联合应用抗菌药与非甾体类抗炎药在白内障超声乳化吸除术后的临床观察

目的观察在白内障术后联合应用抗生素滴眼液与非甾体类抗炎药滴眼液,探讨在白内障超乳术后联合应用抗生素滴眼液与非甾体类抗炎药的安全性与有效性。方法随机选择无并发症的白内障患者180例(180只眼),随机分为3组,每组60只眼,施行白内障超声乳化吸除联合人工晶体植入术。A组:术后单独使用妥布霉素地塞米松滴眼液;B组:术后联合使用妥布霉素地塞米松滴眼液与普拉洛芬滴眼液;C组:术后联合使用加替沙星滴眼液与普拉洛芬滴眼液。分别于术后第3天,7天和14天测量眼压。各指标均采用均数±标准差(χ—±s)表示,组间均数比较采用单因素方差分析,组间的多重比较采用q检验法,以P<0.05有统计学意义。结果术后A组与B组眼压测定值均较C组明显增高(P<0.01),B组眼压测定值较A组降低(P<0.05)。结论加替沙星滴眼液与普拉洛芬滴眼液联合使用具有安全性高的特点,可用于白内障超声乳化术后的患者。     

Novel modes of antifungal drug administration

Administration of antifungals by routes other than that for which the agent was designed or approved have been utilised in attempts to provide directed therapy, reduce adverse effects and improve drug penetration into selected infection sites, such as the central nervous system, lungs and peritoneum. The most widely investigated agent utilising a novel method of drug delivery is amphotericin B. Dose forms for this agent include topicals (aerosol, nasal spray, irrigations, pastes, absorbable sponges, impregnated bone cement and gelatin), oral dosage forms (solutions, suspensions, tablets and so on) and ophthalmic preparations (drops, ointments and injections). Amphotericin B has been administered by routes such as oral, endobronchial, intrathecal, intracisternal, intra-articular, intraperitoneal, ophthalmic and as an antibiotic ‘line lock’. Nystatin has been administered as an aerosol, percutaneous paste and bladder washes. Azoles, such as miconazole, fluconazole, ketoconazole and posaconazole, have been administered by novel methods but to a lesser degree. Most of these reports involve miconazole. The dose forms and routes of administration for azoles have included irrigants (bladder, joint), ophthalmic preparations (eye drops, intraocular injections, ointments), impregnated bone cement, endobronchial and intrathecal administration. Finally, both methylene blue (bladder washes) and flucytosine (peritoneal lavage, ophthalmic eye drops) have also been employed. Adequate evaluations of both the safety and efficacy of these therapies are most often hindered by prior or concomitant antifungal therapies, comorbidities and the lack of controlled clinical trials. In addition, the availability of newer treatment options, which demonstrate significant improvement in drug distribution and treatment-related adverse effects make many such novel modes of administration less practical or necessary. In contrast, the inhalation of antifungal aerosols, such as amphotericin B, is rapidly becoming a viable prophylactic option.     

Novel modes of antifungal drug administration

Administration of antifungals by routes other than that for which the agent was designed or approved have been utilised in attempts to provide directed therapy, reduce adverse effects and improve drug penetration into selected infection sites, such as the central nervous system, lungs and peritoneum. The most widely investigated agent utilising a novel method of drug delivery is amphotericin B. Dose forms for this agent include topicals (aerosol, nasal spray, irrigations, pastes, absorbable sponges, impregnated bone cement and gelatin), oral dosage forms (solutions, suspensions, tablets and so on) and ophthalmic preparations (drops, ointments and injections). Amphotericin B has been administered by routes such as oral, endobronchial, intrathecal, intracisternal, intra-articular, intraperitoneal, ophthalmic and as an antibiotic 'line lock'. Nystatin has been administered as an aerosol, percutaneous paste and bladder washes. Azoles, such as miconazole, fluconazole, ketoconazole and posaconazole, have been administered by novel methods but to a lesser degree. Most of these reports involve miconazole. The dose forms and routes of administration for azoles have included irrigants (bladder, joint), ophthalmic preparations (eye drops, intraocular injections, ointments), impregnated bone cement, endobronchial and intrathecal administration. Finally, both methylene blue (bladder washes) and flucytosine (peritoneal lavage, ophthalmic eye drops) have also been employed. Adequate evaluations of both the safety and efficacy of these therapies are most often hindered by prior or concomitant antifungal therapies, comorbidities and the lack of controlled clinical trials. In addition, the availability of newer treatment options, which demonstrate significant improvement in drug distribution and treatment-related adverse effects make many such novel modes of administration less practical or necessary. In contrast, the inhalation of antifungal aerosols, such as amphotericin B, is rapidly becoming a viable prophylactic option.     

滴眼液使用方法与贮藏条件调查分析

目的：对汕头大学·香港中文大学联合汕头国际眼科中心（以下简称“我院”）经营的滴眼液说明书上标注的内容进行汇总、分析,为医护人员和患者正确、合理使用和贮藏滴眼液以及滴眼液生产企业改进说明书提供参考。方法：调查2014年1—6月我院经营的67份滴眼液说明书,对药品用法用量、不良反应、注意事项、药物过量、贮藏、有效期等项目内容进行汇总和分析。结果：调查的67份滴眼液说明书中,国产滴眼液35份,进口滴眼液32份。各滴眼液说明书在用量用法、注意事项、药物过量、贮藏项目中不同程度地标注用药前检查包装及药品性状、清洁双手、滴眼体位、剂量、方法、过量和长期使用的不良反应、贮藏环境、开封和未开封滴眼液使用和保存时限等信息及相关注意事项,普遍缺少直观的图示用以指导用药方法或滴眼部位。结论：不同品牌、种类的滴眼液使用剂量、间隔、方法和贮藏条件、期限有较大不同,滴眼液开封后使用、贮藏时限远低于未开封条件下的有效期。     

非甾体抗炎滴眼液的不良反应观察

目的探讨非甾体抗炎滴眼液对眼表的不良反应,以指导临床使用。方法将100例（100只眼）白内障超声乳化术后的患者随机分成2组,术后A组给予典必殊眼液4周,B组给予典必殊眼液1周,普拉洛芬眼液3周,均为每日4次。术后每周对随访患者进行观察。根据不良反应判别为无副作用、轻度、中度、重度、极重度。结果术后4周时A组仅有3例出现轻度不良反应;B组有11例出现轻度、有1例出现中度、有2例出现严重不良反应。有1例没有到我院随访,且每日使用6次,连续使用3周后出现极严重不良反应。结论白内障术后使用非甾体抗炎滴眼液对眼表的不良反应大,希望能引起临床医生的重视。     

早产儿用复方托吡卡胺眼水散瞳的研究

目的研究复方托吡卡胺眼水在不同胎龄早产儿散瞳效果,加强其在早产儿眼底病筛查的管理。方法在低胎龄和高胎龄早产儿的左右眼分别滴用2次和3次复方托吡卡胺眼水。按距双眼第一次点眼散瞳时间长短将其随机平均分成A、B、C三组。A组距双眼第一次点眼散瞳时间45min行双眼瞳孔直径测量及眼底检查;B组为60min;C组是90min。结果 A、B组中左、右眼散瞳直径无差异(P>0.05),C组左眼散瞳直径比右眼小(P<0.05)。无论散瞳时间的长短,低胎龄和高胎龄早产儿组的平均瞳孔直径比较无差异(P>0.05)。结论滴2次复方托吡卡胺眼水60min后行眼底检查更安全有效,并且复发托吡卡胺眼水对不同胎龄的早产儿散瞳效果无差异。     

Comparison of Azelastine Eye Drops with Levocabastine Eye Drops in the Treatment of Seasonal Allergic Conjunctivitis

Summary

A randomised, multicentre parallel group study was undertaken to compare the efficacy and safety of 0.05% azelastine eye drops (101 patients) in an open manner with 0.05% levocabastine eye drops (103 patients) and in a double-blind manner with placebo (103 patients) during a 14-day treatment period involving patients with seasonal allergic conjunctivitis. The three main eye symptoms, scored on a four-point scale, were itching, lacrimation and conjunctival redness; the primary efficacy variable was the responder rate on day 3. Responders were patients whose sum score of the three main eye symptoms decreased by at least three points from a baseline score of at least six points. In addition to these main symptoms, five other symptoms were recorded on days 0, 3, 7 and 14, and patients kept daily diaries of the three main eye symptoms and swollen eyelids. The responder rate after 3 days of treatment was 69% in patients treated with azelastine, 59% in patients treated with levocabastine and 51% in the placebo group. Only the difference in responder rates between azelastine and placebo eye drops was statistically significant (p = 0.02). The improvements in other ocular symptoms and entries in the patients’ diaries closely reflected the changes reported by the investigators. No serious adverse events occurred throughout the study. Nine patients (three in the azelastine, five in the levocabastine and one in the placebo group) terminated the study prematurely due to poor tolerability. Adverse drug reactions, mainly a mild, transient irritation and a bitter or unpleasant taste, were reported in 37% of patients receiving azelastine eye drops, 31% of patients receiving levocabastine and 9% of placebo patients. Overall tolerability was assessed as very good or good in 86% of azelastine- and levocabastinetreated patients, and in 95% of the patients receiving placebo. The results of this study indicate that azelastine possesses a tolerability profile at least comparable to that of levocabastine eye drops, but additionally appears to have a slightly quicker onset of effect, and confirm the therapeutic potential of azelastine eye drops in the treatment of allergic conjunctivitis.     

Comparison of azelastine eye drops with levocabastine eye drops in the treatment of seasonal allergic conjunctivitis

A randomised, multicentre parallel group study was undertaken to compare the efficacy and safety of 0.05% azelastine eye drops (101 patients) in an open manner with 0.05% levocabastine eye drops (103 patients) and in a double-blind manner with placebo (103 patients) during a 14-day treatment period involving patients with seasonal allergic conjunctivitis. The three main eye symptoms, scored on a four-point scale, were itching, lacrimation and conjunctival redness; the primary efficacy variable was the responder rate on day 3. Responders were patients whose sum score of the three main eye symptoms decreased by at least three points from a baseline score of at least six points. In addition to these main symptoms, five other symptoms were recorded on days 0, 3, 7 and 14, and patients kept daily diaries of the three main eye symptoms and swollen eyelids. The responder rate after 3 days of treatment was 69% in patients treated with azelastine, 59% in patients treated with levocabastine and 51% in the placebo group. Only the difference in responder rates between azelastine and placebo eye drops was statistically significant (p = 0.02). The improvements in other ocular symptoms and entries in the patients' diaries closely reflected the changes reported by the investigators. No serious adverse events occurred throughout the study. Nine patients (three in the azelastine, five in the levocabastine and one in the placebo group) terminated the study prematurely due to poor tolerability. Adverse drug reactions, mainly a mild, transient irritation and a bitter or unpleasant taste, were reported in 37% of patients receiving azelastine eye drops, 31% of patients receiving levocabastine and 9% of placebo patients. Overall tolerability was assessed as very good or good in 86% of azelastine- and levocabastine-treated patients, and in 95% of the patients receiving placebo. The results of this study indicate that azelastine possesses a tolerability profile at least comparable to that of levocabastine eye drops, but additionally appears to have a slightly quicker onset of effect, and confirm the therapeutic potential of azelastine eye drops in the treatment of allergic conjunctivitis.     

Pharmaceutical investigation of vancomycin hydrochloride eye drops and their topical application to MRSA eye infection]

Two formulations of 0.5% vancomycin hydrochloride (VM) eye drops (VM-B and VM-C eye drops) were prepared by dissolving commercial VM powder for injection with preserved water B (PWB) containing phosphate buffer and preserved water C (PWC) containing only antimicrobial preservative, respectively. The VM-B eye drops have neutral pH (about 6.3), and the VM-C eye drops acidic pH of about 3.5. The pharmaceutical examination of these eye drops was performed regarding its clinical application to MRSA eye infection. In an irritability test using a rabbit's eye, the average number of winks after instillation of one drop of VM-B eye drops was 0.8 times/min and significantly smaller than that of VM-C eye drops (2.0 times/min). In dark storage at 4 degrees C, no change of VM concentration in both eye drops was observed for 25 weeks after preparation and the mean residual concentrations as determined by the HPLC-UV (240 nm) method were constant over 90% for 8 weeks, of the initial concentration. However, the residual VM concentration of VM-B eye drops under a room condition declined to 58% after 4 weeks and 20% after 8 weeks, and VM in light storage at 40 degrees C was not detectable after 8 weeks. The drug concentration of VM-C eye drops declined to 83% after 4 weeks and 74% after 8 weeks under a room condition, and to 46% after 4 weeks and 20% after 8 weeks under light storage at 40 degrees C. Under these storage conditions, the precipitation of VM related crystals was observed in both the eye drops when the residual percentage of VM was lower than 80%. Judging from HPLC chromatograms of a solution of the precipitated crystals, it was suggested that this crystal was degradation products of VM. The VM-B eye drops was applied to a patient with MRSA eye infection, because other medication was not effective. After continuous instillation of a drop per times every hour to both eyes, MRSA in corneal culture turned out negative after one week, and the clinical condition was remarkably improved. On the basis of the result of eye-irritability, VM-B eye drops with neutral pH was suggested to be superior to acidic VM-C eye drops from a safety point of view. It was also indicated that VM-B eye drops can be effectively used for 8 weeks under dark storage at 4 degrees C for MRSA eye infection, which is a useful piece information for the proper usage of the VM eye drops.     

2015—2019年天津市眼科医院局部抗青光眼用药的使用情况分析

目的 分析2015—2019年天津市眼科医院局部抗青光眼药品的使用情况及发展趋势。方法 对天津市眼科医院2015—2019年局部抗青光眼药品的销售金额、用药频度（DDDs）、日均费用（DDC）、排序比（B/A）等进行回顾性统计分析。结果 前列腺素衍生物类局部抗青光眼药品的销售金额远高于其他4类药品销售金额。拉坦前列素滴眼液（国产）、拉坦前列素滴眼液（进口）、曲伏前列素滴眼液、盐酸卡替洛尔滴眼液、酒石酸溴莫尼定滴眼液、布林佐胺滴眼液稳居本院用药金额前6位。盐酸卡替洛尔滴眼液DDD稳居第1位。除了2015—2016年盐酸卡替洛尔滴眼液的DDC值略有上升外,其他滴眼液的DDC值均维持不变或呈下降的趋势。盐酸卡替洛尔滴眼液的B/A最高。结论 本院局部抗青光眼药品使用基本合理,前列腺素衍生物类药物逐渐成为抗青光眼的一线用药。     

添加季铵盐类防腐剂的加替沙星滴眼液抑菌效力的检测与评价

目的 对添加季铵盐类防腐剂的加替沙星滴眼液抑菌效力进行检测和评价.方法 选取添加含苯扎氯铵和苯扎溴铵防腐剂的加替沙星滴眼液,并按照中国药典2015版(ChP2015)四部通则1121抑菌效力检查法,采用铜绿假单胞菌、大肠埃希菌、金黄色葡萄球菌、白色念珠菌、黑曲霉5种菌株,对添加以及不添加两种防腐剂的滴眼液进行了效力测定.结果 根据中国药典2015版标准规定,选取的3批样品中,添加防腐剂的加替沙星滴眼液达到抑菌效力标准的液"A",或至少达到抑菌效力"B";未添加防腐剂的加替沙星滴眼液未能达到抑菌效力标准"B".结论 0.005%苯扎氯铵和0.01%苯扎溴铵皆可作为加替沙星滴眼液的季铵盐类防腐剂;不含防腐剂的滴眼液中,应适当添加抑菌效力测试测得最低剂量的防腐剂.     

Comparative in vitro investigation of the forces exerted by eye drops and eye spray

Topical administration of ophthalmic drugs is predominantly carried out in the form of eye drops. The application of an eye spray represents a feasible alternative to drop instillation with regard to the clinical efficacy. In this study the forces exerted during the application of eye drops and eye spray to a surface were measured in vitro and compared with each other. Whereas the maximal forces that occurred with a falling drop tended to increase with greater application distance, the forces decreased with spraying. From an application distance of 3 cm the eye spray proved to have a more favorable mechanical force effect than the eye drops. In view of the loss of experimental liquid caused by spray application as well as the diameter of the spray cone, a spray distance of from 4 cm to 5 cm can be deemed to be optimal.     

2种方案治疗老年长期干眼症的疗效观察与药物经济学评价

目的：探讨玻璃酸钠滴眼液与羧甲基纤维素钠滴眼液治疗老年长期干眼症的疗效与药物经济学评价。方法：采用随机数字表法,将100例老年干眼症住院患者分为玻璃酸钠滴眼液（ A组）与羧甲基纤维素钠滴眼液（ B组）,观察2组患者的疗效,并进行成本-效果分析。结果：治疗后,A、B组患者总有效率分别为100％（50／50）、90％（45／50）,差异有统计学意义（P＜0.05）;平均医疗费用分别为833.62元、799.6元,成本-效果比分别为833.62、888.44。结论：患者使用玻璃酸钠滴眼液在治疗效果上及成本-效果比上均优于羧甲基纤维素钠滴眼液,可临床长期用药。     

Ocular pharmacokinetics of thiamphenicol in rabbits.

The ocular pharmacokinetics of thiamphenicol (TAP, CAS 15318-45-3) was studied in rabbits by means of the assessment of its ocular and systemic absorption, and urinary excretion after instillation of 0.5% TAP eye drops. TAP concentrations in aqueous humor, plasma and urine were evaluated by a coupled LC/GC method (detection limit = 0.1 ng/ml), because the necessity to have a technique much more sensitive than the traditional chromatographic ones available in order to quantify the very low drug concentrations in biological fluids produced by the ocular treatment, and generally by a topical administration. The intravenous route was chosen as reference and allowed the absolute bioavailability to be estimated. TAP proved to be well absorbed through the cornea with the peak aqueous humor concentration of 110 ng/ml at 45 min following the instillation. The good ocular absorption of TAP was confirmed by the plasma concentrations observed after instillation of 0.5% eye drops. In any case, these concentrations were more than 1000 times lower than those observed after the intravenous treatment at the dose normally used for infectious diseases, allowing to exclude any systemic toxicity of TAP eye drops. The absolute ocular bioavailability was 16.2% when estimated from the AUC values and 34.0% from the cumulative urinary excretion values.     

壳聚糖对阿昔洛韦滴眼液离体角膜渗透促进作用的考察

目的：考察壳聚糖（CS）对阿昔洛韦（ACV）滴眼液（ACV-CS）离体角膜渗透促进作用,为研制新型ACV滴眼液奠定基础.方法：以CS为增黏剂及吸收促进剂,制备ACV-CS滴眼液;以不加CS的ACV滴眼液为对照,采用Franz扩散池法考察CS对ACV滴眼液离体角膜渗透促进作用.结果：与不加ACV滴眼液相比,ACV-CS滴眼液的黏性显著增加;给药20 min后,ACV-CS滴眼液对离体角膜的累积渗透药量明显大于不加CS的ACV滴眼液（P＆lt;0.05）.结论：CS对ACV滴眼液离体角膜渗透具有明显的促进作用,值得进一步研究.     

聚乙二醇滴眼液治疗干眼症的疗效观察

目的:探讨聚乙二醇滴眼液治疗干眼症的疗效。方法:60例干眼症患者分为A组与B组,各30例。A组给予聚乙二醇滴眼液滴眼,B组给予0.05%羧甲基纤维素滴眼液滴眼。连续用药1周后评价疗效,并记录患者干眼症状的变化及记录泪液分泌试验(SIT)、泪膜破裂时间(BUT)结果。结果:2组眼部各症状较治疗前均有改善;2组治疗前、后SIT值差异无统计学意义;A组BUT明显较B组延长,并且在120min时差异具有显著性。结论:聚乙二醇滴眼液是一种长效缓解干眼的有效药物。     

2001-2004年我院抗过敏滴眼液使用情况分析

目的客观分析我院抗过敏滴眼液的使用情况及发展趋势,为临床合理用药提供依据。方法用DDD分析法对我院2001-2004年4年间抗过敏滴眼液的使用情况进行统计和分析。结果4年来我院抗过敏滴眼液在用药金额、用药频度和销售量方面都呈上升趋势。DDD s排序前5位的是复方萘甲唑啉、萘扑维、新乐敦、色甘酸钠、那素达滴眼液。按销售金额排序为洛度沙胺、复方萘甲唑啉、萘扑维、新乐敦、吡嘧司特钾滴眼液。结论我院抗过敏滴眼液使用合理,临床以使用减轻充血剂-组胺受体阻断药的复方制剂占抗过敏滴眼液市场的主导地位。     

2001—2004年我院抗过敏滴眼液使用情况分析

目的客观分析我院抗过敏滴眼液的使用情况及发展趋势，为临床合理用药提供依据。方法用DDD分析法对我院2001—2004年4年间抗过敏滴眼液的使用情况进行统计和分析。结果4年来我院抗过敏滴眼液在用药金额、用药频度和销售量方面都呈上升趋势。DDDs排序前5位的是复方萘甲唑啉、萘扑维、新乐敦、色甘酸钠、那素达滴眼液。按销售金额排序为洛度沙胺、复方萘甲唑啉、萘扑维、新乐敦、吡嘧司特钾滴眼液。结论我院抗过敏滴眼液使用合理，临床以使用减轻充血剂．组胺受体阻断药的复方制剂占抗过敏滴眼液市场的主导地位。     

盐酸溴己新片联合羟糖甘滴眼液治疗干眼症的疗效观察

目的:观察盐酸溴己新片联合羟糖甘滴眼液治疗干眼症的疗效。方法:66例干眼症患者随机分为A组与B组,各33例,A组以羟糖甘滴眼液滴双眼,B组口服盐酸溴己新片+羟糖甘滴眼液滴双眼,8周为1个疗程。结果:治疗前2组眼部症状评分、泪液分泌量、泪膜破裂时间、角膜荧光染色评分比较,差异无统计学意义(P值均>0.05)。治疗1个疗程后,2组眼部症状评分、泪液分泌量、泪膜破裂时间、角膜荧光染色评分改善情况比较,均优于治疗前(P值均<0.05),且治疗效果B组优于A组(P值均<0.05)。结论:干眼症患者在常规使用羟糖甘滴眼液的基础上加服盐酸溴己新片疗效较好。     

盐酸左氧氟沙星缓释滴眼液的毒性及刺激性反应

目的:进行盐酸左氧氟沙星缓释滴眼液的安全性评价。方法:采用琼脂扩散法,以褪色指数和溶解指数为指标得到的细胞反应级数评价该滴眼液的体外细胞毒性;20只小鼠一次性静脉注射盐酸左氧氟沙星缓释滴眼液(15mg·kg-1)进行急性毒性实验,观察14d内小鼠死亡数和体质量变化;12只兔敷贴滴眼液(1.5mg·d-1,连续用药7d)进行皮肤刺激性实验,观察末次用药24h后1、24、48、72h的红斑和水肿评分。结果:盐酸左氧氟沙星缓释滴眼液体外细胞毒性反应为1级;14d内小鼠无死亡且体质量变化没有明显差异;兔皮肤红斑和水肿评分均小于0.05,评价均为无刺激性。结论:盐酸左氧氟沙星缓释滴眼液具有良好的生物安全性。