Study On Micellar Preparation Of Diammonium Glycyrrhizinate Polyion Complex For Injection

Diammonium glycyrrhizinate(DG) has been widely used in acute and chronic hepatitis. In order to maintain relatively constant plasma concentration and reduce the side effects, a sustained released PIC micelle of intravenous injection was designed and prepared by using a grafted copolymer mPEG-g-PAHy which loaded DG to form Polyion complex (PIC) micelles.Firstly, a series of novel grafted copolymers composed of derivatives of poly (aspartic acid) as main chain and monomethoxy poly (ethylene glycol)(mPEG) as soluble side chain were designed and prepared, which were poly(ethylene glycol)-grafed-poly-α,β-polyasparthydrazide (mPEG-g-PAHy) with different grafting degree. The final products were identified using UV, IR and 1H-NMR.In order to evaluate the security of mPEG-g-PAHy the haemolysis test of mPEG-g-PAHy in vitro,acute toxicity test, and stimulation of mPEG-g-PAHy on vein and muscle were examined respectively.According to literature, UV spectrophotomatry was developed for in vitro assay during the studies of physicochemical properties, entrapped efficiency and release.In the preformulation researches the physicochemical properties of DG was investigatied, which benefit pharmaceutics form design. On the basis of pharmaceutical preformulation studies,single-factor tests were carried and based on tests about the influence of formulation and manufacture process on the mean diameter and entrapped efficiency. The optimal freeze-drying formulation was selected, the mean diameter and entrapped efficiency before and after freeze-drying were studied.The physicochemical properties such as pH values, particle size, zeta potential and entrapped efficiency of DG-loaded PIC micelles were studied. Simultaneously, the stability of DG-loaded PIC micelles Freeze-drying injection was detected through acceleration and long-term tests respectively. The drug release in vitro was investigated in different medium. The release rate of DG-PIC micelle is slower than DG solution in 154mmol/L,pH7.4 PBS,In this study,a new type of biocompatible grafted copolymer were synthesized, which were poly(ethylene glycol)-grafted-poly-α,β-polyasparthydrazide (PEG-g-PAHy) with different grafting degrees.PEG-g-PAHy can be a good candidate for charged drugs,such as protein、peptide and gene.