Luye Pharmaceutical Co.

Yantai, China

Luye Pharmaceutical Co.

Yantai, China

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Sun Y.,CAS Qingdao Institute of Oceanology | Sun Y.,Shandong University of Traditional Chinese Medicine | Zhang J.,Shandong Academy of Occupational Health and Occupational Disease | Yan Y.,Shandong Academy of Occupational Health and Occupational Disease | And 4 more authors.
Environmental Toxicology and Pharmacology | Year: 2011

To investigate the potential protective effect of C-phycocyanin (PC) on paraquat (PQ)-induced acute lung injury, rats were divided into control, PQ-treated and PQ. +. PC-treated groups. Rats in PQ-treated group were orally administered with 50. mg/kg PQ, and rats in PQ. +. PC-treated group were intraperitoneally injected with 50. mg/kg PC after administration of PQ. At 8, 24, 48 and 72. h after treatments, GSH-Px and SOD activities, MDA levels in plasma and BALF, HYP, NF-κB, IκB-α and TNF-α contents in lung tissues were measured. The pathological changes in lung were observed. After treatment with PC, the levels of MDA and the relative contents of NF-κB and TNF-α were significantly decreased, the activities of GSH-Px and SOD and the relative contents of IκB-α were significantly increased. The degree of rat lung damage was obviously reduced in PQ. +. PC-treated group. The results suggested that PC treatment significantly attenuated PQ-induced acute lung injury. © 2011 Elsevier B.V.


Wu F.-K.,Shenyang Pharmaceutical University | Wu F.-K.,Xiamen Institute for Drug Control | Qiu Y.-K.,Xiamen University | Zhao H.-Y.,Xiamen University | And 4 more authors.
Journal of Asian Natural Products Research | Year: 2011

To study the chemical composition of the skin of Bufo bufo gargarizans, various chromatographic methods were used in the isolation procedures and the structures of isolated compounds were determined based on NMR and MS analysis. As a result, two new compounds were isolated from its ethanolic extract and characterized as N-[2-hydroxy-2-(4-hydroxyphenyl)ethyl]-N-methylurea (1) and 19-oxocinobufotalin 3-adipoylarginine ester (2), together with 11 known compounds. Isolated bufadienolides showed significant inhibition effect against human hepatocellular carcinoma cell line SMMC-7721 in vitro. © 2011 Taylor & Francis.


Zhao H.-Y.,Xiamen University | Wu F.-K.,Xiamen Institute for Drug Control | Qiu Y.-K.,Xiamen University | Wu Z.,Xiamen University | And 2 more authors.
Journal of Asian Natural Products Research | Year: 2010

To study the chemical composition of the skin of Bufo bufo gargarizans, many kinds of chromatography methods were used in the isolation procedures, while the structures of isolated compounds were determined on the basis of their NMR and MS spectral analysis. As a result, two new compounds were isolated from its ethanolic extract and characterized as cinobufotalin 3-nonanedioylarginine ester (8) and bufotalin 3-pimeloylarginine ester (14). Furthermore, 13 known compounds were obtained. Isolated bufadienolides showed significant inhibition effect against SMMC-7721 cell lines in vitro. © 2010 Taylor & Francis.


Zhang R.R.,Jilin University | Zhang R.R.,Luye Pharmaceutical Company Ltd | Li X.,Jilin University | Li X.,Luye Pharmaceutical Company Ltd | And 15 more authors.
PLoS ONE | Year: 2014

Triple reuptake inhibitors (TRIs) are currently being developed as a new class of promising antidepressants that block serotonin (5-HT), dopamine (DA) and norepinephrine (NE) transporters, thereby increasing extracellular monoamine concentrations. The purpose of this study was to investigate the effects of LPM570065, a novel TRI and a desvenlafaxine prodrug, on extracellular 5-HT, DA and NE levels in the rat striatum after acute and chronic administration relative to desvenlafaxine, using High Performance Liquid Chromatography (HPLC) and microdialysis. Acute administration was performed by providing rodents with oral solutions (0.06 mmol•kg-1 p.o.), oral suspensions (0.06 mmol•kg-1 p.o.) and intravenous solutions (0.04 mmol•kg-1 i.v.) of LPM570065 and desvenlafaxine. Oral suspensions (0.06 mmol•kg-1•day21) of the two drugs were also administered for a 14-day chronic period. HPLC analysis revealed that LPM570065 rapidly penetrated the rat striatum, converted into desvenlafaxine and exhibited larger total exposure compared with the administration of desvenlafaxine. Microdialysis revealed that acute and chronic administration of oral suspension of LPM570065 increased the 5-HT, DA and NE levels more than the relative administration of desvenlafaxine. Unlike desvenlafaxine, acute administration of an intravenous LPM570065 solution did not induce the undesirable 90% decrease in extracellular 5-HT levels. In contrast to the fully dose-dependent elevation of 5-HT induced by desvenlafaxine, the acute administration of LPM570065 showed a capped increase in extracellular 5-HT levels when combined with WAY-100635. Additionally, forced swim test demonstrated that acute and chronic administration of LPM570065 reduced the immobility time more than the relative administration of desvenlafaxine. These data suggest that LPM570065 may have greater efficacy and/or a more rapid onset of antidepressant action than desvenlafaxine and also counterbalance the harmful effects of desvenlafaxine on 5-HT neurotransmission related to 5-HT1A autoreceptors. Thus, this new class of drugs, TRIs has the potential to provide a new therapeutic mechanism for treating depression. © 2014 Zhang et al.


Shi Y.,Jilin University | Shi Y.,Luye Pharmaceutical Co | Huang W.,Jilin University | Liang R.,Jilin University | And 11 more authors.
International Journal of Nanomedicine | Year: 2013

To improve the pharmacokinetics and stability of recombinant human erythropoietin (rhEPO), rhEPO was successfully formulated into poly(ethylene glycol)-poly(d,l-lactide) (PEG-PLA) di-block copolymeric micelles at diameters ranging from 60 to 200nm with narrow poly-dispersity indices (PDIs; PDI<0.3) and trace amount of protein aggregation. The zeta potential of the spherical micelles was in the range of -3.78 to 4.65mV and the highest encapsulation efficiency of rhEPO in the PEG-PLA micelles was about 80%. In vitro release profiles indicated that the stability of rhEPO in the micelles was improved significantly and only a trace amount of aggregate was found. Pharmacokinetic studies in rats showed highly enhanced plasma retention time of the rhEPO-loaded PEG-PLA micelles in comparison with the native rhEPO group. Increased hemoglobin concentrations were also found in the rat study. Native polyacrylamide gel electrophoresis results demonstrated that rhEPO was successfully encapsulated into the micelles, which was stable in phosphate buffered saline with different pHs and concentrations of NaCl. Therefore, PEG-PLA micelles can be a potential protein drug delivery system. © 2013 Shi et al, publisher and licensee Dove Medical Press Ltd.


Shi Y.,Jilin University | Shi Y.,Luye Pharmaceutical Co. | Sun F.,Jilin University | Wang D.,Jilin University | And 11 more authors.
Journal of Nanoparticle Research | Year: 2013

A composite micelle of ionic complex encapsulated into poly(ethylene glycol)-poly(d,l-lactide) (PEG-PLA) di-block copolymeric micelles was used for protein drug delivery to improve its pharmacokinetic performance. In this study, recombinant human erythropoietin (rhEPO, as a model protein) was formulated with lysine into composite micelles at a diameter of 71.5 nm with narrow polydispersity indices (PDIs < 0.3). Only a trace amount of protein was in aggregate form. The zeta potential of the spherical micelles was ranging from -0.54 to 1.39 mv, and encapsulation efficiency is high (80 %). The stability of rhEPO was improved significantly in composite micelles in vitro. Pharmacokinetic studies in rats showed significant, enhanced plasma retention of the composite micelles in comparison with native rhEPO. Areas under curve (AUCs) of the rhEPO released from the composite micelles were 4.5- and 2.3-folds higher than those of the native rhEPO and rhEPO-loaded PEG-PLA micelle, respectively. In addition, the composite micelles exhibited good biocompatibility using MTT (3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyl tetrazolium bromide) assay with human embryonic kidney (HEK293T) cells. All these features are preferable for utilizing the composite micelles as a novel protein delivery system. © 2013 Springer Science+Business Media Dordrecht.


Li X.-J.,Yantai University | Zhang X.-M.,Yantai University | Zhang X.-M.,Luye Pharmaceutical Co. | Wang M.,Yantai University | And 3 more authors.
Chinese Journal of New Drugs | Year: 2016

Objective: To prepare nanoparticles containing curcumin modified by tumor penetrating peptides, iRGD, and to evaluate their physicochemical characters and potential tumor targeting performance in vitro and in vivo. Methods: The iRGD-PEG-PLGA was synthesized by thiol method, and the iRGD-modified curcumin nanoparticles were prepared by nanoprecipitation. The particle size, encapsulation efficiency, drug loading and in vitro release behavior were investigated. Flow cytometry and laser confocal microscopy were used to investigate tumor cellular uptake in vitro. In vivo imaging system was used to investigate its penetrating and targeting ability in the tumor-bearing nude mice. Results: The average particle size of iRGD-modified curcumin nanoparticles was (83.9±1.6) nm, the encapsulation efficiencies was (81.32±2.83)%, and the drug loading was (3.07±0.15)%. The accumulative release amount was approximately 80%, and the modification of iRGD did not affect the physicochemical characters of the nanoparticles. The results of cellular uptake in vitro indicated that the targeting activity of the iRGD-modified nanoparticles was higher than that of unmodifid nanoparticles, and they were located around the nucleus in the tumor cell. In vivo imaging of the iRGD-modified nanoparticles exhibited the remarkable tumor targeting ability in nude mice. Conclusion: iRGD-modified nanoparticles show the significant targeting and penetrating ability in cellular uptake and in vivo imaging. This will be a promising drug delivery system of anti-cancer drugs. © 2016, Chinese Journal of New Drugs Co. Ltd. All right reserved.


Zhang F.-P.,Yantai University | Ma P.-K.,Yantai University | Wang Z.,Yantai University | Lian S.-N.,Yantai University | And 2 more authors.
Chinese Journal of New Drugs | Year: 2015

Objective: To prepare insulin-loaded microspheres with a novel biodegradable material termed polyketal(PCADK) and evaluate their release behavior in vitro. Methods: The polyketal (PCADK) was synthesized by using 1, 4-cyclohexanedimethanol(CDM) and 2, 2-dimethoxypropane (DMP). The chemical structure of PCADK was confirmed by 1H NMR and the molecular weights(Mw) of the polymers were determined by gel permeation chromatography (GPC); the microspheres were fabricated through a new solvent evaporation process-in-situ S/O/W process. The drug loading and encapsulation efficiency were detected and calculated via HPLC; the release experiment of microspheres was conducted in phosphate buffer solution(pH=2.0, 4.5, 7.4). Results: A polymer with an Mw of approximately 6 500 was obtained; the prepared microspheres had round appearance and plicate surface with drug loading of about 3.90% and encapsulation efficiency of 68%; the in vitro release experiments showed that the microspheres degraded faster in acid solution than that in alkaline and neutral environment. Conclusion: The microspheres prepared by the novel polymer material-PCADK have high drug loading and encapsulation efficiency as well as pH-sensitive release kinetics. ©, 2015, Chinese Journal of New Drugs Co. Ltd. All right reserved.

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