白芷饮片质量研究

目的:白芷饮片的质量研究。方法:建立薄层鉴别方法和HPLC法测定白芷中2种成分的含量。结果:TLC色谱能同时检出欧前胡素和异欧前胡素;HPIC法测定欧前胡素和异欧前胡素的线性范围分别为0.02495～0.22455μg和0.01521～0.13689μg,平均回收率分别为99.72%(RSD为1.59%,n=6),97.69%(RSD为2.06%,n=6)。结论:定性、定量方法简便、准确,重现性好,能有效控制白芷饮片的内在质量。     

HPLC法测定白芷中4个香豆素类成分的含量

目的:建立HPLC法同时测定白芷中花椒毒酚、佛手柑内酯、欧前胡素和异欧前胡素含量的方法,比较不同产地白芷的成分含量变化。方法:采用Zorbax SB-C₁₈色谱柱（150 mm×4.6 mm,5μm）,流动相组成为乙腈和水,线性梯度洗脱,检测波长300 nm,流速1.0 ml·min^-1。结果:在一定的浓度范围内,花椒毒酚、佛手柑内酯、欧前胡素和异欧前胡素的浓度与峰面积线性关系良好且具备良好的加样回收率。结论:本试验建立的HPLC方法简便易行,可用于白芷中4个活性成分的含量测定。     

HPLC法测定广东省某地区不同药店白芷饮片中欧前胡素和异欧前胡素的含量对比

目的 通过测定白芷中欧前胡素、异欧前胡素含量,分析省内某地区不同厂家在售白芷饮片的质量。方法 色谱条件为Suplco C18(250mm×4.0 mm,5μm)色谱柱,甲醇-水（60∶40）为流动相,流速：1 ml/min,进样量：10μl,柱温35℃,检测波长300 nm。结果 南方医院的白芷欧前胡素含量0.73%,异欧前胡素为0.42%;东方大药房为1.56%和0.56%;宝芝林为0.84%和0.59%;二天堂为1.49%和0.67%;保健堂为0.43%和0.28%;广药集团为0.41%和0.27%;民意堂为0.74%和0.46%。结论 不同厂家出产的白芷的欧前胡素和异欧前胡素含量相差较大,因此不同厂家出产的白芷有效成分差别较大,市面出产的白芷质量参差不齐。     

HPLC法同时测定关节解痛膏中的辣椒素、二氢辣椒素、欧前胡素和异欧前胡素

目的：建立HPLC测定关节解痛膏中辣椒素、二氢辣椒素、欧前胡素和异欧前胡素含量的方法。方法：CAPCELL PAK C18色谱柱（250 mm×4.6 mm,5μm）;流速：0.8 ml·min^-1;流动相A：甲醇-乙腈（1∶1）,流动相B：1%磷酸溶液,梯度洗脱;检测波长分别为280 nm（辣椒素和二氢辣椒素）和254 nm（欧前胡素和异欧前胡素）。结果：辣椒素、二氢辣椒素、欧前胡素和异欧前胡素分别在0.298-5.956μg（r=0.999 8）、0.152-3.044μg（r=0.999 6）、0.018-0.352μg（r=0.999 5）、0.010-0.204μg（r=0.999 3）范围内进样量与峰面积呈良好的线性关系,平均加样回收率分别为97.8%、97.0%、96.6%、98.1%,RSD分别为1.02%、0.76%、0.65%、1.35%（n=6）。结论：方法简便、准确、灵敏、重复性好,可作为关节解痛膏中辣椒素、二氢辣椒素、欧前胡素和异欧前胡素的含量控制方法。     

高效液相色谱法测定清眩片中欧前胡素和异欧前胡素的含量

目的建立清眩片中欧前胡素和异欧前胡素含量测定的方法。方法采用高效液相色谱法,色谱柱：C18-A色谱柱（伊利特,200mm×4．6mm,5μm）;流动相：甲醇水（55：45）;流速：1．0mL·min^-1;检测波长：300nm。结果欧前胡素和异欧前胡素进样量分别在0．0151～0．1359μg和0．0105～0．0945μg与峰面积具有良好的线性关系（r=0．9999）,平均加样回收率分别为99．6％和100．6％,RSD分别为0．56％（n=6）和1．92％（n=6）。结论本方法能够快速、准确、方便的检测清眩片中欧前胡素和异欧前胡素的含量,可作为清眩片质量评价的依据。     

HPLC法同时测定不同产地白芷中2种香豆素的含量

目的采用HPLC法同时测定不同产地白芷中 2种香豆素的含量。方法色谱柱为岛津UL TRONVX ODS (2 5 0mm× 4 6mm ) ,5 μm柱 ,流动相为乙腈 水 (V∶V =6 5∶ 35 ) ,流速为0 8mL·min-1,检测波长 2 4 9nm。结果欧前胡素在 5～ 5 0mg·L-1(r =0 9999) ,异欧前胡素在2～ 2 0mg·L-1(r =0 9998)内线性关系良好 ,欧前胡素和异欧前胡素平均回收率分别为 98 4 %、96 3% ,RSD分别为 1 2 %、1 7%。结论不同产地白芷中 2种香豆素总量存在较大差异 ,可为评价不同产地白芷质量提供依据     

白芷香豆素类化合物的成分分析及CO_2超临界萃取工艺的研究

目的:建立以高效液相色谱(HPLC)法分析白芷香豆素类化合物的成分及CO2超临界流体法萃取白芷中香豆素类成分的的方法。方法:采用正交试验设计考察萃取压力、萃取温度、萃取时间及药材粒度对总香豆素收率的影响,用HPLC法检测萃取物中欧前胡素和异欧前胡素的含量。结果:欧前胡素、异欧前胡素的检测浓度线性范围分别为29.4～235.2、10～80μg/ml,平均回收率分别为(100.46±1.42)%、(99.94±1.18)%(n=3),相对标准差分别为1.76%、1.62%;以无水乙醇作为改性剂,白芷在萃取压力35MPa、萃取温度45℃、药材粒度60目、萃取时间3h时总香豆素收率最高。结论:萃取压力、药材粒度、萃取时间对总香豆素萃取收率均有显著影响;所建立的分析方法精密度高、简便快速,适于欧前胡素和异欧前胡素的含量测定。     

RP-HPLC法测定大鼠血浆中香柑内酯、欧前胡素和蛇床子素及其药动学研究

目的：建立测定大鼠血浆中香豆素类成分香柑内酯、欧前胡素和蛇床子素血药浓度的方法,并研究其在大鼠体内的药动学。方法：大鼠灌胃蛇床子提取物（900mg／kg）,分别于给药前及给药后0．25、0．5、0．75、1、2、3、4、6、8、12h取血,以反相高效液相色谱法测定血浆中香豆素类成分香柑内酯、欧前胡素和蛇床子素的血药浓度。色谱柱为Diamonsil C18（150mm×4．6mm,5gm）,流动相为乙腈．150mmol／L醋酸铵水溶液（50：50,V／V,醋酸调pH值至4．3）,流速为1．0ml／min,紫外检测波长为320nm,进样量为10μl。以非房室模型法（统计矩法）分析药动学参数。结果：香柑内酯、欧前胡素和蛇床子素质量浓度在0．1～5．0、0．5～25．0、2．0～100．0μg／ml范围内与各指标成分和相对应的峰面积积分值比呈良好线性关系。香柑内酯、欧前胡素、蛇床子素精密度试验的RsD≤8．8％,准确度在（91．8±2．01）％～（102．6±0．40）％之间,提取回收率在81．3％～92．8％之间,稳定性试验的RSD〈15％。香柑内酯、欧前胡素、蛇床子素的AUC0-∞分别为（5．53±1．07）、（22．67±3．65）、（39．60±4．56）μg·h／ml;t1/2分别为（3．33±0．39）、（2．27±0．55）、（2．24±0．35）h;Cmax分别为（1．18±0．22）、（7．03±1．27）、（13．16±1．37）μg／ml。结论：该方法简便、灵敏、专属性好,可用于大鼠体内香柑内酯、欧前胡素和蛇床子素的药动学研究。     

HPLC测定13种白芷中欧前胡素和异欧前胡素的含量

目的：建立一种控制白芷药材质量的方法。方法采用HPLC法，甲醇-水(70：30)为流动相，检测波长254nm。结果：欧前胡素在0．974-3．896μg范围内线性关系良好；异欧前胡素在0.360-2．640μg范围内线性关系良好。精密度及加样回收率良好。结论：该方法准确、迅速、重复性好，可用于白芷药材的质量控制。     

白芷中有效成分的筛选、分析及对大鼠血管活性的影响

目的对白芷中有效成分欧前胡素和异欧前胡素进行筛选和鉴定,并考察其对大鼠血管活性的影响。方法利用细胞膜色谱法(CMC)和气质联用法(GC/MS)对白芷中的有效成分进行筛选和鉴定,筛选过程采用大鼠动脉细胞膜色谱柱(50mm×1.0mm),37℃条件下用pH 7.4的磷酸钠缓冲液作为流动相,通过大鼠离体腹主动脉环实验对活性成分进行研究。结果欧前胡素和异欧前胡素在大鼠动脉细胞膜制成的细胞膜色谱系统中,能够产生与维拉帕米类似的药理作用。这2种成分能够显著抑制由重酒石酸去甲肾上腺素(NE)和氯化钙(CaCl2)诱导的血管收缩作用。结论在用白芷治疗血管疾病过程中,欧前胡素和异欧前胡素将作为2种主要发挥药理作用的有效成分。     

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。