在奎宁存在下四碘荧光素与新洁而灭缔合反应的研究

研究了在奎宁存在下四碘荧光素与新洁而灭的缔合反应。在pH 7.9～8.6范围内新浩而灭与四碘荧光素、奎宁形成稳定的三元离子缔合物(λ_max545 nm)。用1,2-二氯乙烷萃取时e=5.8×10⁴ 1·mol^-1·cm^-1。测出缔合物组成为1∶1∶1。研究了测定微量新浩而灭的条件和方法。2×10^-7～4×10^-6M新洁而灭符合Lambert-Beer定律,多数胺与生物碱不干扰测定。比较了在奎宁存在下17种酸性染料与新洁而灭的萃取—分光光度体系,确定荧光素类显色剂的效果优于类似结构的磺酞类显色剂。     

Thymosin beta4 inhibits benzalkonium chloride-mediated apoptosis in corneal and conjunctival epithelial cells in vitro

Thymosin beta-4 (Tβ₄) is known to promote ocular wound healing, to decrease ocular inflammation, and to have anti-apoptotic effects on corneal epithelium. In this study, the effect of Tβ₄ on the survival of human ocular surface epithelial cells exposed to benzalkonium chloride (BAK) was measured. Human conjunctival epithelial cells (HC0597) or human corneal epithelial cells (HCET) were treated with 0%, 0.001%, 0.01%, or 0.1% BAK for 15 min. After 3 or 24 h of recovery in culture medium containing 1 μg/ml Tβ₄, a dosage that has been demonstrated effective in several published studies, DNA synthesis was measured using a colorimetric BrdU incorporation assay. Both conjunctival and corneal epithelial DNA synthesis was inhibited by BAK in a dose-dependent manner. Tβ₄ did not protect the epithelial cells from BAK-induced inhibition of proliferation. To assess the ability of Tβ₄ to prevent apoptosis, epithelial cells were treated with 0.01% BAK + Tβ₄ and cell death was measured using a colorimetric assay. BAK-induced apoptosis increased throughout the duration of the assay, which was carried out to 5 days in culture. Treatment of HC0597 cells with Tβ₄ significantly inhibited the apoptosis shown to be initiated by BAK. Treatment of non-transformed human corneal epithelial cells (HCEC) with Tβ₄ also significantly inhibited the apoptosis shown to be initiated by BAK at later times in culture. Ocular solutions containing BAK as a preservative are typically used for extended periods of time. This study suggests that Tβ₄ may be able to overcome the apoptotic side effect of BAK, and may be a useful additive to solutions containing this preservative.     

Effects of SofZia‐preserved travoprost and benzalkonium chloride‐preserved latanoprost on the ocular surface – a multicentre randomized single‐masked study

Purpose: To assess the effect of SofZia‐preserved travoprost on ocular surface conditions in comparison with benzalkonium chloride (BAK)‐preserved latanoprost. Methods: A prospective randomized multicentre single‐masked comparative study. Patients with open‐angle glaucoma or ocular hypertension who had been treated with BAK‐preserved latanoprost 0.005% (Xalatan^®) monotherapy for at least 3 months. Patients were enrolled at 23 facilities. Patients were randomly divided into the X‐X group, continuous use of Xalatan^®, or the X‐T group, switching from Xalatan^® to SofZia‐preserved travoprost 0.004% (TravatanZ^®), and followed for 3 months. The superficial punctate keratopathy (SPK), conjunctival epitheliopathy, hyperaemia, tear break‐up time (TBUT) and intraocular pressure (IOP) were examined for each patient in a masked manner. Changes in the frequency of keratoconjunctival epitheliopathy were evaluated 3 months after study initiation. Intra‐ and intergroup comparisons of changes in SPK, conjunctival epitheliopathy, hyperaemia, TBUT and IOP were also carried out. Results: Two hundred twenty patients participated and 215 completed the 3‐month study. The frequency of keratoconjunctival epitheliopathy significantly decreased in the X‐T group (p = 0.036) and the intergroup difference was also significant (p = 0.001). SPK scores and TBUT were significantly improved in the X‐T group (p = 0.034, 0.049), also with significant intergroup differences in the cornea excluding the inferior area and TBUT. There were no significant intergroup differences in changes of the hyperaemia scores and the IOP reduction. Conclusion: Switching to SofZia‐preserved travoprost after BAK‐preserved latanoprost resulted in a lower incidence of keratoconjunctival epitheliopathy, especially in the cornea, with no clinically relevant changes in hyperaemia and IOP.     

HPLC法测定氟康唑滴眼液中苯扎溴铵的含量

目的建立HPLC法测定氟康唑滴眼液中苯扎溴铵的含量。方法色谱柱为C18（150 mm×4.6 mm,5μm）;流动相：0.015 mol.L-1辛烷磺酸钠及0.02 mol.L-1乙酸钠溶液（含0.05%三乙胺,用冰乙酸调节pH值至4.0±0.2）-甲醇-乙腈（25：15：60）;流速：1.0 m l.m in-1;检测波长：262 nm;进样量20μl。结果苯扎溴铵在17.98~359.6 mg.L-1浓度范围线性关系良好（r=0.9997）,最小检出量约为1.0 ng,平均回收率为100.45%,RSD为0.94%。结论本法简便,快速,准确,灵敏度高,重复性好,可用于氟康唑滴眼液中苯扎溴铵的含量测定。     

Benzalkonium chloride interferes with energy production,secretion and morphology in human blood platelets

Benzalkonium chloride (BC) is a bactericidal compound used as a topical antiseptic and as a preservative in various products for local treatment, e.g., eye and nose drops. BC is toxic to human cells, including those of the respiratory mucosa. Few studies have, however, focused on what cellular functions BC interferes with. The effects of BC were studied on washed human blood platelets in vitro. Cellular energy production as well as secretion were studied. Incubation of platelets with BC resulted in rapid swelling and toxic morphological changes. After incubation with BC oxidation of [1-¹⁴C] palmitate was inhibited, and both lactate dehydrogenase and endogenous serotonin were spontaneously released. Thrombin-induced secretion of serotonin was strongly reduced after BC exposure. Histological changes with increased size, spherical form, decreased numbers of pseudopodia, loss of an intact continuous tubulus system and reduced number of granules were found by scanning and transmission electron microscopy. It is concluded that the toxic effects of BC are because of interference with membrane function and energy production.     

Overview of the BAK-free travoprost/timolol BAK-free fixed combination

Introduction: Glaucoma is the second leading cause of blindness globally, representing a significant public health concern. More than 60 million people are affected by glaucoma worldwide; as this population ages, the number is expected to increase. Glaucoma is a collection of heterogeneous diseases sharing common clinical characteristics. The goal of treatment is to prevent significant visual dysfunction through reduction of intraocular pressure (IOP).

Areas covered: This is a review of the current literature about combination therapeutic regimens for the reduction of IOP, focusing on the risk : benefit profile of a fixed-combination therapy using travoprost and timolol.

Expert opinion: Since the debut of prostaglandin analogues in the 1990s, only modest innovation has occurred in glaucoma pharmacology. A growing body of research has established that the preservative benzalkonium chloride (BAK) might not be the benign contributor expected of excipient ingredients. Thus, BAK-free treatments were developed, with the goal of IOP reduction without furthering ocular surface disease symptoms. The BAK-free travoprost/timolol combination represents an important addition to glaucoma medication options and may fill an unmet need in this therapeutic arena.     

The effects of topical nasal steroids on rat respiratory mucosa in vivo, with special reference to benzalkonium chloride

Fifty rats were treated with topical nasal steroids with and without the preservative benzalkonium chloride in their right nostril twice daily for 21 days, while the left nostrils were exposed to 0.9% NaCl. By cutting the noses serially in frontal sections, the structure of the mucosal lining of all parts of the nose could be investigated. Areas with squamous cell metaplasia were observed in all nostrils exposed to topical steroids containing benzalkonium chloride. Such alterations were not observed in any nasal cavities exposed to the topical nasal steroid without the preservative or to 0.9% NaCl. In conclusion, benzalkonium chloride appears to be potentially toxic to the mucosa in vivo.     

Benzalkonium Chloride: A Bronchoconstricting Preservative in Continuous Albuterol Nebulizer Solutions

For convenience, many pediatric hospitals are preparing solutions for continuous nebulized albuterol using the 0.5% 20‐ml multidose albuterol dropper bottle. This product contains benzalkonium chloride (BAC) that, by itself, produces bronchospasm that is dose dependent and cumulative. The bronchoconstrictive effects of BAC are greater in patients with more severe airway obstruction and increased airway responsiveness. Use of BAC‐containing albuterol during severe acute asthma exacerbations may antagonize the bronchodilator response to albuterol, prolong treatment, and increase the risk of albuterol‐related systemic adverse effects. Such a deleterious effect of BAC is difficult to detect because some patients improve slowly or may even worsen during treatment. We recommend that only preservative‐free albuterol products be used.     

不含苯扎氯铵的抗青光眼滴眼液疗效及安全性的Meta分析

目的通过荟萃分析评价不含苯扎氯铵(BAK)的滴眼液治疗青光眼和高眼压症的有效性及安全性。设计荟萃分析。研究对象Medline(1966-2011年)、EMbase(1966-2010年)、Cochrane图书馆(2010年)及中国生物医学文献数据库CBM(1979-2010年)有关含与不含BAK的滴眼液治疗青光眼和高眼压症的临床对照研究文献资料。方法采用Cochrane系统评价的方法检索文献,按照纳入和排除标准限定研究对象,通过Jadad评分量表进行文献质量评估后,使用Cochrane协作网提供的RevMan 4.2统计软件进行Meta分析,以获得两者治疗青光眼和高眼压症的疗效及安全性是否有差异的相关证据。主要指标眼压,药物不良反应。结果纳入含与不含BAK的滴眼液治疗青光眼和高眼压症的临床对照研究6项(2313眼)。Meta分析结果显示,两类滴眼液均能有效降低眼压,两类滴眼液的降眼压幅度差异为0.08 mm Hg(95%CI,-0.10~0.27)(P=0.38)。随访期内发生相对较多的三种药物不良反应为结膜充血(10.98%)、过敏性结膜炎(4.84%)和干眼(3.11%)。采用固定效应模型进行Mete分析,用两类滴眼液者发生结膜充血、过敏性结膜炎和眼干的合并比值比分别为1.37(95%CI,1.05~1.80)、2.1(95%CI,1.26~3.48)和1.69(95%CI,1.13~2.53)(P<0.05)。结论不含BAK的滴眼液降眼压效果与含有BAK的滴眼液的差异无统计学意义且安全性更高,但尚需更多高质量的前瞻性临床对照研究进一步证实。     

胶原润眼液对新洁尔灭所致兔干眼症的治疗

目的评价胶原润眼液对防腐剂新洁尔灭所致兔干眼症的治疗效果。方法通过摘除兔眼泪腺,使用新洁尔灭制备干眼模型并应用胶原润眼液对其进行治疗。SchirmerI试验检测泪液分泌情况,并行虎红角膜染色、眼睑组织病理检查。结果与模型组相比,治疗组兔眼充血、水肿等术后症状较轻;虎红着色评分值第10天、第14天模型组均高于治疗组:模型组分别为(5.5±2.5)分、(5.9±1.8)分,治疗组分别为(2.6±1.5)分、(2.3±1.8)分,差异均有统计学意义(P<0.05,P<0.01);治疗组给予胶原润眼液后第5天、第10天、第14天,模型组与治疗组SchirmerI试验滤纸湿长值差异均无统计学意义(均为P>0.05);治疗组较模型组兔眼角膜上皮细胞层次增多,内皮层细胞空泡变性减少;眼睑内皮下血管扩张充血程度和腺体增生程度均较轻。结论胶原润眼液对防腐剂新洁尔灭所致的兔干眼症具有一定的缓解和治疗作用。