格列吡嗪小肠吸收机制的研究

目的对格列吡嗪在大鼠小肠中的吸收机制进行研究。方法采用外翻肠囊法研究格列吡嗪在大鼠小肠中的吸收特征。结果离体肠吸收实验结果表明,格列吡嗪在大鼠的十二指肠、空肠、回肠和结肠4个肠段均有吸收,但在空肠中吸收最多;在高浓度和低浓度时,格列吡嗪累积吸收-时间曲线均呈线性,表明格列吡嗪在各肠段的吸收机制为被动扩散;增溶剂的加入可在一定程度上提高格列吡嗪的吸收;肠营养液的pH值小于格列吡嗪的pKa值时,格列吡嗪在溶液中多以分子型存在,分子型药物在小肠中易被吸收。结论格列吡嗪在大鼠的空肠段吸收为主,吸收机制为被动扩散,增溶剂的加入,提高了格列吡嗪在肠黏膜的通透性。     

滨蒿提取物中3种二咖啡酰奎宁酸的含量测定

目的建立滨蒿提取物中3,4-二咖啡酰奎宁酸、3,5-二咖啡酰奎宁酸和4,5-二咖啡酰奎宁酸的含量测定方法。方法采用HPLC法测定,色谱条件:Shim-pack VP-ODS色谱柱(250mm×4.6mm,5μm);流动相:乙腈-0.036mol·L~(-1)磷酸二元梯度洗脱;流速:1.0mL·min~(-1);柱温:30℃,检测波长:327nm。结果 3,4-二咖啡酰奎宁酸、3,5-二咖啡酰奎宁酸和4,5-二咖啡酰奎宁酸分别在0.010 3~0.309,0.009 7~0.291和0.010 5~0.315mg·mL~(-1)范围内与峰面积呈良好的线性关系(r=0.999 9);加样回收率分别为99.23%,101.30%和100.63%;RSD值分别为1.59%,0.83%和1.23%(n=6);样品溶液在32h内稳定。结论该方法操作简便,重复性好,可用于滨蒿提取物的质量控制。     

灯盏细辛中4种酚酸类有效成分的HPLC法测定

建立了HPLC法同时测定灯盏细辛中3,5-二咖啡酰基奎宁酸、1,5-二咖啡酰基奎宁酸、4,5-二咖啡酰基奎宁酸和飞蓬酯乙4种酚酸类有效成分的含量.采用C 18柱,流动相为乙腈-甲醇-0.5%甲酸溶液(梯度洗脱),流速1.0 ml/min,检测波长325nm.4种成分分别在0.1～2.5μg(r=0.999 8)、0.01～1μg(r=0.999 8)、0.1～2.5μg(r=0.999 6)和0.1～2.5μg(r=0.999 8)范围内线性关系良好,平均回收率分别为101.2%、102.3%、101.3%和101.8%.     

四妙勇安汤中绿原酸、甘草苷、阿魏酸在大鼠离体小肠的吸收动力学研究

目的研究四妙勇安汤中绿原酸、甘草苷、阿魏酸的大鼠离体小肠吸收动力学。方法通过外翻肠囊法进行离体肠吸收实验,HPLC法测定不同取样时间肠内液中绿原酸、甘草苷、阿魏酸的含量并计算累计吸收量,以累计吸收量对时间作线性回归分析,计算吸收动力学参数。采用Kromasil 100-5 C18色谱柱(250mm×4.6 mm,4μm),流速:1.0 m L·min-1,柱温:25℃,其中绿原酸以乙腈-0.4%磷酸水为流动相按13:87比例洗脱,检测波长:327 nm;阿魏酸、甘草苷以乙腈(A)-1%醋酸(B)为流动相进行梯度洗脱(0~25min,80%~60%B),检测波长:245 nm。结果绿原酸吸收动力学方程为Y=0.937X-8.111,r=0.982;甘草苷吸收动力学方程为Y=0.150X-0.936,r=0.983;阿魏酸吸收动力学方程为Y=0.049X+1.448,r=0.995。结论四妙勇安汤中绿原酸、甘草苷和阿魏酸在大鼠离体小肠的吸收为一级动力学过程。     

连翘苷在大鼠小肠的吸收特性研究

目的 研究连翘苷在大鼠小肠的吸收特性。方法 采用外翻肠囊法建立连翘苷大鼠小肠吸收模型,HPLC测定连翘苷的含量,分别进行大鼠小肠的十二指肠、空肠、回肠3个肠段、不同浓度吸收特性研究,以及P-糖蛋白(P-gp)抑制剂盐酸维拉帕米和吸收促进剂吐温-80对连翘苷吸收的影响研究。结果 连翘苷浓度为10,20,40 μg·mL^-1 3个浓度时,吸收速度常数ka无显著性差异(P>0.05);在不同肠段中的吸收,通过量由多到少依次为回肠>空肠>十二指肠;加入盐酸维拉帕米和吐温-80的小组与正常组相比,吸收速度常数ka无显著性差异(P>0.05)。结论 在试验剂量范围内,连翘苷的吸收呈一级动力学过程,吸收机制主要为被动扩散;连翘苷不是P-糖蛋白的底物。     

HPLC-DAD法同时测定清开灵注射液中7个酚酸类成分

目的:建立同时测定清开灵注射液中7个酚酸类成分(新绿原酸、绿原酸、隐绿原酸、咖啡酸、3,4-二咖啡酰奎宁酸、3,5-二咖啡酰奎宁酸、4,5-二咖啡酰奎宁酸)含量的方法。方法:采用Agilent Zorbax SB-C18色谱柱(250 mm×4.6 mm,5μm),流动相为0.1%甲酸水溶液(A)-乙腈(B),梯度洗脱,流速为0.5 mL·min-1,检测波长327 nm,柱温30℃。结果:80min内7个待测组分分离度良好,在各自的检测范围内与峰面积呈良好的线性,其相关系数均大于0.9998,加样回收率为96.1%～103.9%。应用所建立的方法同时测定了清开灵注射液中新绿原酸、绿原酸、隐绿原酸、咖啡酸、4,5-二咖啡酰奎宁酸、3,4-二咖啡酰奎宁酸、3,5-二咖啡酰奎宁酸共7个成分的含量,并对5个不同批次的注射液进行了含量测定,其结果有一定的差异。结论:本法可为清开灵注射液中酚酸类成分的质量控制提供参考。     

UFLC法测定四季抗病毒合剂中4种成分的质量浓度

目的测定四季抗病毒合剂中绿原酸、1,3-二咖啡酰奎宁酸、木犀草苷和3,5-二咖啡酰奎宁酸的质量浓度。方法采用超快速液相色谱(UFLC)法。色谱条件:色谱柱为Kromasil C18色谱柱(250mm×4.6mm,5μm);流动相为乙腈-3.0g·L~(-1)磷酸溶液梯度洗脱;流速为0.8mL·min~(-1);检测波长为348nm;柱温为35℃。结果绿原酸、1,3-二咖啡酰奎宁酸、木犀草苷和3,5-二咖啡酰奎宁酸的线性范围分别为24.00~960.00,22.00~880.00,3.00~120.00和24.00~960.00μg·mL~(-1),相关系数分别为0.999 3,0.999 2,0.999 6和0.999 3;平均回收率分别为98.62%(RSD=1.16%),98.90%(RSD=1.67%),98.37%(RSD=0.95%)和98.35%(RSD=0.91%);12批制剂中绿原酸、1,3-二咖啡酰奎宁酸、木犀草苷和3,5-二咖啡酰奎宁酸的平均质量浓度分别为142.91,191.39,16.89和140.20μg·mL~(-1),RSD值分别为0.97%,1.05%,1.16%和1.20%。结论文章测定的4种成分及建立的方法,可用于四季抗病毒合剂的质量评价。     

HPLC法同时测定绵茵陈中绿原酸等4种有效成分的含量

目的建立RP-HPLC法同时测定绵茵陈中绿原酸、3,5-二咖啡酰奎宁酸、4,5-二咖啡酰奎宁酸和金丝桃苷共4种有效成分的含量。方法采用RP-HPLC法。色谱柱为Phenomenex Luna C18柱(250 mm×4.6 mm,5μm),以乙腈-体积分数0.05%磷酸水为流动相,梯度洗脱,检测波长为345 nm,流速1.0 mL·min-1,柱温30℃。结果绿原酸、3,5-二咖啡酰奎宁酸、4,5-二咖啡酰奎宁酸和金丝桃苷质量浓度分别在2.609⁸3.50 mg·L-1(r=0.999 9)、1.85383.50 mg·L-1(r=0.999 9)、1.853⁵9.31 mg·L-1(r=0.999 6)、0.948 059.31 mg·L-1(r=0.999 6)、0.948 0³0.34 mg·L-1(r=0.999 8)和0.450 630.34 mg·L-1(r=0.999 8)和0.450 6¹4.42 mg·L-1(r=0.999 9)内与峰面积呈良好的线性关系,平均加样回收率(n=9)分别为96.3%、101.2%、101.4%和96.5%。结论该方法准确可靠,可用于绵茵陈的质量控制。     

3种杏香兔耳风提取物抑菌活性的研究

目的研究杏香兔耳风提取物A、杏香兔耳风提取物B及杏香兔耳风提取物C的抑菌活性。方法采用琼脂扩散法和平板稀释法,探讨了3种杏香兔耳风提取物的抑菌活性,测定了其抑菌直径和最低抑菌浓度。结果3种杏香兔耳风提取物对细菌有良好的抑制作用,酵母菌次之,霉菌最弱。结论3种杏香兔耳风提取物均有较好的开发利用价值。     

高效液相色谱法测定汉源金丝皇菊中3个活性成分的含量

目的建立同时测定汉源金丝皇菊中3个活性成分(绿原酸、木犀草苷和3,5-O-二咖啡酰基奎宁酸)含量的高效液相色谱方法。方法采用Agilent Poroshell 120 EC-C18(4.6 mm×150 mm,4μm)色谱柱分离;流动相为乙腈-0.1%磷酸溶液,梯度洗脱;流速1.0 mL/min;检测波长348 nm;柱温30℃。结果所测3个活性成分浓度在一定范围内呈良好的线性关系,r>0.9957;平均加样回收率分别为101.29%、96.63%、97.65%,RSD≤1.01%。结论经方法学验证,建立的分析方法简便、准确,灵敏度高,专属性强,可作为汉源金丝皇菊质量控制方法之一。     

The effect of inhibitors of folic acid absorption on the transfer rate constants in the rat everted proximal jejunum: A method for their evaluation from a three-compartment model

When solute transfer through the intestinal in vitro everted sac preparation is described by a three-compartment system, solute transfer rate constants can be derived for the mucosal and serosal permeability barriers. A catenary variant has been presented as well as a mammillary one where paracellular movement of solute is additionally allowed for. The first order differential rate equations governing the change in solute concentration in all three compartments with respect to time have been solved and the explicit analytical solutions provided. Since these solutions are cumbersome to use in the estimation of the required rate constants, a least squares procedure has been applied directly to the differential form of the rate equations in order to derive the rate constants without recourse to the analytical solutions. Verification of the solutions and of the estimated rate constants was by substitution of the latter into the former to test the goodness of fit for folic acid absorption data. Both variants take into account the simultaneous fluid movement which occurs during absorption experiments and which complicates the interpretation of absorption data. The mammillary model showed that only 10% of folic acid movement could pass directly through the paracellular pathways and that the bulk of folate movement is probably through the epithelial cells. However the catenary model without paracellular movement gave just as good fit to the data and was used subsequently. Experiments investigating the effect of substances implicated in folate malabsorption were analyzed in terms of the catenary model for folic acid absorption, in order to investigate their effects on the transfer rate constants free from the complicating effects on fluid movement. When pronounced inhibition took place, as with methotrexate, the mucosal rate constants were reduced, whereas the serosal rate constants were elevated. Also, the forward (k₁₂) mucosal rate constant correlated significantly with the overall folate transfer in contrast to the other rate constants. These observations are consonant with the concept of a mucosally sited entry step exerting a controlling influence over the transfer rate of folic acid rather than a serosally sited exit process and with the conclusion that this may be the site of action of substances causing folate malabsorption.     

头孢唑肟致尿毒症透析患者中枢神经系统不良反应1例

目的研究连翘苷在大鼠小肠的吸收特性。方法采用外翻肠囊法建立连翘苷大鼠小肠吸收模型,HPLC测定连翘苷的含量,分别进行大鼠小肠的十二指肠、空肠、回肠3个肠段、不同浓度吸收特性研究,以及P-糖蛋白（P-gp）抑制剂盐酸维拉帕米和吸收促进剂吐温-80对连翘苷吸收的影响研究。结果连翘苷浓度为10,20,40μg.mL-1 3个浓度时,吸收速度常数ka无显著性差异（P〉0.05）;在不同肠段中的吸收,通过量由多到少依次为回肠〉空肠〉十二指肠;加入盐酸维拉帕米和吐温-80的小组与正常组相比,吸收速度常数ka无显著性差异（P〉0.05）。结论在试验剂量范围内,连翘苷的吸收呈一级动力学过程,吸收机制主要为被动扩散;连翘苷不是P-糖蛋白的底物。     

大鼠离体外翻肠囊模型对豆腐果苷分肠段吸收初步研究

目的:基于大鼠离体外翻肠囊模型探讨豆腐果苷在不同肠段的吸收情况。方法:建立豆腐果苷及其代谢产物高效液相色谱同时检测方法。在不同肠段(十二指肠、空肠、回肠、结肠)的外翻肠囊模型中加入含豆腐果苷的Krebs-Ringer液,不同时间点(5,10,15,30,45,60,75,90 min)取样并测定囊内药物浓度,比较四个肠段对豆腐果苷的吸收情况。结果:所建立的高效液相色谱法成功应用于豆腐果苷及其代谢产物同时检测。豆腐果苷及其代谢产物吸收迅速并呈明显的时间依赖性,十二指肠段的吸收与代谢情况均高于其他肠段。结论:十二指肠肠段是豆腐果苷分肠段吸收与代谢的主要部位,这是豆腐果苷肠段代谢研究的首次报道。     

外翻肠囊法研究姜黄素促进葫芦素B肠段吸收作用

目的:建立大鼠肠吸收模型,考察对葫芦素B的吸收以及姜黄素对葫芦素B吸收的促进作用。方法:采用大鼠离体外翻肠囊模型,通过HPLC法测定肠囊内样品溶液中葫芦素B的含量,研究葫芦素B在不同肠段的吸收特性和不同比例姜黄素对葫芦素B的促吸收作用。结果:葫芦素B的肠吸收随其浓度的升高而增大,当葫芦素B联合不同比例姜黄素后,百分吸收率(P%)、累计吸收量(Q)和吸收速率常数K_a值均具有显著性差异。结论:葫芦素B主要吸收部位为十二指肠,且在大鼠肠内主要以被动扩散方式吸收;姜黄素能够促进葫芦素B的大鼠肠吸收,且呈浓度依赖性。     

外翻肠囊法比较黄芩苷磷脂复合物与黄芩苷在大鼠小肠的吸收

目的比较黄芩苷磷脂复合物和黄芩苷在离体小肠中累积吸收的差异。方法采用外翻肠囊法制备离体小肠吸收模型,用HPLC测定小肠吸收的黄芩苷。结果黄芩苷及黄芩苷磷脂复合物在120 min内透过肠壁的黄芩苷含量均随时间的延长而增多;黄芩苷在小肠的吸收显著多于黄芩苷磷脂复合物（P〈0.05）。结论黄芩苷在小肠的吸收量大于黄芩苷磷脂复合物,黄芩苷磷脂复合物增加黄芩苷吸收的部位不在小肠。     

溴吡斯的明在大鼠离体肠的吸收动力学

目的观察溴吡斯的明在各肠段的吸收动力学特征。方法采用大鼠外翻肠囊模型,反相离子对色谱法测定不同浓度(25、50、100 mg.L-1)的溴吡斯的明在各肠段的吸收量,计算吸收速率常数(Ka)和表观渗透系数(Papp),并考察P-糖蛋白抑制剂(环孢素和维拉帕米)对药物吸收的影响。结果在25、50、100 mg.L-1溴吡斯的明条件下,Ka按十二指肠、空肠、回肠、结肠依次减小,不同浓度溴吡斯的明对同一肠段的Ka无显著影响(P>0.05),十二指肠、空肠、回肠间的Ka无显著差异(P>0.05),在50、100 mg.L-1溴吡斯的明条件下,结肠的Ka与十二指肠、空肠、回肠比较有显著差异(P<0.05,P<0.01)。随着溴吡斯的明浓度增加,各肠段Papp显著降低,不同肠段间的Papp有显著差异(P<0.05,P<0.01)。P-糖蛋白抑制剂对溴吡斯的明吸收无影响(P>0.05)。结论溴吡斯的明在十二指肠有较好吸收,在空肠和回肠有一定吸收,在结肠中吸收较少。     

Antitussive,expectorant, and anti-inflammatory activities of four caffeoylquinic acids isolated from Tussilago farfara

Context: The flower bud of Tussilago farfara L. (Compositae) (FTF) is one of the traditional Chinese medicinal herbs used to treat cough, phlegm, bronchitic, and asthmatic conditions.

Objective: The objective of this study is to isolate four caffeoylquinic acids from the ethyl acetate extract (EtE) of FTF and to evaluate their antitussive, expectorant, and anti-inflammatory activities.

Materials and methods: The structures of compounds 1–4 isolated from EtE were determined by spectral analysis. Mice were orally treated with these compounds and their mixture (in a ratio of 5:28:41:26 as in EtE) at doses of 10 and 20?mg/kg once daily for 3 d. The antitussive and expectorant activities were evaluated separately with the ammonia liquor-induced model and the phenol red secretion model. The anti-inflammation activity was evaluated using leukocyte count in the bronchoalveolar lavage fluid after ammonia liquor-induced acute airway inflammation.

Results: The four compounds were identified as chlorogenic acid (1), 3,5-dicaffeoylquinic acid (2), 3,4-dicaffeoylquinic acid (3), and 4,5-dicaffeoylquinic acid (4). All compounds, especially compound 4 (58.0% inhibition in cough frequency), showed a significant antitussive effect. However, the mixture was the most effective to inhibit the cough frequency by 61.7%. All compounds also showed a significant expectorant effect, while compound 2 was the most potent to enhance the phenol red secretion by 35.7%. All compounds significantly alleviated inflammation, but compound 4 showed the strongest effect to inhibit the leukocytosis by 49.7%.

Discussion and conclusion: The caffeoylquinic acids and their mixture, exhibiting significant antitussive, expectorant, and anti-inflammatory effects, could be considered as the main effective ingredients of FTF, and they may act in a collective and synergistic way.     

Intestinal absorption characteristics of ketoprofen in rats

The present study aims to investigate the intestinal absorption characteristics of ketoprofen in rats. The pharmacokinetic profile of ketoprofen was evaluated following a single p.o. administration of ketoprofen (1 mg/kg) to rats in the absence and presence of benzoic acid or lactic acid (2 and 10 mg/kg), the substrates of monocarboxylic acid transporters. The pharmacokinetic profiles of ketoprofen (1 mg/kg) were significantly altered by the concurrent use of benzoic acid or lactic acid (10 mg/kg), compared with the control (given ketoprofen alone). The Cmax and AUC of ketoprofen in the presence of benzoic acid or lactic acid (10 mg/kg) were significantly (p<0.05) lower than those from the control group, while there was no significant change in Tmax and the terminal plasma half-life (T1/2) of ketoprofen. These results suggest that ketoprofen shares a common transport pathway with benzoic acid and lactic acid during the intestinal absorption in rats.     

齐酞酸钠在大鼠肠道吸收动力学研究

目的:研究齐酞酸钠(OAHDPS)在大鼠肠道内的吸收特性.方法:采用大鼠在体小肠吸收实验方法,测定OAHDPS在不同剂量(100,50,25μg·mL-1)下结扎和不结扎胆管条件下的小肠吸收量和吸收速率常数(Ke),并比较各个肠段的吸收.结果:研究表明,OAHDPS在肠道内的吸收机制是被动扩散方式,且在小肠的吸收不受胆汁等分泌物的影响;在肠道正常pH值情况下,平均Ke为(0.162±0.012)h-1;各个肠段对OAHDPS均有吸收且Ke无显著差异.结论:在OAHDPS口服剂型设计时应首先考虑肠溶缓释制剂.     

UPLC/Q-TRAP-MS分析一元羧酸转运体对白头翁五环三萜皂苷吸收的影响

目的：考察白头翁五环三萜皂苷B3,BD,B7,B10,B11在十二指肠、空肠、回肠中的膜通透性,并研究小肠上皮MCTs对5种五环三萜皂苷吸收的影响。方法：采用大鼠外翻肠囊实验,建立超高效液相色谱-三重四级-线性离子肼-质谱（UPLC/Q-TRAP-MS）法,通过一元羧酸转运体（MCTs）抑制剂阿魏酸、苯甲酸和布洛芬实验进行考察。结果：5种白头翁皂苷类成分在十二指肠段中的表观渗透率（P_app）最高（P<0.05或P<0.01）,空肠段次之,回肠段最小;阿魏酸、苯甲酸、布洛芬在十二指肠、空肠、回肠中对白头翁皂苷均有抑制作用（P<0.05,P<0.01）。结论：十二指肠可能为该类皂苷吸收的主要部位;白头翁皂苷可能为MCTs的底物。