AIM　To improve the treatment efficacy of anti-tumor drug mitoxantrone, the conjugation of mitoxantrone-loaded nanospheres and anti-C-erbB-2 monoclonal antibodies were prepared. METHODS Mitoxantrone-loaded nanospheres were prepared with emulsion-heating solidification technique. A heterobifunctional reagent, N-succinimidyl 3-(2-pyridyldithio) propionate (SPDP), was used as the crosslinker of mitoxantrone-loaded nanospheres and anti-C-erbB-2 monoclonal antibodies; pharmaceutical properties of immunonanocapsuls were studied; the conjugates of nanospheres and monoclonal antibodies was confirmed with immunological methods such as slide agglutination test, fluorescent immunossay and rosset formation test, fluorescent staining and scanning electron microscope. RESULTS　Mitoxantrone-loaded nanospheres were spherical, with smooth surface and median diameter of 0.665 micron. When stored at 3-5, 20-25 and 37℃, RH 75% for three months, the appearance, morphology, size distribution, drug loading and in vitro release characteristics showed no significant change and the stability was satisfactory. The size analysis demonstrated that there was no obvious increase in the particle size of nanoparticles after conjugation. Immunological tests indicate highly selective binding of antibody-targeted nanospheres to C-erbB-2-overexpressing cells SK-BR-3. CONCLUSION　The conjugation of mitoxantrone-loaded nanospheres and anti-C-erbB-2 monoclonal antibodies can keep the activity of anti-C-erbB-2 and increase the therapeutic efficacy of anti-mammary cancer drugs.

AIM　To determine whether ONO-1078 {pranlukast, 4-oxo-8-［p-(4-phenylbutyloxy) benzoyl-amino]-2-(tetrazol-5-yl)-4H-1-benzopyran hemihydrate}, a potent leukotriene antagonist, has protective effect on focal cerebral ischemia in mice. METHODS　Focal cerebral ischemia was induced by permanent middle cerebral artery (MCA) occlusion in mice. ONO-1078 (0.01, 0.05, 0.10 mg*kg-1), dexamethasone (0.5 mg*kg-1), nimodipine (0.2 mg*kg-1) or saline (control) were injected ip once daily for 3 days, and 30 min before MCA occlusion. Twenty-four hours after cerebral ischemia, the neurological scores were evaluated, infarct volumes and areas of the right and left cerebral hemispheres were measured by computer imaging analysis. RESULTS　ONO-1078, dexamethasone and nimodipine reduced the neurological scores. ONO-1078 and dexamethasone reduced the ratio of right/left hemisphere area, indicating inhibition of brain edema, while nimodipine showed no effect. ONO-1078 dose-dependently reduced infarct size, and dexamethasone and nimodipine showed the same effect. CONCLUSION　ONO-1078 showed protective effect on focal cerebral ischemia. This may represent a novel approach to the treatment of acute cerebral ischemia.

AIM　To predict skin permeability of drugs with theoretical parameters. METHODS　The semiempirical self-consistent field molecular calculation AM1 method is utilized to obtain the structural parameters of drug molecules. Stepwise multiple regression analysis or BP neural network is then utilized to establish the correlation between skin permeability of drugs and their structural parameters. RESULTS　The calculated human skin permeability coefficients (kp) of 22 model drugs in vitro or the R values (R=absorbed/unabsorbed) of 17 drugs in vivo are in good agreement with their observed values. CONCLUSION　Theoretical parameters can be used to predict skin permeability of drugs.

AIM　To investigate the effect of particle size and high speed flow of helium gas on the systemic absorption of indomethacin using a needle-less injection system. METHODS　Poly-L-lactic acid microspheres containing indomethacin was prepared by the o/w solvent evaporation technique. After anesthetizing the male hairless rat, microspheres filled in the tube cartridge was accelerated by a stream of helium gas at various velocity in the HeliosTM gun system, and then was introduced to the abdominal skin. RESULTS　Introduction of indomethacin to the hairless rat skin was proportionally increased with enhancing the helium pressure (supersonic flow). Bioavailability and Cmax were also dependent on the helium pressure. CONCLUSION　This method can be used to deliver the powered drug and/or microparticulate systems into the skin tissues and the systemic circulation.

AIM　To explore the biotransformation of compound 7-(4-chlorbenzyl)-7,8,13,13a-tetrahydroberberine in the rabbit. METHODS　Analyze the rabbit bile sample with HPLC, LC/MS and LC/NMR. RESULTS　A metabolite and unchanged 7-(4-chlorbenzyl)-7,8,13,13a-tetrahydroberberine were found in the rabit bile, the metabolite was characterized and its structure was elucidated. CONCLUSION　Compound 7-(4-chlorbenzyl)-7,8,13,13a-tetrahydroberberine is metabolized by demethylation at 10-OCH3 position.

AIM　To study the pharmacokinetics and bioavailability of clinafloxacin in rats. METHODS　The drug concentration was determined by HPLC. The main pharmacokinetic parameters were obtained by 3P87 program. An RP-C18 was used as the stationary phase. The mobile phase was a mixture of acetonitrile-0.05 mol*L-1 citric acid triethylamine (pH 2.5) (20∶80). The flow rate was 1.0 mL*min-1. The UV absorbance detector was set at 300 nm. RESULTS　A good linearity was obtained from 0.03-20 μg*mL-1 of clinafloxacin in rat plasma with γ=0.9998. The plasma concentration-time curve of clinafloxacin conformed to one compartment open model. After ig administration of 50 mg*kg-1 and 100 mg*kg-1 dose of clinafloxacin in six rats, mean Cmax and AUC values increased in proportion to dose. Mean T1/2 appeared to be independent of dose. Mean AUC was 65±6 and 27±4 μg*h*mL-1 respectively after iv and ig adminostration of 100 mg*kg-1 dose. The extent of bioavailability (F) of clinafloxacin was 42%. CONCLUSION　The results of the pharmacokinetic study of clinafloxacin showed that it exhibited first order kinetic characteristics and the bioavailability is low.

AIM　To develop a method for the determination of trimebutine maleate in rat plasma by using high performance capillary electrophoresis. The method was employed to pharmacokinetic analysis of trimebutine maleate. METHODS　Plasma samples were deproteinized with acetonitrile (containing ephedrine hydrochloride as internal standard) and the supernatant was dried under N2 stream at 50℃. The residue was dissolved with methanol-water (1∶1) and injected into the capillary by siphon. The electrophoresis was performed in uncoated fused-silica capillary and the voltage was 10 kV. The running buffer was 0.03 mol*L-1 NaH2PO4 (pH 6.0). The eluate was detected at 214 nm by UV detection. RESULTS　The recovery for trimebutine maleate in rat plasma was 72.8%-87.9%. The calibration curve in plasma was linear over the range 5-200 μg*L-1. The limit of quantitation was 5 μg*L-1. The intraday relative standard deviation (n=6) and the interday relative standard deviation (n=18) were less than 14%. The highest concentration in plasma was observed at 30 min after ig trimebutine maleate to rats. The pharmacokinetic results were AUC0-∞=8 μg*min*mL-1, T1/2(Ke)=173 min and Ke=5.6×10-3 min-1. CONCLUSION　The method is accurate, sensitive and suitable for pharmacokinetic study of trimebutine maleate.

AIM　To study the electrochemical behavior of ofloxacin at Pt/GC ion implantation modified electrode. METHODS　With Pt/GC ion implantation modified electrode as working electrode, the behavior of ofloxacin was studied by voltammetry in 0.40 mol*L-1 KCl solution. RESULTS　A sensitive reductive peak of ofloxacin was obtained by linear sweep voltammetry. The peak potential was -1.35 V (vs SCE). The peak current was proportional to the concentration of ofloxacin over the range of 1.0×10-6-3.0×10-5 mol*L-1 with the detection limit of 5.0×10-7 mol*L-1. The behavior of reduction wave was studied and applied to determination of ofloxacin in tablets. CONCLUSION　The reduction process was irreversible. The element composition, atomicity form and depth of distribution at the surface of Pt/GC electrode were determined by Auger electron spectroscopy (AES), X-ray photoelectron spectroscopy (XPS) and scannig electron microscope (SEM). The catalysis behavior and reaction mechanism at Pt/GC modified electrode was also studied.

AIM　To research the chemical constituents from dried roots of Uncaria yunanensis Hsia.C.C. METHODS　Modern chromatography was used to isolate chemical components. Their structure were identified by spectral analysis. RESULTS　Seven compounds were isolated and identified as 3β,6β,19α-trihydroxyurs-12-en-28 oic acid (I), 23-nor-24-esomethylene-3β,6β-19α-trihydroxyurs-12-en-28 oic acid (II), 3-oxo-6β,19α-dihydroxyurs-12-en-28 oic acid (III), oleanic acid (IV), 5,7,3′,4′-tetrahydroxy-flavan-3-ol (V), β-yohimbine (VI) and diangoutengjian I (VII). CONCLUSION　All of the above compounds were isolated for the first time from the root of this plant. Among them, compound VII is a new one.

AIM　To determine the effects of glycoconjugates and their glycans from Lycium barbarum L. on inhibiting low density lipoprotein (LDL) peroxidation. METHODS　Using Cu2+-induced oxidation as a model, the oxidative production of thiobarbituric acid-reactive substances (TBARS) and the LDL electrophoresis migration on agarose gel were measured. RESULTS　The effects of glycoconjugates and their glycans from Lycium barbarum L. on inhibiting LDL peroxidation were different, among them, glycoconjugate LbGp5 showed the best effect on inhibiting LDLperoxidation. CONCLUSION　The glycoconjugates can inhibit LDL peroxidatin while their glycans showed no effects on inhibiting LDL peroxidation.