芙朴感冒颗粒对斑马鱼胚胎发育的影响

摘要：目的:研究芙朴感冒颗粒对斑马鱼胚胎发育的影响,为临床安全用药提供相关参考资料。方法:选择6 h的斑马鱼胚胎为实验模型,设置空白对照组和芙朴感冒颗粒低、中、高（10,20,50 g·L-1）浓度组,显微镜下观察并记录斑马鱼胚胎发育情况,检测自主运动次数、心率、畸形率、孵化率、泳速等,以初步分析芙朴感冒颗粒对斑马鱼胚胎发育的影响。结果:芙朴感冒颗粒可致斑马鱼胚胎发育畸形,主要表现为心包囊肿、充血和脊柱弯曲;芙朴感冒颗粒能明显抑制斑马鱼胚胎自主运动和心率;芙朴感冒颗粒低浓度时促进胚胎孵化和斑马鱼胚胎孵育后仔鱼的泳速,高浓度则抑制胚胎孵化和仔鱼泳速。结论:芙朴感冒颗粒可影响斑马鱼胚胎的正常发育。     

HPLC法测定芙朴感冒颗粒中橙皮苷的含量

目的:建立了测定芙朴感冒颗粒中橙皮苷的HPLC测定方法.方法:采用C18柱(250 mm×4.6 mm,5μm),甲醇-水-冰醋酸(30:65:5)为流动相,检测波长为280 nm.结果:橙皮苷在10～100μg/mL浓度范围内呈良好的线性关系,r=0.999 9.平均回收率为98.62%,RSD为1.72%.结论:本法简便、快速,可用于该制剂的质量控制.     

HPLC法同时测定芙朴感冒颗粒中芦丁等3种成分

目的建立同时测定芙朴感冒颗粒中芦丁、橙皮苷、牛蒡苷3种成分的HPLC方法。方法采用Agilent C18色谱柱(150mm×4.6mm,5μm),柱温35℃,流动相为乙腈-1%冰醋酸,梯度洗脱,检测波长280nm,体积流量1.0mL·min-1。结果 3种成分均达到基线分离,芦丁、橙皮苷、牛蒡苷进样量分别在21.68～216.80,21.08～210.80,1039.00～10390.00ng与峰面积线性关系良好,平均回收率分别为97.8%、98.3%、99.6%。结论该方法准确可靠,可用于芙朴感冒颗粒的质量控制。     

HPLC法测定芙扑感冒颗粒中橙皮苷的含量

目的:建立了测定芙朴感冒颗粒中橙皮苷的HPLC测定方法。方法:采用C18柱(250mm×4.6mm,5μm),甲醇-水-冰醋酸(30∶65∶5)为流动相,检测波长为280nm。结果:橙皮苷在10～100μg/mL浓度范围内呈良好的线性关系,r=0.9999。平均回收率为98.62%,RSD为1.72%。结论:本法简便、快速,可用于该制剂的质量控制。     

四季感冒颗粒质量控制研究

目的 建立四季感冒颗粒的质量标准.方法 采用薄层色谱法鉴别桔梗、香附(炒)和陈皮;采用高效液相色谱法测定橙皮苷的含量.结果 TLC斑点清晰集中;橙皮苷检测浓度在12.12μg·mL-1～109.08μg*mL-1范围内与峰面积积分值呈良好线性关系(r=0.9993);平均回收率为99.75%,RSD=0.94%(n= 6).结论 所建标准可用于四季感冒颗粒的质量控制.     

不同纯度和浓度橙皮苷对大鼠在体肠吸收比较研究

目的:比较研究不同纯度和浓度的橙皮苷在大鼠体肠吸收情况,初步探讨橙皮苷的吸收机理.方法:运用大鼠在体肠灌流模型,收集灌流流出液,并采用HPLC测定橙皮苷和酚红在灌流液中的浓度,对橙皮苷吸收特性进行研究.结果与结论:橙皮苷在大鼠肠道的吸收常数Ka随浓度的升高而显著降低(P<0.01),但纯度升高时Ka降低不显著(P>0.05);橙皮苷提取物中的共存成分可增加其吸收,吸收方式现可排除被动吸收,但有仍待于进一步研究.     

5种中成药治疗外感风热型慢性咽炎的药物成本-效果比较

目的：对5种中成药治疗外感风热型慢性咽炎的药效与经济学情况进行比较分析,为临床合理用药提供参考。方法将本院门诊部治疗的241例外感风热型慢性咽炎患者按不同用药随机分成5组,即清开灵片组、感咳双清胶囊组、芙朴感冒颗粒组、一清胶囊组和清开灵颗粒组。比较5组的总有效率,进而进行成本-效果分析。结果清开灵片组总有效率为95.7%,感咳双清胶囊组为95.8%、芙朴感冒颗粒组为98.0%,一清胶囊组为95.9%,清开灵颗粒组为97.9%。各组总有效率接近,差异无统计学意义;成本-效果分析结果显示,清开灵片组的成本-效果比最小（C/E=1.13）,为最佳治疗方案。结论清开灵片在临床外感风热型慢性咽炎用药中具有一定优势,临床疗效确切,且成本低。     

栀子大黄汤有效成分在体肠吸收研究

目的：研究栀子大黄汤中栀子苷、柚皮苷、橙皮苷和新橙皮苷4种有效成分的大鼠在体肠吸收动力学。方法：运用大鼠在体单向灌流重量法进行肠吸收实验,考察不同吸收部位和药物浓度下的肠吸收动力学,采用HPLC法测定有效成分的浓度。结果：栀子苷、柚皮苷和新橙皮苷在小肠的吸收速率常数（Ka）和有效渗透系数（Peff）显著大于结肠（P〈0.05）;橙皮苷在十二指肠和空肠吸收参数显著大于回肠和结肠（P〈0.05）;药物浓度在一定范围内对栀子苷、柚皮苷和新橙皮苷的Ka和Peff无显著影响（P〉0.05）,橙皮苷的Ka和Peff随浓度的升高先增加后降低。结论：栀子大黄汤中4种有效成分在全肠道均有吸收;栀子苷、柚皮苷和新橙皮苷的吸收机制为被动扩散,橙皮苷在吸收过程中存在高浓度饱和现象,推测吸收机制为主动转运或易化扩散。     

综合评分法优化柴银感冒颗粒提取液的澄清工艺

目的优化柴银感冒颗粒提取液的澄清工艺,以提高产品出膏率。方法采用正交实验设计,以出膏率、总黄酮含量、橙皮苷含量为评分指标,筛选柴银感冒颗粒提取液的澄清工艺条件。结果柴银感冒颗粒提取液的澄清条件为:药液浓度为1∶6,澄清剂浓度为1.0%,澄清剂用量为4B2A(每100 mL待处理溶液加入配制好的B黏胶液4 mL,A黏胶液2mL),不调pH值。结论该工艺简便,可行,既保证了产品质量,又提高了出膏率,适用于生产实际。     

坤复康片中芍药内酯苷在Caco-2细胞模型中的吸收特征研究

目的 研究坤复康片中的芍药内酯苷在Caco-2细胞模型中的跨膜吸收特征,探讨人小肠对芍药内酯苷的吸收和转运.方法 研究了不同药物浓度、pH值、温度和抑制剂对芍药内酯苷在Transwell细胞培养板中从顶膜(apical,AP)到基底(basolateral,BL)的双向渗透吸收的影响.结果 芍药内酯苷以3种测试浓度给药...     

抗肿瘤药物西美替尼在Caco-2细胞模型中的吸收转运

目的研究抗肿瘤药物西美替尼在Caco-2细胞模型中的吸收转运。方法建立Caco-2细胞转运模型,采用HPLC法测定药物浓度,计算表观渗透系数(P_app),研究西美替尼的Caco-2细胞跨膜转运情况。结果西美替尼在转运过程中没有明显的浓度依赖性。在低浓度范围内,药物的转运速率随着浓度的增加而增加;在较高浓度时达到饱和。西美替尼不同浓度的P_app值(3.91×10^-5、3.29×10^-5、1.90×10^-5和0.95×10^-5cm·s^-1)基本都大于难吸收药物的临界值(1×10^-5cm·s^-1)。西美替尼在Caco-2细胞中的转运呈现较强的方向性,从肠腔面到基底面的P_app值显著大于从基底面到肠腔面的P_app值（2.36～7.58倍）。ATP抑制剂叠氮化钠能显著降低西美替尼的正向转运程度,并升高其反向转运程度。当加入葡萄糖后,从肠腔面到基底面的跨膜转运程度显著降低。结论西美替尼主要是以转运载体介导的主动转运方式被吸收,其小肠吸收情况较好。     

去氢骆驼蓬碱衍生物DH-004大鼠在体肠吸收动力学研究

目的考察去氢骆驼蓬碱衍生物DH-004大鼠在体肠吸收动力学特征,探讨其可能的吸收机制。方法建立UPLC法测定灌流液中DH-004浓度,用大鼠在体单向肠灌流模型考察不同质量浓度的DH-004在不同肠段的吸收特征。结果 DH-004在全肠段均有吸收。20.0μg·mL^-1 DH-004在十二指肠、空肠、回肠和结肠的吸收速率常数(K_a)分别为(11.66±3.84)×10^-2,(10.85±2.65)×10^-2,(7.48±1.70)×10^-2和(4.75±1.14)×10^-2 min,药物表观渗透系数(P_app)分别为(1.47±0.33)×10^-2,(1.55±0.20)×10^-2,(1.25±0.10)×10^-2和(0.98±0.22)×10^-2 cm·min^-1。DH-004在十二指肠段与空肠段的K_a均明显大于其在回肠和结肠的K_a(均P<0.05)。结论 DH-004在大鼠小肠全段有不同程度地吸收,十二指肠和空肠可能为其主要吸收部位。     

复方黄甘颗粒对罗丹明123和6-羧基荧光素经肠黏膜转运的影响

目的：观察复方黄甘颗粒对P-糖蛋白（P-gp）底物罗丹明123（R123）和非P-gp底物6-羧基荧光素（CF）经肠黏膜转运的影响,为复方黄甘颗粒与P-gp底物药物合理联用提供依据。方法：20只SPF级SD雄性大鼠,体重（250±20）g,用随机数字表法分为生理盐水组和复方黄甘颗粒组,每组10只。分别给予生理盐水20mL/kg和1.0g/L复方黄甘颗粒溶液20mL/kg灌胃,2次/d,连续7d。1周后大鼠禁食16～18h,用10%水合氯醛（3mL/kg）腹腔麻醉,取空肠标本3～4cm,用体外扩散池法检测2组大鼠空肠黏膜对R123和CF透过性的影响,比较2组吸收方向转运[黏膜侧（M）-浆膜侧（S）]和分泌方向转运（S-M）的表观渗透系数（Papp）及泵出比（ER）。结果：生理盐水组与复方黄甘组R123吸收方向的Papp分别为（3.54±0.86）×10-6和（2.39±0.44）×10-6cm/s,分泌方向的Papp分别为（8.68±3.76）×10-6和（8.34±2.47）×10-6cm/s;生理盐水组与复方黄甘组CF吸收方向的Papp分别为（5.40±3.20）×10-6cm/s和（3.28±1.41）×10-6cm/s,分泌方向的Papp分别为（5.09±1.71）×10-6cm/s和（3.98±1.02）×10-6cm/s;差异均无统计学意义（均P〉0.05）。生理盐水组R123的ER为2.45,CF的ER为0.94;复方黄甘组R123的ER为3.50,CF的ER为1.21。结论：复方黄甘颗粒对肠黏膜P-gp的活性无明显影响,提示复方黄甘颗粒与R123类似的P-gp底物药物联合应用较为安全。     

Determination of site of absorption of propranolol in rat gut using in situ single-pass intestinal perfusion

Previously, permeability and site of intestinal absorption of propranolol have been reported using the Ussing chamber. In the present study, the utility of Single-Pass Intestinal Perfusion to study permeability and site of intestinal absorption of propranolol was evaluated in rats. Drug permeability in different regions of rat intestine viz. duodenum, jejunum, ileum and colon was measured. Propranolol (30 μg/ml) solution was perfused in situ in each intestinal segment of rats. Effective permeability (Peff) of propranolol in each segment was calculated and site of absorption was determined. The Peff of propranolol in rat duodenum, jejunum, ileum and colon was calculated to be 0.3316×10(-4) cm/s, 0.4035×10(-4)cm/s, 0.5092×10(-4) cm/s and 0.7167×10(-4) cm/s, respectively. The above results suggest that permeability of propranolol was highest through colon compared to other intestinal sites, which is in close agreement to that reported previously. In conclusion, in situ single pass intestinal perfusion can be used effectively to study intestinal permeability as well as site of intestinal absorption of compounds in rats.     

橙皮苷脂质体凝胶的制备及其透皮吸收研究

目的:制备橙皮苷脂质体凝胶并对其体外释药和透皮吸收情况进行考察。方法:采用薄膜超声法制备橙皮苷脂质体,以包封率为主要评价指标,在单因素实验基础上采用Box-Behnken响应面法优化处方,并对最优处方制备的橙皮苷脂质体凝胶进行各项理化指标、体外释放模型和透皮吸收进行考察。结果:橙皮苷脂质体最优处方为磷胆比2.35∶1、磷药比7.43∶1、水合介质pH 6.54。橙皮苷脂质体粒径(207.87±13.27)nm,PDI (0.36±0.02),Zeta电位(-40.60±3.32)mV,包封率(58.21±0.90)%,橙皮苷脂质体凝胶体外释药曲线符合Ritger-Peppas方程(R²_adj=0.998 9)。结论:橙皮苷脂质体凝胶黏度适宜,易于涂展,体外释药具有明显的缓释效果且透皮吸收特性良好,该制备方法稳定可行,适用于橙皮苷脂质体凝胶的制备。     

Solubility,Stability, Physicochemical Characteristics and <Emphasis Type="BoldItalic">In Vitro</Emphasis> Ocular Tissue Permeability of Hesperidin: A Natural Bioflavonoid

Purpose  Hesperidin holds potential in treating age-related macular degeneration, cataract and diabetic retinopathy. The aim of this study, constituting the first step towards efficient ocular delivery of hesperidin, was to determine its physicochemical properties and in vitro ocular tissue permeability. Methods  pH dependent aqueous solubility and stability were investigated following standard protocols. Permeability of hesperidin across excised rabbit cornea, sclera, and sclera plus retinal pigmented epithelium (RPE) was determined using a side-bi-side diffusion apparatus. Results  Hesperidin demonstrated poor, pH independent, aqueous solubility. Solubility improved dramatically in the presence of 2-hydroxypropyl-beta-cyclodextrin (HP-β-CD) and the results supported 1:1 complex formation. Solutions were stable in the pH and temperature (25, 40°C) conditions tested, except for samples stored at pH 9. Transcorneal permeability in the apical-basal and basal-apical directions was 1.11 ± 0.86 × 10⁻⁶ and 1.16 ± 0.05 × 10⁻⁶ cm/s, respectively. The scleral tissue was more permeable (10.2 ± 2.1 × 10⁻⁶ cm/s). However, permeability across sclera/choroid/RPE in the sclera to retina and retina to sclera direction was 0.82 ± 0.69 × 10⁻⁶, 1.52 ± 0.78 × 10⁻⁶ cm/s, respectively, demonstrating the barrier properties of the RPE. Conclusion  Our results suggest that stable ophthalmic solutions of hesperidin can be prepared and that hesperidin can efficiently permeate across the corneal tissue. Further investigation into its penetration into the back-of-the eye ocular tissues is warranted.     

陈皮配方颗粒质量标准研究

目的建立陈皮配方颗粒的质量标准。方法采用薄层色谱(TLC)法进行定性鉴别;运用傅立叶变换红外光谱(FTIR)法进行检验;采用高效液相色谱(HPLC)法测定方中橙皮苷含量,色谱柱为Agilent HC-C18柱(250 mm×4.6 mm,5μm),甲醇-醋酸-水(35∶4∶61)为流动相,流速为0.8 mL/min,柱温为30℃,检测波长为283.4 nm。结果用薄层色谱法检出了方中的橙皮苷。红外光谱法对陈皮配方颗粒所含基团进行了详细分析。高效液相色谱法测定的橙皮苷进样量线性范围为0.676～4.056μg,回归方程为Y=600.759 62 X-21.199,r=0.999 9,平均回收率为97.61%,RSD=0.80%(n=6)。结论所建立的方法简便、准确、重现性好,可作为陈皮配方颗粒的质量控制方法。     

In vitro study of intestinal transport of arsenite, monomethylarsonous acid, and dimethylarsinous acid by Caco-2 cell line

Arsenic is a pollutant widely distributed in the environment. There are numerous studies on the toxicity of trivalent arsenic forms As(III), MMA(III), and DMA(III), but few data are available on the processes of digestion and absorption of these arsenic species and the mechanisms involved are unknown. The present study evaluated the processes involved in intestinal absorption of trivalent arsenic species, using the Caco-2 cell model as system. The apparent permeability values obtained for As(III) in apical-basolateral direction (4.6±0.3)×10(-6)cm/s, showing moderate intestinal absorption. Transport of MMA(III) [P(app)=(7.0±0.9)×10(-6)cm/s] and DMA(III) [P(app)=(10.6±1.4)×10(-6)cm/s] is greater than that of As(III). The cellular retention of As(III) (0.9-2.4%) was less than that observed for MMA(III) (30%) and DMA(III) (35%). A substantial paracellular component was observed in transport of As(III) and MMA(III), whereas DMA(III) does not use this pathway for its absorption. For all the trivalent species, transport depends on temperature, with an active transcellular component for MMA(III) and DMA(III). Variations in pH do not affect transport of these species. The presence of GSH and green tea extract significantly alters transport of As(III) across Caco-2 cells.     

高效液相色谱法测定暑湿感冒颗粒中防风和陈皮含量

目的采用高效液相色谱梯度洗脱法同时测定暑湿感冒颗粒中5-O-甲基维斯阿米醇苷、升麻苷、橙皮苷含量。方法色谱柱为Phenomenex C18柱（250 mm×4.6 mm,5μm）,流动相为甲醇-水,梯度洗脱,流速1 mL/min,检测波长290 nm,柱温30℃。结果 5-O-甲基维斯阿米醇苷、升麻苷对照品、橙皮苷的进样量线性范围分别为0.053～0.426μg（r=0.9999）、0.128～1.021μg（r=0.9999）、0.110～0.877μg（r=0.999 9）,平均回收率分别为102.9%,98.0%,100.6%,RSD分别为2.2%,1.9%,1.7%（n=6）。结论该方法专属性、重复性好,可用于暑湿感冒颗粒的质量控制。