中药制剂中违禁添加10种化学降糖药的HPLC-DAD法测定

建立了HPLC-DAD法同时检测中药制剂中违禁添加的氯磺丙脲、甲苯磺丁脲、格列吡嗪、格列齐特、盐酸吡格列酮、米格列奈、格列本脲、格列美脲、那格列奈和格列喹酮10种化学降糖药.采用C_(18)色谱柱,以0.2%三乙胺水溶液(用磷酸调至pH 3.5)-甲醇为流动相,梯度洗脱,检测波长220 nm.10种药物分别在5～50和10～100μg/ml浓度范围内线性关系良好,检测限为0.35～3.87μg/ml.     

复方盐酸二甲双胍胶囊在人体内药物动力学和生物等效性研究

目的:研究复方盐酸二甲双胍胶囊在健康男性受试者体内药物动力学和相对生物利用度。方法:20名男性受试者随机交叉口服复方二甲双胍胶囊[试验品2粒或合用格华止与格列本脲片(参比药)各1片],用HPLC方法分别测定血浆中二甲双胍和格列本脲浓度,计算药物动力学参数和相对生物利用度。结果:口服试验药或参比药后二甲双胍的Cmax分别为(1 112±350)和(1 040±340)ng/ml;tp分别为(2.5±0.7)和(2.5±0.9)h;AUC0→∞分别为(6 018.2±1 123.8)和(6 070.4±1 626.8)ng.h/ml;格列本脲的Cmax分别为(65.7±23.4)和(69.1±20.8)ng/ml;tp分别为(3.1±0.9)和(3.2±0.9)h;AUC0→∞分别为(303.2±81.8)和(318.2±92.3)ng.h/ml;二甲双胍和格列本脲的相对生物利用度分别为(102.5±17.5)%和(97.0±15.9)%。结论:统计学分析表明复方二甲双胍胶囊与联合服用格华止与格列本脲片具有生物等效性。     

高效液相色谱法测定消糖灵胶囊中格列本脲的含量

目的 探讨用高效液相色谱法测定消糖灵胶囊中格列本脲的含量.方法 采用HP ODS-Hypersil色谱柱(4.6 mm×200 mm,5μm)柱温:20℃,流动相:甲醇-0.005 mol/L磷酸二氢胺(pH3.5,70:30),流速:0.8 ml/min,检测波长:300 nm.结果 格列本脲在0.141～2.25 μm范围内呈较好的线性关系(r=0.999 9,n=5),平均回收率为99.18%,RSD为1.72%(n=3).结论 HPLC法测定格列本脲简便、快捷、灵敏,可以作为消糖灵胶囊含量的测定方法.     

反相高效液相色谱法检测 十味玉泉胶囊中添加的格列苯脲

目的检测十味玉泉胶囊中添加的格列苯脲。方法采用反相高效液相色谱法,以甲醇一磷酸二氢铵(6:3)为流动相,C18为固定相,流速1.20ml/min,在274μm波长处进行定性定量分析。结果供试品中检出格列苯脲,其含量为1.1mg/粒(RSD=0.81%,n=5)。结论本方法简便,准确,专属性好。     

高效液相色谱法测定消糖灵胶囊中格列本脲的含量

目的探讨用高效液相色谱法测定消糖灵胶囊中格列本脲的含量。方法采用HPODS-Hypersil色谱柱(4.6mm×200mm,5μm)柱温:20℃,流动相:甲醇-0.005mol/L磷酸二氢胺(pH3.5,70∶30),流速:0.8ml/min,检测波长:300nm。结果格列本脲在0.141～2.25μg范围内呈较好的线性关系(r=0.9999,n=5),平均回收率为99.18%,RSD为1.72%(n=3)。结论HPLC法测定格列本脲简便、快捷、灵敏,可以作为消糖灵胶囊含量的测定方法。     

人胎盘ATP结合盒转运蛋白对格列本脲胎盘转运的影响

目的研究成熟胎盘ATP结合盒转运蛋白对格列本脲胎盘透过率的影响。方法建立人胎盘体外循环灌注模型40例,分为4组(n=10),分别用格列本脲、格列本脲和维拉帕米(PGP抑制剂组)、格列本脲和尼卡地平(BCRP抑制剂组)、格列本脲和吲哚美辛(MRPs抑制剂组)循环灌注3 h,计算各组格列本脲的胎盘透过率和清除指数。结果 3 h循环结束后,4组格列本脲的平均胎盘透过率分别为(0.78±0.66)%、(2.17±0.90)%、(1.45±0.70)%、(3.65±2.10)%,与格列本脲组相比,加入抑制剂后各组格列本脲胎盘透过率均有增加(P<0.05),MRPs抑制剂组透过率高于PGP抑制剂组和BCRP抑制剂组(P<0.05);4组格列本脲相对透过率分别为(0.03±0.02)、(0.08±0.04)、(0.05±0.02)、(0.13±0.05),PGP抑制剂组和MRPs抑制剂组的清除指数均高于格列本脲组(P<0.05),且MRPs抑制剂组高于PGP抑制剂组(P<0.05)。结论 PGP、BCRP、MRPs抑制剂均不同程度地参与了格列本脲的胎盘转运,其中,MRPs抑制剂的影响可能更为显著。     

HPLC法测定消渴丸中格列本脲的含量

消渴丸是由葛根地黄等7味中药及西药格列本脲制成.成功为滋肾养阴,益气生津.用于治疗糖尿病.格列本脲是降糖的主要有效成分.且格列本脲有许多不良反应 ,所以笔者建立了高效液相色谱法(HPLC)测定消渴丸中格列本脲的方法,以控制格列本脲的含量,保证药品质量及用药安全.     

高效液相色谱法测定复方二甲双胍格列本脲片中杂质双氰胺的含量

目的:建立以高效液相色谱法测定复方二甲双胍格列本脲片中杂质双氰胺含量的方法。方法:色谱柱为Maeherey-Nagel不锈钢柱,流动相为甲醇-1.7%磷酸二氢铵(30∶70),检测波长为218nm,流速为1.0ml/min,进样量为20μl,柱温为室温。结果:双氰胺检测浓度在0.0 625~1.000μg/ml范围内线性关系良好,平均加样回收率为96.53%(RSD=1.66%)。结论:本方法灵敏度高,结果准确、可靠,专属性强,操作简便、快速,适合于复方二甲双胍格列本脲片中杂质双氰胺的含量测定。     

糖尿乐胶囊中格列本脲的测定

对糖尿乐胶囊中违法添加的格列本脲成分进行确认和定量测定.采用TLC法及HPLC法对格列本脲进行定性鉴别;以对羟基苯甲酸丁酯作为内标物,采用HPLC法对格列本脲进行含量测定.结果批号为20030101、20020928、20030207的样品均检出格列本脲;其含量值分别0.157mg/粒、0.138mg/粒、0.076mg/粒.     

格列本脲和盐酸二甲双胍合用致低血糖1例

崔××,女69a,因右侧肢体无力20d,左侧肢体无力3d,加重1d入院,诊断为多发性脑梗死,糖尿病,酮症酸中毒.治疗上主要以血塞通和腹蛇抗栓酶溶栓,以改善脑代谢;以格列本脲(glibenclamide)合用盐酸二甲双胍(dimethyl biguamidehydrochloride)治疗糖尿病.患者于4月9日服格列本脲5mg bid,4月11日合用二甲双胍25mg tid,17日下午(即给格列本脲8d,盐酸二甲双胍6d后),突然意识不清,唤之反应迟钝.体检:BP:135/60mmHg(18/8kPa),心率80beats/min,律齐,血糖1.37mmol/L.急予50%GS100ml,iv,神志逐渐清晰,体征尚稳定,暂停降糖药,给5%GS500ml维持,次日10:00测血糖9.57mmol/L),神志清.     

Synthesis,Cytotoxicity and Antileishmanial Activity of Some N-(2-(indol-3-yl)ethyl)-7-chloroquinolin-4-amines

We report herein the condensation of 4,7-dichloroquinoline (1) with tryptamine (2) and D-tryptophan methyl ester (3) . Hydrolysis of the methyl ester adduct (5) yielded the free acid (6) . The compounds were evaluated in vitro for activity against four different species of Leishmania promastigote forms and for cytotoxic activity against Kb and Vero cells. Compound (5) showed good activity against the Leishmania species tested, while all three compounds displayed moderate activity in both Kb and Vero cells.     

Efficacy of gut lavage,hemodialysis, and hemoperfusion in the therapy of paraquat or diquat intoxication

Clinical and in vitro investigations were carried out to test the efficacy of gut lavage, hemodialysis, and hemoperfusion in the treatment of poisoning with paraquat or diquat. In a patient suffering from diquat intoxication 130 times more diquat was removed by gut lavage 30 h after ingestion than was removed by complete aspiration of the gastric contents.Determination of in vitro clearances for paraquat and diquat by hemodialysis showed that, at serum concentrations of 1–2 ppm, such as are frequently encountered in poisoning in man, toxicologically relevant quantities of herbicide cannot be removed from the body. At a concentration of 20 ppm, on the other hand, hemodialysis proved to be effective, the clearance being 70 ml/min at a blood flow rate of 100 ml/min. The efficacy of hemoperfusion with coated activated charcoal was on the whole better. Especially at concentrations around 1–2 ppm, the clearance values for hemoperfusion were some 5–7 times higher than those for hemodialysis.In a patient suffering from paraquat poisoning, both hemodialysis as well as hemoperfusion were carried out. The in vitro results could be confirmed: At serum concentrations of paraquat less than 1 ppm no clearance could be obtained by hemodialysis while by hemoperfusion with activated charcoal quite high clearance values were measured and the serum level dropped down to zero.

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Zusammenfassung Klinische Untersuchungen und Laboratoriumsversuche wurden durchgeführt, um die Wirksamkeit von Darmspülung, Hämodialyse und Hämoperfusion bei Paraquat- und Deiquat-Vergiftungen zu prüfen.Bei einem Patienten wurde 30 Std nach Deiquat-Aufnahme durch Darmspülung 130mal mehr Deiquat entfernt als durch vollständige Aspiration des Mageninhaltes. In vitro-Versuche ergaben, daß bei Blutserumkonzentrationen von 1–2 ppm, die bei Vergiftungen oft gemessen werden, durch Hämodialyse keine toxikologisch relevanten Paraquat- oder Deiquat-Mengen entfernt werden können. Dagegen erwies sich die Hämodialyse bei 20 ppm und einer Blutumlaufgeschwindigkeit von 100 ml/min mit einer Clearance von 70 ml/min als wirksam. Die Hämoperfusion mit beschicheter Aktivkohle war in diesen Versuchen aber eindeutig überlegen, denn insbesondere bei Konzentrationen um 1–2 ppm waren die Clearance-Werte 5–7mal höher als bei der Hämodialyse.Die in vitro-Ergebnisse wurden bei einem Patienten mit einer Paraquat-Vergiftung bestätigt: Bei Konzentrationen unter 1 ppm war die Hämodialyse wirkungslos, während durch Hämoperfusion relativ hohe Clearance-Werte erreicht wurden, so daß der Serumspiegel rasch unter die Nachweisgrenze abfiel.

     

In vitro studies on sterically stabilized liposomes (SL) as enzyme carriers in organophosphorus (OP) antagonism

This study describes a new approach for organophosphorous (OP) antidotal treatment by encapsulating an OP hydrolyzing enzyme, OPA anhydrolase (OPAA), within sterically stabilized liposomes. The recombinant OPAA enzyme was derived from Alteromonas strain JD6. It has broad substrate specificity to a wide range of OP compounds: DFP and the nerve agents, soman and sarin. Liposomes encapsulating OPAA (SL)* were made by mechanical dispersion method. Hydrolysis of DFP by (SL)* was measured by following an increase of fluoride ion concentration using a fluoride ion selective electrode. OPAA entrapped in the carrier liposomes rapidly hydrolyze DFP, with the rate of DFP hydrolysis directly proportional to the amount of (SL)* added to the solution. Liposomal carriers containing no enzyme did not hydrolyze DFP. The reaction was linear and the rate of hydrolysis was first order in the substrate. This enzyme carrier system serves as a biodegradable protective environment for the recombinant OP-metabolizing enzyme, OPAA, resulting in prolongation of enzymatic concentration in the body. These studies suggest that the protection of OP intoxication can be strikingly enhanced by adding OPAA encapsulated within (SL)* to pralidoxime and atropine.     

Lung disease and PKCs

The lung offers a rich opportunity for development of therapeutic strategies focused on isozymes of protein kinase C (PKCs). PKCs are important in many cellular responses in the lung, and existing therapies for pulmonary disorders are inadequate. The lung poses unique challenges as it interfaces with air and blood, contains a pulmonary and systemic circulation, and consists of many cell types. Key structures are bronchial and pulmonary vessels, branching airways, and distal air sacs defined by alveolar walls containing capillaries and interstitial space. The cellular composition of each vessel, airway, and alveolar wall is heterogeneous. Injurious environmental stimuli signal through PKCs and cause a variety of disorders. Edema formation and pulmonary hypertension (PHTN) result from derangements in endothelial, smooth muscle (SM), and/or adventitial fibroblast cell phenotype. Asthma, chronic obstructive pulmonary disease (COPD), and lung cancer are characterized by distinctive pathological changes in airway epithelial, SM, and mucous-generating cells. Acute and chronic pneumonitis and fibrosis occur in the alveolar space and interstitium with type 2 pneumocytes and interstitial fibroblasts/myofibroblasts playing a prominent role. At each site, inflammatory, immune, and vascular progenitor cells contribute to the injury and repair process. Many strategies have been used to investigate PKCs in lung injury. Isolated organ preparations and whole animal studies are powerful approaches especially when genetically engineered mice are used. More analysis of PKC isozymes in normal and diseased human lung tissue and cells is needed to complement this work. Since opposing or counter-regulatory effects of selected PKCs in the same cell or tissue have been found, it may be desirable to target more than one PKC isozyme and potentially in different directions. Because multiple signaling pathways contribute to the key cellular responses important in lung biology, therapeutic strategies targeting PKCs may be more effective if combined with inhibitors of other pathways for additive or synergistic effect. Mechanisms that regulate PKC activity, including phosphorylation and interaction with isozyme-specific binding proteins, are also potential therapeutic targets. Key isotypes of PKC involved in lung pathophysiology are summarized and current and evolving therapeutic approaches to target them are identified.     

Steroidal sapogenin contents in some domestic plants

In order to find out the values of the steroid resources for the future use. the compositions and contents of steroidal sapogenins from 13 domestic plants have been investigated. As a result,Dioscorea nipponica, D. quinqueloba andSmilax china were found to have large amount of diosgenin. And pennogenin inTrillium kamtschaticum andParis verticillata, yuccagenin inAllium fistulosum, hecogenin inAgave americana and neochlorogenin inSolanum nigum were appeared to be major steroidal sapogenins.