暑药团售热

暑药团售是药店夏季"冷"经营的一个热点,虽然业务模式相似,但个中巧妙各有不同。

基于改进Apriori算法的钟以泽治疗银屑病中药处方配伍提取及规律研究

目的：应用改进Apriori算法对钟以泽教授的处方进行统计。方法：应用数据挖掘技术中的Apriori算法进行统计并加以改进。结果：统计出从单味药到7味药团的使用频次并进行排列。结论：对于钟以泽教授治疗银屑病中医处方的统计中,单味药、2味药对、3味药团、6味药团的统计具有意义,单味药的统计意义在于能够看出每一味药物的使用频次,2味药对和3味药团统计的意义在于可以看出药团的加减使用组合情况,6味药团的统计意义在于可以通过药物加减推断出疾病的分型和相关症状的加减。

基于SWOT-PEST矩阵模型的美团买药板块发展策略研究

随着“互联网+”药物新零售形式的发展,网络购药成为当下消费新常态,本文以美团买药板块为例,运用SWOT-PEST矩阵模型探讨美团买药板块发展的现状及其优势、劣势、机会、威胁,认为美团买药板块应重点完善自身线上交易平台,提高优惠力度,实行差异化个性化服务来留住消费者;实现新消费体验,解决消费者买药难,买药贵的痛点问题。完善自身服务售后体验,提高消费者的使用信心;积极和线下的各种渠道合作,与线下药店和社区下沉市场建立紧密伙伴关系,利用线下的渠道帮助美团减轻运营成本;推动互联网支付系统,在线上支付上面进一步简化操作,并且积极推动医保支付。推动实现“人-医药-场景”三位一体消费模式等发展策略。

Construction and Evaluation of Merged Pharmacophore Based on Peroxisome Proliferator Receptor-Alpha Agonists

Pharmacophore is a commonly used method for molecular simulation, including ligand-based pharmacophore （LBP） and structure-based pharmacophore （SBP）. LBP can be utilized to identify active compounds usual with lower accuracy, and SBP is able to use for distin- guishing active compounds from inactive compounds with frequently higher missing rates. Merged pharmacophore （MP） is presented to integrate advantages and avoid shortcomings of LBP and SBP. In this work, LBP and SBP models were constructed for the study of per- oxisome proliferator receptor-alpha （PPARα） agonists. According to the comparison of the two types of pharmacophore models, mainly and secondarily pharmacological features were identified. The weight and tolerance values of these pharmacological features were adjusted to construct MP models by single-factor explorations and orthogonal experimental design based on SBP model. Then, the reliability and screening efficiency of the best MP model were validated by three databases. The best MP model was utilized to compute PPARα activity of compounds from traditional Chinese medicine. The screening efficiency of MP model outperformed individual LBP or SBP model for PPARα agonists, and was similar to combinatorial screening of LBP and SBP. However, MP model might have an advantage over the combination of LBP and SBP in evaluating the activity of compounds and avoiding the inconsistent prediction of LBP and SBP, which would be beneficial to guide drug design and optimization.

中枢多巴胺系统在痛觉调制中的作用研究

中枢多巴胺 (DA)系统参与痛觉调制的作用已得到肯定。但由于研究方法的不同 ,所得结果也有较大差异。不同的中枢部位或核团不同DA受体亚型介导的痛觉调制作用不尽相同。

3D-QSAR Analysis of DDPH Derivatives for α_1-Adrenoceptor Antagonist Activity

Aim and methods The study of three-dimensional quantitative structure-activity relationship （3D-QSAR） of DDPH and its derivatives has been performed using Apex-3D programme. Results The result indicates that substituents of para- and ortho-positions in phenyl ring of aryloxyalkylamine greatly influence the bioactivity. Conclusion The biophore model and 3D-QSAR equation help us not only further understand receptor-ligand interactions, but also design new compounds with better bioactivity.

New lead discovery for novel M_1 agonists:pharmacophore model based on DISCO computation and virtual screening

To discover new lead compounds for M1 agonists. Ten typical M1 agonists were superimposed to build a M1 agonists 3D-pharmacophore model using distance-comparisons （DISCO） method without the previous knowledge of the three-dimensional structure of M1 receptor. Virtual screening strategy was used to analyze the Available Chemicals Directory-Screening Compounds （ACD-SC） to identify possible new hits. Twenty-two compounds which fit the pharmacophore model well and are not similar with known M1 agonists were purchased in order to evaluate their M1 receptor agonist activity. One of them shows M1 receptor agonist activity with EC50 of 4.90 μmol/L and maximum response. Multiple of 10.0 which shows it worthy of further study as a new lead compound for M1 agonists.

Screening for cyclooxygenase 2 inhibitors from natural compounds of Radix Glycyrrhizae using computer simulation

Objective： To explore the molecular basis of the effects of Gancao （Radix Glycyrrhizae, GC） on inflammation throughthe inhibition of cyclooxygenase 2 （COX-2）. Methods： The Discovery Studio 4.5 System was used to predict thephysicochemical properties of GC molecular compounds. The Ligand Profiler was used to screen for natural GCcomponents that could combine with the COX-2 pharmacophores. The AutoDock Vina 1.1.2 software was used for themolecular docking of the natural GC components with the COX-2 protein. Results： The aromatics were the closest to thenon-steroidal anti-inflammatory drugs in terms of the three properties, namely molecular weight, molecular surface area,and molecular solubility, followed by the flavonoids; whereas the terpenoids/saponins differed most from thenon-steroidal anti-inflammatory drugs in terms of the three properties; and the aliphatics were inconsistent. One hundredand eighteen small molecules were obtained through the pharmacophore screening using GC. The molecular bindingenergy （MBE） results demonstrated that the MBE value of the flavonoids/aromatics, obtained from their binding with theCOX-2 protein, was lower than that obtained from their binding with the substrate, metabolism of arachidonic acid,whereas the MBE value of the aliphatics/terpenoids, obtained from their binding with the COX-2 protein, was higherthan that obtained from their binding with the substrate, arachidonic acid. Finally, further filtration, based on thephysicochemical properties and the molecular binding energies of the small molecules, was carried out. Forty-twonatural GC components, including 35 flavonoid and 7 aromatic constituents, with low binding energies and potentialinhibitory effects on COX-2, were screened. Conclusion： Using the three-step program, pharmacophore screening,molecular docking, and physicochemical properties analysis, we screened out 35 flavonoid molecules and 7 aromaticmolecules, which may be potential COX-2 inhibitors, from GC. Two of the 35 flavonoid molecules （licochalcone A andglabridin） have been confirmed in the laboratory to have inhibitory effects on COX-2. Our findings provide a materialbasis for the development of non-steroidal GC drugs.

Computational Evaluation of Selectivity of Triazole-and Amide-Based Drug Candidates, Flavanone Derivatives and Synthesized Steroid Compounds for Treatment of Diabetes Type II

Inhibition of 11βHSD1 （11-beta-hydroxysteroid dehydrogenase 1） is a promising strategy in drug treatment of diabetes. Several 11βHSDI inhibitors have been proposed; however, their selectivity to 11βHSD1 over its isozyme 11βHSD2 （11-beta-hydroxysteroid dehydrogenase 2） has not been fully reported. The authors sought to provide a short list of top potent and selective compounds along with their detailed binding modes and pharmacophore models, Molecular docking was used for initial screening of a set of 23 potent inhibitors reported by previous experimental studies. After that, selected promising entries were reassessed by molecular dynamics simulations, followed by hydrogen bond analysis. Pharmacophore models of all drug candidates and binding modes of some selected drugs were analyzed. Among the 23 compounds, only four inhibitors were identified as potent and selective drug candidates. Binding energies, 3D pharmacophores and binding modes of the four compounds with 11βHSDI are also discussed in detail in this study.

P物质对继发性高血压大鼠的血压调节作用

为了探究不同浓度的P物质溶液对继发性高血压大鼠的血压调节作用,从而为临床找到一适合的降压药物而提供理论基础。本实验采取高盐饮食诱导的方法建立高血压大鼠的模型,通过脑核团给药的方式,向大鼠侧脑室分别注射浓度为0.1nmol、0.5nmol和1nmol的P物质溶液以及0.9%生理盐水,利用大鼠无创血压测定仪对其血压进行测定,并将测定的数据结果与大鼠的初始血压值进行比对,结果显示:注射P物质后的高血压大鼠的血压值有所降低,且降压效果与P物质浓度有关,降压效果最佳的浓度为1nmol。说明P物质能够参与继发性高血压大鼠的血压调节作用,且浓度越高,降压效果越好。

Three-dimensional common-feature hypotheses for Toll-like receptor 7 agonists

Toll-like receptor 7 （TLR7）, the best known TLRs, has been demonstrated to be useful in fighting against infectious disease. In our study, three-dimensional （3D） pharmacophore models were constructed from a set of 5 TLR7 agonists. Among the 10 common-featured models generated by program Discovery Studio/HipHop, a hypothesis （Hypo2） including one hydrogen-bond donor （D）, one hydrogen-bond acceptor （A）, and two hydrophobic （H） features was considered to be important in evaluating the ligands with TLR7 agonistic activity. The obtained pharmacophore model was further validated using a set of test molecules and the Catalyst TLR7-agonist-subset database. Hypo2 has been shown to identify a range of highly potent TLR7 agonists. Finally, the obtained pharmacophore was further validated using docking studies. Taken together, this model can be utilized as a guide for future studies to design the structurally novel TLR7 agonists.

Insights into the discovery of new 5-HT1A receptor ligands:receptor based pharmacophore

5-HT1A receptor is a crucial therapeutic target for the treatment of anxiety, depression, pain, etc. Design and preparation of potent 5-HT1A receptor ligands for drug discovery has attracted extensive attention in the past few years. In this paper, a three dimensional model of human 5-HT1A receptor was constructed by means of homology modeling. And the docking of MP349 to the receptor suggested a reliable binding mode for 5-HT1A receptor ligand. Based on this ligand-receptor binding mode, an elaborate receptor structure based pharmacophore model was established, which revealed many important features responsible for ligand and 5-HT1A receptor interactions. A virtual screening experiment verified the ability of this pharmacophore model to discover true 5-HT1A receptor ligand. The results of this research would provide important information for further optimizations of 5-HT1A receptor ligands and guide related new lead discoveries.

Pharmacophore identification and validation for human nAChR α7 agonists

Human nAChR u7 is the potential target for schizophrenia cognitive disorders, and it is meaningful to develop selective human nAChR α7 agonists for the clinical treatment of the disease. Because the crystal structure ofα7 receptor has not been resolved, ligand-based drug design strategy was took in this work. A 3D QSAR pharmacophore model was built by HypoGen method, and its quality was evaluated by cost function. Furthermore, the pharmacophore model was validated with activity prediction of test set and was cross-validated based on Fisher＇s Randomization Method. By Enrichment Factor and AU-ROC analysis, the final pharmacophore, which is consisted of one HBA, two Hydrophobic and one PosIonizable, was selected and it fitted well with the docking result of α7 homology model and the ligand. The pharmacophore is expected for the following virtual screening and lead optimization of human nAChR α7 agonists, which is important for the development and discovery of novel antipsychotics.

In silico pharmacophore models to predict endogenous substrates for human multidrug resistance-associated proteins

Multidrug resistance-associated proteins （MRPs） can effiux structurally diverse drugs, drug conjugates, drug metabolites, as well as other small molecules out of the cells, and this is the main cause of producing multidrug resistance （MDR） of some anticaneer drugs. Therefore, it is crucial to uncover the molecular features of MRPs substrates in developing anti-MDR cancer therapy. In the present study, common feature pharmacophore models were developed by employing CATALYST Pharmacophore Modeling and Analysis tools using substrates of MRPs, including MRP1, -2, -3, -4, -5, -6, -8 and MRPs family, respectively. The models were validated using independent decoy sets generated in DUD-E, and the ones with best A UC （area under the curve） scores were chosen to predict endogenous substrates by screening the Human Metabolome Database （HMDB）. A number of molecules obtained by pharmacophore screening have been validated in the literatures. By comparing physical properties （ALOGP, Molecular_PolarSurfaceArea, Molecular_Volume, Molecular_Weight, Num H Acceptors, Num H Donors） and scaffold features of the screened candidates with the known substrates, we found that： 1） The two sets have consistent ALOGP, Molecule_Volume and Molecule_Weight distribution trend; 2） Substrates of MRP1 have a better lipophilicity than the other subtypes, which is consistent with the two hydrophobic centers on the MRP1 pharmacophore; 3） In the aspect of the scaffold structures, they have the identical or similar backbone fragments.

Predicting hiCE inhibitors based upon pharmacophore models derived from the receptor and its ligands

Human intestinal carboxyl esterase （hiCE） is a drug target for ameliorating irinotecan-induced diarrhea. By reducing irinotecan- induced diarrhea, hiCE inhibitors can improve the anti-cancer efficacy of irinotecan. To find effective hiCE inhibitors, a new virtual screening protocol that combines pharmacophore models derived from the hiCE structure and its ligands has been pro- posed. The hiCE structure has been constructed through homology techniques using hCESI＇s crystal structure. The hiCE structure was optimized via molecular dynamics simulations with the most known active hiCE inhibitors docked into the structure. An optimized pharmacophore, derived from the receptor, was then generated. A ligand-based pharmacophore was also generated from a larger set of known hiCE inhibitors. The final hiCE inhibitor predictions were based upon the virtual screening hits from both ligand-based and receptor-based pharmacophore models. The hit rates from the ligand-based and receptor-based pharmacophore models are 88% and 86%, respectively. The final hit rate is 94%. The two models are highly consistent with one another （85%）. This proves that both models are reliable.

Comparative pharmacophore modeling of human adenosine receptor A1 and A3 antagonists

Adenosine receptors are promising therapeutic targets in drug discovery. In this study, three-dimensional pharmacophore mod- els of human adenosine receptor A1 and A3 antagonists were developed based on 26 and 23 diverse compounds, respectively. The best A1 pharmacophore model （A1-Hopyl） consists of four features： one hydrogen bond donor, one hydrophobic point and two ring aromatics, while the best A3 pharmacophore model （A3_Hopyl） also has four features： one hydrogen bond ac- ceptor, one hydrophobic point and two ring aromatics. The correlation coefficients were 0.840 for A1 test set with 146 diverse compounds and 0.827 for A3 test set with 238 diverse compounds. In the simulated virtual screening experiments, high en- richment factors of 6.51 and 6.90 were obtained for A1_Hopyl and A3_Hopyl models, respectively. Moreover, two models also showed high subtype-selectivity in the simulated virtual screening experiments. These results could be helpful for the dis- covery of novel potent and selective A1 and A3 antagonists.

Polymers with tertiary amine groups for drug delivery and bioimaging

Over the past decade, biopolymers have gained great interests especially in biomedicine due to their physical properties and/or chemical structures changes in response to external stimuli in a certain time fiarne or at a specific location. Among them, poly（β-amino ester）s, methacrylate-based block copolymers and polypeptide with tertiary amine groups have been extensively studied and exhibit pH sensitive properties due to the protonation of tertiary amine groups. The pH values in normal organs, tissues, and subcellular compartments are always different from those in pathological tissues. These interesting properties allow their applications in a variety of fields ranging from diagnosis and therapeutics of diseases. Here, we review the recent progress of poly（β-amino ester）s, methacrylate-based block copolymers and polypeptide with tertiary amine groups and their applications in drug delivery and bioimaging.

Clinical and economic benefits of a pharmacist in a multidisciplinary team for Chinese outpatients with gastrointestinal stromal tumors

The multidisciplinary approach is beneficial to the treatment of gastrointestinal stromal tumors(GISTs).However,pharmacists are seldom incorporated into a multidisciplinary team(MDT)of GIST.In the present study,we evaluated the clinical and economic benefits of a pharmacist in an MDT of GIST.This was a retrospective study that included 240 GIST patients receiving imatinib therapy.The GIST MDT pharmacist developed and validated an HPLC method to monitor the trough concentrations of imatinib in GIST patients.Besides,the pharmacist also provided patient education and pharmaceutical care services and collected the data for analysis.The 240 GIST patients received the services provided by the pharmacist.The trough concentrations in 25.42%of the 240 patients were less than 1100 ng/m L.The main genotypes of 121 in the 240 patients were KIT exon 11 mutations,wild type,and KIT exon 9 mutations.Moreover,13 GIST patients with trough concentrations less than 1100 ng/m L were confirmed to have low compliance.The adverse reactions were primarily mild and tolerable,except that 13 GIST patients were adjusted to lower doses because of the intolerable adverse reactions.The daily cost could be lowered by monitoring the trough concentrations and dose reductions.Collectively,a pharmacist included in a GIST MDT could increase the compliance of Chinese GIST patients to imatinib therapy and improve the efficacy,safety,and economy of imatinib therapy.

A facile access for the C–N bond formation by transition metal-free oxidative coupling of benzylic C–H bonds and amides

Using 2,3-dichloro-5,6-dicyano-p-benzoquinone(DDQ)as the oxidant,we communicate an efficient oxidative C–N coupling of benzylic C–H bonds with amides to afford a series of amination products in good yields.A wide range of functional groups as well as various sulfonamides and carboxamides are well tolerated.Moreover,this reaction involves both the challenging C–H functionalization and C–N bond formation.