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Preparation Of Levofloxacin/carboxymethyl Chitosan Controlled-releasing Microsphere And Its Early Treatment Effect Of Seawater Immersed Wound

Posted on:2005-11-29Degree:DoctorType:Dissertation
Country:ChinaCandidate:H L ShenFull Text:PDF
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BackgroundThe incidence of seawater immersed wound is very high in contemporary naval warfare. There exist various of pathogenic bacteria in seawater, which is hyperosmotic and basic. Seawater immersion will exacerbate the injury of wounded tissue. Unfortunately, no applicable dressing has been made especially for this kind of wound by now. To meet the urgent needs of current military medicine, a kind of controlled release microsphere made of levofloxacin(LVEX) and carboxymethyl chitosan (CMC), which may be effective in treatment of such wound, is to be preparedLVFX is a sort of broad-spectrum antibiotic. It can affect the function of DNA gyrase in bacteria, which results in the inhibition of the duplication and transformation of DNA. Chitosan is obtained by deacetylation of chitin. It is degradable and has little toxicity and good biological compatibility. By carboxymethylation, chitosan changes into CMC, which is soluble in water and have the advantage to be used as accessory in dmg preparation.This LVFX microsphere may be convenient for use and can keep taking effect for a long time, which is beneficial for the treatment of seawater soaked wounds.Objectives1. To prepare LVFX/CMC microsphere with stable drug release characteristic through emucific^orH:hemcoTOSslinking procedure.2. To establish a method of HPLC for assaying the concentration of LVFX. And to find out the trend in changes of LVFX concentration after application of the microsphere in wound3. To set up an animal model of seawater immersed wound and to investigate die changes of some criteria on infection and inflammation as well as the LVEX concentration in wound and serum within 72 h. Methods1. Determine the main factors which affected the quality of rnicrosphere through inspecting the factors one by one. Then screen out the optimized formula by an orthogonal test containing fonnulas with different factors at different levels. The best formula was determined by a score , which came from the result of a formula : SXmean diameter of microspheresXrange of diameter) +S3enveloping rate^SXpercentage of drug content). Microspheres were made according to the optimized formula and there drug release rate during a certain period of time was recorded and compared with that of LVFX powder though basket rotation method An emulation based on Higuchi equation was made to determine the correlation of drug release rate and time.2. A concis was made at the right hind limb of rabbit, where the rnicrosphere and LVFX powder were applied in two groups respectively. Samples of tissue were taken 0.5 cm to the edge of incision and blood samples were obtained from the vein at the ear edge at 6h, 12h, 24h, 48h, and 72h after the drug administration. Then the concentration of LVFX in these samples was assayed by HPLC.3. At first, seawater salinity, pH value, pathogenic bacteria types of the seawater was determined Then the animal experiment was performed Rabbits were immersed into seawater up to the thoracic part for 60 min after a concis was made at the right hind limb. When taken out of water, the control group was wrapped directly while the rnicrosphere group received rnicrosphere before wrapping In both groups, tissue samples were taken 0.5 cm to the edge of incision with aseptic technique before and at 6h, 12h, 24h, 48h, and 72h after the immersion, when blood samples were alsoobtained Ham the vein at the ear edge. The bacteria colonies of the samples were counted though tissue culture. The endotoxin was quantitated through coloration of 320 compound ABC-ELISA was used to determine the TNF- a content of the specimens. And the concentration of LVFX in these samples was assayed by HPLC. Results1. The optimized formula was: CMC concentration 4%,CMC/LVFX 1.5, CMC/GD 0.5 and rotating speed 250 rpm The drug release character of the microsphere accorded with Higuchi equation: Q = 4.223tl/2+ 21.045, r=0.9831, with a Tso of 47.01h. And 72.02% of the drug was released in 7 days, which showed significant controDed release effect2. The peak of serums LVF...
Keywords/Search Tags:Levof Ioxacin, Chitosan, Control Ied-reIease, Seawater, Wound, Infection, Endotoxin, TNF-α
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