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??OBJECTIVE To prepare ion-sensitive ophthalmic in situ gel containing bendazac lysine (BDZL-ISG) and preliminarily study its rheological behavior, in vitro drug release, corneal permeation, and pharmacokinetics in rabbit aqueous humor. METHODS Single factor investigation was carried out to optimize the formulation, taking viscosity and gelling capacity as evaluation indices. Using aqueous solution or eye drops as control, the in vitro release of the formulation was evaluated by dialysis membrane method. Then, the corneal permeation experiment of the optimum formulation was carried out with Franz diffusion cell. The pharmacokinetics of BDZL-ISG in rabbit aqueous humor was preliminarily studied by microdialysis. RESULTS Compared with the control group, the optimum formulation had shear thinning behavior and significant sustained release effect. There was no significant difference in the corneal permeation between the two groups. The RESULTS of pharmacokinetic study showed that ??_max (13.25 ??g??L^-1) and AUC_0-t of BZDL-ISG were 2.38 and 2.2 times higher than those of BDZL eye drops respectively, which suggested that the ocular bioavailability of BDZL was greatly enhanced by the optimum in situ gel formulation. CONCLUSION With significant sustained release effect, the ion-sensitive ophthalmic in situ gel will become a promising alterative formulation for bendazac lysine for treatment of cataracts.     

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??OBJECTIVE To prepare lappaconitine(LA)-loaded chitosan/ sodium ??-glycerophosphate(CS/??-GP) thermosensitive hydrogels and investigate its phase transition mechanism of gel formation process and release properties in vitro. METHODS The injectable CS/??-GP thermosensitive hydrogels were prepared with biodegradable CS as carrier material and ??-GP as coagulation accelerator. The release behavior in vitro was studied by dynamic dialysis, and the phase transition mechanism of gel formation process was further investigated by rheological method. RESULTS The optimized process condition was as follows:the concentration of ??-GP and CS was 560 and 22 mg??mL^-1, respectively, CS was dissolved by 0.1 mol??L^-1 HOAc, and the valume ratio of CS to ??-GP was 8.75??1.25(V/V), the gelation time of CS/??-GP thermosensitive hydrogels with volume ratio of 8.75??1.25(V/V) at 37 ?? was 5 min 38 s. The in vitro release study showed that these injectable CS/??-GP thermosensitive hydrogels had sustained release effect for LA, and the release behavior could be well described by the Higuchi model and Korsmeyer-Peppas model. The mechanism of LA releasing from CS/??-GP thermosensitive hydrogels was attributed to drug dissolution and diffusion. Rheological studies showed that the CS/??-GP thermosensitive hydrogels belonged to thixotropic system and exhibited non-Newtonian and shear-thinning fluid behavior as well as ??solid-like?? gelatin behavior. CONCLUSION LA-Loaded CS/??-GP injectable thermosensitive hydrogels with good elasticity and gel strength properties are prepared successfully, and they show sustained release effect of LA in vitro.     

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??OBJECTIVE To compare the chemical composition and therapeutic effect between Prunella vulgaris L stem leaf and ear, thus to provide evidence for judging whether the stem leaf of Prunella vulgaris L can substitute the ear as an herbal medicine. METHODS Aqueous extracts of the stem leaf and ear of Prunella vulgaris L from different producing areas were analyzed with HPLC-ESI-MSⁿ. The anti-inflammatory effects were observed by inflammatory models of ear edema induced by dimethylbenzene in mice and hind paw edema induced by carrageenan in rats.Enzyme-linked immunosorbent assay (ELISA) was used to detect the plasma level of TNF-?? and antioxidant activities were detected by ABTS method. RESULTS Prunella vulgaris L stem leaf and ear were not significantly different in chemical composition, both of which contained mainly triterpenoids, flavonoids, phenolic acids and other substances. Compared with the model group, Prunella vulgaris L ear significantly reduced the hind paw edema in rats induced by carrageenan from 1 h after oral administration (P<0.05), while the onset time of stem leaf was later than 1 h.Both groups could significantly reduce the ear edema in mice induced by dimethylbenzene(P<0.01). The TNF-?? levels in the Prunella vulgaris L stem leaf and ear groups [(24.16??1.24) and (24.33??2.36 )ng??mL^-1] were lower than that in the model group [(31.34??1.94) ng??mL^-1] (P<0.01).Prunella vulgaris L stem leaf and ear groups showed strong antioxidant activities in the ABTS^??+ scavenging test. CONCLUSION The contents of the main constituents in Prunella vulgaris L stem leaf and ear have significance differences.The RESULTS of animal tests indicate that the aqueous extracts of Prunella vulgaris L stem leaf and ear have significant anti-inflammatory and antioxidant effects.     

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??OBJECTIVE To establish a measuring method for microdialysis probe recovery of ginsenoside Rg₁ and investigate the effects of flow rate, concentration and using times of probe on the recovery in vivo and in vitro. METHODS Dialysis method and retrodialysis method were used for the study. The concentration of ginsenoside Rg₁ in brain and blood dialysate was determined by LC-MS/MS and the probe recovery was calculated. RESULTS The recoveries of brain and blood microdialysis probes showed good stability within 10 h, with average values of 17.0% and 34.4% respectively for ginsenoside Rg₁ at 1.5 ??L??min^-1. Concentrations (50,200,500,1 000 ng??mL^-1) had no obvious effect on recovery. At the same concentration, the recovery of brain and blood probes for ginsenoside Rg₁ decreased with the increase of flow rate (0.5, 1.0, 1.5, 2.0, 3.0 ??L??min^-1) in vitro and in vivo. The dialysis recoveries of brain and blood probes in vitro were (40.6??4.3)%, (23.5??2.3)%, (17.7??0.8)%, (12.2??1.1)%, (8.8??0.6)% and (70.6??3.6)%, (46.0??2.1)%, (32.9??1.6)%, (25.6??0.7)%, (18.2??1.3)%, respectively. The recoveries of dialysis and retrodialysis in vitro were approximately equal, and the recovery detected by retrodialysis in vivo was similar with the in vitro results. Probe used for no more than 3 times still kept high transmittance by flushing with 2% heparin sodium and ultrapure water successively. CONCLUSION Retrodialysis method can be used to study brain and blood probe recovery in vivo, and microdialysis can be used for simutaneous pharmacokinetic studies of ginsenoside Rg₁ in intercelluar fluid and blood.     

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??OBJECTIVE To develop a LC-MS method for simultaneously quantifying four anti-tuberculosis drugs [isoniazid(INH)??pyrazinamide(PZA)?? ethambutol(EMB) and rifampicin(RIF)] in human cerebrospinal fluid and to help guide the clinical medication. METHODS The drugs in cerebrospinal fluid were extracted by acetonitrile precipitation, and separated on ZORBAX Bonus-RP column(2.1 mm??150 mm,3.5 ??m) with the mobile phase of aqueous solution(containing 0.1% formic acid)-acetonitrile(containing 0.1% formic acid)(80??20) at a flow rate of 0.25 mL??min^-1. Multiple reaction monitoring(MRM) mode was performed combined with electrospray ionization source operating in the positive ionization mode. RESULTS The liner calibration curves of INH??PZA??EMB and RIF were obtained in the concentration range of 20-5 000(r=0.998 6), 120-30 000(r=0.997 7), 20-5 000(r=0.999 4), 60-15 000(r=0.996 2)ng??mL^-1, respectively. The intra-and inter-day precision was less than 15% and the absolute recovery was above 75%. This method was successfully applied to analyze the drugs in cerebrospinal fluid from six clinical samples. CONCLUSION The method is rapid, simple, sensitive and accurate, and proved to be suitable for clinical therapeutic drug monitoring.     

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??OBJECTIVE To study the influence of bioavailability of Epimedium flavonoids after processing by suet oil. METHODS Pharmacokinetics parameters of rats Epimedium flavonoids and icariin and baohuoside ?? was determining by the method of pharmacology effect and plasma concentration method. RESULTS The concentration of the Epimedium flavonoids, icariin and baohuoside ?? in micelles groups were higher than that of the active pharmaceutical ingredient(API). ??_max were increased by 77.94%, 38.99% and 49.90%; AUC_0-t increased by 95.19%, 37.76% and 43.49%; AUC_0-?? increased by 119.35%, 35.37% and 46.26% on Epimedium flavonoids, icariin and baohuoside ?? group. CONCLUSION Suet oil improved the bioavailability of Epimedium flavonoids and promoted its absorption.     

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??OBJECTIVE To study the chemical constituents from the rhizome of Drynaria fortunei and the protective effects of them on PC12 cells induced by A??_25-35. METHODS The compounds were isolated and purified by silica gel, Sephadex LH-20, ODS column chromatography, and their structures were identified on basis of spectroscopic methods, such as MS and NMR. PC12 cells were treated with A??_25-35 to establish the Alzheimer' s disease models. The compounds of different concentrations were added into culture medium to detect the protection. MTT assay was used to detect cell vitality and to observe the protective effects of compounds on PC12 cells induced by A??_25-35. RESULTS Nine compounds were isolated and identified as naringin(1), neoeriocitrin(2), 5,7-dihydroxychromone-7-neohesperidoside(3), (E)-4-O-??-D-glucopyranosyl caffeic acid(4), kaempferol(5), luteolin(6), protocatechoic acid(7), psoralen(8), and ??-sitosterol(9) . The cell experiments were performed on the compounds 1-8 and the results showed they can promote the proliferation of PC12 cells. The cell vitality increase with concentration rising, and the difference is statistically significant (P<0.05). CONCLUSION Compounds 1-8 play an important role in protecting A??_25-35-induced injury in PC12 cells and they are the main active components of Drynaria fortunei in the protection of central nervous function.     

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??OBJECTIVE To study the chemical constituents of the aqueous extract from the aerial part of Sibiraea angustata. METHODS The constituents were isolated by various chromatographic techniques(HP-20 macroporous absorption resin, Sephadex LH-20 gel, Reverse-phase silical gel and PHPLC) and their structures were determined on the basis of physicochemical properties and their spectroscopic data, as well as the literatures. RESULTS Twelve compounds were separated and identified as veratric acid(1),(+)-cycloolivil(2), 3,7-dimethyl-3(E)-6-octadien-5-one-1-O-??-D-glucoside(3), 3,7-dimethyl-3(Z)-6-octadien-5-one-1-O-??-D-glucoside(4), 1-O-??-D-glucopyranosyl(1??2)-??-D-glucopyranosyl-3,7-dimethyl-2(E)-6-heptdiene(5),(7R,8S)-dihydrodehydrodiconiferyl alcohol-9??-O-??-D-glucopyranoside(6),(+)-1-hydroxypinoresinol-1-??-D-glucoside(7), skimmin(8), kaempferol 3-O-??-L-arabinopyranosyl-(1??6)-??-D-galactopyranoside(9), isorhamnetin-3-O-??-D-galactopyranosyl(1??6)-??-D-glucopyranoside(10), isorhamnetin 3-O-??-arabinopyranosyl-(1??6)-??-galactopyranoside(11), and quercetin 3-O-[2''-O-(E)-caffeoyl]-??-L-arabinopyranosyl-(1??6)-??-D-galactopyranoside(12). CONCLUSION All compounds are obtained from the genus of Sibiraea for the first time.     

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??OBJECTIVE To prepare and characterize paroxetine resinate, and evaluate the in vitro drug release rate and taste-masking effect. METHODS A full factorial design was first conceived and applied to screen some process and formulation parameters (reaction temperature, stirring speed, drug concentration in solution and the ratio of resin to drug) on the key responses of resinationprocess, such as drug utilization ratio, drug loading and complexation constant. The paroxetine resinate was then characterized and evaluated by scanning electronic microscope (SEM), differential scanning calorimetry (DSC), in vitro drug release test and panel test of taste-masking. RESULTS The resin/drug ratio and reaction temperature were identified as the most important factors on paroxetine resinate preparation.The drug-resin complex was successfully formed via ion exchange mechanism rather than physical absorption with complete in vitro drug release (>96%) in acidic or salt solution and good taste-masking effect.CONCLUSION Paroxetine resinate with good performance can be prepared via optimization of process and formulation parameters, which will facilitate the development of generic paroxetine suspension.     

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??OBJECTIVE To study the chemical constituents from the tubers of Hemsleya penxianensis. METHODS The constituents were isolated from the tubers of H. penxianensis and purified by column chromatography, and the structures were identified by spectral analysis and chemical methods. RESULTS Five compounds were isolated from the tubers of H. penxianensis and the structures were identified as 2??,3??,16??,20, 24-pentahydroxycucurbita-5, 25(E)-diene-11,22-dione(1), cucurbitacin ??a(2), cucurbitacin ??_b(3), hemslecins G(4), and jinfushanencins B(5). CONCLUSION Compound 1 is a new compound.