Application of Modeling Drugs in Animal Models of Chemical Phlebitis: Review

Objective: This review aims to determine the impact of different drugs and methods on the successful establishment of an animal model for chemical phlebitis (CP). Design: Search the Cochrane Library, ProQuest Academic Journal Library, PubMed, Web of Science, Ovid, Embase, CINAHL complete (EESCO) and other related databases to determine the literature. Screen out articles consistent with this review and summarize them. Results: Since the establishment of the database, a total of 1463 articles have been retrieved. After reading the title, abstract and full text, and excluding non-related and duplicate articles, 22 reports were finally included. Among them, there are 8 articles using different medication methods to compare the effects of establishing a CP model. The included articles explored the effects of different animal models, drug types, and their dose, concentration, speed, and time on the CP model. Conclusion: The factors of dose, concentration and time were positively correlated with the incidence of CP. The effect of speed factors on CP and the results of different animal models are inconsistent. It requires further research in the future.

Energy pharmacological effects of chemical drugs

Background:To study the energy pharmacological effects of chemical drugs.Methods:The energy pharmacological effects of chemical drugs were studied using a literature induction method.Results:Chemical drugs have energy properties,which can be expressed in terms of cold,hot,warm,and cool.The energy properties of chemical drugs have energy pharmacological effects,which are related to the bond energy release and absorption of intermolecular chemical bonds,where the release of energy from chemical bonds indicates a warm-hot energy pharmacological effect and the absorption of energy indicates a cold energy pharmacological effect.The mechanisms of chemical drug energy may be related to the presence of temperature-sensitive ion channels in the body.Conclusion:Chemical drugs exhibit energy pharmacological effects.

Bi_(2)O_(3)/ZnO nanocomposite:Synthesis,characterizations and its application in electrochemical detection of balofloxacin as an antibiotic drug

In the present work,a chemically modified electrode has been fabricated utilizing Bi_(2)O_(3)/ZnO nanocomposite.The nanocomposite was synthesized by simple sonochemical method and characterized for its structural and morphological properties by using XRD,FESEM,EDAX,HRTEM and XPS techniques.The results clearly indicated co-existence of Bi_(2)O_(3) and ZnO in the nanocomposite with chemical interaction between them.Bi_(2)O_(3)/ZnO nanocomposite based glassy carbon electrode(GCE)was utilized for sensitive voltammetric detection of an anti-biotic drug(balofloxacin).The modification amplified the electroactive surface area of the sensor,thus providing more sites for oxidation of analyte.Cyclic and square wave voltammograms revealed that Bi_(2)O_(3)/ZnO modified electrode provides excellent electrocatalytic action towards balofloxacin oxidation.The current exhibited a wide linear response in concentration range of 150e1000 nM and detection limit of 40.5 nM was attained.The modified electrode offered advantages in terms of simplicity of preparation,fair stability(RSD 1.45%),appreciable reproducibility(RSD 2.03%)and selectivity.The proposed sensor was applied for determining balofloxacin in commercial pharmaceutical formulations and blood serum samples with the mean recoveries of 99.09% and 99.5%,respectively.

Computational Chemistry and Molecular Modeling Techniques for the Study of Micropeptin EI-964: Insights into Its Chemical Reactivity and Potential Pharmaceutical Properties

Micropeptin EI-964 is a cyclic peptide compound isolated from a marine cyanobacterium with potent inhibitory activity against serine proteases, particularly chymotrypsin and trypsin. It has shown promising activity against various cancer cell lines, making it a candidate for drug development. The unique structure and activity of Micropeptin EI-964 make it a promising lead compound for the development of novel serine protease inhibitors and anti-cancer drugs. Computational Chemistry and Molecular Modeling techniques can provide valuable insights into the chemical reactivity and pharmaceutical properties of Micropeptin EI-964, guiding the design and development of new compounds with enhanced bioactivity and improved drug-like properties.

Fluorescence imaging of drug target proteins using chemical probes

Fluorescence imaging can provide valuable information on the expression,distribution,and activity of drug target proteins.Chemical probes are useful small-molecule tools for fluorescence imaging with high structural flexibility and biocompatibility.In this review,we briefly introduce two classes of fluorescent probes for the visualization of drug target proteins.Enzymatically activatable probes make use of the specific enzymatic transformations that generally produce a fluorogenic response upon reacting with target enzymes.Alternatively,specific imaging can be conferred with a ligand that drives the probes to target proteins,where the labeling relies on noncovalent binding,covalent inhibition,or traceless labeling by ligand-directed chemistry.

The Relationship between Drug－and Chemical－exposure and Birth Defects during Pregnancy

A case-control study was conducted in 36 hospitals of the urban and suburban areas of shanghai about the relationships between birth defects and drug use and chemical exposures during pregnancy in the period of july 1987-December 1990.The case group was composed if 1,609 subjects,and the control group 3,218 cases.On stall'stical analysl's,it was.found that a correlation ed'sted between birth defects and the intake Of APC and diazepam,and the exposure to pesticides,organic solvents.benzene,synthetic resin and physical.factors(noises)on foe part of foe mother.and the exposure to harmful chemicals and physical factors and the smoking of 20 or more cigarettes a day on the part Of the father.It is also found that foe familial heredilary history of the parents and multigravavidity,malnutrition,common colds,hepatitis and diarrhea during pregnancy may also be relaied to the birth defects.

Published the papers of GC-MS analysis—Chemical drug

Song Qi, Liu Hu; Gao Shu. Screening and quantitative analysis of volatile markers in the breath of patients with breast cancer Acta Universitatis Medicinalis Anhui, 2010, 45（01） ：76-79.

Published the papers of HPLC-MS analysis—Chemical drug

Sun Guoxiang, Ding Nan, Song Yuqing, Wang Zhen, Song Liangwei. Determination of Guaiacol salicylate in Guacetisal by HPLCmethod and qualitative identification of relevant substances by HPLC-MS

Commentary: Unexpected Novel Chemical Weapon Agents Designed by Innocuous Drug-Development AI (Artificial Intelligence) Algorithm

Recent publications reveal the disturbing information that a minor edit to an algorithm being used for designing legitimate drug candidates redirected the program in a way that resulted in the surprising design of novel chemical warfare agent candidates. Although this outcome was not the result of nefarious intent, and appropriate chemical defense authorities were notified, the potential implications of some misapplication of a drug-design algorithm for nefarious purposes are clear. This Commentary summarizes how otherwise benign Artificial Intelligence (AI) algorithms used for drug discovery can be easily reversed to design novel chemical warfare agents for which no effective antidote will be available, or perhaps even envisioned.

Chemical Reactivity Properties, Drug-Likeness Features and Bioactivity Scores of the Cholecystokinin Peptide Hormone

Five density functionals, CAM-B3LYP, LC-ωPBE, MN12SX, N12SX and ωB97XD, in connection with the Def2TZVP basis set were assessed together with the SMD solvation model for the calculation of the molecular and chemical reactivity properties of the Cholecystokinin peptide hormone (CCK-8) in the presence of water. All the chemical reactivity descriptors for the systems were calculated via Conceptual Density Functional Theory (CDFT). The potential bioavailability and druggability as well as the bioactivity scoresfor CCK-8 were predicted through different methodologies already reported in the literature which have been previously validated during the study of different peptidic systems. The conclusion was that the CCK-8 peptide will be moderately bioactive regarding all the interactions.

Chemical proteomics:terra incognita for novel drug target profiling

The growing demand for new therapeutic strategies in the medical and pharmaceutic fields has resulted in a pressing need for novel druggable targets.Paradoxically,however,the targets of certain drugs that are already widely used in clinical practice have largely not been annotated.Because the pharmacologic effects of a drug can only be appreciated when its interactions with cellular components are clearly delineated,an integrated deconvolution of drug-target interactions for each drug is necessary.The emerging field of chemical proteomics represents a powerful mass spectrometry(MS)-based affinity chromatography approach for identifying proteome-wide small molecule-protein interactions and mapping these interactions to signaling and metabolic pathways.This technique could comprehensively characterize drug targets,profile the toxicity of known drugs,and identify possible off-target activities.With the use of this technique,candidate drug molecules could be optimized,and predictable side effects might consequently be avoided.Herein,we provide a holistic overview of the major chemical proteomic approaches and highlight recent advances in this area as well as its potential applications in drug discovery.

Physicochemical and elemental studies of Hydrocotyle javanica Thunb. for standardization as herbal drug

Objective: To explore the leaves of Hydrocotyle javanica Thunb. as a source of safe and effective antibacterial herbal medicine.Methods: The standardization was validated by stepwise physicochemical studies,element analysis, determination of ash values, fluorescence analysis, assessment of moisture content, extractive values in different solvent systems and extraction methods.Heavy metal contents, mineral and element contents were analysed by atomic absorption spectrophotometry, inductively coupled plasma-mass spectrometer and CHNS/O analyser, respectively.Results: The methanol extract of the folklore medicinal plant having antibacterial efficacy contained flavonoids and phenolic OH groups. The ICP multi standard indicated the presence of three major compounds with molecular mass of 161 190 and 221 Da. Heavy metals viz. lead, mercury and copper content were 4.38 ppm, < 0.05 ppm and 24.70 ppm,respectively. Minerals content of calcium, phosphorus, potassium and iron were 1 190.94 mg/100 g, 375.57 mg/100 g, 2 820 mg/100 g and 340.20 mg/100 g of plant sample, respectively. Elements like carbon, hydrogen, nitrogen and sulphur contents were38.18%, 5.67%, 2.23% and 0.51%, respectively. Heavy metal profile of the tested plant was within the permissible limits of the regulatory authorities.Conclusions: Hence the present physicochemical and elements studies reveals that the plant Hydrocotyle javanica Thunb. could be a potent source of herbal preparation as well as a safe and novel synthetic antibacterial drug.

Drug adulteration analysis based on complexation with cyclodextrin and metal ions using ion mobility spectrometry

Drug adulteration and contamination are serious threats to human health therefore,their accurate monitoring is very important.Allopurinol(Alp)and theophylline(Thp)are commonly used drugs for the treatment of gout and bronchitis,while their isomers hypoxanthine(Hyt)and theobromine(Thm)have no effect and affect the efficacy of the drug.In this work,the drug isomers of Alp/Hyt and Thp/Thm are simply mixed withα-,β-,γ-cyclodextrin(CD)and metal ions and separated using trapped ion mobility spectrometry-mass spectrometry(TIMS-MS).TIMS-MS results showed that Alp/Hyt and Thp/Thm isomers could interact with CD and metal ions and form corresponding binary or ternary complexes to achieve their TIMS separation.Different metal ions and CDs showed different separation effect for the isomers,among which Alp and Hyt could be successfully distinguished from the complexes of[Alp/Hyt+γ-CD+Cu–H]^(+)with separation resolution(RP–P)of 1.51;whereas Thp and Thm could be baseline separated by[Thp/Thm+γ-CD+Ca–H]^(+)with RP–P of 1.96.Besides,chemical calculations revealed that the complexes were in the inclusion forms,and microscopic interactions were somewhat different,making their mobility separation.Moreover,relative and absolute quantification was investigated with an internal standard to determine the precise isomers content,and good linearity(R^(2)>0.99)was obtained.Finally,the method was applied for the adulteration detection where different drugs and urine were analyzed.In addition,due to the advantages of fast speed,simple operation,high sensitivity,and no chromatographic separation required,the proposed method provides an effective strategy for the drug adulteration detection of isomers.

The role of drug utilization evaluation in medical sciences

Background:Drug utilization evaluation(DUE)is defined by the World Health Organization(WHO)and focuses on the medical,social,and economic consequences of pharmaceutical marketing,distribution,prescribing,and usage in society.The WHO recommends a physician to every 1000 people.According to the recent data from the Health Ministry in 2019,in which 1.16 million doctors are of active population with just 80%,or 0.9 million,practicing.As a result,a ratio of 0.68 doctors for every 1000 people,which is much below as per the WHO reports.This article describes history,types,WHO guidelines,need and purpose of DUE.Objective:The main aim of this paper is to provide information about the rational use of medication in outpa­tient and inpatient department with special emphasis of DUEs.It also provides awareness directly to healthcare professionals,researchers,academicians,pharmacist and nurses to reduce the irrationality of medicines.Methods:The method used to compile this review information gathered from websites,Google scholar,PubMed,Research gate,and studies published on DUE from July 20 to Oct 22 were included as source of information.Results:We studied more than 35 published study on DUE,that reveals most of the physicians prescribed branded drugs not generic drugs,but WHO prescribing indicator allows to prescribe generic drugs in the hospital pharmacy to maintain better inventory control.It may also help to prevent pharmacist misunderstanding during dispensing.Conclusion:The use of generic prescription names avoids the possibility of medication product duplication and lowers patient costs.It is important to remember that incorrect medication prescriptions have impact on both patients and their family members.WHO indicators identify irrational prescribing behaviours to make therapy more rational and cost-effective.

Drug-induced liver injury and COVID-19:Use of artificial intelligence and the updated Roussel Uclaf Causality Assessment Method in clinical practice

BACKGROUND Liver injury is a relevant condition in coronavirus disease 2019(COVID-19)inpatients.Pathophysiology varies from direct infection by virus,systemic inflammation or drug-induced adverse reaction(DILI).DILI detection and monitoring is clinically relevant,as it may contribute to poor prognosis,prolonged hospitalization and increase indirect healthcare costs.Artificial Intelligence(AI)applied in data mining of electronic medical records combining abnormal liver tests,keyword searching tools,and risk factors analysis is a relevant opportunity for early DILI detection by automated algorithms.AIM To describe DILI cases in COVID-19 inpatients detected from data mining in electronic medical records(EMR)using AI and the updated Roussel Uclaf Causality Assessment Method(RUCAM).METHODS The study was conducted in March 2021 in a hospital in southern Brazil.The NoHarm©system uses AI to support decision making in clinical pharmacy.Hospital admissions were 100523 during this period,of which 478 met the inclusion criteria.From these,290 inpatients were excluded due to alternative causes of liver injury and/or due to not having COVID-19.We manually reviewed the EMR of 188 patients for DILI investigation.Absence of clinical information excluded most eligible patients.The DILI assessment causality was possible via the updated RUCAM in 17 patients.RESULTS Mean patient age was 53 years(SD±18.37;range 22-83),most were male(70%),and admitted to the non-intensive care unit sector(65%).Liver injury pattern was mainly mixed,mean time to normalization of liver markers was 10 d,and mean length of hospitalization was 20.5 d(SD±16;range 7-70).Almost all patients recovered from DILI and one patient died of multiple organ failure.There were 31 suspected drugs with the following RUCAM score:Possible(n=24),probable(n=5),and unlikely(n=2).DILI agents in our study were ivermectin,bicalutamide,linezolid,azithromycin,ceftriaxone,amoxicillin-clavulanate,tocilizumab,piperacillin-tazobactam,and albendazole.Lack of essential clinical information excluded most patients.Although rare,DILI is a relevant clinical condition in COVID-19 patients and may contribute to poor prognostics.CONCLUSION The incidence of DILI in COVID-19 inpatients is rare and the absence of relevant clinical information on EMR may underestimate DILI rates.Prospects involve creation and validation of alerts for risk factors in all DILI patients based on RUCAM assessment causality,alterations of liver biomarkers and AI and machine learning.

含氟冰片酯的合成、结构表征及活性研究

【目的】合成4种含氟的冰片酯,分析其结构及活性。【方法】以对甲苯磺酸为催化剂,通过含氟羧酸和冰片反应合成4种含氟的冰片酯衍生物,采用1HNMR,13CNMR表征冰片酯的结构。通过AutoDock Vina软件对4种含氟冰片酯与P-糖蛋白进行分子对接。【结果】合成了4种含氟的冰片酯,分别是2-氯-4-三氟甲基苯甲酸冰片酯、2-氯-5-氟苯甲酸冰片酯、2-氯-5-三氟甲基苯甲酸冰片酯、3-三氟甲基苯甲酸冰片酯。冰片酯的结构通过1HNMR、13CNMR证实。4种含氟冰片酯与P-糖蛋白有较好的结合能力。【结论】合成了4种含氟的冰片酯化合物,含氟的冰片酯丰富了冰片衍生物的类型,对扩大冰片的应用范围有一定参考价值。

兽用化学药品血药浓度法生物等效性试验注册资料技术评审要点及常见问题

生物等效性试验作为兽药获批上市的关键试验,其研究过程和技术评审都要遵循特定的法规和指导原则。以药动学参数为终点的血药浓度法生物等效性试验是目前普遍采用的研究方法,适用于药物活性成分吸收进入体循环具有全身作用的剂型(大多数内服剂型和特殊注射剂)。本文根据生物等效性定义、相关法规和指导原则,结合近年来新兽药注册资料,对血药浓度法生物等效性试验资料的技术评审要点及常见问题进行梳理,旨在为新兽药的研发和注册提供参考。

三七药对的研究进展

三七作为临床常用中药,在临床应用中有多种药对形式。围绕近年来基于网络药理学的三七药对、传统三七药对及三七药对配伍前后化学成分变化的实验研究进行归纳和总结,系统阐释三七药对在临床应用的作用机制和科学内涵,为进一步研究三七药对使用规律、配伍理论、临床应用等方面提供新的思路。

化学生物学课程实践性教学探索——以药物化学ChEMBL数据库应用为例

化学生物学作为一门新兴的交叉学科,在教学中需要引入当前先进的信息学内容。在课程的教学中常常涉及大量的化合物及药物的知识介绍,我们在教学中尝试引入药物化学信息ChEMBL数据库的内容到本科生化学生物学课程中。ChEMBL是一个开放数据库,包含大量药物化合物的结构、功能和药代动力学等信息。这些数据定期从主要发表的文献中提取,然后通过进一步的策划和标准化,以最大限度地提高它们在化学生物学和药物发现研究中的效用。将ChEMBL数据资源引入到化学生物学本科教学中,使学生能够利用网络数据对所学到的药物分子进行分析,取得了较好的教学效果。

新精神活性物质“毒品化”处理的法理不兼容性研究

新精神活性物质长期被作为毒品看待,但这与毒品犯罪的行政犯属性相矛盾。事实上,新精神活性物质与毒品的法律属性和规范属性不在同一层面,在是否应当管制,列管的方式、边界上也与毒品有重大差异。简单地将制造、贩卖、运输新精神活性物质的行为直接认定为毒品犯罪,有违罪刑法定原则,甚至有可能违反宪法和立法法。司法实践中,已经出现涉新精神活性物质案件定性和定罪量刑的困难和矛盾,在将其认定为毒品犯罪的同时,或采用法定最低刑处理,或认定为未遂犯和不能犯。新精神活性物质与毒品并不兼容,不能将列管不明的新精神活性物质等同于毒品,更不能将未列管的物质认定为毒品。在坚持罪刑法定原则的前提下,对新精神活性物质应当秉持理性和审慎态度,跳出固有的“毒品化”思维,使其回归其药品及化学品的本质属性,这是解决新精神活性物质定罪量刑疑难问题的关键。