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Study on the Synthesis, Colon Targeting Characteristics and Pharmacodynamics of Pectin-ketoprofen Prodrug

Author: ZuoMiaoMiao
Tutor: ZhangSanQi；GuYi；FangKunQuan
School: Fourth Military Medical University
Course: Pharmacy
Keywords: Colonic targeting prodrug Ketoprofen Pectin Ulcerative colitis
CLC: R96
Type: Master's thesis
Year: 2005
Downloads: 178
Quote: 1
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Abstract


Objective : Synthesis of pectin - ketoprofen prodrug and determination of their drug loading capacity , the filter having the highest drug loading amount of a prodrug ; the establishment of ketoprofen in biological samples by high-performance liquid chromatography (HPLC) detection method ; observation pectin - ketoprofen prodrug for colon in vitro release characteristics ; explore the pectin - ketoprofen prodrug in the gastrointestinal tract in rats in different parts of the contents and distribution of the mucous membrane and the plasma concentration change ; through animal experiments , observation of the former lay the foundation for the efficacy of the drug treatment of ulcerative colitis in rats to find the ideal new drug for the treatment of ulcerative colitis . Method : 1. Ketoprofen , pectin in DMSO in the presence of N , N' - dicyclohexyl carbodiimide (DCC) under the conditions according to the type of weight ratio combining pectin - a prodrug of ketoprofen , to the product was added to a mixed solvent of ethanol / diethyl ether ( 1:1 ) , to obtain the precipitation of the pectin connected , and the precipitate was re- dissolved in dimethyl sulfoxide (DMSO) , adding ethanol / diethyl ether ( 1:1 ) a mixed solvent of 40 ml the precipitated polysaccharide connection object . Dissolving the precipitation step was repeated once , and finally the precipitate was dispersed in ethanol , the ethanol was removed by suction filtration , 8000mL 80% ethanol after dialysis for 48 hours at 60 ° C and dried for 24 hours to obtain a polysaccharide connecting object . 2 according to the different weight than synthetic prodrug at 2 mol · L -1 < / sup > NaOH solution , hydrolysis 30min , 1h , 2h , 3h , 4h, determine the prodrug completely hydrolyzed required time , and measured using HPLC drug loading capacity , to filter out the most reasonable reaction weight ratio of the prodrug to obtain the highest drug loading .

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