复方氧氟地米滴耳剂的制备

目的 研制复方氧氟地米滴耳剂。方法 在单方氧氟沙星滴耳剂处方基础上，拟定处方与制备工艺，加入皮质激素、冰片，用吐温代替乙醇，增加药物溶解度，并进行稳定性与刺激性的试验。结果 处方设计合理，制备工艺可行，制剂稳定，药液对外耳道无刺激。结论 该制剂处方合理，质量可控，制剂质量稳定，临床疗效较好。     

氧氟沙星滴耳剂治疗中耳炎的药效学研究

观察了氧氟沙星滴耳剂的体外抑菌作用和对致病菌所致动物中耳炎的试验疗效。结果表明：本制剂对全部试验菌的ＭＩＣ９０为０．５－１．０ｍｇ／Ｌ，敏感率为１００％。对由金黄色葡萄球菌和绿脓杆菌引起豚鼠化脓性中耳炎均有显著的治疗作用，效果优于２．５％氯霉素滴耳剂。试验结果提示：氧氟沙星滴耳剂浓度．３％为宜。     

复方氧氟地米滴耳剂的制备

目的研制复方氧氟地米滴耳剂.方法在单方氧氟沙星滴耳剂处方基础上,拟定处方与制备工艺,加入皮质激素、冰片,用吐温代替乙醇,增加药物溶解度,并进行稳定性与刺激性的试验.结果处方设计合理,制备工艺可行,制剂稳定,药液对外耳道无刺激.结论该制剂处方合理,质量可控,制剂质量稳定,临床疗效较好.     

复方氧氟地米滴耳剂的制备

目的研制复方氧氟地米滴耳剂.方法在单方氧氟沙星滴耳剂处方基础上,拟定处方与制备工艺,加入皮质激素、冰片,用吐温代替乙醇,增加药物溶解度,并进行稳定性与刺激性的试验.结果处方设计合理,制备工艺可行,制剂稳定,药液对外耳道无刺激.结论该制剂处方合理,质量可控,制剂质量稳定,临床疗效较好.     

氧氟沙星复合膜剂在局部抗感染治疗中的应用

氧氟沙星（OFLX）复合膜剂是我院科研制剂。氧氟沙星为第三代喹诺酮类抗菌药物，具有抗菌谱广、高效、低毒等优点，已广泛应用于临床，其剂型有针剂、片剂、滴耳剂、滴眼剂等，复合膜剂的研制和临床应用在国内来见报道。我院研制成功的氧氟沙星复合膜剂[1]对多种局部感染性疾病     

氧氟沙星滴耳剂治疗中耳炎的药效学研究

观察了氧氟沙星滴耳剂的体外抑菌作用和对致病而所致动物中耳炎的试验疗效。结果表明:本制剂对全体试验面的MIC₉₀为0.5—1.0mg几,敏感率为100%.对由金黄色葡萄球菌和绿脓杆菌引起的豚鼠化脓性中耳炎均有显著的治疗作用。效果优于2.5%氧霉素滴耳剂。试验结果提示。氧氟沙星滴耳剂浓度以0.3%为宜。     

氧氟沙星制剂开发及应用研究概况

综述了氧氟沙星片剂、颗粒剂、注射剂、滴眼剂、滴耳剂、滴丸剂、眼膏剂、涤剂、凝胶剂、脂质体、微囊、控释制剂的开发及应用研究概况。     

氧氟沙星滴耳剂治疗中耳炎的药效学研究

观察了氧氟沙星滴耳剂的体外抑菌作用和对致病而所致动物中耳炎的试验疗效。结果表明：本制剂对全体试验面的ＭＩＣ＿（９０）为０．５—１．０ｍｇ几,敏感率为１００％．对由金黄色葡萄球菌和绿脓杆菌引起的豚鼠化脓性中耳炎均有显著的治疗作用。效果优于２．５％氧霉素滴耳剂。试验结果提示。氧氟沙星滴耳剂浓度以０．３％为宜。     

氧氟沙星滴耳剂在乳突术中的应用51例临床观察

氧氟沙星滴耳剂在乳突术中的应用５１例临床观察宁德地区第二医院程道俊，朱忠寿宁德地区第一医院陈缪安氧氟沙星滴耳剂在乳突根治中的应用还较少报道。我们自１９９４年６月～１９９５年８月，将０．３％氧氟沙星滴耳剂（江苏如皋市制药厂生产）扩大应用于乳突根治术中术...     

左氧氟沙星滴耳液的制备及临床应用

目的：制备左氧氟沙星滴耳液，观察临床疗效。方法：将左氧氟沙星制成滴耳液，建立质量控制方法，并进行稳定性、刺激性及临床疗效观察。结果：制备的滴耳剂质量可靠，疗效确切。结论：本制剂制备工艺合理，质控方法可靠，临床疗效满意。     

HPLC法测定氧氟沙星滴耳液中氧氟沙星的含量

目的建立测定氧氟沙星滴耳液中氧氟沙星含量的HPLC方法。方法采用Dikma Diamonsil C18柱(4.6 mm×150 mm,5μm),乙腈-0.1%三乙胺溶液(14∶86,H3PO4调节pH值至3.0)为流动相,柱温35℃,流速1.0 mL/min,Waters 996 PDA检测器,检测波长294 nm。结果进样量在0.153 9～3.078 0μg范围内线性关系良好,r=0.999 9(n=6),平均回收率99.84%,RSD=0.56%。结论该方法准确、简便、重现性好,可用于氧氟沙星滴耳液的含量测定。     

A benefit-risk assessment of ofloxacin otic solution in ear infection.

Ofloxacin is a fluoroquinolone antibacterial with potent bactericidal activities and the topical otological preparation of this drug has been clinically utilised since the late 1980s. The rate of eradication with ofloxacin ranges from 83.3% to 100% for all pathogens commonly isolated from middle ear effusions in cases of otitis media and otitis externa. Despite the significant length of its usage, emergence of resistant pathogens has been rarely encountered in clinical trials; only two strains of Pseudomonas aeruginosa have been documented with decreased susceptibility to ofloxacin following the use of the otic solution.Ear infections, including otitis externa, chronic suppurative otitis media and otorrhoea associated with tympanostomy tubes, are common problems in clinical practice. The potential complications associated with ear infection can be otological, extratemporal, or even psychosocial. They are sometimes fatal and the effect can be long-lasting and detrimental. The use of an effective topical antibacterial with high cost-effectiveness is definitely warranted. As regards various clinical aspects, including overall success rate, symptomatic relief of otalgia and otorrhoea, ofloxacin otic solution was found to be more effective than comparator agents, be it a topical antibacterial, a systemic antibacterial or combination drugs.The systemic absorption of fluoroquinolones is minimal after topical application. Ofloxacin otic solution 0.3% has been shown to have a low rate of adverse drug reactions. Adverse reactions to ofloxacin otic solution were generally mild. The lack of ototoxic effect from ofloxacin eardrops, even in the concentration higher than 0.3%, has been demonstrated in animal studies. In the clinical setting, no increase in bone-conduction threshold has been shown after the treatment of topical ofloxacin otic solution. There have not been any reports of ototoxicity with ofloxacin otic solution since its approval.To conclude, ofloxacin otic solution 0.3% is clinically effective in the treatment of otitis externa and chronic suppurative otitis media in particular with respect to the overall cure rate, relief of otalgia and otorrhoea. It is well tolerated, with minimal adverse effects. It is not associated with any ototoxicity both experimentally and clinically.     

Ofloxacin otic solution: a review of its use in the management of ear infections.

Ofloxacin is a synthetic fluoroquinolone antibacterial agent that inhibits the supercoiling activity of bacterial DNA gyrase, halting DNA replication. Ofloxacin has been formulated as a 0.3% otic solution for the treatment of ear infections. Topical administration of ofloxacin otic solution 0.3% produces very high concentrations of drug in the ear, thus broadening the spectrum of activity of ofloxacin greatly, to cover most common ear pathogens. Results of clinical trials indicate that ofloxacin otic solution 0.3% is as effective as topical neomycin/polymixin B/hydrocortisone preparations in the treatment of otitis externa (clinical cure rate >80% in adults and >95% in children for both treatments) and oral amoxicillin/clavulanic acid in the treatment of otitis media in the presence of tympanostomy tubes in children (clinical cure rates 76 and 69% for ofloxacin and amoxicillin/clavulanic acid, respectively). It is also effective in the treatment of chronic suppurative otitis media in adolescents and adults with perforated tympanic membranes (75 to 91% clinical cure rate). Because of the limited systemic absorption after topical administration, ofloxacin otic solution 0.3% is well tolerated. Adverse events were usually classed as mild to moderate, with < or =2% considered severe. The most frequent adverse events were bitter taste (5%), primarily in patients with non-intact tympanic membranes, and pruritis (2%). The incidence of adverse events with ofloxacin otic solution 0.3% was similar to that with other ototopical preparations and significantly less than that with oral amoxicillin/clavulanic acid. Unlike comparative ototopical antibacterials, ofloxacin was not ototoxic or chondrotoxic in animal studies. In addition, no ototoxicity was detected in clinical studies in humans. CONCLUSIONS: Ofloxacin otic solution 0.3% is clinically effective in the treatment of otitis externa and otitis media in patients with tympanic membrane perforations or tympanostomy tubes. The high concentrations achieved with this ototopical solution render it active against a broad spectrum of organisms. It is well tolerated, avoiding many systemic adverse events, and is not associated with ototoxicity. As the first ototopical agent approved for use in patients with non-intact tympanic membranes, ofloxacin otic solution 0.3% provides a valuable advantage over current treatment alternatives.     

Once-daily ofloxacin otic solution versus neomycin sulfate/polymyxin B sulfate/hydrocortisone otic suspension four times a day: a multicenter, randomized, evaluator-blinded trial to compare the efficacy, safety, and pain relief in pediatric patients with otitis externa

INTRODUCTION: Otitis externa (OE) is an infection of the external auditory canal affecting children and adults and is associated with symptoms of local pain and tenderness. Twice-daily topical treatment with ofloxacin otic solution (0.3% [Floxin otic solution]) for 10 days has been reported to be as effective and well tolerated as neomycin sulfate/polymyxin B sulfate/hydrocortisone otic suspension (Cortisporin otic suspension) administered four times daily for 10 days. OBJECTIVE: This study compared the efficacy, safety, and ear-pain resolution of once-daily ofloxacin otic solution (0.3%) versus neomycin sulfate/polymyxin B sulfate/hydrocortisone otic suspension administered four times daily, in children with OE. RESEARCH DESIGN, PATIENTS, AND METHODS: This multicenter, randomized, parallel-group, evaluator-blinded study was conducted at 34 centers in 278 pediatric OE patients aged 6 months to 12 years. Patients received five drops of ofloxacin otic solution (0.3%) in the affected ears once daily or three drops of neomycin sulfate/polymyxin B sulfate/hydrocortisone otic suspension four times daily, for 7-10 days. Patient evaluations were performed at pretherapy (day 1), end of therapy (days 7-9), and test of cure (7-10 days post-treatment) visits. Data for 208 patients were clinically evaluable and those for 90 patients were microbiologically evaluable. Scores were obtained for patient assessments of pain severity. MAIN OUTCOME MEASURES: The overall clinical response was cure in the clinically evaluable patients, demonstrated by resolution of OE signs and symptoms at the test of cure visit. The overall clinical-microbiological response was cure in the microbiologically evaluable patients demonstrated by both clinical cure and microbiological eradication. RESULTS: For the clinically evaluable patients, equivalent cure rates were obtained between the once-daily ofloxacin-treated and four-times-daily neomycin sulfate/polymyxin B sulfate/hydrocortisone-treated patients (93.8% and 94.7%, respectively). For the clinically and microbiologically evaluable patients, the overall cure rates were 96.4% versus 97.1% for the ofloxacin-treated and neomycin sulfate/polymyxin B sulfate/hydrocortisone-treated patients, respectively. The eradication rates for the prevalent pathogen, Pseudomonas aeruginosa, were 98% versus 100% for ofloxacin-treated and neomycin sulfate/polymyxin B sulfate/hydrocortisone-treated patients, respectively. Decreases in pain severity were similar in both treatment groups. Statistical analyses were limited by the small numbers of patients in each treatment group. CONCLUSION: In the treatment of OE in children, once-daily ofloxacin otic solution was as effective and safe as neomycin sulfate/polymyxin B sulfate/hydrocortisone otic suspension given four times daily. The two treatments provide rapid and comparable pain relief; however, ofloxacin otic solution does not have the risk of ototoxicity associated with neomycin and provides effective pain relief without adjunctive steroids.     

氧氟沙星与氯霉素滴耳液治疗化脓性中耳炎的比较

目的：比较氧氟沙星与氯霉素对化脓性中耳炎的疗效。方法：用０．３％氧氟沙星滴耳液治疗化脓性中耳炎４０例（男性２３例，女性１７例，共４０耳，年龄３８±ｓ１０ａ）；同时用０．２５％氯霉素滴耳液作对照４０例（男性２１例，女性１９例，共４０耳；年龄４０±１１ａ）。早晚各１次滴耳５～１０滴，疗程７ｄ。结果：氧氟沙星组及氯霉素组的临床有效率分别为７８％和４８％，细菌清除率分别为８８％和５５％，２组有显著性差异（Ｐ＜０．０１）。结论：氧氟沙星滴耳液对治疗化脓性中耳炎有高效、安全、实用等特点。     

Once-daily ofloxacin otic solution versus neomycin sulfate/polymyxin B sulfate/hydrocortisone otic suspension four times a day: a multicenter,randomized, evaluator-blinded trial to compare the efficacy,safety, and pain relief in pediatric patients with otitis externa

ABSTRACT

Introduction: Otitis externa (OE) is an infection of the external auditory canal affecting children and adults and is associated with symptoms of local pain and tenderness. Twice-daily topical treatment with ofloxacin otic solution (0.3% [Floxin otic solution]) for 10 days has been reported to be as effective and well tolerated as neomycin sulfate/polymyxin B sulfate/hydrocortisone otic suspension (Cortisporin otic suspension) administered four times daily for 10 days.

Objective: This study compared the efficacy, safety, and ear-pain resolution of once-daily ofloxacin otic solution (0.3%) versus neomycin sulfate/polymyxin B sulfate/hydrocortisone otic suspension administered four times daily, in children with OE.

Research design, patients, and methods: This multicenter, randomized, parallel-group, evaluator-blinded study was conducted at 34 centers in 278 pediatric OE patients aged 6 months to 12 years. Patients received five drops of ofloxacin otic solution (0.3%) in the affected ears once daily or three drops of neomycin sulfate/polymyxin B sulfate/hydrocortisone otic suspension four times daily, for 7–10 days. Patient evaluations were performed at pretherapy (day 1), end of therapy (days 7–9), and test of cure (7–10 days post-treatment) visits. Data for 208 patients were clinically evaluable and those for 90 patients were microbiologically evaluable. Scores were obtained for patient assessments of pain severity.

Main outcome measures: The overall clinical response was cure in the clinically evaluable patients, demonstrated by resolution of OE signs and symptoms at the test of cure visit. The overall clinical-microbiological response was cure in the microbiologically evaluable patients demonstrated by both clinical cure and microbiological eradication.

Results: For the clinically evaluable patients, equivalent cure rates were obtained between the once-daily ofloxacin-treated and four-times-daily neomycin sulfate/polymyxin B sulfate/hydrocortisone-treated patients (93.8% and 94.7%, respectively). For the clinically and microbiologically evaluable patients, the overall cure rates were 96.4% versus 97.1% for the ofloxacin-treated and neomycin sulfate/polymyxin B sulfate/hydrocortisone-treated patients, respectively. The eradication rates for the prevalent pathogen, Pseudomonas aeruginosa, were 98% versus 100% for ofloxacin-treated and neomycin sulfate/polymyxin B sulfate/hydrocortisone-treated patients, respectively. Decreases in pain severity were similar in both treatment groups. Statistical analyses were limited by the small numbers of patients in each treatment group.

Conclusion: In the treatment of OE in children, once-daily ofloxacin otic solution was as effective and safe as neomycin sulfate/polymyxin B sulfate/hydrocortisone otic suspension given four times daily. The two treatments provide rapid and comparable pain relief; however, ofloxacin otic solution does not have the risk of ototoxicity associated with neomycin and provides effective pain relief without adjunctive steroids.     

氧氟沙星包合物的制备、表征及其包合机制的分析

目的：研究氧氟沙星与环糊精（包括β-环糊精和羟丙基β-环糊精）包合物的制备过程,包合物的结构表征以及包合机制。方法：采用超声法制备包合物,并采用各种不同的方法对形成的包合物进行表征和识别,包括荧光光谱法、紫外-可见分光光度法和核磁共振法等。荧光光谱法计算包合常数（K）以及包合比（n）,同时研究室温条件下不同浓度的环糊精及其衍生物以及不同的酸碱度对包合作用的影响,核磁共振法用于研究包合机制。结果：溶液中不同的pH对氧氟沙星的存在形式影响不同;不同pH条件下,环糊精对氧氟沙星具有不同的包合能力,其中β-环糊精（β-CD）在中性条件下更容易与氧氟沙星进行包合,其包合常数为1 300;而羟丙基β-环糊精（HP-β-CD）更容易在酸性性条件下与氧氟沙星进行包合,其包合常数为1 640。在研究的浓度范围内,环糊精分子与氧氟沙星分子是按1：1形成包合物的。结论：氧氟沙星与环糊精在实验条件下形成了稳定的包合物,氧氟沙星分子是从环糊精及其衍生物的大口端包合进入到空腔内。     

Bacteriological evaluation of ofloxacin otic solution]

Clinical trials of ofloxacin (OFLX) otic solution, such as an early phase II study, a dose-finding study, a phase III double-blind comparative study and open studies, were conducted in the period from February 1988 to October 1989. In these studies, organisms were isolated from secretions of middle ear in patients with chronic otitis media and acute exacerbation of chronic otitis media, and from secretions of external ear in patients with external otitis. These organisms were subjected to identification, followed by determination of susceptibilities to OFLX and the other antibacterials. Results obtained are summarized as follows: 1. In total, 746 organisms were defined as the presumable causative organisms in 439 patients with otitis media and 80 with external otitis. Among the isolates, aerobic Gram-positive organisms were most prevalent, with an isolation rate of 66.9%, followed by aerobic Gram-negative organisms (32.4%), and obligate anaerobes (0.7%). Staphylococcus aureus and Pseudomonas aeruginosa were the organisms isolated most frequently among aerobic Gram-positive and Gram-negative bacteria, respectively. 2. The MIC90 of OFLX against the above 746 strains was 6.25 micrograms/ml. At this level, OFLX was 8 times more potent than cefmenoxime (CMX), and 32 times more potent than fosfomycin (FOM) and fradiomycin (FRM). It was postulated that OFLX retained higher local level than the MIC90 of the drug at 2 hours after topical adaptation of the otic solution, and had enough "above the MIC" and "time above MIC". 3. The MIC90 of OFLX against glucose-nonfermentative Gram-negative rods (GNF-GNR) including P. aeruginosa, which were isolated in 32.6% of the 519 patients, was superior to those of CMX, FOM, and FRM. The well-balanced antibacterial activity of OFLX was thought to be one of the properties of OFLX otic solution. 4. Previously-reported post antibiotic effect of OFLX was thought to be another property of OFLX otic solution. In conclusion, OFLX otic solution appeared to be clinically useful, because it possessed advantageous properties beyond other clinically-available otic solutions.     

腺苷钴胺水溶液的光降解动力学研究

目的：考察腺苷钴胺水溶液的光降解动力学特征。方法：运用HPLC法测定水溶液中腺苷钴胺含量及有关物质。考察样品浓度、光强度、温度、pH对腺苷钴胺水溶液光稳定性的影响。结果：经线性拟合对比分析,腺苷钴胺溶液的光降解反应级数为n=1,腺苷钴胺溶液对光极敏感,在pH2．5—3．5的溶液中相对稳定,腺苷钴胺溶液的光降解随样品浓度的降低、光强度的升高而增加,恒温避光加速试验中腺苷钴胺溶液的光降解并不随温度的升高而升高,但恒温光照加速试验中温度的升高明显加速腺苷钴胺溶液的光降解。结论：腺苷钴胺溶液光降解属近似一级动力学过程,光降解速率受溶液pH影响显著,热可加速腺苷钴胺溶液的光降解。     

Photoreactivity of biologically active compounds. XVIII. Photostability of ofloxacin in the solid state and in a tablet formulation

The photostability of ofloxacin in the solid state has been investigated. The change in colour of uncoated and film coated ofloxacin tablets and compressed ofloxacin was studied as a function of irradiance level and total exposure energy. The degradation of ofloxacin in the various preparations was quantified by HPLC and the antimicrobial activity was determined for selected tablets. The structure of two main degradation products from ofloxacin in the solid state has been postulated from LC-MS analysis. Both products have an absorption cut-off below 400 nm and cannot explain the observed change in tablet colour. There was no apparent relationship between the change in colour and the loss of active substance or antibacterial activity for the preparations investigated. The change in colour was easily detectable at rather low exposure levels. Apparently, there was a difference in light sensitivity between the two film-coated tablet batches investigated. The results obtained were partly dependent on the conditions within the radiation chamber (e.g., exposure time and irradiance level), which emphasizes the importance of testing the samples under various conditions unless the results are unequivocal. The tablets were sensitive to visible light although ofloxacin only has a neglectible absorption above 400 nm. The film coated ofloxacin tablets did, however, absorb above 400 nm with a cut-off at approximately 520 nm. A change in tablet coating to include a component that filters visible light in addition to UV radiation might provide a solution to the discolouration problem and prevent batch to batch variations with respect to light sensitivity.