Studies On The Synthesis And In Vitro Release Of Colon-specific Polymer Drugs

5-Aminosalicylic acid(5-ASA) is one of the preferred drugs that are used to treat inflammatory bowel disease (IBD) in clinical. Now, the research of its delivery systems has become a hot problem for the disadvantages of conventional ones. The purpose of this paper is to prepare some colon-specific polymer drugs, in order to provide an effective method for the clinical application of 5-ASA.Firstly, the synthetic process of 5-ASA was investigated. With salicylic acid and aniline as starting materials, 5-ASA was synthesized by diazotization, coincidence, reduction, and the yield reached 80%~81% on salicylic acid. It also investigated the influencing factors of the synthesis and found out the optimal reaction conditions. Salifying methods by acidification or basification, two processes to purify 5-ASA, were compared with each other. DSC and IR spectra test indicated the product refined by acidification-salifying method had higher purity, so it was more suitable for industry. In this paper, a preliminary study on the preparation process of 5-ASA was made by substituting sulfanilic acid for aniline, and the feasibility was discussed.Secondly, 5-acrylamidesalicylic acid was synthesized with the homemade 5-ASA as starting material, and the yield was 51%, which was improved greatly by comparison to the literature (40%). Next, when initiated by azodiisobutyronitrile, poly(5-AASA) and poly(5-AASA-co-NVP) were obtained by homopolymerization or copolymerization with NVP in N,N-dimethylformamide. The products were characterized through DSC, IR, ~1H-NMR, and the results indicated they were the objective substances.Finally, drug release in vitro was made, and the effects of pH were investigated. The results showed, little drug was released from those polymer drugs after 24h in acid condition, however the majority was released after 6h in mild base condition. While NVP was incorporated into polymer drug, it had little effect on release in acid condition, but drug release rate in base condition increased markedly. As a result, the release rate of 5-ASA can be controlled by changing the proportion of NVP in copolymer. Grounded on physiological characteristic of gstrointestinal tract of man, the pH-based release of polymer drugs could be used to deliver drug to colon, and become an effective clinical method.