The objectives of the present study were to prepare stealthy etoposide proliposomes and study the pharmacokinetics in rabbits. Blank stealthy liposomes were prepared by film dispersion method. Stealthy etoposide lipos...The objectives of the present study were to prepare stealthy etoposide proliposomes and study the pharmacokinetics in rabbits. Blank stealthy liposomes were prepared by film dispersion method. Stealthy etoposide liposomes were prepared by using the ammonium sulfate gradient loading procedure. Vacuum freeze-drying technique was used to dry stealthy etoposide liposomes. Encapsulation efficiency of stealthy etoposide proliposomes was determined by Sephadex chromatography. The morphology was observed by transmission electronic microscope. The particle size and zeta potential were measured by using electrophoretic light scattering technology. The pharmacokinetics in rabbits was evaluated by comparison with etoposide injection and conventional liposomes, respectively. Mean encapsulation efficiency of stealthy etoposide proliposomes was 83.92% ± 3.65% （n = 3）. The liposomes were round or oval. Mean particle size was （124.5 ±26.9） nm, and zeta potential was （-39.50 ±1.04） mV. Following intravenous injection administration at a dose of 1.5 mg/kg etoposide, the three kinds of etoposide preparations were fitted with the two-compartment model. T1/2 β and A UC values of stealthy etoposide proliposomes were （19.26 ± 3.16） h and （26.04 ±3.53） μg/h/mL, respectively. T1/2 β and AUC values of etoposide injection were （0.94 ± 0.21） h and （0.98 ± 0.26） μg/h/mL, respectively. T1/2β and AUC values of conventional liposomes were （7.99 ± 1.36） h and （11.65 ± 1.70） μg/h/mL, respectively. Results indicated that the stealthy etoposide proliposomes could significantly extend the duration of etoposide in blood circulation.展开更多
Aim The objectives of the present study were to prepare stealthy vincristine plus quinacrine liposomes and evaluate the pharmacokinetics in Sprague-Dawley rats. Methods Anti-resistant stealthy liposomes were prepared ...Aim The objectives of the present study were to prepare stealthy vincristine plus quinacrine liposomes and evaluate the pharmacokinetics in Sprague-Dawley rats. Methods Anti-resistant stealthy liposomes were prepared by incorporating vincristine with quinacrine together using the ammonium sulfate gradient loading procedure. For the pharmacokinetic study, Sprague-Dawley rats were divided into two groups： each rat in the Group Ⅰwas administered intravenously via tail vein as stealthy liposomal vincristine plus quinacrine, and the Group Ⅱ similarly given as a mixture solution of free vincristine plus free quinacrine. The concentrations of vincristine and quinacrine in plasma were measured by HPLC with diode array detection and fluorescence detection, respectively. Results The mean particle size of stealthy liposomes was 135.9 ±7.1 nm and the encapsulation efficiencies of stealthy liposomes were 〉 90% for vincristine, and 〉 85% for quinacrine, respectively. Administered as the stealthy vincristine plus quinacrine liposomes, the plasma exposures of both vincristine and quinacrine were significantly extended, and the mean concentrations of both vincristine and quinacrine were significantly higher compared to those given as the mixture solution of free vincristine plus free quinacrine. The Cmax, t1/2, AUC0-24 h values of vincristine for stealthy liposomal group were significantly increased, but the total clearance Cl values decreased, as compared to those of free drug group, respectively. Similarly, the Cmax, t1/2 and AUC0-24 h values of quinacrine for the stealthy liposomal group were significantly increased, but the total clearance C1 values decreased, as compared to those of free quinacrine. Conclusion The anti-resistant stealthy liposomes are successfully prepared by incorporating vincristine with quinacrine, and the liposomes extend significantly the duration in blood circulation and improve evidently the plasma concentrations of both vincristine and quinacrine.展开更多
Aim To develop and validate a RP-HPLC method for the analysis of paclitaxel in a solid dispersion. Methods Paclitaxel and the internal standard norethisterone were separated using a Phenomenex ODS 3 column and monitor...Aim To develop and validate a RP-HPLC method for the analysis of paclitaxel in a solid dispersion. Methods Paclitaxel and the internal standard norethisterone were separated using a Phenomenex ODS 3 column and monitored at a wavelength at 227 nm. The isocratic mobile phase consisting of methanol-acetonitrile-water （40：30：30, V/V） was pumped at a flow-rate of 1.0 mL·min^-1. The dissolution studies were performed according to published studies. Results Under these chromatographic conditions, the calibration curve was linear in the range of 4-40 μg·mL ^-1 with the correlation coefficient of 0.9999. The mean recovery was 98.42 % （RSD = 1.19 %）. At the 60 min time point, the dissolution of paclitaxel from the solid dispersion was nearly 100 %, however, the original form of paclitaxel was about 30 %. Conclusion The method was proven to be specific, accurate and precise for determining the dissolution of paclitaxel from solid dispersion.展开更多
Gelatin has been used in hard capsule shells for more than a century, and some shortcomings have appeared, such as high moisture content and risk of transmitting diseases of animal origin to people. Based on available...Gelatin has been used in hard capsule shells for more than a century, and some shortcomings have appeared, such as high moisture content and risk of transmitting diseases of animal origin to people. Based on available studies regarding gelatin and vegetable shells, we developed a new type of algal polysaccharide capsule (APPC) shells. To test whether our products can replace commercial gelatin shells, we measured in-vivo plasma concentration of 12 selected volunteers with a model drug, ibuprofen, using high performance liquid chromatography (HPLC), by calculating the relative bioavailability of APPC and Qualicaps referenced to gelatin capsules and assessing bioequivalence of the three types of shells, and calculated pharmacokinetic parameters with the software DAS 2.0 (China). The results show that APPC shells possess bioequivalence with Qualicaps and gelatin shells. Moreover, the disintegration behavior of four types of shells (APPC, Vegcaps , Qualicaps and gelatin shells) with the content of lactose and radioactive element (99mTc) was observed via gamma-scintigraphic images. The bioavailability and gamma-scintigraphic studies showed that APPC was not statistically different from other vegetable and gelatin capsule shells with respect to in-vivo behavior. Hence, it can be concluded that APPCs are exchangeable with other vegetable and gelatin shells.展开更多
Aflatoxins are produced mainly by Aspergillus flavus and Aspergillus parasiticus, and can be found in many grains such as peanuts, soybeans and com. This study aimed to qualitatively and quantitatively evaluate the pr...Aflatoxins are produced mainly by Aspergillus flavus and Aspergillus parasiticus, and can be found in many grains such as peanuts, soybeans and com. This study aimed to qualitatively and quantitatively evaluate the production of aflatoxin in liquid media using strains of Aspergillus flavus obtained from peanuts marketed in the city of Fortaleza, CEo Strains of Aspergillus flavus were inoculated into a liquid medium malt extract and after 2 days inoculated into a second medium containing sucrose 5%, MgSO4·7H20 0.1%, KH2PO4 1%, ZnSO4·7H2O 0.0176 g, and cultured for 3 more days. The media were kept at room temperature ranging from 24°C to 32 °C with agitation of 130 rpm and aeration of 4.17 Llmin. Qualitative analysis was performed by thin layer chromatography and quantitatively by high performance liquid chromatography with fluorescence detection, demonstrating the production of aflatoxin B I （588 mg/L） and B2 （929 mg/L）.展开更多
Emblica officinalis （E. oJficinalis） dried fruits were evaluated for its antitrypanosomal activity and cytotoxic effects. Vero cell line maintained in DMEM （Dubecco＇s Modified Eagle Medium） and incubated with Try...Emblica officinalis （E. oJficinalis） dried fruits were evaluated for its antitrypanosomal activity and cytotoxic effects. Vero cell line maintained in DMEM （Dubecco＇s Modified Eagle Medium） and incubated with Trypanosoma evansi for more than 12 h. MPE was added to the Vero cell culture medium at different concentrations （250-1,000 μg/mL） with trypanosomes concentration （1 × 106 trypanosomes/mL in each ELISA plate well） and incubated at appropriate conditions for 72 h. In-vitro cytotoxieity of MPE of E. officinalis was determined on Vero cells at concentrations （（1.56-100 ~tg/mL）. Acute toxicity and in-vivo infectivity tests were done in mice. Obtained MPE ofE. officinalis underwent process of purification via column chromatography, preparative chromatography and HPLC （higher performance liquid chromatography） with bioassay at different strata on Alsever＇s medium. In-vivo assay for trypanocidal activity, MPE and PPFs （partially purified fractions） of E. officinalis with two sets of mice, each mouse was inoculated with 1 × 104/mL oftrypanosomes and treated （48 h post inoculation） at concentrations （12.5, 25, 50, 100 and 200 mg/kg body weight） were administered at dose rate of 100 [tL per mouse via intraperitoneal route （in treating parassitemic mice） to different groups of mice, 6 mice per concentration. HPLC of partially purified fractions ofE. officinalis was carried out with mobile phase ofacetonitdle： water （40：60） in gradient mode. In vitro, MPE induced immobilization and killing of the parasites in concentration-time dependent manner. Significant reduction of trypanosomes counts from concentration of 250μg/mL and complete killing of trypanosomes at 5th hour of observation, which was statistically equivalent to 4th hour of Diminazine Aceturate （Berenil）, standard reference drug used. HPLC of the partially purified fractions revealed two major prominent peaks at retention time of 1-4 min. In vivo, both MPE and PPFs of test material did prolong lives of mice by 6-9 days but could not cure them. At concentration of 2,000 kg/kg body weight of MPE in acute test, all mice survived. For in-vivo infectivity test, mice injected with immobilized trypanosomes developed parasitemia and died while, the other group survived. MPE, PPFs and Diminazine Aceturate were toxic to Vero cells at all concentrations exception of 1.56, 1.56-3.13 and 1.56-6.25 μg/mL, respectively. From this report, PPFs ofE. officinalis dried fruits demonstrated potential pathway for a new development oftrypanocide in near future if additional investigations are put in place.展开更多
This study examined the distribution and elimination of Norfloxacin （NFLX） in Fenneropenaeus chinensis ovary and egg and newly hatched larvae. Mature parental shrimp were exposed to 4 or 10mgL-1 NFLX for 2 or 5d. Ov...This study examined the distribution and elimination of Norfloxacin （NFLX） in Fenneropenaeus chinensis ovary and egg and newly hatched larvae. Mature parental shrimp were exposed to 4 or 10mgL-1 NFLX for 2 or 5d. Ovary and eggs of the shrimp were sampled after spawning in order to detect NFLX residue using high-performance liquid chromatography （HPLC）. Re- suits showed that NFLX residue accumulated in F. chinensis eggs after the parental exposure, with the highest residue detected in ovary. To examine the fate of NFLX residue in larvae, we further determined the concentration of NFLX residue in F. chinensis eggs and larvae at 4 different developmental stages after 24-h exposure. From the newly metamorphosed larvae （Oh post-metamorphosis, h.p.m）, samples were taken at different time intervals to 72 h,p.m. HPLC assay showed that the concentrations of NFLX residue in zoea exposed to 4 and 10mgL-1 NFLX were the highest at 1.5h, i.e., 0.332 and 0.454μgg-1, respectively. At the two NFLX expo- sure levels, the elimination time of half NFLX （half life） in nauplius was 45.36 and 49.85h, respectively, followed by that in zoea （31.68 and 33.13 h）, mysis larvae （42.24 and 47.28 h） and postlarvae （24.48 and 30.96 h）. Both NFLX exposure levels had a germi- cidal effect. The distribution and elimination of NFLX residue in F. chinensis tissue, eggs and larvae correlated well with the drug exposure level. The disappearance of NFLX residue coincided with the larval growth, and the half-life of NFLX decreased with the larval development.展开更多
Incubation of camazepam [3-(N,N-dimethyl) carbamoyloxy-7-chloro-1- methyl-1,3-dihydro-5-phenyl-2H-1,4-benzodiazepin-2-one] with rat liver microsomes and cofactors produced a 3-(N-methyl-N-hydroxymethyl) carbamoyloxy d...Incubation of camazepam [3-(N,N-dimethyl) carbamoyloxy-7-chloro-1- methyl-1,3-dihydro-5-phenyl-2H-1,4-benzodiazepin-2-one] with rat liver microsomes and cofactors produced a 3-(N-methyl-N-hydroxymethyl) carbamoyloxy derivative as the most abundant metabolite.This metabolite was thermally unstable and was isolated from a metabolite mixture by normal-phase High-Performance Liquid Chromatography.Its struc- ture was established by chemical ionization and ^(252)Cf plasma desorption time-of-flight mass spectral analyses.展开更多
Callus cultures of Hyoscyamus niger L. were initiated from leaf segments cultured on Murashige and Skoog （MS） medium supplemented with 0.5 mg/L Benzyl Adenine （BA） and 0, 1, 2 and 3 mg/L Naphthalene acetic acid （...Callus cultures of Hyoscyamus niger L. were initiated from leaf segments cultured on Murashige and Skoog （MS） medium supplemented with 0.5 mg/L Benzyl Adenine （BA） and 0, 1, 2 and 3 mg/L Naphthalene acetic acid （ NAA ）. Half of cultures were incubated under light of 16 hr/day, while the other half was incubated under complete darkness. The incubation temperature was 25 ± 1 ℃in both incubation conditions. The fresh and dry weight of the produced callus was obtained after six weeks of incubation. Callus produced were recultured on medium that gave the highest production of callus. Constant weight （300 mg） of callus was cultured in each of these medium supplemented with abiotic elicitor of 50 g/L sucrose, 200 mg/L NaCI, 50 or 100 mg/L proline and 2 mg/L BA each one added separately and incubated under complete darkness. The fresh and dry weights of callus were measured after six weeks. HPLC was used to determine the tropane alkaloids （Hyoscyamine and Scopolamine）. The results showed that the significant highest average of fresh and dry weight of callus （112 and 89.6 mg） achieved using the medium contained 0.5 mg/L BA and 2 mg/L NAA under dark condition. The amount of fresh and dry weight of callus produced under dark condition was significantly higher than that produced under light condition, with increase in percentage of 51.3 and 37.62% respectively. The addition of abiotic elicitors caused reduction in both fresh and dry weight of callus, therefore the highest fresh weight average was 1,727 mg using 100 mg/L proline. The results indicated that addition of 50 or 100 mg/L proline led to increase in Hyoscyamine concentration of 58.03 and 21.37% respectively compared with the control. While other abiotic elicitors were found to cause reduction in Hyoscyamine concentration. Percentage of Scopolamine concentration were increased to 129.03, 166.94, 205.51 and 149.20% after addition of sucrose （50 g/L）, NaC1 （200 mg/L） and proline （50 or 100 mg/L） respectively compared with the control.展开更多
We developed a chiral HPLC method for the separation and analysis ofnaftopidil enantiomers. The two enantiomers of naflopidil were separated using a Chiralpak AD-H （250 mm×4.6 mm, 5 μm） column and monitored at...We developed a chiral HPLC method for the separation and analysis ofnaftopidil enantiomers. The two enantiomers of naflopidil were separated using a Chiralpak AD-H （250 mm×4.6 mm, 5 μm） column and monitored at the wavelength of 283 nm. The isocratic mobile phase consisting of hexane-isopropanol-diethylamine （85：15：0.1, v/v/v） was pumped at a flow rate of 1.0 mL/min. Under these chromatographic conditions, R-naflopidil and S-naftopidil were well separated and had good linearity in the ranges of 0.78-50 μg/mL （r = 0.9999） and 0.84-54 μg/mL （r = 0.9998）, respectively. The relative standard deviations （RSD） of intra- and inter-day assays were no more than 0.5% and 0.7%, respectively. This improved method for the separation and quantitative determination of naflopidil enantiomers can be used for the quality control of synthesized naflopidil product.展开更多
Novel anti-resistant liposomes have been developed to overcome intrinsic resistance in leukemia.Anticancer agent epirubicin and apoptotic inducer amlodipine were encapsulated into the liposome aqueous core,and the sur...Novel anti-resistant liposomes have been developed to overcome intrinsic resistance in leukemia.Anticancer agent epirubicin and apoptotic inducer amlodipine were encapsulated into the liposome aqueous core,and the surface of the liposome was modified using dequalinium.The objective of the present study was to establish a high performance liquid chromatography （HPLC） method for the determination of epirubicin,amlodipine and dequalinium in the liposomes.Analysis was performed on an ODS column with an isocratic elution at ambient temperature.Mobile phase was consisted of acetonitrile,0.02 M NaH_2PO_4 and triethylamine（34：66：0.3,v/v/v,pH 4.0）.The detection wavelength was set at 240 nm and the flow rate was 1.0 mL/min.The results showed that the calibration curves of epirubicin,amlodipine and dequalinium were linear in the range of（1-50）μg/mL（r^2= 0.9999）, respectively.The mean recoveries of epirubicin,amlodipine,and dequalinium were in the range of 95.86%-97.52%,97.17%-98.92% and 98.04%-101.13%,respectively.The contents of epirubicin,amlodipine and dequalinium in the liposomes were in the range of（564.2-606.1）μg/mL,（641.0-704.0）μg/mL,and（816.0-898.0）μg/mL,respectively.The encapsulation efficiencies of epirubicin and amlodipine were around 90%,and the modification rate of dequalinium was approximate 70μg/μmol lipids.The proposed HPLC method was simple and accurate for the simultaneous determination of epirubicin,amlodipine and dequalinium in newly developed anti-resistant liposomes.展开更多
Objective: To assess the safety of individual medication of Guo's Ma Qian Decoction on the basis of effective treatment of fluorosis of bone with Guo's therapy. Methods: One hundred and fourteen cases of moder...Objective: To assess the safety of individual medication of Guo's Ma Qian Decoction on the basis of effective treatment of fluorosis of bone with Guo's therapy. Methods: One hundred and fourteen cases of moderate fluorosis of bone were randomly divided into a treatment group (n=60) and a control group (n=54) between December 2007 and August 2009 by using the block randomized method and a central random system. At the same time of basic treatment, the patients in the treatment group were orally administrated with Guo's Ma Qian Decoction. The initial dose of Ma Qian Zi (Semen Strychni) was 0.4 g and increased by 0.05 g every two days, with the doses of other drugs unchanged, until the patient had "nux vomica response". For the patients with no "nux vomica response", the dosage was continued to increase and the maximum dosage was not more than 1.2 g/day. The control group was treated with decoction placebo. The changes of strychnine and brucine contents before and after processing and after decoction of Ma Qian Zi (Semen Strychni) were determined with reversed-phase high-performance liquid chromatography, which were controlled within ranges stipulated in the Pharmacopeia; Adverse events were analyzed; Blood strychnine and brucine contents in 10 cases who had taken the drugs were determined. Results: 1) Strychnine (2.125%) and brucine (1.425%) contents before processing of Ma Qian Zi and 1.88% and 1.31% after processing all conformed with the standards of strychnine (1.2-2.2%) and brucine (no less than 0.8%) stipulated in the Pharmacopeia. When the maximum dosage of Ma Qian Zi was 1.2 g/day, strychnine in the decoction was 11.17 mg and brucine was 7.44 mg, which all conformed with the maximum limited amount (strychnine 13.32 and brucine no less than 4.8 mg) stipulated in the Pharmacopeia. 2) Eight cases had "nux vomica response" in the treatment group and one case in the control group, with a significant difference between the two groups (P<0.05). 3) Altogether 18 cases had adverse events, with an incidence rate of 15.38% (8 cases) in the treatment group and 18.52% (10 cases) in the control group, with no difference between the two groups (P>0.05); Among them, 10 cases (8.77%) with the adverse event were not related with therapeutic drugs, with an incidence rate of 6.67% (4 cases) in the treatment and 11.11% (6 cases) in the control group, with no significant difference between the two groups (P>0.05). Seven cases had suspicious relative adverse events, the risk in the treatment group was 0.658 times of the control group, with no significant difference (P>0.05), and one case had the toxic reaction of nux-vomica seed. 4) Strychnine and brucine were unable to be detected in the blood in all points of time in the 10 cases who had taken the drugs, indicating that plasma strychnine and brucine contents were lower than the minimum detectable amount (10 ng), and accumulation of strychnine and brucine were not found in blood of the patient during and after administration for 8 weeks. Conclusion: The individual medication of Ma Qian Zi (Semen Strychni) in the Guo's therapy has a better safety.展开更多
A control system used in high performance liquid chromatograph(HPLC) was described.The control system adopting low pressure gradient elution was tested with different initial and end volume fractions,and four types of...A control system used in high performance liquid chromatograph(HPLC) was described.The control system adopting low pressure gradient elution was tested with different initial and end volume fractions,and four types of gradient elution curves.The experimental results verified the theoretical analyses of the applied method.This self-designed control system can achieve approving accuracy,repeatability and low cost,which has a bright outlook for domestic applications.展开更多
基金Research Projects of Heilongjiang Science and Technology Department (Grant No.GC05C31601).
文摘The objectives of the present study were to prepare stealthy etoposide proliposomes and study the pharmacokinetics in rabbits. Blank stealthy liposomes were prepared by film dispersion method. Stealthy etoposide liposomes were prepared by using the ammonium sulfate gradient loading procedure. Vacuum freeze-drying technique was used to dry stealthy etoposide liposomes. Encapsulation efficiency of stealthy etoposide proliposomes was determined by Sephadex chromatography. The morphology was observed by transmission electronic microscope. The particle size and zeta potential were measured by using electrophoretic light scattering technology. The pharmacokinetics in rabbits was evaluated by comparison with etoposide injection and conventional liposomes, respectively. Mean encapsulation efficiency of stealthy etoposide proliposomes was 83.92% ± 3.65% （n = 3）. The liposomes were round or oval. Mean particle size was （124.5 ±26.9） nm, and zeta potential was （-39.50 ±1.04） mV. Following intravenous injection administration at a dose of 1.5 mg/kg etoposide, the three kinds of etoposide preparations were fitted with the two-compartment model. T1/2 β and A UC values of stealthy etoposide proliposomes were （19.26 ± 3.16） h and （26.04 ±3.53） μg/h/mL, respectively. T1/2 β and AUC values of etoposide injection were （0.94 ± 0.21） h and （0.98 ± 0.26） μg/h/mL, respectively. T1/2β and AUC values of conventional liposomes were （7.99 ± 1.36） h and （11.65 ± 1.70） μg/h/mL, respectively. Results indicated that the stealthy etoposide proliposomes could significantly extend the duration of etoposide in blood circulation.
基金National Natural Science Foundation of China(No.30572260).
文摘Aim The objectives of the present study were to prepare stealthy vincristine plus quinacrine liposomes and evaluate the pharmacokinetics in Sprague-Dawley rats. Methods Anti-resistant stealthy liposomes were prepared by incorporating vincristine with quinacrine together using the ammonium sulfate gradient loading procedure. For the pharmacokinetic study, Sprague-Dawley rats were divided into two groups： each rat in the Group Ⅰwas administered intravenously via tail vein as stealthy liposomal vincristine plus quinacrine, and the Group Ⅱ similarly given as a mixture solution of free vincristine plus free quinacrine. The concentrations of vincristine and quinacrine in plasma were measured by HPLC with diode array detection and fluorescence detection, respectively. Results The mean particle size of stealthy liposomes was 135.9 ±7.1 nm and the encapsulation efficiencies of stealthy liposomes were 〉 90% for vincristine, and 〉 85% for quinacrine, respectively. Administered as the stealthy vincristine plus quinacrine liposomes, the plasma exposures of both vincristine and quinacrine were significantly extended, and the mean concentrations of both vincristine and quinacrine were significantly higher compared to those given as the mixture solution of free vincristine plus free quinacrine. The Cmax, t1/2, AUC0-24 h values of vincristine for stealthy liposomal group were significantly increased, but the total clearance Cl values decreased, as compared to those of free drug group, respectively. Similarly, the Cmax, t1/2 and AUC0-24 h values of quinacrine for the stealthy liposomal group were significantly increased, but the total clearance C1 values decreased, as compared to those of free quinacrine. Conclusion The anti-resistant stealthy liposomes are successfully prepared by incorporating vincristine with quinacrine, and the liposomes extend significantly the duration in blood circulation and improve evidently the plasma concentrations of both vincristine and quinacrine.
文摘Aim To develop and validate a RP-HPLC method for the analysis of paclitaxel in a solid dispersion. Methods Paclitaxel and the internal standard norethisterone were separated using a Phenomenex ODS 3 column and monitored at a wavelength at 227 nm. The isocratic mobile phase consisting of methanol-acetonitrile-water （40：30：30, V/V） was pumped at a flow-rate of 1.0 mL·min^-1. The dissolution studies were performed according to published studies. Results Under these chromatographic conditions, the calibration curve was linear in the range of 4-40 μg·mL ^-1 with the correlation coefficient of 0.9999. The mean recovery was 98.42 % （RSD = 1.19 %）. At the 60 min time point, the dissolution of paclitaxel from the solid dispersion was nearly 100 %, however, the original form of paclitaxel was about 30 %. Conclusion The method was proven to be specific, accurate and precise for determining the dissolution of paclitaxel from solid dispersion.
基金Supported by the National High Technology Research and Development Program of China (863 program) (No. 2007AA091604)the Knowledge Innovation Project of Chinese Academy of Sciences(No. KZCX2-YW-209)
文摘Gelatin has been used in hard capsule shells for more than a century, and some shortcomings have appeared, such as high moisture content and risk of transmitting diseases of animal origin to people. Based on available studies regarding gelatin and vegetable shells, we developed a new type of algal polysaccharide capsule (APPC) shells. To test whether our products can replace commercial gelatin shells, we measured in-vivo plasma concentration of 12 selected volunteers with a model drug, ibuprofen, using high performance liquid chromatography (HPLC), by calculating the relative bioavailability of APPC and Qualicaps referenced to gelatin capsules and assessing bioequivalence of the three types of shells, and calculated pharmacokinetic parameters with the software DAS 2.0 (China). The results show that APPC shells possess bioequivalence with Qualicaps and gelatin shells. Moreover, the disintegration behavior of four types of shells (APPC, Vegcaps , Qualicaps and gelatin shells) with the content of lactose and radioactive element (99mTc) was observed via gamma-scintigraphic images. The bioavailability and gamma-scintigraphic studies showed that APPC was not statistically different from other vegetable and gelatin capsule shells with respect to in-vivo behavior. Hence, it can be concluded that APPCs are exchangeable with other vegetable and gelatin shells.
文摘Aflatoxins are produced mainly by Aspergillus flavus and Aspergillus parasiticus, and can be found in many grains such as peanuts, soybeans and com. This study aimed to qualitatively and quantitatively evaluate the production of aflatoxin in liquid media using strains of Aspergillus flavus obtained from peanuts marketed in the city of Fortaleza, CEo Strains of Aspergillus flavus were inoculated into a liquid medium malt extract and after 2 days inoculated into a second medium containing sucrose 5%, MgSO4·7H20 0.1%, KH2PO4 1%, ZnSO4·7H2O 0.0176 g, and cultured for 3 more days. The media were kept at room temperature ranging from 24°C to 32 °C with agitation of 130 rpm and aeration of 4.17 Llmin. Qualitative analysis was performed by thin layer chromatography and quantitatively by high performance liquid chromatography with fluorescence detection, demonstrating the production of aflatoxin B I （588 mg/L） and B2 （929 mg/L）.
文摘Emblica officinalis （E. oJficinalis） dried fruits were evaluated for its antitrypanosomal activity and cytotoxic effects. Vero cell line maintained in DMEM （Dubecco＇s Modified Eagle Medium） and incubated with Trypanosoma evansi for more than 12 h. MPE was added to the Vero cell culture medium at different concentrations （250-1,000 μg/mL） with trypanosomes concentration （1 × 106 trypanosomes/mL in each ELISA plate well） and incubated at appropriate conditions for 72 h. In-vitro cytotoxieity of MPE of E. officinalis was determined on Vero cells at concentrations （（1.56-100 ~tg/mL）. Acute toxicity and in-vivo infectivity tests were done in mice. Obtained MPE ofE. officinalis underwent process of purification via column chromatography, preparative chromatography and HPLC （higher performance liquid chromatography） with bioassay at different strata on Alsever＇s medium. In-vivo assay for trypanocidal activity, MPE and PPFs （partially purified fractions） of E. officinalis with two sets of mice, each mouse was inoculated with 1 × 104/mL oftrypanosomes and treated （48 h post inoculation） at concentrations （12.5, 25, 50, 100 and 200 mg/kg body weight） were administered at dose rate of 100 [tL per mouse via intraperitoneal route （in treating parassitemic mice） to different groups of mice, 6 mice per concentration. HPLC of partially purified fractions ofE. officinalis was carried out with mobile phase ofacetonitdle： water （40：60） in gradient mode. In vitro, MPE induced immobilization and killing of the parasites in concentration-time dependent manner. Significant reduction of trypanosomes counts from concentration of 250μg/mL and complete killing of trypanosomes at 5th hour of observation, which was statistically equivalent to 4th hour of Diminazine Aceturate （Berenil）, standard reference drug used. HPLC of the partially purified fractions revealed two major prominent peaks at retention time of 1-4 min. In vivo, both MPE and PPFs of test material did prolong lives of mice by 6-9 days but could not cure them. At concentration of 2,000 kg/kg body weight of MPE in acute test, all mice survived. For in-vivo infectivity test, mice injected with immobilized trypanosomes developed parasitemia and died while, the other group survived. MPE, PPFs and Diminazine Aceturate were toxic to Vero cells at all concentrations exception of 1.56, 1.56-3.13 and 1.56-6.25 μg/mL, respectively. From this report, PPFs ofE. officinalis dried fruits demonstrated potential pathway for a new development oftrypanocide in near future if additional investigations are put in place.
基金supported by the Earmarked Fund for Modern Agro-industry Technology Research System,China(No.CARS-47)the Special Fund for Agro-scientific Research in the Public Interest of China(No.201103034)
文摘This study examined the distribution and elimination of Norfloxacin （NFLX） in Fenneropenaeus chinensis ovary and egg and newly hatched larvae. Mature parental shrimp were exposed to 4 or 10mgL-1 NFLX for 2 or 5d. Ovary and eggs of the shrimp were sampled after spawning in order to detect NFLX residue using high-performance liquid chromatography （HPLC）. Re- suits showed that NFLX residue accumulated in F. chinensis eggs after the parental exposure, with the highest residue detected in ovary. To examine the fate of NFLX residue in larvae, we further determined the concentration of NFLX residue in F. chinensis eggs and larvae at 4 different developmental stages after 24-h exposure. From the newly metamorphosed larvae （Oh post-metamorphosis, h.p.m）, samples were taken at different time intervals to 72 h,p.m. HPLC assay showed that the concentrations of NFLX residue in zoea exposed to 4 and 10mgL-1 NFLX were the highest at 1.5h, i.e., 0.332 and 0.454μgg-1, respectively. At the two NFLX expo- sure levels, the elimination time of half NFLX （half life） in nauplius was 45.36 and 49.85h, respectively, followed by that in zoea （31.68 and 33.13 h）, mysis larvae （42.24 and 47.28 h） and postlarvae （24.48 and 30.96 h）. Both NFLX exposure levels had a germi- cidal effect. The distribution and elimination of NFLX residue in F. chinensis tissue, eggs and larvae correlated well with the drug exposure level. The disappearance of NFLX residue coincided with the larval growth, and the half-life of NFLX decreased with the larval development.
文摘Incubation of camazepam [3-(N,N-dimethyl) carbamoyloxy-7-chloro-1- methyl-1,3-dihydro-5-phenyl-2H-1,4-benzodiazepin-2-one] with rat liver microsomes and cofactors produced a 3-(N-methyl-N-hydroxymethyl) carbamoyloxy derivative as the most abundant metabolite.This metabolite was thermally unstable and was isolated from a metabolite mixture by normal-phase High-Performance Liquid Chromatography.Its struc- ture was established by chemical ionization and ^(252)Cf plasma desorption time-of-flight mass spectral analyses.
文摘Callus cultures of Hyoscyamus niger L. were initiated from leaf segments cultured on Murashige and Skoog （MS） medium supplemented with 0.5 mg/L Benzyl Adenine （BA） and 0, 1, 2 and 3 mg/L Naphthalene acetic acid （ NAA ）. Half of cultures were incubated under light of 16 hr/day, while the other half was incubated under complete darkness. The incubation temperature was 25 ± 1 ℃in both incubation conditions. The fresh and dry weight of the produced callus was obtained after six weeks of incubation. Callus produced were recultured on medium that gave the highest production of callus. Constant weight （300 mg） of callus was cultured in each of these medium supplemented with abiotic elicitor of 50 g/L sucrose, 200 mg/L NaCI, 50 or 100 mg/L proline and 2 mg/L BA each one added separately and incubated under complete darkness. The fresh and dry weights of callus were measured after six weeks. HPLC was used to determine the tropane alkaloids （Hyoscyamine and Scopolamine）. The results showed that the significant highest average of fresh and dry weight of callus （112 and 89.6 mg） achieved using the medium contained 0.5 mg/L BA and 2 mg/L NAA under dark condition. The amount of fresh and dry weight of callus produced under dark condition was significantly higher than that produced under light condition, with increase in percentage of 51.3 and 37.62% respectively. The addition of abiotic elicitors caused reduction in both fresh and dry weight of callus, therefore the highest fresh weight average was 1,727 mg using 100 mg/L proline. The results indicated that addition of 50 or 100 mg/L proline led to increase in Hyoscyamine concentration of 58.03 and 21.37% respectively compared with the control. While other abiotic elicitors were found to cause reduction in Hyoscyamine concentration. Percentage of Scopolamine concentration were increased to 129.03, 166.94, 205.51 and 149.20% after addition of sucrose （50 g/L）, NaC1 （200 mg/L） and proline （50 or 100 mg/L） respectively compared with the control.
基金Guangzhou Science and Technology Projects of Apecial Areas of Innovative Medicines (Grant No.2006Z2-E4011)2006 Guangdong Province Technology Projects (Grant No. 2006B35501003)
文摘We developed a chiral HPLC method for the separation and analysis ofnaftopidil enantiomers. The two enantiomers of naflopidil were separated using a Chiralpak AD-H （250 mm×4.6 mm, 5 μm） column and monitored at the wavelength of 283 nm. The isocratic mobile phase consisting of hexane-isopropanol-diethylamine （85：15：0.1, v/v/v） was pumped at a flow rate of 1.0 mL/min. Under these chromatographic conditions, R-naflopidil and S-naftopidil were well separated and had good linearity in the ranges of 0.78-50 μg/mL （r = 0.9999） and 0.84-54 μg/mL （r = 0.9998）, respectively. The relative standard deviations （RSD） of intra- and inter-day assays were no more than 0.5% and 0.7%, respectively. This improved method for the separation and quantitative determination of naflopidil enantiomers can be used for the quality control of synthesized naflopidil product.
基金Beijing Natural Science Foundation(Grant No. 7091005)National Natural Science Foundation of China(Grant No.30772664)
文摘Novel anti-resistant liposomes have been developed to overcome intrinsic resistance in leukemia.Anticancer agent epirubicin and apoptotic inducer amlodipine were encapsulated into the liposome aqueous core,and the surface of the liposome was modified using dequalinium.The objective of the present study was to establish a high performance liquid chromatography （HPLC） method for the determination of epirubicin,amlodipine and dequalinium in the liposomes.Analysis was performed on an ODS column with an isocratic elution at ambient temperature.Mobile phase was consisted of acetonitrile,0.02 M NaH_2PO_4 and triethylamine（34：66：0.3,v/v/v,pH 4.0）.The detection wavelength was set at 240 nm and the flow rate was 1.0 mL/min.The results showed that the calibration curves of epirubicin,amlodipine and dequalinium were linear in the range of（1-50）μg/mL（r^2= 0.9999）, respectively.The mean recoveries of epirubicin,amlodipine,and dequalinium were in the range of 95.86%-97.52%,97.17%-98.92% and 98.04%-101.13%,respectively.The contents of epirubicin,amlodipine and dequalinium in the liposomes were in the range of（564.2-606.1）μg/mL,（641.0-704.0）μg/mL,and（816.0-898.0）μg/mL,respectively.The encapsulation efficiencies of epirubicin and amlodipine were around 90%,and the modification rate of dequalinium was approximate 70μg/μmol lipids.The proposed HPLC method was simple and accurate for the simultaneous determination of epirubicin,amlodipine and dequalinium in newly developed anti-resistant liposomes.
基金supported by a grant from "The 11th Five" National Science and Technology Support Project (2006BAI04A09-2)
文摘Objective: To assess the safety of individual medication of Guo's Ma Qian Decoction on the basis of effective treatment of fluorosis of bone with Guo's therapy. Methods: One hundred and fourteen cases of moderate fluorosis of bone were randomly divided into a treatment group (n=60) and a control group (n=54) between December 2007 and August 2009 by using the block randomized method and a central random system. At the same time of basic treatment, the patients in the treatment group were orally administrated with Guo's Ma Qian Decoction. The initial dose of Ma Qian Zi (Semen Strychni) was 0.4 g and increased by 0.05 g every two days, with the doses of other drugs unchanged, until the patient had "nux vomica response". For the patients with no "nux vomica response", the dosage was continued to increase and the maximum dosage was not more than 1.2 g/day. The control group was treated with decoction placebo. The changes of strychnine and brucine contents before and after processing and after decoction of Ma Qian Zi (Semen Strychni) were determined with reversed-phase high-performance liquid chromatography, which were controlled within ranges stipulated in the Pharmacopeia; Adverse events were analyzed; Blood strychnine and brucine contents in 10 cases who had taken the drugs were determined. Results: 1) Strychnine (2.125%) and brucine (1.425%) contents before processing of Ma Qian Zi and 1.88% and 1.31% after processing all conformed with the standards of strychnine (1.2-2.2%) and brucine (no less than 0.8%) stipulated in the Pharmacopeia. When the maximum dosage of Ma Qian Zi was 1.2 g/day, strychnine in the decoction was 11.17 mg and brucine was 7.44 mg, which all conformed with the maximum limited amount (strychnine 13.32 and brucine no less than 4.8 mg) stipulated in the Pharmacopeia. 2) Eight cases had "nux vomica response" in the treatment group and one case in the control group, with a significant difference between the two groups (P<0.05). 3) Altogether 18 cases had adverse events, with an incidence rate of 15.38% (8 cases) in the treatment group and 18.52% (10 cases) in the control group, with no difference between the two groups (P>0.05); Among them, 10 cases (8.77%) with the adverse event were not related with therapeutic drugs, with an incidence rate of 6.67% (4 cases) in the treatment and 11.11% (6 cases) in the control group, with no significant difference between the two groups (P>0.05). Seven cases had suspicious relative adverse events, the risk in the treatment group was 0.658 times of the control group, with no significant difference (P>0.05), and one case had the toxic reaction of nux-vomica seed. 4) Strychnine and brucine were unable to be detected in the blood in all points of time in the 10 cases who had taken the drugs, indicating that plasma strychnine and brucine contents were lower than the minimum detectable amount (10 ng), and accumulation of strychnine and brucine were not found in blood of the patient during and after administration for 8 weeks. Conclusion: The individual medication of Ma Qian Zi (Semen Strychni) in the Guo's therapy has a better safety.
基金the National High Technology Research and Development Program (863) of China(No. 2009AA04Z326)the National Natural Science Foundation of China (Nos. 60671059, 60871091 and60588101)+1 种基金the National Basic Research Program (973) of China (Nos. 2005CB724302 and 2005CB724303)the 111 Project from the Ministry of Education of China(No. B08020)
文摘A control system used in high performance liquid chromatograph(HPLC) was described.The control system adopting low pressure gradient elution was tested with different initial and end volume fractions,and four types of gradient elution curves.The experimental results verified the theoretical analyses of the applied method.This self-designed control system can achieve approving accuracy,repeatability and low cost,which has a bright outlook for domestic applications.
