依诺沙星滴眼液抑菌剂考察

目的 建立测定依诺沙星滴眼液中抑菌剂硫柳汞、羟苯乙酯和苯扎溴铵的HPLC含量测定方法,并对这3种抑菌剂的稳定性进行考察。方法 选用C₁₈柱,以1%三乙胺溶液（用磷酸调节pH值至3.0）为流动相A,以甲醇为流动相B,进行梯度洗脱;检测波长苯扎溴铵为218 nm,羟苯乙酯和硫柳汞为262 nm,进样量为20 μL。同时考察抑菌剂的稳定性。结果 羟苯乙酯、硫柳汞和苯扎溴铵之间的分离度分别为19.7,48.7。硫柳汞在9.1~151.4 μg·mL^-1、羟苯乙酯在2.1~41.2 μg·mL^-1、苯扎溴铵在21.8~218.0 μg·mL^-1内均呈现良好的线性关系（r=0.999,1.000,0.999）,其检出限分别为1.4,1.2,13.1 ng。在高温条件下,硫柳汞和羟苯乙酯含量均略有下降;在紫外光照条件下,硫柳汞含量下降明显;苯扎溴铵几乎不受高温和紫外光照的影响。结论 该方法灵敏度高,能够有效评估滴眼液中抑菌剂的含量。     

HPLC同时测定双氯芬酸钠滴眼液中3种抑菌剂的含量

目的 建立HPLC同时测定双氯芬酸钠滴眼液中羟苯乙酯、硫柳汞和苯扎氯铵含量的方法。方法 用十八烷基键合硅胶为填充剂,以1%三乙胺溶液（磷酸调节pH值至3.0）为流动相A,以甲醇为流动相B,进行梯度洗脱;流速1.0 mL·min^-1,柱温40℃,检测波长254 nm。结果 羟苯乙酯在20.58~205.8 μg·mL^-1、硫柳汞在8.242~82.42 μg·mL^-1、苯扎氯铵n-C₁₂H₂₅取代物在12.88~128.8 μg·mL^-1、苯扎氯铵n-C₁₄H₂₉取代物在6.624~66.24 μg·mL^-1内线性良好（r≥0.999 8）,平均回收率为99.3%~102.5%（n=9）。结论 该方法简单、准确、重复性好,可用于控制双氯芬酸钠滴眼液中羟苯乙酯、硫柳汞和苯扎氯铵的含量。     

HPLC法同时测定吡诺克辛钠滴眼液中不同抑菌剂的含量

目的：建立同时测定吡诺克辛钠滴眼液中不同抑菌剂（硫柳汞钠、羟苯甲酯、羟苯乙酯、羟苯丙酯）含量的HPLC法。方法：采用C18色谱柱（4.6 mm×150 mm,5 μm）,流动相为0.005 mol·L^-1的醋酸铵溶液（每1000 mL中含三乙胺10 mL,用冰醋酸调节pH值至5.0±0.5）-乙腈（70：30）,流速为1.0 mL·min^-1,检测波长为256 nm,柱温为30℃。结果：硫柳汞钠、羟苯甲酯、羟苯乙酯和羟苯丙酯在各自的检测质量浓度范围内线性关系良好,r为0.9993~1.0000,检测限分别为2.3、0.4、0.7、1.1 ng;4种抑菌剂的平均回收率为100.4%~102.7%（RSD≤1.4,n=9）。结论：本文建立的方法结果准确可靠,可作为吡诺克辛钠滴眼液中不同抑菌剂的质量控制方法。     

HPLC法测定妥布霉素滴眼液中5种抑菌剂

目的 建立同时测定妥布霉素滴眼液中5种抑菌剂(羟苯乙酯、硫柳汞、羟苯丙酯、苯扎溴铵和苯扎氯铵)的HPLC方法。方法 采用Agilent Zorbax SB-C₁₈ (4.6 mm×150 mm,5 μm)色谱柱,流动相A为1%三乙胺（磷酸调节pH值至3.5±0.05）;流动相B为甲醇,梯度洗脱,流速为1.0 mL·min^-1,柱温35 ℃,检测波长为214 nm。结果 羟苯乙酯、硫柳汞、羟苯丙酯、苯扎溴铵/苯扎氯铵各峰均分离良好;羟苯乙酯在0.77～192.5 μg·mL-1范围内线性关系良好(r=0.999 5),平均回收率为100.0%(RSD=0.9%,n=9);硫柳汞在2.16～541.0 μg·mL^-1范围内线性关系良好(r=0.999 7),平均回收率为100.1%(RSD=0.6%,n=9);羟苯丙酯在0.84～209.8 μg·mL^-1范围内线性关系良好(r=1.000 0),平均回收率为100.3%(RSD=1.0%,n=9);苯扎溴铵在4.36～1090 μg·mL^-1范围内线性关系良好(r=0.9992),平均回收率为100.2%(RSD=0.5%,n=9);苯扎氯铵（n-C12H25）3.22～805.0 μg·mL^-1范围内线性关系良好(r=0.999 8),平均回收率为100.1%(RSD=1.1%,n=9);苯扎氯铵（n-C14H29）1.66～413.9 μg·mL^-1范围内线性关系良好(r=1.000 0),平均回收率为100.1%(RSD=0.6%,n=9)。结论 该方法准确、灵敏、简便,可用于妥布霉素滴眼液中羟苯乙酯、硫柳汞、羟丙丙酯、苯扎溴铵及苯扎氯铵5种抑菌剂的检查。     

HPLC测定苄达赖氨酸滴眼液中3种抑菌剂含量

目的 建立同时测定苄达赖氨酸滴眼液中3种抑菌剂(羟苯乙酯、硫柳汞、苯扎氯铵)含量的高效液相色谱法。方法 Kromasil C₁₈色谱柱(4.6 mm×250 mm,5 μm);流动相：1%三乙胺溶液(用磷酸调pH值至3.0)(A)-甲醇(B),梯度洗脱：0~2?min,B 50%;2~17 min,B 50%→90%;17~29 min,B 90%;29~30 min,B 90%→50%;流速：1.0 mL·min^-1;检测波长：262 nm;进样量：20 μL;柱温：40 ℃。结果 羟苯乙酯、硫柳汞和苯扎氯铵的峰面积与浓度的线性关系良好(r>0.999),线性范围分别为：0.07~1.32,0.38~9.51,3.26~32.6 μg·mL^-1,加样回收率为99.0%~100.3%。结论 本方法灵敏,快速,准确,重复性好,可用于苄达赖氨酸滴眼液中抑菌剂的含量测定。     

HPLC法测定牛磺酸滴眼液中3种抑菌剂含量

摘 要 目的：建立同时测定牛磺酸滴眼液中3种抑菌剂(羟苯甲酯、羟苯乙酯、羟苯丙酯)含量的HPLC方法。方法: Phenomenex Gemini C18色谱柱（250 mm×4.6 mm,5 μm）;流动相：1%冰醋酸溶液 甲醇（40〖KG*9〗∶〖KG-*2〗60）;流速：1.0ml·min-1;检测波长：254nm;进样量：20 μl;柱温：25℃。结果: 羟苯甲酯、羟苯乙酯、羟苯丙酯的峰面积与浓度的线性关系良好（r＞0.999）,线性范围分别为1.00～19.94 μg·mL^-1,2.01～20.08 μg·mL^-1,0.21～10.46 μg·mL^-1,加样回收率为99.20%～99.90%,RSD为1.34%～1.54%（n=9）。 结论: 该方法准确、专属性强,稳定且无干扰,可用于牛磺酸滴眼液中抑菌剂的含量分析。     

复方鱼腥草合剂中3个有效成分及防腐剂的含量测定

目的 考察市售复方鱼腥草合剂的质量。方法 收集10批不同厂家生产的复方鱼腥草合剂,应用HPLC测定3个有效成分（绿原酸、连翘酯苷A、黄芩苷）及防腐剂（苯甲酸钠、羟苯乙酯）含量。结果 10批复方鱼腥草合剂中绿原酸的含量为29.74~84.13μg·mL^-1、连翘酯苷A的含量为22.69~113.44 μg·mL^-1、黄芩苷的含量为0.587~1.662 mg·mL^-1;苯甲酸钠和羟苯乙酯含量均符合标准规定。结论 复方鱼腥草合剂质量情况较乐观,但是不同批次内在质量有较大差异,现行标准的质量控制方法较简单,不能有效控制其质量,建议修订完善标准。     

高效液相色谱法同时测定复方硫酸新霉素滴眼液中7种抑菌剂

目的 建立同时测定复方硫酸新霉素滴眼液中羟苯甲酯、羟苯乙酯、羟苯丙酯、苯甲酸钠、硫柳汞、苯扎氯铵、苯扎溴铵7种抑菌剂含量的高效液相色谱(HPLC)法.方法 色谱柱为月旭Ultimate?XB-C18柱(150 mm×4.6 mm,5μm),流动相为甲醇-磷酸水溶液(pH=3.5),梯度洗脱,流速为1.0 mL/min,...     

HPLC测定口服液体制剂中防腐剂和甜味剂的含量

目的 建立快速定性定量检测口服液体制剂中违法添加防腐剂和甜味剂的高效液相色谱法。方法 ZORBAX SB-C₁₈色谱柱(4.6 mm×250 mm,5 μm),流动相：甲醇-0.02 mol·L^-1乙酸铵溶液,梯度洗脱,流速：1.0 mL·min^-1,检测波长：240 nm,柱温：25 ℃。结果 安赛蜜、苯甲酸、山梨酸、糖精钠、脱氢乙酸、羟苯甲酯、羟苯乙酯、羟苯丙酯、羟苯丁酯在5~100 μg·mL^-1内线性关系良好(r>0.999),检测限分别为0.02,0.04,0.01,0.10,0.06,0.01,0.01,0.01,0.01 μg·mL^-1,平均回收率在90.0%~110.0%内,精密度和重复性均<2.0%(n=6)。结论 该方法简单、可靠、准确,可用于口服液体制剂中防腐剂和甜味剂含量的测定。     

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。     

胰岛素鼻腔喷雾剂的大鼠鼻纤毛毒性考察

目的：考察胰岛素鼻腔喷雾剂的鼻纤毛毒性。方法：扫描电镜观察鼻喷雾剂对大卤粘膜表面形态的影响。结果：大鼠给予胰岛素鼻喷雾剂后,扫描电镜观察,其鼻中卫粘膜的纤毛形态与给予生理盐水的对照组无显著差异。结论：上述胰岛素鼻喷雾剂无急性鼻粘膜纤毛毒性。     

鼻腔给药系统的鼻粘膜毒性及解决途径

就鼻腔给药系统可能导致的鼻粘膜毒性的评价方法、易产生毒性的制剂组分及解决毒性的方法进行简要的综述。     

慢性鼻窦炎-鼻息肉鼻内镜手术110例临床观察

目的探讨鼻内镜手术治疗慢性鼻窦炎-鼻息肉的临床效果。方法回顾性分析我院2010—2012年收治的110例慢性鼻窦炎-鼻息肉患者的临床资料和随访情况。结果 110例患者鼻内镜手术的总有效率为73.6%,其中Ⅰ型患者的总有效率高于Ⅱ型、Ⅲ型患者（P〈0.05）,Ⅱ型患者的总有效率高于Ⅲ型（P〈0.05）。结论鼻内镜手术是鼻科临床上鼻窦炎-鼻息肉手术的首选方法,具有创伤小、疗效好、术后并发症少等优点。     

Intranasal Delivery of RS-93522, a Dihydropyridine-Type Calcium-Channel Antagonist

Pharmaceutical Research -     

Insulin Containing Nanocomplexes Formed by Self-Assembly from Biodegradable Amine-Modified Poly(Vinyl Alcohol)-Graft-Poly(<Emphasis Type="SmallCaps">l</Emphasis>-Lactide): Bioavailability and Nasal Tolerability in Rats

Purpose The bioavailability and local tolerability of insulin containing nanocomplexes from amine-modified poly(vinyl alcohol)-graft-poly(l-lactide) were studied in rats. Histology of the nasal epithelium was studied to document integrity of the mucosa. Methods Nanocomplexes (NC) were prepared by spontaneous self-assembly of insulin and the water-soluble amphiphilic polymer. Changes in blood glucose and insulin blood concentration were monitored in anesthetized rats using a glucose meter and enzyme-linked immunosorbent assay, respectively. Histological sections of the nasal cavity were examined after H&E staining by light microscopy. Results NC reduced blood glucose level in fasted healthy rats by 20% after 50–80 min and in streptozotocin induced diabetic rats by 30% within 75–95 min compared to basal levels. In both animal models significant concentrations of human insulin were detected, with relative bioavailabilities F_rel of 2.8 up to 8.3%. The more hydrophobic, lactic acid grafted polyester were more effective at a threefold higher polymer concentration, increasing the relative bioavailability F_rel of a 5 IU/kg dose from 2.8 to 5.7%. Histological examination of the nasal mucosa after 4 h showed no signs of toxicity at the site of nasal administration. Conclusions These results demonstrate that the NC significantly enhanced insulin absorption, suggesting that amphiphilic biodegradable comb-polymers offer a promising approach for nasal peptide delivery.     

The Effect of Nasal Patency on the Clearance of Radiolabeled Saline in Healthy Volunteers

Purpose. The objective of this study was to investigate the effect ofnasal cavity patency on the penetration, deposition, and clearance ofan aqueous isotonic saline solution. Methods. The study was carried out as a single center, open,randomized, 2-way cross-over in healthy volunteers. Nasal patency wasassessed using misting patterns on a cold metal surface at the beginningand end of study. 100 l of technetium-99m radiolabeled saline solutionwas introduced into either the most or least patent nasal cavity usinga purpose designed spray device. The distribution and residence timeof the radiolabel was followed for 2 hours using gamma scintigraphy. Results. The mean times to 50% clearance were34 ± 7 and 28 ± 12minutes (±s.d.) for the side view of the least and most patent nasalcavity respectively. Total clearance of the radiolabelled saline from thenose was not affected by patency. Between 7 and 3% of theradiolabelled saline solution remained in the nasal cavity at the end of imaging.Using endoscopy to track the clearance of an aqueous solution of fooddye using the same delivery procedure, identified this region as hairin the nasal vestibule. The dye was seen to dry in this region alongwith the mucus. Conclusions. Nasal patency affects the initial, but not total clearanceof solutions, however, the remaining solution may not be available fordrug delivery.     

鼻中隔术后应用金霉素眼膏行鼻腔换药65例临床观察

目的:通过对鼻内镜下鼻中隔手术后应用金霉素眼膏鼻腔换药患者治愈结果的临床观察研究,为临床诊治提供有价值的参考。方法:随机选用年龄相近的鼻内镜下鼻中隔手术后患者65例,其中35例于术后第3天开始应用金霉素眼膏鼻腔换药,将术后换药治愈结果进行统计学分析。结果:65例鼻中隔术者中应用金霉素眼膏行鼻腔换药明显优于生理盐水换药,术后伤口愈合更快,结痂渗血明显减少。结论:鼻中隔术后应用金霉素眼膏行鼻腔换药,可提高术后治愈率,减少并发症发生率,值得临床的推广使用。     

Nasal Epithelial Permeation of Thymotrinan (TP3) Versus Thymocartin (TP4): Competitive Metabolism and Self-Enhancement

Purpose. To investigate concentration dependent permeabilities andmetabolism kinetics of thymotrinan (TP3) versus thymocartin (TP4)in nasal epithelium in vitro. Methods. Excised bovine nasal mucosa was used as an in vitro model.Permeabilities were studied in a diffusion chamber, metabolism kineticsin a reflection kinetics set-up. Studies were performed at various TP3and TP4 concentrations. The ³H-mannitol flux was measured to monitorjunctional permeability. Potential Ca²⁺-complexation was investigatedusing a Ca²⁺-selective electrode. Results. Permeability of TP3 was negligible at 0.1 and 0.2 mM andincreased drastically above 0.4 mM up to 2 × 10^–5 cm s^–1. In thepresence of 2 mM TP4 the TP3 permeabilites were significantly above(4 × 10^–5 cm s^–1) the level of TP3 without TP4, and TP3 metabolismwas totally inhibited. TP3 and TP4 showed a significant concentrationdependent effect on the permeability of ³H-mannitol. Ahyperosmolarity effect of the peptide solutions was excluded. Transepithelialelectrical resistance (TEER; 30 cm²) was unchanged by either TP3 orTP4. At 1 mM TP3 the mucosal-to-serosal permeability was four timeshigher than serosal-to-mucosal, indicating enzyme polarization. Inreflection kinetics studies, TP3 degradation was slightly higher on themucosal than on the serosal side. TP3 and TP4 followed the samenon-linear metabolism kinetics. Conclusions. Increase in permeability at high TP concentrationsinvolves competitive enzyme saturation combined with self-enhancedparacellular permeation.     

鼻腔给药系统的研究新进展

近年来药物的鼻腔给药系统受到了越来越多的关注.全球众多制药行业都在致力于基因和多肽类药物新型鼻腔给药系统的研发.现阐述了鼻腔生理特点和药物鼻黏膜转运机制及其影响因素,并对近年来鼻腔给药系统的促吸收途径和发展动向作一概述.     

眼镜蛇神经毒素粉末剂的鼻黏膜纤毛毒性考察

目的:考察浙江产眼镜蛇神经毒素鼻用粉末剂(神经毒素粉剂)的鼻黏膜纤毛毒性。方法:以在体蟾蜍上腭模型,观察神经毒素粉剂对鼻纤毛摆动的影响;运用组织病理学方法,在给于家兔神经毒素粉剂后1,3,5,7d时,取鼻中隔黏膜进行光学显微镜观察。结果:神经毒素粉剂抑制鼻纤毛摆动强度,但停止用药后8~9h纤毛摆动可完全恢复,且纤毛形态无明显改变;家兔给予神经毒素粉剂后1,3,5d,其鼻中隔黏膜与空白对照组差异无显著性。第7天,黏膜上皮松化,黏膜轻度充血,但基底膜完整。结论:神经毒素粉剂无急性不可逆性鼻黏膜纤毛毒性。