTT method.In vivo 28 guinea pigs,randomly divided into four groups,were used for evaluating either intravitreal 6 μl of the two types of triamcinolone suspension or 18 μ1 of their supernatant.Following the injections,the eyes were monitored by biomicroscopy,ophthalmoscopy,tonometry,electroretinography,and histology.The Dunnett's test was used to analyze in vitro cell viability.Paired sample t-test and Generalized Estimating Equations (GEE) were respectively used to compare electroretinography data and intraocular pressure between experimental eyes and the control eyes.Results The undiluted supernatant of Transton and Tongyong was toxic to human scleral fibroblasts when compared with their control groups(MTT values =0.046 ±0.036 and 0.044 ±0.05 versus 0.367 ± 0.106 and 0.413 ± 0.128) (P ＜ 0.01) or with the BSS group (0.368 ±0.106 and 0.441 ±0.137) (P ＜0.01).1∶15 or greater dilution of supernatant of Transton and Tongyong did not show cytotoxicity on cultured human retinal pigment epithelium cells or Müller cell (P ＞ 0.05),but 1∶15 dilution of Tongyong supematant showed cytotoxicity on the Müller cells (MTT value =0.366 ± 0.062 versus 0.417 ± 0.042 for BSS) (P =0.03).In vivo,neither intravitreal 6 μl (0.25 mg,equivalent to 4 mg in 0.1 ml for human eyes) of the suspension nor 18 μl(equivalent resultant preservative concentration to intravitreal 4 mg in 0.1 ml for rabbit eyes) of the supernatant of Transton and Tongyong showed ocular toxicity.Conclusion The equivalent dose (6 μl) to 4 mg in 0.1 ml intravitreal suspension for human eye or equivalent resultant preservative concentration to 0.1 ml intravitreal suspension for rabbit eye is found safe in guinea pig eyes.
