Ionic Liquids for Therapeutic and Drug Delivery Applications | Bentham Science
Ionic Liquids for Therapeutic and Drug Delivery Applications

Page: [26 - 41] Pages: 16

  • * (Excluding Mailing and Handling)

Abstract

Background: Ionic liquids (ILs) are ionic compounds with highly tunable and remarkable properties which make them an important candidate in multiple domains such as extraction, synthesis, analytics, catalysis, biotechnology, therapeutics as well as pharmaceutical sciences.

Objective: This review systematically highlights the classification, properties and toxicity of ionic liquids. It focuses on exploring the biological activity of ionic liquids, which includes antimicrobial and anticancer property along with an emphasis on the concept of Active Pharmaceutical Ingredient- Ionic Liquids (API-ILs) for explaining the emulsifier and solubility enhancement property of ILs. An elaborative discussion on the application of ILs for the development of oral, transdermal and topical drug delivery systems has also been presented with suitable literature support.

Conclusion: Ionic liquids possess exceptional potential in the field of medicine, biology and chemistry.

Keywords: Ionic liquids, active pharmaceutical ingredient-ionic liquids, antimicrobial, anticancer, oral drug delivery, transdermal drug delivery.

Graphical Abstract

[1]
Gomes JM, Silva SS, Reis RL. Biocompatible ionic liquids: Fundamental behaviours and applications. Chem Soc Rev 2019; 48(15): 4317-35.
[http://dx.doi.org/10.1039/C9CS00016J] [PMID: 31225558]
[2]
Broderick EM, Serban M, Mezza B, Bhattacharyya A. Scientific approach for a cleaner environment using ionic liquids. ACS Sustainable Chem Eng 2017; 5: 3681-4.
[http://dx.doi.org/10.1021/acssuschemeng.6b02953]
[3]
Hanif S, Oschmann B, Spetter D, Tahir MN, Tremel W, Zentel R. Block copolymers from ionic liquids for the preparation of thin carbonaceous shells. Beilstein J Org Chem 2017; 13: 1693-701.
[http://dx.doi.org/10.3762/bjoc.13.163] [PMID: 28904612]
[4]
Smiglak M, Reichert WM, Holbrey JD, et al. Combustible ionic liquids by design: Is laboratory safety another ionic liquid myth? Chem Commun (Camb) 2006; 24(24): 2554-6.
[http://dx.doi.org/10.1039/b602086k] [PMID: 16779475]
[5]
Katritzky AR, Singh S, Kirichenko K, et al. 1-butyl-3-methylimidazolium 3,5-dinitro-1,2,4-triazolate: A novel ionic liquid containing a rigid, planar energetic anion. Chem Commun (Camb) 2005; 7(7): 868-70.
[http://dx.doi.org/10.1039/b414683b] [PMID: 15700064]
[6]
Santos JI, Goncalves AMM, Pereira JL, et al. Environmental safety of cholinium-based ionic liquids: Assessing structure-ecotoxicity relationships. Green Chem 2015; 17: 4657-68.
[http://dx.doi.org/10.1039/C5GC01129A]
[7]
Porkodi J, Nagarajan S, Kandasamy E. Synthesis and characterization of 1-Isopropyl imidazolium based bronsted room temperature ionic liquids. J Chem Pharm Res 2015; 7: 852-5.
[8]
Shamsuri AA, Dzulkefly KA. Synthesizing of ionic liquids from different chemical reactions. Singap J Sci Res 2011; 1: 246-52.
[http://dx.doi.org/10.3923/sjsres.2011.246.252]
[9]
Shi F, Gu Y, Zhang Q, Deng Y. Development of ionic liquids as green reaction media and catalysts. Catal Surv Asia 2004; 8: 179-86.
[http://dx.doi.org/10.1023/B:CATS.0000038536.55980.f3]
[10]
Ratti R. Ionic liquids: Synthesis and applications in catalysis. Adv Chem 2014; 2014: Article ID 729842.
[11]
Qian W, Texter J, Yan F. Frontiers in poly (ionic liquid)s: Syntheses and applications. Chem Soc Rev 2017; 46(4): 1124-59.
[http://dx.doi.org/10.1039/C6CS00620E] [PMID: 28180218]
[12]
Fan JP, Yu JX, Yang XM, Zhang XH, Yuan TT, Peng HL. Preparation, characterization, and application of multiple stimuli-responsive rattle-type magnetic hollow molecular imprinted poly (ionic liquids) nanospheres (Fe3O4@void@PILMIP) for specific recognition of protein. Chem Eng J 2018; 337: 722-32.
[http://dx.doi.org/10.1016/j.cej.2017.12.159]
[13]
Noshadi I, Walker BW, Portillo-Lara R, et al. Engineering biodegradable and biocompatible bio-ionic liquid conjugated hydrogels with tunable conductivity and mechanical properties. Sci Rep 2017; 7(1): 4345.
[http://dx.doi.org/10.1038/s41598-017-04280-w] [PMID: 28659629]
[14]
Pernak J, Rzemieniecki T, Materna K. Ionic liquids “in a nutshell” (history, properties and development). Chemik 2016; 70: 471-80.
[15]
Welton T. Ionic liquids: A brief history. Biophys Rev 2018; 10(3): 691-706.
[http://dx.doi.org/10.1007/s12551-018-0419-2] [PMID: 29700779]
[16]
Shah FU, Glavatskih S, Antzutkin ON. Boron in tribology: From borates to ionic liquids. Tribol Lett 2013; 51: 281-301.
[http://dx.doi.org/10.1007/s11249-013-0181-3]
[17]
Sowmiah S, Srinivasadesikan V, Tseng MC, Chu YH. On the chemical stabilities of ionic liquids. Molecules 2009; 14(9): 3780-813.
[http://dx.doi.org/10.3390/molecules14093780] [PMID: 19783957]
[18]
Wilkes JS. A short history of ionic liquids- From molten salts to neoteric solvents. Green Chem 2002; 4: 73-80.
[http://dx.doi.org/10.1039/b110838g]
[19]
Plechkova NV, Seddon KR. Applications of ionic liquids in the chemical industry. Chem Soc Rev 2008; 37(1): 123-50.
[http://dx.doi.org/10.1039/B006677J] [PMID: 18197338]
[20]
Hough WL, Smiglak M, Rodriguez H, et al. The third evolution of ionic liquids: Active pharmaceutical ingredients. New J Chem 2007; 31: 1429-36.
[http://dx.doi.org/10.1039/b706677p]
[21]
Tavares APM, Rodriguez O, Macedo EA. New generations of ionic liquids applied to enzymatic biocatalysis. London, UK: Intech Open 2013; pp. 537-56.
[22]
Egorova KS, Gordeev EG, Ananikov VP. Biological activity of ionic liquids and their application in pharmaceutics and medicine. Chem Rev 2017; 117(10): 7132-89.
[http://dx.doi.org/10.1021/acs.chemrev.6b00562] [PMID: 28125212]
[23]
Suresh, Sandhu JS. Recent advances in ionic liquids: Green unconventional solvents of this century: Part I. Green Chem Lett Rev 2011; 4: 289-310.
[http://dx.doi.org/10.1080/17518253.2011.572294]
[24]
Feng R, Zhao D, Guo Y. Revisiting characteristics of ionic liquids: A review for further application development. J Environ Prot (Irvine Calif) 2010; 1: 95-104.
[http://dx.doi.org/10.4236/jep.2010.12012]
[25]
Bhattacharyya S, Shah FU. Thermal stability of choline based amino acid ionic liquids. J Mol Liq 2018; 266: 597-602.
[http://dx.doi.org/10.1016/j.molliq.2018.06.096]
[26]
Irge DD. Ionic liquids: A review on greener chemistry applications, quality ionic liquid synthesis and economical viability in a chemical processes. Am J Phys Chem 2016; 5: 74-9.
[http://dx.doi.org/10.11648/j.ajpc.20160503.14]
[27]
Anderson JL, Ding R, Ellern A, Armstrong DW. Structure and properties of high stability geminal dicationic ionic liquids. J Am Chem Soc 2005; 127(2): 593-604.
[http://dx.doi.org/10.1021/ja046521u] [PMID: 15643883]
[28]
Claros M, Graber TA, Brito I, Albanez J, Gavin JA. Synthesis and thermal properties of two new dicationic ionic liquids. J Chil Chem Soc 2010; 55: 396-8.
[http://dx.doi.org/10.4067/S0717-97072010000300027]
[29]
Bier M, Dietrich S. Vapour pressure of ionic liquids. Mol Physics: An Int J Interface between. Chem Phys 2010; 108: 211-4.
[30]
Murugesan S, Linhardt RJ. Ionic liquids in carbohydrate chemistry- Current trends and future directions. Curr Org Synth 2005; 2: 437-51.
[http://dx.doi.org/10.2174/157017905774322640]
[31]
Shishu KA, Kumar N, Goindi GS. Ionic liquids as promising carriers in drug delivery. USA: Studium Press LLC 2014; pp. 209-42.
[32]
Bhattacharjee A, Luís A, Lopes-da-Silva JA, Freire MG, Carvalho PJ, Coutinho JA. Thermophysical properties of sulfonium- and ammonium-based ionic liquids. Fluid Phase Equilib 2014; 381: 36-45.
[http://dx.doi.org/10.1016/j.fluid.2014.08.005] [PMID: 25516634]
[33]
Singh G, Kumar A. Ionic liquids: Physico-chemical, solvent properties and their application in chemical processes. Indian J Chem 2008; 47A: 495-503.
[34]
Keskin S, Kayrak-Talay D, Akman U, Hortacsu O. A review of ionic liquids towards supercritical fluid applications. J Supercrit Fluids 2007; 43: 150-80.
[http://dx.doi.org/10.1016/j.supflu.2007.05.013]
[35]
Rani MA, Brant A, Crowhurst L, et al. Understanding the polarity of ionic liquids. Phys Chem Chem Phys 2011; 13(37): 16831-40.
[http://dx.doi.org/10.1039/c1cp21262a] [PMID: 21858359]
[36]
Ahmed K, Auni A, Ara G, Rahman MM, Mollah MYA, Susan MABH. Solvatochromic and fluorescence spectroscopic studies on polarity of ionic liquid and ionic liquid-based binary systems. J Bangladesh Chem Soc 2012; 25: 146-58.
[http://dx.doi.org/10.3329/jbcs.v25i2.15067]
[37]
Laus G, Bentivoglio G, Schottenberger H, et al. Ionic liquids: Current developments, potential and drawbacks for industrial applications. Lenzinger Berichte 2005; 84: 71-85.
[38]
Papancea A, Patachia S, Porzsolt A. Conductivity studies of imidazolium-based ionic liquids in aqueous solution. Bulletin Transilvania Univ Brasov 2015; 8: 67-72.
[39]
Barrosse-Antle LE, Bond AM, Compton RG, O’Mahony AM, Rogers EI, Silvester DS. Voltammetry in room temperature ionic liquids: comparisons and contrasts with conventional electrochemical solvents. Chem Asian J 2010; 5(2): 202-30.
[http://dx.doi.org/10.1002/asia.200900191] [PMID: 20013990]
[40]
Barthen P, Frank W, Ignatiev N. Development of low viscous ionic liquids: The dependence of the viscosity on the mass of the ions. Ionics 2015; 21: 149-59.
[http://dx.doi.org/10.1007/s11581-014-1153-9]
[41]
Zhang S, Sun N, He X, Lu X, Zhang X. Physical properties of ionic liquids: Database and evaluation. J Phys Chem Ref Data 2006; 35: 1475-517.
[http://dx.doi.org/10.1063/1.2204959]
[42]
Rooney D, Jacquemin J, Gardas R. Thermophysical properties of ionic liquids. Top Curr Chem 2010; 290: 185-212.
[http://dx.doi.org/10.1007/128_2008_32] [PMID: 21107798]
[43]
Belay K, Abisa Z. Properties, applications and synthesis of ionic liquids in chemistry: A review. World J Pharm Med Res 2015; 1: 32-9.
[44]
Ghandi K. A review of ionic liquids, their limits and applications. Green Sustainable Chem 2014; 4: 44-53.
[http://dx.doi.org/10.4236/gsc.2014.41008]
[45]
Zhao H. Review: Current studies on some physical properties of ionic liquids. Phys Chem Liquids 2003; 41: 545-57.
[http://dx.doi.org/10.1080/003191031000117319]
[46]
Bubalo MC, Radošević K, Redovniković IR, Slivac I, Srček VG. Toxicity mechanisms of ionic liquids. Arh Hig Rada Toksikol 2017; 68(3): 171-9.
[http://dx.doi.org/10.1515/aiht-2017-68-2979] [PMID: 28976886]
[47]
Ventura SPM, Marques CS, Rosatella AA, Afonso CAM, Gonçalves F, Coutinho JAP. Toxicity assessment of various ionic liquid families towards Vibrio fischeri marine bacteria. Ecotoxicol Environ Saf 2012; 76(2): 162-8.
[http://dx.doi.org/10.1016/j.ecoenv.2011.10.006] [PMID: 22019310]
[48]
Frade RFM, Afonso CAM. Impact of ionic liquids in environment and humans: An overview. Hum Exp Toxicol 2010; 29(12): 1038-54.
[http://dx.doi.org/10.1177/0960327110371259] [PMID: 20511289]
[49]
Hwang JH, Park H, Choi DW, Nam KT, Lim KM. Investigation of dermal toxicity of ionic liquids in monolayer-cultured skin cells and 3D reconstructed human skin models. Toxicol In Vitro 2018; 46: 194-202.
[http://dx.doi.org/10.1016/j.tiv.2017.09.025] [PMID: 28958837]
[50]
Ruokonen SK, Sanwald C, Robciuc A, et al. Correlation between ionic liquid cytotoxicity and liposome-ionic liquid interactions. chemistry. Chem Eur J 2018; 24(11): 2669-80.
[http://dx.doi.org/10.1002/chem.201704924] [PMID: 29265502]
[51]
Sakamoto M, Ohama Y, Aoki S, et al. Effect of ionic liquids on the hatching of artemia salina cysts. Aust J Chem 2018; 71: 492-6.
[http://dx.doi.org/10.1071/CH18117]
[52]
Shekhawat BP, Pokharkar BV. Understanding peroral absorption: Regulatory aspects and contemporary approaches to tackling solubility and permeability hurdles. Acta Pharm Sin B 2017; 7(3): 260-80.
[http://dx.doi.org/10.1016/j.apsb.2016.09.005] [PMID: 28540164]
[53]
Shamshina JL, Barber PS, Rogers RD. Ionic liquids in drug delivery. Expert Opin Drug Deliv 2013; 10(10): 1367-81.
[http://dx.doi.org/10.1517/17425247.2013.808185] [PMID: 23795613]
[54]
Shiflett MB, Scurto AM. Current state and future directions. ACS Symposium Series ACS Symposium Series. 1-13. 2017.
[55]
Egorova KS, Seitkalieva MM, Posvyatenko AV, Khrustalev VN, Ananikov VP. Cytotoxic activity of salicylic acid-containing drug models with ionic and covalent binding. ACS Med Chem Lett 2015; 6(11): 1099-104.
[http://dx.doi.org/10.1021/acsmedchemlett.5b00258] [PMID: 26617961]
[56]
Marrucho IM, Branco LC, Rebelo LPN. Ionic liquids in pharmaceutical applications. Annu Rev Chem Biomol Eng 2014; 5: 527-46.
[http://dx.doi.org/10.1146/annurev-chembioeng-060713-040024] [PMID: 24910920]
[57]
Araujo JMM, Florindo C, Pereiro AB, et al. Cholinium-based ionic liquids with pharmaceutically active anions. RSC Advances 2014; 4: 28126-32.
[http://dx.doi.org/10.1039/C3RA47615D]
[58]
Shadid M, Gurau G, Shamshina JL, et al. Sulfasalazine in ionic liquid form with improved solubility and exposure. MedChemComm 2015; 6: 1837-41.
[http://dx.doi.org/10.1039/C5MD00290G]
[59]
Shamshina JL, Cojocaru OA, Kelley SP, et al. Acyclovir as an ionic liquid cation or anion can improve aqueous solubility. ACS Omega 2017; 2(7): 3483-93.
[http://dx.doi.org/10.1021/acsomega.7b00554] [PMID: 31457670]
[60]
Keramatnia F, Jouyban A, Valizadeh H, Delazar A, Shayanfar A. Ketoconazole ionic liquids with citric and tartaric acid: Synthesis, characterization and solubility study. Fluid Phase Equilib 2016; 425: 108-13.
[http://dx.doi.org/10.1016/j.fluid.2016.05.016]
[61]
Mizuuchi H, Jaitely V, Murdan S, Florence AT. Room temperature ionic liquids and their mixtures: Potential pharmaceutical solvents. Eur J Pharm Sci 2008; 33(4-5): 326-31.
[http://dx.doi.org/10.1016/j.ejps.2008.01.002] [PMID: 18291630]
[62]
Mehrdad A, Miri AH. Influence of 1-butyl-3-methyl imidazolium bromide, ionic liquid as co-solvent on aqueous solubility of acetaminophen. J Mol Liq 2016; 221: 1162-7.
[http://dx.doi.org/10.1016/j.molliq.2016.07.002]
[63]
Mehrdad A, Miri AH. Aqueous solubility of acetaminophen in the presence of 1-hexyl-3-methyl imidazolium bromide, ionic liquid as co-solvent. Fluid Phase Equilib 2006; 425: 51-6.
[http://dx.doi.org/10.1016/j.fluid.2016.05.012]
[64]
Ramos-Rodrigueza DA, Rodriguez-Hidalgo MDR, Soto-Figueroa C, Vicente L. Molecular and mesoscopic study of ionic liquids and their use as solvents of active agents released by polymeric vehicles. Mol Physics: Int J Interface Chem Phys 2010; 108: 657-65.
[http://dx.doi.org/10.1080/00268971003657094]
[65]
Patra D, Barakat C. Unique role of ionic liquid [bmin][BF4] during curcumin-surfactant association and micellization of cationic, anionic and non-ionic surfactant solutions. Spectrochim Acta A Mol Biomol Spectrosc 2011; 79(5): 1823-8.
[http://dx.doi.org/10.1016/j.saa.2011.05.064] [PMID: 21684197]
[66]
Dandpat SS, Sarkar M. Investigating the molecular and aggregated states of a drug molecule rutaecarpine using spectroscopy, microscopy, crystallography and computational studies. Phys Chem Chem Phys 2015; 17(21): 13992-4002.
[http://dx.doi.org/10.1039/C5CP01980J] [PMID: 25948504]
[67]
Singh O, Kaur R, Aswal VK, Mahajan RK. Composition and concentration gradient induced structural transition from micelles to vesicles in the mixed system of ionic liquid-diclofenac sodium. Langmuir 2016; 32(26): 6638-47.
[http://dx.doi.org/10.1021/acs.langmuir.6b01175] [PMID: 27267864]
[68]
Pal A, Yadav A. Binding interactions of anesthetic drug with surface active ionic liquid. J Mol Liq 2016; 222: 471-9.
[http://dx.doi.org/10.1016/j.molliq.2016.07.076]
[69]
Agatemor C, Ibsen KN, Tanner EEL, Mitragotri S. Ionic liquids for addressing unmet needs in healthcare. Bioeng Transl Med 2018; 3(1): 7-25.
[http://dx.doi.org/10.1002/btm2.10083] [PMID: 29376130]
[70]
Pinto PCAG, Saraiva MLMFS. Ionic liquids: A pharmaceutical perspective. Nova Science Publishers, Portugal 2014; pp. 1-41.
[71]
Frizzo CP, Gindri IM, Tier AZ, Buriol L, Moreira DN, Martins MAP. Pharmaceutical salts: solids to liquids by using ionic liquid design. London, UK: IntechOpen 2013; pp. 557-79.
[72]
Miwa Y, Hamamoto H, Ishida T. Lidocaine self-sacrificially improves the skin permeation of the acidic and poorly water-soluble drug etodolac via its transformation into an ionic liquid. Eur J Pharm Biopharm 2016; 102: 92-100.
[http://dx.doi.org/10.1016/j.ejpb.2016.03.003] [PMID: 26945484]
[73]
Sahbaz Y, Williams HD, Nguyen TH, et al. Transformation of poorly water-soluble drugs into lipophilic ionic liquids enhances oral drug exposure from lipid based formulations. Mol Pharm 2015; 12(6): 1980-91.
[http://dx.doi.org/10.1021/mp500790t] [PMID: 25905624]
[74]
Zakrewsky M, Mitragotri S. Therapeutic RNAi robed with ionic liquid moieties as a simple, scalable prodrug platform for treating skin disease. J Control Release 2016; 242: 80-8.
[http://dx.doi.org/10.1016/j.jconrel.2016.09.003] [PMID: 27612407]
[75]
Bica K, Rijksen C, Nieuwenhuyzen M, Rogers RD. In search of pure liquid salt forms of aspirin: Ionic liquid approaches with acetylsalicylic acid and salicylic acid. Phys Chem Chem Phys 2010; 12(8): 2011-7.
[http://dx.doi.org/10.1039/b923855g] [PMID: 20145871]
[76]
Hough WL, Rogers RD. Ionic liquids then and now: From solvents to materials to active pharmaceutical ingredients. Bull Chem Soc Jpn 2007; 80: 2262-9.
[http://dx.doi.org/10.1246/bcsj.80.2262]
[77]
Bica K, Rodríguez H, Gurau G, et al. Pharmaceutically active ionic liquids with solids handling, enhanced thermal stability, and fast release. Chem Commun (Camb) 2012; 48(44): 5422-4.
[http://dx.doi.org/10.1039/c2cc30959a] [PMID: 22534649]
[78]
Stoimenovski J, MacFarlane DR, Bica K, Rogers RD. Crystalline vs. ionic liquid salt forms of active pharmaceutical ingredients: A position paper. Pharm Res 2010; 27(4): 521-6.
[http://dx.doi.org/10.1007/s11095-009-0030-0] [PMID: 20143257]
[79]
Jordan A, Gathergood N. Designing safer and greener antibiotics. Antibiotics (Basel) 2013; 2(3): 419-38.
[http://dx.doi.org/10.3390/antibiotics2030419] [PMID: 27029311]
[80]
Docherty KM, Kulpa CF. Toxicity and antimicrobial activity of imidazolium and pyridinium ionic liquids. Green Chem 2005; 7: 185-9.
[http://dx.doi.org/10.1039/b419172b]
[81]
Venkata NY, Reddy GKK, Lalithamanasa P, Venugopalan VP. The ionic liquid 1-alkyl-3-methylimidazolium demonstrates comparable antimicrobial and antibiofilm behavior to a cationic surfactant. Biofouling 2012; 28(10): 1141-9.
[http://dx.doi.org/10.1080/08927014.2012.736966] [PMID: 23092364]
[82]
Miskiewicz A, Ceranowicz P, Szymczak M, Bartuś K, Kowalczyk P. The use of liquids ionic fluids as pharmaceutically active substances helpful in combating nosocomial infections induced by klebsiella pneumoniae new delhi strain, acinetobacter baumannii and enterococcus species. Int J Mol Sci 2018; 19(9): 2779.
[http://dx.doi.org/10.3390/ijms19092779] [PMID: 30223584]
[83]
Forero DO, Castro R, Gutierrez M, et al. Novel alkylimidazolium ionic liquids as an antibacterial alternative to pathogens of the skin and soft tissue infections. Molecules 2018; 23(9): 2354.
[http://dx.doi.org/10.3390/molecules23092354] [PMID: 30223457]
[84]
Yu Y, Nie Y. Toxicity and antimicrobial activities of ionic liquids with halogen anion. J Environ Prot (Irvine Calif) 2011; 2: 298-303.
[http://dx.doi.org/10.4236/jep.2011.23033]
[85]
Hajfarajollah H, Mokhtarani B, Sharifi A, Mirzaei M, Afaghi A. Toxicity of various kinds of ionic liquids towards the cell growth and end product formation of the probiotic strain, propionibacterium freudenreichii. RSC Advances 2014; 4: 13153-60.
[http://dx.doi.org/10.1039/C4RA00925H]
[86]
Zhang C, Malhotra SV, Francis AJ. Toxicity of ionic liquids to Clostridium sp. and effects on uranium biosorption. J Hazard Mater 2014; 264: 246-53.
[http://dx.doi.org/10.1016/j.jhazmat.2013.11.003] [PMID: 24316798]
[87]
O’Toole GA, Wathier M, Zegans ME, Shanks RMQ, Kowalski R, Grinstaff MW. Diphosphonium ionic liquids as broad-spectrum antimicrobial agents. Cornea 2012; 31(7): 810-6.
[http://dx.doi.org/10.1097/ICO.0b013e31823f0a86] [PMID: 22236790]
[88]
Ferraz R, Teixeira V, Rodrigues D, et al. Antibacterial activity of ionic liquids based on ampicillin against resistant bacteria. RSC Advances 2014; 4: 4301-7.
[http://dx.doi.org/10.1039/C3RA44286A]
[89]
Carson L, Chau PKW, Earle MJ, et al. Antibiofilm activities of 1-alkyl-3-methylimidazolium chloride ionic liquids. Green Chem 2009; 11: 492-7.
[http://dx.doi.org/10.1039/b821842k]
[90]
Busetti A, Crawford DE, Earle MJ, et al. Antimicrobial and antibiofilm activities of 1-alkylquinolinium bromide ionic liquids. Green Chem 2010; 12: 420-5.
[http://dx.doi.org/10.1039/b919872e]
[91]
Walkiewicz F, Materna K, Kropacz A, et al. Multifunctional long-alkyl-chain quaternary ammonium azolate based ionic liquids. New J Chem 2010; 34: 2281-9.
[http://dx.doi.org/10.1039/c0nj00228c]
[92]
Ismail Hossain M, El-Harbawi M, Noaman YA, et al. Synthesis and anti-microbial activity of hydroxylammonium ionic liquids. Chemosphere 2011; 84(1): 101-4.
[http://dx.doi.org/10.1016/j.chemosphere.2011.02.048] [PMID: 21421256]
[93]
Ventura SPM, e Silva FA, Gonçalves AMM, Pereira JL, Gonçalves F, Coutinho JAP. Ecotoxicity analysis of cholinium-based ionic liquids to Vibrio fischeri marine bacteria. Ecotoxicol Environ Saf 2014; 102: 48-54.
[http://dx.doi.org/10.1016/j.ecoenv.2014.01.003] [PMID: 24580821]
[94]
Xu Q, Zheng Z, Wang B, Mao H, Yan F. Zinc ion coordinated poly(ionic liquid) antimicrobial membranes for wound healing. ACS Appl Mater Interfaces 2017; 9(17): 14656-64.
[http://dx.doi.org/10.1021/acsami.7b01677] [PMID: 28418650]
[95]
Zheng Z, Guo J, Mao H, Xu Q, Qin J, Yan F. Metal-containing poly(ionic liquid) membranes for antibacterial applications. ACS Biomater Sci Eng 2017; 3: 922-8.
[http://dx.doi.org/10.1021/acsbiomaterials.7b00165]
[96]
Rajathi K, Rajendran A. Antimicrobial activity of silver nanoparticles from substituted and unsubstituted imidazolium ionic liquids. Int J Pharm Sci Res 2017; 8: 1000-6.
[97]
Mangrule V, Pore Y, Disouza J. Synthesis and physicochemical studies of fluconazole ionic liquids. J Pharm Sci 2017; 7: 084-9.
[98]
Ashishie PB, Inah BE, Ayi AA. Evaluation of antimicrobial activity of ionic liquid-assisted synthesis of monometallic silver and bimetallic copper-silver nanoparticles. Int J Sci 2018; 7: 25-31.
[http://dx.doi.org/10.18483/ijSci.1637]
[99]
Moodley KG. Roles of ionic liquids in medicines for the treatment of cancer and tuberculosis. Pharma Chem 2019; 11: 1-19.
[100]
Dias AR, Costa-Rodrigues J, Fernandes MH, Ferraz R, Prudêncio C. The anticancer potential of ionic liquids. ChemMedChem 2017; 12(1): 11-8.
[http://dx.doi.org/10.1002/cmdc.201600480] [PMID: 27911045]
[101]
Kaushik NK, Attri P, Kaushik N, Choi EH. Synthesis and antiproliferative activity of ammonium and imidazolium ionic liquids against T98G brain cancer cells. Molecules 2012; 17(12): 13727-39.
[http://dx.doi.org/10.3390/molecules171213727] [PMID: 23174892]
[102]
Kumar V, Malhotra SV. Study on the potential anti-cancer activity of phosphonium and ammonium-based ionic liquids. Bioorg Med Chem Lett 2009; 19(16): 4643-6.
[http://dx.doi.org/10.1016/j.bmcl.2009.06.086] [PMID: 19615902]
[103]
Egorova KS, Ananikov VP. Toxicity of ionic liquids: eco(cyto)activity as complicated, but unavoidable parameter for task-specific optimization. ChemSusChem 2014; 7(2): 336-60.
[http://dx.doi.org/10.1002/cssc.201300459] [PMID: 24399804]
[104]
Malhotra SV, Kumar V. A profile of the in vitro anti-tumor activity of imidazolium-based ionic liquids. Bioorg Med Chem Lett 2010; 20(2): 581-5.
[http://dx.doi.org/10.1016/j.bmcl.2009.11.085] [PMID: 20006501]
[105]
Kumar RA, Papaïconomou N, Lee JM, Salminen J, Clark DS, Prausnitz JM. In vitro cytotoxicities of ionic liquids: effect of cation rings, functional groups, and anions. Environ Toxicol 2009; 24(4): 388-95.
[http://dx.doi.org/10.1002/tox.20443] [PMID: 18825729]
[106]
Frade RFM, Rosatella AA, Marques CS, et al. Toxicological evaluation on human colon carcinoma cell line (CaCo-2) of ionic liquids based on imidazolium, guanidinium, ammonium, phosphonium, pyridinium and pyrrolidinium cations. Green Chem 2009; 11: 1660-5.
[http://dx.doi.org/10.1039/b914284n]
[107]
Frade RFM, Matias A, Branco LC, Afonso CAM, Duarte CMM. Effect of ionic liquids on human colon carcinoma HT29 and CaCo-2 cell lines. Green Chem 2007; 9: 873-7.
[http://dx.doi.org/10.1039/b617526k]
[108]
Cvjetko M, Radošević K, Tomica A, Slivac I, Vorkapić-Furač J, Srček VG. Cytotoxic effects of imidazolium ionic liquids on fish and human cell lines. Arh Hig Rada Toksikol 2012; 63(1): 15-20.
[http://dx.doi.org/10.2478/10004-1254-63-2012-2132] [PMID: 22450201]
[109]
Jing C, Li X, Zhang J, Wang J. Responses of the antioxidant system in QGY-7701 cells to the cytotoxicity and apoptosis induced by 1-octyl-3-methylimidazolium chloride. J Biochem Mol Toxicol 2013; 27(6): 330-6.
[http://dx.doi.org/10.1002/jbt.21495] [PMID: 23696008]
[110]
Zhang Z, Fu S, Duan H, Lin Y, Yang Y. Brand-new function of well-designed ionic liquid: Inhibitor of tumor cell growth. Chem Res Chin Univ 2010; 26: 757-60.
[111]
Karadag A, Akbas H. Phosphazene-based ionic liquids. London, UK: Intechopen 2018; pp. 27-46.
[112]
Dorj B, Won JE, Purevdorj O, et al. A novel therapeutic design of microporous-structured biopolymer scaffolds for drug loading and delivery. Acta Biomater 2014; 10(3): 1238-50.
[http://dx.doi.org/10.1016/j.actbio.2013.11.002] [PMID: 24239677]
[113]
Kim MH, An S, Won K, Kim HJ, Lee SH. Entrapment of enzymes into cellulose–biopolymer composite hydrogel beads using biocompatible ionic liquid. J Mol Catal, B Enzym 2012; 75: 68-72.
[http://dx.doi.org/10.1016/j.molcatb.2011.11.011]
[114]
Fileti EE, Chaban VV. Imidazolium ionic liquid helps to disperse fullerenes in water. J Phys Chem Lett 2014; 5(11): 1795-800.
[http://dx.doi.org/10.1021/jz500609x] [PMID: 26273856]
[115]
Hua D, Jiang J, Kuang L, Jiang J, Zheng W, Liang H. Smart chitosan-based stimuli-responsive nanocarriers for the controlled delivery of hydrophobic pharmaceuticals. Macromolecules 2011; 44: 1298-302.
[http://dx.doi.org/10.1021/ma102568p]
[116]
Saha A, Payra S, Verma SK, Mandal M, Thareja S, Banerjee S. In silico binding affinity to cyclooxygenase-II and green synthesis of benzylpyrazolyl coumarin derivatives. RSC Advances 2015; 5: 100978-83.
[http://dx.doi.org/10.1039/C5RA16643H]
[117]
Shaji J, Patole V. Protein and peptide drug delivery: Oral approaches. Indian J Pharm Sci 2008; 70(3): 269-77.
[http://dx.doi.org/10.4103/0250-474X.42967] [PMID: 20046732]
[118]
Sintra TE, Shimizu K, Ventura SPM, Shimizu S, Canongia Lopes JN, Coutinho JAP. Enhanced dissolution of ibuprofen using ionic liquids as catanionic hydrotropes. Phys Chem Chem Phys 2018; 20(3): 2094-103.
[http://dx.doi.org/10.1039/C7CP07569C] [PMID: 29302650]
[119]
Jesus AR, Soromenho MRC, Raposo LR, et al. Enhancement of water solubility of poorly water-soluble drugs by new biocompatible N-acetyl amino acid N-alkyl cholinium-based ionic liquids. Eur J Pharm Biopharm 2019; 137: 227-32.
[http://dx.doi.org/10.1016/j.ejpb.2019.03.004] [PMID: 30836180]
[120]
Williams HD, Sahbaz Y, Ford L, Nguyen TH, Scammells PJ, Porter CJH. Ionic liquids provide unique opportunities for oral drug delivery: structure optimization and in vivo evidence of utility. Chem Commun (Camb) 2014; 50(14): 1688-90.
[http://dx.doi.org/10.1039/C3CC48650H] [PMID: 24394756]
[121]
Mahkam M, Hosseinzadeh F, Galehassadi M. Preparation of ionic liquid functionalized silica nanoparticles for oral drug delivery. J Biomater Nanobiotechnol 2012; 3: 391-5.
[http://dx.doi.org/10.4236/jbnb.2012.33038]
[122]
Hosseinzadeh F, Mahkam M, Galehassadi M. Synthesis and characterization of ionic liquid functionalized polymers for drug delivery of an anti-inflammatory drug. Designed Mono Poly 2012; 15: 379-88.
[http://dx.doi.org/10.1080/1385772X.2012.686689]
[123]
Banerjee A, Ibsen K, Brown T, Chen R, Agatemor C, Mitragotri S. Ionic liquids for oral insulin delivery. Proc Natl Acad Sci USA 2018; 115(28): 7296-301.
[http://dx.doi.org/10.1073/pnas.1722338115] [PMID: 29941553]
[124]
Kaur J, Kaur J, Jaiswal S, Gupta GD. Recent advances in topical drug delivery system. Indo American J Pharm Res 2016; 6: 6353-69.
[125]
Dobler D, Schmidts T, Klingenhöfer I, Runkel F. Ionic liquids as ingredients in topical drug delivery systems. Int J Pharm 2013; 441(1-2): 620-7.
[http://dx.doi.org/10.1016/j.ijpharm.2012.10.035] [PMID: 23123180]
[126]
Santos de Almeida T, Júlio A, Saraiva N, et al. Choline- versus imidazole-based ionic liquids as functional ingredients in topical delivery systems: cytotoxicity, solubility, and skin permeation studies. Drug Dev Ind Pharm 2017; 43(11): 1858-65.
[http://dx.doi.org/10.1080/03639045.2017.1349788] [PMID: 28665154]
[127]
Caparica R, Júlio A, Baby AR, et al. Choline-amino acid ionic liquids as green functional excipients to enhance drug solubility. Pharmaceutics 2018; 10(4): 288.
[http://dx.doi.org/10.3390/pharmaceutics10040288] [PMID: 30572636]
[128]
Qiu Z, Texter J. Ionic liquids in microemulsions. Curr Opin Colloid Interface Sci 2008; 13: 252-62.
[http://dx.doi.org/10.1016/j.cocis.2007.10.005]
[129]
Moniruzzaman M, Kamiya N, Goto M. Ionic liquid based microemulsion with pharmaceutically accepted components: Formulation and potential applications. J Colloid Interface Sci 2010; 352(1): 136-42.
[http://dx.doi.org/10.1016/j.jcis.2010.08.035] [PMID: 20825949]
[130]
Goindi S, Arora P, Kumar N, Puri A. Development of novel ionic liquid-based microemulsion formulation for dermal delivery of 5-Fluorouracil. AAPS PharmSciTech 2014; 15(4): 810-21.
[http://dx.doi.org/10.1208/s12249-014-0103-1] [PMID: 24668136]
[131]
Goindi S, Kaur R, Kaur R. An ionic liquid-in-water microemulsion as a potential carrier for topical delivery of poorly water soluble drug: Development, ex-vivo and in-vivo evaluation. Int J Pharm 2015; 495(2): 913-23.
[http://dx.doi.org/10.1016/j.ijpharm.2015.09.066] [PMID: 26456294]
[132]
Alkilani AZ, McCrudden MTC, Donnelly RF. Transdermal drug delivery: Innovative pharmaceutical developments based on disruption of the barrier properties of the stratum corneum. Pharmaceutics 2015; 7(4): 438-70.
[http://dx.doi.org/10.3390/pharmaceutics7040438] [PMID: 26506371]
[133]
Sidat Z, Marimuthu T, Kumar P, et al. Ionic liquids as potential and synergistic permeation enhancers for transdermal drug delivery. Pharmaceutics 2019; 11(2): 96.
[http://dx.doi.org/10.3390/pharmaceutics11020096] [PMID: 30813375]
[134]
Moniruzzaman M, Tahara Y, Tamura M, Kamiya N, Goto M. Ionic liquid-assisted transdermal delivery of sparingly soluble drugs. Chem Commun (Camb) 2010; 46(9): 1452-4.
[http://dx.doi.org/10.1039/b907462g] [PMID: 20162145]
[135]
Monti D, Egiziano E, Burgalassi S, et al. Ionic liquids as potential enhancers for transdermal drug delivery. Int J Pharm 2017; 516(1-2): 45-51.
[http://dx.doi.org/10.1016/j.ijpharm.2016.11.020] [PMID: 27836753]
[136]
Wang C, Zhu J, Zhang D, et al. Ionic liquid - microemulsions assisting in the transdermal delivery of Dencichine: Preparation, in-vitro and in-vivo evaluations, and investigation of the permeation mechanism. Int J Pharm 2018; 535(1-2): 120-31.
[http://dx.doi.org/10.1016/j.ijpharm.2017.10.024] [PMID: 29104058]
[137]
Zakrewsky M, Lovejoy KS, Kern TL, et al. Ionic liquids as a class of materials for transdermal delivery and pathogen neutralization. Proc Natl Acad Sci USA 2014; 111(37): 13313-8.
[http://dx.doi.org/10.1073/pnas.1403995111] [PMID: 25157174]
[138]
Harada LK, Pereira JFB, Campos WF, et al. Insights into protein-ionic liquid interactions aiming at macromolecule delivery systems. J Braz Chem Soc 2018; 29: 1983-98.
[http://dx.doi.org/10.21577/0103-5053.20180141]
[139]
Qi QM, Mitragotri S. Mechanistic study of transdermal delivery of macromolecules assisted by ionic liquids. J Control Release 2019; 311-312: 162-9.
[http://dx.doi.org/10.1016/j.jconrel.2019.08.029] [PMID: 31465826]
[140]
Tanner EEL, Curreri AM, Balkaran JPR, et al. Design principles of ionic liquids for transdermal drug delivery. Adv Mater 2019; 31(27) e1901103
[http://dx.doi.org/10.1002/adma.201901103] [PMID: 31112631]
[141]
Chopra H, Kumar P, Singh I. Ionic liquid-based transdermal delivery of propranolol: A patent evaluation of US2018/0169033A1. Pharm Pat Anal 2019; 8(5): 203-9.
[http://dx.doi.org/10.4155/ppa-2019-0018] [PMID: 31612799]
Request history8.2.26PHP Version283msRequest Duration28MBMemory UsageGET article/{article_id}/{param?}Route
  • warninglog[06:12:01] LOG.warning: Optional parameter $article_id declared before required parameter $request i...
  • warninglog[06:12:02] LOG.warning: trim(): Passing null to parameter #1 ($string) of type string is deprecated ...
  • warninglog[06:12:02] LOG.warning: Function strftime() is deprecated in /home/betabenthamscien/public_html/stor...
  • warninglog[06:12:02] LOG.warning: Function strftime() is deprecated in /home/betabenthamscien/public_html/stor...
  • Booting (123ms)time
  • Application (160ms)time
  • 1 x Application (56.64%)
    160ms
    1 x Booting (43.36%)
    123ms
    8 templates were rendered
    • articlearticle.blade.php#?blade
    • includes.journal_rightmenujournal_rightmenu.blade.php#?blade
    • includes.article_top_bannerarticle_top_banner.blade.php#?blade
    • includes.article_referencearticle_reference.blade.php#?blade
    • layouts.appapp.blade.php#?blade
    • layouts._login_access_login_access.blade.php#?blade
    • layouts._main_menu_main_menu.blade.php#?blade
    • layouts._footer_menu_footer_menu.blade.php#?blade
    uri
    GET article/{article_id}/{param?}
    middleware
    web, check_user_access
    controller
    App\Http\Controllers\ArticleController@GetArticleDetails
    namespace
    App\Http\Controllers
    where
    as
    article
    file
    app/Http/Controllers/ArticleController.php:1974-2510
    35 statements were executed, 2 of which were duplicates, 33 unique. Show only duplicated85.55ms
    • Connection Establishedalphaeurekaselec_live_10_06_2022UserAccessCheck.php#24
      Backtrace
      • 9. middleware::check_user_access:24
      • 10. vendor/laravel/framework/src/Illuminate/Pipeline/Pipeline.php:183
      • 11. vendor/laravel/framework/src/Illuminate/Routing/Middleware/SubstituteBindings.php:50
      • 12. vendor/laravel/framework/src/Illuminate/Pipeline/Pipeline.php:183
      • 13. vendor/laravel/framework/src/Illuminate/Foundation/Http/Middleware/VerifyCsrfToken.php:88
    • INSERT INTO visitor_ip_address (ip_address,visitor_agent,visitor_count, created_on,updated_on) VALUES ('59651772','',1,1735020721,1735020721) ON DUPLICATE KEY UPDATE visitor_count=visitor_count + 1, updated_on=1735020721
      1.91msalphaeurekaselec_live_10_06_2022UserAccessCheck.php#24
      Backtrace
      • 11. middleware::check_user_access:24
      • 12. vendor/laravel/framework/src/Illuminate/Pipeline/Pipeline.php:183
      • 13. vendor/laravel/framework/src/Illuminate/Routing/Middleware/SubstituteBindings.php:50
      • 14. vendor/laravel/framework/src/Illuminate/Pipeline/Pipeline.php:183
      • 15. vendor/laravel/framework/src/Illuminate/Foundation/Http/Middleware/VerifyCsrfToken.php:88
    • INSERT INTO visitor_ip_address_detail (ip_address,visitor_url,visitor_count, created_on,updated_on) VALUES ('59651772','/article/102570',1,1735020721,1735020721)
      1.4msalphaeurekaselec_live_10_06_2022UserAccessCheck.php#27
      Backtrace
      • 11. middleware::check_user_access:27
      • 12. vendor/laravel/framework/src/Illuminate/Pipeline/Pipeline.php:183
      • 13. vendor/laravel/framework/src/Illuminate/Routing/Middleware/SubstituteBindings.php:50
      • 14. vendor/laravel/framework/src/Illuminate/Pipeline/Pipeline.php:183
      • 15. vendor/laravel/framework/src/Illuminate/Foundation/Http/Middleware/VerifyCsrfToken.php:88
    • (select `user_id`, `to_ip`, `from_ip` from (select user_id, to_ip, from_ip FROM user_access_journal_volume_trail WHERE to_ip >= 59651772 ORDER BY to_ip ASC LIMIT 1) as `tjv` where `from_ip` <= 59651772) union (select `user_id`, `to_ip`, `from_ip` from (select user_id, to_ip, from_ip FROM user_access_journal_volume_corporate WHERE to_ip >= 59651772 ORDER BY to_ip ASC LIMIT 1) as `tjv` where `from_ip` <= 59651772) union (select `user_id`, `to_ip`, `from_ip` from (select user_id, to_ip, from_ip FROM user_access_journal_volume_token WHERE to_ip >= 59651772 ORDER BY to_ip ASC LIMIT 1) as `tjv` where `from_ip` <= 59651772) union (select `user_id`, `to_ip`, `from_ip` from (select user_id, to_ip, from_ip FROM user_access_ebook_volume_trail WHERE to_ip >= 59651772 ORDER BY to_ip ASC LIMIT 1) as `tjv` where `from_ip` <= 59651772) union (select `user_id`, `to_ip`, `from_ip` from (select user_id, to_ip, from_ip FROM user_access_ebook_volume_corporate WHERE to_ip >= 59651772 ORDER BY to_ip ASC LIMIT 1) as `tjv` where `from_ip` <= 59651772) union (select `user_id`, `to_ip`, `from_ip` from (select user_id, to_ip, from_ip FROM user_access_ebook_volume_token WHERE to_ip >= 59651772 ORDER BY to_ip ASC LIMIT 1) as `tjv` where `from_ip` <= 59651772) union (select `user_id`, `to_ip`, `from_ip` from (select user_id, to_ip, from_ip FROM user_access_issue_trail WHERE to_ip >= 59651772 ORDER BY to_ip ASC LIMIT 1) as `tjv` where `from_ip` <= 59651772) union (select `user_id`, `to_ip`, `from_ip` from (select user_id, to_ip, from_ip FROM user_access_issue_corporate WHERE to_ip >= 59651772 ORDER BY to_ip ASC LIMIT 1) as `tjv` where `from_ip` <= 59651772) union (select `user_id`, `to_ip`, `from_ip` from (select user_id, to_ip, from_ip FROM user_access_issue_token WHERE to_ip >= 59651772 ORDER BY to_ip ASC LIMIT 1) as `tjv` where `from_ip` <= 59651772) union (select `user_id`, `to_ip`, `from_ip` from (select user_id, to_ip, from_ip FROM user_access_article_trail WHERE to_ip >= 59651772 ORDER BY to_ip ASC LIMIT 1) as `tjv` where `from_ip` <= 59651772) union (select `user_id`, `to_ip`, `from_ip` from (select user_id, to_ip, from_ip FROM user_access_article_corporate WHERE to_ip >= 59651772 ORDER BY to_ip ASC LIMIT 1) as `tjv` where `from_ip` <= 59651772) union (select `user_id`, `to_ip`, `from_ip` from (select user_id, to_ip, from_ip FROM user_access_article_token WHERE to_ip >= 59651772 ORDER BY to_ip ASC LIMIT 1) as `tjv` where `from_ip` <= 59651772) union (select `user_id`, `to_ip`, `from_ip` from (select user_id, to_ip, from_ip FROM user_access_chapter_trail WHERE to_ip >= 59651772 ORDER BY to_ip ASC LIMIT 1) as `tjv` where `from_ip` <= 59651772) union (select `user_id`, `to_ip`, `from_ip` from (select user_id, to_ip, from_ip FROM user_access_chapter_corporate WHERE to_ip >= 59651772 ORDER BY to_ip ASC LIMIT 1) as `tjv` where `from_ip` <= 59651772) union (select `user_id`, `to_ip`, `from_ip` from (select user_id, to_ip, from_ip FROM user_access_chapter_token WHERE to_ip >= 59651772 ORDER BY to_ip ASC LIMIT 1) as `tjv` where `from_ip` <= 59651772) union (select `user_id`, `to_ip`, `from_ip` from (select user_id, to_ip, from_ip FROM user_access_disease_corporate WHERE to_ip >= 59651772 ORDER BY to_ip ASC LIMIT 1) as `tjv` where `from_ip` <= 59651772) limit 1
      24.28msalphaeurekaselec_live_10_06_2022UserAccess.php#784
      Bindings
      • 0: 59651772
      • 1: 59651772
      • 2: 59651772
      • 3: 59651772
      • 4: 59651772
      • 5: 59651772
      • 6: 59651772
      • 7: 59651772
      • 8: 59651772
      • 9: 59651772
      • 10: 59651772
      • 11: 59651772
      • 12: 59651772
      • 13: 59651772
      • 14: 59651772
      • 15: 59651772
      Backtrace
      • 14. app/Models/UserAccess/UserAccess.php:784
      • 15. middleware::check_user_access:63
      • 16. vendor/laravel/framework/src/Illuminate/Pipeline/Pipeline.php:183
      • 17. vendor/laravel/framework/src/Illuminate/Routing/Middleware/SubstituteBindings.php:50
      • 18. vendor/laravel/framework/src/Illuminate/Pipeline/Pipeline.php:183
    • SELECT at.type_name, p.copyright, p.publisher_location,m.month,y.year, a.publish_on, a.nid article_nid,a.article_id, a.pmid, a.issue_id, a.title, a.abstract,a.podcast,a.altmetric_score,a.altmetric_url,a.kudos_url, a.page_count, a.first_page, a.elocator, a.last_page, i.publication_date, a.file_name, a.file_path, a.doi, a.is_epub,a.epub_type, a.volume_id, a.is_uploaded, a.editor_choice, a.is_epub, j.image_file_name, a.article_no, a.art_type AS article_type, a.supplementary_filename,a.html_filename,a.prc_filename,a.epub_filename, a.graph_abs_lg_filename, a.graph_abs_sm_filename, a.oa_image_lg_filename, a.oa_image_sm_filename, j.journal_banner,a.animated_abstract,a.erratum_in,a.erratum_for, (CASE WHEN a.issue_id =0 THEN j.epub_price ELSE j.price END) AS sell_price, j.epub_price, j.nid AS jour_nid, j.title AS journal_title, j.issn, j.eissn,j.journal_id, j.subtitle AS jour_subtitle, v.volume_id,v.volume_name AS volume, v.year_id, i.title AS issue, i.month_id ,i.type issue_type, j.subtitle,j.formerly_title, ac.subtitle AS epub_title,a.crossmark_enabled,a.text_mining_urls,a.license_urls,a.created, a.receivedate, a.revisedate, a.acceptdate,js.js_title FROM article a LEFT JOIN article_section ac ON a.is_epub = ac.art_sec_id LEFT JOIN journal_section js ON a.js_id = js.js_id LEFT JOIN article_type at ON a.art_type = at.art_type_id LEFT JOIN issue i ON a.issue_id = i.issue_id LEFT JOIN month m ON m.id = i.month_id LEFT JOIN volume v ON v.volume_id = a.volume_id INNER JOIN year y ON y.id = v.year_id INNER JOIN journal j ON j.journal_id = a.journal_id INNER JOIN publisher p ON p.publisher_id = j.publisher_id WHERE a.article_id=102570
      740μsalphaeurekaselec_live_10_06_2022Article.php#408
      Backtrace
      • 11. app/Models/Article.php:408
      • 12. app/Http/Controllers/ArticleController.php:2515
      • 13. app/Http/Controllers/ArticleController.php:2035
      • 14. vendor/laravel/framework/src/Illuminate/Routing/Controller.php:54
      • 15. vendor/laravel/framework/src/Illuminate/Routing/ControllerDispatcher.php:43
    • select * from `journal` where `journal_id` = 172 limit 1
      340μsalphaeurekaselec_live_10_06_2022Journal.php#64
      Bindings
      • 0: 172
      Backtrace
      • 14. app/Models/Journal.php:64
      • 15. app/Http/Controllers/ArticleController.php:2516
      • 16. app/Http/Controllers/ArticleController.php:2035
      • 17. vendor/laravel/framework/src/Illuminate/Routing/Controller.php:54
      • 18. vendor/laravel/framework/src/Illuminate/Routing/ControllerDispatcher.php:43
    • select count(*) as aggregate from (select j.nid as journal_nid,j.flyer_link,j.title ,j.issn,j.eissn,j.keyword, j.journal_id as journal_id, j.subtitle, j.image_file_name,j.description,j.journal_insight_url,j.doi from `subject_journal` as `sj` inner join `journal` as `j` on `j`.`journal_id` = `sj`.`journal_id` where j.journal_status=1 and subject_id IN (SELECT subject_id FROM subject_journal WHERE journal_id=172) and sj.journal_id!=172 group by `j`.`nid`) as `aggregate_table`
      1.07msalphaeurekaselec_live_10_06_2022Subject.php#198
      Backtrace
      • 16. app/Models/Subject.php:198
      • 17. app/Http/Controllers/ArticleController.php:2517
      • 18. app/Http/Controllers/ArticleController.php:2035
      • 19. vendor/laravel/framework/src/Illuminate/Routing/Controller.php:54
      • 20. vendor/laravel/framework/src/Illuminate/Routing/ControllerDispatcher.php:43
    • select j.nid as journal_nid,j.flyer_link,j.title ,j.issn,j.eissn,j.keyword, j.journal_id as journal_id, j.subtitle, j.image_file_name,j.description,j.journal_insight_url,j.doi from `subject_journal` as `sj` inner join `journal` as `j` on `j`.`journal_id` = `sj`.`journal_id` where j.journal_status=1 and subject_id IN (SELECT subject_id FROM subject_journal WHERE journal_id=172) and sj.journal_id!=172 group by `j`.`nid` order by `j`.`journal_id` asc limit 10 offset 0
      830μsalphaeurekaselec_live_10_06_2022Subject.php#198
      Backtrace
      • 14. app/Models/Subject.php:198
      • 15. app/Http/Controllers/ArticleController.php:2517
      • 16. app/Http/Controllers/ArticleController.php:2035
      • 17. vendor/laravel/framework/src/Illuminate/Routing/Controller.php:54
      • 18. vendor/laravel/framework/src/Illuminate/Routing/ControllerDispatcher.php:43
    • select count(*) as aggregate from (select v.nid as volume_id,e.nid,e.title,v.issn,v.eissn,v.isbn,v.eisbn,e.ebook_id, v.image_file_name,v.file_path,v.flyer_link,v.ebook_volume_id, v.volume_name,v.doi,v.year_id,v.introduction from `subject_ebook` as `se` inner join `ebook` as `e` on `e`.`ebook_id` = `se`.`ebook_id` inner join `ebook_volume` as `v` on `v`.`ebook_id` = `se`.`ebook_id` inner join `year` as `y` on `y`.`id` = `v`.`year_id` where subject_id IN (SELECT subject_id FROM subject_journal WHERE journal_id=172) and v.ebook_status='1' and y.year > 2020 group by `v`.`nid`) as `aggregate_table`
      1.51msalphaeurekaselec_live_10_06_2022Subject.php#218
      Backtrace
      • 16. app/Models/Subject.php:218
      • 17. app/Http/Controllers/ArticleController.php:2518
      • 18. app/Http/Controllers/ArticleController.php:2035
      • 19. vendor/laravel/framework/src/Illuminate/Routing/Controller.php:54
      • 20. vendor/laravel/framework/src/Illuminate/Routing/ControllerDispatcher.php:43
    • select v.nid as volume_id,e.nid,e.title,v.issn,v.eissn,v.isbn,v.eisbn,e.ebook_id, v.image_file_name,v.file_path,v.flyer_link,v.ebook_volume_id, v.volume_name,v.doi,v.year_id,v.introduction from `subject_ebook` as `se` inner join `ebook` as `e` on `e`.`ebook_id` = `se`.`ebook_id` inner join `ebook_volume` as `v` on `v`.`ebook_id` = `se`.`ebook_id` inner join `year` as `y` on `y`.`id` = `v`.`year_id` where subject_id IN (SELECT subject_id FROM subject_journal WHERE journal_id=172) and v.ebook_status='1' and y.year > 2020 group by `v`.`nid` order by `v`.`ebook_volume_id` desc limit 10 offset 0
      1.22msalphaeurekaselec_live_10_06_2022Subject.php#218
      Backtrace
      • 14. app/Models/Subject.php:218
      • 15. app/Http/Controllers/ArticleController.php:2518
      • 16. app/Http/Controllers/ArticleController.php:2035
      • 17. vendor/laravel/framework/src/Illuminate/Routing/Controller.php:54
      • 18. vendor/laravel/framework/src/Illuminate/Routing/ControllerDispatcher.php:43
    • select * from `keywords` where `article_id` = '102570'
      970μsalphaeurekaselec_live_10_06_2022Keywords.php#85
      Bindings
      • 0: 102570
      Backtrace
      • 13. app/Models/Keywords.php:85
      • 14. app/Http/Controllers/ArticleController.php:2519
      • 15. app/Http/Controllers/ArticleController.php:2035
      • 16. vendor/laravel/framework/src/Illuminate/Routing/Controller.php:54
      • 17. vendor/laravel/framework/src/Illuminate/Routing/ControllerDispatcher.php:43
    • select * from `article_citation` where `article_id` = '102570'
      6.16msalphaeurekaselec_live_10_06_2022Article.php#1569
      Bindings
      • 0: 102570
      Backtrace
      • 13. app/Models/Article.php:1569
      • 14. app/Http/Controllers/ArticleController.php:2520
      • 15. app/Http/Controllers/ArticleController.php:2035
      • 16. vendor/laravel/framework/src/Illuminate/Routing/Controller.php:54
      • 17. vendor/laravel/framework/src/Illuminate/Routing/ControllerDispatcher.php:43
    • select CONCAT_WS(' ',au.first_name, ' ', ifnull(au.initials,''), ' ', au.last_name) as authors, CONCAT(au.last_name, IFNULL(CONCAT(' ', au.initials), ''), ' ', au.first_name) AS authorsRIS, CONCAT_WS(' ',au.last_name, ' ', ifnull(au.initials,''), ' ', au.first_name) as authorsCiteAs , `au`.*, (GROUP_CONCAT(TRIM(BOTH ', ' FROM CONCAT(ifnull(concat(af.institution,','),''), ifnull(concat(af.department,','),''), ifnull(concat(af.address,','),''), ifnull(concat(af.city,','),''), ifnull(concat(af.country,','),''), ifnull(concat(af.postal_code,','),''), ifnull(concat(af.phone,','),''), ifnull(concat(af.fax,','),''))) SEPARATOR '|')) as `author_affiliation`, (GROUP_CONCAT(TRIM(BOTH ', ' FROM CONCAT(ifnull(concat(af.web_view,','),''))) SEPARATOR '|')) as `web_view` from `author` as `au` left join `author_affiliation` as `af` on `au`.`author_id` = `af`.`author_id` where `au`.`article_id` = '102570' group by `au`.`author_id` order by `au`.`article_id` asc, `au`.`sequence` asc
      1.91msalphaeurekaselec_live_10_06_2022Author.php#86
      Bindings
      • 0: 102570
      Backtrace
      • 13. app/Models/Author.php:86
      • 14. app/Http/Controllers/ArticleController.php:2533
      • 15. app/Http/Controllers/ArticleController.php:2035
      • 16. vendor/laravel/framework/src/Illuminate/Routing/Controller.php:54
      • 17. vendor/laravel/framework/src/Illuminate/Routing/ControllerDispatcher.php:43
    • select `bo`.* from `bundle_offer` as `bo` where `bo`.`bundle_status` = 'A' order by `bo`.`bundle_id` desc
      260μsalphaeurekaselec_live_10_06_2022BundleOffer.php#113
      Bindings
      • 0: A
      Backtrace
      • 13. app/Models/BundleOffer.php:113
      • 14. app/Http/Controllers/ArticleController.php:2535
      • 15. app/Http/Controllers/ArticleController.php:2035
      • 16. vendor/laravel/framework/src/Illuminate/Routing/Controller.php:54
      • 17. vendor/laravel/framework/src/Illuminate/Routing/ControllerDispatcher.php:43
    • select `subtitle` from `journal` where `continues_publication_journal` = 1
      460μsalphaeurekaselec_live_10_06_2022Article.php#1959
      Bindings
      • 0: 1
      Backtrace
      • 13. app/Models/Article.php:1959
      • 14. app/Http/Controllers/ArticleController.php:2062
      • 15. vendor/laravel/framework/src/Illuminate/Routing/Controller.php:54
      • 16. vendor/laravel/framework/src/Illuminate/Routing/ControllerDispatcher.php:43
      • 17. vendor/laravel/framework/src/Illuminate/Routing/Route.php:260
    • Select j.subtitle, v.volume_id as volume_id,v.year_id,y.year as year,v.volume_name, v.total_no_of_issues, i.issue_id as issue_id,i.title as issue, i.publication_date as issue_pub_date from journal j join volume v on j.journal_id = v.journal_id join issue i on v.volume_id = i.volume_id join article a on a.issue_id = i.issue_id join year y on v.year_id = y.id where j.journal_id = 172 and i.is_uploaded = 1 order by v.volume_name+0 desc, i.title+0 desc limit 1
      19.42msalphaeurekaselec_live_10_06_2022Issue.php#295
      Backtrace
      • 11. app/Models/Issue.php:295
      • 12. app/Http/Controllers/ArticleController.php:2068
      • 13. vendor/laravel/framework/src/Illuminate/Routing/Controller.php:54
      • 14. vendor/laravel/framework/src/Illuminate/Routing/ControllerDispatcher.php:43
      • 15. vendor/laravel/framework/src/Illuminate/Routing/Route.php:260
    • select a.nid,a.publish_on, a.pmid,a.article_id,a.doi,j.journal_id,j.subtitle,v.volume_name,a.volume_id as volume_id, a.issue_id,a.title,first_page, last_page, page_count,abstract,ifnull(is_abstract,"y"),asec.title as article_section,at.type_name as article_type_name, a.article_id as ArticleID ,is_epub,epub_price,epub_type,a.created, y.year from `article` as `a` left join `article_section` as `asec` on `asec`.`art_sec_id` = `a`.`is_epub` left join `article_type` as `at` on `at`.`art_type_id` = `a`.`art_type` left join `journal` as `j` on `j`.`journal_id` = `a`.`journal_id` inner join `volume` as `v` on `a`.`volume_id` = `v`.`volume_id` inner join `year` as `y` on `v`.`year_id` = `y`.`id` where a.article_status != "W" and a.is_epub = 1 and a.journal_id = 172 and a.is_uploaded = 1 group by `a`.`article_id` order by `a`.`last_modified` desc
      3.93msalphaeurekaselec_live_10_06_2022Article.php#527
      Backtrace
      • 13. app/Models/Article.php:527
      • 14. app/Http/Controllers/ArticleController.php:2070
      • 15. vendor/laravel/framework/src/Illuminate/Routing/Controller.php:54
      • 16. vendor/laravel/framework/src/Illuminate/Routing/ControllerDispatcher.php:43
      • 17. vendor/laravel/framework/src/Illuminate/Routing/Route.php:260
    • select a.nid,a.publish_on, a.pmid,a.article_id,a.doi,j.journal_id,j.subtitle,v.volume_name,a.volume_id as volume_id, a.issue_id,a.title,first_page, last_page, page_count,abstract,ifnull(is_abstract,"y"),asec.title as article_section,at.type_name as article_type_name, a.article_id as ArticleID ,is_epub,epub_price,epub_type,a.created, y.year from `article` as `a` left join `article_section` as `asec` on `asec`.`art_sec_id` = `a`.`is_epub` left join `article_type` as `at` on `at`.`art_type_id` = `a`.`art_type` left join `journal` as `j` on `j`.`journal_id` = `a`.`journal_id` inner join `volume` as `v` on `a`.`volume_id` = `v`.`volume_id` inner join `year` as `y` on `v`.`year_id` = `y`.`id` where a.article_status != "W" and a.is_epub = 4 and a.journal_id = 172 and a.is_uploaded = 1 group by `a`.`article_id` order by `a`.`last_modified` desc
      1.62msalphaeurekaselec_live_10_06_2022Article.php#527
      Backtrace
      • 13. app/Models/Article.php:527
      • 14. app/Http/Controllers/ArticleController.php:2071
      • 15. vendor/laravel/framework/src/Illuminate/Routing/Controller.php:54
      • 16. vendor/laravel/framework/src/Illuminate/Routing/ControllerDispatcher.php:43
      • 17. vendor/laravel/framework/src/Illuminate/Routing/Route.php:260
    • select pdf, html, epub, prc from `article_metrics` where `article_id` = 102570 limit 1
      840μsalphaeurekaselec_live_10_06_2022Article.php#743
      Bindings
      • 0: 102570
      Backtrace
      • 14. app/Models/Article.php:743
      • 15. app/Http/Controllers/ArticleController.php:2091
      • 16. vendor/laravel/framework/src/Illuminate/Routing/Controller.php:54
      • 17. vendor/laravel/framework/src/Illuminate/Routing/ControllerDispatcher.php:43
      • 18. vendor/laravel/framework/src/Illuminate/Routing/Route.php:260
    • select * from content_by_diseases where content_id = 102570 and content_type = 'article' order by status desc limit 1
      310μsalphaeurekaselec_live_10_06_2022Article.php#750
      Backtrace
      • 11. app/Models/Article.php:750
      • 12. app/Http/Controllers/ArticleController.php:2094
      • 13. vendor/laravel/framework/src/Illuminate/Routing/Controller.php:54
      • 14. vendor/laravel/framework/src/Illuminate/Routing/ControllerDispatcher.php:43
      • 15. vendor/laravel/framework/src/Illuminate/Routing/Route.php:260
    • select * from `node_meta` where `nid` = 176948 limit 1
      190μsalphaeurekaselec_live_10_06_2022Meta.php#59
      Bindings
      • 0: 176948
      Backtrace
      • 14. app/Models/Meta.php:59
      • 15. app/Http/Controllers/ArticleController.php:2101
      • 16. vendor/laravel/framework/src/Illuminate/Routing/Controller.php:54
      • 17. vendor/laravel/framework/src/Illuminate/Routing/ControllerDispatcher.php:43
      • 18. vendor/laravel/framework/src/Illuminate/Routing/Route.php:260
    • select `bo`.* from `bundle_offer` as `bo` where `bo`.`bundle_status` = 'A' order by `bo`.`bundle_id` desc
      210μsalphaeurekaselec_live_10_06_2022BundleOffer.php#113
      Bindings
      • 0: A
      Backtrace
      • 13. app/Models/BundleOffer.php:113
      • 14. app/Http/Controllers/ArticleController.php:2108
      • 15. vendor/laravel/framework/src/Illuminate/Routing/Controller.php:54
      • 16. vendor/laravel/framework/src/Illuminate/Routing/ControllerDispatcher.php:43
      • 17. vendor/laravel/framework/src/Illuminate/Routing/Route.php:260
    • select * from `tbl_ht_submission` as `h` where `h`.`subtitle` = 'CDRR' and (h.proposal_closing_date = 0 OR TO_DAYS(FROM_UNIXTIME(h.proposal_closing_date)) >= TO_DAYS(NOW())) order by `h`.`manuscript` asc
      240μsalphaeurekaselec_live_10_06_2022Article.php#2024
      Bindings
      • 0: CDRR
      Backtrace
      • 13. app/Models/Article.php:2024
      • 14. app/Http/Controllers/ArticleController.php:2112
      • 15. vendor/laravel/framework/src/Illuminate/Routing/Controller.php:54
      • 16. vendor/laravel/framework/src/Illuminate/Routing/ControllerDispatcher.php:43
      • 17. vendor/laravel/framework/src/Illuminate/Routing/Route.php:260
    • select count(*) as total_count, content_type_access_id as access_type from journal_access where content_type_id = '102570' and content_type = 'a' and ( (from_date <= CURDATE() and to_date >= CURDATE() and perpetual= 0) or (from_date is null and to_date is null and perpetual= 1) )
      400μsalphaeurekaselec_live_10_06_2022ContentAccess.php#647
      Backtrace
      • 11. app/Models/ContentAccess.php:647
      • 12. app/Http/Controllers/ArticleController.php:2186
      • 13. vendor/laravel/framework/src/Illuminate/Routing/Controller.php:54
      • 14. vendor/laravel/framework/src/Illuminate/Routing/ControllerDispatcher.php:43
      • 15. vendor/laravel/framework/src/Illuminate/Routing/Route.php:260
    • select count(*) as total_count, content_type_access_id as access_type from journal_access where content_type_id = '9878' and content_type = 'i' and ( (from_date <= CURDATE() and to_date >= CURDATE() and perpetual= 0) or (from_date is null and to_date is null and perpetual= 1) )
      290μsalphaeurekaselec_live_10_06_2022ContentAccess.php#647
      Backtrace
      • 11. app/Models/ContentAccess.php:647
      • 12. app/Http/Controllers/ArticleController.php:2207
      • 13. vendor/laravel/framework/src/Illuminate/Routing/Controller.php:54
      • 14. vendor/laravel/framework/src/Illuminate/Routing/ControllerDispatcher.php:43
      • 15. vendor/laravel/framework/src/Illuminate/Routing/Route.php:260
    • select count(*) as total_count, content_type_access_id as access_type from journal_access where content_type_id = '2763' and content_type = 'v' and ( (from_date <= CURDATE() and to_date >= CURDATE() and perpetual= 0) or (from_date is null and to_date is null and perpetual= 1) )
      260μsalphaeurekaselec_live_10_06_2022ContentAccess.php#647
      Backtrace
      • 11. app/Models/ContentAccess.php:647
      • 12. app/Http/Controllers/ArticleController.php:2231
      • 13. vendor/laravel/framework/src/Illuminate/Routing/Controller.php:54
      • 14. vendor/laravel/framework/src/Illuminate/Routing/ControllerDispatcher.php:43
      • 15. vendor/laravel/framework/src/Illuminate/Routing/Route.php:260
    • (select j.user_access_id,j.volume_id,j.user_id,j.from_ip,j.to_ip,j.type,j.track,"Trial Access" as access_base_text, CASE j.type WHEN 111 THEN true ELSE false END as terms_popup, "S" as content_download_type, null as restricted_user_access_key, null as restricted_user_access_type, CASE j.track WHEN 0 THEN false ELSE true END as tracksAccessByVolume,"volume" as access_level,"" as issue_id,"" as article_id from `user_access_journal_volume_trail` as `j` inner join `user_access_info` as `info` on `j`.`user_access_id` = `info`.`user_access_id` where ((j.from_ip <= 59651772 and j.to_ip >=59651772 )) and ((j.from_date <= 1735020722 and j.to_date >= 1735020722 and j.perpetual= 0) or (j.from_date is null and j.to_date is null and j.perpetual= 1)) and j.volume_id = 2763) union (select j.user_access_id,j.volume_id,j.user_id,j.from_ip,j.to_ip,j.type,j.track,"Subscribed" as access_base_text, false as terms_popup, "S" as content_download_type, null as restricted_user_access_key, null as restricted_user_access_type, CASE j.track WHEN 0 THEN false ELSE true END as tracksAccessByVolume,"volume" as access_level,"" as issue_id,"" as article_id from `user_access_journal_volume_corporate` as `j` inner join `user_access_info` as `info` on `j`.`user_access_id` = `info`.`user_access_id` where ((j.from_ip <= 59651772 and j.to_ip >=59651772 )) and ((j.from_date <= 1735020722 and j.to_date >= 1735020722 and j.perpetual= 0) or (j.from_date is null and j.to_date is null and j.perpetual= 1)) and j.volume_id = 2763) union (select j.user_access_id,j.volume_id,j.user_id,j.from_ip,j.to_ip,j.type,j.track,"Token Based Access" as access_base_text, false as terms_popup, "R" as content_download_type, j.uc_id as restricted_user_access_key, "v" as restricted_user_access_type, CASE j.track WHEN 0 THEN false ELSE true END as tracksAccessByVolume,"volume" as access_level,"" as issue_id,"" as article_id from `user_access_journal_volume_token` as `j` inner join `user_access_info` as `info` on `j`.`user_access_id` = `info`.`user_access_id` where ((j.from_ip <= 59651772 and j.to_ip >=59651772 )) and ((j.from_date <= 1735020722 and j.to_date >= 1735020722 and j.perpetual= 0) or (j.from_date is null and j.to_date is null and j.perpetual= 1)) and j.volume_id = 2763)
      8.29msalphaeurekaselec_live_10_06_2022UserAccess.php#1266
      Backtrace
      • 13. app/Models/UserAccess/UserAccess.php:1266
      • 14. app/Http/Controllers/ArticleController.php:2272
      • 15. vendor/laravel/framework/src/Illuminate/Routing/Controller.php:54
      • 16. vendor/laravel/framework/src/Illuminate/Routing/ControllerDispatcher.php:43
      • 17. vendor/laravel/framework/src/Illuminate/Routing/Route.php:260
    • (select j.user_access_id,j.volume_id,j.user_id,j.from_ip,j.to_ip,j.type,j.track,"Trial Access" as access_base_text, CASE j.type WHEN 111 THEN true ELSE false END as terms_popup, "S" as content_download_type, null as restricted_user_access_key, null as restricted_user_access_type, CASE j.track WHEN 0 THEN false ELSE true END as tracksAccessByVolume,"issue" as access_level,j.issue_id,"" as article_id from `user_access_issue_trail` as `j` inner join `user_access_info` as `info` on `j`.`user_access_id` = `info`.`user_access_id` where ((j.from_ip <= 59651772 and j.to_ip >=59651772 )) and ((j.from_date <= 1735020722 and j.to_date >= 1735020722 and j.perpetual= 0) or (j.from_date is null and j.to_date is null and j.perpetual= 1)) and j.issue_id = 9878) union (select j.user_access_id,j.volume_id,j.user_id,j.from_ip,j.to_ip,j.type,j.track,"Subscribed" as access_base_text, false as terms_popup, "S" as content_download_type, null as restricted_user_access_key, null as restricted_user_access_type, CASE j.track WHEN 0 THEN false ELSE true END as tracksAccessByVolume,"issue" as access_level,j.issue_id,"" as article_id from `user_access_issue_corporate` as `j` inner join `user_access_info` as `info` on `j`.`user_access_id` = `info`.`user_access_id` where ((j.from_ip <= 59651772 and j.to_ip >=59651772 )) and ((j.from_date <= 1735020722 and j.to_date >= 1735020722 and j.perpetual= 0) or (j.from_date is null and j.to_date is null and j.perpetual= 1)) and j.issue_id = 9878) union (select j.user_access_id,j.volume_id,j.user_id,j.from_ip,j.to_ip,j.type,j.track,"Token Based Access" as access_base_text, false as terms_popup, "R" as content_download_type, j.uc_id as restricted_user_access_key, "v" as restricted_user_access_type, CASE j.track WHEN 0 THEN false ELSE true END as tracksAccessByVolume,"issue" as access_level,j.issue_id,"" as article_id from `user_access_issue_token` as `j` inner join `user_access_info` as `info` on `j`.`user_access_id` = `info`.`user_access_id` where ((j.from_ip <= 59651772 and j.to_ip >=59651772 )) and ((j.from_date <= 1735020722 and j.to_date >= 1735020722 and j.perpetual= 0) or (j.from_date is null and j.to_date is null and j.perpetual= 1)) and j.issue_id = 9878)
      560μsalphaeurekaselec_live_10_06_2022UserAccess.php#1266
      Backtrace
      • 13. app/Models/UserAccess/UserAccess.php:1266
      • 14. app/Http/Controllers/ArticleController.php:2297
      • 15. vendor/laravel/framework/src/Illuminate/Routing/Controller.php:54
      • 16. vendor/laravel/framework/src/Illuminate/Routing/ControllerDispatcher.php:43
      • 17. vendor/laravel/framework/src/Illuminate/Routing/Route.php:260
    • (select j.user_access_id,j.volume_id,j.user_id,j.from_ip,j.to_ip,j.type,j.track,"Trial Access" as access_base_text, CASE j.type WHEN 111 THEN true ELSE false END as terms_popup, "S" as content_download_type, null as restricted_user_access_key, null as restricted_user_access_type, CASE j.track WHEN 0 THEN false ELSE true END as tracksAccessByVolume,"article" as access_level, j.issue_id, j.article_id from `user_access_article_trail` as `j` inner join `user_access_info` as `info` on `j`.`user_access_id` = `info`.`user_access_id` where ((j.from_ip <= 59651772 and j.to_ip >=59651772 )) and ((j.from_date <= 1735020722 and j.to_date >= 1735020722 and j.perpetual= 0) or (j.from_date is null and j.to_date is null and j.perpetual= 1)) and j.article_id = 102570) union (select j.user_access_id,j.volume_id,j.user_id,j.from_ip,j.to_ip,j.type,j.track,"Subscribed" as access_base_text, false as terms_popup, "S" as content_download_type, null as restricted_user_access_key, null as restricted_user_access_type, CASE j.track WHEN 0 THEN false ELSE true END as tracksAccessByVolume,"article" as access_level, j.issue_id, j.article_id from `user_access_article_corporate` as `j` inner join `user_access_info` as `info` on `j`.`user_access_id` = `info`.`user_access_id` where ((j.from_ip <= 59651772 and j.to_ip >=59651772 )) and ((j.from_date <= 1735020722 and j.to_date >= 1735020722 and j.perpetual= 0) or (j.from_date is null and j.to_date is null and j.perpetual= 1)) and j.article_id = 102570) union (select j.user_access_id,j.volume_id,j.user_id,j.from_ip,j.to_ip,j.type,j.track,"Token Based Access" as access_base_text, false as terms_popup, "R" as content_download_type, j.uc_id as restricted_user_access_key, "v" as restricted_user_access_type, CASE j.track WHEN 0 THEN false ELSE true END as tracksAccessByVolume,"article" as access_level, j.issue_id, j.article_id from `user_access_article_token` as `j` inner join `user_access_info` as `info` on `j`.`user_access_id` = `info`.`user_access_id` where ((j.from_ip <= 59651772 and j.to_ip >=59651772 )) and ((j.from_date <= 1735020722 and j.to_date >= 1735020722 and j.perpetual= 0) or (j.from_date is null and j.to_date is null and j.perpetual= 1)) and j.article_id = 102570)
      550μsalphaeurekaselec_live_10_06_2022UserAccess.php#1266
      Backtrace
      • 13. app/Models/UserAccess/UserAccess.php:1266
      • 14. app/Http/Controllers/ArticleController.php:2329
      • 15. vendor/laravel/framework/src/Illuminate/Routing/Controller.php:54
      • 16. vendor/laravel/framework/src/Illuminate/Routing/ControllerDispatcher.php:43
      • 17. vendor/laravel/framework/src/Illuminate/Routing/Route.php:260
    • select * from `article` where `first_page` < '26' and is_uploaded = 1 and issue_id = 9878 order by cast(first_page as SIGNED) desc limit 1
      460μsalphaeurekaselec_live_10_06_2022Article.php#1818
      Bindings
      • 0: 26
      Backtrace
      • 14. app/Models/Article.php:1818
      • 15. app/Http/Controllers/ArticleController.php:2470
      • 16. vendor/laravel/framework/src/Illuminate/Routing/Controller.php:54
      • 17. vendor/laravel/framework/src/Illuminate/Routing/ControllerDispatcher.php:43
      • 18. vendor/laravel/framework/src/Illuminate/Routing/Route.php:260
    • select * from `article` where `last_page` > '41' and is_uploaded = 1 and issue_id = 9878 order by cast(first_page as SIGNED) asc limit 1
      370μsalphaeurekaselec_live_10_06_2022Article.php#1830
      Bindings
      • 0: 41
      Backtrace
      • 14. app/Models/Article.php:1830
      • 15. app/Http/Controllers/ArticleController.php:2472
      • 16. vendor/laravel/framework/src/Illuminate/Routing/Controller.php:54
      • 17. vendor/laravel/framework/src/Illuminate/Routing/ControllerDispatcher.php:43
      • 18. vendor/laravel/framework/src/Illuminate/Routing/Route.php:260
    • select `language_id` from `multilanguage` where `short_code` = 'en'
      170μsalphaeurekaselec_live_10_06_2022ArticleController.php#2497
      Bindings
      • 0: en
      Backtrace
      • 14. app/Http/Controllers/ArticleController.php:2497
      • 15. vendor/laravel/framework/src/Illuminate/Routing/Controller.php:54
      • 16. vendor/laravel/framework/src/Illuminate/Routing/ControllerDispatcher.php:43
      • 17. vendor/laravel/framework/src/Illuminate/Routing/Route.php:260
      • 18. vendor/laravel/framework/src/Illuminate/Routing/Route.php:206
    • select `source_lang_label`, `target_lang_label` from `multilanguage_labels` where `target_lang_id` = 1
      160μsalphaeurekaselec_live_10_06_2022MultiLanguage.php#23
      Bindings
      • 0: 1
      Backtrace
      • 13. app/Models/MultiLanguage.php:23
      • 14. app/Http/Controllers/ArticleController.php:2498
      • 15. vendor/laravel/framework/src/Illuminate/Routing/Controller.php:54
      • 16. vendor/laravel/framework/src/Illuminate/Routing/ControllerDispatcher.php:43
      • 17. vendor/laravel/framework/src/Illuminate/Routing/Route.php:260
    • select `id` from `multilanguage_article` where `article_id` = 102570 limit 1
      2.68msalphaeurekaselec_live_10_06_2022ArticleController.php#2506
      Bindings
      • 0: 102570
      Backtrace
      • 16. app/Http/Controllers/ArticleController.php:2506
      • 17. vendor/laravel/framework/src/Illuminate/Routing/Controller.php:54
      • 18. vendor/laravel/framework/src/Illuminate/Routing/ControllerDispatcher.php:43
      • 19. vendor/laravel/framework/src/Illuminate/Routing/Route.php:260
      • 20. vendor/laravel/framework/src/Illuminate/Routing/Route.php:206
    • select b.banner_link, b.banner_name, b.banner_script, b.banner_remarks, b.banner_file_name, b.banner_placement, bd.content_type, bd.content_id from `tbl_banner` as `b` inner join `tbl_banner_detail` as `bd` on `bd`.`banner_id` = `b`.`banner_id` inner join `users` as `u` on `u`.`id` = `b`.`updated_by` inner join `journal` as `j` on `j`.`journal_id` = `bd`.`content_id` where `b`.`banner_journal` = 1 and `bd`.`content_type` = 'J' and `bd`.`content_id` = 172 and `b`.`banner_from_date` <= 1735020722 and `b`.`banner_to_date` >= 1735020722 and `b`.`banner_status` = 'A' order by `b`.`banner_id` desc
      1.21msalphaeurekaselec_live_10_06_2022Banner.php#189
      Bindings
      • 0: 1
      • 1: J
      • 2: 172
      • 3: 1735020722
      • 4: 1735020722
      • 5: A
      Backtrace
      • 13. app/Models/Banner.php:189
      • 14. app/Http/helpers.php:404
      • 17. vendor/laravel/framework/src/Illuminate/Filesystem/Filesystem.php:124
      • 18. vendor/laravel/framework/src/Illuminate/View/Engines/PhpEngine.php:58
      • 19. vendor/laravel/framework/src/Illuminate/View/Engines/CompilerEngine.php:73
    • select count(*) as aggregate from `uc_cart_products` where cart_id='fc8a1c4a64bc5fdd4adcb913d6e5d0ba'
      330μsalphaeurekaselec_live_10_06_2022Cart.php#271
      Backtrace
      • 15. app/Models/Cart.php:271
      • 16. view::layouts._main_menu:13
      • 18. vendor/laravel/framework/src/Illuminate/Filesystem/Filesystem.php:124
      • 19. vendor/laravel/framework/src/Illuminate/View/Engines/PhpEngine.php:58
      • 20. vendor/laravel/framework/src/Illuminate/View/Engines/CompilerEngine.php:73
    App\Models\MultiLanguage
    1MultiLanguage.php#?
        _token
        WfQMKPdYgaVDwli02hL9wd6hoVvpIOZp5pULpmIh
        uc_cart_id
        fc8a1c4a64bc5fdd4adcb913d6e5d0ba
        _previous
        array:1 [ "url" => "https://beta.benthamscience.com/article/102570" ]
        _flash
        array:2 [ "old" => [] "new" => [] ]
        PHPDEBUGBAR_STACK_DATA
        []
        path_info
        /article/102570
        status_code
        200
        
        status_text
        OK
        format
        html
        content_type
        text/html; charset=UTF-8
        request_query
        []
        
        request_request
        []
        
        request_headers
        0 of 0
        array:16 [ "x-https" => array:1 [ 0 => "1" ] "host" => array:1 [ 0 => "beta.benthamscience.com" ] "priority" => array:1 [ 0 => "u=0, i" ] "accept-encoding" => array:1 [ 0 => "gzip, deflate, br, zstd" ] "sec-fetch-dest" => array:1 [ 0 => "document" ] "sec-fetch-user" => array:1 [ 0 => "?1" ] "sec-fetch-mode" => array:1 [ 0 => "navigate" ] "sec-fetch-site" => array:1 [ 0 => "none" ] "accept" => array:1 [ 0 => "text/html,application/xhtml+xml,application/xml;q=0.9,image/avif,image/webp,image/apng,*/*;q=0.8,application/signed-exchange;v=b3;q=0.7" ] "user-agent" => array:1 [ 0 => "Mozilla/5.0 AppleWebKit/537.36 (KHTML, like Gecko; compatible; ClaudeBot/1.0; +claudebot@anthropic.com)" ] "upgrade-insecure-requests" => array:1 [ 0 => "1" ] "sec-ch-ua-platform" => array:1 [ 0 => ""Windows"" ] "sec-ch-ua-mobile" => array:1 [ 0 => "?0" ] "sec-ch-ua" => array:1 [ 0 => ""HeadlessChrome";v="129", "Not=A?Brand";v="8", "Chromium";v="129"" ] "cache-control" => array:1 [ 0 => "no-cache" ] "pragma" => array:1 [ 0 => "no-cache" ] ]
        request_cookies
        []
        
        response_headers
        0 of 0
        array:5 [ "content-type" => array:1 [ 0 => "text/html; charset=UTF-8" ] "cache-control" => array:1 [ 0 => "no-cache, private" ] "date" => array:1 [ 0 => "Tue, 24 Dec 2024 06:12:02 GMT" ] "set-cookie" => array:2 [ 0 => "XSRF-TOKEN=eyJpdiI6IjlIbGNkQ3VuRjlZNXFhK3A4Zk42M2c9PSIsInZhbHVlIjoiSGU5dTF3NmFpWVJ0c0MyR2xHdFRid2NyWWprNDNSV1NqNElFc2haZG94d2wySDhYbEhZVllZT2gwYVFSc2xXZ29lM3Mxdi83ZVlZemRkSlVQeGU1UlpRV2hXQW5zTVhGWTBnRXBwN1pjQ0tEcjFrSGZvOXNBVktVM0VxbGRhbWciLCJtYWMiOiI2OTUwZjc1NTdjZTNmMzUzMGNmZDIxOTJkOTYyZWFhNTcwMzFiZjJiYzU3ZDQ0MTVmODQwYmFhZWEzYzc5YTA4IiwidGFnIjoiIn0%3D; expires=Thu, 26 Dec 2024 18:12:02 GMT; Max-Age=216000; path=/; secure; samesite=strictXSRF-TOKEN=eyJpdiI6IjlIbGNkQ3VuRjlZNXFhK3A4Zk42M2c9PSIsInZhbHVlIjoiSGU5dTF3NmFpWVJ0c0MyR2xHdFRid2NyWWprNDNSV1NqNElFc2haZG94d2wySDhYbEhZVllZT2gwYVFSc2xXZ29lM3Mxd" 1 => "eurekaselectnew_session=eyJpdiI6IlAzdmlqUWplRUhyb0dMd0tBK08ya2c9PSIsInZhbHVlIjoiaU5vQXBVUGx5V2hRR0FBRTdObFlXeVY0WW1Xb2VjL05JcTZoNlM4K0d4cy91MmtVNzlGRWJNTTR4WHZVdEtJY1U0WHc1bk5mM1ByN2JZRXF4TEw2N0ErbGUyVHpReW5lYnZJeXppTS9SMzZIYyt5b1ZFKzhjMVFiZkhRSU4xNHAiLCJtYWMiOiJjNTg1M2RkYTI5MTI3ZDU1YzJmMWNlYTJhNWNhNGIwMjBkNTk3YTk4Zjg5NGM0Nzc5YTI1MTQ0ZTljMTEwZmNmIiwidGFnIjoiIn0%3D; path=/; secure; httponly; samesite=stricteurekaselectnew_session=eyJpdiI6IlAzdmlqUWplRUhyb0dMd0tBK08ya2c9PSIsInZhbHVlIjoiaU5vQXBVUGx5V2hRR0FBRTdObFlXeVY0WW1Xb2VjL05JcTZoNlM4K0d4cy91MmtVNzlGRWJNTTR4WHZV" ] "Set-Cookie" => array:2 [ 0 => "XSRF-TOKEN=eyJpdiI6IjlIbGNkQ3VuRjlZNXFhK3A4Zk42M2c9PSIsInZhbHVlIjoiSGU5dTF3NmFpWVJ0c0MyR2xHdFRid2NyWWprNDNSV1NqNElFc2haZG94d2wySDhYbEhZVllZT2gwYVFSc2xXZ29lM3Mxdi83ZVlZemRkSlVQeGU1UlpRV2hXQW5zTVhGWTBnRXBwN1pjQ0tEcjFrSGZvOXNBVktVM0VxbGRhbWciLCJtYWMiOiI2OTUwZjc1NTdjZTNmMzUzMGNmZDIxOTJkOTYyZWFhNTcwMzFiZjJiYzU3ZDQ0MTVmODQwYmFhZWEzYzc5YTA4IiwidGFnIjoiIn0%3D; expires=Thu, 26-Dec-2024 18:12:02 GMT; path=/; secureXSRF-TOKEN=eyJpdiI6IjlIbGNkQ3VuRjlZNXFhK3A4Zk42M2c9PSIsInZhbHVlIjoiSGU5dTF3NmFpWVJ0c0MyR2xHdFRid2NyWWprNDNSV1NqNElFc2haZG94d2wySDhYbEhZVllZT2gwYVFSc2xXZ29lM3Mxd" 1 => "eurekaselectnew_session=eyJpdiI6IlAzdmlqUWplRUhyb0dMd0tBK08ya2c9PSIsInZhbHVlIjoiaU5vQXBVUGx5V2hRR0FBRTdObFlXeVY0WW1Xb2VjL05JcTZoNlM4K0d4cy91MmtVNzlGRWJNTTR4WHZVdEtJY1U0WHc1bk5mM1ByN2JZRXF4TEw2N0ErbGUyVHpReW5lYnZJeXppTS9SMzZIYyt5b1ZFKzhjMVFiZkhRSU4xNHAiLCJtYWMiOiJjNTg1M2RkYTI5MTI3ZDU1YzJmMWNlYTJhNWNhNGIwMjBkNTk3YTk4Zjg5NGM0Nzc5YTI1MTQ0ZTljMTEwZmNmIiwidGFnIjoiIn0%3D; path=/; secure; httponlyeurekaselectnew_session=eyJpdiI6IlAzdmlqUWplRUhyb0dMd0tBK08ya2c9PSIsInZhbHVlIjoiaU5vQXBVUGx5V2hRR0FBRTdObFlXeVY0WW1Xb2VjL05JcTZoNlM4K0d4cy91MmtVNzlGRWJNTTR4WHZV" ] ]
        session_attributes
        0 of 0
        array:5 [ "_token" => "WfQMKPdYgaVDwli02hL9wd6hoVvpIOZp5pULpmIh" "uc_cart_id" => "fc8a1c4a64bc5fdd4adcb913d6e5d0ba" "_previous" => array:1 [ "url" => "https://beta.benthamscience.com/article/102570" ] "_flash" => array:2 [ "old" => [] "new" => [] ] "PHPDEBUGBAR_STACK_DATA" => [] ]
        ClearShow all
        Date ↕MethodURLData
        #12024-12-24 06:12:02GET/article/10257048351