Clinical Study On Colon Targeting Drug Of Astragalus Polysaccharide

Objective Studying the preparation technology of the colon targeted pellets of Astragalus polysaccharides, and to investigate the clinical efficacy of the new drug by the character observation, microbial limit test, evaluation of formability index, stability study, targeted investigation and the pharmacodynamic toxicology.Methods(1) With reference to the Chinese pharmacopoeia 2015 edition quality evaluation was studied for the crude durg.of Astragalus membranaceus.(2) The extracted of APS by hot water extraction and ethanol precipitation.(3) Colon targeting agents of APS pellets were produced by extrusion-spheronization and fluid bed coating method and the best preparation technology was chosen by response surface optimization method.(4) Microbial limit test was carried out by microbial limit test; The evaluation of the formability index was carried out by the degree of fragmentation, angle of repose and roundness of the pellets; Stability investigation was carried out by accelerated test and long term test; The targeted investigation was carried out by the in vitro dissolution test.(5) Through the establishment of intestinal disorders model the Wistar mice, determination of astragalus polysaccharides micro pill for intestinal flora of the isolated, blood endotoxin content, plasma IL-2 content, ntestinal mucous SIgA content and the pathological samples of ntestinal mucous were observed;Through determination the median lethal dose and the maximumtolerateddose, astragalus polysaccharides micro pill acute toxicity tests.Results(1) Astragalus membranaceus herbs transverse section and powder characteristics, total ash, extract, the content of astragalus glycosides and grape glycosides separately are conform to the requirements of the pharmacopoeia. Huang qi herbs quality is better used in the experiment. Available for the use of active pharmaceutical ingredients.(2) The optimum extract process of APS was eight times solvent, three times extract and each two hours extract.(3) The composition of the pill core:APS powder:avicel:tannic acid:carboxymethylcellulose sodium was 25:15:8:2, the wetting agent was water, the rate of extrusion was 60 r·min-1, the rate of spheronization was 1400 r·min-1, the time of spheronization was 4 min. The best fluidiz bed coating condition was the fan frequency was 29.50 Hz, the pressure of spray gun was 0.70 kg·cm-2, the rate of coating flow was 3 mL·min-1, the dynamiting of colon coating was 15%.The release degree of pill for simulated gastric fluid in 2 h was 0%, The release degree of pill for artificial intestinal fluid in 3 h was less than 5%, The release degree of pill for artificial colon fluid in 2 h was release completely.(4) The micro pill was a gray coated pellets, slightly bitter taste; The microbial limit was in accordance with the Pharmacopoeia provisions; Its had good formability, stability and targeting.(5) The pharmacodynamics test demonstrated that the amount of lactobacillus and bifidobacterium of treated Wisar mice in the intestinal tract, blood endotoxin content was decreased and plasma IL-2 content and ntestinal mucous SIgA content were rised and the intestinal mucosa microscope of rats arrange neatly and unrupture.(6) There were no death and adverse reaction with Wistar mice in the test of median lethal dose. The maximum endure dose test demonstrated that the maximum endure dose of mice was 60 kg, which was 120 times of people weight.Conclusion The preparation method was apply to the preparation of APS pellets, it’s simplicity of operator and had good reproducibility; The quality control method has simple, accurate and can be control the quality of the products effectively; The results of dissolution in vitro show that pellets can be used as colon-specific drug delivery system; The results of pharmacodynamics show that APS pellets are supported the probiotics and inhibited the harmful germs, which are improved the effect of intestinal microecology; The results of acute toxicity test show that APS pellets are non-toxic, the maximum tolerated dose in mice to normal human dose of 100 times.