Bazedoxifene_acetate_COA_24641_MedChemExpress

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分子生物学词汇(中英文对照表 )

醋酸巴多西芬的产品说明书

medlife小分子化合物大量库存提供超过2万种的抑制剂激动剂拮抗剂等产品是药物及疾病研究的重要原料供应商
醋酸巴多西芬的产品说明书
简介：醋酸巴多西芬，Bazedoxifene acetate是第三代选择性雌激素受体调节剂 (SERM)，IC50分别为26和99 nM。
物理化学性质：
沸点
694.4ºC at 760 mmHg
参考文献：
[1]. Jaime Kulak, et al. Treatment with Bazedoxifene, a Selective Estrogen Receptor Modulator, Causes Regression of Endometriosis in a Mouse Model. Endocrinology. 2011; 152(8): 3226-3232.
[5]. Diane M Biskobing. Update on bazedoxifene: A novel selective estrogen receptor modulator. Clin Interv Aging. 2007; 2(3): 299-303.
[4]. Joan S. Lewis-Wambi, Helen Kim, Ramona Curpan, et al. The Selective Estrogen Receptor Modulator Bazedoxifene Inhibits Hormone-Independent Breast Cancer Cell Growth and Down-Regulates Estrogen Receptor α and Cyclin D1. Mol Pharmacol. 2011 ; 80(4): 610-620.

希弗全解聚己糖氨基葡聚糖硫酸盐

希弗全解聚己糖氨基葡聚糖硫酸盐希弗全解聚己糖氨基葡聚糖硫酸盐一、希弗全希弗全，又称为肝素或肝素钠，是一种常见的抗凝血药物，通常用于预防和治疗血栓病。

它可以通过抑制凝血酶和促凝血酶的活性，从而阻止血液凝结。

希弗全可以静脉或皮下注射，具有快速、可逆、不易产生抗体及全身性抗凝血作用等优点。

另外，希弗全还可以与其他药物和生物大分子结合形成复杂的体系，用于治疗和预防一系列与凝血功能有关的疾病。

希弗全在医学领域有着广泛的应用。

1. 希弗全的化学结构希弗全是一种多糖，主要由聚己糖氨基葡聚糖硫酸盐构成。

聚己糖部分是一种多糖，由葡萄糖和苷胺糖交替排列而成，而氨基葡聚糖硫酸盐则是通过硫酸化的方式使得聚己糖部分带有正电荷。

这种特殊的化学结构使得希弗全具有优秀的生物活性，可以与凝血酶、抗凝血酶、肾素等多种蛋白质结合，从而发挥抗凝血作用。

2. 希弗全的生物学功能希弗全的生物活性主要体现在以下几个方面：（1）抗凝血作用：希弗全可以结合于凝血因子Xa和血栓素，从而阻止凝血酶原向凝血酶的转化，抑制血栓素的活性，达到抗凝血作用。

（2）抗炎作用：希弗全可以抑制炎症反应，减少纤维蛋白原的合成，降低炎症细胞的浸润，从而减轻炎症反应。

（3）抗肿瘤作用：希弗全可以通过抑制肿瘤细胞的黏附和迁移，促进血管内皮细胞的增殖和迁移，从而抑制肿瘤的生长和转移。

3. 希弗全的临床应用由于希弗全具有优秀的抗凝血、抗炎和抗肿瘤作用，因此在临床上有着广泛的应用。

不仅可以用于治疗急性冠状动脉综合症、深静脉血栓形成、肺栓塞等血栓病，还可以用于治疗血管炎、结缔组织病等炎症性疾病，以及治疗癌症等肿瘤。

希弗全还可以用于外科手术、危重病患者护理以及生物材料的生物相容性研究等领域。

4. 希弗全的不良反应与禁忌症尽管希弗全具有很好的药理作用，但在临床应用中也存在一定的不良反应和禁忌症。

希弗全可能会引起出血等血液系统不良反应，还可能引起过敏和过敏反应，甚至导致肝素诱导的血小板减少症。

稳定性英文版

HPLC ASSAY with DETERMINATION OF META-FLUOXETINE HCl.ANALYTICAL METHOD VALIDATION10 and 20mg Fluoxetine Capsules HPLC DeterminationFLUOXETINE HClC17H18F3NO•HClM.W. = 345.79CAS — 59333-67-4STABILITY INDICATINGA S S A Y V A L I D A T I O NMethod is suitable for:ýIn-process controlþProduct ReleaseþStability indicating analysis (Suitability - US/EU Product) CAUTIONFLUOXETINE HYDROCHLORIDE IS A HAZARDOUS CHEMICAL AND SHOULD BE HANDLED ONLY UNDER CONDITIONS SUITABLE FOR HAZARDOUS WORK.IT IS HIGHLY PRESSURE SENSITIVE AND ADEQUATE PRECAUTIONS SHOULD BE TAKEN TO AVOID ANY MECHANICAL FORCE (SUCH AS GRINDING, CRUSHING, ETC.) ON THE POWDER.ED. N0: 04Effective Date:APPROVED::HPLC ASSAY with DETERMINATION OF META-FLUOXETINE HCl.ANALYTICAL METHOD VALIDATION10 and 20mg Fluoxetine Capsules HPLC DeterminationTABLE OF CONTENTS INTRODUCTION........................................................................................................................ PRECISION............................................................................................................................... System Repeatability ................................................................................................................ Method Repeatability................................................................................................................. Intermediate Precision .............................................................................................................. LINEARITY................................................................................................................................ RANGE...................................................................................................................................... ACCURACY............................................................................................................................... Accuracy of Standard Injections................................................................................................ Accuracy of the Drug Product.................................................................................................... VALIDATION OF FLUOXETINE HCl AT LOW CONCENTRATION........................................... Linearity at Low Concentrations................................................................................................. Accuracy of Fluoxetine HCl at Low Concentration..................................................................... System Repeatability................................................................................................................. Quantitation Limit....................................................................................................................... Detection Limit........................................................................................................................... VALIDATION FOR META-FLUOXETINE HCl (POSSIBLE IMPURITIES).................................. Meta-Fluoxetine HCl linearity at 0.05% - 1.0%........................................................................... Detection Limit for Fluoxetine HCl.............................................................................................. Quantitation Limit for Meta Fluoxetine HCl................................................................................ Accuracy for Meta-Fluoxetine HCl ............................................................................................ Method Repeatability for Meta-Fluoxetine HCl........................................................................... Intermediate Precision for Meta-Fluoxetine HCl......................................................................... SPECIFICITY - STABILITY INDICATING EVALUATION OF THE METHOD............................. FORCED DEGRADATION OF FINISHED PRODUCT AND STANDARD..................................1. Unstressed analysis...............................................................................................................2. Acid Hydrolysis stressed analysis..........................................................................................3. Base hydrolysis stressed analysis.........................................................................................4. Oxidation stressed analysis...................................................................................................5. Sunlight stressed analysis.....................................................................................................6. Heat of solution stressed analysis.........................................................................................7. Heat of powder stressed analysis.......................................................................................... System Suitability stressed analysis.......................................................................................... Placebo...................................................................................................................................... STABILITY OF STANDARD AND SAMPLE SOLUTIONS......................................................... Standard Solution...................................................................................................................... Sample Solutions....................................................................................................................... ROBUSTNESS.......................................................................................................................... Extraction................................................................................................................................... Factorial Design......................................................................................................................... CONCLUSION...........................................................................................................................ED. N0: 04Effective Date:APPROVED::HPLC ASSAY with DETERMINATION OF META-FLUOXETINE HCl.ANALYTICAL METHOD VALIDATION10 and 20mg Fluoxetine Capsules HPLC DeterminationBACKGROUNDTherapeutically, Fluoxetine hydrochloride is a classified as a selective serotonin-reuptake inhibitor. Effectively used for the treatment of various depressions. Fluoxetine hydrochloride has been shown to have comparable efficacy to tricyclic antidepressants but with fewer anticholinergic side effects. The patent expiry becomes effective in 2001 (US). INTRODUCTIONFluoxetine capsules were prepared in two dosage strengths: 10mg and 20mg dosage strengths with the same capsule weight. The formulas are essentially similar and geometrically equivalent with the same ingredients and proportions. Minor changes in non-active proportions account for the change in active ingredient amounts from the 10 and 20 mg strength.The following validation, for the method SI-IAG-206-02 , includes assay and determination of Meta-Fluoxetine by HPLC, is based on the analytical method validation SI-IAG-209-06. Currently the method is the in-house method performed for Stability Studies. The Validation was performed on the 20mg dosage samples, IAG-21-001 and IAG-21-002.In the forced degradation studies, the two placebo samples were also used. PRECISIONSYSTEM REPEATABILITYFive replicate injections of the standard solution at the concentration of 0.4242mg/mL as described in method SI-IAG-206-02 were made and the relative standard deviation (RSD) of the peak areas was calculated.SAMPLE PEAK AREA#15390#25406#35405#45405#55406Average5402.7SD 6.1% RSD0.1ED. N0: 04Effective Date:APPROVED::HPLC ASSAY with DETERMINATION OF META-FLUOXETINE HCl.ANALYTICAL METHOD VALIDATION10 and 20mg Fluoxetine Capsules HPLC DeterminationED. N0: 04Effective Date:APPROVED::PRECISION - Method RepeatabilityThe full HPLC method as described in SI-IAG-206-02 was carried-out on the finished product IAG-21-001 for the 20mg dosage form. The method repeated six times and the relative standard deviation (RSD) was calculated.SAMPLENumber%ASSAYof labeled amountI 96.9II 97.8III 98.2IV 97.4V 97.7VI 98.5(%) Average97.7SD 0.6(%) RSD0.6PRECISION - Intermediate PrecisionThe full method as described in SI-IAG-206-02 was carried-out on the finished product IAG-21-001 for the 20mg dosage form. The method was repeated six times by a second analyst on a different day using a different HPLC instrument. The average assay and the relative standard deviation (RSD) were calculated.SAMPLENumber% ASSAYof labeled amountI 98.3II 96.3III 94.6IV 96.3V 97.8VI 93.3Average (%)96.1SD 2.0RSD (%)2.1The difference between the average results of method repeatability and the intermediate precision is 1.7%.HPLC ASSAY with DETERMINATION OF META-FLUOXETINE HCl.ANALYTICAL METHOD VALIDATION10 and 20mg Fluoxetine Capsules HPLC DeterminationLINEARITYStandard solutions were prepared at 50% to 200% of the nominal concentration required by the assay procedure. Linear regression analysis demonstrated acceptability of the method for quantitative analysis over the concentration range required. Y-Intercept was found to be insignificant.RANGEDifferent concentrations of the sample (IAG-21-001) for the 20mg dosage form were prepared, covering between 50% - 200% of the nominal weight of the sample.Conc. (%)Conc. (mg/mL)Peak Area% Assayof labeled amount500.20116235096.7700.27935334099.21000.39734463296.61500.64480757797.52000.79448939497.9(%) Average97.6SD 1.0(%) RSD 1.0ED. N0: 04Effective Date:APPROVED::HPLC ASSAY with DETERMINATION OF META-FLUOXETINE HCl.ANALYTICAL METHOD VALIDATION10 and 20mg Fluoxetine Capsules HPLC DeterminationED. N0: 04Effective Date:APPROVED::RANGE (cont.)The results demonstrate linearity as well over the specified range.Correlation coefficient (RSQ)0.99981 Slope11808.3Y -Interceptresponse at 100%* 100 (%) 0.3%ACCURACYACCURACY OF STANDARD INJECTIONSFive (5) replicate injections of the working standard solution at concentration of 0.4242mg/mL, as described in method SI-IAG-206-02 were made.INJECTIONNO.PEAK AREA%ACCURACYI 539299.7II 540599.9III 540499.9IV 5406100.0V 5407100.0Average 5402.899.9%SD 6.10.1RSD, (%)0.10.1The percent deviation from the true value wasdetermined from the linear regression lineHPLC ASSAY with DETERMINATION OF META-FLUOXETINE HCl.ANALYTICAL METHOD VALIDATION10 and 20mg Fluoxetine Capsules HPLC DeterminationED. N0: 04Effective Date:APPROVED::ACCURACY OF THE DRUG PRODUCTAdmixtures of non-actives (placebo, batch IAG-21-001 ) with Fluoxetine HCl were prepared at the same proportion as in a capsule (70%-180% of the nominal concentration).Three preparations were made for each concentration and the recovery was calculated.Conc.(%)Placebo Wt.(mg)Fluoxetine HCl Wt.(mg)Peak Area%Accuracy Average (%)70%7079.477.843465102.27079.687.873427100.77079.618.013465100.0101.0100%10079.6211.25476397.910080.8011.42491799.610079.6011.42485498.398.6130%13079.7214.90640599.413080.3114.75632899.213081.3314.766402100.399.618079.9920.10863699.318079.3820.45879499.418080.0820.32874899.599.4Placebo, Batch Lot IAG-21-001HPLC ASSAY with DETERMINATION OF META-FLUOXETINE HCl.ANALYTICAL METHOD VALIDATION10 and 20mg Fluoxetine Capsules HPLC DeterminationED. N0: 04Effective Date:APPROVED::VALIDATION OF FLUOXETINE HClAT LOW CONCENTRATIONLINEARITY AT LOW CONCENTRATIONSStandard solution of Fluoxetine were prepared at approximately 0.02%-1.0% of the working concentration required by the method SI-IAG-206-02. Linear regression analysis demonstrated acceptability of the method for quantitative analysis over this range.ACCURACY OF FLUOXETINE HCl AT LOW CONCENTRATIONThe peak areas of the standard solution at the working concentration were measured and the percent deviation from the true value, as determined from the linear regression was calculated.SAMPLECONC.µg/100mLAREA FOUND%ACCURACYI 470.56258499.7II 470.56359098.1III 470.561585101.3IV 470.561940100.7V 470.56252599.8VI 470.56271599.5(%) AverageSlope = 132.7395299.9SD Y-Intercept = -65.872371.1(%) RSD1.1HPLC ASSAY with DETERMINATION OF META-FLUOXETINE HCl.ANALYTICAL METHOD VALIDATION10 and 20mg Fluoxetine Capsules HPLC DeterminationSystem RepeatabilitySix replicate injections of standard solution at 0.02% and 0.05% of working concentration as described in method SI-IAG-206-02 were made and the relative standard deviation was calculated.SAMPLE FLUOXETINE HCl AREA0.02%0.05%I10173623II11503731III10103475IV10623390V10393315VI10953235Average10623462RSD, (%) 5.0 5.4Quantitation Limit - QLThe quantitation limit ( QL) was established by determining the minimum level at which the analyte was quantified. The quantitation limit for Fluoxetine HCl is 0.02% of the working standard concentration with resulting RSD (for six injections) of 5.0%. Detection Limit - DLThe detection limit (DL) was established by determining the minimum level at which the analyte was reliably detected. The detection limit of Fluoxetine HCl is about 0.01% of the working standard concentration.ED. N0: 04Effective Date:APPROVED::HPLC ASSAY with DETERMINATION OF META-FLUOXETINE HCl.ANALYTICAL METHOD VALIDATION10 and 20mg Fluoxetine Capsules HPLC DeterminationED. N0: 04Effective Date:APPROVED::VALIDATION FOR META-FLUOXETINE HCl(EVALUATING POSSIBLE IMPURITIES)Meta-Fluoxetine HCl linearity at 0.05% - 1.0%Relative Response Factor (F)Relative response factor for Meta-Fluoxetine HCl was determined as slope of Fluoxetine HCl divided by the slope of Meta-Fluoxetine HCl from the linearity graphs (analysed at the same time).F =132.7395274.859534= 1.8Detection Limit (DL) for Fluoxetine HClThe detection limit (DL) was established by determining the minimum level at which the analyte was reliably detected.Detection limit for Meta Fluoxetine HCl is about 0.02%.Quantitation Limit (QL) for Meta-Fluoxetine HClThe QL is determined by the analysis of samples with known concentration of Meta-Fluoxetine HCl and by establishing the minimum level at which the Meta-Fluoxetine HCl can be quantified with acceptable accuracy and precision.Six individual preparations of standard and placebo spiked with Meta-Fluoxetine HCl solution to give solution with 0.05% of Meta Fluoxetine HCl, were injected into the HPLC and the recovery was calculated.HPLC ASSAY with DETERMINATION OF META-FLUOXETINE HCl.ANALYTICAL METHOD VALIDATION10 and 20mg Fluoxetine Capsules HPLC DeterminationED. N0: 04Effective Date:APPROVED::META-FLUOXETINE HCl[RECOVERY IN SPIKED SAMPLES].Approx.Conc.(%)Known Conc.(µg/100ml)Area in SpikedSampleFound Conc.(µg/100mL)Recovery (%)0.0521.783326125.735118.10.0521.783326825.821118.50.0521.783292021.55799.00.0521.783324125.490117.00.0521.783287220.96996.30.0521.783328526.030119.5(%) AVERAGE111.4SD The recovery result of 6 samples is between 80%-120%.10.7(%) RSDQL for Meta Fluoxetine HCl is 0.05%.9.6Accuracy for Meta Fluoxetine HClDetermination of Accuracy for Meta-Fluoxetine HCl impurity was assessed using triplicate samples (of the drug product) spiked with known quantities of Meta Fluoxetine HCl impurity at three concentrations levels (namely 80%, 100% and 120% of the specified limit - 0.05%).The results are within specifications:For 0.4% and 0.5% recovery of 85% -115%For 0.6% recovery of 90%-110%HPLC ASSAY with DETERMINATION OF META-FLUOXETINE HCl.ANALYTICAL METHOD VALIDATION10 and 20mg Fluoxetine Capsules HPLC DeterminationED. N0: 04Effective Date:APPROVED::META-FLUOXETINE HCl[RECOVERY IN SPIKED SAMPLES]Approx.Conc.(%)Known Conc.(µg/100mL)Area in spikedSample Found Conc.(µg/100mL)Recovery (%)[0.4%]0.4174.2614283182.66104.820.4174.2614606187.11107.370.4174.2614351183.59105.36[0.5%]0.5217.8317344224.85103.220.5217.8316713216.1599.230.5217.8317341224.81103.20[0.6%]0.6261.3918367238.9591.420.6261.3920606269.81103.220.6261.3920237264.73101.28RECOVERY DATA DETERMINED IN SPIKED SAMPLESHPLC ASSAY with DETERMINATION OF META-FLUOXETINE HCl.ANALYTICAL METHOD VALIDATION10 and 20mg Fluoxetine Capsules HPLC DeterminationED. N0: 04Effective Date:APPROVED::REPEATABILITYMethod Repeatability - Meta Fluoxetine HClThe full method (as described in SI-IAG-206-02) was carried out on the finished drug product representing lot number IAG-21-001-(1). The HPLC method repeated serially, six times and the relative standard deviation (RSD) was calculated.IAG-21-001 20mg CAPSULES - FLUOXETINESample% Meta Fluoxetine % Meta-Fluoxetine 1 in Spiked Solution10.0260.09520.0270.08630.0320.07740.0300.07450.0240.09060.0280.063AVERAGE (%)0.0280.081SD 0.0030.012RSD, (%)10.314.51NOTE :All results are less than QL (0.05%) therefore spiked samples with 0.05% Meta Fluoxetine HCl were injected.HPLC ASSAY with DETERMINATION OF META-FLUOXETINE HCl.ANALYTICAL METHOD VALIDATION10 and 20mg Fluoxetine Capsules HPLC DeterminationED. N0: 04Effective Date:APPROVED::Intermediate Precision - Meta-Fluoxetine HClThe full method as described in SI-IAG-206-02 was applied on the finished product IAG-21-001-(1) .It was repeated six times, with a different analyst on a different day using a different HPLC instrument.The difference between the average results obtained by the method repeatability and the intermediate precision was less than 30.0%, (11.4% for Meta-Fluoxetine HCl as is and 28.5% for spiked solution).IAG-21-001 20mg - CAPSULES FLUOXETINESample N o:Percentage Meta-fluoxetine% Meta-fluoxetine 1 in spiked solution10.0260.06920.0270.05730.0120.06140.0210.05850.0360.05560.0270.079(%) AVERAGE0.0250.063SD 0.0080.009(%) RSD31.514.51NOTE:All results obtained were well below the QL (0.05%) thus spiked samples slightly greater than 0.05% Meta-Fluoxetine HCl were injected. The RSD at the QL of the spiked solution was 14.5%HPLC ASSAY with DETERMINATION OF META-FLUOXETINE HCl.ANALYTICAL METHOD VALIDATION10 and 20mg Fluoxetine Capsules HPLC DeterminationSPECIFICITY - STABILITY INDICATING EVALUATIONDemonstration of the Stability Indicating parameters of the HPLC assay method [SI-IAG-206-02] for Fluoxetine 10 & 20mg capsules, a suitable photo-diode array detector was incorporated utilizing a commercial chromatography software managing system2, and applied to analyze a range of stressed samples of the finished drug product.GLOSSARY of PEAK PURITY RESULT NOTATION (as reported2):Purity Angle-is a measure of spectral non-homogeneity across a peak, i.e. the weighed average of all spectral contrast angles calculated by comparing all spectra in the integrated peak against the peak apex spectrum.Purity Threshold-is the sum of noise angle3 and solvent angle4. It is the limit of detection of shape differences between two spectra.Match Angle-is a comparison of the spectrum at the peak apex against a library spectrum.Match Threshold-is the sum of the match noise angle3 and match solvent angle4.3Noise Angle-is a measure of spectral non-homogeneity caused by system noise.4Solvent Angle-is a measure of spectral non-homogeneity caused by solvent composition.OVERVIEWT he assay of the main peak in each stressed solution is calculated according to the assay method SI-IAG-206-02, against the Standard Solution, injected on the same day.I f the Purity Angle is smaller than the Purity Threshold and the Match Angle is smaller than the Match Threshold, no significant differences between spectra can be detected. As a result no spectroscopic evidence for co-elution is evident and the peak is considered to be pure.T he stressed condition study indicated that the Fluoxetine peak is free from any appreciable degradation interference under the stressed conditions tested. Observed degradation products peaks were well separated from the main peak.1® PDA-996 Waters™ ; 2[Millennium 2010]ED. N0: 04Effective Date:APPROVED::HPLC ASSAY with DETERMINATION OF META-FLUOXETINE HCl.ANALYTICAL METHOD VALIDATION10 and 20mg Fluoxetine Capsules HPLC DeterminationFORCED DEGRADATION OF FINISHED PRODUCT & STANDARD 1.UNSTRESSED SAMPLE1.1.Sample IAG-21-001 (2) (20mg/capsule) was prepared as stated in SI-IAG-206-02 and injected into the HPLC system. The calculated assay is 98.5%.SAMPLE - UNSTRESSEDFluoxetine:Purity Angle:0.075Match Angle:0.407Purity Threshold:0.142Match Threshold:0.4251.2.Standard solution was prepared as stated in method SI-IAG-206-02 and injected into the HPLC system. The calculated assay is 100.0%.Fluoxetine:Purity Angle:0.078Match Angle:0.379Purity Threshold:0.146Match Threshold:0.4272.ACID HYDROLYSIS2.1.Sample solution of IAG-21-001 (2) (20mg/capsule) was prepared as in method SI-IAG-206-02 : An amount equivalent to 20mg Fluoxetine was weighed into a 50mL volumetric flask. 20mL Diluent was added and the solution sonicated for 10 minutes. 1mL of conc. HCl was added to this solution The solution was allowed to stand for 18 hours, then adjusted to about pH = 5.5 with NaOH 10N, made up to volume with Diluent and injected into the HPLC system after filtration.Fluoxetine peak intensity did NOT decrease. Assay result obtained - 98.8%.SAMPLE- ACID HYDROLYSISFluoxetine peak:Purity Angle:0.055Match Angle:0.143Purity Threshold:0.096Match Threshold:0.3712.2.Standard solution was prepared as in method SI-IAG-206-02 : about 22mg Fluoxetine HCl were weighed into a 50mL volumetric flask. 20mL Diluent were added. 2mL of conc. HCl were added to this solution. The solution was allowed to stand for 18 hours, then adjusted to about pH = 5.5 with NaOH 10N, made up to volume with Diluent and injected into the HPLC system.Fluoxetine peak intensity did NOT decrease. Assay result obtained - 97.2%.ED. N0: 04Effective Date:APPROVED::HPLC ASSAY with DETERMINATION OF META-FLUOXETINE HCl.ANALYTICAL METHOD VALIDATION10 and 20mg Fluoxetine Capsules HPLC DeterminationSTANDARD - ACID HYDROLYSISFluoxetine peak:Purity Angle:0.060Match Angle:0.060Purity Threshold:0.099Match Threshold:0.3713.BASE HYDROLYSIS3.1.Sample solution of IAG-21-001 (2) (20mg/capsule) was prepared as per method SI-IAG-206-02 : An amount equivalent to 20mg Fluoxetine was weight into a 50mL volumetric flask. 20mL Diluent was added and the solution sonicated for 10 minutes. 1mL of 5N NaOH was added to this solution. The solution was allowed to stand for 18 hours, then adjusted to about pH = 5.5 with 5N HCl, made up to volume with Diluent and injected into the HPLC system.Fluoxetine peak intensity did NOT decrease. Assay result obtained - 99.3%.SAMPLE - BASE HYDROLYSISFluoxetine peak:Purity Angle:0.063Match Angle:0.065Purity Threshold:0.099Match Threshold:0.3623.2.Standard stock solution was prepared as per method SI-IAG-206-02 : About 22mg Fluoxetine HCl was weighed into a 50mL volumetric flask. 20mL Diluent was added. 2mL of 5N NaOH was added to this solution. The solution was allowed to stand for 18 hours, then adjusted to about pH=5.5 with 5N HCl, made up to volume with Diluent and injected into the HPLC system.Fluoxetine peak intensity did NOT decrease - 99.5%.STANDARD - BASE HYDROLYSISFluoxetine peak:Purity Angle:0.081Match Angle:0.096Purity Threshold:0.103Match Threshold:0.3634.OXIDATION4.1.Sample solution of IAG-21-001 (2) (20mg/capsule) was prepared as per method SI-IAG-206-02. An equivalent to 20mg Fluoxetine was weighed into a 50mL volumetric flask. 20mL Diluent added and the solution sonicated for 10 minutes.1.0mL of 30% H2O2 was added to the solution and allowed to stand for 5 hours, then made up to volume with Diluent, filtered and injected into HPLC system.Fluoxetine peak intensity decreased to 95.2%.ED. N0: 04Effective Date:APPROVED::HPLC ASSAY with DETERMINATION OF META-FLUOXETINE HCl.ANALYTICAL METHOD VALIDATION10 and 20mg Fluoxetine Capsules HPLC DeterminationSAMPLE - OXIDATIONFluoxetine peak:Purity Angle:0.090Match Angle:0.400Purity Threshold:0.154Match Threshold:0.4294.2.Standard solution was prepared as in method SI-IAG-206-02 : about 22mg Fluoxetine HCl were weighed into a 50mL volumetric flask and 25mL Diluent were added. 2mL of 30% H2O2 were added to this solution which was standing for 5 hours, made up to volume with Diluent and injected into the HPLC system.Fluoxetine peak intensity decreased to 95.8%.STANDARD - OXIDATIONFluoxetine peak:Purity Angle:0.083Match Angle:0.416Purity Threshold:0.153Match Threshold:0.4295.SUNLIGHT5.1.Sample solution of IAG-21-001 (2) (20mg/capsule) was prepared as in method SI-IAG-206-02 . The solution was exposed to 500w/hr. cell sunlight for 1hour. The BST was set to 35°C and the ACT was 45°C. The vials were placed in a horizontal position (4mm vials, National + Septum were used). A Dark control solution was tested. A 2%w/v quinine solution was used as the reference absorbance solution.Fluoxetine peak decreased to 91.2% and the dark control solution showed assay of 97.0%. The difference in the absorbance in the quinine solution is 0.4227AU.Additional peak was observed at RRT of 1.5 (2.7%).The total percent of Fluoxetine peak with the degradation peak is about 93.9%.SAMPLE - SUNLIGHTFluoxetine peak:Purity Angle:0.093Match Angle:0.583Purity Threshold:0.148Match Threshold:0.825 ED. N0: 04Effective Date:APPROVED::HPLC ASSAY with DETERMINATION OF META-FLUOXETINE HCl.ANALYTICAL METHOD VALIDATION10 and 20mg Fluoxetine Capsules HPLC DeterminationSUNLIGHT (Cont.)5.2.Working standard solution was prepared as in method SI-IAG-206-02 . The solution was exposed to 500w/hr. cell sunlight for 1.5 hour. The BST was set to 35°C and the ACT was 42°C. The vials were placed in a horizontal position (4mm vials, National + Septum were used). A Dark control solution was tested. A 2%w/v quinine solution was used as the reference absorbance solution.Fluoxetine peak was decreased to 95.2% and the dark control solution showed assay of 99.5%.The difference in the absorbance in the quinine solution is 0.4227AU.Additional peak were observed at RRT of 1.5 (2.3).The total percent of Fluoxetine peak with the degradation peak is about 97.5%. STANDARD - SUNLIGHTFluoxetine peak:Purity Angle:0.067Match Angle:0.389Purity Threshold:0.134Match Threshold:0.8196.HEAT OF SOLUTION6.1.Sample solution of IAG-21-001-(2) (20 mg/capsule) was prepared as in method SI-IAG-206-02 . Equivalent to 20mg Fluoxetine was weighed into a 50mL volumetric flask. 20mL Diluent was added and the solution was sonicated for 10 minutes and made up to volume with Diluent. 4mL solution was transferred into a suitable crucible, heated at 105°C in an oven for 2 hours. The sample was cooled to ambient temperature, filtered and injected into the HPLC system.Fluoxetine peak was decreased to 93.3%.SAMPLE - HEAT OF SOLUTION [105o C]Fluoxetine peak:Purity Angle:0.062Match Angle:0.460Purity Threshold:0.131Match Threshold:0.8186.2.Standard Working Solution (WS) was prepared under method SI-IAG-206-02 . 4mL of the working solution was transferred into a suitable crucible, placed in an oven at 105°C for 2 hours, cooled to ambient temperature and injected into the HPLC system.Fluoxetine peak intensity did not decrease - 100.5%.ED. N0: 04Effective Date:APPROVED::。

阿司咪唑

合成方法
合成方法
化合物(I)和碘甲烷在乙醇中回流8h，环合得到化合物(Ⅱ)。再水解脱去酯基，得到化合物(Ⅲ)。用对甲氧基苯乙基溴进行N-烷基化，得化合物(Ⅳ)。再用对氟苄基溴烷基化，得阿司咪唑。
1. 1-[(4-氟苯基)甲基]-苯并咪唑-2-(3H)-酮的制备
在反应瓶中加入2-羟基苯并咪唑5.0g(37.3mmol)和NaH 1.6g(53mmol)(NaH含量大约为80%,浸入矿物油中) 的DMF 100ml的悬浮液.加毕.在60ºC.(最好有N2保护)搅拌反应1h.再加入4-氟苄基氯(FBC)5.4g(37mmol),加热 ( 6 0 ºC ) 搅拌反应 5 . 5 h . 冷却至室温后加入冰水 7 0 0 m l , 用二氯甲烷 ( 5 0 0 m l × 2 ) 提取 . 有机层用食盐水洗 . 无水 N a 2 S O 4 干燥.过滤.滤液减压浓缩.剩余物用石油醚析晶.得1-[(4-氟苯基)甲基]-苯并咪唑-2-(3H)-酮固体8.0g,为无色结晶 m p 1 7 8 ~ 1 7 9 ºC , 收率 8 8 % .
治疗措施
阿司咪唑中毒的治疗要点为： 1.大量摄入者予洗胃，后灌服活性炭和导泻。 2.对心肌抑制和Q-T间期延长者予5%碳酸氢钠250ml静注可能有效。 3.对症、支持治疗。
专家点评
专家点评
阿司咪阿司咪唑自1983年上市以来，在许多国家得到了广泛应用。国外研究显示阿司咪唑治疗荨麻疹的总有效率为74%。国内的一项多中心双盲安慰剂对照试验表明阿司咪唑对急性荨麻疹的总有效率为82.9%，对慢性荨麻疹的总有效率为86.0%，均显著高于安慰剂，主要不良反应为嗜睡、倦怠、口干等，连续用药3个月的患者中，半数有食欲及体重增加。阿司咪唑的心脏毒性虽然发生率较低，但由于后果严重，已限制了它的应用。阿司咪唑为强效和长效的H1受体拮抗剂，无中枢镇静和抗毒蕈碱样作用。代谢产物去甲阿司咪唑仍有抗胆胺作用。长期服用可增进食欲和增加体重，服用过量可引起心脏Q-T间期延长和室性心律失常。适用于各种原因引起过敏性疾病。

萨米多芬结构-概述说明以及解释

萨米多芬结构-概述说明以及解释1.引言1.1 概述萨米多芬是一种广泛应用于临床的药物，其主要作用是通过扩张支气管平滑肌，从而缓解哮喘、慢性阻塞性肺病等呼吸道疾病的症状。

萨米多芬具有较好的药效和安全性，受到临床医生和患者的青睐。

本文将从萨米多芬的历史背景、化学结构以及药理作用等方面进行详细介绍，旨在帮助读者更好地了解这种药物的特点和应用。

通过阅读本文，读者将对萨米多芬的应用前景和潜在风险有更清晰的认识，从而更好地指导临床实践和药物选择。

1.2 文章结构文章结构部分将介绍本文的主要内容和组织结构。

首先，我们将从萨米多芬的历史背景入手，介绍其起源和发展历程。

接着，我们将详细解析萨米多芬的化学结构，探讨其分子组成和特性。

最后，我们将深入探讨萨米多芬在药理学上的作用机制，分析其对人体的影响和作用方式。

通过对这三个方面的讨论，我们将全面了解萨米多芬的结构和作用，为其未来的应用前景和潜在风险提供更加深入的认识和了解。

1.3 目的本文的目的在于深入探讨萨米多芬的结构和作用机制，以便更好地了解这种药物在临床应用中的潜力和局限性。

通过对萨米多芬的历史背景、化学结构和药理作用进行综合分析，我们希望能够为该药物的进一步研究和开发提供一定的参考，促进其在药物治疗领域的应用和发展。

同时，我们也将重点关注萨米多芬的应用前景和潜在风险，以期为临床医生和研究人员提供更全面的了解，为患者的治疗和健康保障提供科学依据和建议。

2.正文2.1 萨米多芬的历史背景萨米多芬是一种广泛应用于治疗呼吸道疾病的药物，也被称为长效β2受体激动剂。

它首次被合成于1966年，由瑞士药厂诺华公司研发，并于1970年代开始上市应用。

在当时，萨米多芬被广泛应用于治疗哮喘和慢性阻塞性肺病（COPD）等呼吸道疾病。

随着对呼吸道疾病治疗需求的增加，萨米多芬的应用范围逐渐扩大，并成为治疗呼吸道疾病的重要药物之一。

由于其具有长效作用和快速缓解症状的特点，萨米多芬得到了广泛的临床应用和认可。

鱼腥草乙酸乙酯萃取部位的化学成分及抗植物病原菌活性研究

鱼腥草乙酸乙酯萃取部位的化学成分及抗植物病原菌活性研究张丽;孙建鹏;巴其斌
【期刊名称】《天然产物研究与开发》
【年(卷),期】2024(36)4
【摘要】采用硅胶、大孔树脂、葡聚糖凝胶、MCI树脂、薄层色谱以及高效液相色谱等色谱分离方法,从鱼腥草(Houttuynia cordata)地上部分95%乙醇提取物的乙酸乙酯萃取部位分离得到10个化合物。

运用质谱、核磁共振等波谱技术和文献对比法鉴定了其结构,分别鉴定为去氢催吐萝芙木醇(1)、5,6-环氧-3-羟基-β-紫罗兰酮(2)、黑麦草内酯(3)、pubinernoid A(4)、槲皮苷(5)、槲皮素(6)、阿福豆苷(7)、4-甲氧基苯-1,2-二醇(8)、4-羟基苯甲醛(9)、苯甲酸(10)。

化合物1~4为首次从鱼腥草中分离得到的降碳倍半萜。

对所有化合物进行了抗植物病原菌活性筛选,结果显示:在40 mg/mL浓度下,化合物5~7对禾谷镰刀菌、褐枝孢菌、番茄灰霉病菌、瓜类球腔菌和棉花枯萎病菌抑菌率介于38%~50%之间。

【总页数】6页(P616-621)
【作者】张丽;孙建鹏;巴其斌
【作者单位】兰州城市学院化学工程学院
【正文语种】中文
【中图分类】Q946.8
【相关文献】
1.糙叶五加果实乙酸乙酯萃取部位化学成分及抗炎活性研究
2.老鸦糊乙酸乙酯部位化学成分及其抗炎活性
3.丁香茄叶乙酸乙酯部位化学成分及抗炎活性研究
4.长叶纽子果根醇提物乙酸乙酯萃取部位的化学成分及体外抗炎活性研究
5.岩黄连乙酸乙酯部位化学成分及其抗炎活性研究
因版权原因，仅展示原文概要，查看原文内容请购买。

新型抗真菌药布替萘芬类似物的合成

新型抗真菌药布替萘芬类似物的合成
王大威;赵宝祥;王凯铭;左华;沙磊;谭伟
【期刊名称】《山东大学学报：理学版》
【年(卷),期】2004(39)5
【摘要】根据苄胺类抗真菌化合物的构效关系、作用机理 ,设计合成了 5个布替萘芬类似物 ,N (2 氯 5 吡啶甲基 ) N 甲基 1 萘甲胺 ,N ,N 二 (4 叔丁基苄基 ) 1 萘甲胺 ,N (4 叔丁基苄基 ) N (2 氯 5 吡啶甲基 ) 1 萘甲胺 ,N ,N 二苄基 4 叔丁基苯甲胺 ,N (2 氯 5 吡啶甲基 ) N 苄基 4 叔丁基苯甲胺 .
【总页数】3页(P99-101)
【关键词】布替萘芬;苄胺类;抗真菌活性;药物合成
【作者】王大威;赵宝祥;王凯铭;左华;沙磊;谭伟
【作者单位】山东大学化学与化工学院有机化学研究所
【正文语种】中文
【中图分类】O623.731
【相关文献】
1.新型催眠镇静药佐匹克隆类似物的合成 [J], 左代姝;张雅芳;沈建民
2.新型抗真菌药—1,3—β—D葡聚糖合成酶抑制剂的研究进展 [J], 唐宁枫
3.新型口服抗真菌药酮康唑的合成 [J], 刘丽琳
4.抗真菌药布替萘芬的合成 [J], 凌云;鲍燕燕;李庶心;王志清
因版权原因，仅展示原文概要，查看原文内容请购买。

s烯虫乙酯结构式 -回复

s烯虫乙酯结构式-回复S-烯虫乙酯（英文名为S-Enalapril)是一种抗高血压和心力衰竭药物，属于ACE抑制剂的一种。

它通过抑制血管紧张素转换酶（ACE），从而阻断血管紧张素转化为血管紧张素Ⅱ的过程，并降低体内血管紧张素Ⅱ水平，从而扩张血管，降低血压。

本文将逐步介绍S-烯虫乙酯的结构、作用机理、药效及副作用等方面，让我们一起来了解这个药物。

首先，让我们来看一下S-烯虫乙酯的结构式。

S-烯虫乙酯分子式为C20H28N2O5，其结构式如下：(图片插入结构式)S-烯虫乙酯是一个酯化合物，它的化学结构中包含一个酯基和一个酰基。

这种结构是由两部分组成的：烯虫胺和乙酸乙酯。

烯虫胺是一种血管紧张素转换酶抑制剂，而乙酸乙酯则是一种酯化合物，它能够增强烯虫胺的药理作用。

S-烯虫乙酯的作用机理是通过抑制血管紧张素转换酶（ACE）来降低血压。

血管紧张素转换酶是一种酶，它能够将血管紧张素Ⅰ转化为血管紧张素Ⅱ。

血管紧张素Ⅱ是一种能够收缩血管的物质，它能够引起血管收缩，增加血压。

而S-烯虫乙酯能够通过抑制血管紧张素转换酶的活性，从而阻断血管紧张素转化为血管紧张素Ⅱ的过程，降低体内血管紧张素Ⅱ水平，从而导致血管扩张，降低血压。

S-烯虫乙酯作为一种抗高血压和心力衰竭药物，具有显著的药效。

它能够降低高血压患者的血压水平，减少心脏的负担。

同时，S-烯虫乙酯还能够改善心脏功能，增加心脏的收缩力，提高冠状动脉血流量，减少冠状动脉阻力，从而改善心力衰竭病人的症状。

然而，S-烯虫乙酯也有一些副作用。

其中最常见的副作用包括头痛、乏力、轻度恶心、咳嗽、喉咙痛、低血压等。

在一些罕见的情况下，S-烯虫乙酯还可能导致皮疹、心动过缓、肺水肿等严重副作用。

因此，在服用S-烯虫乙酯期间，患者应该密切观察自身情况，如发现不适症状应及时就医。

综上所述，S-烯虫乙酯是一种抗高血压和心力衰竭药物，通过抑制血管紧张素转换酶来降低血压。

它能够扩张血管、改善心脏功能，减轻高血压和心力衰竭的症状。

胰岛素抵抗的实验研究

（Ｐ＜０．００１），禁食期血清甘油三酯水平继续下降（Ｐ＜Ｏ．０１），并出现低胆固醇血症（Ｐ＜０．０１）和高脂肪酸血症（Ｐ＜Ｏ．０１）、高胰岛素血症（Ｐ＜Ｏ．０５）；但喂饲大鼠高脂饲料３０或６０天，动物摄入的能量，体重增长，禁食期血清ＴＮＦｄ和正糖钳实验中灌流胰岛素２小时后的血清瘦素水平与对照组比较无显著差别。掌握了脂肪细肥原代培养和传代培养技术。
本工作根据Ｓ自０ｒｌｉｅｎＬＨ的配方制作高脂饲料（ｈｉ曲ｆａｔｄｉｅｔ，ｍ酗ＬＴ），分别喂饲正
常成年ｓＤ大鼠３０天和６０天，用Ｋ瑚ｇｅｎＥｗ方法建立正糖钳技术评估瓜，以葡
萄糖输注率（西ｕｃ０∞ｉｎ向ｓｉｏｎＬａｔｅ，ＧＩＲ）反映ＩＲ，观察ｍ形成和发展过程中禁食期血糖，血脂，血清胰岛素，脂肪细胞大小和相关脂肪细胞源性因子ｌｅｐ血（瘦素）及肿瘤坏死因子ａ（ｔＩ蛐ｏｒｎｅｃｍｓｉｓｆａｃｔｏｒ。ａｌｐｈａ，１ＮＦｄ）的改变。对大鼠附睾脂肪垫脂肪细胞进行体外培养。
论文题目
中国汕和医科大学硕士学位论文
胰岛素抵抗的实验研究
研究生：张荣导师：许荣煜研究员学科：生理学研究方向：脂肪细胞源性因子与胰岛素抵抗所在院所：北京协和医科大学
中国医学科学院基础医学研究所
２００３年６月
中国协和医科大学硕士学位论文
论文：胰岛素抵抗的实验研究
英文缩略语表
缩语
英文原文
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