ABSTRACT
OBJECTIVE： To prepare insoluble anti-tumor drug-loading polymer micelles， and to increase inhibitive effect of insoluble anti-tumor drug. METHODS： Chitosan （CSO） and stearic acid （SA） were used to prepare blank micelles （CSO-SA）， then modified with mPEG and folic acid （FA） to prepare PEG-CSO-SA and FA-PEG-CSO-SA. Characteristic functional groups of CSO-SA， PEG-CSO-SA and FA-PEG-CSO-SA were detected by infrared spectroscopy. The morphology of micelles was observed by transmission electron microscopy. The particle size and Zeta potential of micelles were measured by laser particle size analyzer. Osthole （OST） was used as the model drug and drug-loading micelles （FA-PEG-CSO-SA/OST） were prepared by dialysis. MTT assay was used to detect the inhibitory rate of FA-PEG-CSO-SA， OST solution and FA-PEG-CSO-SA/OST to human liver cancer cell HepG2. Half inhibitory concentration （IC50） was calculated. RESULTS： FA-PEG-CSO-SA was successfully prepared. CSO-SA， PEG-CSO-SA， FA-PEG-CSO-SA were oval in shape； particle sizes were （96.01±5.99）， （112.93±1.06）， （216.01±4.76） nm （n＝3） and Zeta potentials were （39.30±1.75）， （38.03±2.91）， （15.17±2.10） mV （n＝3）， respectively. Encapsulation efficiency and drug-loading amount of OST in FA-PEG-CSO-SA were （84.47±2.07）％ and （16.01±0.90）％ （n＝3）， respectively. The inhibition rates of FA-PEG-CSO-SA to HepG2 cells were＜20％. IC50 of OST solution and FA-PEG-CSO-SA/OST to HepG2 cells were （62.08±5.21）， （27.49±0.50） μg/mL （n＝3）， respectively. CONCLUSIONS： Prepared FA-PEG-CSO-SA can significantly increase inhibitive effect of insoluble drug OST to HepG2 cells， and it is expected to become a new anti-tumor drug carrier.
ABSTRACT
OBJECTIVE:To develop a method for simultaneous determination of geniposide,baicalin,aloe-emodin,rhein, emodin,chrysophanol and physcion in Zhizi jinhua dispersible tablets. METHODS:HPLC method was adopted. The determination was performed on Dimonsil C18 column with mobile phase consisted of methanol-0.05%phosphoric acid(gradient elution)at the flow rate of 0.8 mL/min. The detection wavelength was set at 254 nm,and the column temperature was 25℃. The sample size was 20 μL. RESULTS:The linear ranges of geniposide,baicalin,aloe-emodin,rhein,emodin,chrysophanol and physcion were 0.0323-0.323 μg (r=0.9998),0.1374-1.374μg(r=0.9999),0.00372-0.0372μg(r=0.9997),0.0069-0.069μg(r=0.9995),0.00332-0.0332μg (r=0.9997),0.00864-0.0864 μg(r=0.9997) and 0.00122-0.0122 μg(r=0.9995),respectively. The limits of quantitation were 0.0321,0.1374,0.00372,0.0067,0.00330,0.00864,0.00122 μg,respectively. The limits of detection were 0.0095, 0.0041,0.0012,0.0020,0.0010,0.0026,0.0003 μg,respectively. RSDs of precision,stability and reproducibility tests were all lower than 3%. The average recoveries were 96.54%-99.52%(RSD=1.17%,n=6),97.23%-101.23%(RSD=1.36%,n=6), 97.22%-101.25%(RSD=1.83%,n=6),97.32%-100.23%(RSD=1.09%,n=6),97.99%-102.71%(RSD=1.73%,n=6), 96.99%-100.23%(RSD=1.21%,n=6),96.99%-103.01%(RSD=2.31%,n=6),respectively. CONCLUSIONS:The methods is simple and reproducible. It can be used for the content determination of 7 components in Zhizi jinhua dispersible tablets.
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OBJECTIVE:To prepare Baicalin monolithic osmotic pump tablets and investigate its in vitro drug release behavior. METHODS:Using accumulative release rate as evaluation index,baicalin solid dispersion was prepared to improve solubility,sin-gle factor test and orthogonal test were used to optimize preparation technology(the amount of penetrating agent and pore-forming agent,weight gaining of coating film) of monolithic osmotic pump tablets using baicalin solid dispersion as intermediate. Release rate and mechanism of samples prepared by optimized technology were investigated in 3 kinds of release medium (water,0.1 mol/L HCl,simulated gastric fluid). RESULTS:The optimal preparation technology was that penetrating agent sodium chloride was 30 mg;pore-forming agent polyethylene glycol 400 was 20% amount of excipient cellulose acetate;weight gaining of coating film was 2%. RSD of 12 h accumulative release rate was 1.06%(n=3)for 3 batches of Baicalin monolithic osmotic pump tablets pre-pared by optimized technology. 12 h accumulative release rate of them in 3 kinds of medium were similar to each other,being all more than 80%. Release equation was in line with zero-order drug release model (r=0.9985). CONCLUSIONS:Prepared Ba-icalin monolithic osmotic pump tablets after optimization can release drug at controlled rate.
ABSTRACT
OBJECTIVE:To establish a method for the contents determination and cluster analysis of free and combined anthra-quinone of aloe emodin,rhein,emodin,rhubarb phenol and physcion in commercially available Yiqing granule from different man-ufacturers. METHODS:HPLC was performed on the column of Eclipse plus C18 with mobile phase of methanol-0.1%Phosphoricac-id solution (gradient elution) at a flow rate of 0.8 ml/min,the detection wavelength was 254 nm,the column temperature was 25 ℃,and the injection volume was 20 μl. RESULTS:The linear range was 0.001 6-0.128 0 μg for aloe emodin(r=0.999 9), 0.003 4-0.273 6 μg for rhein(r=0.999 9),0.003 7-0.299 2 μg for emodin(r=0.999 9),0.006 7-0.536 0 μg for rhubarb phenol (r=0.999 9)and 0.001 7-0.134 4 μg(r=0.999 9)for physcion;RSDs of precision,stability and reproducibility tests were lower than 3%;recoveries were 97.77%-101.47%(RSD=1.30%,n=6),98.09%-100.26%(RSD=0.76%,n=6),96.42%-100.38%(RSD=1.58%,n=6),96.63%-102.50%(RSD=2.17%,n=6) and 97.10%-103.70%(RSD=2.47%,n=6),respectively;the content range of total anthraquinone was 0.042-0.218 mg/g, 0.029-0.448 mg/g, 0.022-0.167 mg/g, 0.032-0.284 mg/g and 0.006-0.060 mg/g,combined anthraquinone was 0.010-0.111 mg/g,0.013-0.092 mg/g,0.011-0.097 mg/g,0.030-0.246 mg/g and 0.001-0.034 mg/g,and free anthraquinone was 0.022 3-0.143 mg/g,0.015-0.356 mg/g,0.008-0.071 mg/g,0.006-0.075 mg/g and 0.003-0.032 mg/g. Cluster analysis showed there were 4 batches belonged to Category 1,2 batches belonged to Category 2 and 4 batches belonged to Category 3 for the total anthraquinone in 5 components;4 bathes belonged to Category 1,2 batches belonged to Category 2 and 4 batches belonged to Category 3 for the combined anthraquinone;and 6 bathes belonged to Category 1 and 4 batches belonged to Category 2 for the free anthraquinone. CONCLUSIONS:The method is simple and accurate,and can provide reference for improving the quality and diarrhea efficacy control of Yiqing granule;there were great differences in Rheum palma-tum and combined anthraquinone from different manufacturers.