2.Quality by design based high shear wet granulation process development for the microcrystalline cellulose.
Gan LUO ; Bing XU ; Fei SUN ; Xiang-long CUI ; Xin-yuan SHI ; Yan-jiang QIAO
Acta Pharmaceutica Sinica 2015;50(3):355-359
The design space of the high shear wet granulation process was established and validated within the framework of quality by design (QbD). The system of microcrystalline cellulose-de-ioned water was used in this study. The median granule size and bulk density of granules were identified as critical quality attributes. Plackeet-Burmann experimental design was used to screen these factors as follows: dry mixing time, the impeller and chopper speed of dry mixing, water amount, water addition time, wet massing time, the impeller and chopper speed of wet massing and drying time. And the optimization was implemented with the central composite experimental design based on screened critical process parameters. The design space of the high shear wet granulation process was established based on the quadratic polynomial regression model. Since the P-values of both models were less than 0.05 and values of lack of fit were more than 0.1, the relationship between critical quality attributes and critical process parameters could be well described by the two models. The reliability of design space, illustrated by overlay plot, was improved with the addition of 95% confidence interval. For those granules whose process parameters were in the design space, the granule size could be controlled within 250 to 355 μm, and the bulk density could be controlled within a range of 0.4 to 0.6 g x cm(-3). The robustness and flexibility of the high shear wet granulation process have been enhanced via the establishment of the design space based on the QbD concept.
Cellulose
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chemistry
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Reproducibility of Results
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Technology, Pharmaceutical
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methods
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Water
3.Life quality before and after the treatment of food allergy in infants
Li WANG ; Nianrong WANG ; Wenling GAN ; Jing WEN ; Yan ZHAO ; Xin FAN ; Ya YE
Chinese Journal of Applied Clinical Pediatrics 2015;(21):1649-1651
Objective To investigate the life quality in infants with food allergy before and after treatment by using of Food Allergy Quality of Life Questionnaire - Parent Form(FAQLQ - PF). Methods The severity of eczema in 46 children with food allergy was determined by eczema area and severity index(EASI). The life quality of such infants was assessed by the FAQLQ - PF after 2 - months treatment. Results (1)Among the 50 subjects,46(92% )respon-ded to the tests;the average age was(4. 78 ± 1. 48)months. Twenty - nine(63. 04% )subjects had family history of allergic disease. Egg(73. 91% )was the most common allergen,followed by cow milk(43. 48% ),fish and shrimp (8. 70% ),and carrot(4. 35% ).(2)The scores of EASI,FAQLQ - PF in children with food allergy before treatment were 13. 20 ± 12. 86 and 2. 12 ± 1. 33,respectively,the scores after treatment declined(2. 02 ± 4. 40 and 1. 33 ± 1. 08, respectively),there was a statistical significance(t = 28. 070,4. 014,all P ﹤ 0. 05).(3)Compared with pre - treat-ment,the scores of emotional impact subscale and food anxiety subscale declined,from 2. 10 ± 1. 47 and 2. 63 ± 1. 83 to 1. 30 ± 1. 09 and 1. 68 ± 1. 37,respectively,and there were statistically significant differences(t = 5. 204,8. 818,all P ﹤ 0. 05).(4)There was a positive correlation between the EASI and FAQLQ - PF scores(ρ = 0. 205,P ﹤ 0. 05). Conclusions Food allergy adversely affects the quality of life in infants. The poor life quality is associated with more severe symptoms. The life quality in infants and parents can be improved by standardized treatment.
4.The structure characteristics of prophages of foodborne Enterococcus hirae R17 and their interaction relationships with host bacterium
Zixin PENG ; Siyu ZHANG ; Shaofei YAN ; Wei WANG ; Shuai WANG ; Xin GAN ; Jianzhong ZHANG ; Fengqin LI
Chinese Journal of Food Hygiene 2017;29(4):393-399
Objective This study was to understand the structure characteristics of prophages in the genome of Enterococcus hirae R17,and also to analyze their interaction relationships with the host bacterium.Methods The gene distribution and gene encoding characteristics of prophages in the genome of Enterococcus hirae R17 were identified using the PHAST software.The virulence gene,antimicrobial resistance genes,and environmental resistance genes in the prophages were also analyzed.Results Three prophages were found on the chromosome of Enterococcus hirae,including two incomplete prophage elements (Prophage-1 and Prophage-2) and one complete prophage (Prophage-3).Some function genes of bacteria were found in the sequence of three prophages,including nucleotide transportation and metabolism related genes.One incomplete prophage carrying erythromycin-and bacitracin-resistance genes was identified in the plasmid,which suggested that prophage induced gene horizontal transfer caused erythromycin-and bacitracin-resistance of Enterococcus hirae R17.Conclusion This study laid a solid foundation for the diversity analysis of prophages of Enterococcus hirae.Prophages played an important role in promotion of antimicrobial resistance of enterococci.Scientists should pay more attention to the spread of antimicrobial resistance and pathogenicity induced by prophages.
5.Preparation and characterization of irinotecan hydrochloride loaded PEO-PPO-PEO micelles and its mechanism of decreasing drug intestinal toxicity.
Xin-Xin ZHANG ; Shi-Yan GUO ; Fei-Fei LI ; Yong GAN
Acta Pharmaceutica Sinica 2012;47(11):1534-1540
In this work, we developed PEO-PPO-PEO micelles loaded with irinotecan hydrochloride (CPT-11) using breast cancer resistance protein (BCRP) inhibitory material PEO20-PPO70-PEO20, and studied its mechanism of decreasing CPT-11 induced delayed diarrhea and intestinal toxicity. BCRP-overexpressing MDCKII (MDCKII/BCRP) cells were used to evaluate the effect of PEO20-PPO70-PEO20 and PEO-PPO-PEO micelles on transmembrane transport of CPT-11 in vitro. The biliary excretion, delayed diarrhea and intestinal damage of CPT-11 loaded PEO-PPO-PEO micelles of rats were investigated. The results showed that the obtained micelles could decrease the biliary excretion of CPT-11, ameliorate delayed diarrhea and intestinal toxicity of rats through inhibiting BCRP-mediated CPT-11 efflux. PEO-PPO-PEO micelles were promising carriers to reduce intestinal toxicity of CPTs.
ATP Binding Cassette Transporter, Sub-Family G, Member 2
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ATP-Binding Cassette Transporters
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metabolism
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Animals
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Antineoplastic Agents, Phytogenic
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administration & dosage
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adverse effects
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pharmacokinetics
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Bile
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secretion
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Biological Transport
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Camptothecin
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administration & dosage
;
adverse effects
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analogs & derivatives
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pharmacokinetics
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Cells, Cultured
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Diarrhea
;
chemically induced
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drug therapy
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Dogs
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Drug Carriers
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Intestines
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drug effects
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Madin Darby Canine Kidney Cells
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Male
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Micelles
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Neoplasm Proteins
;
metabolism
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Polyethylene Glycols
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administration & dosage
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chemistry
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Propylene Glycols
;
administration & dosage
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chemistry
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Rats
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Rats, Sprague-Dawley
6.Preliminary study on pH-sensitive lipid bilayer-coated mesoporous silica nanoparticles as a novel drug carrier for antitumor drug.
Fei-Fei LI ; Xin-Xin ZHANG ; Shi-Yan GUO ; Yong GAN ; Juan LI
Acta Pharmaceutica Sinica 2013;48(2):291-297
This study plans to prepare lipid bilayer-coated mesoporous silica nanoparticles (LMSNs) which are pH sensitive with core-shell structure to improve the tumor cell lethality of antitumor drug. The lipid coated mesoporous silica nanoparticles loaded with irinotecan (CPT-11) (CPT-11-LMSNs) were prepared by hot water-film hydration method, and the characterized its morphology, particle size and release in vitro. Meanwhile, the intracellular uptake and cell toxicity of CPT-11-LMSNs and intracellular accumulation of CPT-11 were evaluated on human breast carcinoma cell line (MCF-7). The results indicated that the mean diameter of the spherical LMSNs was (120.27 +/- 5.91) nm. The slow release in simulated normal physiological conditions and a rapid release under simulated intracellular condition demonstrated the pH sensitivity of CPT-11-MSNs in vitro. Moreover, the CPT-11-LMSN could improve the intracellular CPT-11 cumulant 2.1 times and reduce half maximal inhibitory concentration (IC50) values of CPT-11 1.4 times compared with CPT-11-MSNs, demonstrating a stronger cell lethality.
Antineoplastic Agents, Phytogenic
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administration & dosage
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pharmacology
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Camptothecin
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administration & dosage
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analogs & derivatives
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pharmacology
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Cell Proliferation
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drug effects
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Drug Carriers
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Humans
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Hydrogen-Ion Concentration
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Lipid Bilayers
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administration & dosage
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chemistry
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MCF-7 Cells
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Nanoparticles
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Particle Size
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Porosity
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Silicon Dioxide
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administration & dosage
;
chemistry
7.Tracing magnetically labeled mesenchymal stem cells transplanted into rat livers by MRI.
Jin-hua CAI ; Gan-sheng FENG ; Xin WANG ; Guan-xin LIU ; De-ying ZHANG ; Lin-yan HU
Chinese Journal of Hepatology 2007;15(3):170-173
OBJECTIVETo trace magnetically labeled MSCs transplanted into the rat livers by magnetic resonance imaging (MRI).
METHODSFeridex and DAPI labeled rat mesenchymal stem cells (MSCs) were injected via portal veins into carbon tetrachloride treated rats. MRI was performed with a clinical 1.5 T MRI machine immediately before the MSCs injection and at h 1, d 3, d 7, and d 14 after the injection, and then the signal-to-noise ratio (SNR) was measured. MRI findings were compared with the liver histopathologies after the slides were stained with fluorescence dye and Prussian blue.
RESULTSThe SNR for liver was 1.10+/-0.26 at hour 1, 8.18+/-1.55 at day 3, 11.08+/-1.30 at day 7, and 14.15+/-1.02 at day 14 respectively. Within 7 days after the MSCs transplantation, the SNRs of the livers were significantly lower than those before the transplantation (P less than 0.05). Histologically, the blue fluorescent particles under the fluorescence microscopy matched in distribution with the iron particles on the Prussian blue stained slides.
CONCLUSIONThe magnetically labeled MSCs transplanted into livers give rise to an obvious signal decrease, and can be tracked with a 1.5 T clinical MRI machine for up to 7 days after MSCs transplantation.
Animals ; Image Enhancement ; methods ; Liver ; pathology ; Magnetic Resonance Imaging ; Male ; Mesenchymal Stem Cell Transplantation ; Radioactive Tracers ; Rats ; Rats, Wistar
8.J Wave Syndromes: History and Current Controversies.
Tong LIU ; Jifeng ZHENG ; Gan Xin YAN
Korean Circulation Journal 2016;46(5):601-609
The concept of J wave syndromes was first proposed in 2004 by Yan et al for a spectrum of electrocardiographic (ECG) manifestations of prominent J waves that are associated with a potential to predispose affected individuals to ventricular fibrillation (VF). Although the concept of J wave syndromes is widely used and accepted, there has been tremendous debate over the definition of J wave, its ionic and cellular basis and arrhythmogenic mechanism. In this review article, we attempted to discuss the history from which the concept of J wave syndromes (JWS) is evolved and current controversies in JWS.
Brugada Syndrome
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Death, Sudden, Cardiac
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Electrocardiography
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Ventricular Fibrillation
9.The effect of oxidative stress in myocardial cell injury in mice exposed to chronic intermittent hypoxia.
Jian-nan LIU ; Jie-xin ZHANG ; Gan LU ; Yan QIU ; Di YANG ; Guo-yong YIN ; Xi-long ZHANG
Chinese Medical Journal 2010;123(1):74-78
BACKGROUNDObstructive sleep apnea syndrome (OSAS) is an important risk factor for cardiovascular diseases. Chronic intermittent hypoxia (CIH) is considered to be one of the most important causes of cardiovascular diseases in OSA patients. This repeated hypoxia and reoxygenation cycle is similar to hypoxia-reperfusion injury, which initiates oxidative stress. In this study, we observed cardiocytes injury induced by CIH and the effect of N-acetylcysteine (NAC).
METHODSThirty ICR mice were randomly assigned to 3 groups: control, CIH and NAC (CIH + NAC) groups. Malondialdehyde (MDA) and superoxide dismutase (SOD) of cardiocyte homogenates were measured. Serum lipids were measured by an instrument method. Serum cardiac troponin I (cTnI) was detected by enzyme-linked immunosorbent assays (ELISA). Myocardium pathological sections were observed.
RESULTS(1) The SOD activity and MDA concentration of cardiocyte homogenates in the CIH group were significantly higher than in other groups (P < 0.005). The MDA concentration of the NAC group was lower than that of the control group (P < 0.01). (2) The serum cTnI concentration of the CIH and NAC groups was significantly higher than that of the control group (P < 0.01). (3) Serum triglyceride levels in the NAC group were lower than in the other groups (P < 0.01), while there were no significant differences in low density lipoprotein and high density lipoprotein among the three groups. (4) The degeneration of myocardium, transverse striation blurred, and fabric effusion were observed in tissue sections in the CIH and NAC groups. However, normal tissue was found in the control group.
CONCLUSIONThe oxidative stress induced by CIH can injure cardiocytes and the injury effect can be partially inhibited by NAC.
Acetylcysteine ; pharmacology ; Animals ; Free Radical Scavengers ; pharmacology ; Heart ; drug effects ; Hypoxia ; physiopathology ; Malondialdehyde ; metabolism ; Mice ; Mice, Inbred ICR ; Myocardium ; metabolism ; pathology ; Oxidative Stress ; physiology ; Random Allocation ; Superoxide Dismutase ; metabolism
10.Transduction efficiency of recombinant adeno-associated virus 2 in human umbilical cord blood CD34+ hematopoietic stem/progenitor cells.
Yan CHEN ; Fang-Ping CHEN ; Jian-Qiang PENG ; Xiao-Bing WU ; Xin-Hua WU ; Gan FU
Journal of Experimental Hematology 2003;11(6):576-578
To investigate the transduction efficiency of recombinant adeno-associated virus 2 (rAAV-2) in human umbilical cord blood CD34(+) hematopoietic stem/progenitor cells, the CD34(+) cells sorted by the method of magnetic cell sorting from human cord blood were infected with the rAAV-2 expressing the green fluorescent protein (GFP) gene. After transduction for 19 hours, the expression of GFP was detected under fluorescence microscope. The results showed that 43% CD34(+) cells expressed the GFP gene at a multiplicity of infection of 2 x 10(5). It is concluded that the rAAV-2 can transduce human cord blood CD34(+) hematopoietic stem/progenitor cells efficiently.
Antigens, CD34
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analysis
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Dependovirus
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genetics
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Fetal Blood
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cytology
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Genetic Therapy
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Green Fluorescent Proteins
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Hematopoietic Stem Cells
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metabolism
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Humans
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Luminescent Proteins
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genetics
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Recombination, Genetic
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Transduction, Genetic