眼表铁过载小鼠干眼模型的构建和机制研究

目的：通过给小鼠腹腔注射右旋糖酐铁，建立小鼠铁过载干眼模型并初步探索其可能的机制。

方法：将40只雄性C57BL/6小鼠(取右眼为实验眼)用随机数字表法将小鼠分为4组：对照组10只，每次腹腔注射生理盐水0.2mL； 低剂量组、中剂量组、高剂量组各10只为模型组，每次分别腹腔注射浓度为12.5、25、50mg/mL的右旋糖酐铁溶液0.2mL。每3d注射1次，共注射28d。注药后第7、14、28d观察各组小鼠眼表炎症指数、角膜荧光素染色、泪膜破裂时间(BUT)及泪液分泌量(SⅠt)，评估干眼及眼表炎症程度。28d后处死小鼠，取角膜、结膜及泪腺组织，进行HE染色、普鲁士蓝染色以及组织铁检测，评估小鼠炎症反应及铁过载情况； 采用酶联免疫吸附试验(ELISA)检测炎症因子白细胞介素-1β(IL-1β)、肿瘤坏死因子-α(TNF-α)、基质金属蛋白酶-9(MMP-9)的表达情况。

结果：与对照组相比，模型组小鼠出现一系列干眼症状，小鼠眼表炎症指数增高，角膜荧光素染色评分增加，BUT缩短，泪液分泌量减少(均P<0.05)； 模型组小鼠角膜、结膜及泪腺组织均受到不同程度的损伤，各组织眼表铁沉积情况较对照组加重，组织铁含量明显增加(均P<0.01)； 模型组小鼠角膜、结膜及泪腺组织中炎症因子(IL-1β、TNF-α、MMP-9)的含量均高于对照组(均P<0.01)，随着右旋糖酐铁注药时间及浓度增加，小鼠干眼及眼表炎症程度逐渐加重。

结论：腹腔注射右旋糖酐铁可成功建立小鼠铁过载干眼模型，其机制可能与铁过载加重眼表炎症反应有关。     

Microemulsion-based delivery of triamcinolone acetonide to posterior segment of eye using chitosan and butter oil as permeation enhancer: an in vitro and in vivo investigation

The aim of the study was to formulate a microemulsion (ME) using chitosan (CH) and the butter oil (BO) as a permeation enhancer for targeting drug to the posterior segment of the eye, via topical route. Triamcinolone acetonide (TA) was selected as the model drug since it undergoes extensive first-pass metabolism, leading to poor oral bioavailability of 23%. For optimisation of BO concentration, different ratios of TA:BO were prepared by simple physical mixing in the ratio of 1:9 to 9:1 and diffusion study was performed. MEs containing TA, TA:BO and TA CH ME were formulated by water titration method. Globule sizes of TA ME, TA:BO ME and TA CH ME were found to be 66.06?±?0.32?nm, 78.52?±?1.50?nm and 97.30?±?2.50?nm, respectively. In ex vivo diffusion studies using goats eye, TA:BO ME (31.33?±?0.46 and 33.98?±?0.23) and TA CH ME (24.10?±?0.41 and 27.00?±?0.18) showed higher percentage of drug diffusion in comparison to TA ME (13.29?±?0.41and 15.56?±?0.34) and TA solution (8.20?±?1.04 and 10.39?±?0.22) in presence and in absence of vitreous humour. Fluorescence intensity of coumarin-6 (as a marker) loaded ME with BO and CH was found to be higher, confirming their role in altering membrane permeability and facilitating coumarin-6 diffusion to the posterior chamber. Overall, it was concluded that BO enhances the bioavailability of TA across the retina, thereby proving its potential as permeation enhancer in facilitating drug delivery to the posterior segment of the eye.     

BioOcularTM角膜上皮模型EIT法评价眼用制剂包装材料的眼刺激性研究

目的：用BioOcularTM 角膜上皮模型EIT法评价眼用制剂包装材料的眼刺激性。方法：采用BioOcularTM 角膜上皮模型EIT法对6批眼用制剂包装材料的眼刺激性进行检测,并与Draize试验所得的结果相比较。结果：Draize法和BioOcularTM 角膜上皮模型EIT法所得眼刺激性结果均为无刺激性,与Draize法比较,BioOcularTM 角膜上皮模型EIT法与体内试验的分类一致性为100%(6/6)。 结论：三维重组角膜上皮模型 EIT法有潜力作为眼用制剂包装材料眼刺激性试验的替代方法。     

盐酸溴己新吸入粉雾剂的质量与稳定性考察

摘 要 目的：评价自制的盐酸溴己新吸入粉雾剂的质量并考察其稳定性。方法: 采用冷冻干燥 气流粉碎法制备盐酸溴己新吸入粉雾剂,考察其吸湿性及临界相对湿度;测定其粒径和水分并观察粉末形态;检查其细微粒子剂量和递送剂量均一性;开展盐酸溴己新吸入粉雾剂稳定性考察。结果:所制备的盐酸溴己新吸入粉雾剂的临界相对湿度为65%,空气动力学粒径<5 μm,粉末含水量<2%,细微粒子剂量＞30%,递送剂量均一性符合药典要求;稳定性试验中各指标在观察期内无明显变化。结论:所制备的盐酸溴己新吸入粉雾剂适合肺部吸入给药,且具有较好的稳定性。     

星点设计-效应面法优化盐酸溴己新吸入粉雾剂的处方

摘 要 目的：优化盐酸溴己新吸入粉雾剂的处方。方法: 采用冷冻干燥 气流粉碎法制备盐酸溴己新吸入粉雾剂,通过星点设计考察甘露醇（X1）,亮氨酸（X2）和泊洛沙姆188（X3）在辅料中的用量对盐酸溴己新吸入粉雾剂的休止角（Y1）、细微粒子剂量（Y2）和空气动力学粒径（Y3）的影响。根据最佳数学模型绘制效应面,通过重叠等高线图确定最优处方。结果:影响因素和考察指标之间存在定量关系,优化处方为甘露醇：亮氨酸：泊洛沙姆188在处方中的比例为2.4∶〖KG-*2〗2.22∶〖KG-*2〗0.05。较优处方的各指标实测值与预测值较接近。结论:采用星点设计 效应面法完成了盐酸溴己新吸入粉雾剂的多目标同步优化。     

环孢霉素滴眼液联合人工泪液治疗角结膜干燥症患者的临床研究

目的观察环孢霉素滴眼液联合人工泪液治疗角结膜干燥症患者的临床研究及对泪液乳铁蛋白的影响。方法将80例角结膜干燥症患者随机分为对照组和试验组,每组40例。对照组给予聚乙烯醇滴眼液治疗,tid,每次1滴。试验组在对照组的基础上,用环孢霉素滴眼液治疗,tid,每次1滴。2组均持续治疗8周。比较2组患者的乳铁蛋白、泪液分泌试验(SIT)、泪膜破裂时间(BUT)、角膜荧光素染色(FS)评分及药物不良反应发生情况。结果治疗后,试验组和对照组乳铁蛋白分别为(1.72±0.22)和(1.57±0.18)g·L^-1,SIT分别为(13.60±1.90)mm/5 min和(11.65±1.18)mm/5 min,BUT分别为(8.86±1.22)和(7.59±1.11)s,FS评分分别为(0.87±0.10)和(1.43±0.21)分,差异均有统计学意义(均P<0.05)。试验组出现结膜轻度充血3例,眼部刺激2例,药物不良反应发生率为12.50%(5例/40例);对照组出现短暂性视力模糊3例,药物不良反应发生率为7.50%(3例/40例),差异无统计学意义(P>0.05)。结论环孢霉素滴眼液联合人工泪液治疗角结膜干燥症的效果较好,能够增加泪液乳铁蛋白水平,改善泪液环境。     

建立HPLC法测定盐酸洛美沙星滴眼液中5种抑菌剂

目的 建立同时测定盐酸洛美沙星滴眼液中5种抑菌剂(羟苯甲酯、羟苯乙酯、硫柳汞、苯扎溴铵和苯扎氯铵)的HPLC方法。方法 采用Extend C18(4.6mm×250mm, 5μm)色谱柱,流动相为1%三乙胺溶液(磷酸调pH值至3.0)-甲醇,梯度洗脱,流速为1.0mL/min,柱温35℃,检测波长为262nm。结果 羟苯甲酯、羟苯乙酯、硫柳汞、苯扎溴铵/苯扎氯铵各峰均分离良好;羟苯甲酯在0.0410~0.8204mg/mL范围内线性关系良好(r=1.0000),平均回收率为100.2%(RSD=0.8%, n=9);羟苯乙酯在0.0400~0.7996mg/mL范围内线性关系良好(r=1.0000),平均回收率为100.3%(RSD=0.7%, n=9);硫柳汞在0.0806~1.6112mg/mL范围内线性关系良好(r=0.9995),平均回收率为100.8%(RSD=0.9%, n=9);苯扎溴铵在0.0204~0.4076mg/mL范围内线性关系良好(r=0.9998),平均回收率为100.0%(RSD=0.9%, n=9);苯扎氯铵0.0197~0.3932mg/mL范围内线性关系良好(r=1.0000),平均回收率为100.4%(RSD=1.0%, n=9)。结论 该方法准确、灵敏、简便,可用于盐酸洛美沙星滴眼液中羟苯甲酯、羟苯乙酯、硫柳汞、苯扎溴铵及苯扎氯铵5种抑菌剂的检查。     

国产盐酸洛美沙星滴眼液的质量评价#br#

目的 评价国内不同厂家生产的盐酸洛美沙星滴眼液的质量现状及存在问题。方法 按照国家评价性抽验计划总体要求,采用法定检验方法结合探索性研究进行样品检验,统计分析检验结果。结果 共抽取样品153批次,按国家标准检验不合格率0.7%。探索性研究建立了有关物质检查方法,对光降解杂质的来源与结构进行了确证;考察了盐酸洛美沙星滴眼液处方合理性,发现多家企业处方不合理。结论 目前国内盐酸洛美沙星滴眼液总体质量一般;现行标准有待统一和提高;建议企业优化处方,加强内包装材料遮光性。     

Loteprednol etabonate for inflammatory conditions of the anterior segment of the eye: twenty years of clinical experience with a retrometabolically designed corticosteroid

Introduction: Topical corticosteroids are an important pharmacotherapy for the management of various inflammatory conditions affecting the anterior segment of the eye. However, medications in this class are associated with well-known risks including increased intraocular pressure (IOP) and development of cataracts. The topical corticosteroid loteprednol etabonate (LE) was developed with the specific intention of minimizing these side effects.

Areas covered: The focus of this review is to examine published efficacy and safety data for LE, a drug engineered to undergo rapid metabolism to inactive metabolites with the goal of improved safety. Two decades of clinical research focused on LE formulations are reviewed, including the use of LE in combination with tobramycin. The cumulative body of experience affirms the concept that the molecular design of LE confers certain safety benefits without compromising the desired anti-inflammatory efficacy of a topical corticosteroid.

Expert opinion: Loteprednol etabonate is a mainstay for topical therapy of a wide variety of commonplace and niche conditions of the ocular surface and the anterior segment, including in the healing post-operative patient. Its versatility and safety allow eye care providers to recommend both acute induction as well as chronic maintenance therapy with appropriate follow-up.     

N-hydroxymethylglycinate with EDTA is an efficient eye drop preservative with very low toxicity: an in vitro comparative study

Purpose: Preservatives are used in multi-dose ophthalmic topical medications in order to prevent contamination by bacteria and fungi. However, prolonged use of preserved eye drops, as it may happen in dry eye or glaucoma, may damage cells of the ocular surface. Therefore, an important goal is to find preservatives with low toxicity which are mild to host cells, still able to prevent drug contamination so to maintain their sterility and efficacy. Hence, aim of this study has been to compare the relative toxicity on a rabbit corneal cell line of a new preservative, made by the association of N-hydroxy-methyl-glycinate (NIG) with disodium-ethylene diamine tetra-acetate (EDTA), with other known and widely used eye-drops preservatives.

Materials and methods: Rabbit corneal cells (SIRC) were tested either in 96-well plates or in suspension culture. Treatments with preservatives (used at known bacteriostatic concentrations) included: benzalkonium chloride (BAK), polyquaternium-1 (PQ-1), sodium perborate (SP: NaBO_{3 *} H₂O), and NIG?±?EDTA at different concentrations (0.001% and 0.002%), and different treatment times (from 30?minutes to 120?hours). At the end of treatment, cell survival was evaluated by a specific spectrophotometric method through the metabolic conversion of MTT [3-(4,5-dimethylthiazol-2-yl) 2, 5-diphenyltetrazolium bromide] into formazan crystals.

Results: Almost no cell toxicity was evident for NIG and SP at either concentration (0.001% or 0.002%), while a low toxicity was observed for PQ-1 (62% at the highest dose at 120?hours). BAK, as expected, showed the highest toxicity (60–80% at 30?minutes, and over 90% from eight hours onward). EDTA 0.1% alone or in combination with NIG 0.002%, showed no toxicity at 24?hours, and even resulted in cell growth promotion (46% and 38%, respectively), after 48?hours of treatment.

Conclusions: These data show that the new preservative NIG/EDTA, at doses known to have effective antimicrobial properties, has a very low toxicity on corneal cells, and so it can be safely used in multi-dose eye drops.