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991.
Microemulsion formulation of clonixic acid: solubility enhancement and pain reduction 总被引:5,自引:0,他引:5
Clonixic acid is currently marketed as a salt form because of its poor water-solubility. However, the commercial dosage form causes severe pain after intramuscular or intravenous injection. To improve the solubility of clonixic acid and to reduce pain on injection, clonixic acid was incorporated into oil-in-water microemulsions prepared from pre-microemulsion concentrate composed of varying ratios of oil and surfactant mixture. As an oil phase for drug incorporation, up to 14% castor oil could be included in the pre-microemulsion concentrate without a significant increase in droplet size. Both drug contents and droplet size increased as the weight ratio of Tween 20 to Tween 85 decreased. Taken together, when microemulsions were prepared from pre-microemulsion concentrate composed of 5:12:18 weight ratio of castor oil:Tween 20:Tween 85, clonixic acid could be incorporated at 3.2 mg mL(-1) in the microemulsion with a droplet size of less than 120 nm. The osmotic pressure of this microemulsion was remarkably lower than the commercial formulation, irrespective of the dilution ratios. The rat paw-lick test was used to compare pain responses among formulations. The microemulsion formulation significantly reduced the number of rats licking their paws as well as the total licking time, suggesting less pain induction by the microemulsion formulation. The pharmacokinetic parameters of clonixic acid after intravenous administration of the clonixic acid microemulsion to rats were not significantly different from those of the commercial formulation, lysine clonixinate. The present study suggests that microemulsion is an alternative formulation for clonixic acid with improved characteristics. 相似文献
992.
The current developments in liquid chromatography-mass spectrometry (LC-MS) and its applications to the analysis of pharmaceuticals are reviewed. Various mass spectrometric techniques, including electrospray and nanospray ionization, atmospheric pressure chemical ionization and photoionization and their interface with liquid chromatographic techniques are described. These include high performance liquid chromatography, capillary electrophoresis and capillary electrochromatography and the advantages and disadvantages of each technique are discussed. The applications of LC-MS to the studies of in vitro and in vivo drug metabolism, identification and characterization of impurities in pharmaceuticals, analysis of chiral impurities in drug substances and high-throughput LC-MS-MS systems for applications in the "accelerated drug discovery" process are described. 相似文献
993.
Modulation of radioligand binding to the GABA(A)-benzodiazepine receptor complex by a new component from Cyperus rotundus 总被引:2,自引:0,他引:2
Ha JH Lee KY Choi HC Cho J Kang BS Lim JC Lee DU 《Biological & pharmaceutical bulletin》2002,25(1):128-130
Four sesquiterpenes, beta-selinene, isocurcumenol, nootkatone and aristolone and one triterpene, oleanolic acid were isolated from the ethylacetate fraction of the rhizomes of Cyperus rotundus and tested for their ability to modulate gamma-aminobutyric acid (GABA(A))-benzodiazepine receptor function by radioligand binding assays using rat cerebrocortical membranes. Among these compounds, only isocurcumenol, one of the newly identified constituents of this plant, was found to inhibit [3H]Ro15-1788 binding and enhance [3H]flunitrazepam binding in the presence of GABA. These results suggest that isocurcumenol may serve as a benzodiazepine receptor agonist and allosterically modulate GABAergic neurotransmission via enhancement of endogenous receptor ligand binding. 相似文献
994.
995.
996.
Cho YW Motamedi GK Laufenberg I Sohn SI Lim JG Lee H Yi SD Lee JH Kim DK Reba R Gaillard WD Theodore WH Lesser RP Steinlein OK 《Archives of neurology》2003,60(11):1625-1632
BACKGROUND: A Korean family had distinctive clinical and neuroimaging features and carried the same genetic mutation that was found in a previously described Japanese kindred with autosomal dominant nocturnal frontal lobe epilepsy. OBJECTIVE: To describe the first Korean family with autosomal dominant nocturnal frontal lobe epilepsy. METHODS: Members of a large family, including 9 affected individuals from 3 generations, underwent a comprehensive genetic, clinical, electroencephalographic, neuropsychological, and neuroimaging evaluation. Affected members were tested for possible mutations in transmembrane regions 1 through 3 of the neuronal nicotinic acetylcholine receptor alpha4 subunit (CHRNA4) by direct sequencing and subsequent restriction analysis. RESULTS: Seizures began in childhood, presenting as nocturnal episodes of staring, confusion, shouting, perioral movements, unintelligible speech, and hand waving. Some patients had ictal or interictal epileptiform activity in the temporal and/or frontocentral areas. Neurological examination and brain magnetic resonance imaging results showed no abnormalities, except that all patients available for testing had mild to moderate mental retardation. Fluorodeoxyglucose F 18 with positron emission tomography showed mild decreased glucose uptake in the superior and middle frontal regions, more so on the left than on the right. Patient response to carbamazepine was poor. All affected members were heterozygous for the CHRNA4 Ser252Leu mutation. CONCLUSIONS: Disorders associated with mutations in the transmembrane region 2 of CHRNA4 are genetically and phenotypically heterogeneous. Distinctive features of this kindred include (1) mental retardation in all affected members available for testing, (2) abnormal brain findings on fluorodeoxyglucose F 18 with positron emission tomography, (3) poor response to carbamazepine, and (4) full penetrance. 相似文献
997.
998.
The frequency of spontaneous action potentials (SAP) is important in the regulation of hormone secretion. The decrease in K(+) conductance is known as a primary mechanism for increasing SAP frequency. To investigate the nature of K(+) channels that contribute to the frequency regulation of the SAP in rat clonal pituitary GH(3) cells, the effect of various K(+) channel blockers on the SAP and membrane currents were recorded using the patch-clamp technique. A classical inward rectifying K(+) channel blocker, Cs(+) (5 mM), caused an increase in firing frequency and depolarization in after-hyperpolarization (AHP) voltage. An ETHER-A-GO-GO(ERG) type K(+) channel blocker, E-4031 (5 microM), caused no significant effect on the SAP. Tetraethylammonium (TEA, 10 mM) decreased firing frequency and increased the duration of SAP. These effects were not changed by the presence of high concentration of Ca(2+) buffer (10 mM EGTA or BAPTA) in pipette solutions. In voltage-clamp experiments, Cs(+) and E-4031 did not affect outwardly rectifying K(+) currents, but significantly inhibited inwardly rectifying K(+) currents recorded in isotonic K(+) solution. However, the kinetics of Cs(+)-sensitive current and E-4031-sensitive current were distinctive: the time to peak was more immediate and the decay rate was slower in Cs(+)-sensitive current than in E-4031-sensitive current. These results imply that Cs(+) and E-4031 inhibit the distinct components of inwardly rectifying K(+) currents, and that the contribution of the Cs(+)-sensitive current can be immediate on repolarization and can last more effectively over pacemaking potential range than E-4031-sensitive current. 相似文献
999.
OBJECTIVES: To demonstrate the feasibility of opportunistic oral cancer and precancer screening in general dental practice and to determine the prevalence of relevant lesions and risk habits in a population of general dental practice attenders. DESIGN: A prospective demonstration study, recruiting patients opportunistically. SETTING: General dental practices. METHODS: Eighteen general dental practitioners took part in this study. Each attended training sessions to be advised of the study protocol and the criteria of a positive and negative screen. Patients over the age of 35 years were prospectively and opportunistically recruited. Each patient was asked to complete a health questionnaire concerning age, gender, ethnicity, smoking and drinking habits. The dentist then examined the soft tissues and recorded the presence or absence of lesions independently on a second form. The forms were collated and data were analysed to determine prevalence of lesions and associations with risk habits. RESULTS: Data on 2,265 patients were available for analysis. Oral lesions were detected in 319 patients (14.1%). Ninety-four patients (4.2%) had lesions considered to be either malignant or potentially malignant. There was a significant association between positive lesions and male gender(IRR 1.86, 95% CI 1.22-2.82), heavy smoking (males: IRR 3.68, 95% Cl2.10-6.43: female; IRR 3.58, 954b CI 1.35-9.50) and heavy alcohol use in males (IRR 2.98, 95%q CI 1.06-3.47). CONCLUSIONS: The results suggest that patients attending general dental practices are representative of the general population both in terms of lesion prevalence and high risk habits such as smoking and drinking. This supports the view that opportunistic screening in a general dental practice setting may be a realistic alternative to population screening. Further research is needed to determine the cost effectiveness of this approach and to investigate the value of targeting high risk groups within this population. General dental practice is ideal for the evaluation of such systems prior to extending these studies to other healthcare settings. 相似文献
1000.
The objective of this study was to compare the mechanical properties of calcium phosphate cements (CPC) for possible dental applications with varied liquid and powder compositions under the same testing condition. Cements studied in this experiment were divided into two groups of CPC not containing polymer and polymeric CPC (PCPC). Cement powder was formed by combining equimolar amounts of dicalcium phosphate anhydrous and tetracalcium phosphate, or acrylic resin polymer powder mixture. The CPC specimens for the compressive strength (CS) and diametral tensile strength (DTS) measurements were prepared by mixing powder and liquid for 30 s with a powder/liquid ratio of 3:1, and subsequently packing the paste into a brass mould. The specimens were kept at 37 degrees C and 100% relative humidity for 24 h before measurements were conducted on a Universal Testing Machine with a cross-head speed of 1 mm min-1. The CS of CPC was 0.14-10.29 MPa and that of PCPC was 0.26-117.58 MPa. The DTS of CPC was 0.10-4.56 MPa and that of PCPC was 0.07-22.54 MPa. The CS and DTS were very diverse depending on the composition of powder and liquid. Some compositions showed higher values than commercial liners. Thus compositions of 2% carboxymethyl cellulose + 35% citric acid in phosphate buffered saline (PBS), 20% gelatin in PBS, 2% sodium alginate in PBS, 20-40% aqueous acrylic-maleic copolymer solution, and some of the HPMC and PMVE-Ma solutions exhibited promising formulae for dentine regenerating materials. Acrylic resin-PCPC group showed generally higher CS and DTS values. Based on this study, further studies on the reaction with odontoblast and resultant dentine regeneration should be performed using promising compositions. 相似文献