International Journal of Pharmaceutical Sciences and Drug Research最新文献

{"title":"Phytochemical, antioxidant and antidiabetic analysis of leaf and stem extracts of Memecylon malabaricum(C.B.Clarke)Cogn.","authors":"D. H. Tejavathi, B. Sumalatha","doi":"10.25004/ijpsdr.2020.120604","DOIUrl":"https://doi.org/10.25004/ijpsdr.2020.120604","url":null,"abstract":"Memecylon malabaricum (C.B.Clarke) Cogn. belongs to the family Melastomataceae is one of the important medicinal plants in traditional system of medicine. It has been used to treat diabetes, bacterial infections, and skin disorders including Herpes. Hence, the present study deals with the analysis of stem and leaf extracts through GC-MS to identify the bioactive compounds. 29 in stem and 25 phytochemicals in leaf extract were identified. Based on the results of GC-MS analysis further studies were carried out to estimate phenols, flavonoids and total antioxidant activity. It was found that stem methanolic extract has slightly more quantity of phenolics than the leaf extract. However, leaf extract has shown a considerable amount of flavonoids and better antioxidant activity than stem extract as revealed by DPPH, ABTS and reducing power assay. Further, inhibition of the activity of α-amylase by leaf extract was detected through preliminary studies thereby supporting its traditional use to treat diabetes.","PeriodicalId":14278,"journal":{"name":"International Journal of Pharmaceutical Sciences and Drug Research","volume":null,"pages":null},"PeriodicalIF":0.0,"publicationDate":"2020-11-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"91090754","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Selection the Drug Efficacy of Oroidin Derivatives as Hsp90 Inhibitors by Computer Aided Drug Design Method","authors":"S. Sarkar, R. K. Das","doi":"10.25004/ijpsdr.2020.120607","DOIUrl":"https://doi.org/10.25004/ijpsdr.2020.120607","url":null,"abstract":"Heat shock protein 90 (Hsp90) is a conserved molecular chaperone associated with regulation of hundreds of client proteins that are key drivers, regulators and promoters of numerous refractory diseases including cancer. Consequently, Hsp90 is a significant target for the development of harmless anticancer therapies. Marine organisms are the rich source of pharmacological important compounds, especially oroidin. Oroidin, a pyrrole-2-aminoimidazole alkaloid, isolated from the marine sponge Agelas oroides, binds ATP pocket of Hsp90 and suppresses the ATPase activity of the protein. Natural product oroidin was selected as potent inhibitor of Hsp90 and its drug candidature was accordingly improved by substituting various functional groups. Virtual screenings were done through in silico studies, carried out on thirty nine derivatives of oroidin. DFT study was performed with Gaussian16, UB3LYP/6-311G++ (d, p) basis set to investigate the quantum mechanical parameters such as HOMO-LUMO energies, dipole moments. Derived parameters like ionization potential, electron affinity, softness-hardness, chemical potential and electrophilicity index were also calculated. Using AutoDock 4.0 programme, we studied docking of the thirty-nine designed derivatives with macromolecule Hsp90 and recorded the binding energy values of the best conformation out of nine in each docked compound. ADME predictions, molecular descriptor properties, and theoretical toxicity tests were evaluated using preADMET, molinspiration, and OSIRIS property explorer web tools respectively. We found twenty eight derived compounds, each docked at the same region of Hsp90, possessing higher binding energies compare to the precursor oroidin. Seven of them qualified all the rules of drug candidature and could be safe in using as effective drugs for cancer treatment. This study suggests that these compounds could be synthesized for in vitro test and may leads to a novel anticancer therapeutics.","PeriodicalId":14278,"journal":{"name":"International Journal of Pharmaceutical Sciences and Drug Research","volume":null,"pages":null},"PeriodicalIF":0.0,"publicationDate":"2020-11-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"79963599","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Preparation and Evaluation of Extended Release Trilayered Matrix Tablets of Ramipril Using Design of Experiment","authors":"K. Ashwin, T. R. Reddy, P. Nirmala","doi":"10.25004/ijpsdr.2021.130605","DOIUrl":"https://doi.org/10.25004/ijpsdr.2021.130605","url":null,"abstract":"The current work is aimed to design, prepare, and evaluate the trilayer matrix tablets incorporated with ramipril for extended drug release. Twenty-seven formulations (RF1-RF27) for active layer (middle layer) were prepared by direct compression method using 33 Response surface method of polymers of different HPMC K4M, HPMC K15M and xanthan gum (low, middle, and high concentrations) by using Design of experiment software. Based on physico-chemical properties and drug release one formulation was chosen and formulated into extended release trilayered matrix tablets were by varying proportions of polymers by direct compression method and they were evaluated. The best optimized formulation was characterized for FTIR studies. Out of 27 active layer formulations, RF23 was chosen as best based with maximum drug release of 98.11% and was formulated into extended release trilayered matrix tablets (ARF23-HRF23) by varying proportions of polymers. The range of swelling index for all batches (ARF23-HRF23) was 82.34 to 97.46%, similarly the range of drug content was 95.49 to 99.11% and drug released in 24 hours sustainably over an extended period was 84.98 to 98.26% with all highest values exhibited by GRF23. The release order kinetics data indicate the zero-order release with highest (R2) = 0.983 for GRF23 better when compared to marketed product which followed first order showed R2 value 0.962. Further the formulation (GRF23) showed best fit to Korsmeyer-Peppas plots i.e., 0.957 indicating non Fickian (anomalous) transport coupled diffusion and erosion. The FT-IR data assure the compatibilityof drug and excipients. GRF23 was found to be stable for 180 days at accelerated conditions.","PeriodicalId":14278,"journal":{"name":"International Journal of Pharmaceutical Sciences and Drug Research","volume":null,"pages":null},"PeriodicalIF":0.0,"publicationDate":"2020-11-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"90491330","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Antihyperglycemic, Antioxidant and Hepatoprotective Properties of Smilax wightii A.DC. : an Endemic Plant of Western Ghats","authors":"A. Anand, T. Swapna","doi":"10.25004/ijpsdr.2020.120601","DOIUrl":"https://doi.org/10.25004/ijpsdr.2020.120601","url":null,"abstract":"Phytotherapy is an inevitable companion of human civilization. Smilax wightii is an ethnomedicinal plant in Smilacaceae, with unexplored scientifically therapeutic potential. The antihyperglycemic, antioxidant and hepatoprotective capabilities of the methanolic extract of leaf, stem, rhizome and root of S. wightii were inspected in the present study. Hyperglycemia is a manifestation of the prevalent metabolic disorder, Type 2 Diabetes mellitus. Inhibitors of α –glucosidase and α – amylase could be efficiently employed in diabetes mellitus therapy as hypoglycemic agents. In the α –glucosidase and α – amylase inhibitory assays, root and rhizome extracts recorded better antihyperglycemic activity. DPPH radical scavenging activity and total antioxidant capacity were the parameters employed to determine the antioxidant activity. Hepatoprotectivity determines the capability of samples to safeguard the hepatocytes from damage. Novel hepatoprotective agents are in demand since the incidence of liver impairment is on a high among global population. The rhizome extract showed comparatively superior hepatoprotectivity followed by the leaf, stem and root extracts. Rhizome, at 100μg/ml guaranteed a cell viability percentage of 77.43 in the Chang liver cell line treated with Carbon tetrachloride. So the root and rhizome of S. wightii are the therapeutically significant plant parts with hypoglycemic, free radical scavenging and hepatoprotective potentialities.","PeriodicalId":14278,"journal":{"name":"International Journal of Pharmaceutical Sciences and Drug Research","volume":null,"pages":null},"PeriodicalIF":0.0,"publicationDate":"2020-11-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"80555810","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Pharmacokinetic and Pharmacodynamic Interactions Between Concomitantly used Gliclazide with Pravastatin","authors":"T. Haseeb, T. Reddy","doi":"10.25004/ijpsdr.2020.120612","DOIUrl":"https://doi.org/10.25004/ijpsdr.2020.120612","url":null,"abstract":"Diabetic hyperlipidemia is associated with increased lipoproteins in the blood hence, the introduction of a lipid lowering drugs aids in controlling the same. This comedication may lead to drug–drug interactions between anti-diabetic and anti-hyperlipidemic drugs. The current research is aimed at evaluating the pharmacodynamic and pharmacokinetic interactions of gliclazide (anti-diabetic) therapy by pravastatin (anti-hyperlipidemic) when administrated in combination. The studies conducted on rats dosed with gliclazide, pravastatin individually and in combination. Statistical comparisons of plasma concentration – response study in groups with gliclazide alone, pravastatin alone and in combination was carried out. The response study among concentrations and time were calculated employing student’s paired T-Test. The results indicate that gliclazide is completely absorbed with peak plasma concentration of 6.82±0.12 ng/ml and 7.82±0.12 ng/ml when administrated alone and 7.22±0.12 ng/ml and 7.22±0.12 ng/ml when administrated in combination in diabetic rats on first day (day 1) and eighth day (day8) respectively. Similarly peak plasma concentration of pravastatin are 3.92±0.03 ng/ml  and 4.80±0.04 ng/ml when administrated alone and 3.683±0.02 ng/ml    and 4.657±0.04 ng/ml when administrated in combination in diabetic rats  on first day (day 1) and eighth day (day 8) respectively.There was no  statistically noteworthy variation observed  in peak plasma concentration (P>0.05).  Similarly no variations observed in values of tmax, AUC and T1/2. The fasting serum glucose concentrations in normal and STZ-induced diabetic group on first day (day 1) and eighth day (day 8) were analyzed. The reduction of blood glucose levels at different time intervals on administration of gliclazide and pravastatin alone and in combination analyzed and results indicate no significant change in pharmacodynamic parameters. \u0000Hence the results conclude that combinational therapy of gliclazide and pravastatin were found safe and highly potential in treating hyperlipidemia patients.","PeriodicalId":14278,"journal":{"name":"International Journal of Pharmaceutical Sciences and Drug Research","volume":null,"pages":null},"PeriodicalIF":0.0,"publicationDate":"2020-11-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"86020342","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Development and Validation of Stability Indicating RP-HPLC Method for the Simultaneous Estimation of Dapagliflozin Propanediol and Metformin Hydrochloride in Tablet Dosage Form","authors":"N. S. Patel, B. Patel","doi":"10.25004/ijpsdr.2020.120609","DOIUrl":"https://doi.org/10.25004/ijpsdr.2020.120609","url":null,"abstract":"A rapid, precise, accurate, specific and simple stability indicating RP-HPLC method was developed for simultaneous estimation of Dapagliflozin Propanediol (DAPA) and Metformin Hydrochloride (MET) in its tablet dosage form. Method was performed on a column C8 Thermoquest, hypersil division of dimension 250 mm × 4.60 mm having particle size 5 micron. The mobile phase used in the method was 10 mM Ammonium Acetate buffer (pH- 4), Methanol and Acetonitrile in proportion of 30:65:05 respectively. The drug was subjected to acid and alkali hydrolysis, oxidation, photolysis and heat as stress conditions. The method was validated for specificity, linearity, range, precision, accuracy, robustness, LOD, LOQ and system suitability. The flow rate was maintained at 0.8 ml/ min and effluent was monitored at 227 nm. The retention time were observed 5.988 min and 4.661 min for DAPA and MET respectively.  The standard curve was found linear over range of 60-140 μg/ml for DAPA and 300-700 μg/ml for MET with correlation coefficient of 0.9996 for DAPA and 0.9994 for MET. The limit of Detection (LOD) of this method was 1.121 μg/ml for DAPA and 6.162 μg/ml for MET. The limit of Quantitation (LOQ) of this method was 3.396 μg/ml for DAPA and 18.674 μg/ml for MET.  The percentage recovery was found to be in the range of 98-102% at three different levels of a standard addition. The precision (repeatability, intra-day and inter-day) of the method was within the limit (RSD<2%). Degradation products produced because of stress studies did not interfere with the detection of DAPA and MET and the assay can thus be considered stability-indicating. Combination tablet was successfully analysed using the developed method.","PeriodicalId":14278,"journal":{"name":"International Journal of Pharmaceutical Sciences and Drug Research","volume":null,"pages":null},"PeriodicalIF":0.0,"publicationDate":"2020-11-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"84478293","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Formulation and Evaluation of Flurbiprofen Solid Dispersions Incorporated Buccal Patches","authors":"M. Sadik, Abdullah Khan","doi":"10.25004/ijpsdr.2020.120611","DOIUrl":"https://doi.org/10.25004/ijpsdr.2020.120611","url":null,"abstract":"Flurbiprofen is an anti-inflammatory drug used in treating rheumatoid arthritis and ankylosing spondylitis. The present work is aimed at overcoming the deprived solubility of flurbiprofen by solid dispersion (SD) technique. The current paper is  the continuance of the published solid dispersion by considering the best final optimized formulation containing flurbiprofen drug: AQOAT AS: SLS as drug: polymer: surfactant in 1:5:2 ratios, and incorporating it into buccal patches to overcome the gastric side effect and attaining  sustained drug release. In this study 15 buccal patches  were formulated  by adopting  solvent casting technique  using polymers like polyvinyl hydroxyethylcellulose (HEC), hydroxypropryl methyl cellulose E15 (HPMC E15), polyvinyl pyrrolidone (PVP), carbopol and analyzed  for the drug content, drug  diffusion, in-vivo dissolution  and stability studies. All SD loaded patches displayed superior drug release (95% to 99.96%) over 12 h. The formulation BP14 showed excellent drug release extended over 12 h with drug release of 99.96% whereas marketed formulation which is sustained release Tablet showed 96.86% drug release within 6 h. The drug release kinetics show that the buccal patches follow zero order release kinetics with correlation coefficient (R2) ranging between 0.905-0.971 and BP14 formulation shown best R2 value. All the formulations exhibited best fit to Higuchi model with R2 ranging between 0.9911 – 0.9962 indicating drug release by diffusion process. The results conclude that buccal patches are superior alternatives for flurbiprofen that facilitates enhanced drug release for prolonged period of time in the effective management of rheumatoid arthritis.","PeriodicalId":14278,"journal":{"name":"International Journal of Pharmaceutical Sciences and Drug Research","volume":null,"pages":null},"PeriodicalIF":0.0,"publicationDate":"2020-11-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"91510557","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"ANTIUROLITHIATIC ACTIVITY OF NATURAL CONSTITUENTS ISOLATED FROM AERVA LANATA FLOWERS","authors":"Subhashini Naikal James Prameela, Shilpika Nagula","doi":"10.25004/ijpsdr.2020.120610","DOIUrl":"https://doi.org/10.25004/ijpsdr.2020.120610","url":null,"abstract":"A well-known traditional herb Aerva lanata, broadly used in India for treatment of different ailments such as urolithiasis. Pashanabheda is used as antiurolithiatic in Ayurveda. In the present study, flowers of A. lanata were selected for isolation of active constituents and screening for in vitro antiurolithiatic potentials, as literature supports that flowers have the highest quantity of natural components when compared with the other parts. Hydroalcoholic (80%-water, 20%-alcohol) extract of A. lanata flowers was prepared and fractionation with different organic solvents.. The two fractions (ethyl acetate and n-butanol) were subjected to isolation of active constituents using column chromatography technique, followed by purification of the isolated constituents by preparative high performance thin layer chromatography (HPTLC)and then the individual components were characterized by IR spectrophotometery. Finally, in vitro antiurolithiatic activity was screened by nucleation and aggregation assay. In the aggregation assay, gradual decrease in the calcium oxalate (CaOx) crystal nucleation as well as growth was observed by light microscopy. The findings of the nucleation assay indicate that phytoconstituents inhibited the crystallization of CaOx in solution. The size and the number of calcium oxalate crystals decreased with increasing concentration of the phytoconstituents. The increasing concentrations of Quercetin and betulin (100, 200, 300, 400 and 500 μg/mL) inhibited the CaOx crystal growth. The isolated quercetin and betulin from A. lanata have shown antiurolithiatic effect by significantly reducing the CaOx crystal growth.","PeriodicalId":14278,"journal":{"name":"International Journal of Pharmaceutical Sciences and Drug Research","volume":null,"pages":null},"PeriodicalIF":0.0,"publicationDate":"2020-11-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"78532369","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Formulation and Evaluation of Gliclazide Solid Dispersions Incorporated Tablets for Controlled Drug Release","authors":"R. Sunitha, K. Venugopal, S. Satyanarayana","doi":"10.25004/ijpsdr.2020.120606","DOIUrl":"https://doi.org/10.25004/ijpsdr.2020.120606","url":null,"abstract":"The current study deals with formulation and evaluation of gliclazide solid dispersion with HP β Cyclodextrin to enhance solubility and incorporate into tablet formulation for controlled release of gliclazide. Gliclazide solid dispersion (SD) prepared using varying ratios of HP β Cyclodextrin and evaluated. The optimized SD formulation incorporated into tablet by using hydroxypropyl cellulose, HPMC K 100M. The drug dissolution from tablet formulation analyzed and characterize. The formulation SD3 comprising of drug and polymer in 1:3 ratio displayed 43-fold increase in solubility when compared to pure drug. The formulation SD13 displayed maximum yield of 98.96% and maximum drug content of 99% chosen optimal for tablet formulation. FTIR studies revealed that there is no incompatibility between drug and polymers found. XRD studies revealed that the optimized solid dispersion formulation was found to be in amorphous state. Around 15 formulations of controlled release tablet blends evaluated for micrometric properties show that all the formulations posses’ good flow properties. Formulation F15 with maximum drug content of 99.99% and drug release of 99.96 % over 16h was chosen optimal and characterized. The release kinetics suggest that drug release followed zero order and release from tablets was anomalous non- fickian diffusion super case II transport. The results show that combination of solid dispersion and application of hydrophilic and hydrophobic polymers in matrix formation can facilitate better dissolution and absorption profile with greater patient compliance.","PeriodicalId":14278,"journal":{"name":"International Journal of Pharmaceutical Sciences and Drug Research","volume":null,"pages":null},"PeriodicalIF":0.0,"publicationDate":"2020-11-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"74414223","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Molecular-Docking Study of quinazolin-4(3H)-one derivatives against GABAa Receptor Signifies the Novel Approach to Epilepsy Treatment","authors":"Suraj G. Malpani, P. Mohanty, Ashish Jain","doi":"10.25004/ijpsdr.2020.120521","DOIUrl":"https://doi.org/10.25004/ijpsdr.2020.120521","url":null,"abstract":"Nowadays, a lot of new active substances as antiepileptic agents have been developed. One of the protein targets of antiepileptic is selective GABA. Selective GABA is the regulator of CNS activity. In this research, quinazolinone derivatives were used to design the antiepileptic agent through a selective GABA activation. The potential activity of quinazolinone derivatives could be increased by substitution in position 3 of quinazolinone. Molecular docking of selective GABA activation was required to predict their antiepileptic activity. The molecular docking of quinazolinone derivatives was carried out using Autodock viva Ver.1.1.2. Twenty quinazolinone derivatives were docked into GABAa with PDB code 4cof. The interaction was evaluated based on the docking score. Diazepam was used as the reference standard for this research. Twenty quinazolinone derivatives showed the approximate docking score -7.1 to -9.3 kcal/mol. All twenty quinazolinone derivatives which value that have greater docking score compared to diazepam used as a standard compound. Derivative Q-18 had higher binding energy than other quinazolinone derivatives because it has the smallest docking score. All new quinazolinone derivatives are feasible to be synthesize and performed their in vitro evaluation.","PeriodicalId":14278,"journal":{"name":"International Journal of Pharmaceutical Sciences and Drug Research","volume":null,"pages":null},"PeriodicalIF":0.0,"publicationDate":"2020-09-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"85602898","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}