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Based on the chemical structures of magnolol and honokiol,a series of small molecular derivatives were designed for the treatment of Alzheimer's disease.Through the Discovery Studio,five compounds (6a-6e) exhibited the inhibitory activity against Aβ and Tau proteins in all of the designed compounds.Then the five compounds are chemically synthesized and their biological activities were tested by thioflavin T.The result showed that compound 6a had inhibitory effect on the aggregation of two kinds of target proteins at the concentration of 100 μmol/L,which deserves further research.
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The aim of this study was to develop a derivative of chitosan as pharmaceutical excipient used in sustained-release matrix tablets of poorly soluble drugs. A water-soluble quaternary ammonium carboxymethylchitosan was synthesized by a two-step reaction with carboxymethylchitosan [CMCTS], decylalkyl dimethyl ammonium and epichlorohydrin. The elemental analysis showed that the target product with 10.27% of the maximum grafting degree was obtained. To assess the preliminary safety of this biopolymer, cell toxicity assay was employed. In order to further investigate quaternary ammonium carboxymethylchitosan application as pharmaceutical excipient, aspirin was chosen as model drug. The effect of quaternary ammonium CMCTS on aspirin release rate from sustained-release matrix tablets was examined by in-vitrodissolution experiments. The results showed that this biopolymer had a great potential in increasing the dissolution of poorly soluble drug. With the addition of CMCTS-CEDA, the final cumulative release rate of drug rose up to 90%. After 12 h, at the grade of 10, 20 and 50 cps, the drug release rate increased from 58.1 to 90.7%, from 64.1 to 93.9%, from 69.3 to 96.1%, respectively. At the same time, aspirin release rate from sustained-release model was found to be related to the amount of quaternary ammonium CMCTS employed. With the increase of CMCTS-CEDA content, the accumulated release rate increased from 69.1% to 86.7%. The mechanism of aspirin release from sustained-release matrix tablets was also preliminary studied to be Fick diffusion. These data demonstrated that the chitosan derivative has positive effect on drug release from sustained-release matrix tablets
Subject(s)
Aspirin/chemistry , Drug Compounding , Delayed-Action Preparations/chemistry , Chitosan/chemistry , Tablets , Solubility , Quaternary Ammonium Compounds , Biopolymers , EpichlorohydrinABSTRACT
A soft coral Sinularia sp., collected from the South China Sea, was selected to investigate the bioactive and chemical constituents. The EtOAc fraction were isolated by repeatedly silica gel and Sephadex LH-20 column chromatography to obtain lobophytolide A (1), 3-dehydroxylpresinularolide B (2), sarcophine (3), 3 beta-acetoxyisolobophytolide (4), Crassocolide D (5), (3E,7E,11E)-6-acetoxy-3,7,11,15(17)-cembratrien-16,14-olide (6). The structures of compounds 1-6 were determined on the basis of spectroscopic data analysis. All compounds were tested against a small panel of human tumor cell lines. And these compounds were obtained for the first time from this coral.
Subject(s)
Animals , Anthozoa , Chemistry , Diterpenes , Chemistry , Molecular StructureABSTRACT
Biological mass spectrometry has been developed for the largE-scale protein identification. The successful identification of protein in proteomic study is based on an effective match of MS data to the sequence in database. Because of the diversity and heterogeneity of protein modification, the experimental data obtained by mass spectrometry does not match the theoretical value sometimes, which makes about 90 percent or more of the tandem mass spectra not be effectively identified. This has become one of the most important technique issues to be resolved in current proteome research. The N-terminal cyclization of peptides, as one of a variety of modification introduced in sample preparation, has been preliminarily studied in this work. The result showed that N-terminal cyclization occurred at the most of the glutamine(Q) or carbamoylmethyl-cysteine(CAM_C) residues and the reaction is often incomplete or partial, both types of peptides could often exist in its respective state at the same time, and the behavior of modified peptides in revered phase chromatography is also changed. The success rate of protein identification could be obviously improved if adding the N-terminal cyclization modification in the database searching. These results will be very helpful in the mass spectrometric data analysis of proteomic study.
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OBJECTIVE:To make clear the antimicrobials used for inpatients in our hospital from September 1999 to March 2000 METHODS:We sampled the records of discharged patients at the ratio of 1/3 of sickbeds in our hospital,and filled in "the questionnaire of antimicrobials used in clinical department" item by item,finally,we carried out comprehensive analysis RESU_LTS:More than half was administration of single and basic antimicrobial Combined use of antimicrobials for severe and mixed infections was rational The rate of using antimicrobials was high(79 64%),especially in preventing perioperative infections,reached nearly 100% The starting-point was high in choice of drug and the newly-developed,special and expensive drugs occupied the front place in order of consumption Combined use of drugs was unduly prevalent Most of treatment depended on experience The rate of bacterial drug resistance test was only performed in 10% of patients CONCLUSION:Rational use of drugs is the main trend,however,the measure directed against existing problem should be worked out
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0.05).CONCLUS_ION:The present study in rabbits showed no significant interaction between ciprofloxacin and tacrolimus after combined administration of these two drugs in a single dose.
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OBJECTIVE:To select a best therapeutic scheme for diabetes among four kinds of oral hypoglycemic drugs:repaglinide(Novonorm),glibenclamide,gliclazide and glipizide.METHODS:According to the principle of pharmacoeconomics,using cost-effectiveness analysis(CEA),assessment and survey of the influencing factors(price,dosage)were carried out,at the same time,sensitive analysis was performed.RESULTS:The best therapeutic scheme was Novonorm and the rest were gliclazide,glipizide and glibenclamide in sequence.CONCLUSION:The result of sensitive analysis is in keeping with that of CEA,which indicates the credibility of CEA.
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Objective: To compare nephrotoxicity and ototoxicity of gentamycin administered in single dose or multiple dose daily in guinea pigs. Methods: Thirty two male guinea pigs were divided into physiological saline control, single dose group daily (gentamycin, 120 mg/kg, 1/d) and multiple dose group daily (gentamycin, 60 mg/kg, 2/d). The physiopathology of renal and cochlea in guinea pigs were examined using auditory brainstem response (ABR), SC sound irritation and electron microscope. The gentamycin concentrations in serum and in perilymph were monitored by fluorescene polarization immunoassay (FPIA). Results: (1) Compared with control group, both gentamycin single and mulitiple daily doses injuried kidney and cochlea to some extent.The injury of multiple dose groups were worse than that the single dose groups ( P