Ophthalmic drug discovery

Millions of people suffer from a wide variety of ocular diseases, many of which lead to irreversible blindness. The leading causes of irreversible blindness in the elderly--age-related macular degeneration and glaucoma--will continue to effect more individuals as the worldwide population continues to age. Although there are therapies for treating glaucoma, as well as ongoing clinical trials of treatments for age-related macular degeneration, there still is a great need for more efficacious treatments that halt or even reverse ocular diseases. The eye has special attributes that allow local drug delivery and non-invasive clinical assessment of disease, but it is also a highly complex and unique organ, which makes understanding disease pathogenesis and ocular drug discovery challenging. As we learn more about the cellular mechanisms involved in age-related macular degeneration and glaucoma, potentially, new drug targets will emerge. This review provides insight into some of the new approaches to therapy.     

Ophthalmic drug delivery systems

New ophthalmic drug delivery systems are curently receiving increased attention, in part because of the expected emergence of new drugs with short biological half-lives whose usefulness may depend on a more continuous drug supply than eyedrops can provide, but also because of the potential of some delivery systems to reduce the side effects of the more potent drugs recently introduced or presently under investigation. Some ophthalmic delivery systems extend the duration of drug action by enhancement of corneal absorption; these systems include soluble gels and emulsions, hydrophilic ocular inserts, ion-pair associations, prodrugs, and liposomes. Since these systems enhance the “pulse entry” of the drug, they are limited to use with drugs whose dose-related side effects are not serious. Other delivery systems provide for a controlled release of drugs and therefore minimize the pulse entry with which side effects are associated. They can be based on any of several different mechanisms and include both erodible and nonerodible matrices. The various delivery systems that have recently been developed and those that are currently known to be under investigation are described in this paper, along with some observations regarding the future outlook of ophthalmic drug delivery systems.     

眼科抗感染类基本药物在2家眼科专科医院应用的调查分析

目的:为调整我国眼科抗感染类基本药物提供参考。方法:收集某市级眼科专科医院和某县级眼科专科医院2009年眼科抗感染类基本药物应用数据(包括药品名称、规格、剂型、单价、用量和销售金额),采用表格进行信息数据的统计处理。并通过中国知网查询1989-2011年国内期刊公开发表的眼科用药分析及常见的眼科抗感染药物不良反应的文献,对其进行分析。结果:本次调查中,我国《国家基本药物目录.基层医疗卫生机构配备使用部分》(2009年)中的氯霉素滴眼液和《世界卫生组织基本药物示范目录》(17版)中的四环素眼药膏和庆大霉素溶液均未使用;红霉素、左氧氟沙星和阿昔洛韦则都得到了广泛应用;妥布霉素及其复方制剂,则在金额和数量排序中居首位。文献资料显示,红霉素眼膏、左氧氟沙星、阿昔洛韦和妥布霉素不良反应的报道较少,氯霉素和庆大霉素在眼科用药中的不良反应报道较多,由于眼科疾病谱的变化,四环素近年来使用较少。结论:2009年版基本药物目录收录的红霉素眼膏、左氧氟沙星滴眼液和阿昔洛韦滴眼液符合我国基本药物目录的遴选原则;另外,本着"临床首选"的原则建议收录妥布霉素滴眼液。     

Ophthalmic light sensitive nanocarrier systems

The eye is afflicted by chronic vision debilitating neovascular disorders, such as age-related macular degeneration, proliferative diabetic retinopathy, and corneal angiogenesis. Photodynamic therapy (PDT) is an innovative, evolving approach for treating neovascular diseases of the eye. PDT refers to the process of activating a light sensitive agent or carrier with non-thermal light to induce chemical reactions that ameliorate a pathological condition. Key components of PDT include a photosensitizer, a colloidal carrier or formulation and a light source. This article summarizes currently available clinical PDTs, desirable features of PDTs and photosensitizers, useful light sources for PDT and investigational nanosystems, and colloidal carriers for PDT.     

眼部药物动力学研究中的取样技术

综述了眼外周、眼组织液和眼部组织三个部位的特点和常用的取样技术，介绍了各种取样技术的工具，具体部位和注意点。眼部药物动力学过程的考察是药物眼部作用研究的重要方面。眼部取样技术则是动力学研究中的关键。     

眼用冻干载体系统的研究进展

目的介绍眼部给药新剂型眼用冻干载体系统的最新进展。方法查阅近年来国内外相关文献，综述其特点、制备方法、质量标准等。结果与结论眼用冻干载体系统是应用前景广阔的一种眼部药物给药系统。     

眼部用药所致眼损伤

目的 :分析眼部用药所致眼损伤的发生与药物品种及给药方法的关系。方法 :查阅1960年～2000年国内公开发表的医药学期刊有关眼部用药所致眼损伤病例 ,并进行统计、分析。结果与结论 :眼部用药所致眼损伤除药物所致过敏反应外 ,还有错误用药、错误操作、眼科手术中及手术后用药不当等原因     

他克莫司眼用乳液的质量控制

目的建立他克莫司眼用乳液的质量控制方法。方法根据中国药典2005年版眼用制剂项下规定建立他克莫司眼用乳液的质量控制方法,用高效液相色谱法测定他克莫司的含量,观察家兔眼部刺激性,并对制剂的稳定性进行考察。结果他克莫司在6．25～200μg·m^-1浓度内线性关系良好（r=0．9999）,平均回收率为99．83％,RSD为0．59％,方法重现性的RSD为1．04％（n=6）。滴眼后无刺激性,而且稳定性相对较好。结论本方法专属性强、操作简便、结果准确,可用于他克莫司眼用乳液的质量控制。     

金牛眼药质量控制方法研究

摘 要 目的：建立金牛眼药中煅炉甘石和冰片含量测定的方法。方法: 采用乙二胺四乙酸配位滴定法测定炉甘石中氧化锌含量;采用DB WAX石英毛细管柱(30 m×0.32 mm,0.5 μm）,柱温：150℃,进样口温度：180℃,检测器温度：200℃,分流比：5∶〖KG-*2〗1,氮气流速:1 ml·min-1, FID检测器,乙酸乙酯为溶剂,测定冰片含量。结果:氧化锌加样回收率为101.5%,RSD为1.2%（n=9）,冰片在0.1～5.0 μg进样范围内线性关系良好,r=0.999 9;加样回收率为98.18%,RSD为0.8%（n=9）;样品含量测定结果氧化锌为0.38～0.59 g·g-1,冰片为0.13～0.21 g·g-1。结论:建立的方法简便、准确,重复性和稳定性良好,可用于金牛眼药的质量控制。     

新目安眼用凝胶剂等四种眼用制剂离体角膜渗透特性比较研究

摘 要 目的：探索更昔洛韦替代阿昔洛韦组成的新目安眼用凝胶剂离体角膜渗透性能是否优于原目安眼用凝胶剂及市售制剂。方法: HPLC法测定更昔洛韦及阿昔洛韦含量并以此为指标,采用Franz扩散池法,进行离体角膜渗透性实验,建立数学模型,通过数学及统计学处理提取角膜渗透特性参数,比较新目安眼用凝胶剂与目安眼用凝胶剂渗透速度及渗透总量的差异。结果: 新目安眼用凝胶剂角膜渗透特性优于目安眼用凝胶剂（角膜渗透速度是后者的3.452倍,角膜渗透数量是后者的1.832倍）,亦优于市售0.15%更昔洛韦眼用凝胶剂（角膜渗透速度是后者的2.029倍）,市售0.15%更昔洛韦眼用凝胶剂角膜渗透特性优于市售3%阿昔洛韦眼膏（角膜渗透数量是后者的2.028倍）。结论: 新目安眼用凝胶剂离体角膜渗透性能符合眼用制剂需求,更昔洛韦替代阿昔洛韦组成的新目安眼用凝胶剂离体角膜渗透性能优于目安眼用凝胶剂,给药次数及间隔时间基本科学、合理、可行,并为下一步药效、毒理、临床研究提供依据。     

眼用制剂中添加清凉剂的思考

目前在眼用制剂的申报资料中,有较多研制单位采用薄荷脑、冰片、樟脑等作为清凉剂,而文献显示此类物质除具有一定活性外,还具有促进药物透皮吸收的作用。眼用制剂作为直接用于眼部发挥治疗作用的药物制剂,在辅料选择方面应慎重。     

胰岛素经眼给药制剂的研究

实验研制了胰岛素滴眼剂。通过对缓冲液、增粘剂和吸收促进剂的筛选，确定了最佳处方组成：2％胰岛素、1％Brij－78、0．5％EDTA、1％玻璃酸钠的含0.03％对羟基苯甲酸乙酯的硼酸缓冲液。对兔眼试验证明该制剂无刺激性。药效学实验表明用其滴眼后吸收迅速，可显著降低糖尿病兔的血糖。血糖下降持续时间和最大降血糖均与给药剂量呈正相关。     

Ophthalmic preservatives: focus on polyquaternium-1

Introduction: Ophthalmic preservatives, such as polyquaternium-1 (PQ-1), are critical for the inhibition of growth of microbial contaminants in multi-dose bottles of topical medications. These antimicrobial agents must have a high efficacy against pathogenic organisms, while maintaining a favorable tolerability and safety profile.

Areas covered: This review focuses on the ophthalmic preservative PQ-1. For comparison purposes, the most commonly used preservative, benzalkonium chloride (BAK), is also discussed. This survey focuses primarily on data collected during the past 10 years.

Expert opinion: Effective drug delivery requires more than just an active ingredient that achieves its desired biological effect on end-target tissues. In addition, drugs must be stable in the containers that they are stored in, and must possess minimal undesired local and systemic side effects that can cause patients to decrease their adherence. In addressing these concerns, specifically in topical ophthalmic drops, one must take into account the active ingredients, vehicle components and preservatives. Medications with fewer adverse effects may lead to enhanced adherence to therapy; therefore, the induction of such adverse outcomes must be considered by physicians when treating patients with chronic ocular disease. Although BAK will continue to be used in ophthalmic medications, due to its familiarity and compatibility with a broad range of topical ocular formulations, PQ-1 is certainly a viable alternative in the preservative formulary armamentarium.