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目的合成水溶性好,具有缓释特性并无溶血不良反应的葛根素前药。方法通过缩合反应以丁二酸为连接臂,将葛根素与单甲氧基聚乙二醇(Mr=5 000,mPEG5k)共价连接,制备聚乙二醇负载的葛根素前药,并通过TLC,UV,1H-NMR对其进行结构表征;同时测定葛根素前药的水溶性;考察前药在不同pH缓冲液中的释药特性;初步探索前药体外溶血特性。结果合成了聚乙二醇负载的葛根素前药,鉴定为预期产物。其水溶性较葛根素有较大提高;该前药在酸性的条件下稳定性较好,在pH 7.4的生理环境下能够缓慢持续的释药;体外抗溶血特性研究实验结果表明,该前药可避免葛根素的溶血性不良反应。结论与葛根素相比,前药水溶性好,并具有一定的缓释效果,而且可以避免溶血特性,有望成为新一代的葛根素制剂。
Objective To synthesize puerarin prodrugs with good water-solubility, slow-release properties and no hemolysis adverse reactions. Methods The puerarin was covalently linked to monomethoxy polyethylene glycol (Mr = 5000, mPEG5k) via succinic acid as the linker by condensation reaction, and the PEG-loaded puerarin prodrug was prepared by TLC, UV, 1H-NMR. Meanwhile, the water solubility of the puerarin prodrug was determined. The drug release characteristics of the prodrug in different pH buffers were investigated. Results Polyethylene glycol loaded puerarin prodrugs were synthesized and identified as the desired product. Its water solubility is higher than that of puerarin; the prodrug is stable under acidic conditions and can release slowly and continuously under the physiological environment of pH 7.4; the anti-hemolysis characteristics in vitro test results show that the prodrug Avoid puerarin hemolytic adverse reactions. Conclusion Compared with puerarin, the prodrug has good water-solubility, has certain sustained-release effect, and can avoid hemolysis and is expected to become a new generation of puerarin preparations.