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A Four-Dimensional (4D) Stability Indicating Analytical Method Optimization and Potency Assay Prediction Using MS and UV Peak Tracking 利用质谱和紫外峰跟踪技术进行四维稳定性指示分析方法优化和效价预测
Pub Date : 2018-01-01 DOI: 10.21065/1920-4159.1000260
A. Blasko, J. Tam, Ahmad Iah, S. Gunasekera, I. Oshchepkova, A. Galin, A. Vazhentsev, Tashlitsky, D. Adams
A total of 60 peaks generated by forced degradation of three active pharmaceutical ingredients (APIs) were used for the column selection in the development of a stability indicating HPLC-UV analytical method using LC-UV and LC-MS peak tracking. Two mobile phase additives and two organic modifiers were evaluated while screening a list of carefully chosen chromatography columns. The column screening was utilized and the best column selected based on total number of resolved peaks, resolutions, peak widths, and peak shapes. 0.1% TFA in ACN/water was used for the initial screening and optimization of the gradient profile. Three different concentrations of TFA in ACN/water were also evaluated. The optimum TFA concentration, 0.10% (8.77 mM), was considered as optimum for further gradient optimization based on the resolution of critical pairs. After the selection of column, mobile phase and mobile phase modifier (TFA) selection, optimization of the gradient was achieved by a combination of automated chemometric peak tracking and software-based decisions in AutoChrom MS. The correct peak retention equations (i.e., retention time vs. mobile phase ratio) were generated by using first one-step gradients with a wide range of % B followed by optimization in multi-steps gradients. It was found that extrapolation, using quadratic retention models, can lead to large errors in retention time (tR) predictions, especially for poorly-retained components. We present the challenges in resolving the critical resolution pairs, including those with the same m/z, the overestimation and the prediction errors of the software, and why the peaks model (i.e., accuracy of predicted versus experimental) fail at the extremes of the gradient. By using this approach we were able to generate a suitable stability indicating chromatographic method for an extremely challenging sample comprising of three active pharmaceutical ingredients (APIs) and related degradation products with a wide range of hydrophobicity. The APIs were in-house compounds, their identity are blinded in this paper and are not relevant for purpose of the study. There were good matches between the predicted and experimental retention times of the tracked peaks. The peak model was used for the generation of an assay/potency method using the computational tool only.
利用三种活性药物成分(api)强制降解产生的60个峰进行色谱柱选择,建立了一种采用LC-UV和LC-MS峰跟踪的稳定性指示HPLC-UV分析方法。在筛选精心挑选的色谱柱时,对两种流动相添加剂和两种有机改性剂进行了评估。利用色谱柱筛选,根据可分辨峰的总数、分辨率、峰宽和峰形状选择最佳色谱柱。在ACN/water中使用0.1% TFA进行梯度剖面的初步筛选和优化。还对ACN/水中三种不同浓度的TFA进行了评价。基于关键对的分辨率,认为TFA的最佳浓度为0.10% (8.77 mM)是进一步梯度优化的最佳浓度。在选择色谱柱、流动相和流动相修饰剂(TFA)后,在AutoChrom ms中通过自动化学峰跟踪和基于软件的决策相结合来实现梯度的优化。正确的峰保留方程(即保留时间与流动相比)通过使用第一步梯度在较大范围内的% B,然后在多步梯度中进行优化。研究发现,使用二次保留模型的外推会导致保留时间(tR)预测的较大误差,特别是对于保留较差的组件。我们提出了解决关键分辨率对的挑战,包括具有相同m/z的关键分辨率对,软件的高估和预测误差,以及为什么峰值模型(即预测与实验的准确性)在梯度的极端情况下失败。通过使用这种方法,我们能够为包含三种活性药物成分(api)和具有广泛疏水性的相关降解产物的极具挑战性的样品生成合适的稳定性指示色谱方法。原料药是内部化合物,它们的身份在本文中是盲目的,与研究目的无关。跟踪峰的预测保留时间与实验保留时间吻合较好。峰模型仅用于使用计算工具生成测定/效价方法。
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引用次数: 0
How to use Green Technology to Enhance Antioxidant Efficiency of Plant Extracts: A Novel Strategy 如何利用绿色技术提高植物提取物的抗氧化效率:新策略
Pub Date : 2018-01-01 DOI: 10.35248/1920-4159.18.10.264
W. Aboulthana, H. H. Sayed
Nanotechnology is a rapidly growing science of producing and utilizing the nano-sized particles. It was necessary to develop another non-toxic and environmentally friendly procedure for production of nanoparticles by mean of green technology to avoid production of the hazardous chemicals (sodium borohydride, sodium citrate, ascorbate, elemental hydrogen, Tollen’s reagent, N,N-dimethyl formamide and poly (ethylene glycol) block copolymers) produced during the chemical preparation. The metal nanoparticles (MNPs) (silver, gold, platinum, copper and zinc oxide) were biosynthesized through the reaction with plant extract by bio-reduction mechanism. Among all noble MNPs, the silver nanoparticles (AgNPs) are non-toxic and gained boundless interests due to their characteristic properties in addition to their significant antibacterial, antifungal and anti-inflammatory effects. The UV-Vis Spectrophotometer, X-Ray Diffractometer (XRD), Atomic Force Microscopy (AFM), Fourier Transform Infrared (FT-IR) Spectroscopy, Dynamic Light Scattering (DLS), Energy Dispersive X-ray Spectroscopy (EDX), Scanning Electron Microscope (SEM), Field Emission Scanning Electron Microscope (FESEM) and Transmission Electron Microscope (TEM) are considered as the most widely used techniques for characterization of the synthesized nanoparticles. Incorporation of the AgNPs into the plant extracts enhanced the antioxidant properties due to increasing the total polyphenolic compounds which exhibit more antioxidant potentials and possesses significant cytotoxicity and free radical scavenging activity than the crude ones. It was revealed that deposition of the nanoparticles was greatest in liver followed by blood, spleen, kidney, lungs, brain, reproductive organs, thymus and heart. Removal of the nanoparticles from the body through renal clearance is considered as a multifaceted process. The review concluded that it is necessary for undergoing further studies to evaluate the deleterious effects that may be occurred as a result of administration of the nanoparticulated extracts.
纳米技术是一门快速发展的生产和利用纳米粒子的科学。为了避免化学制备过程中产生的有害化学物质(硼氢化钠、柠檬酸钠、抗坏血酸、单质氢、托伦试剂、N、N-二甲基甲酰胺和聚乙二醇嵌段共聚物)的产生,有必要通过绿色技术开发另一种无毒环保的纳米颗粒生产工艺。以植物提取物为原料,通过生物还原反应合成了金属纳米颗粒(银、金、铂、铜和氧化锌)。在所有贵重MNPs中,银纳米颗粒(AgNPs)除了具有显著的抗菌、抗真菌和抗炎作用外,还具有无毒的特性,受到了人们的广泛关注。紫外可见分光光度计、x射线衍射仪(XRD)、原子力显微镜(AFM)、傅里叶变换红外光谱(FT-IR)、动态光散射(DLS)、能量色散x射线光谱(EDX)、扫描电子显微镜(SEM)、场发射扫描电子显微镜(FESEM)和透射电子显微镜(TEM)被认为是表征合成纳米颗粒最广泛使用的技术。在植物提取物中掺入AgNPs,由于增加了总多酚类化合物而增强了抗氧化性能,这些化合物比粗提取物具有更强的抗氧化潜力,并具有显著的细胞毒性和自由基清除活性。结果表明,纳米颗粒在肝脏中的沉积量最大,其次是血液、脾脏、肾脏、肺、脑、生殖器官、胸腺和心脏。通过肾脏清除纳米颗粒被认为是一个多方面的过程。该综述的结论是,有必要进行进一步的研究,以评估纳米关节提取物可能产生的有害影响。
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引用次数: 6
RP-HPLC Profile of Major Phenolics from Brown Marine Macro Algae 褐藻中主要酚类物质的反相高效液相色谱分析
Pub Date : 2018-01-01 DOI: 10.35248/1920-4159.18.10.262
Waghmode Av, Khilare Cj
To exemplify quantitative analysis of major phenolics from a brown marine macro algae Sargassum cinereum, Sargassum ilicifolium, Sargassum tenerrimum and Sargassum wightii by RP-HPLC chromatographic profile. Polyphenol content was determined and quantified by reversed phase high performance liquid chromatography (RP-HPLC) methods.
采用反相高效液相色谱法定量分析了褐藻绿尾马尾、黄尾马尾、黄尾马尾和白尾马尾的主要酚类物质。采用反相高效液相色谱法(RP-HPLC)测定多酚含量。
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引用次数: 3
A Mathematical Model Based on an Adaptive Neuro-Fuzzy Inference System for Matrixes Including Indomethacin 基于自适应神经模糊推理系统的吲哚美辛矩阵数学模型
Pub Date : 2018-01-01 DOI: 10.35248/1920-4159.18.10.258
S. Mirshahi, A. Tajani, A. Haghighizadeh, Alireza Karimpour, O. Rajabi
This study is concerned about prediction of dissolution rate of Insoluble drugs from solid dispersion (SD) polymer matrixes by an Adaptive Neuro-Fuzzy Inference System (ANFIS). Polyethylene Glycols (PEGs) as the SD with different molecular weights were provided and dissolution rate of indomethacin (IND) was obtained experimentally. A USP dissolution method was used to monitor the dissolution profiles of matrixes. The numbers of rules were trained in a systematic procedure using the experimental data. Comparison of IND dissolution rate from different matrixes, Area under the Curve (AUC) of absorbance vs. time diagrams in the first 25 min for 72 different samples was determined. Results show a high correlation between observed and predicted data (r2=0.85). The calculated root mean square error for the results of the ANFIS model is equal to 1.02. The index of area AUC in the first 25 min is more repeatable. It seems that the model has practical value and different ratios of polymer for the desired dissolution rate can be predicted or having different polymer ratios in the matrix can predict the dissolution rate of IND. this method can be suggested for other pharmaceuticals formulations to save time and money to achieve the best formula.
本研究利用自适应神经模糊推理系统(ANFIS)预测固体分散体(SD)聚合物基质中不溶性药物的溶出速率。采用不同分子量的聚乙二醇(peg)作为标配剂,测定了吲哚美辛(IND)的溶出率。采用USP溶出度法监测基质的溶出度。利用实验数据对规则的数量进行了系统的训练。比较了72种不同样品在不同基质中的IND溶出率,测定了前25 min吸光度曲线下面积(AUC)与时间图。结果显示,观测数据与预测数据高度相关(r2=0.85)。ANFIS模型计算结果的均方根误差为1.02。前25 min面积AUC指标重复性较好。该模型具有实用价值,可以预测不同比例的聚合物所需的溶出率,或者在基质中使用不同比例的聚合物可以预测ind的溶出率。该方法可建议用于其他药物配方,以节省时间和金钱,从而获得最佳配方。
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引用次数: 7
A Comparative Study of Solubility Enhancement of Aceclofenac by Solid Dispersion Technique Using Several Polymers 几种聚合物固体分散技术增强乙酰氯芬酸溶解度的比较研究
Pub Date : 2018-01-01 DOI: 10.35248/1920-4159.18.10.259
M. Sarangi, Neha Singh
The attempt has been made to compare the aqueous solubility and dissolution characteristics of Aceclofenac (ACE) enhanced by solid dispersion technique using several water soluble carriers PEG 6000, β-Cyclodextrin (β –CD) and Sodium Carboxy methyl cellulose (Na-CMC). Solid dispersions of ACE were prepared with solvent evaporation method. Solid dispersions with carriers were prepared in drug: carrier (1:1, 1:2, 1:3 and 1:4) ratios. The prepared dispersions were evaluated by solubility, in vitro dissolution studies and X-Ray diffraction studies (XRD). The results from XRD analysis showed that ACE might exist in an amorphous state in the solid dispersion. Considerably improved dissolution profile was obtained by PEG ratios (1:2), whereas there was no significant improvement in dissolution of ACE along with β-CD at higher carrier ratios. Na- CMC showed least dissolution improvement among all carriers. The solid dispersion prepared as AC: PEG 6000 (1:2), exhibited the fastest dissolution among all solid dispersions, was formulated into tablets using direct compression method and further compared with immediate release marketed brands of ACE. The results indicated that formulated tablets displayed better dissolution profiles as compared to existing commercial tablets.
以PEG 6000、β-环糊精(β -CD)和羧甲基纤维素钠(Na-CMC)为载体,对固相分散技术增强的乙酰氯芬酸(ACE)的水溶性和溶出特性进行了比较。采用溶剂蒸发法制备了ACE的固体分散体。以药物与载体(1:1、1:2、1:3、1:4)的比例制备载体固体分散体。通过溶解度、体外溶出度和x射线衍射(XRD)对所制备的分散体进行了评价。XRD分析结果表明,ACE在固体分散体系中可能以非晶态存在。PEG比(1:2)显著改善了β-CD的溶出,而在较高的载体比下,ACE和β-CD的溶出没有显著改善。Na- CMC在所有载体中溶出改善最小。制备的固体分散体为AC: PEG 6000(1:2),在所有固体分散体中溶出最快,采用直接压缩法配制成片剂,并与即刻释放的ACE市售品牌进行比较。结果表明,与现有的市售片剂相比,该制剂具有更好的溶出度。
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引用次数: 10
A Neutraceutical Assessment of Trachyspermum ammi 羊草的中性毒性评价
Pub Date : 2018-01-01 DOI: 10.21065/1920-4159.1000263
Khan Nt, N. Jameel
Trachyspermum ammi commonly known as ajwain is widely used in traditional medical practices to cure numerous ailments related to stomach, abdomen and respiratory tract. Besides it also possess antibacterial, antifungal and anti viral properties. Trachyspermum ammi seed contains essential oils and pharmacological constituents that makes it an effective medicinal herb that is used for primary health. It is less expensive to cultivate and is locally available.
在传统的医学实践中,人们广泛使用石榴莲来治疗与胃、腹部和呼吸道有关的许多疾病。此外,它还具有抗菌、抗真菌和抗病毒的特性。水芹籽含有精油和药理成分,使其成为一种有效的草药,用于初级保健。它的种植成本较低,而且在当地就能买到。
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引用次数: 2
Geographical Variation of Antioxidant Constituent in Garhwal Region of Uttarakhand: Chinese Brake Fern (Pteris vittata) 北阿坎德邦加尔瓦尔地区抗氧化成分的地理变异:中国制动蕨(Pteris vittata)
Pub Date : 2018-01-01 DOI: 10.35248/1920-4159.18.10.266
K. Dobhal, A. Semwal, A. Negi
Numerous kind of antioxidants or protecting agent are present in the living body like Glutathione is the master antioxidant produce by the liver and uses free radicals to purify the body. Natural plant consuming antioxidants content is growing the interest for scientific research as well as industrial purposes. Pteridophytes (fern and fern allies) have drawn attention of plants seekers and horticultures since ancient period. Plant of Pteris vittata were collected from different geographical region of Uttarakhand Garhwal. The maximum yield of plant extract was found via the ethanol solvent i.e. 5.07-9.67%. DPV extract exhibited a maximum inhibition of 89.32 relatively closed to 91.96% inhibition of Ascorbic acid at the concentration of 0.1 mg/ml by DPPH radical scavenging assay method. The IC50 of the DPV extract and Ascorbic acid was found to be 0.543 and 0.495 mg/ml by same. DPV extract showed a maximum inhibition of 72.33 % relatively close to 77.42% inhibition of BHA at the concentration of 0.8 mg/ml by Hydrogen peroxide radical scavenging method. The IC50 value of the DPV extract & BHA was found to be 0.279 ± 0.005 mg/ml & 0.257 ± 0.002 mg/ml by same. DPV extract showed a maximum inhibition of 84.32% relatively close to 87.96% inhibition of ascorbic acid at the concentration of 0.8 mg/ml by Nitrogen oxide scavenging method. The IC50 value of the DPV extract & BHA was found to be 0.233 ± 0.002 mg/ml to 0.218 ± 0.006 mg/ml by same.
生物体内存在多种抗氧化剂或保护剂,如谷胱甘肽是肝脏产生的主要抗氧化剂,利用自由基净化身体。天然植物中抗氧化剂的含量越来越受到科学研究和工业应用的关注。蕨类植物(蕨类和蕨类同属植物)自古以来就受到植物探索者和园艺界的关注。在北阿坎德邦不同的地理区域采集了维塔翼属植物。以乙醇为溶剂提取的植物提取物得率最高,为5.07 ~ 9.67%。DPPH自由基清除试验表明,DPPH提取物在0.1 mg/ml浓度下对抗坏血酸的抑制率最高为89.32%,接近91.96%。结果表明,DPV提取物和抗坏血酸的IC50分别为0.543和0.495 mg/ml。过氧化氢自由基清除率为0.8 mg/ml时,DPV提取物对BHA的最大抑制率为72.33%,相对接近77.42%。结果表明,DPV提取物和BHA的IC50值分别为0.279±0.005 mg/ml和0.257±0.002 mg/ml。DPV提取物对抗坏血酸的最大抑制率为84.32%,接近于0.8 mg/ml的抗坏血酸的抑制率87.96%。DPV提取物和BHA的IC50值为0.233±0.002 mg/ml ~ 0.218±0.006 mg/ml。
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引用次数: 2
Impact of Pharmaceutical Companies’ Promotional Tools on Physicians’ Prescription Patterns: A Systematic Review 医药公司促销手段对医师处方模式的影响:系统回顾
Pub Date : 2018-01-01 DOI: 10.35248/1920-4159.18.10.267
May Alowi, Yusuf Kani
Purpose: The role of pharmaceutical companies’ promotional tools in the prescribing decision of physicians comprises five commonly-used promotional tools: sales promotions; advertising; public relations; direct marketing; and personal selling. The purpose of this paper was to examine the existing literature on promotional tools and then explore which medical practitioners’ demographic factors influence the relationship between the various promotional tools and physicians’ prescription behaviour. Design/methodology/approach: A survey of the literature was carried out across online databases from 2008 to 2018, and 41 reviewed articles were identified. The influence of promotional tools on physician prescribing decisions was identified in the articles. Findings: There have been numerous studies on the effect of promotional tools on physician prescription decision. They demonstrated that promotional tools strongly influence physicians’ prescribing decision, but a few others found only minor or no relation. To resolve this ambiguity, there is a need to precisely understand how promotional tools affect prescribing decisions of physicians, under different contexts and conditions. Research limitations/implications: The study recommends further studies on the influence of each factor on physician prescribing behaviour and an evaluation of the proposed model and moderating variables. Originality/value: This paper provides a significant step towards recognizing the relationship between promotional tools and prescribing behaviour. This research contributes to the debate on the ways prescribing behaviour can be affected.
目的:制药公司的促销工具在医生处方决策中的作用包括五种常用的促销工具:销售促销;广告;公共关系;直接销售;还有个人销售。本文的目的是检查现有文献的促销工具,然后探讨哪些医生的人口因素影响各种促销工具和医生的处方行为之间的关系。设计/方法/方法:对2008年至2018年在线数据库中的文献进行了调查,并确定了41篇综述文章。促销工具对医生处方决定的影响在文章中被确定。研究结果:关于促销工具对医生处方决策的影响已有大量研究。他们表明,促销工具强烈影响医生的处方决定,但少数其他人发现只有轻微或没有关系。为了解决这种歧义,有必要准确地了解促销工具如何影响医生在不同背景和条件下的处方决策。研究局限性/启示:该研究建议进一步研究每个因素对医生处方行为的影响,并对所提出的模型和调节变量进行评估。原创性/价值:本文为认识促销工具和处方行为之间的关系提供了重要的一步。这项研究有助于讨论如何影响处方行为。
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引用次数: 11
NANOPATTERNING: IMPLICATIONS IN REGENERATIVE MEDICINE 纳米图谱:在再生医学中的意义
Pub Date : 2017-12-27 DOI: 10.21065/19204159.9.31
M. Nasr
Regenerative medicine is based on stem cells, which have the ability to differentiate into special type of body cells, and hence, they were proven clinically successful in organ transplantation, as well as in the functional treatment of several diseases (1).
再生医学以干细胞为基础,干细胞具有分化为特殊类型体细胞的能力,因此在器官移植和几种疾病的功能性治疗方面已被临床证明是成功的(1)。
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引用次数: 0
Evaluation of Antioxidant, Cholinesterase Inhibitory Properties, and Antibacterial Potentials of Glycomis Pentaphylla Leaf Extract Relevant to the Treatment of Alzheimer's Disease 与阿尔茨海默病治疗相关的五叶糖提取物的抗氧化、胆碱酯酶抑制特性和抗菌潜力的评价
Pub Date : 2017-12-17 DOI: 10.21065/19204159.9.17
Rezanur Rahman, T. Islam, H. M. Faruquee, S. Akhter, Md. Anwarul Haque
There is a tremendous unmet need to discover more potent and safe drugs for the treatment of Alzheimer’s disease (AD). Reduced cholinergic activity and oxidative stress have been recognized as a major contributing factor in the pathogenesis of AD. Therefore, inhibition of cholinesterase and oxidation are the two promising strategies in the development of a drug for AD. This study determined the anti-acetylcholinesterase (AChE) activity, anti-butyrylcholinesterase (BChE) activity, DPPH free radical scavenging and antioxidant properties of Glycomis pentaphylla (Rutaceae). The objective of this study is to measure G. pentaphylla anti-AChE, anti-BChE, DPPH free radical scavenging, lipid peroxidation inhibition, antibacterial potentials to find out the MIC (minimum inhibitory concentration) against different pathogenic bacteria. G. pentaphylla leaf extract (GPEx) is exploited in the presented research to estimate its anticholinesterase, antioxidant potentials, and antibacterial properties. The cholinesterase inhibitory properties was quantified by modified Ellman method, and antioxidant potentials were evaluated by the assay of radical scavenging, and inhibition of lipid peroxidation. The antibacterial activity and minimum inhibitory concentration (MIC) were determined using agar well diffusion method. The methanolic extract exhibited significant dual acetylcholinesterase (AChE) and butyryl cholinesterase (BChE) effect. The IC50 values of AChE and BChE were 325.1±0.91, and 42.14±3.31 μg/ml. Furthermore, the extract showed radical scavenging ability, and lipid peroxidation inhibitory effect. The IC50 values of the extract for DPPH and hydroxyl free radical scavenging, and lipid peroxidation inhibition assay were 95.6±0.68, 198.0±1.39, and 288.7±0.91 μg/ml, respectively. Phytochemical screening of the extract revealed the presence of significant total phenolics and flavonoids contents. Additionally, the extract showed good effect with the zone of inhibition ranging 12–16 mm in diameter against Salmonella typhi, Pseudomonas aeruginosa, Staphylococcus aureus. The tested sample reflects potential antioxidative and anticholinesterase inhibitory potentiality which may warrant its effectiveness in the treatment of AD along with good antibacterial properties.
在发现治疗阿尔茨海默病(AD)的更有效、更安全的药物方面,存在巨大的未满足需求。胆碱能活性降低和氧化应激已被认为是阿尔茨海默病发病的主要因素。因此,抑制胆碱酯酶和氧化是阿尔茨海默病药物开发中两个有前途的策略。本研究测定了五谷糖的抗乙酰胆碱酯酶(AChE)活性、抗丁基胆碱酯酶(BChE)活性、DPPH自由基清除能力和抗氧化性能。本研究的目的是通过测定五谷葡萄球菌抗ache、抗bche、DPPH自由基清除能力、脂质过氧化抑制能力、抗菌潜能,找出其对不同致病菌的最低抑制浓度(MIC)。本研究利用五味子叶提取物(GPEx)来评估其抗胆碱酯酶、抗氧化潜力和抗菌性能。采用改进的Ellman法定量测定其胆碱酯酶抑制性能,并通过自由基清除和脂质过氧化抑制试验评价其抗氧化能力。采用琼脂孔扩散法测定其抑菌活性和最低抑菌浓度。甲醇提取物具有显著的双乙酰胆碱酯酶(AChE)和丁基胆碱酯酶(BChE)作用。AChE和BChE的IC50值分别为325.1±0.91、42.14±3.31 μg/ml。此外,提取物还具有清除自由基和抑制脂质过氧化的作用。提取物对DPPH和羟基自由基的清除作用IC50分别为95.6±0.68、198.0±1.39和288.7±0.91 μg/ml。提取物的植物化学筛选显示存在显著的总酚和类黄酮含量。该提取物对伤寒沙门菌、铜绿假单胞菌、金黄色葡萄球菌的抑制范围为12 ~ 16 mm。测试样品反映了潜在的抗氧化和抗胆碱酯酶抑制潜力,这可能保证了其治疗AD的有效性以及良好的抗菌性能。
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引用次数: 2
期刊
Journal of Applied Pharmacy
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