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The Study Of Emulsified Isoflurane In Laboratory

Posted on:2004-02-05Degree:DoctorType:Dissertation
Country:ChinaCandidate:X M LiangFull Text:PDF
GTID:1104360092999752Subject:Pharmacology
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Objective To study the influence factors of the preparation of emulsified isoflurane agent, the quality control of, the optimum concentration and equivalent as well.Method The liquid/gas partition coefficient ( L/C) of volatile anesthetics in 30%Intralipid emulsion at various temperature were determined by glass syringe - flask two stage headspace equilibration method with gas chromatography (GC), the temperature index (TI) of L/G and the saturated concentrations(Csat) were calculated as well. Liquid isoflurane was added into 30%Intralipid and shaken vigorously for preparation of emulsified isoflurane (EI). The real concentrations of EI were determined at different shaken-time. The EI of each concentration(3%-9%) was multiply sampled (n=6) and concentrations were determined by GC. Partical sizes, pH values of 30%Intralipid , 6%volEI, 7%volEI, 8%volEI, 9%volEI were determined. The EI (6%vol, 7%vol, 8%vl, 9%vol) prepared in glass ample were exposed in the air. The concentrations were determined by GC from 0 to 300 min. 40 Japan rabbits were divided into 5 group (n=8, groupl: control group; group II: inhalation group; group III: 7%volEI group; group IV: 8%vol group; group V: 9%volEI group). The EI of different concentrations (7%vol, 8%vol, 9%vol) were iv. infused. The minimum induction dose (MID), the dose of Eisol%(DEisol%), MAC, the cardiac anesthetisia index (CI) and the maximal tolerant concentration of end-tidal isoflurane (MTC) were determined. The animals were autopsied after dead and the main organs were histo-pathologically diagnosed as well. 5 rhesus macaques were induced by isoflurane for endotracheal intubation. TheMACiv. and MACmhal were determined separately by means of "up and down".The concentrations of isoflurane in inspired gas, end tidal gas and artery blood were determined at 0.5MAC and 1 .0MAC, respectively.Results I/G of volatile agents decreased linearly with increasing temperature in the range of 15-42 at 1 atm. TI were -3.02%, -3.58%,-4.23%, and -4.45% respectively in order of des, sevo, iso, enf, and halo. Csat of all agents in 30% intralipid were shown in shape of inverse bell with increasing temperature. The lowest Csat of volatile anesthetics were des 3.92%vol, sevo 3.85%vol, iso 8.08%vol, enf 7.28%vol, and halo 12.55%vol, respectively. The emulsifiedisoflurane prepared by mechanically shaken method was good for its physical-chemical stability, solubilty, and partical size, pH as well as distribution were also good. The average partical sizes were arranged from 0.363 m to 0.479 m. None drop bigger than l.5 m was found. The partical sizeand pH were coincident to China Pharmacopeia. The Significant differencesof anesthesia and safety were not observed among 7%volEI, 8%volEI and 9%volEI anesthesia animals by iv. infusion. No abnormality ofPatho-morphological examination were found from the tissues of main organs in 7%volEI group animals. The light injury could be observed in 8%volEIgroup animals. The obvious damage could be observed in 9%volEI group animals. The MACiv was lower than MACinhal while the bloodconcentrations were not significantly different between two delivery routes. The equal end-tidal concentration of isoflurane for iv. delivery and inhalation delivery were 1.40% and 0.85% respectively.Conclusion Isoflurane emulsified in 30%intralipd as vehicle is good for anesthesia, quickly onset and convenient monitor. The preparation of 7%volEI is worth to be further investigated as a new anesthetic drug for clinical practice.
Keywords/Search Tags:isoflurane, 30%Intralipid, intravenous infusion preparation
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